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1. ALT levels, alcohol use, and metabolic risk factors have prognostic relevance for liver-related outcomes in the general population

Author

Ville Männistö, Veikko Salomaa, Antti Jula, Annamari Lundqvist, Satu Männistö, Markus Perola, and Fredrik Åberg

Subjects
Advanced liver disease, Alcohol-related liver disease, Cirrhosis, Metabolic dysfunction-associated steatotic liver disease, Nomenclature, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: A new nomenclature and subclassification for steatotic liver disease (SLD) was recently introduced. We validated the prognostic value of SLD subclasses in a Finnish population-based cohort and explored the impact of metabolic risk factors and alcohol consumption on liver-related outcomes and death. Methods: The study included 23,910 individuals (47% men, mean age 50.5 ± 14.0 years, BMI 27.0 ± 4.7 kg/m2) from the FINRISK and Health 2000 health examination surveys with healthcare registry linkage for severe liver-related outcomes and deaths. SLD was identified by alanine aminotransferase (ALT) levels >20 U/L in women and >30 U/L in men (primary analysis) or fatty liver index (FLI) ≥60 (sensitivity analysis). Results: The prevalence of ALT-defined SLD was 43% (n = 10,380), with subclass rates of 34.5% for metabolic dysfunction-associated steatotic liver disease (MASLD), 4.2% for coexistent MASLD and alcohol-related liver disease (ALD) (i.e., MetALD), and 1.8% for ALD. During a median 13.3-year follow-up, we observed 129 liver-related events. MetALD and ALD increased the age- and sex-adjusted liver-related outcome risk by fourfold (HR 3.83, 95% CI 2.51–5.84, p

Published
2024
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2. Surrogate markers of bile duct disease progression in primary sclerosing cholangitis – A prospective study with repeated ERCP examinations

Author

Martti Färkkilä, Fredrik Åberg, Henrik Alfthan, Kalle Jokelainen, Lauri Puustinen, Hannu Kautiainen, and Andrea Tenca

Subjects
Cholangitis, bile, calprotectin, IL8, alkaline phosphatase, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis (PSC) are lacking. We evaluated the predictive value of serum and biliary biochemistry for the progression of bile duct disease in PSC using repeated endoscopic retrograde cholangiopancreatography (ERCP) examinations to identify surrogate markers for more personalized surveillance. Methods: We conducted a prospective analysis including patients with PSC who underwent ERCP for confirmation of diagnosis, monitoring of disease progression, or dysplasia surveillance. ERCP findings were scored, and dilatation was performed if a dominant stricture was diagnosed or if a cytology brush could not be passed. Bile samples were aspirated for biliary IL8 and calprotectin. We analysed optimal cut-off values and AUCs for 20 laboratory markers and evaluated their association with the time to an ERCP score increase of ≥2 points or first dilatation, whichever came first. Of the 1,002 patients, 653 had ≥2 ERCP examinations and ≥3 years of follow-up. After excluding patients with PSC-overlap syndrome or initial dilatation, 398 patients were included. Results: Of the patients included, 62% had mild or moderate and 38% had advanced bile duct disease. During follow-up, 41% of patients demonstrated progression of disease. Biliary calprotectin (AUC 0.76; 95% CI 0.69 to 0.82) and IL8 (AUC 0.76; 95% CI 0.69 to 0.84) were the only variables that demonstrated predictive value for disease progression and/or need for dilatation. Conclusions: Biliary calprotectin and IL8 are promising surrogate markers for identifying patients with PSC at risk of progression and determining the timing for subsequent imaging. Conventional liver function tests may not be sensitive or specific enough to monitor PSC progression, particularly in the short term. Impact and implications:: Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis are lacking. In this prospective study, based on sequential endoscopic retrograde cholangiopancreatography examinations, biliary calprotectin and IL8 levels turned out to be more sensitive for predicting bile duct progression than traditional liver function tests, such as alkaline phosphatase, in the short term. These findings could lead to more personalized patient surveillance and improve clinical practice by providing a more accurate method for monitoring disease progression and treatment responses. Additionally, these markers have potential as surrogate endpoints in clinical drug trials. The limitation is that measurement of biliary IL8 and calprotectin requires endoscopic retrograde cholangiopancreatography with bile sampling.

Published
2024
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3. TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

Author

Tommi Vasankari, Henri Vähä-Ypyä, Oskari Heikinheimo, Athena Matakidou, Jaakko Kaprio, Eero Vuoksimaa, Ying Wu, Kai Kaarniranta, Peeter Karihtala, Wei Zhou, Caroline Fox, Sanna-Kaisa Herukka, Sarah Smith, Apinya Lertratanakul, Katri Kaukinen, Johannes Kettunen, Minna Männikkö, Eeva Sliz, Markus Perola, Veikko Salomaa, Hilkka Soininen, Ilkka Kalliala, Mika Kähönen, Hao Chen, Andrey Loboda, Laure Morin-Papunen, Terhi Piltonen, Anders Mälarstig, Jason Miller, Jussi Hernesniemi, Henrike Heyne, Sirkku Peltonen, Daniel Gordin, Masahiro Kanai, Benjamin Challis, Juha Sinisalo, David Rice, Fredrik Åberg, Aarno Palotie, Samuli Ripatti, Oili Kaipiainen-Seppänen, Aki Havulinna, Satu Strausz, Tuomo Kiiskinen, Sanni Ruotsalainen, Jukka Koskela, Tuula Palotie, Mark Daly, Howard Jacob, Heiko Runz, Sally John, Robert Plenge, Mark McCarthy, Julie Hunkapiller, Dawn Waterworth, Petri Virolainen, Terhi Kilpi, Jukka Partanen, Anne Pitkäranta, Veli-Matti Kosma, Outi Tuovila, Raimo Pakkanen, Shameek Biswas, Xinli Hu, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Arto Mannermaa, Valtteri Julkunen, Anne Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Adam Ziemann, Jeffrey Waring, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, David Pulford, Martti Färkkilä, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Fedik Rahimov, Joseph Maranville, Tim Lu, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Johanna Huhtakangas, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Hubert Chen, Teemu Niiranen, Kaj Metsärinne, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Audrey Chu, Jaakko Parkkinen, Heikki Joensuu, Tuomo Meretoja, Lauri Aaltonen, Annika Auranen, Päivi Auvinen, Klaus Elenius, Relja Popovic, Bridget Riley-Gillis, Jennifer Schutzman, Heli Lehtonen, Stefan McDonough, Diptee Kulkarni, Terhi Ollila, Hannu Uusitalo, Erich Strauss, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Leena Koulu, David Choy, Anu Jalanko, Risto Kajanne, Mari Kaunisto, Chia-Yen Chen, Robert Yang, Kirsi Auro, Clement Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Susanna Lemmelä, Manuel Rivas, Arto Lehisto, Andrea Ganna, Vincent Llorens, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija Laakkonen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Tero Hiekkalinna, Kati Donner, Kalle Pärn, Elina Kilpeläinen, Hannele Laivuori, Harri Siirtola, Sirpa Soini, Teijo Kuopio, Ioanna Tachmazidou, Katja Kivinen, Pekka Nieminen, Adam Platt, Sanna Toppila-Salmi, Antti Mäkitie, Elmo Saarentaus, Kristiina Aittomäki, Elisabeth Widen, Marja Vääräsmäki, Erkki Isometsä, Laura Addis, Mika Helminen, Taneli Raivio, Mart Kals, Majd Mouded, Hanna Ollila, Vuokko Anttonen, Tarja Kokkola, Robert Graham, Amanda Elliott, Ali Abbasi, Bridget Riley-Gills, Dirk Paul, Katherine Klinger, Deepak Raipal, Antti Hakanen, Raisa Serpi, Johanna Mäkelä, Mengzhen Liu, Neha Raghavan, Adriana Huertas-Vazquez, Nicole Renaud, Roosa Kallionpää, John Eicher, Minna Raivio, Juulia Partanen, Riitta Lahesmaa, Glenda Lassi, Joanna Betts, Rajashree Mishra, Felix Vaura, Joel Rämö, Mary Pat Reeve, Johanna Mattson, Sauli Vuoti, Esa Pitkänen, Joni A Turunen, Stephanie Loomis, Pirkko Pussinen, Aino Salminen, Tuula Salo, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Outi Uimari, Taru Tukiainen, Niko Välimäki, Janet Kumar, Juha Mehtonen, Shabbeer Hassan, Pietro Della Briotta Parolo, Mutaamba Maasha, Javier Garcia-Tabuenca, Jiwoo Lee, Kristin Tsuo, Nina Pitkänen, Eero Punkka, Huei-Yi Shen, Mervi Aavikko, L. Elisa Lahtela, Timo P. Sipilä, Awaisa Ghazal, Sami Koskelainen, Teemu Paajanen, Shuang Luo, Javier Gracia-Tabuenca, Tiina Luukkaala, Iida Vähätalo, Marco Hautalahti, Tom Southerington, Paula Iso-Markku, Jaana Suvisaari, Zhihao Ding, Qingqin S Li, Amy Hart, Perttu Terho, Alessandro Porello, Anastasia Kytölä, Antti Aarnisalo, Aoxing Liu, Argyro Bizaki-Vallaskangas, Auli Toivola, Debby Ngo, Dermot Reilly, Ekaterina Khramtsova, Elisa Rahikkala, Eric Green, Eveliina Salminen, Fabiana Farias, George Okafo, Heidi Silven, Heli Salminen-Mankonen, Henna Palin, Iiris Hovatta, Jaakko Tyrmi, Jae-Hoon Sul, Jenni Aittokallio, Jyrki Pitkänen, Karen He, Katriina Aalto-Setälä, Maarit Niinimäki, Malla-Maria Linna, Marc Jung, Margaret G. Ehm, Marianna Niemi, Meijian Guan, Mike Mendelson, Minna Brunfeldt, Natalia Pujol, Nathan Lawless, Oluwaseun Alexander Dada, Rigbe Weldatsadik, Riikka Arffman, Rion Pendergrass, Sahar Mozaffari, Samuel Lessard, Sanna Siltanen, Shanmukha Sampath Padmanabhuni, Simonne Longerich, Susanna Savukoski, Thomas Damm Als, Timo Hiltunen, Tomi P. Mäkelä, Triin Laisk, Tytti Willberg, Varpu Jokimaa, Aija Kyttälä, Toni T Saari, Aino Aaltonen, Sari Aaltonen, Sari Kärkkäinen, Hilkka Liedes, Miina Ollikainen, Teemu Palviainen, Ilona Ruotsalainen, Mia Urjansson, Markus M Forsberg, Jaakko Lähteenmäki, Pia Nyberg, Jani Tikkanen, Mari E. Niemi, and Rodos Rodosthenous

Subjects
Medicine
Abstract

Introduction A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.Methods and analysis A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.Ethics and dissemination This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Published
2024
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4. Waist-hip ratio is superior to BMI in predicting liver-related outcomes and synergizes with harmful alcohol use

Author

Fredrik Åberg, Martti Färkkilä, Veikko Salomaa, Antti Jula, Satu Männistö, Markus Perola, Annamari Lundqvist, and Ville Männistö

Subjects
Medicine
Abstract

Abstract Background: Obesity is associated with liver disease, but the best obesity-related predictor remains undefined. Controversy exists regarding possible synergism between obesity and alcohol use for liver-related outcomes (LRO). We assessed the predictive performance for LROs, and synergism with alcohol use, of abdominal obesity (waist-hip ratio, WHR), and compared it to overall obesity (body mass index, BMI). Methods: Forty-thousand nine-hundred twenty-two adults attending the Finnish health-examination surveys, FINRISK 1992–2012 and Health 2000 studies, were followed through linkage with electronic healthcare registries for LROs (hospitalizations, cancers, and deaths). Predictive performance of obesity measures (WHR, waist circumference [WC], and BMI) were assessed by Fine-Gray models and time-dependent area-under-the-curve (AUC). Results: There are 355 LROs during a median follow-up of 12.9 years (509047.8 person-years). WHR and WC emerge as more powerful predictors of LROs than BMI. WHR shows significantly better 10-year AUC values for LROs (0.714, 95% CI 0.685–0.743) than WC (0.648, 95% CI 0.617–0.679) or BMI (0.550, 95% CI 0.514–0.585) both overall and separately among men and women. WHR is predictive also in BMI strata. Absolute 10-year risks of LROs are more dependent on WHR than BMI. Moreover, WHR shows a significant supra-additive interaction effect with harmful alcohol use for liver-related outcomes (excess 10-year cumulative incidence of 2.8% from the interaction), which is not seen between BMI and harmful alcohol use. Conclusions: WHR is a better predictor than BMI or WC for LROs, and WHR better reflects the synergism with harmful alcohol use. WHR should be included in clinical assessment when evaluating obesity-related risks for liver outcomes.

Published
2023
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5. CLivD score modifies FIB-4 performance in liver fibrosis detection in the US general population

Author

Mitja Lääperi, Fredrik Åberg, and Ville Männistö

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and aims Steatotic liver disease (SLD) is a growing global concern. The Chronic Liver Disease (CLivD) risk score predicts liver-related outcomes in the general population using easily accessible variables with or without laboratory tests (CLivDlab and CLivDnon-lab). We assessed CLivD’s associations with liver steatosis, fibrosis and its combined performance with fibrosis-4 (FIB-4) for advanced fibrosis detection.Methods Using the National Health and Nutrition Examination Survey data (2017–2020), 3603 participants aged 40–70 years with valid liver stiffness measurements (LSMs) were included. Advanced fibrosis was defined as LSM ≥12 kPa, and SLD as controlled attenuation parameter ≥288 dB/m.Results Significant associations were found between CLivD and SLD and advanced fibrosis. CLivDlab had an area under the curve (AUC) for advanced fibrosis of 0.72 (95% CI 0.68 to 0.77), while CLivDnon-lab had an AUC of 0.68 (95% CI 0.64 to 0.72), both slightly higher than FIB-4 (AUC 0.66, 95% CI 0.60 to 0.72). Among participants without obesity, AUC of CLivDlab was 0.82 (95% CI 0.76 to 0.88) and AUC of CLivDnon-lab was 0.72 (95% CI 0.65 to 0.79). The CLivD score improved FIB-4’s AUC for advanced fibrosis detection from 0.8 at high CLivD scores. A sequential CLivD→FIB-4 strategy outperformed universal FIB-4 testing, enhancing specificity from 72% to 83%, with sensitivity at 51%–53%. This strategy identified a subgroup with a 55% prevalence of advanced fibrosis, while 47% had minimal-risk CLivD scores, eliminating the need for FIB-4 testing.Conclusions The CLivD score, designed for predicting liver-related outcomes, effectively identifies liver steatosis and advanced fibrosis in the general population. Combining CLivD with FIB-4 enhances advanced fibrosis detection accuracy. The CLivD score could enhance population-based liver fibrosis screening, optimising resource allocation.

Published
2023
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6. Association between arterial hypertension and liver outcomes using polygenic risk scores: a population-based study

Author

Fredrik Åberg, Katri Kantojärvi, Ville Männistö, Anna But, Veikko Salomaa, Teemu Niiranen, Martti Färkkilä, Panu Luukkonen, Satu Männistö, Annamari Lundqvist, Markus Perola, and Antti Jula

Subjects
Medicine, Science
Abstract

Abstract Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992–2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01–1.24, and 1.12, 95% CI 1.01–1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31–0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.

Published
2022
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7. Enhanced liver Fibrosis® test predicts liver-related outcomes in the general population

Author

Kustaa Saarinen, Martti Färkkilä, Antti Jula, Iris Erlund, Terhi Vihervaara, Annamari Lundqvist, and Fredrik Åberg

Subjects
ELF test, Non-invasive liver fibrosis test, Prognosis, General population, Liver fibrosis, Cirrhosis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: The Enhanced Liver Fibrosis® (ELF) test exhibits good discriminative performance in detecting advanced liver fibrosis and in predicting liver-related outcomes in patients with specific liver diseases, but large population-based studies are missing. We analysed the predictive performance of the ELF test in a general population cohort. Methods: Data were sourced from the Health 2000 study, a Finnish population-based health examination survey conducted in 2000–2001. Subjects with baseline liver disease were excluded. The ELF test was performed on blood samples collected at baseline. Data were linked with national healthcare registers for liver-related outcomes (hospitalisation, cancer, and death). Results: The cohort comprised 6,040 individuals (mean age 52.7. 45.6% men) with 67 liver-related outcomes during a median 13.1-year follow-up. ELF predicted liver outcomes (unadjusted hazards ratio 2.70, 95% CI 2.16–3.38). with 5- and 10-year AUCs of 0.81 (95% CI 0.71–0.91) and 0.71 (95% CI 0.63–0.79) by competing-risk methodology. The 10-year risks for liver outcomes increased from 0.5% at ELF 40 U/L. Five-year AUCs for ELF were 0.85, 0.87, and 0.88, respectively. The predictive ability of the ELF test decreased with time: the 10-year AUCs were 0.78, 0.69, and 0.82, respectively. Conclusions: The ELF test shows good discriminative performance in predicting liver-related outcomes in a large general population cohort and appears particularly useful for predicting 5-year outcomes in persons with risk factors. Impact and implications: The Enhanced Liver Fibrosis test exhibits good performance for predicting liver-related outcomes (hospitalisation, liver cancer, or liver-related death) in the general population, especially in those with risk factors.

Published
2023
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8. Persistent oral mucosal lesions preceding diagnosis of Crohn's disease and primary sclerosing cholangitis

Author

Karita Nylund, Jaana Helenius‐Hietala, Fredrik Åberg, Jaana Hagström, and Hellevi Ruokonen

Subjects
dentistry, gastroenterology and hepatology, inflammatory bowel disease (IBD), oral medicine, Medicine, Medicine (General), R5-920
Abstract

Abstract Oral mucosal lesions may persist years before symptoms or diagnosis of inflammatory bowel disease (IBD) and subsequent primary sclerosing cholangitis (PSC). Since a dental practitioner may be the first clinician to suspect IBD with extraintestinal manifestations (EIMs), early referral, and close collaboration with a gastroenterologist are recommended.

Published
2023
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9. Recontacting biobank participants to collect lifestyle, behavioural and cognitive information via online questionnaires: lessons from a pilot study within FinnGen

Author

Oskari Heikinheimo, Athena Matakidou, Jaakko Kaprio, Ying Wu, Kai Kaarniranta, Peeter Karihtala, Wei Zhou, Caroline Fox, Sarah Smith, Apinya Lertratanakul, Katri Kaukinen, Johannes Kettunen, Eeva Sliz, Markus Perola, Veikko Salomaa, Hilkka Soininen, Ilkka Kalliala, Mika Kähönen, Hao Chen, Andrey Loboda, Laure Morin-Papunen, Terhi Piltonen, Anders Mälarstig, Jason Miller, Jussi Hernesniemi, Henrike Heyne, Sirkku Peltonen, Daniel Gordin, Masahiro Kanai, Benjamin Challis, Juha Sinisalo, David Rice, Fredrik Åberg, Aarno Palotie, Samuli Ripatti, Oili Kaipiainen-Seppänen, Aki Havulinna, Satu Strausz, Tuomo Kiiskinen, Sanni Ruotsalainen, Jukka Koskela, Tuula Palotie, Mark Daly, Howard Jacob, Heiko Runz, Sally John, Robert Plenge, Mark McCarthy, Julie Hunkapiller, Dawn Waterworth, Petri Virolainen, Terhi Kilpi, Jukka Partanen, Anne Pitkäranta, Veli-Matti Kosma, Outi Tuovila, Raimo Pakkanen, Shameek Biswas, Xinli Hu, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Arto Mannermaa, Valtteri Julkunen, Anne Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Adam Ziemann, Jeffrey Waring, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, David Pulford, Martti Färkkilä, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Fedik Rahimov, Joseph Maranville, Tim Lu, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Johanna Huhtakangas, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Hubert Chen, Teemu Niiranen, Kaj Metsärinne, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Audrey Chu, Jaakko Parkkinen, Heikki Joensuu, Tuomo Meretoja, Lauri Aaltonen, Annika Auranen, Päivi Auvinen, Klaus Elenius, Relja Popovic, Jennifer Schutzman, Heli Lehtonen, Stefan McDonough, Diptee Kulkarni, Terhi Ollila, Hannu Uusitalo, Erich Strauss, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Leena Koulu, David Choy, Anu Jalanko, Risto Kajanne, Mari Kaunisto, Chia-Yen Chen, Robert Yang, Kirsi Auro, Clement Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Susanna Lemmelä, Manuel Rivas, Arto Lehisto, Andrea Ganna, Vincent Llorens, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija Laakkonen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Kati Donner, Kalle Pärn, Elina Kilpeläinen, Hannele Laivuori, Harri Siirtola, Lila Kallio, Sirpa Soini, Teijo Kuopio, Ioanna Tachmazidou, Katja Kivinen, Pekka Nieminen, Adam Platt, Sanna Toppila-Salmi, Antti Mäkitie, Elmo Saarentaus, Kristiina Aittomäki, Elisabeth Widen, Marja Vääräsmäki, Erkki Isometsä, Jari Lahti, Laura Addis, Taneli Raivio, Mart Kals, Majd Mouded, Hanna Ollila, Vuokko Anttonen, Robert Graham, Amanda Elliott, Ali Abbasi, Bridget Riley-Gills, Dirk Paul, Katherine Klinger, Deepak Raipal, Antti Hakanen, Raisa Serpi, Johanna Mäkelä, Mengzhen Liu, Neha Raghavan, Adriana Huertas-Vazquez, Nicole Renaud, Roosa Kallionpää, John Eicher, Minna Raivio, Juulia Partanen, Riitta Lahesmaa, Glenda Lassi, Joanna Betts, Rajashree Mishra, Felix Vaura, Joel Rämö, Mary Pat Reeve, Johanna Mattson, Sauli Vuoti, Esa Pitkänen, Joni A Turunen, Stephanie Loomis, Pirkko Pussinen, Aino Salminen, Tuula Salo, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Outi Uimari, Taru Tukiainen, Niko Välimäki, Janet Kumar, Juha Mehtonen, Shabbeer Hassan, Pietro Della Briotta Parolo, Mutaamba Maasha, Javier Garcia-Tabuenca, Jiwoo Lee, Kristin Tsuo, Nina Pitkänen, Eero Punkka, Huei-Yi Shen, Mervi Aavikko, L. Elisa Lahtela, Timo P. Sipilä, Awaisa Ghazal, Sami Koskelainen, Teemu Paajanen, Shuang Luo, Tiina Luukkaala, Iida Vähätalo, Tero Jyrhämä, Marco Hautalahti, Tom Southerington, Jaana Suvisaari, Zhihao Ding, Qingqin S Li, Amy Hart, Rodosthenis S Rodosthenous, Mari E K Niemi, Merja Perala, Perttu Terho, Theresa Knopp, Enni M Makkonen, Paula Nurmi, Pauli Wihuri, Corianna Moffatt, Paolo Martini, Laura Germine, Viola A Makela, Oona A Karhunen, Tero S Hiekkalinna, Alessandro Porello, Anastasia Kytölä, Antti Aarnisalo, Aoxing Liu, Argyro Bizaki-Vallaskangas, Auli Toivola, Debby Ngo, Dermot Reilly, Ekaterina Khramtsova, Elisa Rahikkala, Eric Green, Eveliina Salminen, Fabiana Farias, George Okafo, Heidi Silven, Heli Salminen-Mankonen, Henna Palin, Iiris Hovatta, Jaakko Tyrmi, Jae-Hoon Sul, Jenni Aittokallio, Jyrki Pitkänen, Karen He, Katriina Aalto-Setälä, Maarit Niinimäki, Malla-Maria Linna, Marc Jung, Margaret G. Ehm, Marianna Niemi, Meijian Guan, Mike Mendelson, Minna Brunfeldt, Natalia Pujol, Nathan Lawless, Oluwaseun Alexander Dada, Rigbe Weldatsadik, Riikka Arffman, Rion Pendergrass, Sahar Mozaffari, Samuel Lessard, Sanna Siltanen, Shanmukha Sampath Padmanabhuni, Simonne Longerich, Susanna Savukoski, Thomas Damm Als, Timo Hiltunen, Tomi P. Mäkelä, Triin Laisk, Tytti Willberg, and Varpu Jokimaa

Subjects
Medicine
Abstract

Objectives To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform.Design Biobank-based recontacting pilot study.Setting Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021.Participants All eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s).Outcome measures The primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies.Results The overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18–69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92.Conclusion In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.

Published
2022
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10. A Dynamic Aspartate‐to‐Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease

Author

Fredrik Åberg, Christopher J. Danford, Maja Thiele, Mats Talbäck, Ditlev Nytoft Rasmussen, Z. Gordon Jiang, Niklas Hammar, Patrik Nasr, Mattias Ekstedt, Anna But, Pauli Puukka, Aleksander Krag, Jouko Sundvall, Iris Erlund, Veikko Salomaa, Per Stål, Stergios Kechagias, Rolf Hultcrantz, Michelle Lai, Nezam Afdhal, Antti Jula, Satu Männistö, Annamari Lundqvist, Markus Perola, Martti Färkkilä, and Hannes Hagström

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

The aspartate‐to‐alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver‐related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population‐based health‐examination surveys (FINRISK, 2002‐2012; n = 18,067) with linked registry data for incident liver‐related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver‐related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol‐related liver disease (ALD). The dynamic AAR model predicted liver‐related outcomes both overall (optimism‐corrected C‐statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver‐related outcomes within 10 years. In independent cohorts, the C‐statistic for predicting liver‐related outcomes up to a 10‐year follow‐up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area‐under‐the‐curve (AUC) for detecting prevalent cirrhosis was 0.80‐0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C‐statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.

Published
2021
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11. Checkpoint Inhibition Causing Complete Remission of Metastatic Combined Hepatocellular-Cholangiocarcinoma after Hepatic Resection

Author

Magnus Rizell, Fredrik Åberg, Mats Perman, Lars Ny, Liselotte Stén, Farida Hashimi, Joar Svanvik, and Per Lindnér

Subjects
checkpoint inhibition, combined hepatocellular-cholangiocarcinoma, sorafenib, immune-related hepatitis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer, speculated to arise from hepatic progenitor cells, and with a worse prognosis than hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) levels may be one prognostic factor. It has been suggested that checkpoint inhibition might be useful in the treatment of HCC where there is an increased expression of PD-1 and PD-L1 in the microenvironment. Its effect on CHC is unknown. We report a case with a large CHC, which was radically resected, but the 53-year-old female patient subsequently developed pulmonary metastases. Histology demonstrated low-differentiated CHC without microsatellite instability. Treatment with sorafenib was started but was stopped due to angioedema. Under subsequent gemcitabine/cisplatin treatment, the metastatic disease progressed with rising AFP levels. A third-line treatment with pembrolizumab was then started, 2 mg/kg b.w. i.v. every third week for 6 months. This resulted in a radiologically complete remission of the pulmonary metastases and AFP levels were normalized (

Published
2020
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12. Serum lipopolysaccharides predict advanced liver disease in the general population

Author

Ville Männistö, Martti Färkkilä, Pirkko Pussinen, Antti Jula, Satu Männistö, Annamari Lundqvist, Liisa Valsta, Veikko Salomaa, Markus Perola, and Fredrik Åberg

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Gut-derived endotoxemia has been implicated in the development of chronic liver disease, but its relevance at the population level remains unclear. We analyzed whether endotoxemia is associated with incident advanced liver disease in the general population. Methods: Serum lipopolysaccharide (LPS) was measured in 6,727 (3,455 male and 3,272 female, mean age 53.4 ± 10.9 years, mean body mass index 27.2 ± 4.5) individuals participating in the Finnish population-based health examination survey FINRISK 1997. Data were linked with electronic health registers for incident advanced liver disease (hospitalization, cancer or death related to liver disease). During a mean follow-up of 16.3 ± 3.8 years (109,282 person-years), 86 liver events occurred. Univariate and multivariate Cox regression, and Kaplan-Meier analyses were performed. Results: Serum LPS predicted incident advanced liver disease with a hazard ratio per 1 SD of 1.41 (95% CI 1.24–1.59; p ≪0.001) when adjusted for age, sex, gamma-glutamyltransferase, metabolic syndrome, alcohol use, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M, waist-hip ratio and type 2 diabetes. This association remained robustly significant in additional multivariate analyses with various levels of adjustment. The association was accentuated among carriers of the PNPLA3 risk variant. The population attributable fraction of the highest LPS tertile for liver events was 29.7%. However, LPS was not associated with all-cause mortality. Conclusion: Serum LPS is associated with hospitalization, cancer or death related to liver disease in the general population, with the highest tertile potentially accounting for 30% of the risk of liver disease. Lay summary: Lipopolysaccharide, a gut-derived bacterial endotoxin, has been implicated in the development of chronic liver disease, but its relevance at the population level remains unclear. We found that serum lipopolysaccharide levels were associated with incident advanced liver disease in the general population, with the highest tertile accounting for up to 30% of the risk of hospitalization, cancer or death related to liver disease. Key words: Cirrhosis, Endotoxemia, Genetics, Gut, Hospitalization

Published
2019
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13. Links between gut microbiome composition and fatty liver disease in a large population sample

Author

Matti O. Ruuskanen, Fredrik Åberg, Ville Männistö, Aki S. Havulinna, Guillaume Méric, Yang Liu, Rohit Loomba, Yoshiki Vázquez-Baeza, Anupriya Tripathi, Liisa M. Valsta, Michael Inouye, Pekka Jousilahti, Veikko Salomaa, Mohit Jain, Rob Knight, Leo Lahti, and Teemu J. Niiranen

Subjects
metagenomics, human gut, fatty liver, fatty liver index, population sample, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Fatty liver disease is the most common liver disease in the world. Its connection with the gut microbiome has been known for at least 80 y, but this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample of 6,269 Finnish participants. We based our models on biometric covariates and gut microbiome compositions from shallow metagenome sequencing. Our classification models could discriminate between individuals with a high FLI (≥60, indicates likely liver steatosis) and low FLI (

Published
2021
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14. Randomised sham-controlled double-blind trial evaluating remote ischaemic preconditioning in solid organ transplantation: a study protocol for the RIPTRANS trial

Author

Ville Sallinen, Anni Pulkkinen, Ilkka Helanterä, Aki Uutela, Karl Lemström, Arie Passov, Simo Syrjälä, Fredrik Åberg, Heikki Mäkisalo, Arno Nordin, Marko Lempinen, Minna Bäcklund, Markus Skrifvars, Teemu Luostarinen, Janne Reitala, Maarit Lång, Ilona Leppänen, Jaakko Långsjö, Juha Grönlund, Pekka Loisa, and Björn Jäschke

Subjects
Medicine
Abstract

Introduction Remote ischaemic preconditioning (RIPC) using a non-invasive pneumatic tourniquet is a potential method for reducing ischaemia-reperfusion injury. RIPC has been extensively studied in animal models and cardiac surgery, but scarcely in solid organ transplantation. RIPC could be an inexpensive and simple method to improve function of transplanted organs. Accordingly, we aim to study whether RIPC performed in brain-dead organ donors improves function and longevity of transplanted organs.Methods and analyses RIPTRANS is a multicentre, sham-controlled, parallel group, randomised superiority trial comparing RIPC intervention versus sham-intervention in brain-dead organ donors scheduled to donate at least one kidney. Recipients of the organs (kidney, liver, pancreas, heart, lungs) from a randomised donor will be included provided that they give written informed consent. The RIPC intervention is performed by inflating a thigh tourniquet to 300 mm Hg 4 times for 5 min. The intervention is done two times: first right after the declaration of brain death and second immediately before transferring the donor to the operating theatre. The sham group receives the tourniquet, but it is not inflated. The primary endpoint is delayed graft function (DGF) in kidney allografts. Secondary endpoints include short-term functional outcomes of transplanted organs, rejections and graft survival in various time points up to 20 years. We aim to show that RIPC reduces the incidence of DGF from 25% to 15%. According to this, the sample size is set to 500 kidney transplant recipients.Ethics and dissemination This study has been approved by Helsinki University Hospital Ethics Committee and Helsinki University Hospital’s Institutional Review Board. The study protocol was be presented at the European Society of Organ Transplantation congress in Copenhagen 14−15 September 2019. The study results will be submitted to an international peer-reviewed scientific journal for publication.Trial registration number NCT03855722.

Published
2020
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15. Oral Health and Liver Disease: Bidirectional Associations—A Narrative Review

Author

Fredrik Åberg and Jaana Helenius-Hietala

Subjects
cirrhosis, oral infections, periodontitis, dysbiosis, oral-gut-liver axis, Dentistry, RK1-715
Abstract

Several links between chronic liver disease and oral health have been described and are discussed in this narrative review. Oral manifestations such as lichen planus, ulcers, xerostomia, erosion and tongue abnormalities seem to be particularly prevalent among patients with chronic liver disease. These may be causal, coincidental, secondary to therapeutic interventions, or attributable to other factors commonly observed in liver disease patients. In addition, findings from both experimental and epidemiological studies suggest that periodontitis can induce liver injury and contribute to the progression of chronic liver disease through periodontitis-induced systemic inflammation, endotoxemia, and gut dysbiosis with increased intestinal translocation. This has brought forward the hypothesis of an oral-gut-liver axis. Preliminary clinical intervention studies indicate that local periodontal treatments may lead to beneficial liver effects, but more human studies are needed to clarify if treatment of periodontitis truly can halt or reverse progression of liver disease and improve liver-related outcomes.

Published
2022
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17. Salivary Biomarkers and Oral Health in Liver Transplant Recipients, with an Emphasis on Diabetes

Author

Annika Emilia Norrman, Taina Tervahartiala, Ella Sahlberg, Timo Sorsa, Hellevi Ruokonen, Lisa Grönroos, Jukka H. Meurman, Helena Isoniemi, Arno Nordin, Fredrik Åberg, and Jaana Helenius-Hietala

Subjects
periodontitis, teeth, liver disease, oral infections, saliva, salivary biomarkers, Medicine (General), R5-920
Abstract

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.

Published
2021
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18. Abdominal obesity and alcohol use modify the impact of genetic risk for incident advanced liver disease in the general population

Author

Panu K. Luukkonen, Martti Färkkilä, Antti Jula, Veikko Salomaa, Satu Männistö, Annamari Lundqvist, Markus Perola, Fredrik Åberg, Department of Medicine, Medicum, HUS Abdominal Center, Clinicum, Centre of Excellence in Complex Disease Genetics, Helsinki University Hospital Area, Gastroenterologian yksikkö, and IV kirurgian klinikka

Subjects
Ifnl4, Serpina1, Tm6sf2, Hepatology, 3121 General medicine, internal medicine and other clinical medicine, Pnpla3, Fdft1
Published
2023

19. Alcohol consumption and metabolic syndrome: Clinical and epidemiological impact on liver disease

Author

Fredrik Åberg, Christopher D. Byrne, Carlos J. Pirola, Ville Männistö, and Silvia Sookoian

Subjects
Metabolic Syndrome, Alcohol Drinking, Hepatology, Risk Factors, Non-alcoholic Fatty Liver Disease, Liver Neoplasms, Humans, Prospective Studies, Obesity
Abstract

Alcohol use and metabolic syndrome are highly prevalent in the population and frequently co-exist. Both are implicated in a large range of health problems, including chronic liver disease, hepatocellular carcinoma, and liver-related outcomes (i.e. decompensation or liver transplantation). Studies have yielded mixed results regarding the effects of mild-moderate alcohol consumption on the risk of metabolic syndrome and fatty liver disease, possibly due to methodological differences. The few available prospective studies have indicated that mild-moderate alcohol use is associated with an increase in liver-related outcomes. This conclusion was substantiated by systems biology analyses suggesting that alcohol and metabolic syndrome may play a similar role in fatty liver disease, potentiating an already existing dysregulation of common vital homeostatic pathways. Alcohol and metabolic factors are independently and jointly associated with liver-related outcomes. Indeed, metabolic syndrome increases the risk of liver-related outcomes, regardless of alcohol intake. Moreover, the components of metabolic syndrome appear to have additive effects when it comes to the risk of liver-related outcomes. A number of population studies have implied that measures of central/abdominal obesity, such as the waist-to-hip ratio, can predict liver-related outcomes more accurately than BMI, including in individuals who consume harmful quantities of alcohol. Many studies even point to synergistic interactions between harmful alcohol use and many metabolic components. This accumulating evidence showing independent, combined, and modifying effects of alcohol and metabolic factors on the onset and progression of chronic liver disease highlights the multifactorial background of liver disease in the population. The available evidence suggests that more holistic approaches could be useful for risk prediction, diagnostics and treatment planning.

Published
2023

20. Development and validation of a model to predict incident chronic liver disease in the general population: The CLivD score

Author

Fredrik Åberg, Panu K. Luukkonen, Anna But, Veikko Salomaa, Annie Britton, Kasper Meidahl Petersen, Stig Egil Bojesen, Mie Balling, Børge G. Nordestgaard, Pauli Puukka, Satu Männistö, Annamari Lundqvist, Markus Perola, Antti Jula, Martti Färkkilä, Clinicum, HUS Abdominal Center, IV kirurgian klinikka, HUS Internal Medicine and Rehabilitation, Department of Medicine, University of Helsinki, Department of Public Health, INDIVIDRUG - Individualized Drug Therapy, and Centre of Excellence in Complex Disease Genetics

Subjects
risk prediction, Hepatology, liver cirrhosis, screening, 3121 General medicine, internal medicine and other clinical medicine, Liver cirrhosis, Screening, morbidity, Morbidity, Mortality, mortality, Risk prediction
Abstract

Background & Aims: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify those at high future risk of severe liver disease. Our aim was to develop and validate a risk pre-diction model for incident chronic liver disease in the general population based on widely available factors. Methods: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40-70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5,058) and Copenhagen City Heart Study (CCHS) (n = 3,049) cohorts. Results: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist-hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally validated Wolbers' C -sta-tistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion (< 2%) of the population with > 10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. Conclusions: Based on widely available risk factors, the Chronic Liver Disease (CLivD) score can be used to predict risk of future advanced liver disease in the general population. Lay summary: Liver disease often progresses silently without symptoms and thus the diagnosis is often delayed until severe complications occur and prognosis becomes poor. In order to identify individuals in the general population who have a high risk of developing severe liver disease in the future, we developed and validated a Chronic Liver Disease (CLivD) risk prediction score, based on age, sex, alcohol use, waist-hip ratio, diabetes, and smoking, with or without measurement of the liver enzyme gamma-glutamyltransferase. The CLivD score can be used as part of health counseling, and for planning further liver investigations and follow-up. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Published
2022

21. Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study

Author

Eliza C. Miller, Anni Kauko, Sarah E. Tom, Hannele Laivuori, Teemu Niiranen, Natalie A. Bello, Aarno Palotie, Mark Daly, Bridget Riley-Gills, Howard Jacob, Dirk Paul, Athena Matakidou, Adam Platt, Heiko Runz, Sally John, George Okafo, Nathan Lawless, Heli Salminen-Mankonen, Robert Plenge, Joseph Maranville, Mark McCarthy, Julie Hunkapiller, Margaret G. Ehm, Kirsi Auro, Simonne Longerich, Caroline Fox, Anders Mälarstig, Katherine Klinger, Deepak Raipal, Eric Green, Robert Graham, Robert Yang, Chris O´ Donnell, Tomi P. Mäkelä, Jaakko Kaprio, Petri Virolainen, Antti Hakanen, Terhi Kilpi, Markus Perola, Jukka Partanen, Anne Pitkäranta, Taneli Raivio, Raisa Serpi, Tarja Laitinen, Veli-Matti Kosma, Jari Laukkanen, Marco Hautalahti, Outi Tuovila, Raimo Pakkanen, Jeffrey Waring, Bridget Riley-Gillis, Fedik Rahimov, Ioanna Tachmazidou, Chia-Yen Chen, Zhihao Ding, Marc Jung, Shameek Biswas, Rion Pendergrass, David Pulford, Neha Raghavan, Adriana Huertas-Vazquez, Jae-Hoon Sul, Xinli Hu, Sahar Mozaffari, Dawn Waterworth, Nicole Renaud, Ma´en Obeidat, Samuli Ripatti, Johanna Schleutker, Mikko Arvas, Olli Carpén, Reetta Hinttala, Johannes Kettunen, Arto Mannermaa, Katriina Aalto-Setälä, Mika Kähönen, Johanna Mäkelä, Reetta Kälviäinen, Valtteri Julkunen, Hilkka Soininen, Anne Remes, Mikko Hiltunen, Jukka Peltola, Minna Raivio, Pentti Tienari, Juha Rinne, Roosa Kallionpää, Juulia Partanen, Ali Abbasi, Adam Ziemann, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, Laura Addis, John Eicher, Qingqin S Li, Karen He, Ekaterina Khramtsova, Martti Färkkilä, Jukka Koskela, Sampsa Pikkarainen, Airi Jussila, Katri Kaukinen, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Tim Lu, Linda McCarthy, Amy Hart, Meijian Guan, Jason Miller, Kirsi Kalpala, Melissa Miller, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Oili Kaipiainen-Seppänen, Johanna Huhtakangas, Nina Mars, Apinya Lertratanakul, Marla Hochfeld, Jorge Esparza Gordillo, Fabiana Farias, Nan Bing, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Riitta Lahesmaa, Glenda Lassi, Hubert Chen, Joanna Betts, Rajashree Mishra, Majd Mouded, Debby Ngo, Felix Vaura, Veikko Salomaa, Kaj Metsärinne, Jenni Aittokallio, Jussi Hernesniemi, Daniel Gordin, Juha Sinisalo, Marja-Riitta Taskinen, Tiinamaija Tuomi, Timo Hiltunen, Amanda Elliott, Mary Pat Reeve, Sanni Ruotsalainen, Benjamin Challis, Audrey Chu, Dermot Reilly, Mike Mendelson, Jaakko Parkkinen, Tuomo Meretoja, Heikki Joensuu, Johanna Mattson, Eveliina Salminen, Annika Auranen, Peeter Karihtala, Päivi Auvinen Klaus Elenius, Esa Pitkänen, Relja Popovic, Jennifer Schutzman, Diptee Kulkarni, Alessandro Porello, Andrey Loboda, Heli Lehtonen, Stefan McDonough, Sauli Vuoti, Kai Kaarniranta, Joni A Turunen, Terhi Ollila, Hannu Uusitalo, Juha Karjalainen, Mengzhen Liu, Stephanie Loomis, Erich Strauss, Hao Chen, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Sirkku Peltonen, Leena Koulu, David Choy, Ying Wu, Pirkko Pussinen, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Vuokko Anttonen, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Oskari Heikinheimo, Ilkka Kalliala, Lauri Aaltonen, Varpu Jokimaa, Marja Vääräsmäki, Outi Uimari, Laure Morin-Papunen, Maarit Niinimäki, Terhi Piltonen, Katja Kivinen, Elisabeth Widen, Taru Tukiainen, Niko Välimäki, Eija Laakkonen, Jaakko Tyrmi, Heidi Silven, Eeva Sliz, Riikka Arffman, Susanna Savukoski, Triin Laisk, Natalia Pujol, Janet Kumar, Iiris Hovatta, Erkki Isometsä, Hanna Ollila, Jaana Suvisaari, Thomas Damm Als, Antti Mäkitie, Argyro Bizaki-Vallaskangas, Sanna Toppila-Salmi, Tytti Willberg, Elmo Saarentaus, Antti Aarnisalo, Elisa Rahikkala, Kristiina Aittomäki, Fredrik Åberg, Mitja Kurki, Aki Havulinna, Juha Mehtonen, Priit Palta, Shabbeer Hassan, Pietro Della, Briotta Parolo, Wei Zhou, Mutaamba Maasha, Susanna Lemmelä, Manuel Rivas, Mari E. Niemi, Aoxing Liu, Arto Lehisto, Andrea Ganna, Vincent Llorens, Henrike Heyne, Joel Rämö, Rodos Rodosthenous, Satu Strausz, Tuula Palotie, Kimmo Palin, Javier Garcia-Tabuenca, Harri Siirtola, Tuomo Kiiskinen, Jiwoo Lee, Kristin Tsuo, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Nina Pitkänen, Samuel Lessard, Clément Chatelain, Perttu Terho, Sirpa Soini, Eero Punkka, Sanna Siltanen, Teijo Kuopio, Anu Jalanko, Huei-Yi Shen, Risto Kajanne, Mervi Aavikko, Henna Palin, Malla-Maria Linna, Masahiro Kanai, L. Elisa Lahtela, Mari Kaunisto, Elina Kilpeläinen, Timo P. Sipilä, Oluwaseun Alexander Dada, Awaisa Ghazal, Anastasia Kytölä, Rigbe Weldatsadik, Kati Donner, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Auli Toivola, Minna Brunfeldt, Hannele Mattsson, Sami Koskelainen, Tero Hiekkalinna, Teemu Paajanen, Kalle Pärn, Mart Kals, Shuang Luo, Shanmukha Sampath Padmanabhuni, Marianna Niemi, Javier Gracia-Tabuenca, Mika Helminen, Tiina Luukkaala, Iida Vähätalo, Jyrki Pitkänen, Sarah Smith, and Tom Southerington

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2–1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2–1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5–3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

Published
2023

23. Three-fold Increased Risk of Death in Budd-Chiari Syndrome Compared to Matched Controls : A Population-based Cohort Study

Author

Fredrik Åberg, Rupesh Rajani, Axel Wester, Linnea Widman, Hannes Hagström, Helsinki University Hospital Area, Clinicum, IV kirurgian klinikka, and HUS Abdominal Center

Subjects
Hepatology, Epidemiology, 3121 General medicine, internal medicine and other clinical medicine, Gastroenterology, Thrombosis, Mortality, Cancer
Abstract

Publisher Copyright: © 2022 AGA Institute Background & Aims: Patients with Budd-Chiari syndrome (BCS) have an elevated risk of overall and liver-specific mortality, but this has not been quantified on a population level nor compared against a matched general population cohort. Methods: We identified all patients in Sweden with a recorded diagnosis of BCS in the Swedish National Patient Register between 1987 and 2016. Patients with BCS were matched for age, sex, and municipality at baseline with up to 10 reference individuals from the general population. Data on cause-specific mortality were obtained from the Causes of Death Register. A Cox regression model was performed to investigate rates of all-cause and cause-specific mortality. Results: A total of 478 patients with BCS were matched with 4603 reference individuals. Of the patients with BCS, 43% were men, the median age was 58 years, 39% had a recorded diagnosis of a precipitating risk factor, and 13% had underlying liver disease. During a follow-up of up to 29 years, 243 (51%) of the patients with BCS died compared with 1346 (29%) of the reference individuals. Overall mortality was 70 per 1000 person-years in patients with BCS compared with 28 per 1000 person-years in reference individuals, translating into an adjusted hazard ratio (aHR) of 3.1 (95% confidence interval [CI], 2.6–3.6). Although liver-related mortality was particularly high (aHR, 47.6; 95% CI, 16.5–137.4), liver disease accounted for only 10% of deaths in BCS. The most common cause of death was cardiovascular disease (aHR, 2.2; 95% CI, 1.7–2.9). Conclusions: Patients with BCS in Sweden had a 3-fold higher risk of death compared with general population reference individuals. Although mortality from liver diseases was high in relative terms, most patients died from cardiovascular causes.

Published
2023

24. Attribution of diabetes to the development of severe liver disease in the general population

Author

Miika Vuorinen, Ville T. Männistö, Veikko Salomaa, Annie Britton, Antti Jula, Satu Männistö, Annamari Lundqvist, Markus Perola, Fredrik Åberg, Clinicum, HUS Abdominal Center, and IV kirurgian klinikka

Subjects
Liver Cirrhosis, RISK, Hepatology, NONALCOHOLIC STEATOHEPATITIS, ALCOHOL-CONSUMPTION, cirrhosis, FATTY LIVER, 3126 Surgery, anesthesiology, intensive care, radiology, FAMILY-HISTORY, MELLITUS, Non-alcoholic Fatty Liver Disease, Risk Factors, CARDIOVASCULAR-DISEASE, HEPATOCELLULAR-CARCINOMA, 3121 General medicine, internal medicine and other clinical medicine, Diabetes Mellitus, Humans, hyperglycaemia, METAANALYSIS, METABOLIC SYNDROME
Abstract

Background and Aims Diabetes is associated with advanced liver disease and predicts mortality regardless of the primary aetiology of the liver disease. Even a family history of diabetes has been linked to advanced liver fibrosis in non-alcoholic fatty liver disease (NAFLD). However, the fraction of liver-related outcomes in the general population that are attributable to diabetes remains unclear. Methods The population attributable fraction (PAF) of diabetes for liver disease as a time-dependent exposure was estimated in the Finnish FINRISK study (n = 28 787) and the British Whitehall II study (n = 7855). We also assessed the predictive ability of a family history of diabetes for liver-related outcomes. Incident diabetes data were from drug purchase/reimbursement and healthcare registries (FINRISK) or follow-up examinations (Whitehall II). Incident severe liver outcomes were identified through linkage with national healthcare registries. Results Diabetes was associated with a two-fold risk of liver-related outcomes in both the FINRISK (HR, 1.92; p < .001) and Whitehall II (HR, 2.37; p < .001) cohorts, and this remained significant after adjusting for multiple confounders. PAF analyses demonstrated that diabetes explained 12-14% of the risk for severe liver-related outcomes after 10 and 20 years of follow-up. Also, maternal diabetes increased the risk of liver-related outcomes in the FINRISK (HR, 1.43; p = .044) and Whitehall II (HR, 2.04; p = .051) cohorts. Conclusion Approximately 12%-14% of severe liver-related outcomes are attributable to diabetes at the population level. The association between maternal diabetes and liver disease might suggest a mitochondrial genetic mechanism.

Published
2022

25. Perioperative kidney injury in liver transplantation: a prospective study with renal histology and measured glomerular filtration rates

Author

Åsa, Norén, Fredrik, Åberg, Johan, Mölne, William, Bennet, Styrbjörn, Friman, and Gustaf, Herlenius

Subjects
Adult, Male, Risk Factors, Calcineurin Inhibitors, Gastroenterology, Humans, Female, Prospective Studies, Acute Kidney Injury, Kidney, Glomerular Filtration Rate, Liver Transplantation
Abstract

Acute kidney injury (AKI) is frequent after liver transplantation (LT), with impact on graft function, morbidity and mortality. Although multifactorial, the pathophysiology of perioperative kidney injury remains unclear. Our aims were to analyze the frequency, evolution and risk factors for kidney impairment during the peri- and early post-operative period.In a prospective, single-center study of 27 adult patients undergoing first single-organ LT, we analyzed measured glomerular filtration rate (mGFR) pre-transplant, at post-operative day (POD) 10, and at 1, 3, 12 and 36 months. Kidney and liver graft biopsies were performed during LT.A median mGFR decline of 45% was detected from pre-transplant to POD 10, correlating strongly with the mGFR evolution from baseline to 12 months (rs = 0.80,The greatest decline in mGFR was evident within 10 days and AKI within hours of LT, irrespective of baseline mGFR and before introduction of calcineurin inhibitors. Very early post-LT kidney injury has substantial consequences for long-term kidney function.

Published
2022

27. PERSISTENT ORAL MUCOSAL LESIONS PRECEDING DIAGNOSIS OF CROHN'S DISEASE AND PRIMARY SCLEROSING CHOLANGITIS A CASE REPORT AND LITERATURE REVIEW

Author

Karita Nylund, Jaana Helenius-Hietala, Fredrik Åberg, Jaana Hagström, and Hellevi Ruokonen

Abstract

Oral mucosal lesions may persist years before diagnosis of inflammatory bowel disease (IBD) and subsequent primary sclerosing cholangitis (PSC). It may be that a dental practitioner may be the first clinician to suspect IBD. Suspect IBD; early referral and close collaboration with a gastroenterologist are recommended.

Published
2023

29. The RETREAT score provides valid predictions regarding hepatocellular carcinoma recurrence after liver transplantation

Author

Andreas Schult, Jenny Abrahamsson, Malin Sternby-Eilard, Magnus Rizell, William Bennet, Fredrik Åberg, Clinicum, HUS Abdominal Center, and IV kirurgian klinikka

Subjects
Male, medicine.medical_specialty, recurrence, Carcinoma, Hepatocellular, medicine.medical_treatment, education, Liver transplantation, Milan criteria, 03 medical and health sciences, 0302 clinical medicine, LT, Risk Factors, Internal medicine, medicine, Humans, Cumulative incidence, HCC, Retrospective Studies, Transplantation, business.industry, Liver Neoplasms, Mean age, Patient survival, Middle Aged, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, digestive system diseases, humanities, Liver Transplantation, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business, prognostic
Abstract

Prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) with knowledge of explant data is important for guiding post-LT surveillance and treatment. The RETREAT score was recently introduced for this purpose, but has not been validated outside the USA. In a retrospective single-center study of 169 consecutive patients undergoing LT in Gothenburg, through 2000-2017 (mean age 57 years, 80% men), there were 34 HCC recurrences during a median 4.6-year follow-up. The 5-year cumulative incidence of HCC recurrence was 0% with RETREAT scores of 0-1 (18%), 11-22% with scores of 2-4 (58%), and 65% with scores of 5-8 (24%). The C-statistic, as a measure of discrimination for prediction of HCC recurrence was 0.762, 0.664, 0.616, and 0.717, for the RETREAT score, Milan criteria, UCSF criteria, and post-MORAL criteria. The RETREAT score had no significant impact on patient survival after HCC recurrence (HR 1.00, P = 0.97). In conclusion, the RETREAT score provided valid predictions of post-LT HCC recurrence in a European setting, with the ability to discriminate between high, intermediate, and low risk for HCC recurrence in a clinically important way. Prognosis after recurrence did not differ according to the RETREAT score in our study.

Published
2021

30. Comparison of various strategies to define the optimal target population for liver fibrosis screening : A population-based cohort study

Author

Fredrik Åberg, Antti Jula, Martti Färkkilä, Veikko Salomaa, Iris Erlund, Satu Männistö, Terhi Vihervaara, Markus Perola, Annamari Lundqvist, Ville Männistö, Clinicum, HUS Abdominal Center, IV kirurgian klinikka, Centre of Excellence in Complex Disease Genetics, University of Helsinki, and Helsinki University Hospital Area

Subjects
Oncology, 3121 General medicine, internal medicine and other clinical medicine, Liver cirrhosis, Gastroenterology, CLivD, Screening, Community, Fibrosis
Abstract

Liver fibrosis screening is recommended in high-risk populations, but the optimal definition of "high risk" remains to be established. We compared the performance of several risk-stratification strategies in a population-based setting.Data were obtained from the Finnish population-based health examination surveys Health 2000 and FINRISK 2002-2012. The Chronic Liver Disease Risk Score (CLivD) was compared to previously published risk-stratification strategies based on elevated liver enzymes, alcohol use, diabetes, fatty liver index, body mass index, and/or metabolic risk factors for their ability to detect either advanced liver fibrosis or incident severe liver events. Advanced fibrosis was defined as an Enhanced Liver Fibrosis (ELFDepending on the cohort, 53%-60% of the population was considered at risk using the CLivD strategy (low-intermediate-high risk, excluding the minimal-risk category), compared to 30%-32% according to the other risk-stratification strategies. The CLivD captured 85%-91% of cases in the population with advanced liver fibrosis and 90% of incident severe liver events within 10 years from baseline. This compares to 33%-44% and 56%-67% captured by the other risk-stratification strategies, respectively. The 10-year cumulative incidence of liver events varied by risk-stratification strategy (1.0%-1.4%).Compared to previously reported traditional risk factor-based strategies, use of the CLivD captured substantially more cases with advanced liver disease in the population and may be superior for targeting further fibrosis screening.

Published
2022

35. Checkpoint Inhibition Causing Complete Remission of Metastatic Combined Hepatocellular-Cholangiocarcinoma after Hepatic Resection

Author

Mats Perman, Joar Svanvik, Per Lindnér, Fredrik Åberg, Liselotte Stén, Magnus Rizell, Lars Ny, and Farida Hashimi

Subjects
0301 basic medicine, Sorafenib, medicine.medical_specialty, Case Report, Pembrolizumab, lcsh:RC254-282, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Immune-related hepatitis, Checkpoint inhibition, medicine, Hepatitis, Cisplatin, business.industry, Combined hepatocellular-cholangiocarcinoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Gemcitabine, digestive system diseases, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Prednisolone, business, Liver cancer, medicine.drug
Abstract

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer, speculated to arise from hepatic progenitor cells, and with a worse prognosis than hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) levels may be one prognostic factor. It has been suggested that checkpoint inhibition might be useful in the treatment of HCC where there is an increased expression of PD-1 and PD-L1 in the microenvironment. Its effect on CHC is unknown. We report a case with a large CHC, which was radically resected, but the 53-year-old female patient subsequently developed pulmonary metastases. Histology demonstrated low-differentiated CHC without microsatellite instability. Treatment with sorafenib was started but was stopped due to angioedema. Under subsequent gemcitabine/cisplatin treatment, the metastatic disease progressed with rising AFP levels. A third-line treatment with pembrolizumab was then started, 2 mg/kg b.w. i.v. every third week for 6 months. This resulted in a radiologically complete remission of the pulmonary metastases and AFP levels were normalized (

Published
2020

36. Health-related quality of life before and after liver transplantation in patients with primary sclerosing cholangitis

Author

Martti Färkkilä, Fredrik Åberg, Harri Sintonen, Marko Vannas, and Helena Isoniemi

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Cholangitis, Sclerosing, Population, Liver transplantation, Gastroenterology, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Risk Factors, Surveys and Questionnaires, Internal medicine, medicine, Humans, In patient, education, Finland, Health related quality of life, education.field_of_study, business.industry, digestive, oral, and skin physiology, Liver failure, Middle Aged, medicine.disease, Liver Transplantation, 3. Good health, Curative treatment, 030220 oncology & carcinogenesis, Quality of Life, Female, 030211 gastroenterology & hepatology, business
Abstract

Background and aims: Liver transplantation (LTx) remains the only curative treatment in patients with primary sclerosing cholangitis (PSC) and liver failure. In Helsinki we have also performed pre-...

Published
2020

37. Drinking and Obesity: Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Interactions

Author

Martti Färkkilä and Fredrik Åberg

Subjects
Male, 0301 basic medicine, Alcoholic liver disease, medicine.medical_specialty, Cirrhosis, Alcohol Drinking, Binge drinking, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, Obesity, Liver Diseases, Alcoholic, Hepatology, business.industry, Fatty liver, medicine.disease, 3. Good health, 030104 developmental biology, Disease Progression, 030211 gastroenterology & hepatology, Steatohepatitis, Metabolic syndrome, business
Abstract

Alcohol and obesity are the main risk factors for alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD), respectively, and they frequently coexist. There are considerable synergistic interaction effects between hazardous alcohol use and obesity-associated metabolic abnormalities in the development and progression of fatty liver disease. Intermittent binge-drinking has been shown to promote steatohepatitis from obesity-related steatosis, and binge-drinking is associated with progression to cirrhosis even when average alcohol intake is within the currently used criteria for a NAFLD diagnosis. Recent longitudinal studies in NAFLD have shown that light-to-moderate alcohol use is associated with fibrosis progression and incident clinical liver disease, suggesting that there is no liver-safe limit of alcohol intake in the presence of NAFLD; a J-shaped association between alcohol and all-cause mortality remains controversial. The interaction effects between alcohol and obesity make the present strict dichotomization of liver disease into alcoholic and NAFLD inappropriate, and require attention in future research, public health policy, individual counseling, and risk stratification.

Published
2020

38. Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies

Author

Ville Männistö, Martti Färkkilä, and Fredrik Åberg

Subjects
Liver Cirrhosis, medicine.medical_specialty, Alcohol Drinking, Drinking, 030508 substance abuse, Medicine (miscellaneous), Binge drinking, Toxicology, Chronic liver disease, Gastroenterology, Binge Drinking, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, NAFLD, Internal medicine, Diabetes mellitus, Nonalcoholic fatty liver disease, medicine, Humans, Obesity, Liver Diseases, Alcoholic, Metabolic Syndrome, Clinical Trials as Topic, business.industry, Liver Diseases, Liver Neoplasms, Fatty liver, Alcoholic, medicine.disease, 3. Good health, Epidemiologic Studies, Psychiatry and Mental health, Metabolic syndrome, 0305 other medical science, Liver cancer, business, 030217 neurology & neurosurgery
Abstract

Coexistence of alcohol use and metabolic risk-the 2 commonest population risk factors for nonviral chronic liver disease-is a growing concern. Clinical evidence and mechanistic evidence point to considerable supraadditive interaction effects for the development and progression of chronic liver disease between hazardous alcohol use and metabolic abnormalities including obesity, diabetes, and the metabolic syndrome (MetS). Intermittent binge drinking once monthly or more often seems to be associated with progression of liver disease even when average alcohol intake is within the currently allowed limits for a diagnosis of nonalcoholic fatty liver disease (NAFLD), and supraadditive interaction between binge drinking and the MetS has been reported. There are contradictory findings regarding the association between low alcohol use and liver steatosis, but, clearly, the mechanisms of alcoholic hepatotoxicity extend beyond simple fat accumulation. The presence of liver steatosis seems to amplify alcoholic hepatotoxicity. Recent longitudinal studies of NAFLD subjects report low alcohol use associated with both increased fibrosis progression and an elevated risk for liver cancer and severe liver disease. There is no clear safe limit of alcohol intake in the presence of NAFLD or metabolic risk. The interaction effects between alcohol and metabolic dysfunction merit increased attention in public health policy, individual counseling, and risk stratification. Based on current evidence, a strict dichotomization of liver disease into either pure alcoholic or nonalcoholic may be inappropriate.

Published
2020

39. Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus

Author

Anna Cederborg, Åsa Norén, Thijs Barten, Björn Lindkvist, William Bennet, Gustaf Herlenius, Maria Castedal, Hanns-Ulrich Marschall, Fredrik Åberg, Clinicum, HUS Abdominal Center, and IV kirurgian klinikka

Subjects
CHRONIC KIDNEY-DISEASE, Adult, Graft Rejection, Kidney, GLOMERULAR-FILTRATION-RATE, GFR, Tacrolimus, Clinical research, Basiliximab, All institutes and research themes of the Radboud University Medical Center, INJURY, Humans, Retrospective Studies, IMMUNOSUPPRESSION, Hepatology, Gastroenterology, DACLIZUMAB ZENAPAX, Antibodies, Monoclonal, Mycophenolic Acid, 3126 Surgery, anesthesiology, intensive care, radiology, Kidney Transplantation, DYSFUNCTION, Liver Transplantation, RECIPIENTS, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], 3121 General medicine, internal medicine and other clinical medicine, Kidney injury, Immunosuppressive Agents
Abstract

Background: Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. im: To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. Methods: In a retrospective cohort study, kidney function was evaluated pre-and postoperatively by mea-sured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 20 0 0 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, tar-get trough levels 10-15 ng/mL, and corticosteroids, n = 203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5-8 ng/mL, delayed until day three, and my-cophenolate mofetil 20 0 0 mg/day, n = 343). Results: Mean mGFR was similar between groups at wait-listing (85.3 vs 84.1 ml/min/1.73m2, p = 0.60), but higher in the revised treatment group at 3 (56.8 vs 63.4 ml/min/1.73m2, p = 0.004) and 12 months post-transplant (60.9 vs 69.7 ml/min/1.73m2, p < 0.001); this difference remained after correcting for mul-tiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p < 0.001), and graft-survival better ( p = 0.01). Conclusion: Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.

Published
2022

40. Global multi-stakeholder endorsement of the MAFLD definition

Author

Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. 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Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. 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Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. 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Hasan, F, Hashim, A, Hassan, I, Hassan, A, Hassan, E, Hassan, M, Hassanin, F, Hassnine, A, Haukeland, J, Hawal, A, He, J, He, Q, He, Y, He, F, Hegazy, M, Hegazy, A, Henegil, O, Hernandez, N, Hernandez-Guerra, M, Higuera-de-la-Tijera, F, Hindy, I, Hirota, K, Ho, L, Hodge, A, Hosny, M, Hou, X, Huang, J, Huang, Y, Huang, Z, Huang, A, Huang, X, Hui-ping, S, Hunyady, B, Hussein, M, Hussein, O, Hussien, S, Ibanez-Samaniego, L, Ibdah, J, Ibrahim, L, Ibrahim, M, Ibrahim, I, Icaza-Chavez, M, Idelbi, S, Idilman, R, Ikeda, M, Indolfi, G, Invernizzi, F, Irshad, I, Isa, H, Iskandar, N, Ismaiel, A, Ismail, M, Ismail, Z, Ismail, F, Iwamoto, H, Jack, K, Jacob, R, Jafarov, F, Jafri, W, Jahshan, H, Jalal, P, Jancoriene, L, Janicko, M, Jayasena, H, Jefferies, M, Jha, V, Ji, F, Ji, Y, Jia, J, Jiang, C, Jiang, N, Jiang, Z, Jin, X, Jin, Y, Jing, X, Jingyu, Q, Jinjolava, M, Jong, F, Jucov, A, Julius, I, Kaddah, M, Kamada, Y, Kamal, A, Kamal, E, Kamel, A, Kao, J, Karin, M, Karlas, T, Kashwaa, M, Katsidzira, L, Kaya, E, Kayasseh, M, Keenan, B, Keklikkiran, C, Keml, W, Khalaf, D, Khalefa, R, Khamis, S, Khater, D, Khattab, H, Khavkin, A, Khlynova, O, Khmis, N, Kobyliak, N, Koffas, A, Koike, K, Kok, K, Koller, T, Komas, N, Korochanskaya, N, Koulla, Y, Koya, S, Kraft, C, Kraja, B, Krawczyk, M, Kuchay, M, Kulkarni, A, Kumar, A, Kumar, M, Lakoh, S, Lam, P, Lan, L, Lange, N, Lankarani, K, Lanthier, N, Lapshyna, K, Lashen, S, Laure, K, Lazebnik, L, Lebrec, D, Lee, S, Lee, W, Lee, Y, Leeming, D, Leite, N, Leon, R, Lesmana, C, Li, J, Li, Q, Li, Y, Li, L, Li, M, Liang, H, Lijuan, T, Lim, S, Lim, L, Lin, S, Lin, H, Lin, R, Lithy, R, Liu, Y, Liu, X, Liu, W, Liu, S, Liu, K, Liu, T, Lonardo, A, Lopez, M, Lopez-Benages, E, Lopez-Jaramillo, P, Lu, H, Lu, L, Lu, Y, Lubel, J, Lui, R, Lupasco, I, Luzina, E, Lv, X, Lynch, K, Ma, H, Machado, M, Maduka, N, Madzharova, K, Magdaong, R, Mahadeva, S, Mahfouz, A, Mahmood, N, Mahmoud, E, Mahrous, M, Maiwall, R, Majeed, A, Majumdar, A, Mak, L, Maklouf, M, Malekzadeh, R, Mandato, C, Mangia, A, Mann, J, Mansour, H, Mansouri, A, Mantovani, A, Mao, J, Maramag, F, Marchesini, G, Marcus, C, Marinho, R, Martinez-Chantar, M, Martins, A, Marwan, R, Mason, K, Masoud, G, Massoud, M, Matamoros, M, Mateos, R, Mawed, A, Mbanya, J, Mbendi, C, Mccolaugh, L, Mcleod, D, Medina, J, Megahed, A, Mehrez, M, Memon, I, Merat, S, Mercado, R, Mesbah, A, Meskini, T, Metwally, M, Metwaly, R, Miao, L, Micah, E, Miele, L, Milivojevic, V, Milovanovic, T, Mina, Y, Mishkovik, M, Mishriki, A, Mitchell, T, Mohamed, A, Mohamed, M, Mohamed, S, Mohammed, S, Mohammed, A, Mohan, V, Mohie, S, Mokhtar, A, Moniem, R, Montilla, M, Morales, J, Morata, M, Moreno-Planas, J, Morise, S, Mosaad, S, Moselhy, M, Mostafa, A, Mostafa, E, Mouane, N, Mousa, N, Moustafa, H, Msherif, A, Muller, K, Munoz, C, Munoz-Urribarri, A, Murillo, O, Mustapha, F, Muzurovic, E, Nabil, Y, Nafady, S, Nagamatsu, A, Nakajima, A, Nakano, D, Nan, Y, Nascimbeni, F, Naseef, M, Nashat, N, Natalia, T, Negro, F, Nersesov, A, Neuman, M, Ng'Wanasayi, M, Ni, Y, Nicoll, A, Niizeki, T, Nikolova, D, Ningning, W, Niriella, M, Nogoibaeva, K, Nordien, R, O Sullivan, C, O'Beirne, J, Obekpa, S, Ocama, P, Ochwoto, M, Ogolodom, M, Ojo, O, Okrostsvaridze, N, Oliveira, C, Omana, R, Omar, O, Omar, H, Omar, M, Omran, S, Omran, R, Osman, M, Owise, N, Owusu-Ansah, T, Padilla- Machaca, P, Palle, S, Pan, Z, Pan, X, Pan, Q, Papaefthymiou, A, Paquissi, F, Par, G, Parkash, A, Payawal, D, Peltekian, K, Peng, X, Peng, L, Peng, Y, Pengoria, R, Perez, M, Perez, J, Perez, N, Persico, M, Pessoa, M, Petta, S, Philip, M, Plaz Torres, M, Polavarapu, N, Poniachik, J, Portincasa, P, Pu, C, Purnak, T, Purwanto, E, Qi, X, Qian, Z, Qiang, Z, Qiao, Z, Qiao, L, Queiroz, A, Rabiee, A, Radwan, M, Rahetilahy, A, Ramadan, Y, Ramadan, D, Ramli, A, Ramm, G, Ran, A, Rankovic, I, Rao, H, Raouf, S, Ray, S, Reau, N, Refaat, A, Reiberger, T, Remes-Troche, J, Reyes, E, Richardson, B, Ridruejo, E, Riestra Jimenez, S, Rizk, I, Roberts, S, Roblero, J, Robles, J, Rockey, D, Rodriguez, M, Rodriguez Hernandez, H, Roman, E, Romeiro, F, Romeo, S, Rosales-Zabal, J, Roshdi, G, Rosso, N, Ruf, A, Ruiz, P, Runes, N, Ruzzenente, A, Ryan, M, Saad, A, Sabbagh, E, Sabbah, M, Saber, S, Sabrey, R, Sabry, R, Saeed, M, Said, D, Said, E, Sakr, M, Salah, Y, Salama, R, Salama, A, Saleh, H, Saleh, A, Salem, A, Salifou, A, Salih, A, Salman, A, Samouda, H, Sanai, F, Sanchez-Avila, J, Sanker, L, Sano, T, Sanz, M, Saparbu, T, Sawhney, R, Sayed, F, Sayed, S, Sayed, A, Sayed, M, Sebastiani, G, Secadas, L, Sediqi, K, Seif, S, Semida, N, Senates, E, Serban, E, Serfaty, L, Seto, W, Sghaier, I, Sha, M, Shabaan, H, Shalaby, L, Shaltout, I, Sharara, A, Sharma, V, Shawa, I, Shawkat, A, Shawky, N, Shehata, O, Sheils, S, Shewaye, A, Shi, G, Shi, J, Shimose, S, Shirono, T, Shou, L, Shrestha, A, Shui, G, Sievert, W, Sigurdardottir, S, Sira, M, Siradj, R, Sison, C, Smyth, L, Soliman, R, Sollano, J, Sombie, R, Sonderup, M, Sood, S, Soriano, G, Stedman, C, Stefanyuk, O, Stimac, D, Strasser, S, Strnad, P, Stuart, K, Su, W, Su, M, Sumida, Y, Sumie, S, Sun, D, Sun, J, Suzuki, H, Svegliati-Baroni, G, Swar, M, Taharboucht, S, Taher, Z, Takamura, S, Tan, L, Tan, S, Tanwandee, T, Tarek, S, Tatiana, G, Tavaglione, F, Tecson, G, Tee, H, Teschke, R, Tharwat, M, Thong, V, Thursz, M, Tine, T, Tiribelli, C, Tolmane, I, Tong, J, Tongo, M, Torkie, M, Torre, A, Torres, E, Trajkovska, M, Treeprasertsuk, S, Tsutsumi, T, Tu, T, Tur, J, Turan, D, Turcan, S, Turkina, S, Tutar, E, Tzeuton, C, Ugiagbe, R, Uygun, A, Vacca, M, Vajro, P, Van der Poorten, D, Van Kleef, L, Vashakidze, E, Velazquez, C, Velazquez, M, Vento, S, Verhoeven, V, Vespasiani-Gentilucci, U, Vethakkan, S, Vilaseca, J, Vitek, L, Volkanovska, A, Wallace, M, Wan, W, Wang, Y, Wang, X, Wang, C, Wang, M, Wangchuk, P, Weltman, M, White, M, Wiegand, J, Wifi, M, Wigg, A, Wilhelmi, M, William, R, Wittenburg, H, Wu, S, Wubeneh, A, Xia, H, Xiao, J, Xiao, X, Xiaofeng, W, Xiong, W, Xu, L, Xu, J, Xu, W, Xu, K, Xu, Y, Xu, S, Xu, M, Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease

Subjects
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Hepatology, Non-alcoholic Fatty Liver Disease, NAFLD, consensu, Gastroenterology, MAFLD, definition, Humans, MAFLD, NAFLD, Human medicine
Abstract

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Published
2022

41. Changes over time in the Chronic Liver Disease risk score predict liver-related outcomes: longitudinal analysis of the Whitehall II study

Author

Fredrik Åberg, Annie Britton, and Panu K. Luukkonen

Subjects
Gastroenterology
Abstract

The Chronic Liver Disease (CLivD) risk score was recently shown to predict future advanced liver disease in the general population. We here investigated the impact of individual CLivD-score changes over time. Participants of both phase 3 (baseline, 1991–1994) and phase 5 (follow-up, 1997–1999) examinations of the Whitehall II study were followed for liver-related outcomes (hospitalization, cancer, death) until December 2019 through linkage with electronic healthcare registers. The CLivD score, its modifiable components (alcohol use, waist–hip ratio [WHR], diabetes, and smoking), and their individual changes were studied. Among 6590 adults (mean age 50 years, 30% women) with a median 21-year follow-up, there were 80 liver outcomes. A rise in the CLivD score between baseline and follow-up examinations significantly increased the risk for liver-related outcomes (adjusted hazard ratio [aHR] 1.62, 95% confidence interval [CI] 1.01–2.60), more so in subjects with baseline intermediate–high CLivD scores (HR 2.4 for a CLivD-change) compared to minimal-low CLivD scores. Adverse changes over time in alcohol use and WHR, and new-onset diabetes also predicted liver outcomes. In contrast to WHR, changes in body weight (kg) showed a U-shaped association with liver outcomes. A change in the CLivD score over time corresponds to a true change in the risk for liver-related outcomes, suggesting the usefulness of the CLivD score for assessing response to liver-directed lifestyle interventions. Changes in WHR predicted liver outcomes better than changes in body weight or waist circumference, independent of body mass index, supporting the WHR in assessing risk for future liver disease.

Published
2022
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45. Incidence of liver-related morbidity and mortality in a population cohort of non-alcoholic fatty liver disease

Author

Jouko Sundvall, Annamari Lundqvist, Markus Perola, Satu Männistö, Martti Färkkilä, Veikko Salomaa, Ville Männistö, Antti Jula, Iris Erlund, Fredrik Åberg, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Department of Medicine, Clinicum, Gastroenterologian yksikkö, and IV kirurgian klinikka

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, FIBROSIS STAGE, Population, PROGRESSION, HOSPITAL DISCHARGE REGISTER, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, LONG-TERM OUTCOMES, Risk Factors, Internal medicine, NAFLD, ALCOHOLIC STEATOHEPATITIS PATIENTS, Medicine, Humans, Cumulative incidence, 030212 general & internal medicine, education, METAANALYSIS, Aged, RISK, education.field_of_study, Hepatology, business.industry, Incidence (epidemiology), Incidence, cirrhosis, Fatty liver, advanced liver disease, Absolute risk reduction, non-alcoholic fatty liver disease, Middle Aged, medicine.disease, CANCER, 3. Good health, Relative risk, 3121 General medicine, internal medicine and other clinical medicine, 030211 gastroenterology & hepatology, Female, business, Kidney disease
Abstract

Background & Aims Non-alcoholic fatty liver disease (NAFLD) increases morbidity and mortality. However, patients in biopsy-based cohorts are highly selected and the absolute risks of liver- and non-liver outcomes in NAFLD in population remains undefined. We analysed both liver-related and non-liver-related outcomes in Finnish population cohorts of NAFLD. Methods We included 10 993 individuals (6707 men, mean age 53.3 +/- 12.6 years) with NAFLD (fatty liver index >= 60) from the Finnish population-based FINRISK and Health 2000 studies. Liver fibrosis was assessed by the dAAR score, and genetic risk by a recent polygenic risk score (PRS-5). Incident liver-related outcomes, cardiovascular disease (CVD), cancer and chronic kidney disease (CKD) were identified through linkage with national registries. Results Mean follow-up was 12.1 years (1128 069 person-years). The crude incidence rate of liver-related outcomes in NAFLD was 0.97/1000 person-years. The cumulative incidence increased with age, being respectively 2.4% and 1.5% at 20 years in men and women aged 60 years at baseline, while the relative risks for CVD and cancer were 9-16 times higher. The risk of CKD exceeded that of liver outcomes at a baseline age around 50 years. 20-year cumulative incidence of liver-related outcomes was 4.3% in the high, and 1.5% in the low PRS-5 group. The dAAR score associated with liver outcomes, but not with extra-hepatic outcomes. Conclusion The absolute risk of liver-related outcomes in NAFLD is low, with much higher risk of CVD and cancer, emphasizing the need for more individualized and holistic risk-stratification in NAFLD.

Published
2021

46. The value of the Advanced Lung Cancer Inflammation Index (ALI) in assessing the prognosis of patients with hepatocellular carcinoma treated with camrelizumab: a retrospective cohort study

Author

Qian, Li, Fei, Ma, Diamantis I, Tsilimigras, Fredrik, Åberg, and Ju Feng, Wang

Subjects
General Medicine
Abstract

The Advanced Lung Cancer Inflammation Index (ALI) is considered a useful prognostic biomarker for clinical outcome in patients with malignancy. However, the prognostic value of ALI in patients with advanced hepatocellular carcinoma (HCC) is unclear. In this study we assessed the prognostic value of the ALI in patients with HCC treated with camrelizumab.This retrospective study analyzed patients with advanced hepatocellular carcinoma treated with the ICI, camrelizumab alone or in combination at Henan Cancer Hospital from January 2017 to January 2020. Sixty-five patients were finally screened for at least 2 years of follow-up according to the inclusion criteria, with no significant differences in patient baseline data. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off point for the ALI which was compared to other clinical indicators for predicting survival. A Kaplan-Meier analysis and Cox proportional analysis were conducted to examine the association between the ALI and patient prognosis.The median overall survival (OS) for the overall group of patients was 383 days, the area under the curve for ALI was 0.815 and the optimal cut-off value for predicting OS was 34.65. The median OS for patients with an ALI score ≤34.65 was 336 days and that for patients with an ALI score34.65 was 524 days. The univariate analysis showed that the Eastern Cooperative Oncology Group (ECOG) score, aspartate aminotransferase (AST) level, and the ALI score predicted OS. The multivariate analysis showed that the ALI score was an independent prognostic factor of OS in patients with advanced HCC who had been treated with immunotherapy [hazard ratio (HR) =0.285, 95% confidence interval (CI): 0.097-0.833, P=0.022]. A nomogram that included ALI performed well relative to the prediction of prognosis after immunotherapy for patients with advanced liver cancer.The ALI may be a new prognostic marker in patients with advanced HCC undergoing immunotherapy.

Published
2022

47. Waist and hip circumference are independently associated with the risk of liver disease in population-based studies

Author

Antti Jula, Annamari Lundqvist, Markku Nissinen, Veikko Salomaa, Fredrik Åberg, Satu Männistö, Markus Perola, Oscar Danielsson, HUS Abdominal Center, Gastroenterologian yksikkö, Clinicum, and IV kirurgian klinikka

Subjects
Male, medicine.medical_specialty, Waist, BODY-COMPOSITION, anthropometric measures, Body Mass Index, SKELETAL-MUSCLE MASS, sarcopenia, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Waist–hip ratio, RATIO, Risk Factors, Internal medicine, fat, Medicine, Humans, 030304 developmental biology, NORMAL-WEIGHT, 0303 health sciences, INSULIN-RESISTANCE, Hepatology, business.industry, Proportional hazards model, Hip Circumference, Waist-Hip Ratio, CARDIOVASCULAR RISK, PREDICTS DEVELOPMENT, Liver Diseases, FATTY LIVER, Anthropometry, medicine.disease, 3. Good health, Cross-Sectional Studies, Sarcopenia, OBESITY, 3121 General medicine, internal medicine and other clinical medicine, 030211 gastroenterology & hepatology, Female, Waist Circumference, business, Body mass index, WHOLE-BODY
Abstract

BACKGROUND & AIMS While several anthropometric measures predict liver disease, the waist-hip ratio (WHR) has shown superiority in previous studies. We analysed independent and joint associations of waist circumference (WC) and hip circumference (HC) with liver disease and liver-related risk factors. METHODS Cross-sectional study (n = 6619) and longitudinal cohort (n = 40 923) comprised individuals from Health 2000 and FINRISK 1992-2012 studies. Prevalent and viral liver diseases were excluded. Longitudinal cohort was linked with national healthcare registers for severe incident liver disease. Linear regression and Cox proportional hazards models were used to analyse anthropometric, lifestyle, metabolic and bioimpedance-related parameters; liver enzymes; and 59 liver-related genetic risk variants. RESULTS WC and HC showed independent and opposite associations with both liver enzymes and incident liver disease among men (HR for liver disease: WC, 1.07, 95% CI 1.03-1.11; HC, 0.96, 95% CI 0.92-0.99; P-range .04 to

Published
2021

48. Serum lipopolysaccharides predict advanced liver disease in the general population

Author

Annamari Lundqvist, Pirkko J. Pussinen, Fredrik Åberg, Ville Männistö, Veikko Salomaa, Liisa Valsta, Satu Männistö, Martti Färkkilä, Markus Perola, Antti Jula, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Department of Medicine, Gastroenterologian yksikkö, University of Helsinki, HUS Head and Neck Center, Department of Oral and Maxillofacial Diseases, and IV kirurgian klinikka

Subjects
medicine.medical_specialty, Cirrhosis, education, Population, Type 2 diabetes, Chronic liver disease, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, Genetics, Internal Medicine, medicine, Immunology and Allergy, Gut, lcsh:RC799-869, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, education.field_of_study, Hepatology, business.industry, Hazard ratio, medicine.disease, Endotoxemia, 3. Good health, Hospitalization, 3121 General medicine, internal medicine and other clinical medicine, Attributable risk, 030211 gastroenterology & hepatology, lcsh:Diseases of the digestive system. Gastroenterology, Metabolic syndrome, business, Research Article
Abstract

Background & Aims Gut-derived endotoxemia has been implicated in the development of chronic liver disease, but its relevance at the population level remains unclear. We analyzed whether endotoxemia is associated with incident advanced liver disease in the general population. Methods Serum lipopolysaccharide (LPS) was measured in 6,727 (3,455 male and 3,272 female, mean age 53.4 ± 10.9 years, mean body mass index 27.2 ± 4.5) individuals participating in the Finnish population-based health examination survey FINRISK 1997. Data were linked with electronic health registers for incident advanced liver disease (hospitalization, cancer or death related to liver disease). During a mean follow-up of 16.3 ± 3.8 years (109,282 person-years), 86 liver events occurred. Univariate and multivariate Cox regression, and Kaplan-Meier analyses were performed. Results Serum LPS predicted incident advanced liver disease with a hazard ratio per 1 SD of 1.41 (95% CI 1.24–1.59; p ≪0.001) when adjusted for age, sex, gamma-glutamyltransferase, metabolic syndrome, alcohol use, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M, waist-hip ratio and type 2 diabetes. This association remained robustly significant in additional multivariate analyses with various levels of adjustment. The association was accentuated among carriers of the PNPLA3 risk variant. The population attributable fraction of the highest LPS tertile for liver events was 29.7%. However, LPS was not associated with all-cause mortality. Conclusion Serum LPS is associated with hospitalization, cancer or death related to liver disease in the general population, with the highest tertile potentially accounting for 30% of the risk of liver disease. Lay summary Lipopolysaccharide, a gut-derived bacterial endotoxin, has been implicated in the development of chronic liver disease, but its relevance at the population level remains unclear. We found that serum lipopolysaccharide levels were associated with incident advanced liver disease in the general population, with the highest tertile accounting for up to 30% of the risk of hospitalization, cancer or death related to liver disease., Graphical abstract Unlabelled Image, Highlights • Serum LPS was associated with incident advanced liver disease in the general population. • LPS was associated with liver-related risk of hospitalization, cancer or death. • The highest LPS tertile may account for up to 30% of the risk of incident liver disease. • The risk of liver disease was accentuated among carriers of the PNPLA3 I143M. • Serum LPS was not associated with all-cause mortality.

Published
2019

49. Genetic and lifestyle risk factors for advanced liver disease among men and women

Author

Perttu Sahlman, Pauli Puukka, Annamari Lundqvist, Antti Jula, Veikko Salomaa, Liisa Valsta, Markus Perola, Markku Nissinen, Fredrik Åberg, Satu Männistö, Martti Färkkilä, HUS Abdominal Center, Gastroenterologian yksikkö, Department of Medicine, INDIVIDRUG - Individualized Drug Therapy, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Staff Services, and IV kirurgian klinikka

Subjects
Male, medicine.medical_specialty, Cirrhosis, ALCOHOL-CONSUMPTION, Population, Binge drinking, 03 medical and health sciences, Liver disease, Sex Factors, 0302 clinical medicine, DRINKING, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, medicine, Humans, FIBROSIS, Risk factor, education, Life Style, Liver Diseases, Alcoholic, METAANALYSIS, METABOLIC SYNDROME, education.field_of_study, Hepatology, business.industry, MORTALITY, Hazard ratio, Age Factors, Gastroenterology, ASSOCIATION, medicine.disease, 3. Good health, BODY-MASS INDEX, Haplotypes, OBESITY, 3121 General medicine, internal medicine and other clinical medicine, 030220 oncology & carcinogenesis, Phospholipases A2, Calcium-Independent, Female, 030211 gastroenterology & hepatology, Metabolic syndrome, Alcohol, business, Body mass index
Abstract

Background and Aim Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption. Methods Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41 260 individuals. Pattern of alcohol consumption and metabolic, lifestyle-related, and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer, or death as end-point. Viral liver diseases were excluded. Results A total of 355 liver events occurred during the mean 12.4-year follow-up (511 789 person-years). In the multivariate model, age (hazard ratio [HR] 1.03, P = 0.0083 for men; HR 1.04, P = 0.0198 for women), waist-to-hip ratio (WHR) (HR 1.52, P = 0.0006 for men; HR 1.58, P = 0.0167 for women), patatin-like phospholipase-containing domain 3 mutations (HR 1.9, P = 0.024 for men; HR 2.7, P = 0.0109 for women), and weekly binge drinking (HR 2.4, P = 0.0024 for men; HR 7.4, P

Published
2019

50. Association of Clinical Factors with the Costs of Kidney Transplantation in the Current Era

Author

Taru K. Lehtonen, Timo Isola, Marko Lempinen, Fredrik Åberg, Ilkka Helanterä, Helena Isoniemi, HUS Abdominal Center, Nefrologian yksikkö, University of Helsinki, IV kirurgian klinikka, HUS Helsinki and Uusimaa Hospital District, and Clinicum

Subjects
Adult, Male, medicine.medical_specialty, IMPACT, medicine.medical_treatment, Delayed Graft Function, 030230 surgery, Kidney transplant, 03 medical and health sciences, 0302 clinical medicine, Highly sensitized, Renal Dialysis, Internal medicine, DIALYSIS, Health care, medicine, Humans, Risk factor, health care economics and organizations, Dialysis, Kidney transplantation, Aged, Original Paper, Transplantation, business.industry, MORTALITY, Health Care Costs, General Medicine, Middle Aged, CARE, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, Kidney Transplantation, 3. Good health, RECIPIENTS, Costs and Cost Analysis, Kidney Failure, Chronic, Female, business, 030217 neurology & neurosurgery
Abstract

BACKGROUND Kidney transplantation is reported to save costs compared to maintenance dialysis. We analyzed the current actual costs of kidney transplantation compared to dialysis, and analyzed risk factors for higher costs after transplantation. MATERIAL AND METHODS Altogether, 338 kidney transplant recipients between 2009 and 2014 were included in this study. All individual-level cost data from specialized health care and data from all reimbursed medication and travel costs were acquired from official records. Cost data were compared before and after transplantation within the same patients starting from dialysis initiation and continued until the end of follow-up at the end of 2015. RESULTS Total annual costs were median 53 275 EUR per patient in dialysis, 59 583 EUR for the first post-transplantation year (P

Published
2019

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