401 results on '"Arthur J. McCullough"'
Search Results
2. Differential role of MLKL in alcohol-associated and non–alcohol-associated fatty liver diseases in mice and humans
- Author
-
Tatsunori Miyata, Xiaoqin Wu, Xiude Fan, Emily Huang, Carlos Sanz-Garcia, Christina K. Cajigas-Du Ross, Sanjoy Roychowdhury, Annette Bellar, Megan R. McMullen, Jaividhya Dasarathy, Daniela S. Allende, Joan Caballeria, Pau Sancho-Bru, Craig J. McClain, Mack Mitchell, Arthur J. McCullough, Svetlana Radaeva, Bruce Barton, Gyongyi Szabo, Srinivasan Dasarathy, and Laura E. Nagy
- Subjects
Hepatology ,Inflammation ,Medicine - Abstract
Hepatocellular death contributes to progression of alcohol–associated (ALD-associated) and non–alcohol-associated (NAFL/NASH) liver diseases. However, receptor-interaction protein kinase 3 (RIP3), an intermediate in necroptotic cell death, contributes to injury in murine models of ALD but not NAFL/NASH. We show here that a differential role for mixed-lineage kinase domain–like protein (MLKL), the downstream effector of RIP3, in murine models of ALD versus NAFL/NASH and that RIP1-RIP3-MLKL can be used as biomarkers to distinguish alcohol-associated hepatitis (AH) from NASH. Phospho-MLKL was higher in livers of patients with NASH compared with AH or healthy controls (HCs). MLKL expression, phosphorylation, oligomerization, and translocation to plasma membrane were induced in WT mice fed diets high in fat, fructose, and cholesterol but not in response to Gao-binge (acute on chronic) ethanol exposure. Mlkl–/– mice were not protected from ethanol-induced hepatocellular injury, which was associated with increased expression of chemokines and neutrophil recruitment. Circulating concentrations of RIP1 and RIP3, but not MLKL, distinguished patients with AH from HCs or patients with NASH. Taken together, these data indicate that MLKL is differentially activated in ALD/AH compared with NAFL/NASH in both murine models and patients. Furthermore, plasma RIP1 and RIP3 may be promising biomarkers for distinguishing AH and NASH.
- Published
- 2021
- Full Text
- View/download PDF
3. The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue
- Author
-
Rebecca C. Schugar, Diana M. Shih, Manya Warrier, Robert N. Helsley, Amy Burrows, Daniel Ferguson, Amanda L. Brown, Anthony D. Gromovsky, Markus Heine, Arunachal Chatterjee, Lin Li, Xinmin S. Li, Zeneng Wang, Belinda Willard, YongHong Meng, Hanjun Kim, Nam Che, Calvin Pan, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Richard E. Morton, Carl D. Langefeld, Swapan K. Das, Lawrence L. Rudel, Nizar Zein, Arthur J. McCullough, Srinivasan Dasarathy, W.H. Wilson Tang, Bernadette O. Erokwu, Chris A. Flask, Markku Laakso, Mete Civelek, Sathyamangla V. Naga Prasad, Joerg Heeren, Aldons J. Lusis, Stanley L. Hazen, and J. Mark Brown
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Summary: Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel. Further, antisense oligonucleotide-mediated knockdown or genetic deletion of the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) conferred protection against obesity in mice. Complimentary mouse and human studies indicate a negative regulatory role for FMO3 in the beiging of white adipose tissue. Collectively, our studies reveal a link between the TMAO-producing enzyme FMO3 and obesity and the beiging of white adipose tissue. : Microbes resident in the human intestine represent a key transmissible environmental factor contributing to obesity and related disorders. Schugar et al. now show that expression of the TMAO-producing enzyme FMO3 is linked to obesity and energy expenditure in both mice and humans. Keywords: microbiota, nutrition, obesity, diabetes, adipose, flavin-containing monooxygenase 3, FMO3
- Published
- 2017
- Full Text
- View/download PDF
4. Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
- Author
-
Yana Sandlers, Rohan R. Shah, Ryan W. Pearce, Jaividhya Dasarathy, Arthur J. McCullough, and Srinivasan Dasarathy
- Subjects
plasma krebs cycle intermediates ,nonalcoholic fatty liver disease (nafld) ,mitochondrial dysfunction ,Medicine - Abstract
Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD (n = 22) and matched control (n = 67) cohorts. Circulating levels of isocitrate and citrate were significantly (p < 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson’s correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted.
- Published
- 2020
- Full Text
- View/download PDF
5. Accuracy of ultrasonographic fatty liver index using point-of-care ultrasound in stratifying non-alcoholic fatty liver disease patients
- Author
-
Achuthan Sourianarayanane and Arthur J McCullough
- Subjects
Hepatology ,Gastroenterology - Published
- 2023
6. Nonalcoholic Steatohepatitis Decompensation and Portal Pressures
- Author
-
Achuthan Sourianarayanane and Arthur J. McCullough
- Subjects
Hepatology ,Gastroenterology - Published
- 2023
7. Development of machine learning model to detect fibrotic non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease
- Author
-
Parikshit Bansal, Daniel Rozenbaum, Manik Aggarwal, Arthur J. McCullough, Agam Bansal, and Rajat Garg
- Subjects
Adult ,Male ,medicine.medical_specialty ,Hepatology ,business.industry ,Fatty liver ,Gastroenterology ,Non alcoholic ,Disease ,Middle Aged ,medicine.disease ,Fibrosis ,Machine Learning ,Cross-Sectional Studies ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Humans ,Female ,In patient ,Steatohepatitis ,business - Published
- 2021
8. Hepatocellular carcinoma in nonalcoholic fatty liver disease with or without cirrhosis: a population-based study
- Author
-
Kanokporn Pinyopornpanish, Arthur J. McCullough, Mohannad Abou Saleh, Srinivasan Dasarathy, Emad Mansoor, Chaisiri Angkurawaranon, Kanokwan Pinyopornpanish, and George Khoudari
- Subjects
Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Disease ,RC799-869 ,Gastroenterology ,Non-alcoholic Fatty Liver Disease ,Liver neoplasms ,Diabetes mellitus ,Internal medicine ,Fatty liver ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Aged ,business.industry ,Research ,Incidence ,General Medicine ,Hepatology ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,digestive system diseases ,Population based study ,Hepatocellular carcinoma ,Liver cirrhosis ,business - Abstract
Background There are limited data regarding the factors associated with hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. We sought to determine the prevalence and factors associated with HCC in NAFLD patients with or without cirrhosis. Methods Adults with NAFLD (June 2015 to May 2020) were identified using the electronic health record database (Explorys Inc, Cleveland, OH) from 26 major integrated US healthcare systems. The prevalence of HCC was calculated. Multivariable analyses adjusting for covariates were performed to evaluate the associated risk factors and the presence of HCC. Results A total of 392,800 NAFLD patients were identified. Among 1110 patients with HCC, 170 (15.3%) had no cirrhosis. The prevalence of HCC in non-cirrhotic and cirrhotic NAFLD patients was 4.6/10,000 persons (95% CI 3.9–5.3), and 374.4/10,000 persons (95% CI 350.9–398.8), respectively. Age > 65 years (adjusted OR; 3.37, 95% CI 2.47–4.59), ever had elevated alanine aminotransferase (2.69; 2.14–3.37), male gender (2.57; 1.88–3.49), smoker (1.75; 1.23–2.49), and diabetes (1.56; 1.15–2.11) were associated with HCC in non-cirrhotic NAFLD (all P 65 years, male gender, Hispanic race, elevated alanine aminotransferase, diabetes and smoker (all P Conclusions These data identified the major risk factors for the development of HCC in NAFLD patients. In the non-cirrhotics, older male patients with smoking history, diabetes and an elevated alanine aminotransferase had highest risk and may need increased judicious monitoring.
- Published
- 2021
9. Non-Alcoholic Fatty Liver Disease: A Practical Guide
- Author
-
Geoffrey C. Farrell, Arthur J. McCullough, Christopher P. Day, Geoffrey C. Farrell, Arthur J. McCullough, Christopher P. Day and Geoffrey C. Farrell, Arthur J. McCullough, Christopher P. Day, Geoffrey C. Farrell, Arthur J. McCullough, Christopher P. Day
- Published
- 2013
10. Macrophage-derived MLKL in alcohol-associated liver disease: Regulation of phagocytosis
- Author
-
Xiaoqin Wu, Xiude Fan, Megan R. McMullen, Tatsunori Miyata, Adam Kim, Vai Pathak, Jianguo Wu, Le Z. Day, Josiah E. Hardesty, Nicole Welch, Jaividhya Dasarathy, Daniela S. Allende, Arthur J. McCullough, Jon M. Jacobs, Daniel M. Rotroff, Srinivasan Dasarathy, and Laura E. Nagy
- Subjects
Hepatology - Abstract
Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3)Bone marrow transplants between MlklTogether, these data indicate that myeloid MLKL restricts ethanol-induced liver inflammation and injury by regulating hepatic immune cell homeostasis and macrophage phagocytosis.
- Published
- 2022
11. Diagnostic and Prognostic Significance of Complement in Patients With Alcohol‐Associated Hepatitis
- Author
-
Emily Huang, Gyongyi Szabo, Mack C. Mitchell, Kyle L. Poulsen, Bruce A. Barton, Arthur J. McCullough, Rebecca L. McCullough, Daniel M. Rotroff, Srinivasan Dasarathy, Annette Bellar, Laura E. Nagy, Adam Kim, Craig J. McClain, Xiude Fan, and Svetlana Radaeva
- Subjects
Adult ,Male ,0301 basic medicine ,Complement factor I ,Article ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,medicine ,Humans ,Hepatitis ,Hepatology ,biology ,Hepatitis, Alcoholic ,business.industry ,Case-control study ,Complement C5 ,Complement C4 ,Complement C3 ,Complement System Proteins ,Complement C2 ,Middle Aged ,Prognosis ,medicine.disease ,Complement (complexity) ,Complement system ,030104 developmental biology ,Case-Control Studies ,Immunology ,Alternative complement pathway ,biology.protein ,Complement Factor D ,Female ,030211 gastroenterology & hepatology ,Factor D ,business ,Biomarkers ,Complement Factor B - Abstract
Background and aims Given the lack of effective therapies and high mortality in acute alcohol-associated hepatitis (AH), it is important to develop rationally designed biomarkers for effective disease management. Complement, a critical component of the innate immune system, contributes to uncontrolled inflammatory responses leading to liver injury, but is also involved in hepatic regeneration. Here, we investigated whether a panel of complement proteins and activation products would provide useful biomarkers for severity of AH and aid in predicting 90-day mortality. Approach and results Plasma samples collected at time of diagnosis from 254 patients with moderate and severe AH recruited from four medical centers and 31 healthy persons were used to quantify complement proteins by enzyme-linked immunosorbent assay and Luminex arrays. Components of the classical and lectin pathways, including complement factors C2, C4b, and C4d, as well as complement factor I (CFI) and C5, were reduced in AH patients compared to healthy persons. In contrast, components of the alternative pathway, including complement factor Ba (CFBa) and factor D (CFD), were increased. Markers of complement activation were also differentially evident, with C5a increased and the soluble terminal complement complex (sC5b9) decreased in AH. Mannose-binding lectin, C4b, CFI, C5, and sC5b9 were negatively correlated with Model for End-Stage Liver Disease score, whereas CFBa and CFD were positively associated with disease severity. Lower CFI and sC5b9 were associated with increased 90-day mortality in AH. Conclusions Taken together, these data indicate that AH is associated with a profound disruption of complement. Inclusion of complement, especially CFI and sC5b9, along with other laboratory indicators, could improve diagnostic and prognostic indications of disease severity and risk of mortality for AH patients.
- Published
- 2020
12. IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis
- Author
-
Gyongyi Szabo, Mack Mitchell, Craig J. McClain, Srinivasan Dasarathy, Bruce Barton, Arthur J. McCullough, Laura E. Nagy, Aimee Kroll‐Desrosiers, David Tornai, Hyesung Alice Min, Svetlana Radaeva, M. E. Blair Holbein, Lisa Casey, and Jennifer Cuthbert
- Subjects
Adult ,Male ,Hepatology ,Hepatitis, Alcoholic ,Receptors, Interleukin-1 ,Middle Aged ,Methylprednisolone ,Severity of Illness Index ,End Stage Liver Disease ,Interleukin 1 Receptor Antagonist Protein ,Zinc ,Adrenal Cortex Hormones ,Humans ,Female ,Pentoxifylline - Abstract
Patients with severe alcohol-associated hepatitis (AH) have high mortality. Corticosteroids improve survival only for 30 days. We targeted inflammation, cellular injury, and gut leakiness in a randomized clinical trial comparing combination therapy to corticosteroids on 180-day survival.Subjects with a clinical diagnosis of severe AH (Model for End-Stage Liver Disease [MELD]20, Maddrey discriminant function [MDF]32) were randomized to receive methylprednisolone (PRED; 28 days) or a combination of anakinra (14 days) plus pentoxifylline (28 days) plus zinc (COMB; 180 days). The primary endpoint was survival at 180 days. The study was designed in 2013, initiated in October 2014, and completed in March 2018. Five hundred patients were screened to randomize 104 subjects with a clinical diagnosis of AH with a MELD score20. Fifty-three patients were randomized into the COMB and 50 to the PRED treatment; 1 dropped out of the study before randomization. Mean age was 45.3 ± 10.4 years; 60.6% were males, 92.3% White, and mean MELD 25.7 ± 3.9. Kaplan-Meier survival estimate at 180 days was 67.9% in COMB and 56% in PRED (HR = 0.69; p = 0.3001). Survival curves separated by 90 days (COMB, 69.8%; PRED, 58.0%; HR = 0.69; p = 0.28). Survival at 28 days was similar between the COMB (83.4%) and PRED groups (81.2%; HR = 0.91; p = 0.85). There were no unexpected serious adverse events, and incidence of infection was comparable between groups. MELD 20-25 and MELD26 strata showed nonsignificant treatment effects in favor of COMB.A combination of anakinra, pentoxifylline plus zinc provides similar survival benefits compared to corticosteroid therapy in severe AH.
- Published
- 2022
13. Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice
- Author
-
Anagha Kadam, Tatsunori Miyata, Robert N Helsley, Venkateshwari Varadharajan, Naseer Sangwan, Emily C Huang, Rakhee Banerjee, Amanda L Brown, Kevin K Fung, William J Massey, Chase Neumann, Danny Orabi, Lucas J Osborn, Rebecca C Schugar, Megan R McMullen, Annette Bellar, Kyle L Poulsen, Adam Kim, Vai Pathak, Marko Mrdjen, James T Anderson, Belinda Willard, Craig J McClain, Mack Mitchell, Arthur J McCullough, Svetlana Radaeva, Bruce Barton, Gyongyi Szabo, Srinivasan Dasarathy, Jose Carlos Garcia-Garcia, Daniel M Rotroff, Daniela S Allende, Zeneng Wang, Stanley L Hazen, Laura E Nagy, and Jonathan Mark Brown
- Subjects
QH301-705.5 ,Science ,microbiome ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,Hepatitis ,Methylamines ,Mice ,Random Allocation ,Animals ,Biology (General) ,General Immunology and Microbiology ,Bacteria ,Ethanol ,General Neuroscience ,General Medicine ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,nutrition ,Chemical and Drug Induced Liver Injury, Chronic ,Medicine ,Female ,liver disease ,metabolism - Abstract
BACKGROUNDThere is mounting evidence that microbes resident in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested.METHODSWe used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing.RESULTSWe show the gut microbial choline metabolite trimethylamine (TMA) is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome.CONCLUSIONSThe microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury.
- Published
- 2022
14. Author response: Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice
- Author
-
Anagha Kadam, Tatsunori Miyata, Robert N Helsley, Venkateshwari Varadharajan, Naseer Sangwan, Emily C Huang, Rakhee Banerjee, Amanda L Brown, Kevin K Fung, William J Massey, Chase Neumann, Danny Orabi, Lucas J Osborn, Rebecca C Schugar, Megan R McMullen, Annette Bellar, Kyle L Poulsen, Adam Kim, Vai Pathak, Marko Mrdjen, James T Anderson, Belinda Willard, Craig J McClain, Mack Mitchell, Arthur J McCullough, Svetlana Radaeva, Bruce Barton, Gyongyi Szabo, Srinivasan Dasarathy, Jose Carlos Garcia-Garcia, Daniel M Rotroff, Daniela S Allende, Zeneng Wang, Stanley L Hazen, Laura E Nagy, and Jonathan Mark Brown
- Published
- 2022
15. Fatty Liver Disease: NASH and Related Disorders
- Author
-
Geoffrey C. Farrell, Jacob George, Pauline de la M. Hall, Arthur J. McCullough, Geoffrey C. Farrell, Jacob George, Pauline de la M. Hall, Arthur J. McCullough and Geoffrey C. Farrell, Jacob George, Pauline de la M. Hall, Arthur J. McCullough, Geoffrey C. Farrell, Jacob George, Pauline de la M. Hall, Arthur J. McCullough
- Published
- 2008
16. Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis
- Author
-
Leila Gobejishvili, Vatsalya Vatsalya, Svetlana Radaeva, Matthew C. Cave, Arthur J. McCullough, K. Cameron Falkner, Bruce A. Barton, Gyongyi Szabo, Craig J. McClain, Maiying Kong, John Craycroft, Mack C. Mitchell, and Srinivasan Dasarathy
- Subjects
Alcoholic liver disease ,medicine.medical_specialty ,Necrosis ,macromolecular substances ,Alcohol use disorder ,Severity of Illness Index ,Gastroenterology ,Article ,Keratin 18 ,End Stage Liver Disease ,Liver disease ,Model for End-Stage Liver Disease ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Humans ,Liver injury ,Keratin-18 ,Hepatology ,Hepatitis, Alcoholic ,business.industry ,Prognosis ,medicine.disease ,medicine.symptom ,Acute Alcoholic Hepatitis ,business ,Biomarkers - Abstract
Background & Aims Acute alcoholic hepatitis (AAH) is a major cause of liver-related morbidity and mortality; there are no good blood biomarkers for diagnosis or determining magnitude of cell death. Keratin 18 (KRT18, also called K18), found in epithelial cells, is released from hepatocytes upon death. We investigated whether level of K18 is a better marker of hepatocyte death than standard biomarkers and might be used to identify patients with AAH at risk for death within 90 days. Methods We analyzed data from 173 participants in a large trial performed at 4 medical centers. Participants with AAH were classified as severe (n = 57, model for end-stage liver disease [MELD] scores above 20) or moderate (n = 27, MELD scores from 12 to 19); 38 participants had alcohol use disorder with mild (n = 28) or no liver injury (n = 10); 34 participants had nonalcoholic steatohepatitis; and 17 participants were healthy (controls). We quantified serum levels of K18 using ELISAs and APOPTOSENSE kits. Results Serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the ratio of AST:ALT did not correlate with MELD scores. Patients with alcohol use disorder had higher serum levels of ALT than patients with severe AAH. Levels of K18M65 and K18M30 had statistically significant increases as liver disease worsened, as did the degree of necrosis (ratio of K18 M65:M30). The ratio of K18M65:ALT was increased in serum from patients with AAH compared with controls. Serum levels of K18 identified patients who died within 90 days with greater accuracy than commonly used static biomarkers. Conclusions There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers (AST, ALT, and the AST:ALT ratio). The ratio of K18M65:M30 might be used as marker of mechanism of hepatocyte death, and the ratio of K18M65:ALT might be used to distinguish patients with AAH from patients with nonalcoholic steatohepatitis. Serum levels of K18 might be used to identify patients with severe AAH at risk for death. ClinicalTrials.gov identifier # NCT01922895 and NCT01809132 .
- Published
- 2020
17. Accuracy of Noninvasive Fibrosis Scores to Detect Advanced Fibrosis in Patients With Type-2 Diabetes With Biopsy-proven Nonalcoholic Fatty Liver Disease
- Author
-
Amandeep Singh, Arthur J. McCullough, Rocio Lopez, Fred Poordad, William D. Carey, Mohit Gupta, Falgun Gosai, Naim Alkhouri, Eric Lawitz, and Mohamed Tausif Siddiqui
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Biopsy ,Population ,Type 2 diabetes ,Severity of Illness Index ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Fibrosis ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Aspartate Aminotransferases ,education ,education.field_of_study ,medicine.diagnostic_test ,Platelet Count ,business.industry ,Fatty liver ,Alanine Transaminase ,medicine.disease ,Diabetes Mellitus, Type 2 ,Liver ,030220 oncology & carcinogenesis ,Liver biopsy ,Female ,030211 gastroenterology & hepatology ,business ,Body mass index - Abstract
Background Recent guidelines have recommended screening for nonalcoholic fatty liver disease (NAFLD) and case finding of advanced disease with fibrosis in patients with type-2 diabetes (T2D). The aim of this study is to assess the accuracy of commonly used noninvasive scores to predict the presence of advanced fibrosis (AF) in a large cohort of diabetics in real-life settings. Patients and methods Using International Classification of Diseases, Ninth Revision (ICD-9) codes, all patients with the diagnosis of T2D who had a liver biopsy for suspected NAFLD between January 2000 and December 2015, were identified and analyzed. Patients with secondary causes of hepatic steatosis were excluded. AST/ALT ratio, aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4) index, and Nonalcoholic fatty liver disease Fibrosis Score (NFS) were calculated to predict advanced disease. Sensitivity, specificity, and area under the receiver operator curve were calculated and compared with liver biopsies to predict the overall accuracy of each score. Results A total of 1319 patients with T2D underwent liver biopsy for suspected NAFLD. After exclusions, 1,157 subjects were included in the final analysis. Our cohort consisted of 64.6% females and 88.4% were whites. Overall, 85% of the population was overweight or obese (body mass index>25 kg/m). Liver biopsy showed 31.7% with AF [Nonalcoholic Steatohepatitis Clinical Research Network (NASH-CRN) stage 3 to 4]. In comparison to liver biopsy, for the diagnosis of AF, AST/ALT>1.4, APRI>1.5, FIB-4>2.67, and NFS>0.676 had reasonable specificities of 84.2%, 97.4%, 69.9%, and 93% but poor sensitivities of 27.4%, 16.5%, 6.7%, and 44.1%, respectively. Even at lower cutoff values of AST/ALT≥1, APRI≥1, and FIB-4≥1.45 sensitivities remained low at 60.7%, 27.9%, and 72.6%, respectively, except for NFS ≥-1.455 with sensitivity of 94.6%, but at this cutoff, its specificity decreased to 16.9%. The area under the receiver operator curve to detect AF was 0.62, 0.74, 0.77, and 0.72, respectively. Conclusions In this large cohort of adult patients with T2D and NAFLD, commonly used fibrosis scores had reasonable specificity, but poor sensitivity for detecting AF in diabetics. The development of reliable biomarkers for NAFLD/NASH in diabetics is urgently needed.
- Published
- 2020
18. Hospital readmission following transjugular intrahepatic portosystemic shunt: a 14-year single-center experience
- Author
-
Tavankit Singh, Jennifer Bullen, Arthur J. McCullough, Catherine F. Vozzo, Baljendra Kapoor, and Shashank Sarvepalli
- Subjects
medicine.medical_specialty ,business.industry ,liver cirrhosis ,medicine.medical_treatment ,Gastroenterology ,portal hypertension ,Original Articles ,Odds ratio ,medicine.disease ,Single Center ,Confidence interval ,Surgery ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,hospital readmission ,030220 oncology & carcinogenesis ,transjugular intrahepatic portosystemic shunt ,Medicine ,Portal hypertension ,030211 gastroenterology & hepatology ,business ,Complication ,Transjugular intrahepatic portosystemic shunt ,Hepatic encephalopathy - Abstract
BackgroundPlacement of a transjugular intrahepatic portosystemic shunt (TIPS) is a relatively common procedure used to treat complications of portal hypertension. However, only limited data exist regarding the hospital-readmission rate after TIPS placement and no studies have addressed the causes of hospital readmission. We therefore sought to identify the 30-day hospital-readmission rate after TIPS placement at our institution and to determine potential causes and predictors of readmission.MethodsWe reviewed our electronic medical-records system at our institution between 2004 and 2017 to identify patients who had undergone primary TIPS placement with polytetrafluoroethylene-covered stents and to determine the 30-day readmission rate among these patients. A series of univariable logistic-regression models were fit to assess potential predictors of 30-day readmission.ResultsA total of 566 patients were included in the analysis. The 30-day readmission rate after TIPS placement was 36%. The most common causes for readmission were confusion (48%), infection (15%), bleeding (11%), and fluid overload (7%). A higher Model for End-Stage Liver Disease (MELD) score corresponded with a higher rate of readmission (odds ratio associated with each 1-unit increase in MELD score: 1.06; 95% confidence interval: 1.02–1.09; P = 0.001). Other potential predictors, including indication for TIPS placement, were not significantly associated with a higher readmission rate.ConclusionsThe 30-day readmission rate after TIPS placement with covered stents is high, with nearly half of these readmissions due to hepatic encephalopathy—a known complication of TIPS placement. Novel interventions to help reduce the TIPS readmission rate should be prioritized in future research.
- Published
- 2019
19. Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis
- Author
-
Ali Aminian, Faiz U Shariff, Vance L. Albaugh, James Bena, Rickesha Wilson, Steven E. Nissen, Abbas Al-Kurd, Hana Fayazzadeh, Stacy A. Brethauer, Tavankit Singh, Jian Jin, Noe A. Rodriguez, Naim Alkhouri, Philip R. Schauer, Arthur J. McCullough, and Srinivasan Dasarathy
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Sleeve gastrectomy ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Biopsy ,Bariatric Surgery ,Kaplan-Meier Estimate ,Liver transplantation ,Lower risk ,Non-alcoholic Fatty Liver Disease ,medicine ,Humans ,Cumulative incidence ,Obesity ,Propensity Score ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Incidence ,Hazard ratio ,Body Weight ,Liver Neoplasms ,General Medicine ,Middle Aged ,Surgery ,Liver ,Cardiovascular Diseases ,Liver biopsy ,Median body ,Female ,business ,Mace - Abstract
Importance No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH). Objective To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis. Design, setting, and participants In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021. Exposures Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care. Main outcomes and measures The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework. Results A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2). Conclusions and relevance Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.
- Published
- 2021
20. Accuracy of steatosis and fibrosis NAFLD scores in relation to vibration controlled transient elastography: An NHANES analysis
- Author
-
Achuthan Sourianarayanane and Arthur J McCullough
- Subjects
Liver Cirrhosis ,Hepatology ,Non-alcoholic Fatty Liver Disease ,Gastroenterology ,Elasticity Imaging Techniques ,Humans ,Prospective Studies ,Nutrition Surveys ,Vibration - Abstract
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and increasing in the United States. Based on patient characteristics and biochemical profiles, predictive indices have been formulated to evaluate the presence and severity of NAFLD. This study evaluates the accuracy of these indices versus vibration-controlled transient elastography (VCTE™) to screen at-risk populations for NAFLD.Subjects from the NHANES datasets (2017-2018) without other liver diseases with completed VCTE™ data were studied (n = 5062). Hepatic steatosis and fibrosis scores were calculated and compared with controlled attenuation parameter (CAP) and elastography measurements of VCTE™, respectively.The prevalence of NAFLD was 58.5%. Against a CAP cut-off value of ≥238 dB/m for diagnosing fatty liver, the US fatty liver index [US-FLI] had the highest positive predictive value (90%) and specificity (63.7%). The coefficient of correlation against CAP was strong for fatty liver index [FLI] (r = 0.645) and US-FLI (r = 0.608). The hepatic steatosis index [HSI] had the highest negative predictive value (82.1%) and sensitivity (75%) for ruling out steatosis. HSI and FLI, which use commonly obtained clinical parameters, had a high diagnostic odds ratios (21.2 and 18.6, respectively) compared to US-FLI (4.97), which requires insulin levels in the calculation. These findings were similar across all ethnicities studied.US-FLI is a reliable scoring system to diagnose patients with fatty liver. HSI and FLI are more easily calculated and can be used in clinical practices to diagnose NAFLD in at-risk populations.
- Published
- 2022
21. Hepatocellular Carcinoma in Patients Without Cirrhosis: The Fibrosis Stage Distribution, Characteristics and Survival
- Author
-
Srinivasan Dasarathy, Kanokwan Pinyopornpanish, Wael Al-Yaman, Arthur J. McCullough, and Carlos Romero-Marrero
- Subjects
Adult ,Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Carcinoma, Hepatocellular ,Physiology ,Hepacivirus ,Milan criteria ,Gastroenterology ,Article ,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 ,Retrospective Studies ,business.industry ,Liver Neoplasms ,Hepatitis C ,Hepatitis B ,medicine.disease ,Fibrosis ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,business ,Viral hepatitis - Abstract
BACKGROUND: The data on hepatocellular carcinoma (HCC) patients without liver cirrhosis is scarce. AIMS: To study the epidemiology, underlying etiology and fibrosis distribution in noncirrhotic HCC and compare the survival outcomes to cirrhotic HCC. METHODS: We conducted a retrospective study including all adult patients diagnosed with HCC at two US tertiary academic centers from 2000 to 2015. Univariable and multivariable Cox regression analyses were performed to evaluate the variables associated with patient survival. RESULTS: Two thousand two hundred and thirty-seven HCC patients were included in the final analysis, of which, 13% had no liver cirrhosis. The most common underlying liver disease in non-cirrhotic patients was cryptogenic cause (40%), followed by nonalcoholic fatty liver disease (NAFLD) (25.2%) and hepatitis C (19%). The percentage of F0–F1, F2, and F3 was 72%, 17%, and 11% (cryptogenic cause); 69%, 12%, and 19% (NAFLD); 50%, 17%, and 33% (alcohol); 33%, 39%, and 28% (hepatitis B); 20%, 40%, and 40% (hemochromatosis); and 12%, 40%, and 48% (hepatitis C), respectively. In non-cirrhotic compared to cirrhotic patients, the tumor was more likely to be larger and fell outside Milan criteria (all p < 0.001). Cirrhotic patients had significant shorter survival than non-cirrhotic patients (p < 0.001). On the multivariable analysis, having liver cirrhosis (HR 1.48; 1.21–1.82, p < 0.001), combined viral hepatitis and alcohol use (HR 1.51; 1.23–1.88, p < 0.001), morbid obesity (HR 1.31; 1.01–1.69, p = 0.040) and underweight (HR 2.06; 1.27–3.34, p = 0.004) were associated with worse patient survival. CONCLUSIONS: The fibrosis distribution in non-cirrhotic HCC differed among each etiology of liver diseases. Despite more advanced HCC, patients without cirrhosis had significantly longer survival than those with cirrhosis.
- Published
- 2021
22. Impact of sleeve gastrectomy and Roux-en-Y gastric bypass on biopsy-proven non-alcoholic fatty liver disease
- Author
-
Tavankit Singh, Ali Aminian, Roman Vangoitsenhoven, Neal Mehta, Philip R. Schauer, Stacy A. Brethauer, Arthur J. McCullough, Deepa V. Cherla, and Noe A. Rodriguez
- Subjects
Adult ,Male ,medicine.medical_specialty ,Sleeve gastrectomy ,Biopsy ,medicine.medical_treatment ,Gastric Bypass ,Bariatric Surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Liver Function Tests ,Gastrectomy ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Humans ,Medicine ,Aspartate Aminotransferases ,Obesity ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,Alanine Transaminase ,Middle Aged ,medicine.disease ,Roux-en-Y anastomosis ,digestive system diseases ,Treatment Outcome ,030220 oncology & carcinogenesis ,Liver biopsy ,Female ,030211 gastroenterology & hepatology ,Surgery ,Liver function ,Steatohepatitis ,Metabolic syndrome ,business ,Liver function tests - Abstract
Non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Our aim was to study the long-term effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on NAFLD/NASH. Between 2008 and 2015, 3813 patients had an intraoperative liver biopsy performed at the time of primary RYGB and SG at a single academic center. Utilizing strict inclusion criteria, 487 patients with biopsy-proven NAFLD who had abnormal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values (≥ 40 IU/L) at baseline were identified. Matching of SG to RYGB patients (1:4) was performed via logistic regression and propensity scores adjusting for clinical and liver histological characteristics. Changes in liver function tests (LFTs) at least 1 year after surgery were compared to baseline values and between the surgical groups. A total of 310 (weighted) patients (SG n = 62, and RYGB n = 248) with a median follow-up time of 4 years (range, 1–10) were included in the analysis. The distribution of covariates was well-balanced after propensity matching. In 84% of patients, LFT values normalized after bariatric surgery at the last follow-up time. The proportions of patients having normalized LFT values did not differ significantly between the SG and RYGB groups (82% vs. 84%, p = 0.66). The AST decreased from (SG: 49.1 ± 21.5 vs. RYGB: 49.3 ± 22.0, p = 0.93) at baseline to (SG: 28.0 ± 16.5 vs. RYGB: 26.5 ± 15.5, p = 0.33) at the last follow-up. Similarly, a significant reduction in ALT values from (SG: 61.7 ± 30.0 vs. RYGB 59.4 ± 24.9, p = 0.75) at baseline to (SG: 27.2 ± 21.5 vs. RYGB: 26.1 ± 19.2, p = 0.52) at the last follow-up was observed. In patients with biopsy-proven NAFLD/NASH, abnormal LFTs are normalized in most SG and RYGB patients by the end of the first postoperative year and remain normal until the last follow-up. This study also suggests that both bariatric procedures are similarly effective in improving liver function.
- Published
- 2019
23. Awareness of Nonalcoholic Fatty Liver Disease Is Increasing but Remains Very Low in a Representative US Cohort
- Author
-
Mohit Gupta, Naim Alkhouri, Shailainder Singh, Amaninder Dhaliwal, Rocio Lopez, Atul Kumar, Mazen Noureddin, Amandeep Singh, William D. Carey, and Arthur J. McCullough
- Subjects
medicine.medical_specialty ,National Health and Nutrition Examination Survey ,Physiology ,business.industry ,Gastroenterology ,nutritional and metabolic diseases ,medicine.disease ,Logistic regression ,Chronic liver disease ,digestive system diseases ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Diabetes mellitus ,Nonalcoholic fatty liver disease ,Cohort ,medicine ,030211 gastroenterology & hepatology ,Metabolic syndrome ,business - Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in the USA. Interestingly, most patients with NAFLD are unaware of having any liver disease (LD). We aimed to assess the awareness of suspected NAFLD and factors associated with being aware of LD. Adult subjects with suspected NAFLD (BMI > 25) with elevated ALT in the absence of secondary causes of LD who participated in the continuous national health and nutrition examination survey (NHANES) during 2001–2016 were identified and analyzed. Trends of NAFLD awareness were then assessed in periods of 4 years each. Multivariable logistic regression analysis was performed to assess factors associated with LD awareness. A total of 7033 subjects were included in the final analysis (1731, 1757, 1711, and 1834 subjects for the periods of 2001–2004, 2005–2008, 2009–2012, and 2013–2016, respectively). Over the study duration, an increase in BMI, waist circumference, diabetes, and HbA1c; and a decrease in the number of smokers, platelets count, bilirubin, total cholesterol, and LDL level were noticed (p
- Published
- 2019
24. Biomarkers of Macrophage Activation and Immune Danger Signals Predict Clinical Outcomes in Alcoholic Hepatitis
- Author
-
Craig J. McClain, Mack C. Mitchell, Patrick Lowe, David Tornai, Svetlana Radaeva, Adeyinka Charles Adejumo, Bruce A. Barton, Arthur J. McCullough, Aimee R. Kroll-Desrosiers, Karen Kodys, Banishree Saha, Gyongyi Szabo, and Srinivasan Dasarathy
- Subjects
0301 basic medicine ,Kaplan-Meier Estimate ,Severity of Illness Index ,Gastroenterology ,Liver disease ,0302 clinical medicine ,Liver Function Tests ,Cause of Death ,Osteopontin ,Academic Medical Centers ,Membrane Glycoproteins ,biology ,Middle Aged ,Prognosis ,Disease Progression ,030211 gastroenterology & hepatology ,Acute Alcoholic Hepatitis ,Lipopolysaccharide binding protein ,Adult ,medicine.medical_specialty ,Alcoholic hepatitis ,Enzyme-Linked Immunosorbent Assay ,HMGB1 ,Risk Assessment ,Article ,03 medical and health sciences ,Immune system ,Antigens, CD ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Aged ,Proportional Hazards Models ,Hepatology ,Cluster of differentiation ,Hepatitis, Alcoholic ,business.industry ,Macrophage Activation ,medicine.disease ,Survival Analysis ,United States ,030104 developmental biology ,ROC Curve ,Case-Control Studies ,Multivariate Analysis ,biology.protein ,Carrier Proteins ,business ,Biomarkers ,Acute-Phase Proteins - Abstract
Although mortality due to acute alcoholic hepatitis (AH) correlates with Model for End-Stage Liver Disease (MELD) scores, biomarkers are critically needed to manage this disease. Increases in inflammatory markers and macrophage activation are associated with acute AH and could be potential biomarkers of clinical events and/or mortality. We enrolled 89 clinically diagnosed AH patients in four US academic medical centers. Plasma from AH patients had a significant increase in gut microbial translocation indicators (endotoxin, bacterial 16S ribosomal DNA) and host response indicators (soluble cluster of differentiation 14 [sCD14] and lipopolysaccharide binding protein [LBP]) compared to controls. Patient MELD score and Glasgow Alcoholic Hepatitis score (GAHS) correlated with endotoxin levels. AH patients also had a significant increase in high mobility group protein 1 (HMGB1), a sterile danger signal molecule, and osteopontin (OPN), a multifunctional phosphoprotein involved in neutrophil activation, compared to controls. Increased levels of OPN positively correlated with increasing MELD score, GAHS, and LBP levels. Consistent with these results, AH patients had significantly increased circulating levels of macrophage activation (sCD163 and sCD206) markers compared to healthy controls, and sCD163 and sCD206 significantly and positively correlated with OPN, HMGB1, and LBP levels as well as with MELD score and GAHS. These findings indicate a connection between microbial translocation, immune cell activation, and AH severity. Plasma sCD14, OPN, sCD163, and sCD206 levels were significantly higher in nonsurvivors than survivors. In multivariate regression models, we identified sCD14, sCD163, and OPN as independent predictors of 90-day mortality, infection, and organ failure development, respectively. Conclusion: Our study suggests that sCD14, LBP, OPN, sCD163, and sCD206 are biomarkers to indicate severity and predict clinical outcomes in AH.
- Published
- 2019
25. Hepatic Mitochondrial Defects in a Nonalcoholic Fatty Liver Disease Mouse Model Are Associated with Increased Degradation of Oxidative Phosphorylation Subunits
- Author
-
Takhar Kasumov, Sergei Ilchenko, Ahmad Borzou, Daniela S. Allende, Srinivasan Dasarathy, Andrew Haddad, Chunki Kim, Arthur J. McCullough, Kwangwon Lee, Rovshan G. Sadygov, and Abdullah Osme
- Subjects
Male ,Proteomics ,0301 basic medicine ,medicine.medical_specialty ,Normal diet ,Oxidative phosphorylation ,Protein degradation ,medicine.disease_cause ,Biochemistry ,Oxidative Phosphorylation ,Analytical Chemistry ,Mitochondrial Proteins ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Tandem Mass Spectrometry ,Internal medicine ,Nonalcoholic fatty liver disease ,Autophagy ,medicine ,Animals ,Citrate synthase ,Molecular Biology ,Mice, Knockout ,biology ,Cholesterol ,Research ,Fatty Acids ,Mitophagy ,nutritional and metabolic diseases ,medicine.disease ,Mitochondria ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,Liver ,chemistry ,Diet, Western ,030220 oncology & carcinogenesis ,Proteolysis ,biology.protein ,Steatosis ,Reactive Oxygen Species ,Oxidative stress ,Half-Life - Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the (2)H(2)O-metabolic labeling approach to test the hypothesis that the reduced stability of oxidative phosphorylation proteins contributes to mitochondrial dysfunction in a diet-induced mouse model of NAFLD. A high fat diet containing cholesterol (a so-called Western diet (WD)) led to hepatic oxidative stress, steatosis, inflammation and mild fibrosis, all markers of NAFLD, in low density cholesterol (LDL) receptor deficient (LDLR(−/−)) mice. In addition, compared with controls (LDLR(−/−) mice on normal diet), livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting mitochondrial impairment. Proteome dynamics study revealed that mitochondrial defects are associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41 ± 0.46 versus 5.15 ± 0.49 day, p < 0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome b-c1 complex subunit 1 (5.9 ± 0.1 versus 3.4 ± 0.8 day), ATP synthase subunit α (6.3 ± 0.4 versus 5.5 ± 0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5 ± 0.6 versus 6.5 ± 0.2 day) (p < 0.05). These changes were associated with impaired complex III and F0F1-ATP synthase activities. Markers of mitophagy were increased, but proteasomal degradation activity were reduced in NAFLD mice liver, suggesting that ATP deficiency because of reduced stability of oxidative phosphorylation complex subunits contributed to inhibition of ubiquitin-proteasome and activation of mitophagy. In conclusion, the (2)H(2)O-metabolic labeling approach shows that increased degradation of hepatic oxidative phosphorylation subunits contributed to mitochondrial impairment in NAFLD mice.
- Published
- 2018
26. Effect of Alcohol Consumption on Survival in Nonalcoholic Fatty Liver Disease: A National Prospective Cohort Study
- Author
-
Kaveh Hajifathalian, Babak Torabi Sagvand, and Arthur J. McCullough
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Hepatology ,National Health and Nutrition Examination Survey ,business.industry ,Proportional hazards model ,Hazard ratio ,medicine.disease ,National Death Index ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,030211 gastroenterology & hepatology ,Prospective cohort study ,business ,Survival rate ,Cohort study - Abstract
Nonalcoholic fatty liver disease (NAFLD) comprises more than two thirds of patients with chronic liver disease in the United States. The effect of alcohol consumption on survival in patients with NAFLD is not clear. We gathered data on National Health and Nutrition Examination Survey participants from 1988 to 2010, and linked them to the National Death Index for follow-up of their survival. We diagnosed NAFLD based on a previously validated biochemical model (Hepatic Steatosis Index). We built multivariate Cox proportional hazards models to evaluate the effect of alcohol consumption on survival of patients with NAFLD. After excluding participants with significant alcohol use, viral hepatitis, or increased transferrin saturation, 4,568 participants with NAFLD were included in the analysis. In a Cox model adjusted for age, sex, and smoking history, drinking 0.5-1.5 drinks per day decreased the risk of overall mortality by 41% (hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.40-0.85, P = 0.005) compared with not drinking. Drinking ≥1.5 drinks per day showed a trend toward harm (HR = 1.16, 95% CI 0.99-1.36, P = 0.119). After further adjustment for race, physical activity, education level, diabetes, and fiber and polyunsaturated fatty acid intake, drinking 0.5-1.5 drinks per day continued to show a significant protective effect (HR = 0.64, 95% CI 0.42-0.97, P = 0.035), and drinking ≥1.5 drinks per day showed a significant harmful effect on mortality (HR = 1.45, 95% CI 1.01-2.10, P = 0.047). Among patients with NAFLD, modest alcohol consumption is associated with a significant decrease in all-cause mortality, whereas drinking ≥1.5 drinks per day is associated with an increase in mortality. These results help to inform the discussion of potential risks and benefits of alcohol use in patients with NAFLD.
- Published
- 2018
27. Differential role of MLKL in alcohol-associated and non–alcohol-associated fatty liver diseases in mice and humans
- Author
-
Sanjoy Roychowdhury, Srinivasan Dasarathy, Joan Caballería, Megan R. McMullen, Craig J. McClain, Emily Huang, Gyongyi Szabo, Pau Sancho-Bru, Svetlana Radaeva, Tatsunori Miyata, Xiaoqin Wu, Xiude Fan, Bruce A. Barton, Mack C. Mitchell, Christina K. Cajigas-Du Ross, Annette Bellar, Laura E. Nagy, Jaividhya Dasarathy, Arthur J. McCullough, Daniela S. Allende, and Carlos Sanz-Garcia
- Subjects
0301 basic medicine ,Male ,Chemokine ,Hepatitis ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Phosphorylation ,Mice, Knockout ,biology ,Cell Death ,Kinase ,Fatty liver ,General Medicine ,Middle Aged ,Liver ,030220 oncology & carcinogenesis ,Receptor-Interacting Protein Serine-Threonine Kinases ,Medicine ,Female ,medicine.symptom ,Signal Transduction ,Research Article ,Adult ,medicine.medical_specialty ,Programmed cell death ,Inflammation ,digestive system ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Animals ,Protein kinase A ,Ethanol ,Hepatology ,Cholesterol ,business.industry ,Cell Membrane ,nutritional and metabolic diseases ,medicine.disease ,digestive system diseases ,Fatty Liver ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,chemistry ,biology.protein ,business ,Transcriptome ,Protein Kinases - Abstract
Hepatocellular death contributes to progression of alcohol-associated (ALD-associated) and non-alcohol-associated (NAFL/NASH) liver diseases. However, receptor-interaction protein kinase 3 (RIP3), an intermediate in necroptotic cell death, contributes to injury in murine models of ALD but not NAFL/NASH. We show here that a differential role for mixed-lineage kinase domain-like protein (MLKL), the downstream effector of RIP3, in murine models of ALD versus NAFL/NASH and that RIP1-RIP3-MLKL can be used as biomarkers to distinguish alcohol-associated hepatitis (AH) from NASH. Phospho-MLKL was higher in livers of patients with NASH compared with AH or healthy controls (HCs). MLKL expression, phosphorylation, oligomerization, and translocation to plasma membrane were induced in WT mice fed diets high in fat, fructose, and cholesterol but not in response to Gao-binge (acute on chronic) ethanol exposure. Mlkl-/- mice were not protected from ethanol-induced hepatocellular injury, which was associated with increased expression of chemokines and neutrophil recruitment. Circulating concentrations of RIP1 and RIP3, but not MLKL, distinguished patients with AH from HCs or patients with NASH. Taken together, these data indicate that MLKL is differentially activated in ALD/AH compared with NAFL/NASH in both murine models and patients. Furthermore, plasma RIP1 and RIP3 may be promising biomarkers for distinguishing AH and NASH.
- Published
- 2021
28. The Association of Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma
- Author
-
Muhammad Talal Sarmini, Srinivasan Dasarathy, Mohammad Alomari, Mohammad Maysara Asfari, Rocio Lopez, and Arthur J. McCullough
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Carcinoma, Hepatocellular ,Adolescent ,Hepatitis C virus ,medicine.disease_cause ,Logistic regression ,digestive system ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Hepatitis B virus ,Aged, 80 and over ,Hepatology ,business.industry ,Liver Neoplasms ,Gastroenterology ,nutritional and metabolic diseases ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,digestive system diseases ,Cross-Sectional Studies ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cohort ,030211 gastroenterology & hepatology ,Female ,business - Abstract
BACKGROUND Current guidelines recommend surveillance for hepatocellular carcinoma (HCC) in high-risk patients. This high risk is defined by the presence of cirrhosis. However, HCC due to underlying nonalcoholic steatohepatitis (NASH), even without progressing to cirrhosis, is a rising concern. Hence, we aimed to determine the association of HCC with NASH using a large national database. METHODS A cross-sectional study was performed using the 2012 National Inpatient Sample. The study group was all adult patients' age 18-90 years who have a diagnosis of NASH which was identified using the International Classification of Diseases 9th version (ICD-9) codes. The control group included the rest of adult individuals without discharge records of NASH. We identified the diagnosis of HCC in both study and control groups using the ICD-9 codes. We calculated the association between NASH and HCC using univariable and multivariate logistic regression. RESULTS Totally, 30 712 524 hospitalizations were included in our study. This cohort included 218 950 patients with NASH (study group) and 30 493 574 patients without NASH (control group). The study group patients aged 57.3 ± 0.10 years (59.4% females) comparing to 54.5 ± 0.11 years (57.1% female) in the control group. HCC prevalence in subjects with NASH was 0.50% [95% confidence interval (CI): 0.41-0.59] compared to 0.21% (95% CI: 0.20-0.23) in subjects without NASH (P
- Published
- 2020
29. Association of non-alcoholic fatty liver disease and polycystic ovarian syndrome
- Author
-
Muhammad Talal Sarmini, Yamen Ezzaizi, Firas Baidoun, Yasser Al-Khadra, Mohammad Maysara Asfari, Srinivasan Dasarathy, and Arthur J. McCullough
- Subjects
Adult ,medicine.medical_specialty ,endocrine system diseases ,030209 endocrinology & metabolism ,Disease ,Comorbidity ,Logistic regression ,liver ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Endocrine system ,Medicine ,Humans ,Obesity ,Risk factor ,nonalcoholic steatohepatitis ,lcsh:RC799-869 ,Aged ,Data Management ,Dyslipidemias ,Hepatology ,business.industry ,Fatty liver ,Gastroenterology ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Cross-Sectional Studies ,Case-Control Studies ,diabetes mellitus ,Hypertension ,030211 gastroenterology & hepatology ,Female ,lcsh:Diseases of the digestive system. Gastroenterology ,Insulin Resistance ,business ,Polycystic Ovary Syndrome - Abstract
BackgroundPolycystic ovarian syndrome (PCOS) is a common endocrine disorder in women. Women with PCOS have androgen excess as a defining feature. They also have increased insulin resistance and obesity, which are also risk factors for non-alcoholic fatty liver disease (NAFLD). However, published data regarding PCOS as independent risk factor for NAFLD remain controversial. Therefore, we conducted this study to evaluate the association between PCOS and NAFLD using a large national database.MethodsWe identified adult female patients (≥18 years) with PCOS using the National Inpatient Sample database between 2002 and 2014. The control group included patients who did not have a diagnosis of PCOS. Multivariate logistic regression analysis was performed to study the association of NAFLD with PCOS.ResultsOut of a total of 50 785 354 women, 77 415 (0.15%) had PCOS. These patients were younger (32.7 vs 54.8; pConclusionOur study showed that patients with PCOS have four times higher risk of developing NAFLD compared with women without PCOS. Further studies are needed to assess if specific PCOS treatments can affect NAFLD progression.
- Published
- 2020
30. Exercise Training Rapidly Increases Hepatic Insulin Extraction in NAFLD
- Author
-
Christopher A Flask, Ciaran E. Fealy, Christopher L. Axelrod, Adithya Hari, Jacob M. Haus, John P. Kirwan, Arthur J. McCullough, Nutrition and Movement Sciences, and RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health
- Subjects
Blood Glucose ,medicine.medical_specialty ,obesity ,medicine.medical_treatment ,Physical Therapy, Sports Therapy and Rehabilitation ,Carbohydrate metabolism ,nafld ,Article ,GLUCOSE ,resistance ,03 medical and health sciences ,0302 clinical medicine ,Oxygen Consumption ,Glucagon-Like Peptide 1 ,Heart Rate ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,Heart rate ,medicine ,Aerobic exercise ,Humans ,Insulin ,Orthopedics and Sports Medicine ,Exercise ,Adiponectin ,C-Peptide ,business.industry ,HEPATIC INSULIN EXTRACTION ,Area under the curve ,association ,030229 sport sciences ,Middle Aged ,medicine.disease ,Lipid Metabolism ,peptide ,secretion ,short-term exercise ,AEROBIC EXERCISE TRAINING ,Endocrinology ,Basal (medicine) ,Liver ,fatty liver-disease ,Carbohydrate Metabolism ,Insulin Resistance ,business - Abstract
Purpose We aimed to determine the immediacy of exercise intervention on liver-specific metabolic processes in nonalcoholic fatty liver disease. Methods We undertook a short-term (7-d) exercise training study (60 min.d(-1) treadmill walking at 80%-85% of maximal heart rate) in obese adults (N= 13, 58 +/- 3 yr, 34.3 +/- 1.1 kg.m(-2), >5% hepatic lipid by(1)H-magnetic resonance spectroscopy). Insulin sensitivity index was estimated by oral glucose tolerance test using the Soonthorpun model. Hepatic insulin extraction (HIE) was calculated as the molar difference in area under the curve (AUC) for insulin and C-peptide (HIE = 1 - (AUC(Insulin)/AUC(C-Pep))). Results The increases in HIE, (V) over dotO(2max), and insulin sensitivity index after the intervention were 9.8%, 9.8%, and 34%, respectively (all,P< 0.05). Basal fat oxidation increased (pre: 47 +/- 6 mg.min(-1)vs post: 65 +/- 6 mg.min(-1),P< 0.05) and carbohydrate oxidation decreased (pre: 160 +/- 20 mg.min(-1)vs post: 112 +/- 15 mg.min(-1),P< 0.05) with exercise training. After the intervention, HIE correlated positively with adiponectin (r= 0.56,P< 0.05) and negatively with TNF-alpha (r= -0.78,P< 0.001). Conclusions By increasing HIE along with peripheral insulin sensitivity, aerobic exercise training rapidly reverses some of the underlying physiological mechanisms associated with nonalcoholic fatty liver disease, in a weight loss-independent manner. This reversal could potentially act through adipokine-related pathways.
- Published
- 2020
31. AGA Clinical Practice Update on Bariatric Surgery in Cirrhosis: Expert Review
- Author
-
Julie K. Heimbach, Arthur J. McCullough, and Heather Patton
- Subjects
Nonalcoholic steatohepatitis ,Liver Cirrhosis ,medicine.medical_specialty ,Sleeve gastrectomy ,Cirrhosis ,Hepatology ,Extramural ,business.industry ,General surgery ,medicine.medical_treatment ,Gastroenterology ,MEDLINE ,Bariatric Surgery ,medicine.disease ,Article ,Clinical Practice ,Nonalcoholic fatty liver disease ,medicine ,Humans ,business - Published
- 2020
32. β-Hydroxybutyrate is reduced in humans with obesity-related NAFLD and displays a dose-dependent effect on skeletal muscle mitochondrial respiration in vitro
- Author
-
Melissa L. Erickson, William T. King, Christopher A Flask, Christopher L. Axelrod, Jacob T. Mey, John P. Kirwan, and Arthur J. McCullough
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,Proton Magnetic Resonance Spectroscopy ,Muscle Fibers, Skeletal ,Dose dependence ,030209 endocrinology & metabolism ,Ketone Bodies ,Fatty Acids, Nonesterified ,In Vitro Techniques ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Physiology (medical) ,Internal medicine ,Ketogenesis ,Nonalcoholic fatty liver disease ,Medicine ,Humans ,Obesity ,Muscle, Skeletal ,Aged ,3-Hydroxybutyric Acid ,business.industry ,Skeletal muscle ,Middle Aged ,medicine.disease ,Mitochondrial respiration ,In vitro ,Mitochondria, Muscle ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Liver ,Case-Control Studies ,Glucose Clamp Technique ,Female ,Insulin Resistance ,business ,Research Article - Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation and impaired insulin sensitivity. Reduced hepatic ketogenesis may promote these pathologies, but data are inconclusive in humans and the link between NAFLD and reduced insulin sensitivity remains obscure. We investigated individuals with obesity-related NAFLD and hypothesized that β-hydroxybutyrate (βOHB; the predominant ketone species) would be reduced and related to hepatic fat accumulation and insulin sensitivity. Furthermore, we hypothesized that ketones would impact skeletal muscle mitochondrial respiration in vitro. Hepatic fat was assessed by 1H-MRS in 22 participants in a parallel design, case control study [Control: n = 7, age 50 ± 6 yr, body mass index (BMI) 30 ± 1 kg/m2; NAFLD: n = 15, age 57 ± 3 yr, BMI 35 ± 1 kg/m2]. Plasma assessments were conducted in the fasted state. Whole body insulin sensitivity was determined by the gold-standard hyperinsulinemic-euglycemic clamp. The effect of ketone dose (0.5–5.0 mM) on mitochondrial respiration was conducted in human skeletal muscle cell culture. Fasting βOHB, a surrogate measure of hepatic ketogenesis, was reduced in NAFLD (−15.6%, P < 0.01) and correlated negatively with liver fat ( r2 = 0.21, P = 0.03) and positively with insulin sensitivity ( r2 = 0.30, P = 0.01). Skeletal muscle mitochondrial oxygen consumption increased with low-dose ketones, attributable to increases in basal respiration (135%, P < 0.05) and ATP-linked oxygen consumption (136%, P < 0.05). NAFLD pathophysiology includes impaired hepatic ketogenesis, which is associated with hepatic fat accumulation and impaired insulin sensitivity. This reduced capacity to produce ketones may be a potential link between NAFLD and NAFLD-associated reductions in whole body insulin sensitivity, whereby ketone concentrations impact skeletal muscle mitochondrial respiration.
- Published
- 2020
33. Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
- Author
-
Jaividhya Dasarathy, Srinivasan Dasarathy, Arthur J. McCullough, Yana Sandlers, Rohan R. Shah, and Ryan W. Pearce
- Subjects
0301 basic medicine ,medicine.medical_specialty ,lcsh:Medicine ,Inflammation ,digestive system ,Article ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Internal medicine ,Nonalcoholic fatty liver disease ,mitochondrial dysfunction ,medicine ,business.industry ,lcsh:R ,Area under the curve ,nutritional and metabolic diseases ,General Medicine ,nonalcoholic fatty liver disease (nafld) ,medicine.disease ,Pathophysiology ,digestive system diseases ,3. Good health ,Citric acid cycle ,030104 developmental biology ,Endocrinology ,030211 gastroenterology & hepatology ,Liver function ,medicine.symptom ,Metabolic syndrome ,business ,plasma krebs cycle intermediates - Abstract
Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD (n = 22) and matched control (n = 67) cohorts. Circulating levels of isocitrate and citrate were significantly (p <, 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson&rsquo, s correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted.
- Published
- 2020
34. Trends in pioglitazone use among U.S. adults with type 2 diabetes and suspected nonalcoholic fatty liver disease
- Author
-
Alexander Chaitoff, Michael B. Rothberg, Arthur J. McCullough, Phuc Le, and Naim Alkhouri
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Cirrhosis ,National Health and Nutrition Examination Survey ,Population ,Type 2 diabetes ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Diabetes mellitus ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Prevalence ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,education ,Retrospective Studies ,Pharmacology ,education.field_of_study ,Pioglitazone ,business.industry ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Nutrition Surveys ,United States ,030104 developmental biology ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,030220 oncology & carcinogenesis ,Female ,Steatosis ,business ,medicine.drug - Abstract
Background: We aimed to estimate population-based trends in the prevalence of coexisting type 2 diabetes (T2D) and suspected nonalcoholic fatty liver disease (NAFLD) and pioglitazone use among U.S. adults.Research design and methods: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2003 to 2016. We included people aged ≥18 years who had HbA1C >6.4%, fasting plasma glucose >125 mg/dL, or were told they had diabetes by a doctor. Suspected NAFLD was defined using a hepatic steatosis index of >36. Prevalence was estimated for each 2-year survey cycle. Trends were analyzed using logistic regression, accounting for the complex survey design.Results: Total sample size was 40,323 U.S. adults, of which 5690 had T2D. Age-adjusted prevalence of T2D with NAFLD increased from 5.6% in 2003-2004 to 6.8% in 2015-2016 (p-value
- Published
- 2019
35. Bariatric Surgery in Patients with Cirrhosis and Portal Hypertension
- Author
-
Ali Aminian, Arthur J. McCullough, Zubaidah Nor Hanipah, Stacy A. Brethauer, Philip R. Schauer, Suriya Punchai, and Srinivasan Dasarathy
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Sleeve gastrectomy ,Cirrhosis ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Bariatric Surgery ,030209 endocrinology & metabolism ,03 medical and health sciences ,0302 clinical medicine ,Hematoma ,Weight loss ,Interquartile range ,Hypertension, Portal ,Weight Loss ,Humans ,Medicine ,Retrospective Studies ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Obesity, Morbid ,Endoscopy ,Surgery ,Treatment Outcome ,Portal hypertension ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Dyslipidemia - Abstract
Studies on bariatric patients with cirrhosis and portal hypertension are limited. The aim of this study was to review our experience in cirrhotic patients with portal hypertension who had bariatric surgery. All cirrhotic patients with portal hypertension who underwent laparoscopic bariatric surgery, from 2007 to 2017, were retrospectively reviewed. Thirteen patients were included; eight (62%) were female. The median age was 54 years (interquartile range, IQR 49–60) and median BMI was 48 kg/m2 (IQR 43–55). Portal hypertension was diagnosed based on endoscopy (n = 5), imaging studies (n = 3), intraoperative increased collateral circulation (n = 2), and endoscopy and imaging studies (n = 3). The bariatric procedures included sleeve gastrectomy (n = 10, 77%) and Roux-en-Y gastric bypass (n = 3, 23%). The median length of hospital stay was 3 days (IQR 2–4). Three 30-day complications occurred including wound infection (n = 1), intra-abdominal hematoma (n = 1), and subcutaneous hematoma (n = 1). No intraoperative or 30-day mortalities. There were 11 patients (85%) at 1-year follow-up and 9 patients (69%) at 2-year follow-up. At 2 years, the median percentage of excess weight loss (EWL) and total weight loss (TWL) were 49 and 25%, respectively. There was significant improvement in diabetes (100%), dyslipidemia (100%), and hypertension (50%) at 2 years after surgery. Bariatric surgery in selected cirrhotic patients with portal hypertension is relatively safe and effective.
- Published
- 2018
36. Considerations for bariatric surgery in patients with cirrhosis
- Author
-
Arthur J. McCullough, George Boon-Bee Goh, and Philip R. Schauer
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Bariatric Surgery ,Context (language use) ,Disease ,Severity of Illness Index ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Weight loss ,Diabetes mellitus ,Hypertension, Portal ,Prevalence ,medicine ,Humans ,Metabolic Syndrome ,business.industry ,Patient Selection ,Fatty liver ,Gastroenterology ,Minireviews ,General Medicine ,medicine.disease ,Obesity, Morbid ,Surgery ,Liver ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Metabolic syndrome ,medicine.symptom ,Steatohepatitis ,business - Abstract
With the ever increasing global obesity pandemic, clinical burden from obesity related complications are anticipated in parallel. Bariatric surgery, a treatment approved for weight loss in morbidly obese patients, has reported to be associated with good outcomes, such as reversal of type two diabetes mellitus and reducing all-cause mortality on a long term basis. However, complications from bariatric surgery have similarly been reported. In particular, with the onslaught of non-alcoholic fatty liver disease (NAFLD) epidemic, in associated with obesity and metabolic syndrome, there is increasing prevalence of NAFLD related liver cirrhosis, which potentially connotes more risk of specific complications for surgery. Bariatric surgeons may encounter, either expectedly or unexpectedly, patients with non-alcoholic steatohepatitis (NASH) and NASH related cirrhosis more frequently. As such, the issues and considerations surrounding their medical care/surgery warrant careful deliberation to ensure the best outcomes. These considerations include severity of cirrhosis, liver synthetic function, portal hypertension and the impact of surgical factors. This review explores these considerations comprehensively and emphasizes the best approach to managing cirrhotic patients in the context of bariatric surgery.
- Published
- 2018
37. Stable isotope-based flux studies in nonalcoholic fatty liver disease
- Author
-
Stephen F. Previs, Takhar Kasumov, and Arthur J. McCullough
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Cirrhosis ,Chronic liver disease ,digestive system ,Gastroenterology ,Article ,Mass Spectrometry ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Isotopes ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Diabetes mellitus ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Pharmacology ,Chemistry ,nutritional and metabolic diseases ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Endocrinology ,030211 gastroenterology & hepatology ,Steatosis ,Steatohepatitis ,Flux (metabolism) - Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression. This review focuses mainly on the utilization of mass spectrometry-based methods for the understanding of metabolic abnormalities in the different stages of NAFLD. For example, stable isotopes-based flux studies demonstrated multi-organ insulin resistance, dysregulated glucose, lipids and lipoprotein metabolism in patients with NAFLD. We also review recent developments in the stable isotope-based technologies for the study of mitochondrial dysfunction, oxidative stress and fibrogenesis in NAFLD. We highlight the limitations of current methodologies, discuss the emerging areas of research in this field, and future directions for the applications of stable isotopes to study NAFLD and its complications.
- Published
- 2018
38. The association of nonalcoholic steatohepatitis and obstructive sleep apnea
- Author
-
Rocio Lopez, Mohammad Maysara Asfari, Arthur J. McCullough, Srinivasan Dasarathy, and Fadi Niyazi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Databases, Factual ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,Prevalence ,Humans ,Medicine ,030212 general & internal medicine ,Risk factor ,Aged ,Sleep Apnea, Obstructive ,Hepatology ,business.industry ,Gastroenterology ,Case-control study ,Sleep apnea ,Odds ratio ,Middle Aged ,medicine.disease ,United States ,Confidence interval ,nervous system diseases ,respiratory tract diseases ,Obstructive sleep apnea ,Cross-Sectional Studies ,Case-Control Studies ,Female ,030211 gastroenterology & hepatology ,Metabolic syndrome ,business ,Dyslipidemia - Abstract
BACKGROUND AND AIM The association between obstructive sleep apnea (OSA) and abnormal liver enzymes has been reported in multiple studies. The existing literature regarding the relationship between OSA and nonalcoholic steatohepatitis (NASH) is conflicting. Thus we aimed to determine the relationship between OSA and NASH from a large database. PATIENTS AND METHODS A cross-sectional study was performed using the 2012 Nationwide Inpatient Sample. We identified adult patients (18-90 years) who had a diagnosis of OSA using the International Classification of Diseases 9th version codes. The control group was comprised of adult individuals with no discharge records of OSA. NASH diagnosis was also identified using the International Classification of Diseases 9th version codes. The association between OSA and NASH was calculated using univariable and multivariable logistic regression. RESULTS A total of 30 712 524 hospitalizations were included. The OSA group included 1 490 150 patients versus 29 222 374 in the control non-OSA group. The OSA group average age was 61.8±0.07 years (44.2% females) compared with 57.0±0.11 years (60.1% females) in the non-OSA group. NASH prevalence was significantly higher in the OSA group compared with the non-OSA group [2% (95% confidence interval (CI): 1.9, 2.1) vs. 0.65% (95% CI: 0.63, 0.66), P
- Published
- 2017
39. Medical Management of Portal Hypertension and Its Complications
- Author
-
Tavankit Singh and Arthur J. McCullough
- Subjects
medicine.medical_specialty ,Cirrhosis ,business.industry ,medicine.medical_treatment ,Portal venous pressure ,Gastroenterology ,Gastric varices ,Liver transplantation ,medicine.disease ,Hepatorenal syndrome ,Internal medicine ,Ascites ,medicine ,Portal hypertension ,Radiology, Nuclear Medicine and imaging ,Surgery ,medicine.symptom ,business ,Hepatic encephalopathy - Abstract
Portal hypertension, most commonly caused by cirrhosis, is defined as an elevated hepatic venous pressure gradient that can lead to complications including ascites, hepatic, esophageal/gastric varices, hepatic encephalopathy, and hepatorenal syndrome. While these complications are initially managed by medical and endoscopic treatments, progressive decompensation of liver disease may lead to liver transplantation.
- Published
- 2017
40. Association Between Small Intestinal Bacterial Overgrowth by Glucose Breath Test and Coronary Artery Disease
- Author
-
P N Thota, Arthur J. McCullough, Aldo L. Schenone, Andre Fialho, Andrea Fialho, Gursimran Kochhar, and Bo Shen
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Coronary Disease ,030204 cardiovascular system & hematology ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Intestine, Small ,Small intestinal bacterial overgrowth ,medicine ,Humans ,Risk factor ,Aged ,Retrospective Studies ,Breath test ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Odds ratio ,Middle Aged ,medicine.disease ,Gastrointestinal Microbiome ,Coronary arteries ,Glucose ,medicine.anatomical_structure ,Breath Tests ,Cardiology ,Female ,030211 gastroenterology & hepatology ,business ,Methane ,Hydrogen ,Kidney disease - Abstract
A possible role of gut bacteria and their metabolic by-products in the development of coronary artery disease (CAD) is suspected. There is a lack of studies evaluating the association of small intestinal bacterial overgrowth (SIBO) with the development of CAD. To evaluate the frequency and risk factors for angiography-confirmed CAD in patients with or without SIBO. A total of 1059 patients tested for SIBO using the glucose hydrogen/methane breath test from 2006 to 2014 were evaluated. In total, 160 had coronary artery angiography and were included in the study. SIBO-positive patients were compared to SIBO-negative patients. Demographic, clinical, and laboratory variables and the presence of CAD on coronary angiography were analyzed. Patients with SIBO had a higher frequency of CAD (78.9 vs. 38.6%, p
- Published
- 2017
41. Hyaluronic acid 35 normalizes TLR4 signaling in Kupffer cells from ethanol-fed rats via regulation of microRNA291b and its target Tollip
- Author
-
Sanjoy Roychowdhury, Rebecca L. McCullough, Damien Bellos, Megan R. McMullen, Arthur J. McCullough, Katherine S. Pollard, Carol de la Motte, Pierre Gholam, Paramananda Saikia, and Laura E. Nagy
- Subjects
0301 basic medicine ,Lipopolysaccharide ,Kupffer Cells ,lcsh:Medicine ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,microRNA ,medicine ,Animals ,Humans ,Hyaluronic Acid ,lcsh:Science ,Liver Diseases, Alcoholic ,Sensitization ,Messenger RNA ,Multidisciplinary ,Ethanol ,Tumor Necrosis Factor-alpha ,Chemistry ,Macrophages ,TOLLIP ,lcsh:R ,Intracellular Signaling Peptides and Proteins ,Transfection ,Rats ,3. Good health ,Cell biology ,Toll-Like Receptor 4 ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,TLR4 ,Tumor necrosis factor alpha ,lcsh:Q ,Signal Transduction - Abstract
TLR4 signaling in hepatic macrophages is increased after chronic ethanol feeding. Treatment of hepatic macrophages after chronic ethanol feeding with small-specific sized hyaluronic acid 35 (HA35) normalizes TLR4 signaling; however, the mechanisms for HA35 action are not completely understood. Here we used Next Generation Sequencing of microRNAs to identify negative regulators of TLR4 signaling reciprocally modulated by ethanol and HA35 in hepatic macrophages. Eleven microRNAs were up-regulated by ethanol; only 4 microRNAs, including miR291b, were decreased by HA35. Bioinformatics analysis identified Tollip, a negative regulator of TLR4, as a target of miR291b. Tollip expression was decreased in hepatic macrophages from ethanol-fed rats, but treatment with HA35 or transfection with a miR291b hairpin inhibitor restored Tollip expression and normalized TLR4-stimulated TNFα expression. In peripheral blood monocytes isolated from patients with alcoholic hepatitis, expression of TNFα mRNA was robustly increased in response to challenge with lipopolysaccharide. Importantly, pre-treatment with HA35 reduced TNFα expression by more than 50%. Taken together, we have identified miR291b as a critical miRNA up-regulated by ethanol. Normalization of the miR291b → Tollip pathway by HA35 ameliorated ethanol-induced sensitization of TLR4 signaling in macrophages/monocytes, suggesting that HA35 may be a novel therapeutic agent in the treatment of ALD.
- Published
- 2017
42. S1074 LDL:HDL Ratio as a Risk Factor for Non-Alcoholic Steatohepatitis (NASH) in Non-Obese Non-Alcoholic Fatty Liver Disease (NAFLD) Patients
- Author
-
Manik Aggarwal, Brittany Mitchell, and Arthur J. McCullough
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Fatty liver ,Gastroenterology ,Non alcoholic ,Disease ,medicine.disease ,Non obese ,Internal medicine ,medicine ,Risk factor ,Steatohepatitis ,business - Published
- 2020
43. S0089 Acute Pancreatitis and Metabolic Syndrome: Prevalence, Trends, and Outcomes
- Author
-
John A. Vargo, Madhusudhan R. Sanaka, Rajat Garg, Amandeep Singh, Hassan Siddiki, Amit Bhatt, Sunguk Jang, Arthur J. McCullough, Prabhleen Chahal, Tyler Stevens, Mohamed Tausif Siddiqui, and Pravallika Chadalavada
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Acute pancreatitis ,Metabolic syndrome ,medicine.disease ,business - Published
- 2020
44. 13 CHEMOPREVENTIVE EFFECT OF STATIN ON HEPATOCELLULAR CARCINOMA IN NON-ALCOHOLIC STEATOHEPATITIS PATIENTS WITH CIRRHOSIS
- Author
-
Kanokwan Pinyopornpanish, Wael Al-Yaman, Arthur J. McCullough, William D. Carey, Carlos Romero-Marrero, and Robert S. Butler
- Subjects
medicine.medical_specialty ,Cirrhosis ,Statin ,Hepatology ,business.industry ,medicine.drug_class ,Gastroenterology ,Non alcoholic ,medicine.disease ,AASLD Abstracts ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Steatohepatitis ,business - Published
- 2021
45. Sa352 DEVELOPMENT AND VALIDATION OF MACHINE LEARNING MODEL FOR DETECTION OF PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS AT RISK OF PROGRESSION TO CIRRHOSIS (FIBROTIC-NASH)
- Author
-
Arthur J. McCullough, Daniel Rozenbaum, Manik Aggarwal, Muhammad Zarrar Khan, and Rajat Garg
- Subjects
medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Non alcoholic ,Steatohepatitis ,medicine.disease ,business - Published
- 2021
46. 587 MACHINE LEARNING MODEL CORRECTLY IDENTIFIES PATIENTS WITH ADVANCED LIVER FIBROSIS WHICH ARE INDETERMINATE BY FIB-4 INDEX IN NON-ALCOHOLIC FATTY LIVER DISEASE
- Author
-
Manik Aggarwal, Jacob Shreve, and Arthur J. McCullough
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Liver fibrosis ,Fatty liver ,Gastroenterology ,Non alcoholic ,Disease ,Fib 4 index ,medicine.disease ,Internal medicine ,medicine ,Indeterminate ,business - Published
- 2021
47. Current Modalities of Fibrosis Assessment in Non-alcoholic Fatty Liver Disease
- Author
-
George Boon-Bee Goh, Mark C.C. Cheah, and Arthur J. McCullough
- Subjects
medicine.medical_specialty ,Review Article ,Disease ,Gastroenterology ,03 medical and health sciences ,Modalities ,0302 clinical medicine ,Fibrosis ,NAFLD ,Internal medicine ,medicine ,Fibrosis assessment ,Hepatology ,medicine.diagnostic_test ,business.industry ,Fatty liver ,Gold standard (test) ,medicine.disease ,Magnetic resonance elastography ,030220 oncology & carcinogenesis ,Liver biopsy ,030211 gastroenterology & hepatology ,Radiology ,Steatohepatitis ,business ,Transient elastography - Abstract
Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health concern. In the subset of NAFLD patients with non-alcoholic steatohepatitis (NASH), the presence of significant fibrosis at index assessment is associated with poor prognosis and increased mortality. Hence, there is a growing need to accurately assess and stage fibrosis. Liver biopsy, the current gold standard, has limitations with sampling error and is invasive, with associated inherent risk. This has led to a host of non-invasive means of assessing fibrosis, which has garnered relevance in a disease that requires serial assessment of fibrosis longitudinally over time. This review discusses, comprehensively, the various tools available to the clinician for the assessment of fibrosis, including the various scoring systems used in liver biopsy, the non-invasive means of serum biomarkers, such as the highly-validated NAFLD fibrosis score, and the imaging-based modalities, such as transient elastography and magnetic resonance elastography.
- Published
- 2017
48. The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue
- Author
-
Stanley L. Hazen, Arthur J. McCullough, Mete Civelek, Anthony D. Gromovsky, J. Mark Brown, Christopher A Flask, Amanda L. Brown, W.H. Wilson Tang, Swapan K Das, Mark J. Graham, Lin Li, Belinda Willard, Calvin Pan, Zeneng Wang, Rosanne M. Crooke, Sathyamangla V. Naga Prasad, Aldons J. Lusis, Daniel Ferguson, Diana M. Shih, Srinivasan Dasarathy, Nam Che, Robert N. Helsley, Nizar N. Zein, Manya Warrier, Yong Hong Meng, Joerg Heeren, Markus Heine, Bernadette O. Erokwu, Arunachal Chatterjee, Richard E. Morton, Rebecca C. Schugar, Richard G. Lee, Markku Laakso, Lawrence L. Rudel, Hanjun Kim, Xinmin S. Li, Amy C. Burrows, and Carl D. Langefeld
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Cell ,Subcutaneous Fat ,Gene Expression ,Adipose tissue ,Flavin-containing monooxygenase ,White adipose tissue ,030204 cardiovascular system & hematology ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Methylamines ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Inbred strain ,Diabetes mellitus ,Internal medicine ,medicine ,Animals ,Humans ,Adipocytes, Beige ,Obesity ,lcsh:QH301-705.5 ,Mice, Knockout ,chemistry.chemical_classification ,Gene knockdown ,business.industry ,Monooxygenase ,medicine.disease ,3. Good health ,Mice, Inbred C57BL ,medicine.anatomical_structure ,030104 developmental biology ,Endocrinology ,Enzyme ,lcsh:Biology (General) ,Diabetes Mellitus, Type 2 ,Biochemistry ,chemistry ,Oxygenases ,Female ,business - Abstract
Summary: Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel. Further, antisense oligonucleotide-mediated knockdown or genetic deletion of the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) conferred protection against obesity in mice. Complimentary mouse and human studies indicate a negative regulatory role for FMO3 in the beiging of white adipose tissue. Collectively, our studies reveal a link between the TMAO-producing enzyme FMO3 and obesity and the beiging of white adipose tissue. : Microbes resident in the human intestine represent a key transmissible environmental factor contributing to obesity and related disorders. Schugar et al. now show that expression of the TMAO-producing enzyme FMO3 is linked to obesity and energy expenditure in both mice and humans. Keywords: microbiota, nutrition, obesity, diabetes, adipose, flavin-containing monooxygenase 3, FMO3
- Published
- 2017
49. Stage of fibrosis and portal pressure correlation in nonalcoholic steatohepatitis
- Author
-
Abinav Humar, Jyothsna Talluri, Achuthan Sourianarayanane, and Arthur J. McCullough
- Subjects
Adult ,Liver Cirrhosis ,Male ,Nonalcoholic steatohepatitis ,medicine.medical_specialty ,Biopsy ,Hepatitis C virus ,Liver fibrosis ,Portal venous pressure ,medicine.disease_cause ,Severity of Illness Index ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Fibrosis ,Internal medicine ,Humans ,Medicine ,Stage (cooking) ,Hepatology ,medicine.diagnostic_test ,business.industry ,Venous pressure ,Middle Aged ,medicine.disease ,Hepatitis C ,Portal Pressure ,digestive system diseases ,Liver ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,business - Abstract
Hepatic venous pressure gradient (HVPG) measurement correlates with staging of liver fibrosis. Patients with nonalcoholic steatohepatitis (NASH) have a different pattern of fibrosis compared with hepatitis C virus (HCV) with possible alterations in pressures.The aim of this study was to compare portal pressures with the stage of fibrosis in NASH in comparison with other liver diseases.Records of all patients who had undergone transjugular liver biopsy with pressure measurements between January 2001 and June 2013 were reviewed. Wedge hepatic venous pressure (WHVP) and HVPG were compared with stages of fibrosis in liver diseases of different etiologies.Among 142 patients included in this study, the liver disease etiology was as follows: HCV (26.6%) and NASH (24.6%), with the remaining (38.7%) grouped under other categories. The mean age of the patients was 51.2±11.5 years, with more men with HCV (73.1%) compared with NASH (51.4%) in terms of etiology (P=0.046). There were strong correlations between the stage of fibrosis with both the HVPG (r=0.64; P0.0001) and the WHVP (r=0.63; P0.0001) in NASH patients. Compared with HCV patients, NASH patients had a lower HVPG (3.4±2.4 vs. 7.5±11 mmHg/stage; P=0.01) with a coefficient estimate of -0.24 (P=0.017) and WHVP (9.6±5.5 vs. 14.6±15.2 mmHg/stage; P=0.03) for the stage of fibrosis.HVPG and WHVP measurements were strongly correlated with stages of fibrosis in NASH. Patients with NASH had lower HVPG and WHVP for each stage of fibrosis compared with HCV patients. This raises the concern of underestimation of pressures by HVPG in NASH etiology for the stage of disease or increased fibrosis despite lower pressures in them.
- Published
- 2017
50. Anthony S. Tavill, M.D., F.A.C.P., F.R.C.P., F.A.C.G. (1936‐2016)
- Author
-
Arthur J. McCullough
- Subjects
Physics ,England ,Hepatology ,Stereochemistry ,Gastroenterology ,History, 20th Century ,History, 21st Century - Published
- 2016
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.