Search

Abstract The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05–4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43–1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Abstract Background Liver transplantation is the only curative treatment for patients with end-stage liver disease. Short-term survival has improved due to improved surgical techniques and greater efficacy of immunosuppressive drugs. However, long-term survival has not improved to the same extent as the short-term survival, and the 10-year survival after liver transplantation is 60%. In addition to liver- and transplant-related causes, comorbidities such as cardiovascular, pulmonary, renal, and metabolic diseases have emerged as leading causes of morbidity and mortality in liver transplant recipients. The objective of this study is to assess the burden of comorbidities and identify both liver- and transplant-related risk factors as well as traditional risk factors that contribute to the pathogenesis of comorbidity in liver transplant recipients. Methods/design The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study is an observational, longitudinal study. We aim to include all adult liver transplant recipients in Denmark (n = approx. 600). Participants will be matched by sex and age to controls from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). Physical and biological measures including blood pressure, ankle–brachial index, spirometry, exhaled nitric oxide, electrocardiogram, transthoracic echocardiography, computed tomography (CT) angiography of the heart, unenhanced CT of chest and abdomen and blood samples will be collected using uniform protocols in participants in DACOLT, CGPS, and CCHS. Blood samples will be collected and stored in a research biobank. Follow-up examinations at regular intervals up to 10 years of follow-up are planned. Discussion There is no international consensus standard for optimal clinical care or monitoring of liver transplant recipients. This study will determine prevalence, incidence and risk factors for comorbidity in liver transplant recipients and may be used to provide evidence for guidelines on management, treatment and screening and thereby contribute to improvement of the long-term survival. Trial registration ClinicalTrials.gov: NCT04777032; date of registration: March 02, 2021.

Objective About half of the rheumatology trainees do not use a portfolio. This project was established to reach consensus about the content of a EULAR portfolio for Rheumatology training and subsequently develop portfolio assessment forms.Methods After establishing a portfolio working group (WG), including nine rheumatologists and one educationalist, a systematic literature review (SLR) on the content and structure of portfolios for postgraduate learning was conducted (November 2018). This was followed by a survey among WG members and members of the EMerging EUlar NETwork, inquiring about the content and structure of existing national portfolios. The portfolio WG selected the key components of the portfolio, taking previous experience and feasibility into account. Assessment forms (eg, case-based discussion) were developed and pilot-tested.Results 13/2034 articles were included in the SLR (12 high/1 moderate risk of bias). Information on procedural skills, personal reflections, learning goals and multisource feedback was most often included a portfolio. Twenty-five respondents completed the survey (response≈50%). Feedback from assessors, reflective writing and formulation of learning goals were considered important dimensions to be covered in a portfolio. Six key components of the portfolio were established: curriculum vitae, personal development plan, clinical work, professional behaviours, education and research activities. Suggested minimal content for each component was formulated. Four assessment forms were successfully pilot-tested by 11 rheumatologists and their trainees.Conclusion A EULAR portfolio for Rheumatology training and assessment forms were developed. Portfolio implementation, particularly in countries without an existing portfolio, may promote a higher standard of rheumatology training across Europe.

Objective Little is known about the prognosis of infections in patients with ankylosing spondylitis (AS) compared with patients without AS. The purpose of this study was to examine whether AS is associated with poorer outcomes in patients who are hospitalised with pneumonia.Methods In a population-based cohort study including patients with hospitalised pneumonia with and without AS, we compared 90-day rates of mortality, all-cause readmission (90 days post-discharge) and pulmonary complications including pulmonary embolism, empyema and pulmonary abscess. We used Cox regression analyses to compute crude and adjusted HRs while adjusting for sex, age and level of comorbidity.Results A total of 387 796 patients (median age 71 years) were hospitalised for pneumonia in Denmark between 1997 and 2017. Among these, 842 (0.2%) had AS (median age 65 years). The 90-day mortality was 12.5% in patients with AS and 15.5% in patients with non-AS pneumonia, with crude and adjusted 90-day HRs of 0.79 (95% CI 0.66 to 0.96) and 0.95 (95% CI 0.79 to 1.16), respectively. The 90-day post-discharge readmission rate was 27.3% in patients with AS and 25.4% in patients without AS, with a corresponding adjusted readmission HR of 1.12 (95% CI 0.98 to 1.27). Relative risk of pulmonary complications among patients with AS compared with patients without AS decreased over the study period, with adjusted HRs of 1.63 (95% CI 0.82 to 3.27) in 1997–2006 falling to 0.62 (95% CI 0.31 to 1.23) in 2007–2017.Conclusions AS is not associated with increased mortality following hospitalisation for pneumonia. Furthermore, no increased risk of readmission or pulmonary complications in patients with AS was detected in recent study years.

Objective Patients with rheumatoid arthritis (RA) experience an increased risk of infections, but the prognosis of infections is unclear. We examined if patients with RA have worse outcomes from pneumonia than non-RA individuals.Methods In a population-based cohort study, we computed 90-day mortality rates and crude and adjusted HRs comparing pneumonia patients with and without RA. Among patients with RA, we evaluated prognostic effects of RA medications including prednisolone and disease activity as assessed by C reactive protein (CRP) or platelet levels measured 30–180 days before admission to avoid any influence from the subsequent infection.Results Among 52 577 patients hospitalised for the first time with pneumonia, 1220 (2.3%) had RA. The 90-day mortality was 19.9% for patients with RA and 18.9% for non-RA patients (adjusted 90-day HR of 1.05 (95% CI 0.92 to 1.19)). Compared with CRP levels

Else Helene Ibfelt,1 Jan Sørensen,2,3 Dorte V Jensen,4,5 Lene Dreyer,5,6 Berit Schiøttz‑Christensen,7 Pia H Thygesen,8 Ada Colic,9 Johnny L Raun,10 Natalia Manilo,11 Anne Rødgaard,4 Uta E Poulsen,12 Claus Rasmussen,13 Torben Hansen,14 Babara Unger,15 Randi Pelck,16 Anita Kincses,17 Henrik Nordin,18 Tove Lorenzen,19 Ali Theibich,20 Inger Marie Jensen Hansen,21 Jakob Espesen,22 Jolanta Grydehøj,23 Mette Holland-Fischer,24 Anne Gitte Loft,25 Merete Lund Hetland4,26 1Research Centre for Prevention and Health, Capital Region of Denmark, Rigshospitalet – Glostrup, Denmark; 2Centre of Health Economics Research, Institute of Public health, University of Southern Denmark, Odense, Denmark; 3Healthcare Outcome Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland; 4DANBiO and Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet – Glostrup, Glostrup, 5Center for Rheumatology and Spine Diseases, Gentofte University Hospital, Hellerup, 6The Parker Institute, Frederiksberg and Bispebjerg Hospital, Frederiksberg, 7Spine Centre of Southern Denmark, Hospital Lillebaelt, Middelfart, 8Department of Rheumatology, Odense University Hospital, Odense, 9Department of Rheumatology, Sydvestjysk Sygehus, Esbjerg/Grintsted, 10Department of Internal Medicine and Rheumatology, SLB – Fredericia Hospital, Fredericia, 11Department of Rheumatology, Frederiksberg Hospital, Copenhagen, 12Department of Rheumatology, Gigthospital Gråsten, Gråsten, 13Clinic of Internal Medicine, Rheumatology, Regionshospital Nordjylland, Hjørring, 14Department of Rheumatology, Holbæk sygehus, Holbæk, 15Department of Internal Medicine/Rheumatology, Hospitalsenheden Horsens, Horsens, 16Department of Rheumatology, Zealand University Hospital, Køge, 17Department of Rheumatology, Nordsjællands Hospitaler, Hillerød, 18Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, 19Department of Rheumatology, Silkeborg Regional Hospital and University Clinic, Silkeborg, 20Department of Rheumatology, Slagelse Hospital, Slagelse, 21Department of Rheumatology and University of Southern Denmark, Svendborg Hospital, Odense, 22Department of Internal Medicine, Vejle Hospital, Vejle, 23Department of Rheumatology, Regional Hospital, West Jutland, Herning, 24Department of Rheumatology, Aalborg University Hospital, Ålborg, 25Department of Rheumatology, Aarhus University Hospital, Aarhus, 26Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Objectives: In Denmark, patients with rheumatoid arthritis (RA) are registered in the nationwide clinical DANBIO quality register and the Danish National Patient Registry (DNPR). The aim was to study the validity of the RA diagnosis and to estimate the completeness of relevant RA cases in each registry.Study design and setting: Patients registered for the first time in 2011 with a diagnosis of RA were identified in DANBIO and DNPR in January 2013. For DNPR, filters were applied to reduce false-positive cases. The diagnosis was verified by a review of patient records. We calculated the positive predictive values (PPVs) of the RA diagnosis registrations in DANBIO and DNPR, and estimated the registry completeness of relevant RA cases for both DANBIO and DNPR. Updated data from 2011 to 2015 from DANBIO were retrieved to identify patients with delayed registration, and the registry completeness and PPV was recalculated.Results: We identified 1,678 unique patients in DANBIO or in DNPR. The PPV (2013 dataset) was 92% in DANBIO and 79% in DNPR. PPV for DANBIO on the 2015 update was 96%. The registry completeness of relevant RA cases was 43% in DANBIO, increasing to 91% in the 2015 update and 90% in DNPR.Conclusion: DANBIO held a high proportion of true RA cases (96%) and was found to be superior to the DNPR (79%) with regard to the validity of the diagnosis. Both registries were estimated to have a high completeness of RA cases treated in hospital care (~90%). Keywords: rheumatoid arthritis, validity, incidence, clinical registry, Denmark

Background Obesity is associated with metabolic derangement and non-alcoholic fatty liver disease ( NAFLD). Macrophages are involved in liver inflammation and fibrosis, and soluble (s) CD163 is a macrophage activation marker. Objectives To associate s CD163 with parameters of paediatric obesity and NAFLD, as well as changes in these parameters during lifestyle intervention. Methods We studied 117 obese children during a 10-week lifestyle intervention; 71 completed the 12-month follow-up. We recorded clinical and biochemical data, and performed liver ultrasonography. Results Baseline s CD163 was higher in children with elevated alanine transaminase ( ALT) (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L−1, P = 0.03), steatosis (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L−1, P = 0.01) and high paediatric NAFLD fibrosis index (2.3 ± 0.7 vs. 1.9 ± 0.6 mg L−1, P = 0.03). Baseline s CD163 was independently associated with ALT, cholesterol and high-sensitivity C-reactive protein (hs- CRP). The change in s CD163 during lifestyle intervention was associated with changes in ALT, homeostatic model assessment of insulin resistance ( HOMA- IR), hs- CRP and cholesterol, and inversely associated with the change in high-density lipoprotein cholesterol. Conclusion s CD163 was associated with markers of liver injury and metabolic parameters in obese children, and changes in these parameters during lifestyle intervention. This may suggest that activated macrophages play a role in NAFLD and s CD163 may serve as a marker of liver disease severity and treatment effect. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Decompressing the portal hypertension by inserting a transjugular intrahepatic porto-systemic shunt (TIPS) in undernourished liver cirrhosis patients results in gains in body weight. It is important to understand whether this reflects an advantageous or unfavourable shift in nutrition status. This to some extent can be judged from the changes in the patients'' adipokine patterns. We, therefore, examined the circulating levels of the most important adipokines before and after the TIPS procedure. Methods: Twenty-five liver cirrhosis patients were examined before TIPS insertion and followed for six months after the procedure. Their body composition was determined by the bioimpedance technique. The serum concentrations of adiponectin, retinol binding protein 4 (RBP4), and leptin were measured. Results: The TIPS procedure induced a 12% increase in body cell mass (P = 0.03) but did not change the body fat mass. At six months, serum adiponectin was increased by 60% (mean ± SD, 10.7 ± 6.1 vs. 16.9 ± 8.9 mg/L; P = 0.001), serum RBP4 was decreased by 45% (28.6 ± 20.0 vs. 16.3 ± 9.6 mg/L; P = 0.01), and the leptin levels remained unchanged. Conclusions: The TIPS-related tissue build up was accompanied by increased adiponectin and decreased RBP4. Such changes are associated with an anabolic condition where the adipose tissue possesses residual capacity for energy storage. TIPS, therefore, can be considered to be nutritionally beneficial to cirrhosis patients. [Copyright &y& Elsevier]

Background/objectives: Soluble CD163 (sCD163), a macrophage activation marker, is upregulated in conditions of macrophage proliferation and activation. Elevated sCD163 levels have been associated with liver disease severity and progression. During liver transplantation, the implanted liver is exposed to ischaemia and reperfusion injury, resulting in an acute inflammatory response and macrophage activation. The relationship between sCD163 levels during liver transplantation and the development of early allograft dysfunction (EAD) has not been investigated., Methods: We included 27 cirrhosis patients (age 55 [range 32-72] years, 23 men) on the waiting list for liver transplantation. Alcohol consumption and viral hepatitis were the most frequent causes for cirrhosis. Patients were characterised by standard biochemical analysis and based on clinical disease severity scores. Information about donor, graft and course of the liver transplantation was recorded. sCD163 levels were measured at the time of liver transplantation before surgery, 2 h after reperfusion, and then at 24 h after transplantation., Results: We observed above-normal sCD163 levels at baseline (5.9 mg/L [4.7-8.8]). Two hours after reperfusion, sCD163 levels increased significantly from baseline (8.4 mg/L [7.4-10.9]; P  < 0.01). Twenty-four hours after transplantation, sCD163 levels were significantly reduced compared with baseline (3.7 mg/L [2.9-5.5]; P  < 0.01). However, in patients with EAD (n = 16), sCD163 levels were increased compared with patients without EAD (4.1 [3.2-7.4] vs. 3.1 [2.8-3.8] mg/L; P  = 0.03)., Conclusions: We observed elevated sCD163 levels in patients with EAD after liver transplantation, confirming macrophage activation to play a role in EAD. Thus, sCD163 may be used as an early marker for EAD after liver transplantation, but larger studies are warranted to validate these findings.

Hepatic encephalopathy (HE) is a common feature of acute-on-chronic liver failure (ACLF). Although ammonia, inflammation, and cerebral oxygenation are associated with HE in acute liver failure, their roles in ACLF are unknown. The aim of this prospective, longitudinal study was to determine the role of these pathophysiological variables in ACLF patients with and without HE. We studied 101 patients with ACLF admitted to the intensive care unit. Severity of ACLF and HE, arterial ammonia, jugular venous oxygen saturation (JVO2 ), white blood cell count (WCC), and C-reactive protein were measured at days 0, 1, 3, and 7. Patients were followed until death or hospital discharge. Mortality was high (51 patients, 50.5%), especially in patients with HE of whom 35 of 53 (66.0%) died regardless of ACLF severity. At baseline, increased WCC and abnormal JVO2 (high or low) were independent predictors of death. Further deterioration in inflammation, JVO2 , and ammonia were also predictive of mortality. JVO2 deviation and hyperammonemia were associated with the presence and severity of HE; improvement in these parameters was associated with a reduction in HE grade. No direct interaction was observed between these variables in regards to mortality or HE. In conclusion, this study describes potential mechanisms of HE in ACLF indicating that ammonia and abnormal cerebral oxygenation are important. The results suggest that ammonia, JVO2 , and WCC are important prognostic biomarkers and therapeutic targets. The relative roles of these pathophysiological factors in the pathogenesis of HE in ACLF or guiding therapy to improve survival requires future study. Liver Transplantation 22 732-742 2016 AASLD., (© 2016 American Association for the Study of Liver Diseases.)

Background & Aims: Cirrhotic patients with acute decompensation frequently develop acute-on-chronic liver failure (ACLF), which is associated with high mortality rates. Recently, a specific score for these patients has been developed using the CANONIC study database. The aims of this study were to develop and validate the CLIF-C AD score, a specific prognostic score for hospitalised cirrhotic patients with acute decompensation (AD), but without ACLF, and to compare this with the Child-Pugh, MELD, and MELD-Na scores., Methods: The derivation set included 1016 CANONIC study patients without ACLF. Proportional hazards models considering liver transplantation as a competing risk were used to identify score parameters. Estimated coefficients were used as relative weights to compute the CLIF-C ADs. External validation was performed in 225 cirrhotic AD patients. CLIF-C ADs was also tested for sequential use., Results: Age, serum sodium, white-cell count, creatinine and INR were selected as the best predictors of mortality. The C-index for prediction of mortality was better for CLIF-C ADs compared with Child-Pugh, MELD, and MELD-Nas at predicting 3- and 12-month mortality in the derivation, internal validation and the external dataset. CLIF-C ADs improved in its ability to predict 3-month mortality using data from days 2, 3-7, and 8-15 (C-index: 0.72, 0.75, and 0.77 respectively)., Conclusions: The new CLIF-C ADs is more accurate than other liver scores in predicting prognosis in hospitalised cirrhotic patients without ACLF. CLIF-C ADs therefore may be used to identify a high-risk cohort for intensive management and a low-risk group that may be discharged early., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate long-term complications and survival in patients with Budd-Chiari syndrome (BCS) referred to a Danish transjugular intrahepatic portosystemic shunt (TIPS) centre., Methods: Twenty-one consecutive patients from 1997-2008 were retrospectively included [15 women and 6 men, median age 40 years (range 17-66 years)]. Eighteen Danish patients came from the 1.8 million catchment population of Aarhus University Hospital and three patients were referred from Scandinavian hospitals. Management consisted of tests for underlying haematological, endocrinological, or hypercoagulative disorders parallel to initiation of specific treatment of BCS., Results: BCS was mainly caused by thrombophilic (33%) or myeloproliferative (19%) disorders. Forty-three percents had symptoms for less than one week with ascites as the most prevalent finding. Fourteen (67%) were treated with TIPS and 7 (33%) were manageable with treatment of the underlying condition and diuretics. The median follow-up time for the TIPS-treated patients was 50 mo (range 15-117 mo), and none required subsequent liver transplantation. Ascites control was achieved in all TIPS patients with a marked reduction in the dose of diuretics. A total of 14 TIPS revisions were needed, mostly of uncovered stents. Two died during follow-up: One non-TIPS patient worsened after 6 mo and died in relation to transplantation, and one TIPS patient died 4 years after the TIPS-procedure, unrelated to BCS., Conclusion: In our BCS cohort TIPS-treated patients have near-complete survival, reduced need for diuretics and compared to historical data a reduced need for liver transplantation.

Background & Aims: Cirrhosis of the liver is characterised by insulin resistance and low levels of insulin-like growth factor I (IGF-I). Lack of IGF-I may contribute to this insulin resistance, as IGF-I increases insulin sensitivity. This study aimed to determine the effects of normalisation of IGF-I on insulin action in cirrhosis., Methods: This article is a randomised sequence-crossover placebo controlled study. Eight patients with cirrhosis and eight controls were studied following treatment with IGF-I (50 μg/kg twice daily) or saline. Insulin action, glucose utilisation and endogenous glucose production were measured during the euglycaemic hyperinsulinaemic clamp., Results: The patients with cirrhosis had normal fasting glucose level, but increased levels of insulin (P < 0.05) and C-peptide (P < 0.05). Insulin resistance resulted from a defect in glycogen synthesis, whereas insulin-mediated suppression of glucose production was unaltered. In cirrhosis, IGF-I treatment normalised free (from 0.07 ± 0.01 to 0.26 ± 0.05 μg/L) and total IGF-I (from 73 ± 6 to 250 ± 39 μg/L), whereas in controls, the IGF-I level increased into the upper physiological range (free IGF-I from 0.23 ± 0.02 to 0.61 ± 0.06 μg/L; total IGF-I from 200 ± 19 to 500 ± 50 μg/L) (all P-values < 0.05). In cirrhosis, IGF-I treatment did not change fasting glucose, insulin or C-peptide levels (P > 0.05). In the controls, insulin and C-peptide levels decreased (P < 0.05). IGF-I treatment did not improve insulin sensitivity in cirrhosis., Conclusions: Because normalisation of IGF-I levels did not affect insulin sensitivity lack of IGF-I is unlikely to result in insulin resistance in cirrhosis. IGF-I supplementation is therefore unlikely to improve insulin action in patients with cirrhosis., (© 2011 John Wiley & Sons A/S.)

Background: Cirrhotic cardiomyopathy is described as latent cardiac failure. However, it remains to be investigated whether the myocardial dysfunction is present even at rest., Aims: The aim of the present study was to quantify left ventricular function at rest by means of tissue Doppler imaging in patients with cirrhosis and relate the findings to liver status and cirrhosis aetiology., Methods: Forty-four consecutive patients and 23 age-matched healthy controls were included. Conventional echocardiographic- and tissue Doppler-derived indices of systolic and diastolic function were obtained. Liver function was quantified by the galactose elimination capacity and clinical stage by the Child-Pugh and MELD scores., Results: Both systolic and diastolic myocardial functions were compromised in the patients at rest. Left ventricular ejection fraction (56.4 ± 6.1 vs. 59.9 ± 3.9%, P<0.02), mean peak systolic tissue velocity (4.6 ± 0.9 vs. 5.6 ± 0.7 cm/s, P<0.001) and mean systolic strain rate (-1.23 ± 0.19 vs. -1.5 ± 0.14/s, P<0.001) were all reduced in cirrhosis patients. Thirty-four patients (54%) had diastolic dysfunction, 11 had impaired diastolic relaxation pattern (25%), 12 had the more severe pseudonormal filling pattern (27%) and one had restrictive filling or severe diastolic dysfunction (2%). None of the echocardiographic findings were related to the cirrhosis aetiology., Conclusion: Tissue Doppler imaging during rest detected substantial systolic and diastolic myocardial dysfunction in cirrhotic patients. This supports the existence of a distinct cirrhotic cardiomyopathy., (© 2011 John Wiley & Sons A/S.)

Objective: Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis., Methods: One hundred and sixteen (65 females) obese children with a median age of 12.3 (7-15) years were examined before and after a 10-week stay at a weight loss camp. Examination included anthropometry and fasting blood samples measuring plasma glucose, serum insulin, SHBG, DHEAS, testosterone, 17β-oestradiol, FSH and LH., Results: Body mass index (BMI) decreased (P<0.01), insulin sensitivity and SHBG increased (P<0.01), independent of gender and puberty. The changes in insulin sensitivity and the changes in SHBG correlated significantly (P<0.01) independent of gender, puberty and the changes in BMI. Testosterone increased in boys (P<0.01) and tended to decrease in girls (P=0.05, in girls after menarche (P=0.03)). FSH increased in boys and girls. LH increased in boys and was unchanged in girls., Conclusions: During weight loss, insulin sensitivity and SHBG increased significantly in obese children, and the changes in insulin sensitivity and the changes in SHBG correlated significantly independent of gender, puberty and the changes in BMI. There was sexual dimorphism in the changes of testosterone, with the changes in boys towards increased virilisation and the changes in girls towards less virilisation.

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7-7.3]. Fasting (f)-insulin increased from 123 +/- 81 to 193 +/- 124 pmol/l (P = 0.03), whereas f-glucose was unchanged (6.0 +/- 0.8 vs. 6.2 +/- 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7-22%) and 53% (CI: 14-90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 +/- 1.82 vs. 4.85 +/- 2.37 mg.kg(-1).min(-1)) and glucose tracer-based rate of disappearance were unchanged (5.01 +/- 1.61 vs. 4.97 +/- 2.13 mg.kg(-1).min(-1)). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 +/- 0.42 vs. 2.42 +/- 0.58 mg.kg(-1).min(-1)) and was suppressed equally by insulin (1.1 +/- 0.1 vs. 1.0 +/- 0.1 mg.kg(-1).min(-1)). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.

Aim: To study complement activation in 46 patients with alcoholic cirrhosis and ascites but no spontaneous bacterial peritonitis (SBP) and 10 healthy controls., Methods: Complement activation was determined by the measurement of soluble membrane attack complex (sMAC) concentrations in ascites and plasma. In patients, metabolic liver function was determined by the galactose elimination capacity and the clinical status assessed by the Model of End-Stage Liver Disease and Child-Pugh scores., Results: Ascites sMAC levels were markedly higher than in the corresponding plasma sample (median (range): 596 (170 - 1519) vs 160 (77 - 848) μg/L; P < 0.01). Ascites sMAC levels correlated positively with liver status. There was no relationship between ascites sMAC and leukocyte count. No relationship between ascites sMAC and blood C-reactive protein, albumin or neutrophile count was found. Plasma sMAC concentrations were slightly higher in patients than in controls [130 μg/L (70 - 204); P = 0.04]. Neither sMAC in ascites nor plasma was related to mortality., Conclusion: The increased sMAC concentration in ascites and plasma indicate an activation of the complement system in cirrhosis even in the absence of SBP. This was particularly evident in the peritoneal fluid and most marked in patients with preserved liver status. The high ascites sMAC levels may reflect transudation of membrane attack complexes from the liver. Whether this complement activation has any clinical implications remains to be clarified.

Objective: Patients with liver cirrhosis have diminished hepatic IGF-I generation, resulting in low circulating levels, whereas data on IGF-I in ascites are sparse. Therefore, we compared the IGF-system in serum and ascites from cirrhotic patients., Design and Patients: The study comprised 43 patients (12 females) with ascites and liver function of 58 +/- 10% of normal. Serum and ascites were collected concomitantly in the fasting state. In 11 patients, second serum and ascitic samples were collected within the first week. Eleven matched controls were also included. All samples were assayed for IGF-related parameters by immunoassays and by cell-based IGF-I bioassay., Results: As compared with controls, serum total IGF-I, total IGF-II, pro-IGF-II and bioactive IGF-I were reduced in liver patients, whereas IGF-binding protein 1 (IGFBP-1), IGFBP-2 and the soluble IGF-II receptor were elevated (P < 0.005 for all). In ascites, all IGF-related peptides but pro-IGF-II were further reduced as compared with serum (P < 0.001). By contrast, bioactive IGF-I was fourfold elevated in ascites as compared with serum (2.20 +/- 0.33 vs. 0.55 +/- 0.08 microg/l, P < 0.001). In ascites, the IGF-I bioactivity signal was completely blocked by addition of IGFBP-3. Repetitive measurements (n = 11) in ascites showed that all peptides but IGFBP-1 remained unchanged within 1 week., Conclusions: It is a novel observation that the in vitro bioactivity of IGF-I can be higher in fluids from an extravascular compartment than in serum, in contrast to immunoreactive levels. This supports different roles for endocrine and paracrine/autocrine IGF-I, but the pathophysiological significance of our observation remains to be clarified.

Aim: To investigate the effect of transjugular intrahepatic porto-systemic shunt (TIPS) on malnutrition in portal hypertensive cirrhotic patients., Methods: Twenty-one patients with liver cirrhosis and clinical indications for TIPS insertion were investigated before and 1, 4, 12, 52 wk after TIPS. For each patient we assayed body composition parameters [dry lean mass, fat mass, total body water (TBW)], routine liver and kidney function tests, and free fatty acids (FFA). Glucose and insulin were measured for the calculation of the homeostasis model assessment insulin resistance (HOMA-IR); liver function was measured by the galactose elimination capacity (GEC); the severity of liver disease was graded by model for end-stage liver disease (MELD)., Results: Porto-systemic gradient decreased after TIPS (6.0 +/- 2.1 mmHg vs 15.8 +/- 4.8 mmHg, P < 0.001). Patients were divided in two groups according to initial body mass index. After TIPS, normal weight patients had an increase in dry lean mass (from 10.9 +/- 5.9 kg to 12.7 +/- 5.6 kg, P = 0.031) and TBW (from 34.5 +/- 7.6 L to 40.2 +/- 10.8 L, P = 0.007), as well as insulin (from 88.9 +/- 49.2 pmol/L to 164.7 +/- 107.0 pmol/L, P = 0.009) and HOMA-IR (from 3.36% +/- 2.18% to 6.18% +/- 4.82%, P = 0.023). In overweight patients only FFA increased significantly (from 0.59 +/- 0.24 mmol/L to 0.93 +/- 0.34 mmol/L, P = 0.023)., Conclusion: TIPS procedure is effective in lowering portal pressure in patients with portal hypertension and improves body composition without significant changes in metabolic parameters.

Objective: Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) into patients with liver cirrhosis usually induces a gain in body cell mass. Changes in the IGF system in favor of anabolism may be involved. We, therefore measured blood concentrations of the components of the IGF system in cirrhosis patients before and after elective TIPS., Design and Methods: The study comprised 17 patients and 11 healthy controls. Patients were examined before and 1, 4, 12, and 52 weeks after TIPS. Biochemical analyses of the IGF system were compared with changes in body composition (bioimpedance analysis), glucose and insulin, and metabolic liver function (galactose elimination capacity)., Results: After TIPS, body cell mass rose by 3.2 kg (95% confidence interval (CI): 1.0-5.5) at 52 weeks, in correlation with baseline liver function (r(2)=0.22; P=0.03). Peripheral blood concentrations of total IGF1 and 2, bioactive IGF1, and the IGF-binding proteins (IGFBP-1, -2, and -3) remained unchanged throughout the study period. There was no change in fasting glucose, whereas fasting insulin rose by 40% (CI: 11-77%) and glucagon by 58% (CI: 11-132%) from baseline to 52 weeks after TIPS., Conclusion: Our data confirm that TIPS was associated with an increase in body cell mass in patients with liver cirrhosis, but without any change in the circulating IGF system. Thus, the results do not support the notion that effects on the circulating IGF system are involved in the anabolic effects of TIPS insertion.

Background: Wilson's disease (WD) can present in a fulminant form with hepatocellular dysfunction, hemolysis and multiorgan failure (Wilson's crisis). We present a previously healthy young woman with severe WD whose WD severity score was 13. A score >11 indicates a poor chance of survival and liver transplantation will usually be recommended., Methods: Penicillamine and acetylcysteine were initially administered, but the patient deteriorated further, and extracorporeal liver support with the Prometheus FPSA (fractionated plasma separation and adsorption) system was initiated. The patient was treated 6 h daily during 3 consecutive days., Results: Severe hemolysis was reduced to low-grade hemolysis, with no further need for transfusions. The mental state improved and after 4 months practically all biochemical markers were normalized., Conclusions: This is the first report of FPSA albumin dialysis of a patient with Wilson's crisis and the first report in which a patient with a WD score >11 survived without transplantation.