Characteristics of liver transplant candidates delisted following recompensation and predictors of such delisting in alcohol-related liver disease: a case-control study

Whether and when recovery beyond the need for transplant may occur in patients listed for decompensation remains unclear. This study aimed to investigate the characteristics of patients delisted following recompensation. Seventy-seven patients who were listed between 2005 and 2015 for decompensation, but later delisted following recompensation were included. Alcohol-related liver disease (ALD) was the underlying etiology in the majority (n=47, 61%). Listing characteristics of these patients were compared with those of decompensated ALD patients who either underwent deceased donor liver transplantation or died on the waiting list. The model for end-stage liver disease (MELD) score <20 and serum albumin ≥32g/l at listing were the only independent predictors of recompensation/delisting in ALD. The probability of recompensation was 70% when both factors were present at listing. Interestingly, about a tenth of decompensated ALD patients who died on the waiting list (median duration on waiting list 11 months) and a quarter of decompensated ALD patients who underwent living donor liver transplantation (median duration on waiting list 2 months) also had both factors at listing. In conclusion, ALD seems to be the most favorable etiology for recompensation beyond the need for transplantation. Both MELD and serum albumin at listing independently predict recompensation/delisting in ALD. It seems advisable to implement a period of observation for ALD patients with both favorable factors, before embarking on living donor liver transplantation

EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update

Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years

Genetic variation spectrum in ATP7B gene identified in Latvian patients with Wilson disease

Funding Information: This study was partially financed by the grant of Riga Stradin©≤s University, Department of Doctoral studies, grant of Roche Academy, and the funds of Latvian Council of Science (No. 09.1384; No 10.0010.02 and No. 05.0023). Publisher Copyright: © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.Background: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by allelic variants in ATP7B gene. More than 500 distinct variants have been reported, the most common WD causing allelic variant in the patients from Central, Eastern, and Northern Europe is H1069Q. Methods: All Latvian patients with clinically confirmed WD were screened for the most common mutation p.H1069Q by PCR Bi-PASA method. Direct DNA sequencing of gene ATP7B (all 21 exons) was performed for the patients with WD symptoms, being either heterozygous for H1069Q or without it on any allele. Results: We identified 15 different allelic variants along with eight non-disease-causing allelic variants. Based on the gene molecular analysis and patients' clinical data variant p.His1069Gln was found in 66.9% of WD alleles. Wide clinical variability was observed among individuals with the same ATP7B genotype. The results of our study confirm that neurological manifestations of WD are typically present later than the liver disease but no significant association between the presence/absence of the most common genetic variant and mode of initial WD presentation or age at presentation was identified. Conclusions: (1) The most prevalent mutation in Latvian patients with Wilson disease was c.3207C>A (p.His1069Gln); (2) No significant phenotype–genotype correlation was found in Latvian patients with Wilson disease; (3) The estimated prevalence of Wilson disease in Latvia is 1 of 24,000 cases which is higher than frequently quoted prevalence of 1: 30,000.publishersversionPeer reviewe

Characteristics of chronic hepatitis B patients who underwent liver biopsies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87030/1/j.1365-2893.2010.01364.x.pd

Use of Flash Glucose-Sensing Technology for 12 months as a Replacement for Blood Glucose Monitoring in Insulin-treated Type 2 Diabetes

Introduction: Published evaluations of sensor glucose monitoring use in insulin treated type 2 diabetes are limited. The aim of this study was to assess the impact of flash glucose-sensing technology as a replacement for self-monitoring of blood glucose (SMBG) over a 12-month period in participants with type 2 diabetes who were on intensive insulin therapy. Methods: An open-label, randomized, controlled study in adults with type 2 diabetes on intensive insulin therapy from 26 European diabetes centers aimed at assessing flash glucose sensing technology was conducted. Participants (N = 224) were randomized (1:2 respectively) to a control group (n = 75) that used SMBG (FreeStyle Lite™) or to an intervention group (n = 149) which used sensor glucose data (FreeStyle Libre™ Flash Glucose Monitoring System) for self-management over 6 months. All intervention group participants who completed the 6-month treatment phase continued into an additional 6-month open-access phase. Results: A total of 139 intervention participants completed the 6-month treatment phase and continued into the open-access phase. At 12 months (end of open-access period), time in hypoglycemia [sensor glucose <3.9 mmol/L (70 mg/dL)] was reduced by 50% compared to baseline [−0.70 ± 1.85/24 h (mean ± standard deviation); p = 0.0002]. Nocturnal hypoglycemia [2300 to 0600 hours, <3.9 mmol/L (70 mg/dL)] was reduced by 52%; p = 0.0002. There was no change in time in range [sensor glucose 3.9–10.0 mmol/L (70–180 mg/dL)]. SMBG testing fell from a mean of 3.9 (median 3.9) times/day at baseline to 0.2 (0.0), with an average frequency of sensor scanning of 7.1 (5.7) times/day at 12 months, and mean sensor utilization was 83.6 ± 13.8% (median 88.3%) during the open-access phase. During this 6-month extension period no device-related serious adverse events were reported. Nine participants reported 16 instances of device-related adverse events (e.g. infection, allergy) and 28 participants (20.1%) experienced 134 occurrences of anticipated skin symptoms/sensor-insertion events expected with device use (e.g. erythema, itching and rash). Conclusion: The use of flash glucose-sensing technology for glycemic management in individuals with type 2 diabetes treated by intensive insulin therapy over 12 months was associated with a sustained reduction in hypoglycemia and safely and effectively replaced SMBG. Trial Registration: ClinicalTrials.gov identifier, NCT02082184

Adverse events related to low dose corticosteroids in autoimmune hepatitis

Background: Autoimmune hepatitis requires long-term therapy, and systemic corticosteroids are the backbone of therapeutic management. Prolonged use of corticosteroids may lead to adverse events but data from long-term studies are mainly derived from studies in rheumatic diseases. Aim: To assess cataract, diabetes and fractures in relation to corticosteroid doses in the long-term maintenance treatment of patients with autoimmune hepatitis. Methods: We retrospectively collected data on 476 patients (77% women) with an established diagnosis of autoimmune hepatitis. Binary logistic regression with a generalised estimating equation was used to analyse the association between current corticosteroid use and the incidence of cataract, diabetes and fractures with onset after autoimmune hepatitis diagnosis. We corrected for sex, age, cirrhosis at diagnosis and predniso(lo)ne use in the prior 3 years to account for possible ongoing effects. Results: A total of 6634 years, with a median of 13 (range 1-40) per patient were recorded. The median age at diagnosis was 44 years (range 2-88). Adverse events were documented in 120 (25%) patients. Low-dose predniso(lo)ne (0.1-5.0 mg/d) increased the odds of fractures whereas higher doses (>5.0 mg/d) increased the odds of cataracts and diabetes. Budesonide increased the odds of cataract and fractures; this effect was independent of predniso(lo)ne use in the prior 1, 2 or 3 years. Conclusions: Even low doses of corticosteroids frequently lead to substantial adverse events refuting the assumption that adverse events are prevented by administering low doses

Methods for selecting the best evidence to inform a NICE technology appraisal on selective internal radiation therapies for hepatocellular carcinoma

Background: Systematic reviews of medical devices are particularly challenging as the quality of evidence tends to be more limited than evidence on pharmaceutical products. This article describes the methods used to identify, select and critically appraise the best available evidence on selective internal radiation therapy devices for treating hepatocellular carcinoma, to inform a technology appraisal for the National Institute for Health and Care Excellence. Methods: A comprehensive search of ten medical databases and six grey literature sources was undertaken to identify studies of three devices (TheraSphere®, SIR-Spheres® and QuiremSpheres®) for treating hepatocellular carcinoma. The large evidence base was scoped before deciding what level of evidence to include for data extraction and critical appraisal. The methodological quality of the included studies was assessed using criteria relevant to each study design. Results: Electronic searches identified 4755 records; over 1000 met eligibility criteria after screening titles and abstracts. A hierarchical process was used to scope these records, prioritising comparative studies over non-comparative studies, where available. 194 full papers were ordered; 64 met the eligibility criteria. For each intervention, studies were prioritised by study design and applicability to current UK practice, resulting in 20 studies subjected to critical appraisal and data extraction. Only two trials had a low overall risk of bias. In view of the poor quality of the research evidence, our technology appraisal focused on the two higher quality trials, including a thorough critique of their reliability and generalisability to current UK practice. The 18 poorer quality studies were briefly summarised; many were very small and results were often contradictory. No definitive conclusions could be drawn from the poorer quality research evidence available. Conclusions: A systematic, pragmatic process was used to select and critically appraise the vast quantity of research evidence available in order to present the most reliable evidence on which to develop recommendations

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120