Explore the vast range of titles available.

The rate of alcohol relapse among patients who underwent liver transplantation for alcoholic hepatitis (AH) is not precisely known. Synthesize the available evidence on liver transplantation for AH to assess alcohol relapse and 6-month survival. Meta-analysis of trials evaluating liver transplantation for AH, either clinically severe or diagnosed on the explant. Eleven studies were included. The pooled estimate rate for alcohol relapse was 0.22 (95% CI = 0.12-0.36) in overall analysis with high heterogeneity between studies (I2 = 76%), 0.20 (95% CI = 0.07-0.43) in the subgroup analysis including patients with clinically severe AH (I2 = 84%), 0.14 (95% CI = 0.08-0.23) among patients with clinically severe AH in sensitivity analysis excluding the discrepant studies that did not use stringent selection criteria for liver transplantation (I2 = 0%), and 0.15 (95% CI = 0.07-0.27) for recurrent harmful alcohol consumption among patients with clinically severe AH (I2 = 3%). The risk of alcohol relapse was not different between AH transplanted patients and patients with alcoholic cirrhosis who underwent elective liver transplantation in sensitivity analysis excluding the discrepant studies (OR = 1.68, 95%CI = 0.79-3.58, p = 0.2, I2 = 16%). The pooled estimate rate for 6-month survival was 0.85 (95% CI = 0.77-0.91, I2 = 49%), and 0.80 among patients transplanted for clinically severe AH (95% CI = 0.69-0.88, I2 = 30%). AH transplanted patients had similar 6-month survival to patients with alcoholic cirrhosis who underwent elective liver transplantation (OR = 2.00, 95% CI = 0.95-4.23, p = 0.07, I2 = 0%). Using stringent selection criteria, 14% of patients with clinically severe AH have alcohol relapse after liver transplantation. The percentage of alcohol relapse of AH transplanted patients is similar than that of patients who underwent elective liver transplantation.

Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear. To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death. Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78). At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20-0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20-1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis. Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis.

Objectives To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma. Methods In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model. Results Biliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE ( p  < 0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p  < 0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p  < 0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p  < 0.01), and between the dose of chemotherapy and intrahepatic biloma ( p  = 0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE ( p  = 0.025). Conclusions DEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis. Key points • DEB-TACE demonstrated more therapy-related hepatic locoregional complications compared to cTACE . • TACE-related hepatic locoregional toxicities occurred more frequently with high baseline PT value . • cTACE may be more appropriate in patients with high baseline PT value .

To evaluate the efficacy and safety of purine analogs (azathioprine, 6-mercaptopurine (6-MP)) in the prevention of postoperative recurrence in Crohn's disease (CD). We searched MEDLINE, the Cochrane Library, and EMBASE. The primary end points, clinical and endoscopic recurrence at 1 and 2 years, and safety were analyzed by the methods of Peto and Der Simonian and Laird. Four controlled trials enrolled 433 patients and compared azathioprine (n=3) or (6-MP) (n=1) with control arms (placebo with or without antibiotic induction therapy or mesalamine). In the overall analysis, purine analogs were more effective than control arms in preventing clinical recurrence at 1 year (mean difference, 95% confidence interval (CI): 8, 1-15%, P=0.021, number needed to treat (NNT)=13) and 2 years (mean difference, 95% CI: 13%, 2-24%, P=0.018, NNT=8). In sensitivity analyses, the efficacy of purine analogs was superior to that of placebo for the prevention of clinical and endoscopic recurrence at 1 year (mean differences, 95% CI: 13, 1.8-25%, P=0.025, NNT=7, and 23%, 9-37%, P=0.0016, NNT=4, respectively). At 1 year, in the overall analysis, purine analogs were more effective than control arms were in preventing severe (i2-4) endoscopic recurrence (mean difference, CI 95%: 15, 1.8-29%, P=0.026, NNT=7), but they were not effective in the prevention of very severe (i3-4) recurrence. The rate of adverse events leading to drug withdrawal was higher in thiopurine-treated patients than in control arms (17.2 vs. 9.8%, respectively, P=0.021). Purine analogs are more effective than placebo in preventing both clinical and endoscopic postoperative recurrence in CD, but they are associated with a higher rate of adverse events leading to drug withdrawal.

[...]the behaviour of some binge drinkers may overlap that of chronic drinkers, with several binges over several consecutive days. Main findings Consequences Addictive behaviour High correlation with alcoholism screening tests Alcohol dependence Risk in behavioural habits Unintentional injuries Social disability Interpersonal violence Higher risk of mortality Fetal alcohol syndrome Child neglect Loss of productivity Suicide Sexually transmitted diseases Unintended pregnancy Cardiovascular system Prolongation of PR and QTc interval Atrial fibrillation and ventricular arrhythmias Hypertension Haemorrhagic and ischaemic strokes Acute myocardial infarction Conversely, data concerning the impact of binge drinking on the liver are limited. 3 5 21 Therefore, the question arises as to whether specialists in liver disease should be concerned by the increase in binge drinkers.

Felix Stickel and colleagues report the results of a genome-wide association study of alcohol-related cirrhosis. They confirm PNPLA3 as a susceptibility locus and identify new association signals in MBOAT7 and TM6SF2 . Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world 1 , 2 , 3 . We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 ( P = 1.03 × 10 −9 ) and TM6SF2 ( P = 7.89 × 10 −10 ) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis ( P = 1.54 × 10 −48 ) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.

In recent years, advances have been made for treating ascites in patients with cirrhosis. Recent studies have indicated that several treatments that have been used for a long time in the management of portal hypertension may have beneficial effects that were not previously identified. Long‐term albumin infusion may improve survival in patients with cirrhosis and ascites while beta‐blockers may reduce ascites occurrence. Transjugular intrahepatic porto‐systemic shunt (TIPS) placement may also improve survival in selected patients in addition to the control with ascites. Low‐flow ascites pump insertion can be another option for some patients with intractable ascites. In this review, we summarize the latest data related to the management of ascites occurring in cirrhosis. There are still unanswered questions, such as the optimal use of albumin as a long‐term therapy, the place of beta‐blockers, and the best timing for TIPS placement to improve the natural history of ascites, as well as the optimal stent diameter to reduce the risk of shunt‐related side‐effects. These issued should be addressed in future studies.

ObjectivesVariants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), and membrane bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis. Within this population, PNPLA3 rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to explore possible risk associations of TM6SF2 rs58542926 and MBOAT7 rs641738 with HCC.MethodsRisk variants in PNPLA3, TM6SF2, and MBOAT7 were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analyzed using multivariate logistic regression.ResultsThe development of HCC was independently associated with PNPLA3 rs738409 (ORadjusted 1.84 [95% CI 1.55-2.18], p = 1.85 × 10-12) and TM6SF2 rs58542926 (ORadjusted 1.66 [1.30-2.13], p = 5.13 × 10-05), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (ORadjusted 1.04 [0.88-1.24], p = 0.61) was not significant. The population-attributable fractions were 43.5% for PNPLA3 rs738409, 11.5% for TM6SF2 rs58542926, and 49.9% for the carriage of both the variants combined.ConclusionsCarriage of TM6SF2 rs58542926 is an additional risk factor for the development of HCC in people with alcohol-related cirrhosis. Carriage of both PNPLA3 rs738409 and TM6SF2 rs58542926 accounts for half of the attributable risk for HCC in this population. Genotyping will allow for more precise HCC risk-stratification of patients with alcohol-related cirrhosis, and genotype-guided screening algorithms would optimize patient care.

Background Transjugular intrahepatic portosystemic shunt (TIPS) may be used as a salvage treatment in patients with cirrhosis and refractory variceal bleeding. Aim To synthesize the available evidence on the efficacy of TIPS in patients with cirrhosis and refractory variceal bleeding. Methods Meta‐analysis of trials evaluating TIPS in patients with cirrhosis and refractory variceal bleeding, including subgroup analysis to assess the impact of recent changes in the management of variceal bleeding (i.e., the use of Polytetrafluoroethylene‐covered TIPS and the availability of pre‐emptive TIPS as a first‐line treatment for acute variceal bleeding). Results Twenty‐three studies with 1430 patients were included. The pooled estimate rates were 0.33 (95% CI = 0.29–0.37) for death at 1 month–6 weeks, 0.46 (95% CI = 0.40–0.52) for death at 1 year, and 0.09 (95% CI = 0.06–0.11) for death due to rebleeding in the follow‐up. The pooled estimate rates for death at 1 month or 6 weeks were similar in subgroup analyses including studies that did not use covered TIPS or that did not include patients after the pre‐emptive TIPS area compared to the ones that did (pooled estimate rate 0.33 [95% CI = 0.28–0.38] and 0.32 [95% CI = 0.25–0.39], respectively). The pooled estimate rates were 0.16 (95% CI = 0.13–0.18) for rebleeding, 0.25 (95% CI = 0.17–0.36) for occurrence of hepatic encephalopathy, and 0.08 (95% CI = 0.05–0.13) for access to liver transplantation after TIPS insertion. Conclusions One third of patients with cirrhosis and refractory variceal bleeding treated with salvage TIPS died within the first 6 weeks. Recent improvements in the management of variceal bleeding did not improve the survival of patients presenting with refractory variceal bleeding.

IntroductionVariants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926) and membrane bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis. PNPLA3 rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC) within this population. The aim of this study was to explore possible risk associations of TM6SF2 rs58542926 and MBOAT7 rs641738 and the development of HCC.MethodsRisk variants in PNPLA3, TM6SF2 and MBOAT7 were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analysed using multivariate logistic regression.ResultsThe development of HCC was independently associated with PNPLA3 rs738409 (OR 1.84 [95% CI 1.55–2.18], p=1.85×10–12) and TM6SF2 rs58542926 (OR 1.66 [1.30–2.13], p=5.13×10–05) using an additive model and after controlling for sex, age, body mass index and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR 1.04 [0.88–1.24], p=0.61) was not significant. The population-attributable fractions were 43.5% for PNPLA3 rs738409, 11.5% for TM6SF2 rs58542926, and 49.9% for carriage of both variants combined.ConclusionsCarriage of TM6SF2 rs58542926 is an additional risk factor for the development of HCC in people with alcohol–related cirrhosis. Carriage of both PNPLA3 rs738409 and TM6SF2 rs58542926 accounts for half of the attributable risk for HCC in this population. Genotyping will allow for more precise HCC risk stratification of patients with alcohol-related cirrhosis, and genotype-guided screening algorithms would optimise patient care.