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Hepatic encephalopathy (HE) is a common complication of advanced liver disease causing brain dysfunction. This is likely due to the accumulation of unfiltered toxins within the bloodstream. A known risk factor for developing or worsening HE is the placement of a transjugular intrahepatic portosystemic shunt (TIPS), which connects the pre-hepatic and post-hepatic circulation allowing some blood to bypass the dysfunctional liver and decreases portal hypertension. To better understand the pathophysiology of post-TIPS HE, we conducted a multi-center prospective cohort study employing metabolomic analyses on hepatic vein and peripheral vein blood samples from participants with cirrhosis undergoing elective TIPS placement, measuring chemical modifications and changes in concentrations of metabolites resulting from TIPS placement. In doing so, we identified numerous alterations in metabolites, including bile acids, glycerophosphocholines, and bilirubins possibly implicated in the development and severity of HE.

Background Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for the treatment of NASH. Aim To assess the relative rank-order of different pharmacological interventions in fibrosis improvement and NASH resolution. Methods A comprehensive search of several databases was conducted by an experienced librarian. We included randomised controlled-trials (RCTs) comparing pharmacological interventions in patients with biopsy-proven NASH. The primary outcome was ≥1 stage improvement in fibrosis. The secondary outcome was NASH resolution. Results A total of 26 RCTs with 23 interventions met the eligibility criteria. Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively. For NASH resolution, semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively. Lanifibranor, obeticholic acid, pioglitazone and vitamin E were significantly better than placebo in achieving ≥1 stage of fibrosis improvement. Conversely, semaglutide, liraglutide, vitamine E plus pioglitazone, pioglitazone, lanifibranor and obeticholic acid were significantly better than placebo in achieving NASH resolution. Conclusion These data provide relative rank-order efficacy of various NASH therapies in terms of their improvements in liver fibrosis and NASH resolution. Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.

Background and aims Chronic hepatitis B (CHB) can lead to hepatocellular carcinoma (HCC). While both tenofovir disoproxil (TDF) and entecavir (ETV) have been shown to reduce the risk of HCC, their comparative effectiveness is unclear. We estimated the comparative effectiveness of these two agents in reducing the risk of HCC in patients with CHB, through a systematic review and meta-analysis. Approach and results We searched multiple electronic databases from January 1, 1998, to October 31, 2019, for randomized controlled trials and observational comparative effectiveness studies in adults with CHB treated with ETV compared to TDF, reporting the incidence of HCC (minimum follow-up 12 months). Primary outcome was incidence of HCC, calculated as incidence rate ratio (IRR) with 95% confidence interval (CI, unadjusted analysis) and hazard ratio (HR) with 95% CI (adjusted analysis, where reported). Of 1,971 records identified, 14 studies (263,947 person-years) were included for quantitative analysis. On unadjusted meta-analysis of 14 studies, the risk of HCC was not statistically different between ETV and TDF (IRR, 1.28; 95% CI, 0.99-1.66). When using available adjusted data (multivariate or propensity-matched data), the risk of HCC among patients treated with ETV was 27% higher when compared to TDF (seven studies; 95% CI, 1.01-1.60, P = 0.04). Additional analysis of adjusted data when separately reported among patients with cirrhosis demonstrated an adjusted HR of 0.90 (95% CI, 0.66-1.23), suggesting no difference between ETV-treated and TDF-treated groups. The overall confidence in estimates was very low (observational studies, high heterogeneity). Conclusions TDF may be associated with lower risk of HCC when compared to ETV.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers’ opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient’s HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 U.S. medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient’s HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; p

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Previous studies have established a correlation between increasing chronological age and risk of cirrhosis. This pattern raised interest in the role of telomeres and the telomerase complex in the pathogenesis of liver fibrosis and cirrhosis. This review aims to summarize and analyze the current understanding of telomere regulation in hepatocytes and lymphocytes and how this ultimately relates to the development of liver fibrosis. Notably, in chronic viral hepatitis, telomere shortening in hepatocytes and lymphocytes occurs in such a way that may promote further viral replication while also leading to liver damage. However, while telomere shortening occurs in both hepatocytes and lymphocytes and ultimately results in cellular death, the mechanisms of telomere loss appear to be initiated by independent processes. The understanding of telomere maintenance on a hepatic and immune system level in both viral and non-viral etiologies of cirrhosis may open doors to novel therapeutic strategies. (Gut Liver 2019;13:11-15)

The impact of achieving a sustained viral response on extrahepatic manifestations after liver transplant is unclear. In this study, our aim was to evaluate whether sustained viral responses in hepatitis C-positive liver transplant recipients can lead to improved nonhepatic outcomes.We studied 84 consecutive liver transplant recipients who achieved a sustained viral response with direct-acting antiviral agents at the University of California Los Angeles. We collected laboratory data before and after the sustained viral response was achieved. Paired t tests were performed.The mean age and standard deviation of our cohort was 62.4 ± 7.6 years. The mean time from achieving a sustained viral response to last follow-up in our cohort was 19.5 ± 10.8 months. In the entire cohort, there were no changes in mean fasting blood glucose (123 ± 42 vs 120 ± 35 mg/dL; P = .49). We observed a significant improvement in renal function in recipients with stage 1 and 2 chronic kidney disease (82 ± 15 vs 71.16 ± 16 mL/min/1.73 m2; P ⟨ .001) and in those treated within 3 months of liver transplant (75 ± 28 vs 61 ± 16 mL/min/1.73 m2; P = .035). Fasting blood glucose decreased in recipients with a diagnosis of impaired fasting blood glucose (109 ± 16 vs 103 ± 13 mg/dL; P = .001).The benefits on glucose metabolism and renal function after a sustained viral response in liver transplant recipients appear to be limited to those with early chronic kidney disease and those treated soon after transplant. The potential benefits from direct-acting antiviral agents on these parameters may be overshadowed by the effects of immunosuppressant therapy.

Improved short- and long-term survival of liver transplant recipients has led to increased focus on complications of both the early and late posttransplant periods. A variety of metabolic complications have been observed in the post–orthotopic liver transplant population, including hypertension, hyperlipidemia, obesity, diabetes mellitus, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. Although only a small proportion of patients experience metabolic complications prior to transplantation, the prevalence of these complications posttransplantation reaches or exceeds that of the general population. This is of particular concern, as cardiovascular disease is the second leading cause of death in the late transplant period. A number of mechanisms mediate these metabolic complications, including reversal of cirrhosis pathophysiology, patient lifestyle factors, and immunosuppressive medications. Titration and modification of immunosuppression have been demonstrated to improve and sometimes even eliminate these conditions. Therefore, given the multiple etiologies contributing to the metabolic derangements, an effective management approach must incorporate lifestyle modifications, immunosuppression titration, and medical management. Best practices and understanding of the mechanisms underlying these complications allow for discussion of initial therapies and strategies; however, further study is necessary to determine the optimal management of metabolic complications over time.