Severe Cholestatic Hepatitis Secondary to SARS-CoV-2.

Liver injury is a common manifestation of coronavirus disease 2019 (COVID-19), with most injuries manifesting as transient mild hepatocellular injury. Cholestatic injury occurs less commonly and is typically mild. Severe cholestatic injury is rare, with only 4 cases reported in the literature. We present a 70-year-old woman with no known liver disease who presented with severe COVID-19 and developed severe cholestatic hepatitis. A liver biopsy was performed demonstrating bile duct injury, uncommonly reported in patients with COVID-19. This complication needs greater awareness because it has been known to cause progressive liver disease requiring transplantation.

Tumor aggressiveness is independent of radiation quality in murine hepatocellular carcinoma and mammary tumor models.

PURPOSE: Estimating cancer risk associated with interplanetary space travel is complicated. Human exposure data to high atomic number, high-energy (HZE) radiation is lacking, so data from low linear energy transfer (low-LET) γ-ray radiation is used in risk models, with the assumption that HZE and γ-ray radiation have comparable biological effects. This assumption has been challenged by reports indicating that HZE radiation might produce more aggressive tumors. The goal of this research is to test whether high-LET HZE radiation induced tumors are more aggressive. MATERIALS AND METHODS: Murine models of mammary and liver cancer were used to compare the impact of exposure to 0.2Gy of 300MeV/n silicon ions, 3 Gy of γ-rays or no radiation. Numerous measures of tumor aggressiveness were assessed. RESULTS: For the mammary cancer models, there was no significant change in the tumor latency or metastasis in silicon-irradiated mice compared to controls. For the liver cancer models, we observed an increase in tumor incidence but not tumor aggressiveness in irradiated mice. CONCLUSION: Tumors in the HZE-irradiated mice were not more aggressive than those arising from exposure to low-LET γ-rays or spontaneously. Thus, enhanced aggressiveness does not appear to be a uniform characteristic of all tumors in HZE-irradiated animals.

Liver Transplantation in the Obese Cirrhotic Patient.

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.

Vemurafenib-induced granulomatous hepatitis.

Vemurafenib (Zelboraf; Genentech, CA) is a highly effective oral chemotherapy agent for patients with metastatic melanoma who carry the BRAF V600E mutation. Side effects of this protein kinase inhibitor (PKI) include arthralgia, rash, and fatigue, which are reported in up to one third of treated patients. Mild abnormalities in liver biochemistries were reported with vemurafenib use in 30% of subjects, 11% developed severe laboratory abnormalities, and acute liver failure has been reported (Table ). Herein, a case of severe vemurafenib-induced granulomatous hepatitis leading to chronic cholestasis is reported along with a review of the hepatotoxicity of other PKIs.

Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease in the United States, afflicting an estimated 80 to 100 million Americans. Nonalcoholic fatty liver disease is a spectrum of liver diseases composed of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). Although nonalcoholic fatty liver has a negligible risk of progression, patients with NASH often develop cirrhosis or hepatocellular carcinoma. Although liver biopsy is required to diagnose NASH, only patients with a high risk of NASH or advanced fibrosis require this evaluation. Despite the high prevalence of NAFLD, well-defined screening recommendations are currently lacking. In this review, suggestions for screening, diagnosis, and initial work-up of NAFLD are given on the basis of established guidelines and recent publications. Proposed drug treatments of NASH are also discussed, highlighting the study outcomes, as well as proposed uses and limitations of these drugs. The literature was searched in PubMed using search terms nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, with filters of "English language." A date range of January 1, 2000, to May 1, 2015, was used for the search. The bibliographies of key references were also searched manually, and seminal publications before the year 2000 were included.