Novel treatments for alcoholic hepatitis.

PURPOSE OF REVIEW: The current article aims to review the latest literature on updates in therapeutics for alcohol-associated liver disease (ALD), integration of treatment of alcohol use disorder (AUD) into the management of ALD, and the role of liver transplantation for alcoholic hepatitis. RECENT FINDINGS: ALD has recently become the most common indication for liver transplantation due to the increasing prevalence of AUD and the paucity of therapeutic options. There is broad consensus on the importance of early identification of AUD and the incorporation of its treatment in the management of ALD. New targets for treatment of alcoholic hepatitis include the gut-liver axis, anti-inflammatory drugs, antioxidants, and drugs with hepatic regenerative potential. Fecal transplantation in particular has had favorable outcomes at 1 year. n-Acetylcysteine in addition to corticosteroids, granulocyte colony stimulating factor, and IL-22 have also shown improved short-term outcomes. A number of other therapies are being studied in clinical trials and their results are anxiously awaited. SUMMARY: In summary, there are several promising therapeutic options under clinical investigation for the treatment of alcoholic hepatitis and ALD; however, alcohol abstinence is key. In the absence of other effective therapies, liver transplantation for ALD remains a life-saving treatment with excellent patient and graft survival.

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

Statin Use is Protective Against Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Case-control Study.

BACKGROUND AND GOAL: The incidence of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is rising. We aimed to characterize risk factors for NAFLD-HCC development. METHODS: We performed a retrospective case-control study of HCC cases from a cohort of NAFLD patients who underwent at least 2 computed tomography scans. NAFLD-HCC cases confirmed on contrast imaging and/or biopsy were included. Controls were NAFLD patients without HCC matched by sex and age. Clinical variables were assessed. Visceral adipose tissue and subcutaneous adipose tissue were measured by computed tomography at 2 timepoints: before HCC diagnosis and at diagnosis. RESULTS: We identified 102 subjects [34 HCC cases, 68 controls, 65% (n=66) males, mean age: 69 y] from 2002 to 2016. Cirrhosis was present in 91%. In multivariate analysis, statin use was protective against HCC [odds ratio (OR)=0.20, 95% confidence interval (CI): 0.07-0.60, P=0.004], while hypertension was a risk factor for HCC (OR=5.80, 95% CI: 2.01-16.75, P=0.001). In multivariate analysis, visceral adipose tissue in males was higher before HCC diagnosis and declined by HCC diagnosis in 86%, which was a significant difference compared with controls (OR=2.78, 95% CI: 1.10-7.44, P=0.04). CONCLUSIONS: In a cohort of NAFLD-HCC patients, statin use was protective against HCC, while hypertension conferred an increased risk. Visceral adiposity at baseline was not a risk factor, but was higher in male patients before HCC development, declining in the majority by HCC diagnosis.

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

Internet Published Policies Regarding Liver Transplant Eligibility and Substance Use in United States Transplant Centers.

Liver transplant centers in the United States retain great autonomy in determining eligibility criteria for a liver transplant. This study aims to define the availability and content of liver transplant centers' publicly available Internet policies regarding eligibility criteria for liver transplant. Three trained undergraduate students performed a structured pilot-tested assessment of official websites of the United Network for Organ Sharing-registered liver transplant centers. All 141 liver transplant centers had an accessible website. Some account of eligibility criteria was provided by 53% of centers, while 32% of centers discussed substance use. Only 17% discussed their policy regarding alcohol use in candidates with underlying alcohol use disorder, and only 2% stipulated that 6 months of abstinence was required. While exclusion based on substance use or age was discussed infrequently, insurance coverage requirements, the need for social support, and the need for adherence to medical care were mentioned in 21%, 37%, and 23% of centers, respectively. Conclusion: In 2018, half of liver transplant centers provided some information on their official websites regarding eligibility criteria for liver transplant. Detailed information regarding substance use disorders and social health requirements was rare. The Internet is infrequently used by liver transplant centers as a means to publicly share information regarding selection criteria.

A case of syphilitic hepatitis in an HIV-infected patient.

While the incidence of syphilis has been persistently on the rise in the United States, hepatitis as a complication of early syphilis is relatively uncommon. We present a case of a 51-year-old homosexual, HIV-positive man who presented with acute cholestatic hepatitis with a predominantly elevated alkaline phosphatase. After laboratory studies and imaging were unrevealing, a liver biopsy was performed that showed expanded portal tracts with a predominantly lymphoplasmacytic infiltrate and prominent bile ductular proliferation with periductal neutrophils. Testing revealed a positive rapid plasma reagin, and a subsequent Warthin-Starry stain of the liver tissue demonstrated the presence of scattered spirochetes, confirmed as Treponema pallidum spirochetes on immunohistochemistry testing. These findings confirmed a diagnosis of syphilitic hepatitis. With therapy, symptoms and liver enzymes rapidly normalized. Given the persistent rise in syphilis incidence along with the morbidity and mortality associated with a missed diagnosis, keen suspicion, early identification, and treatment are crucial.