Addressing sex-based disparities in liver transplantation.

PURPOSE OF REVIEW: Disparities in access to liver transplantation by sex have been well described, disadvantaging women. Understanding the multifactorial causes of these disparities as well as the variety of proposed solutions is critical to improving access to this life-saving intervention for women. This review aims to summarize the current body of evidence on observed sex disparities in liver transplantation and highlight actionable, evidence-based mechanisms by which these disparities can be addressed. RECENT FINDINGS: Strategies for addressing sex disparities in liver transplantation include increasing organ utilization, changing allocation policy, and leveraging public policies to reduce the incidence of end-stage liver disease. Several other promising interventions are currently being explored. SUMMARY: In the United States, women face additional barriers to liver transplantation on the basis of sex. Immediate action is necessary to systematically address these inequities.

Prospective clinical trials and novel therapies in the medical management of severe alcohol-associated hepatitis.

Content available: Author Interview and Audio Recording.

Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease.

Naltrexone is an approved drug for management of alcohol use disorder (AUD), but data in patients with liver disease (LD) are limited. We aimed to evaluate the safety of naltrexone in those with LD. This is a retrospective cohort of adults with and without LD who were prescribed naltrexone for AUD from 2015 to 2019 in a safety-net setting. Naltrexone hepatic safety was determined by liver enzyme changes during and after compared to before naltrexone prescription as well as rates of subsequent hospitalization and death by Kaplan-Meier methods. Factors associated with hospitalization were examined by Cox regression. Of 160 patients prescribed naltrexone for AUD, 100 (63%) had LD and 47 (47%) of those with LD had cirrhosis (47% decompensated). The total cohort, LD, and cirrhosis groups had lower adjusted mean aspartate aminotransferase and alanine aminotransferase levels after versus before naltrexone prescription (p < 0.001). Two-year survival was 97.7% (95% confidence interval [CI], 84.6-99.7), 95.4% (95% CI, 82.8-98.8), 90.8% (95% CI, 73.5-97.0), and 81.3% (95% CI, 41.2-93.8) in those without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis groups (p = 0.46), respectively. Alcohol-related 2-year hospitalization rates were 8.2% (95% CI, 2.7-24), 27.7% (95% CI, 16.6-44.0), 40.5% (95% CI, 24.8-61.6), and 41.7% (95% CI, 23.3-66.6) for the groups without LD, LD without cirrhosis, cirrhosis, and decompensated cirrhosis (p = 0.007), respectively. Independent predictors of subsequent hospitalization were LD, (hazard ratio [HR], 3.70; 95% CI, 1.19-11.51; p = 0.02), cirrhosis (HR, 5.16; 95% CI, 1.69-15.75), and shorter duration (≤30 days) of naltrexone prescription (HR, 2.50; 95% CI, 1.l2-5.20; p = 0.01). Conclusion: Naltrexone is safe to use in patients with underlying LD, including those with compensated cirrhosis. Although encouraging, more safety data are needed for those with decompensated cirrhosis.

Contemporary strategies to assess and manage liver donor steatosis: a review.

PURPOSE OF REVIEW: Due to a persistent shortage of donor livers, attention has turned toward ways of utilizing marginal grafts, particularly those with steatosis, without incurring inferior outcomes. Here we review the evaluation and utilization of steatotic liver allografts, highlight recently published data, and discuss novel methods of graft rehabilitation. RECENT FINDINGS: Although severe liver allograft (>60%) steatosis has been associated with inferior graft and recipient outcomes, mild (<30%) steatosis has not. There is ongoing debate regarding safe utilization of grafts with moderate (30-60%) steatosis. Presently, no established protocols for evaluating steatosis in donor candidates or utilizing such grafts exist. Liver biopsy is accepted as the gold standard technique, though noninvasive methods have shown promise in accurately predicting steatosis. More recently, machine perfusion has been shown to enhance ex situ liver function and reduce steatosis, emerging as a potential means of optimizing steatotic grafts prior to transplantation. SUMMARY: Steatotic liver allografts constitute a large proportion of deceased donor organs. Further work is necessary to define safe upper limits for the acceptable degree of steatosis, develop standardized evaluation protocols, and establish utilization guidelines that prioritize safety. Machine perfusion has shown promise in rehabilitating steatotic grafts and offers the possibility of expanding the deceased donor pool.

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation.

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81-0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R2 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.