Faculty Bibliography

With the increasing incidence of hepatocellular carcinoma (HCC) in both the United States and globally, the role of liver transplantation in management continues to be an area of active conversation as it is often considered the gold standard in the treatment of HCC. The use of living donor liver transplantation (LDLT) and the indications in the setting of malignancy, both generally and in HCC specifically, are frequently debated. In terms of both overall survival and recurrence-free survival, LDLT is at least equivalent to DDLT, especially when performed for disease within Milan criteria. Emerging and compelling evidence suggests that LDLT is superior to DDLT in treating HCC as there is a significant decrease in waitlist mortality. As the oncologic indications for liver transplantation continue to expand and the gap between organ demand and organ availability continues to worsen, high volumes centers should consider using LDLT to shrink the ever-expanding waitlist.

The main aim of antiviral therapy in patients with chronic hepatitis B (CHB) is to prevent disease progression and reduce the risk of hepatocellular carcinoma (HCC). In general, treatment is recommended for select patient groups viewed as being at higher risk of developing adverse outcomes from CHB. However, patients who do not meet treatment criteria under current international guidelines may still benefit from antiviral therapy to reduce CHB-related complications. Moreover, well-tolerated antiviral drugs that are highly effective at suppressing viral replication are now widely available, and withholding therapy from patients with viremia is increasingly controversial. In this article, we review traditional treatment paradigms and argue the merits of expanding treatment eligibility to patients with CHB who do not meet current treatment criteria.

INTRODUCTION/BACKGROUND:Split liver transplantation (SLT) emerged due to its potential to contribute to the organ pool and reduce organ shortage. However, SLT is technically challenging and has been associated with higher rates of postoperative complications leading to concerns about graft and patient survival. Moreover, there are few studies on matched-pair adult recipients of SLT and whole-liver transplant (WLT), with conflicting results. METHODS:This retrospective study analyze outcomes among adults who underwent SLT at our institution from 2010 to 2019. A 1:1 propensity score matching analysis was performed based on important donor and recipient variables. Baseline characteristics and postoperative outcomes were analyzed and compared between groups. Actuarial graft and patient survival were analyzed by KM curves. RESULTS:Out of 592 adults receiving a LT in our institution, 21 SLT adult recipients were identified and matched with 21 adults undergoing WLT. As expected donor age was significantly lower in SLT recipients (16 (15-22) vs. 32 (17-47), P = .012). Additional donor characteristics, including anthropometrics, and ischemic times were similar between groups. Baseline recipient characteristics and postoperative outcomes, including length of stay, vascular complications, biliary complications, and re-transplantation were comparable between SLT and WLT recipients. Graft (95/95/95 vs. 100/94/94, P = .98) and patient (100/100/100 vs. 100/94/94, P = .30) survival at 1-, 3-, 5-years, were similar between the SLT- and WLT group, respectively. CONCLUSION/CONCLUSIONS:Split liver transplantation has the potential to increase the availability of organs for adult recipients without compromising individual outcomes.

Background/UNASSIGNED:The use of pediatric grafts for liver transplantation (LT) into adult recipients is rare, and reported outcomes are conflicting. The aim of this study is to evaluate the outcomes in adult recipients following LT with grafts from deceased pediatric donors. Methods/UNASSIGNED:A retrospective study identifying adult LT between 2010 and 2020 using pediatric deceased donor liver grafts was conducted. Adults undergoing LT with deceased donor pediatric grafts (age ≤ 12) were identified and matched 1:2 with adults receiving adult grafts (age ≥ 18) based on recipient age (±10 y), model for end-stage liver disease (MELD) score at transplant (±5 points) and etiology of liver disease. To assess real liver size differences between the pediatric-donor and adult-donor groups, patients receiving a graft from a donor between 13 and 17 y were excluded from the main analysis and studied independently. Outcomes between the groups were compared. Complication rates were identified and graded using Clavien-Dindo classification. Graft and patient survival were assessed by Kaplan-Meier curves. Results/UNASSIGNED: = 0.48). Conclusions/UNASSIGNED:Excellent patient and graft survival is achievable with LT using young pediatric deceased donor grafts in smaller adult recipients. Outcomes are comparable with recipients of age and MELD-matched adult donors. Careful donor MELD-score recipient matching and close monitoring for potential biliary and vascular complications are crucial to achieve acceptable outcomes.

Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver-related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol-associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. Multivariable Cox proportional hazards regression was used to assess for associations between alcohol use and mortality, cirrhosis decompensation (new ascites, encephalopathy, or variceal bleeding), and hepatocellular carcinoma (HCC). At baseline, 36.4% of patients endorsed alcohol use and 17.1% had unhealthy alcohol use. During a mean 4.9 years of follow-up, 25,806 (57.9%) patients died, 9,409 (21.4%) developed a new decompensation, and 4,733 (11.1%) developed HCC. In patients with ALD-cirrhosis and HCV-cirrhosis, unhealthy alcohol use, compared with no alcohol use, was associated with higher risks of mortality (adjusted hazard ratio [aHR] = 1.13, 95% confidence interval [CI] = 1.07-1.19 and aHR = 1.14, 95% CI = 1.08-1.20, respectively) and decompensation (aHR = 1.18, 95% CI = 1.07-1.30 and aHR = 1.08, 95% CI = 1.00-1.16, respectively). Alcohol use was not associated with HCC, regardless of cirrhosis etiology. Conclusion: Unhealthy alcohol use was common in patients with cirrhosis and was associated with higher risks of mortality and cirrhosis decompensation in patients with HCV-cirrhosis and ALD-cirrhosis. Therefore, health care providers should make every effort to help patients achieve abstinence. The lack of association between alcohol use and HCC merits further investigation.

INTRODUCTION:In hepatitis C (HCV) patients, obesity and/or diabetes may increase the risk of liver-related outcomes. We aimed to determine whether diabetes and/or obesity are associated with adverse outcomes in direct-acting antiviral (DAA)-treated HCV patients. METHODS:). Diabetes was defined by ICD-9/10 codes in association with hemoglobin A1c > 6.5% or medication prescriptions. Patients were followed from 180 days post-DAA initiation until 2/14/2019 to assess for development of cirrhosis, decompensations, hepatocellular carcinoma (HCC), and death. Multivariable Cox proportional hazards regression models were used to determine the association between diabetes and/or obesity and outcomes. RESULTS:During a mean follow-up of 3 years, 10.1% patients died, 5.0% were newly diagnosed with cirrhosis, 4.7% had a decompensation and 4.0% developed HCC. Diabetes was associated with an increased risk of mortality (AHR = 1.25, 95% CI 1.10-1.42), cirrhosis (AHR = 1.31, 95% CI 1.16-1.48), decompensation (AHR = 1.74, 95% CI 1.31-2.31), and HCC (AHR = 1.32, 95% CI 1.01-1.72) among patients without baseline cirrhosis. Compared to normal-weight persons, obese persons had a higher risk of cirrhosis, but overweight and obese persons had lower risk of mortality and HCC. CONCLUSIONS:In this large DAA-treated Veterans cohort, pre-DAA diabetes increases mortality and liver-related events independent of SVR. Continued vigilance is warranted in patients with diabetes despite SVR. Elevated BMI categories appear to have improved outcomes, although further studies are needed to understand those associations.

BACKGROUND & AIMS:Patients with chronic hepatitis B (CHB) infection routinely undergo screening for hepatocellular carcinoma (HCC), but the efficacy of screening remains unclear. We aimed to evaluate the impact of screening with ultrasound and/or serum alpha-fetoprotein (AFP) on HCC-related mortality in patients with CHB. METHODS:We performed a matched case-control study of patients with CHB receiving care through the Veterans Affairs (VA) health administration. Cases were patients who died of HCC between 01/01/2004 and 12/31/2017, while controls were patients with CHB who did not die of HCC. Cases were matched to controls by CHB diagnosis date, age, sex, race/ethnicity, cirrhosis, antiviral therapy exposure, hepatitis B e antigen status, and viral load. We identified screening ultrasound and AFPs obtained in the 4 years preceding HCC diagnosis in cases and the equivalent index date in controls. Using conditional logistic regression, we compared cases and controls with respect to receipt of screening. A lower likelihood of screening in cases corresponds to an association between screening and reduced risk of HCC-related mortality. RESULTS:We identified 169 cases, matched to 169 controls. Fewer cases than controls underwent screening with either screening modality (33.7% vs. 58.6%) or both modalities (19.5% vs. 34.4%). In multivariable conditional logistic regression, screening with either modality was associated with a lower risk of HCC-related mortality (adjusted odds ratio [aOR] 0.21, 95% CI 0.09-0.50), as was screening with both modalities (aOR of 0.13; 95% CI 0.04-0.43). CONCLUSIONS:HCC screening was associated with a substantial reduction in HCC-related mortality in VA patients with CHB. LAY SUMMARY:Patients with hepatitis B infection have a high risk of developing liver cancer. It is therefore recommended that they undergo frequent screening for liver cancer, but whether this leads to a lower risk of dying from liver cancer is not clear. In this study, we show that liver cancer screening is associated with a reduction in the mortality from liver cancer in patients with hepatitis B infection.