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The ongoing burden of COVID-19 in persons with end stage liver failure necessitates the development of sound and rational policies for organ transplantation in this population. Following our initial experience with two COVID-19 recovered recipients who died shortly after transplant, we adjusted our center policies, re-evaluated outcomes, and retrospectively analyzed the clinical course of the subsequent seven COVID-19 recovered recipients. There were two early deaths and 5 successful outcomes. Both deceased patients shared common characteristics in that they had positive SARS-CoV2 PCR tests proximal to transplant (7-17 days), had acute on chronic liver failure, and suffered thromboembolic phenomena. After a careful review of clinical and virological outcome predictors, we instituted policy changes to avoid transplantation in these circumstances. We believe that our series offers useful insights into the unique challenges that confront transplant centers in the COVID-19 era and could guide future discussions regarding this important area.

In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown.Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use.A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94).Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.

Background & Aims Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT to inform pre-LT candidate selection and post-LT addiction care. Methods Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006–2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes. Results Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, 4 distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 [abstinent](n = 103; 71%), pattern 2 [late/non-heavy](n = 9; 6.2%), pattern 3 [early/non-heavy](n = 22; 15%), pattern 4 [early/heavy](n = 12; 8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH. Conclusions A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care.

Patients with cirrhosis have high admission and readmission rates, and it is estimated that a quarter are potentially preventable. Little data are available regarding nonmedical factors impacting triage decisions in this patient population. This study sought to explore such factors as well as to determine provider perspectives on low-acuity clinical presentations to the emergency department, including ascites and hepatic encephalopathy. A survey was distributed in four liver transplant centers to both emergency medicine and hepatology providers, who included attending physicians, house staff, and advanced practitioners; 196 surveys were returned (estimated response rate 50.6%). Emergency medicine providers identified several influential nonmedical factors impacting inpatient triage decisions, including input from a hepatologist (77.7%), inadequate patient access to outpatient specialty care (68.6%), and patient need for diagnostic testing for a procedure (65.6%). When given patient-based scenarios of low-acuity cases, such as ascites requiring paracentesis, only 7.0% believed patients should be hospitalized while 48.9% said these patients would be hospitalized at their institution (P < 0.0001). For mild hepatic encephalopathy, the comparable numbers were 19.5% and 55.2%, respectively (P < 0.001). Several perceived barriers were cited for this discrepancy, including limited resources both in the outpatient setting and emergency department. Most providers believed that an emergency department observation unit protocol would influence triage toward an emergency department observation unit visit instead of inpatient admission for both ascites requiring large volume paracentesis (83.2%) and mild hepatic encephalopathy (79.4%). Conclusion: Many nonmedical factors that influence inpatient triage for patients with cirrhosis could be targeted for quality improvement initiatives. In some scenarios, providers are limited by resource availability, which results in triage to an inpatient admission even when they believe this is not the most appropriate disposition. (Hepatology Communications 2018;2:237-244).

Goals: The goal of the study is to assess the effect of direct-acting antivirals (DAAs) on the model for end-stage liver disease-sodium (MELD-Na) score and on specific decompensations related to hepatitis C virus (HCV) cirrhosis. The aim of our study was to identify a specific cohort of patients with cirrhosis, if any, that should be targeted for treatment with DAAs. Background: The development of DAAs has provided safe and well-tolerated treatment options for patients with advanced liver disease. However, controversy remains in terms of optimal timing of treatment and whether this treatment should be offered before or following liver transplantation. Methods: We identified all patients with HCV cirrhosis who initiated treatment with DAA therapy at Johns Hopkins Hospital between July 2014 and June 2016. We identified a subset of patients who had decompensated cirrhosis and recorded their MELD-Na scores and decompensations pre- and post-treatment. Results: Fifty-six patients achieved sustained virologic response with decompensated HCV cirrhosis. The group demonstrated a significant decrease in median MELD-Na score following treatment from 12 to 10.5. Furthermore, a significant percentage of patients experienced resolution of ascites following DAA therapy with 19 patients (35.2%) clearing their ascites posttreatment. Of the 19 patients who cleared ascites, MELD-Na score decreased from a median of 12 (interquartile range [IQR] 11–18) to 11 (IQR 8–14), P = 0.01. Conclusions: Our findings suggest that patients with ascites as their main decompensation should be considered for the treatment with DAAs, while awaiting liver transplant given that the MELD-Na score showed only modest improvement and thus would not affect liver transplant (LT) listing priority.

OBJECTIVES: We aimed to investigate the accuracy of the Milan, University of California San Francisco, and Up-to-7 criteria in predicting tumor recurrence after liver transplant for hepatocellular carcinoma. MATERIALS AND METHODS: For this study, 165 patients with deceased-donor liver transplant for hepatocellular carcinoma were evaluated. The Milan, University of California San Francisco, and Up-to-7 criteria were calculated based on explant pathology. RESULTS: Tumor recurrence rate after liver transplant was 14.6%. Of 165 patients, 115 (70%) were within Milan, 131 (79%) were within University of California San Francisco, and 135 (82%) were within Up-to-7 criteria. The odds ratio of tumor recurrence in patients outside versus within criteria for Milan, University of California San Francisco, and Up-to-7 was 3.6 (95% confidence interval, 1.5–9.1; P = .005), 7.5 (95% confidence interval, 2.5–19.3; P < .001), and 7.5 (95% confidence interval, 2.9–19.6; P < .001) times higher, respectively. The sensitivity of being outside of Milan in predicting tumor recurrence was comparable to University of California San Francisco and Up-to-7 criteria (56.5%, 56.5%, and 52.2%, respectively). Specificity was highest in Up-to-7 (87.3%) versus 85.2% for University of California San Francisco and 73.9% for Milan criteria. The area under the curve for Milan, University of California San Francisco, and Up-to-7 criteria was 0.63, 0.65, and 0.63. CONCLUSIONS: Application of standard criteria has significantly improved prediction of hepatocellular carcinoma recurrence. However, these criteria are inadequate, supporting the importance of other factors, including tumor biology. Research is ongoing in discovering novel biomarkers as predictors of tumor recurrence.

Background and Aim SpyGlass® cholangiopancreatoscopy system has shown early success in aiding diagnosis and management of pancreaticobiliary diseases. We aimed to assess the technical success, clinical success, diagnostic yield, therapeutic yield, and safety of the SpyGlass® system at a single institution. Methods A retrospective, single-center review of consecutive patients who underwent endoscopic retrograde cholangiopancreatography with SpyGlass® between January 2008 and August 2013 for a variety of indications. Technical success was defined as the procedure being completed as planned. Clinical success was defined as a successful outcome using diagnostic, clinical, laboratory, or imaging evidence. Results SpyGlass® cholangioscopy was carried out in 88 patients (49 females, mean age 56.9 ± 15.5 years). Indications were diagnostic in 67 and therapeutic in 21. Overall, technical success was seen in 87.5% and clinical success in 77.3%. Thirty-nine patients with indeterminate biliary stricture had technical and clinical success rates of 92.3% and 74.4%, respectively. In this subgroup, malignancy was ultimately diagnosed in 13 with 12 patients diagnosed by SpyGlass® and confirmed by surgical specimens in 12/12 cases; positive predictive value 100%). In the 23 remaining patients with indeterminate biliary strictures, one was later found to have malignancy (negative predictive value 95.8%) after 1 year of follow up. In the 13 therapeutic cases of stone removal, technical and clinical success was seen in 77.0% for both. Overall, adverse events were seen in 15.9%. Conclusions SpyGlass® demonstrated acceptable technical and clinical success rates in both diagnostic and therapeutic procedures. In particular, it allows for an accurate rate of diagnosis of indeterminate biliary strictures.

Curative therapy for hepatocellular carcinoma is liver transplant. To date, the Milan Criteria remain the best pretransplant clinical surrogate for tumor behavior and overall prognosis. Microvascular invasion portends a poor prognosis; however, it is often undetectable before transplant. Furthermore, its pretransplant indicators are not well established. In this study, we investigated the presurgical and pathologic predictors of microvascular invasion in patients with hepatocellular carcinoma.Between August 2000 and August 2013, 156 liver transplants were performed for hepatocellular carcinoma at the Johns Hopkins Medical Center. Information on clinical characteristics and pathology data, including microvascular invasion, were available for 107 patients on liver explants. Logistic regression was used to assess the effects of Milan Criteria, alpha-fetoprotein, tumor differentiation, and multilobar involvement on the presence of microvascular invasion on explant pathology.In 107 patients, 24 (22%) had microvascular invasion on pathology. In patients with microvascular invasion, 41% were outside of Milan Criteria versus 19.3% of patients within but without microvascular invasion. In patients with microvascular invasion, the rate of poor differentiation and alpha-fetoprotein level1000 ng/mL were more common than in patients without microvascular invasion; however, on univariate and multivariable analyses, Milan Criteria, alphafetoprotein level, multilobar involvement, and differentiation did not reach statistical significance in predicting microvascular invasion on pathology.In this study, potential predictors of microvascular invasion, including Milan Criteria, alphafetoprotein level, tumor differentiation, and multilobar involvement, were not predictive. Preoperative prediction of microvascular invasion remains a challenge, suggesting the need for future studies.

SpyGlass® cholangiopancreatoscopy system has shown early success in aiding diagnosis and management of pancreaticobiliary diseases. We aimed to assess the technical success, clinical success, diagnostic yield, therapeutic yield, and safety of the SpyGlass® system at a single institution.A retrospective, single-center review of consecutive patients who underwent endoscopic retrograde cholangiopancreatography with SpyGlass® between January 2008 and August 2013 for a variety of indications. Technical success was defined as the procedure being completed as planned. Clinical success was defined as a successful outcome using diagnostic, clinical, laboratory, or imaging evidence.SpyGlass® cholangioscopy was carried out in 88 patients (49 females, mean age 56.9 ± 15.5 years). Indications were diagnostic in 67 and therapeutic in 21. Overall, technical success was seen in 87.5% and clinical success in 77.3%. Thirty-nine patients with indeterminate biliary stricture had technical and clinical success rates of 92.3% and 74.4%, respectively. In this subgroup, malignancy was ultimately diagnosed in 13 with 12 patients diagnosed by SpyGlass® and confirmed by surgical specimens in 12/12 cases; positive predictive value 100%). In the 23 remaining patients with indeterminate biliary strictures, one was later found to have malignancy (negative predictive value 95.8%) after 1 year of follow up. In the 13 therapeutic cases of stone removal, technical and clinical success was seen in 77.0% for both. Overall, adverse events were seen in 15.9%.SpyGlass® demonstrated acceptable technical and clinical success rates in both diagnostic and therapeutic procedures. In particular, it allows for an accurate rate of diagnosis of indeterminate biliary strictures.