Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

Health care-related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease.

BACKGROUND: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). METHODS: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. RESULTS: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. CONCLUSIONS: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.

Single-center experience with early liver transplantation for acute alcohol-related hepatitis-Limitations of the SALT score and directions for future study.

Alcohol-related liver disease (ALD) is the leading indication for liver transplantation worldwide. Since Mathurin et al. described their experience in providing early liver transplantation for patients with ALD in 2011, other centers have followed suit with generally favorable survival outcomes. This patient population poses a unique clinical challenge given the expedited nature of the evaluation and the lack of any significant sobriety period prior to transplantation. The SALT (Sustained Alcohol Use Post-Liver Transplant) score is a standardized psychometric tool increasingly used to help stratify the risk of relapse and guide listing decisions for these challenging clinical situations. In 2018, our center introduced a protocol for early liver transplantation for acute alcohol-related hepatitis (AAH). In this article, we offer a retrospective review of 26 patients transplanted between May 2018 and May 2021, including at least 1-year follow-up, and compare outcomes to initial SALT scores; we further identify additional factors that may impact post-transplant success. As transplant committees continue to weigh the ethical dilemma of denying lifesaving treatment against the obligation to remain stewards of a limited resource, we aim to contribute to a more nuanced understanding of risk regarding early transplantation for ALD.

Preferred language and disease severity predict evaluation for liver transplantation among patients admitted with alcohol-associated hepatitis.

BACKGROUND: Liver transplantation (LT) for alcohol-associated hepatitis (AH) is a relatively new practice and limited work exists surrounding the role social determinants of health may play in evaluation. This includes language that defines how patients interact with the healthcare system. We explored characteristics of patients with AH evaluated for LT within an integrated health system. METHODS: Using a system-wide registry, we identified admissions for AH from 1 January 2016 to 31 July 2021. A multivariable logistic regression model was developed to evaluate independent predictors of LT evaluation. RESULTS: Among 1723 patients with AH, 95 patients (5.5%) underwent evaluation for LT. Evaluated patients were more likely have English as their preferred language (95.8% vs 87.9%, P = 0.020), and had higher INR (2.0 vs 1.4, P < 0.001) and bilirubin (6.2 vs 2.9, P < 0.001). AH patients who underwent evaluation had a lower burden of mood and stress disorders (10.5% vs 19.2%, P < 0.05). Patients with English preferred language had a greater than three times adjusted odds of LT evaluation compared with all others when adjusting for clinical disease severity, insurance status, sex, and psychiatric comorbid conditions (OR, 3.20; 95% CI, 1.14-9.02). CONCLUSION: Patients with AH evaluated for LT were more likely to have English as their preferred language, more psychiatric comorbidities, and more severe liver disease. Despite adjustment for psychiatric comorbidities and disease severity, English preferred language remained the strongest predictor of evaluation. As programs expand LT for AH, it is vital to build equitable systems that account for the interaction between language and healthcare in transplantation.

Preemptive antiviral therapy in lung transplantation from hepatitis C donors results in a rapid and sustained virologic response.

Objective: The study objective was to assess the safety and efficacy of a preemptive direct-acting antiviral therapy in lung transplants from hepatitis C virus donors to uninfected recipients. Methods: This study is a prospective, open-label, nonrandomized, pilot trial. Recipients of hepatitis C virus nucleic acid test positive donor lungs underwent preemptive direct-acting antiviral therapy with glecaprevir 300 mg/pibrentasvir 120 mg for 8 weeks from January 1, 2019, to December 31, 2020. Recipients of nucleic acid test positive lungs were compared with recipients of lungs from nucleic acid test negative donors. Primary end points were Kaplan-Meier survival and sustained virologic response. Secondary outcomes included primary graft dysfunction, rejection, and infection. Results: Fifty-nine lung transplantations were included: 16 nucleic acid test positive and 43 nucleic acid test negative. Twelve nucleic acid test positive recipients (75%) developed hepatitis C virus viremia. Median time to clearance was 7 days. All nucleic acid test positive patients had undetectable hepatitis C virus RNA by week 3, and all alive patients (n = 15) remained negative during follow-up with 100% sustained virologic response at 12 months. One nucleic acid test positive patient died of primary graft dysfunction and multiorgan failure. Three of 43 nucleic acid test negative patients (7%) had hepatitis C virus antibody positive donors. None of them developed hepatitis C virus viremia. One-year survival was 94% for nucleic acid test positive recipients and 91% for nucleic acid test negative recipients. There was no difference in primary graft dysfunction, rejection, or infection. One-year survival for nucleic acid test positive recipients was similar to a historical cohort of the Scientific Registry of Transplant Recipients (89%). Conclusions: Recipients of hepatitis C virus nucleic acid test positive lungs have similar survival as recipients of nucleic acid test negative lungs. Preemptive direct-acting antiviral therapy results in rapid viral clearance and sustained virologic response at 12 months. Preemptive direct-acting antiviral may partially prevent hepatitis C virus transmission.

The incidence and natural history of ascites after liver transplantation.

BACKGROUND: Ascites is common in cirrhosis but uncommon after liver transplant. We aimed to characterize the incidence, natural history, and current management strategies of post-transplant ascites. METHODS: We performed a retrospective cohort study of patients who underwent liver transplantation at 2 centers. We included patients who underwent deceased donor whole graft liver transplants between 2002 and 2019. Chart review identified patients with post-transplant ascites, requiring a paracentesis between 1 and 6-month post-transplants. Detailed chart review identified clinical and transplant characteristics, evaluation of ascites etiology, and treatments. RESULTS: Of 1591 patients who successfully underwent a first-time orthotopic liver transplant for chronic liver disease, 101 (6.3%) developed post-transplant ascites. Only 62% of these patients required large volume paracentesis for ascites before transplant. 36% of patients with post-transplant ascites had early allograft dysfunction. Most patients with post-transplant ascites (73%) required a paracentesis within 2 months of transplant, but 27% had delayed ascites onset. From 2002 to 2019, ascites studies were obtained less often, and hepatic vein pressure measurement was performed more often. Diuretics were the mainstay of treatment (58%). The use of albumin infusion and splenic artery embolization to treat post-transplant ascites increased over time. Larger pre-transplant spleen size was associated with a greater number of post-transplant paracenteses (r=0.32 and p=0.003). For patients who underwent splenic intervention, paracentesis frequency was significantly reduced (1.6-0.4 paracenteses/month, p=0.0001). The majority (72%) of patients had clinical resolution of their ascites at 6-month post-transplant. CONCLUSIONS: Persistent or recurrent ascites continues to be a clinical issue in the modern era of liver transplantation. Most had clinical resolution within 6 months, some requiring intervention.

Resection of NAFLD/NASH-related Hepatocellular Carcinoma (HCC): Clinical Features and Outcomes Compared with HCC Due to Other Etiologies.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies. METHODS: Demographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients. RESULTS: Among 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly >5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant. CONCLUSIONS: Patients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs.

Analysis of a Simulation Model to Estimate Long-term Outcomes in Patients with Nonalcoholic Fatty Liver Disease.

Importance: Quantitative assessment of disease progression in patients with nonalcoholic fatty liver disease (NAFLD) has not been systematically examined using competing liver-related and non-liver-related mortality. Objective: To estimate long-term outcomes in NAFLD, accounting for competing liver-related and non-liver-related mortality associated with the different fibrosis stages of NAFLD using a simulated patient population. Design, Setting, and Participants: This decision analytical modeling study used individual-level state-transition simulation analysis and was conducted from September 1, 2017, to September 1, 2021. A publicly available interactive tool, dubbed NAFLD Simulator, was developed that simulates the natural history of NAFLD by age and fibrosis stage at the time of (hypothetical) diagnosis defined by liver biopsy. Model health states were defined by fibrosis states F0 to F4, decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver transplant. Simulated patients could experience nonalcoholic steatohepatitis resolution, and their fibrosis stage could progress or regress. Transition probabilities between states were estimated from the literature as well as calibration, and the model reproduced the outcomes of a large observational study. Exposure: Simulated natural history of NAFLD. Main Outcomes and Measures: Main outcomes were life expectancy; all cause, liver-related, and non-liver-related mortality; and cumulative incidence of decompensated cirrhosis and/or HCC. Results: The model included 1 000 000 simulated patients with a mean (range) age of 49 (18-75) years at baseline, including 66% women. The life expectancy of patients aged 49 years was 25.3 (95% CI, 20.1-29.8) years for those with F0, 25.1 (95% CI, 20.1-29.4) years for those with F1, 23.6 (95% CI, 18.3-28.2) years for those with F2, 21.1 (95% CI, 15.6-26.3) years for those with F3, and 13.8 (95% CI, 10.3-17.6) years for those with F4 at the time of diagnosis. The estimated 10-year liver-related mortality was 0.1% (95% uncertainty interval [UI], <0.1%-0.2%) in F0, 0.2% (95% UI, 0.1%-0.4%) in F1, 1.0% (95% UI, 0.6%-1.7%) in F2, 4.0% (95% UI, 2.5%-5.9%) in F3, and 29.3% (95% UI, 21.8%-35.9%) in F4. The corresponding 10-year non-liver-related mortality was 1.8% (95% UI, 0.6%-5.0%) in F0, 2.4% (95% UI, 0.8%-6.3%) in F1, 5.2% (95% UI, 2.0%-11.9%) in F2, 9.7% (95% UI, 4.3%-18.1%) in F3, and 15.6% (95% UI, 10.1%-21.7%) in F4. Among patients aged 65 years, estimated 10-year non-liver-related mortality was higher than liver-related mortality in all fibrosis stages (eg, F2: 16.7% vs 0.8%; F3: 28.8% vs 3.0%; F4: 40.8% vs 21.9%). Conclusions and Relevance: This decision analytic model study simulated stage-specific long-term outcomes, including liver- and non-liver-related mortality in patients with NAFLD. Depending on age and fibrosis stage, non-liver-related mortality was higher than liver-related mortality in patients with NAFLD. By translating surrogate markers into clinical outcomes, the NAFLD Simulator could be used as an educational tool among patients and clinicians to increase awareness of the health consequences of NAFLD.

Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave.

The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on the efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients (SOTRs) who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 vaccine-matched solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Breakthrough SARS-CoV-2 infections occurred in 11 (5%) of SOTRs who received tixagevimab/cilgavimab and in 32 (14%) of SOTRs in the control group (p < .001). In the tixagevimab/cilgavimab group, SOTRs who received the 150-150 mg dose had a higher incidence of breakthrough infections compared to those who received the 300-300 mg dose (p = .025). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients, respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Temporal trends and impact of willingness to accept organs from donors with hepatitis C virus.

Direct-acting antivirals (DAA) transformed hepatitis C virus (HCV) treatment in 2014; however, their impact on transplant candidates' willingness to accept (CWTA) organs from HCV+ donors remains uncertain. We retrospectively studied Organ Procurement and Transplantation Network data from 2008 to 2019, investigating CWTA different organs from HCV+ donors over time, using segmented multivariable logistic regression, and how that influenced wait-time and deceased-donor transplantation (DDTx) probability, using multivariable logistic or linear regression. We found that DAA availability was associated with a marked increase in CWTA in all organs from HCV+ donors except intestine. By December 2020, 40% of kidney, 33% of kidney-pancreas, 42% of pancreas, over 50% of liver, heart, lung, heart-lung, and 9% of intestine candidates waitlisted were CWTA an organ from HCV+ donors. Compared with pre-DAA, yearly CWTA kidney from HCV+ donors increased post-DAA 1.78 1.811.83 -fold, kidney-pancreas 2 .52 2.78 3.07 -fold, pancreas 3.15 3.69 4.43 -fold, liver 1.53 1.541.56 -fold, heart 1 .92 2.02 .08 -fold, and lung 2.00 2.12 .20 -fold. CWTA kidney and liver from HCV+ donors significantly increased DDTx probability post-DAA (1.98 2.042.1 -fold and 1.24 1.291.33 -fold, respectively) and shortened kidney candidates' wait-time78 90101 days (Mean with 95% CI). CWTA organs from HCV+ donors rose significantly with DAA availability, benefitting kidney and liver candidates with increased DDTx rates and shortened kidney candidates' wait time. Further long-term outcomes investigation and standardized organ from HCV+ donors' education could improve both provider and patient acceptance and utilization.

Influence of donor and recipient hepatitis B virus infection on long-term outcomes after kidney transplantation.

BACKGROUND: The demand for transplantable kidneys continues to outstrip supply, and the risk of donor-derived infection limits utilization. The effect of donor or recipient HBV status, defined by surface antigen (HBsAg) positivity, on long-term survival outcomes of kidney transplant (KT) is unknown. METHODS: We conducted a retrospective cohort study based on Organ Procurement and Transplantation Network (OPTN) data from 2000 to 2019. We identified three cohorts based on donor (D) or recipient (R) HBsAg status: D-R, D-R+, and D+R-. Pairwise comparisons of patient survival (PS) and all-cause graft survival (GS) after propensity score matching were performed to assess the effect of HBV infection in KT recipients. RESULTS: Our findings showed that there were no statistically significant differences in PS and GS among D-R, D-R+, and D+R-groups, nor was the patient or GS different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg- donors. CONCLUSIONS: HBsAg+ status was not associated with worse PS or GS after KT. Prior to broadly advocating utilization of HbsAg+ kidneys, further studies assessing KT recipient morbidity and safety are necessary.

Transjugular Intrahepatic Portosystemic Shunt Placement for Portal Hypertension: Meta-Analysis of Safety and Efficacy of 8 mm vs. 10 mm Stents.

INTRODUCTION: Hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement remains a leading adverse event. Controversy remains regarding the optimal stent diameter given that smaller stents may decrease the amount of shunted blood and decrease the risk of HE, but stent patency and/or clinical adequacy of portal decompression may also be affected. We aim to provide meta-analysis-based evidence regarding the safety and efficacy of 8 mm vs. 10 mm stents during TIPS placement. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched for studies comparing 8 mm and 10 mm stents during TIPS placement for portal hypertension decompression in cirrhotic patients. Randomized controlled trials and cohort studies were prioritized for inclusion. Overall evaluation of quality and bias for each study was performed. The outcomes assessed were the prevalence of HE, rebleeding or failure to control refractory ascites, and overall survival. Subgroup analysis based on TIPS indication was conducted. RESULTS: Five studies with a total number of 489 cirrhotic patients were identified. The pooled hazard ratio (HR) of post-TIPS HE was significantly lower in patients in the 8 mm stent group than in the 10 mm stent group (HR: 0.68, 95% CI: 0.51~0.92, p value < 0.0001). The combined HR of post-TIPS rebleeding/the need for paracentesis was significantly higher in patients in the 8 mm stent group than in the 10 mm stent group (HR: 1.76, 95% CI: 1.22~2.55, p value < 0.0001). There was no statistically significant difference in the overall survival between the 8 mm and 10 mm stent groups. The combined risk of HE in the variceal bleeding subgroup was statistically lower (HR: 0.52, CI: 0.34-0.80) with an 8 mm stent compared with a 10 mm stent. The combined risk of both rebleeding/paracentesis and survival was not statistically significant between 8 mm and 10 mm stent use in subgroup analysis. CONCLUSION: 8 mm stents during TIPS placement are associated with a significant lower risk of HE compared to 10 mm stents (32% decreased risk), as well as a 76% increased risk of rebleeding/paracentesis. Meta-analysis results suggest that there is not one superior stent choice for all clinical scenarios and that the TIPS indication of variceal bleeding or refractory ascites might have different appropriate selection of the shunt diameter.

Projected prevalence and mortality associated with alcohol-related liver disease in the USA, 2019-40: a modelling study.

BACKGROUND: Alcohol-related liver disease is the leading indication for liver transplantation in the USA. After remaining stable for over three decades, the number of deaths due to alcohol-related liver disease has been increasing as a result of increased high-risk drinking. We aimed to project trends in alcohol-related cirrhosis and deaths in the USA up to 2040 and assess the effect of potential changes in alcohol consumption on those trends. METHODS: In this modelling study, we developed a multicohort state-transition (Markov) model of high-risk alcohol drinking patterns and alcohol-related liver disease in high-risk drinking populations born in 1900-2016 in the USA projected up to 2040. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions, National Institute of Alcohol Abuse and Alcoholism, US National Death Index, National Vital Statistics System, and published studies. We modelled trends in alcohol-related liver disease under three projected scenarios: the status quo scenario, in which current trends continued; a moderate intervention scenario, in which trends in high-risk drinking reduced to 2001 levels under some hypothetical moderate intervention; and a strong intervention, in which trends in high-risk drinking decreased by 3·5% per year under some hypothetical strong intervention. The primary outcome was to project deaths associated with alcohol-related liver disease from 2019 to 2040 for each pattern of alcohol consumption under the different scenarios. FINDINGS: Our model closely reproduced the observed trends in deaths due to alcohol-related liver disease from 2005 to 2018. Under the status quo scenario, age-standardised deaths due to alcohol-related liver disease are expected to increase from 8·23 (95% uncertainty interval [UI] 7·92-9·29) per 100 000 person-years in 2019 to 15·20 (13·93-16·19) per 100 000 person-years in 2040, and from 2019 to 2040, 1 003 400 (95% CI 896 800-1 036 200) people are projected to die from alcohol-related liver disease, resulting in 1 128 400 (1 113 200-1 308 400) DALYs by 2040. Under the moderate intervention scenario, age-standardised deaths due to alcohol-related liver disease would increase to 14·49 (95% UI 12·55-14·57) per 100 000 person-years by 2040, with 968 100 (95% UI 845 600-975 900) individuals projected to die between 2019 and 2040-35 300 fewer deaths than under the status quo scenario (a 3·5% decrease). Whereas, under the strong intervention scenario, age-standardised deaths due to alcohol-related liver disease would peak at 8·65 (95% UI 8·12-9·51) per 100 000 person-years in 2024 and decrease to 7·60 (6·96-8·10) per 100 000 person-years in 2040, with 704 300 (95% CI 632 700-731 500) individuals projected to die from alcohol-related liver disease in the USA between 2019 and 2040-299 100 fewer deaths than under the status quo scenario (a 29·8% decrease). INTERPRETATION: Without substantial changes in drinking culture or interventions to address high-risk drinking, the disease burden and deaths due to alcohol-related liver disease will worsen in the USA. Additional interventions are urgently needed to reduce mortality and morbidity associated with alcohol-related liver disease. FUNDING: American Cancer Society and the Robert Wood Johnson Health Policy Research Fellowship.

Residents Take the Lead: A Modern Collaborative Approach to Research During Residency.

BACKGROUND: Participation in scholarship is a requirement for Internal Medicine (IM) residencies, but programs struggle to successfully integrate research into busy clinical schedules. In 2013, the IM residency at Brigham and Women's Hospital implemented the Housestaff Research Project (HRP)- a novel residency-wide research initiative designed to facilitate participation in scholarship. The HRP had two components-a formal research curriculum and an infrastructure that provided funding and mentorship for resident-led, housestaff wide projects. METHODS: This is a mixed-methods study of 190 IM residents and two HRP-supported research projects. Seventy-seven residents responded to an electronic survey about their interests in research exposure in residency. Fifty-six residents responded to an electronic survey about their participation in the HRP. The success of HRP-supported projects was evaluated through resident comments, interviews with three residents leading the first two HRPs and a description of the success of the projects based on resident involvement and dissemination of the results. RESULTS: Eighty-seven percent (n= 67/77) of residents were interested in additional research exposure during residency. Ninety-five percent (n = 53/56) of residents had heard of the HRP, and 77% had participate in at least one aspect of it. Approximately 20 residents were directly involved in the two resident-led projects. HRP-supported projects resulted in presentations at three local and three national conferences, one manuscript in press, and one manuscript in preparation. The resident project leaders felt that a strength and unique aspect of the HRP was the collaboration with co-residents. CONCLUSION: The HRP successfully created a culture of research and scholarship within the residency. The HRP leaders and residents that participated in HRP-supported projects expressed the most direct benefits from the program. All residents were exposed to research concepts and methods. Future directions for the HRP include selecting projects that maximize the number of resident participants and integrating a more robust research curriculum.

Computed Tomography Findings as a Novel Predictor of Alcohol-Associated Hepatitis Outcomes.

BACKGROUND: Accurate prediction of outcomes for alcohol-associated hepatitis (AH) is critical, as prognosis determines treatment eligibility. Computed tomography (CT) features may provide prognostic information beyond traditional models. AIMS: Our aim was to identify CT features that predict outcomes in AH. METHODS: We studied 108 patients retrospectively with definite or probable AH, who underwent admission abdominal CT. A radiologist blinded to outcome evaluated eight CT features. The primary outcome was 90-day mortality. RESULTS: Twenty-five (23.2%) patients died within 90 days. While traditional prognostic tools, including Maddrey discriminant function (DF), predicted 90-day mortality (OR 1.01 [1.00, 1.03], P = 0.02), abdominal CT findings were also accurate predictors. On abdominal CT, patients with severe AH had larger volume of ascites (moderate/large volume: 34.0 vs. 8.2%, P < 0.0001), longer liver length (17.1 vs. 15.1 cm, P = 0.001), greater liver heterogeneity (moderate/severe: 21.3 vs. 8.2%, P = 0.007), and more likely to have splenomegaly (42.6 vs. 18.0%, P = 0.009) than those with mild AH. Univariate analysis revealed that ascites volume (OR 2.59 [1.35, 4.96], P = 0.004) predicted 90-day mortality. In multivariate analysis, degree of ascites predicted 90-day mortality when controlling for Maddrey DF (OR 2.36 [1.19, 4.69], P = 0.01) and trended toward significance when controlling for MELD score (OR 2.02 [0.95, 4.30], P = 0.07). CONCLUSION: CT findings in AH differentiate disease severity and predict 90-day mortality; therefore, the role of CT warrants further investigation as a tool in AH management.

Do Social Determinants Define "Too Sick" to Transplant in Patients With End-stage Liver Disease?

BACKGROUND: Delisting for being "too sick" to be transplanted is subjective. Previous work has demonstrated that the mortality of patients delisted for "too sick" is unexpectedly low. Transplant centers use their best clinical judgment for determining "too sick," but it is unclear how social determinants influence decisions to delist for "too sick." We hypothesized that social determinants and Donor Service Area (DSA) characteristics may be associated with determination of "too sick" to transplant. METHODS: Data were obtained from the Scientific Registry of Transplant Recipients for adults listed and removed from the liver transplant waitlist from 2002 to 2017. Patients were included if delisted for "too sick." Our primary outcome was Model for End-Stage Liver Disease (MELD) score at waitlist removal for "too sick." Regression assessed the association between social determinants and MELD at removal for "too sick." RESULTS: We included 5250 delisted for "too sick" at 127 centers, in 53 DSAs, over 16 years. The mean MELD at delisting for "too sick" was 25.8 (SD ± 11.2). On adjusted analysis, social determinants including age, race, sex, and education predicted the MELD at delisting for "too sick" (P < 0.05). CONCLUSIONS: There is variation in delisting MELD for "too sick" score across DSA and time. While social determinants at the patient and system level are associated with delisting practices, the interplay of these variables warrants additional research. In addition, center outcome reports should include waitlist removal rate for "too sick" and waitlist death ratios, so waitlist management practice at individual centers can be monitored.

Liver transplantation with suprahepatic caval anastomosis including inferior vena cava stent.

Budd Chiari syndrome (BCS) results from hepatic outflow obstruction. Endovascular management to restore venous patency, including inferior vena cava (IVC) angioplasty with stenting, and transjugular intrahepatic shunt (TIPS) placement to decompress liver congestion, have become standard of care. Herein, we describe a patient with BCS requiring liver transplantation and the surgical technique of suprahepatic IVC anastomosis including thoracic extension of an IVC stent with a review of the relevant literature. A 29-year-old female with BCS due to polycythemia vera, who had been previously managed with TIPS and IVC stent placement, was taken for liver transplantation. Preoperative imaging confirmed stent extension into the thoracic IVC and the stent was unable to be removed intraoperatively. The thoracic IVC was clamped through the diaphragm at the level of the right atrium and the stent was left in place and incorporated within the suprahepatic anastomosis with good vascular outcome at one year follow up. Diligent preoperative preparation is essential with adequate imaging and cardiac surgical consultation in patients with malpositioned stents. Review of the literature shows four cases in which performing the suprahepatic anastomosis including an embedded stent is a viable alternative that allows for avoidance of a thoracotomy.

Immediate administration of antiviral therapy after transplantation of hepatitis C-infected livers into uninfected recipients: Implications for therapeutic planning.

The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.

Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study.

BACKGROUND: Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts. METHODS: Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244. FINDINGS: 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0). INTERPRETATION: Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known. FUNDING: American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.