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.

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. MethodsIn 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 wi...

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 HCVpositive 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.

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Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).

Background: The hepatitis C virus (HCV) care cascade has changed dramatically following the introduction of direct-acting anti-virals (DAAs). Up-to-date estimates of the cascade are needed to monitor progress, identify key gaps and inform policy.Aim: To estimate the current and future HCV care cascade in the United States, nationally and in select subpopulations of interest. Methods:We used a previously validated mathematical model to simulate the landscape of HCV in the United States from 2011 onwards, accounting for HCV screening policy updates, newer HCV treatments and rising HCV incidence. Results: By the end of 2018, of 4.29 million HCV persons alive, 2.71 million (63%) were actively viremic, 2.24 million (52%) aware and 1.58 million (37%) cured. By 2030, under the status quo, of 3.65 million HCV persons alive, 1.88 million (51%) would be viremic, 2.25 million (62%) aware and 1.77 million (49%) cured. The HCV care cascade in 2018 differed substantially by subpopulation: of 1.34 million incarcerated HCV persons, 96% were viremic, 36% aware and 4% cured; of 0.87 million HCV persons in Medicare, 31% were viremic, 72% aware and 69% cured; and of 0.37 million HCV persons in Medicaid, 49% were viremic, 54% aware and 51% cured. Implementing universal screening, providing unrestricted treatment and controlling HCV incidence were factors found to have the largest effect on improving the HCV care cascade. Conclusions: Since the launch of DAAs, the HCV care cascade has shifted towards higher awareness and treatment rates; however, additional interventions are needed to move towards HCV elimination. | 67 CHHATWAL eT AL. Aware

Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost-effective or cost-saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6-week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. (Hepatology 2018;67:837-846).

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e17 (https://www. gastrojournal.org/cme/home). Learning Objective: Upon completion of this CME activity, successful learners will be able to state the expected short-and long-term outcomes of a patient with severe, medically refractory, acute alcohol-associated hepatitis presented with 2 different transplant eligibility policies: early (ie, without minimum period of sobriety) versus delayed (eg, 6-month wait) liver transplantation. BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcoholassociated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. METHODS: We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant. RESULTS: Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplanta...