§ Drs. Murphy and Parikh contributed equally and are co-senior authors Author contributions: Dr. Singal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design (Singal and Parikh); Acquisition, analysis and interpretation of the data (all authors); Drafting of the manuscript (Singal); Critical revision of the manuscript for important intellectual content (all authors); Obtained funding (Singal, Parikh); Administrative, technical, and material support (Singal and Parikh); Study supervision (Singal) Conflicts of Interest: Amit Singal was on speakers bureau for Gilead, Bayer, and Bristol Meyers Squibb. He has served on advisory boards for Gilead, Abbvie, Bayer, Eisai, Wako Diagnostics, Roche, and Exact Sciences. He serves as a consultant to Bayer, Eisai, Roche, and Glycotest. He has received research funding from Gilead and Abbvie. Neil Mehta has received research funding from Wako Diagnostics. Anjana Pillai serves as a consultant and is on speakers bureau for Eisai and BTG. Jordan Feld has received research support from Gilead, Abbvie, Merck, and Janssen. Binu John has served on advisory boards for Eisai. Catherine Frenette is on speakers bureaus for Bayer, Bristol Meyers Squibb, Gilead, Merck, Abbvie, and Eisai. She served on advisory boards for Gilead, Eisai, and Wako. She served as a consultant for Bayer and Gilead. She received research funding from Bayer. Parvez Mantry is on speakers bureaus and served on advisory boards for Gilead, Abbvie, Bayer, BMS, Eisai, Merck, and BTG. He has received research funding from Gilead and Sirtex. Michael Leise has received research funding from Abbvie. Kalyan Ram Bhamidimarri serves as scientific advisory board member for Gilead, Merck, and Abbvie. He has received research funding from Gilead. Laura Kulik is on speakers bureau for Eisai, Gilead, and Dova. She serves as an advisory board member for BMS, Eisai, Bayer, Exelixis Reena Salgia is on speakers bureau for Bayer. She has served on advisory boards for Bayer, Eisai, and Exelixis. Sanjaya Satapathy has received research support from Gilead and Bayer.He has served on advisory boards or as a consultant for Abbvie and Gilead.

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Background & Aims:The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the US. We evaluated the impact of the pandemic on temporal trends for LT including ALD. Approach & Results: Utilizing data from United Network for Organ Sharing, we analyzed waitlist outcomes in the US through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019 and February 29, 2020 were defined as the "pre-COVID" era and after April 1, 2020 were defined as the "COVID" era. Interrupted time-series analyses utilizing monthly count data from 2016-2020 were constructed to evaluate rate change for listing and LT prior to and during the COVID-19 pandemic. Rates for listings (P=0.19) and LT (P=0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P <0.001) and NASH (-13.18%; P <0.001). There was a significant increase in ALD listing (+7.26%; P <0.001) and LT (10.67%; P <0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcoholic hepatitis (+50%). ALD patients presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a MELD-Na > 30. Conclusions: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on healthcare resources.

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Background & Aims Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. We investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. Methods We performed a case–control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls), from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. Results The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% CI, 0.32–0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5±0.9 years) vs non-users (mean, 59.2±1.1 years) (P=.001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20– 0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67–11.44) vs AOR for non-users, 17.60 (95% CI, 3.88–79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40–0.77) (P=.01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7–41.3 months) and 24.1 months for non-users (95% CI, 19.02–29.30 months) (P=.008). Conclusion In a case–control study of women with HCC vs female controls at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.