The term acute-on-chronic liver failure (ACLF) is intended to identify patients with chronic liver disease who develop rapid deterioration of liver function and high short-term mortality after an acute insult. The two prominent definitions (European Association for the Study of the Liver [EASL] and Asian Pacific Association for the Study of the Liver [APASL]) differ, and existing literature applies to narrow patient groups. We sought to compare ACLF incidence and mortality among a diverse cohort of patients with compensated cirrhosis, using both definitions. This was a retrospective cohort study of patients with incident compensated cirrhosis in the Veterans Health Administration from 2008 to 2016. First ACLF events were identified for each definition. Incidence rates were computed as events per 1,000 person-years, and mortality was calculated at 28 and 90 days. Among 80,383 patients with cirrhosis with 3.35 years median follow-up, 783 developed EASL and APASL ACLF, 4,296 developed EASL ACLF alone, and 574 developed APASL ACLF alone. The incidence rate of APASL ACLF was 5.7 per 1,000 person-years (95% confidence interval [CI]: 5.4-6.0), and the incidence rate of EASL ACLF was 20. 1 (95% CI: 19.5-20.6). The 28-day and 90-day mortalities for APASL ACLF were 41.9% and 56.1%, respectively, and were 37.6% and 50.4% for EASL ACLF. The median bilirubin level at diagnosis of EASL-alone ACLF was 2.0 mg/dL (interquartile range: 1.1-4.0). Patients with hepatitis C or nonalcoholic fatty liver disease had among the lowest ACLF incidence rates but had the highest short-term mortality. Conclusion: There is significant discordance in ACLF events by EASL and APASL criteria. The majority of patients with EASL-alone ACLF have preserved liver function, suggesting the need for more liver-

Background and Aims Vaccination against SARS-CoV-2 has rapidly expanded, however clinical trials excluded patients taking immunosuppressive medications such as those with inflammatory bowel disease (IBD). Therefore, we explored real-world effectiveness of COVID-19 vaccination on subsequent infection in IBD patients with diverse exposure to immunosuppressive medications. Methods This was a retrospective cohort study of patients in the Veterans Health Administration with IBD diagnosed prior to 12/18/20, the start date of the VHA patient vaccination program. IBD medication exposures included 5-aminosalicylic acid, thiopurines, anti-tumor necrosis factor biologic agents, vedolizumab, ustekinumab, tofacitinib, methotrexate, and corticosteroid use. We used inverse probability weighting and Cox regression with vaccination status as a time-updating exposure, and computed vaccine effectiveness from incidence rates. Results The cohort comprised 14,697 patients, 7,321 of whom received at least one vaccine dose (45.2% Pfizer, 54.8% Moderna). The cohort had median age 68 years, was 92.2% male, 80.4% white, and 61.8% with ulcerative colitis. In follow-up data through April 20, 2021, unvaccinated individuals had the highest raw proportion of SARS-CoV-2 infection (197 [1.34%] versus 7 [0.11%] fully vaccinated). Full vaccination status, but not partial vaccination status, was associated with a 69% reduced hazard of infection relative to an unvaccinated status (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.17-0.56, p<0.001), corresponding to an 80.4% effectiveness. Conclusion Full vaccination (>7 days after the 2 nd dose) against SARS-CoV-2 infection has an approximately 80.4% effectiveness in a broad IBD cohort with diverse exposure to immunosuppressive medications. These results may serve to increase patient and provider willingness to pursue vaccination in these settings.

Background and aims: Acute on chronic liver failure (ACLF) yields the highest risk of short-term mortality, along the spectrum of cirrhosis. We evaluated whether the rising prevalence of nonalcoholic steatohepatitis (NASH) in the United States is reflected among waitlist registrants with ACLF. Methods: We analyzed the United Network for Organ Sharing (UNOS) registry, years 2005-2017. Patients with ACLF were identified using the EASL-CLIF criteria and categorized into those with NASH, alcoholic liver disease (ALD), and hepatitis C virus (HCV) infection. Statistical analysis included linear regression and Chow's test to determine significance and divergence in trends, and Fine and Grey's competing risks and Cox proportional hazards regression to assess waitlist outcomes. Results: Between 2005 and 2017, waitlist registrants for NASH-ACLF rose 331.6% (p<0.001). ALD-ACLF increased 206.3% (p<0.001), while HCV-ACLF declined 45.2% (p=0.018). This increase in NASH-ACLF occurred across all UNOS regions, rising by 666.7% in region 11. The NASH-ACLF population is aging, and currently 31.5% of the group is age 65 or older. Although NASH-ACLF candidates did not have greater 90-day waitlist mortality (SHR=0.84, 95% CI 0.77-0.92) relative to other etiologies, since 2014, 90-day waitlist mortality has improved for ALD-ACLF (HR=0.78, 95% CI 0.70-0.88) and HCV-ACLF (HR=0.76, 95% CI 0.67-0.85) but not for NASH (HR=0.93, 95% CI 0.81-1.08). Conclusions: NASH is the fastest rising etiology of cirrhosis among transplant registrants with ACLF in the United States. Since 2014, waitlist outcomes have 4 improved for ALD-ACLF and HCV-ACLF, but not for NASH-ACLF. With the aging NASH population, patients with NASH-ACLF may eventually have the highest risk of death on the waiting list.

Healthcare delivery in the rural developing world is limited by a severe shortage of health workers as well as profound communicative and geographic barriers. Understaffed hospitals are forced to provide care for patients that reside at a great distance from the institutions themselves, sometimes more than 100 miles away. Community health workers (CHWs), volunteers from local villages, have been integral in bridging this patient-physician gap, but still lose enormous of amounts of time in transit between hospital and village. We report the results of a retrospective mobile health (mHealth) pilot at St. Gabriel's Hospital in Malawi designed to eliminate many of these trips in favor of communication via text messages. A group of 75 CHWs were supplied with cell phones and trained to utilize the network for a variety of usage cases, including patient adherence reporting, appointment reminders, and physician queries. At the end of the pilot, the hospital saved approximately 2,048 hours of worker time, $2,750 on net ($3,000 in fuel savings minus $250 in operational costs), and doubled the capacity of the tuberculosis treatment program (up to 200 patients). We conclude that mHealth interventions can provide cost-effective solutions to communication barriers in the setting of rural hospitals in the developing world.