BACKGROUND AND AIMS:Metabolic dysfunction-associated steatotic liver disease (MASLD) is the fastest-rising cause of HCC. A third of MASLD-HCC occur in the absence of cirrhosis, but tools to predict MASLD-HCC are lacking. Our study aimed to examine whether liver stiffness measurement (LSM) is associated with HCC risk in MASLD, identify if LSM thresholds can predict HCC risk, and identify patients for cost-effective HCC surveillance. APPROACH AND RESULTS:We conducted a retrospective study of the Veterans Analysis of Liver Disease (VALID) cohort and included patients with MASLD who underwent transient elastography between May 27, 2014, and June 1, 2023. HCC incidence rates were calculated, and we fit multivariable Cox proportional models to study the association of LSM with HCC risk. Among 30,414 participants with MASLD followed over 69,974 person-years (PY), HCC risk increased by 18% with every 5 kPa increase in LSM (subdistribution hazard ratio: 1.18, 95% CI: 1.14-1.21). The annual incidence of HCC per 100 PY was 0.34 (0.24-0.49) with LSM 10-14.9, 0.45 (0.27-0.76) with LSM 15-19.9, 0.78 (0.50-1.20) for LSM 20-24.9, and 0.94 (0.68-1.29) per 100 PY with LSM ≥25 kPa. In patients with MASLD without cirrhosis or clinically significant portal hypertension, diabetes, and an LSM of ≥10 kPa, annual HCC rates were 0.46 per 100 PY (0.29-0.78), which is above the previously described threshold for cost-effectiveness for HCC surveillance. CONCLUSIONS:LSM is associated with HCC risk in MASLD. HCC surveillance should be considered in noncirrhotic MASLD with diabetes and LSM of ≥10 kPa.

Studying seroprevalence, the prevalence of SARS-CoV-2 antibodies in blood, produces more reliable estimates of infection burden compared with diagnosed cases. In this analysis, United States Nationwide Commercial Laboratory Seroprevalence Study data are used to calculate pediatric seroprevalence trends and their correlation with state-level vaccination. We tested SARS-CoV-2 antibodies residual serum specimens from pediatric patients during September 2021 to December 2022 for (1) presence of antinucleocapsid (anti-N; infection-induced) antibodies and (2) semiquantitative anti–spike protein (anti-S; vaccination- and infection-induced) immunoglobulin G antibody concentrations. Seroprevalence trends and antibody concentrations by age group over time were evaluated. State-level correlations were calculated between geometric mean concentrations and vaccination data. By December 2022, more than 90% of children older than 2 years showed evidence of SARS-CoV-2 infection. In contrast, seroprevalence in infants younger than 1 year fluctuated around 60% from February 2022 on. Older age groups generally exhibited higher anti-N seroprevalence and higher anti-S antibody concentrations. A positive correlation was observed between state-level geometric mean antibody concentration and vaccination rates for children aged 5 to 11 and 12 to 17 years, but not for those aged 6 months to 4 years. Between September 2021 and November/December 2022, anti-N seroprevalence increased across all age groups except for children younger than 1 year. Seropositivity among these infants remained around 60%. Furthermore, the lowest anti-S concentrations were found in children aged 6 months to 4 years. Given that young children had the lowest seroprevalence, vaccination of those who are pregnant and eligible young children could increase protection through generating an increase in antibody titers.

Background:While insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD) are well established in obese individuals, their connection in lean populations remains underexplored. Methods:This cross-sectional study investigated the relations of IR with MASLD and advanced liver fibrosis based on data from the 2017-2020 US National Health and Nutrition Examination Surveys. The subjects were lean adults (non-Asian body mass index [BMI] < 25 kg/m2, Asian BMI <23 kg/m2) with transient elastography data, free from viral hepatitis, human immunodeficiency virus, excessive alcohol use, and diabetes. Multivariable generalized linear and logistic regression models were used to relate IR measures to hepatic fat content and visceral adiposity. The IR measures included homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and homeostasis model assessment of β-cell function (HOMA-β). Results:Among 860 lean adults (median age 53 years; 48% female; 38% White; mean BMI 22.5 kg/m2), the age-adjusted prevalence of MASLD was 8.9%. Among individuals with MASLD, 84% had a high visceral adiposity index (>1.92). The percent change in controlled attenuation parameter associated with HOMA-IR, QUICKI, and HOMA-β was 11.62 (95% confidence interval [CI]: 6.31, 16.93), 0.76 (95% CI: 0.26, 1.26), and -162.72 (95% CI: -260.94, -64.50), respectively. HOMA-IR (adjusted odds ratio [aOR]: 2.60, 95% CI: 1.36, 4.98), QUICKI (aOR: 1.06, 95% CI: 1.01, 1.11), and HOMA-β (aOR: 0.04, 95% CI: 0.01, 0.56) were each associated with MASLD. HOMA-IR was associated with advanced liver fibrosis (aOR: 1.51, 95% CI: 1.19, 2.15). Conclusion:MASLD and advanced liver fibrosis in lean individuals are linked to IR, independently of excess adiposity. Assessing IR could aid in identifying lean individuals at high risk of MASLD and liver fibrosis, regardless of diabetes status.

Background/Objectives: Understanding attitudes and behaviors related to vaccination is critical for enhancing COVID-19 vaccination acceptance and reducing disparities in vaccination coverage. This study examines disparities in vaccine-related attitudes and COVID-19 vaccine hesitancy in the United States in relation to community-level social vulnerability. Methods: This study analyzed cross-sectional national surveys conducted repeatedly between July 2020 and August 2021 (n = 6716). We assessed the association between county-level social vulnerability and general vaccine-related attitudes, as well as COVID-19 vaccine hesitancy. We developed Poisson models with robust variance estimation. The analysis also included the association of county social vulnerability with parental COVID-19 vaccine hesitancy. Results: Living in counties with high Socioeconomic Status vulnerability was associated with less vaccine support (adjusted Prevalence Ratio (aPR) 1.10; 95% CI 1.05–1.14) and residing in counties with high Household Characteristics vulnerability was associated with higher likelihood of COVID-19 vaccine hesitancy (aPR 1.13; 95% CI 1.07–1.20). In contrast, high vulnerability in the Racial and Ethnic Minority was associated with more positive attitudes toward vaccines (aPR 0.91; 95% CI 0.88–0.94) and lower COVID-19 vaccine hesitancy for both themselves (aPR 0.81; 95% CI 0.76–0.87) and children (aPR 0.84; 95% CI 0.75–0.94), after adjusting for sociodemographic factors. Conclusions: Our study highlights the importance of addressing vulnerabilities related to socioeconomic status and household characteristics to reduce disparities in vaccine perceptions and hesitancy in socially vulnerable populations. The findings provide evidence for targeted public health interventions at the community level. They also demonstrate that the relationship between social vulnerability and vaccine attitudes varies across different vulnerability components.

Objective: We conducted a national US study of SARS-CoV-2 seroprevalence by Social Vulnerability Index (SVI) that included pediatric data and compared the Delta and Omicron periods during the COVID-19 pandemic. The objective of the current study was to assess the association between SVI and seroprevalence of infection-induced SARS-CoV-2 antibodies by period (Delta vs Omicron) and age group. Methods: We used results of infection-induced SARS-CoV-2 antibody assays of clinical sera specimens (N = 406 469) from 50 US states from September 2021 through February 2022 to estimate seroprevalence overall and by county SVI tercile. Bivariate analyses and multilevel logistic regression models assessed the association of seropositivity with SVI and its themes by age group (0-17, ≥18 y) and period (Delta: September–November 2021; Omicron: December 2021–February 2022). Results: Aggregate infection-induced SARS-CoV-2 antibody seroprevalence increased at all 3 SVI levels; it ranged from 25.8% to 33.5% in September 2021 and from 53.1% to 63.5% in February 2022. Of the 4 SVI themes, socioeconomic status had the strongest association with seroprevalence. During the Delta period, we found significantly more infections per reported case among people living in a county with high SVI (odds ratio [OR] = 2.76; 95% CI, 2.31-3.21) than in a county with low SVI (OR = 1.65; 95% CI, 1.33-1.97); we found no significant difference during the Omicron period. Otherwise, findings were consistent across subanalyses by age group and period. Conclusions: Among both children and adults, and during both the Delta and Omicron periods, counties with high SVI had significantly higher SARS-CoV-2 antibody seroprevalence than counties with low SVI did. These disparities reinforce SVI’s value in identifying communities that need tailored prevention efforts during public health emergencies and resources to recover from their effects.

ABSTRACT During September to December 2021, school mask policies to mitigate SARS-CoV-2 transmission varied throughout the US. We compared infection-induced seroprevalence estimates and estimated seroconversion among children residing in areas with and without school mask requirements. We estimated infection-induced seroprevalence among children in three age groups (5–17, 5–11, and 12–17 years) in areas with and without school district mask requirements for two time points: September 1–30, 2021 and December 15, 2021 to January 14, 2022. Robust Poisson regression models estimated population seroconversion over the semester among initially seronegative children. Permutation tests assessed for significant differences in the estimated population seroconversion due to incident infections by school district mask policy. Residing in an area with no school mask requirement was associated with higher infection-induced seroprevalence among children aged 5–17 years (adjusted prevalence ratio [aPR] = 1.18, 95% confidence interval [CI]: 1.10, 1.26), and those aged 5–11 years (aPR) = 1.21, 95% CI: 1.10, 1.32) and those aged 12–17 years (aPR = 1.16, 95% CI: 1.07, 1.26), compared with areas requiring masks in school. Estimated population seroconversion during the semester was also significantly higher among children in districts without mask policies than those with school mask requirements among all age groups (5–17 years: 23.7% vs 18.1%, P < 0.001; 5–11 years: 6.4% vs 4.5%, P = 0.002;12–17 years: 27.2% vs 21.0%, P < 0.001). During the U.S. Fall 2021 semester, areas with school mask requirements had lower infection-induced seroprevalence and an estimated lower proportion of seroconversion due to incident infection among school-aged children compared with areas without school mask requirements; causality cannot necessarily be inferred from these associations. IMPORTANCE During the U.S. Fall 2021 school semester, the estimated proportion of previously uninfected school-aged children who experienced a first infection with SARS-CoV-2 was lower in areas where public school district policies required masks for all staff and students compared with areas where the school districts had no mask requirements. Because children are more likely than adults to experience asymptomatic or mild SARS-CoV-2 infections, the presence of infection-induced antibodies is a more accurate measure of infection history than clinical testing. The proportion of children with these antibodies (i.e., seroprevalence) can improve our understanding of SARS-CoV-2 by detecting more infections and eliminating potential bias due to local testing and reporting practices. Enhanced robustness of surveillance for respiratory infections in children, including records of mitigation policies in communities and schools, as well as seroprevalence data, would establish a better evidence base for policy decisions and response measures during future respiratory outbreaks.

In the United States, people living with HIV (PLWH) in rural areas fare worse along the HIV care continuum than their urban counterparts; this may be due in part to limited geographic access to care. We estimated drive time to care for PLWH, focusing on urban-rural differences. Adult Medicaid enrollees living with HIV and their usual care clinicians were identified using administrative claims data from 14 states (Medicaid Analytic eXtract, 2009-2012). We used geographic network analysis to calculate one-way drive time from the enrollee's ZIP code tabulation area centroid to their clinician's practice address, then examined urban-rural differences using bivariate statistics. Additional analyses included altering the definition of rurality; examining subsamples based on the state of residence, services received, and clinician specialty; and adjusting for individual and county characteristics. Across n = 49,596 PLWH, median drive time to care was 12.8 min (interquartile range 26.3). Median drive time for rural enrollees (43.6 (82.0)) was nearly four times longer than for urban enrollees (11.9 (20.6) minutes, p < 0.0001), and drive times exceeded one hour for 38% of rural enrollees (versus 12% of urban, p < 0.0001). Urban-rural disparities remained in all additional analyses. Sustained efforts to circumvent limited geographic access to care are critical for rural areas.

Background Trends in estimates of US pediatric SARS-CoV-2 infection-induced seroprevalence from commercial laboratory specimens may overrepresent children with frequent health care needs. We examined seroprevalence trends and compared seroprevalence estimates by testing type and diagnostic coding. Methods Cross-sectional convenience samples of residual sera September 2021-February 2022 from 52 US jurisdictions were assayed for infection-induced SARS-CoV-2 antibodies; monthly seroprevalence estimates were calculated by age group. Multivariate logistic analyses compared seroprevalence estimates for specimens associated with International Classification of Diseases-Tenth Revision (ICD-10) codes and laboratory orders indicating well-child care with estimates for other pediatric specimens. Results Infection-induced SARS-CoV-2 seroprevalence increased in each age group, from 30% to 68% (1-4 years), 38% to 77% (5-11 years), and 40% to 74% (12-17 years). On multivariate analysis, patients with well-child ICD-10 codes were seropositive more often than other patients aged 1-17 years (adjusted prevalence ratio [aPR] 1.04; 95% confidence interval [CI], 1.02-1.07); children aged 9-11 years receiving standard lipid screening were seropositive more often than those receiving other laboratory tests (aPR, 1.05; 95% CI, 1.02-1.08). Conclusions Infection-induced seroprevalence more than doubled among children younger than 12 years between September 2021 and February 2022, and increased 85% in adolescents. Differences in seroprevalence by care type did not substantially impact US pediatric seroprevalence estimates. Epidemiologically important differences in infection-induced SARS-CoV-2 antibody seroprevalence estimates were not seen between children receiving well-child care and those with acute or chronic conditions, indicating that care type is not an important source of bias for US pediatric seroprevalence estimates.

Background Sero-surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can reveal trends and differences in subgroups and capture undetected or unreported infections that are not included in case-based surveillance systems. Methods Cross-sectional, convenience samples of remnant sera from clinical laboratories from 51 U.S. jurisdictions were assayed for infection-induced SARS-CoV-2 antibodies biweekly from October 25, 2020, to July 11, 2021, and monthly from September 6, 2021, to February 26, 2022. Test results were analyzed for trends in infection-induced, nucleocapsid-protein seroprevalence using mixed effects models that adjusted for demographic variables and assay type. Findings Analyses of 1,469,792 serum specimens revealed U.S. infection-induced SARS-CoV-2 seroprevalence increased from 8.0% (95% confidence interval (CI): 7.9%-8.1%) in November 2020 to 58.2% (CI: 57.4%-58.9%) in February 2022. The U.S. ratio of the change in estimated seroprevalence to the change in reported case prevalence was 2.8 (CI: 2.8-2.9) during winter 2020-2021, 2.3 (CI: 2.0-2.5) during summer 2021, and 3.1 (CI: 3.0-3.3) during winter 2021-2022. Change in seroprevalence to change in case prevalence ratios ranged from 2.6 (CI: 2.3-2.8) to 3.5 (CI: 3.3-3.7) by region in winter 2021-2022. Interpretation Ratios of the change in seroprevalence to the change in case prevalence suggest a high proportion of infections were not detected by case-based surveillance during periods of increased transmission. The largest increases in the seroprevalence to case prevalence ratios coincided with the spread of the B.1.1.529 (Omicron) variant and with increased accessibility of home testing. Ratios varied by region and season with the highest ratios in the midwestern and southern United States during winter 2021-2022. Our results demonstrate that reported case counts did not fully capture differing underlying infection rates and demonstrate the value of serosurveillance in understanding the full burden of infection. Levels of infection-induced antibody seroprevalence, particularly spikes during periods of increased transmission, are important to contextualize vaccine effectiveness data as the susceptibility to infection of the U.S. population changes. Copyright Published by Elsevier Ltd.

Background and aimsStudies have demonstrated that reducing farnesoid X receptor activity with ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme in human lung, intestinal and cholangiocytes organoids in vitro, in human lungs and livers perfused ex situ, reducing internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. This offers a potential novel target against coronavirus disease 2019 (COVID-19). The objective of our study was to compare the association between UDCA exposure and SARS-CoV-2 infection, as well as varying severities of COVID-19, in a large national cohort of participants with cirrhosis. MethodsIn this retrospective cohort study among participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver cohort, we compared participants with exposure to UDCA, with a propensity score (PS) matched group of participants without UDCA exposure, matched for clinical characteristics, and vaccination status. The outcomes included SARS-CoV-2 infection, symptomatic, at least moderate, severe, or critical COVID-19, and COVID-19-related death. ResultsWe compared 1607 participants with cirrhosis who were on UDCA, with 1607 PS-matched controls. On multivariable logistic regression, UDCA exposure was associated with reduced odds of developing SARS-CoV-2 infection (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.41-0.71, p < 0.0001). Among patients who developed COVID-19, UDCA use was associated with reduced disease severity, including symptomatic COVID-19 (aOR 0.54, 95% CI 0.39-0.73, p < 0.0001), at least moderate COVID-19 (aOR 0.51, 95% CI 0.32-0.81, p = 0.005), and severe or critical COVID-19 (aOR 0.48, 95% CI 0.25-0.94, p = 0.03). ConclusionsIn participants with cirrhosis, UDCA exposure was associated with both a decrease in SARS-CoV-2 infection, and reduction in symptomatic, at least moderate, and severe/critical COVID-19.

Studies have demonstrated that reducing farnesoid X receptor activity with ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme in human lung, intestinal and cholangiocytes organoids in vitro, in human lungs and livers perfused ex situ, reducing internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. This offers a potential novel target against coronavirus disease 2019 (COVID-19). The objective of our study was to compare the association between UDCA exposure and SARS-CoV-2 infection, as well as varying severities of COVID-19, in a large national cohort of participants with cirrhosis. In this retrospective cohort study among participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver cohort, we compared participants with exposure to UDCA, with a propensity score (PS) matched group of participants without UDCA exposure, matched for clinical characteristics, and vaccination status. The outcomes included SARS-CoV-2 infection, symptomatic, at least moderate, severe, or critical COVID-19, and COVID-19-related death. We compared 1607 participants with cirrhosis who were on UDCA, with 1607 PS-matched controls. On multivariable logistic regression, UDCA exposure was associated with reduced odds of developing SARS-CoV-2 infection (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.41–0.71, p  < 0.0001). Among patients who developed COVID-19, UDCA use was associated with reduced disease severity, including symptomatic COVID-19 (aOR 0.54, 95% CI 0.39–0.73, p  < 0.0001), at least moderate COVID-19 (aOR 0.51, 95% CI 0.32–0.81, p  = 0.005), and severe or critical COVID-19 (aOR 0.48, 95% CI 0.25–0.94, p  = 0.03). In participants with cirrhosis, UDCA exposure was associated with both a decrease in SARS-CoV-2 infection, and reduction in symptomatic, at least moderate, and severe/critical COVID-19.

Background and Aims: Immunity to SARS‐CoV‐2 can be infection or vaccine‐induced. Cirrhosis is associated with vaccine hyporesponsiveness, but whether there is decreased immunity after SARS‐CoV‐2 infection in unvaccinated patients with cirrhosis is unknown. The objective of our study was to compare infection‐induced and vaccine‐induced immunity against COVID‐19 among patients with cirrhosis. Methods: This was a retrospective cohort study among US Veterans with cirrhosis between November 27, 2020, and November 16, 2021, comparing a vaccine‐induced immunity group, defined as participants without a documented SARS‐CoV‐2 infection but fully vaccinated with two doses of an mRNA vaccine, and infection‐associated immunity group, defined as unvaccinated participants who had a positive SARS‐CoV‐2 polymerase chain reaction (PCR). Both groups were propensity score matched for observed characteristics, including location, and the date of the immunity acquiring event, to control for the community prevalence of COVID‐19 variants. The outcome was a positive SARS‐CoV‐2 PCR more than 60 days after previous infection in the infection‐induced, or after full vaccination in the vaccine‐induced immunity group. Results: We compared 634 participants in the infection‐induced immunity group with 27,131 participants in the vaccine‐induced immunity group using inverse propensity of treatment weighting. Vaccine‐induced immunity was associated with a reduced odds of developing SARS‐CoV‐2 infection (adjusted hazard ratio [aHR], 0.18; 95% confidence interval [CI], 0.16–0.20, p < 0.0001). On multivariable logistic regression, vaccine‐induced immunity was associated with reduced odds of developing symptomatic (adjusted odds ratio [aOR], 0.36; 95% CI, 0.33–0.41, p < 0.0001), moderate/severe/critical (aOR, 0.27; 95% CI, 0.22–0.31, p < 0.0001), and severe or critical COVID‐19 (aOR, 0.20; 95% CI, 0.16–0.26, p < 0.001), compared with infection‐induced immunity. Conclusions: In participants with cirrhosis, vaccine‐induced immunity is associated with reduced risk of developing COVID‐19, compared with infection‐induced immunity.

BACKGROUND:Rural populations experience a disproportionate cancer burden relative to urban populations. One possibility is that rural populations are more likely to hold counterproductive cancer beliefs such as fatalism and information overload that undermine prevention and screening behaviors.METHODS:Between 2016 and 2020, 12 U.S. cancer centers surveyed adults in their service areas using online and in-person survey instruments. Participants (N = 10,362) were designated as rural (n = 3,821) or urban (n = 6,541). All participants were 18 and older (M = 56.97, SD = 16.55), predominately non-Hispanic White (81%), and female (57%). Participants completed three items measuring cancer fatalism ("It seems like everything causes cancer," "There's not much you can do to lower your chances of getting cancer," and "When I think about cancer, I automatically think about death") and one item measuring cancer information overload ("There are so many different recommendations about preventing cancer, it's hard to know which ones to follow").RESULTS:Compared with urban residents, rural residents were more likely to believe that (i) everything causes cancer (OR = 1.29; 95% CI, 1.17-1.43); (ii) prevention is not possible (OR = 1.34; 95% CI, 1.19-1.51); and (iii) there are too many different recommendations about cancer prevention (OR = 1.26; 95% CI, 1.13-1.41), and cancer is always fatal (OR = 1.21; 95% CI, 1.11-1.33).CONCLUSIONS:Compared with their urban counterparts, rural populations exhibited higher levels of cancer fatalism and cancer information overload.IMPACT:Future interventions targeting rural populations should account for higher levels of fatalism and information overload.

BACKGROUND & AIMS:Cirrhosis is associated with immune dysregulation and hyporesponsiveness to several vaccines including those against COVID-19. Our aim was to compare outcomes between patients with cirrhosis who received 3 doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines to a propensity-matched control group of patients at similar risk of infection who received 2 doses.METHODS:This was a retrospective cohort study of patients with cirrhosis who received 2 or 3 doses of a COVID-19 mRNA vaccine at the Veterans Health Administration. Participants who received 3 doses of the vaccine (n = 13,041) were propensity score matched with 13,041 controls who received 2 doses, and studied between July 18, 2021 and February 11, 2022, when B.1.617.2 (delta) and B.1.1.529 (omicron) were the predominant variants. Outcomes were aggregated as all cases with COVID-19, symptomatic COVD-19, with at least moderate COVID-19, or severe or critical COVID-19.RESULTS:Receipt of the third dose of a COVID-19 mRNA vaccine was associated with an 80.7% reduction in COVID-19 (95% CI 39.2-89.1, p <0.001), an 80.4% reduction in symptomatic COVID-19, an 80% reduction in moderate, severe or critical COVID-19, (95% CI 34.5-87.6%, p = 0.005), a 100% reduction in severe or critical COVID-19 (95% CI 99.2-100.0, p = 0.01), and a 100% reduction in COVID-19-related death (95% CI 99.8-100.0, p = 0.007). The magnitude of reduction in COVID-19 was greater with the third dose of BNT 162b2 than mRNA-1273 and among participants with compensated rather than decompensated cirrhosis.CONCLUSIONS:Administration of a third dose of a COVID-19 mRNA vaccine was associated with a more significant reduction in COVID-19 in patients with cirrhosis than in the general population, suggesting that the third dose can overcome vaccine hyporesponsiveness in this population.LAY SUMMARY:Cirrhosis is associated with decreased responsiveness to several vaccines, including those against COVID-19. In this study of 26,082 participants with cirrhosis during the delta and omicron surge, receipt of the third dose of the vaccine was associated with an 80% reduction in COVID-19, a 100% reduction in severe/critical COVID-19, and a 100% reduction in COVID-19-related death. These findings support the importance of a third dose of mRNA vaccine among patients with cirrhosis.

BACKGROUND AND AIMS:Patients develop breakthrough COVID-19 infection despite vaccination. The aim of this study was to identify outcomes in patients with cirrhosis who developed postvaccination COVID-19. METHODS:We performed a retrospective cohort study among US veterans with cirrhosis and postvaccination or unvaccinated COVID-19. Patients were considered fully vaccinated if COVID-19 was diagnosed 14 days after the second dose of either the Pfizer BNT162b2, the Moderna 1273-mRNA, or the single-dose Janssen Ad.26.COV2.S vaccines and partially vaccinated if COVID-19 was diagnosed 7 days after the first dose of any vaccine but prior to full vaccination. We investigated the association of postvaccination COVID-19 with mortality. RESULTS:We identified 3242 unvaccinated and 254 postvaccination COVID-19 patients with cirrhosis (82 after full and 172 after partial vaccination). In a multivariable analysis of a 1:2 propensity-matched cohort including vaccinated (n = 254) and unvaccinated (n = 508) participants, postvaccination COVID-19 was associated with reduced risk of death (adjusted HR [aHR], 0.21; 95% CI, 0.11-0.42). The reduction was observed after both full (aHR, 0.22; 95% CI, 0.08-0.63) and partial (aHR, 0.19; 95% CI, 0.07-0.54) vaccination, following the 1273-mRNA (aHR, 0.12; 95% CI 0.04-0.37) and BNT162b2 (aHR, 0.27; 95% CI, 0.10-0.71) vaccines and among patients with compensated (aHR, 0.19; 95% CI, 0.08-0.45) and decompensated (aHR, 0.27; 95% CI, 0.08-0.90) cirrhosis. Findings were consistent in a sensitivity analysis restricted to participants who developed COVID-19 after vaccine availability. CONCLUSIONS:Though patients with cirrhosis can develop breakthrough COVID-19 after full or partial vaccination, these infections are associated with reduced mortality.