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Backgrounds and Aims: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)‐related end‐stage liver disease (ESLD). We assess aetiology‐based hospitalizations for ESLD in the United States, 2016–2019. Methods: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision. Results: National hospitalization rates for non‐alcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100 000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100 000 persons in 2016 to 58.5 in 2019 (−6.5% AAPC). Hospitalizations for ESLD in alcohol‐related liver disease (ALD) increased as well. Conclusions: Hospitalization rates for NAFLD‐ and ALD‐related ESLD increased steadily, while those for HCV‐related ESLD decreased during the direct‐acting antivirals era. [ABSTRACT FROM AUTHOR]

Background & Aims: With the recent improvement in the treatment of hepatitis C virus (HCV) infection, a better understanding of the infection burden is needed. We aimed to (a) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (b) identify at‐risk populations for HCV infection in the United States (US) general population. Methods: Population‐based analyses using the National Health and Nutrition Examination Survey (2013‐2018) were performed with a focus on HCV infection. We analysed the prevalence of HCV infection based on the health insurance status before the direct‐acting antiviral (DAA) era (2013‐2014) and during the DAA era (2015‐2018). Results: The age‐adjusted prevalence of active HCV infection (HCV RNA [+]) was 0.92% (95% confidence interval, 0.71%‐1.19%) in the US non‐institutionalized civilian population. Although the prevalence of active HCV infection has remained stable, the prevalence of resolved HCV infection has increased after the introduction of DAA. In terms of health insurance coverage, the prevalence of active HCV infection decreased, and the prevalence of resolved HCV infection increased among individuals who had health insurance, especially private health insurance. The independent risk factors of active HCV infection were 40‐69 years group, male, less than high school education, unmarried, below poverty status, being born in the US, history of blood transfusion and not having private health insurance. Conclusion: The burden of active HCV infection has decreased among individuals who had health insurance, especially private health insurance, during the DAA era. [ABSTRACT FROM AUTHOR]

Recently, international experts proposed redefining non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD), based on modified criteria. It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on all-cause and cause-specific mortality in US adults. We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD, with adjustments for known risk factors. During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk of all-cause mortality (hazard ratio [HR] 1.17; 95% CI 1.04-1.32). Furthermore, MAFLD was associated with a higher risk of cardiovascular mortality. NAFLD per se did not increase the risk of all-cause mortality. Individuals who met both definitions had a higher risk of all-cause mortality (HR 1.13, 95% CI 1.00-1.26), while individuals who met the definition for MAFLD but not NAFLD had a 1.7-fold higher risk of all-cause mortality (HR 1.66, 95% CI 1.19-2.32). Estimates for all-cause mortality were higher for those with advanced fibrosis and MAFLD than for those with advanced fibrosis and NAFLD. In this US population-based study, MAFLD was associated with an increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors. Our findings provide further support for the idea that non-alcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may help improve our understanding of predictors that increase the risk of death. [Display omitted] • Metabolic dysfunction-associated fatty liver disease (MAFLD) was associated with increased all-cause and cardiovascular mortality. • NAFLD was associated with increased all-cause mortality among individuals with known metabolic risk factors. • Advanced fibrosis in MAFLD was associated with higher estimates for all-cause mortality than in NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aims: Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic progressive illness with a spectrum of disease severity from steatosis to end-stage liver disease. Emerging evidence suggests total serum bilirubin levels are inversely related to the prevalence of metabolic syndrome including NAFLD. We investigated the effects of bilirubin on all-cause and cause-specific mortality stratified by NAFLD status., Methods: We used the third National Health and Nutrition Examination Survey Cohort (1988-1994) and linked mortality dataset through 2019. Cox-regression models were constructed to assess the association between bilirubin levels categorized by quartile with all-cause and cause-specific mortality., Results: During the median follow-up of 324 months (n=11,078), higher bilirubin levels were associated with a reduction in risk of all-cause mortality in the multivariate model (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.71-0.97 for quarter 4 [highest bilirubin levels] vs. quarter 1 [lowest bilirubin levels], p for trend=0.033). Higher bilirubin levels were associated with a lower risk for all-cause mortality in individuals with NAFLD (HR; 0.68, 95% CI: 0.55-0.86 for quarter 4, p for trend=0.010); however, this protective association with higher bilirubin levels was not noted in those without NAFLD. Higher bilirubin levels were associated with a lower risk for cardiovascular and cancer-related mortality in individuals with NAFLD., Conclusions: In this large nationally representative sample of American adults, higher bilirubin levels in NAFLD were associated with a lower risk of all-cause mortality, which may be derived from a lower risk of cardiovascular/cancer-related mortality.

Background: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease., Aims: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic., Methods: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes., Results: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men., Conclusions: The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD., Competing Interests: Declaration of Competing Interest None of the authors have any relevant conflict of interest or other financial disclosures., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: During the global coronavirus disease 2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic., Methods: Population-based analyses were performed on United States national mortality records (2017-2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC)., Results: Quarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease before the COVID-19 pandemic (QPC, 1.9%) accelerated during the COVID-19 pandemic (QPC, 6.6%). Although ALD-related mortality increased steeply compared with viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD., Conclusion: All-cause mortality for ALD and nonalcoholic fatty liver disease rapidly accelerated during the COVID-19 pandemic compared with the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aim: The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear., Method: We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations., Result: There were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09-1.16]), 53% lower in Blacks (RR: 0.47 [0.45-0.49]) and 5% lower among other racial minorities (0.95 [0.91-0.99]). The rate was higher among females (RR:4.02 [3.93-4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03-2.10] and 1.33 [0.96-1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites., Conclusion: The hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.

The introduction of direct-acting antiviral (DAA) agents and the opioid epidemic have resulted in an increased interest in liver transplantation (LT) of organs from donors with hepatitis C virus (HCV)-related viremia. 1 In March of 2015, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) implemented a policy to perform HCV nucleic acid testing (NAT) in all HCV-seropositive donors. An open-label, single-center experience with 10 patients using a multistep informed consent reported successful transplantation of HCV-seropositive viremic (HCV-V) kidneys into HCV-seronegative recipients. 2 Subsequently, a case was reported in which an HCV-V liver was transplanted into a HCV-seronegative recipient. 3 In collaboration with OPTN/UNOS, we identified cases in which HCV-V deceased donor livers were transplanted into HCV-seronegative recipients., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.

Background: In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation., Methods: Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist (WL) registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016., Results: From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD WL additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% confidence interval, 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (≥60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low body mass index (<18.5) and diabetes mellitus were significant predictors for 1-year WL mortality., Conclusions: Alcoholic liver disease-related WL registrations and liver transplantation have increased over the past decade with a disproportionate increase in young and middle-aged adults. These subpopulations within the ALD cohort need to be evaluated in future studies to improve our understanding of factors associated with these alarming trends.