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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: An association between depression and metabolic dysfunction-associated fatty liver disease (MAFLD) appears logical on the basis of previous observations linking depression to nonalcoholic fatty liver disease. We aim to investigate the association between depression and MAFLD and significant fibrosis., Methods: This cross-sectional study was conducted on data from National Health and Nutrition Examination Survey, 2017 to March 2020 Pre-pandemic dataset. Depression and depression-related functional impairment were assessed using the Patient Health Questionnaire (PHQ-9). MAFLD, based on the criteria proposed by an international expert panel, and significant fibrosis were defined by transient elastography., Results: Of the 3327 individuals (mean age: 46.9 years, 50.2 % men), the prevalence of depression and functional impairment due to depression was higher among individuals with MAFLD or significant fibrosis than among those without. Individuals with depression were approximately 70 % more likely to have MAFLD than those without. In multivariable analyses, depression was associated with an increased risk of MAFLD (odds ratio [OR]: 1.77, 95 % confidence interval [CI]:1.33-2.36 for ≥263 dB/m and OR: 1.70, 95 % CI: 1.20-2.41 for ≥285 dB/m). These associations were more pronounced in postmenopausal women than premenopausal women. In terms of significant fibrosis, depression remained an independent predictor of significant fibrosis; however, it attenuated after adjustment for body mass index., Limitations: Temporal causality and residual confounders could not be entirely investigated due to the study design., Conclusions: Depression was independently associated with MAFLD and significant fibrosis in a nationally representative sample of adults in the US., Competing Interests: Conflict of interest None of the authors have any relevant conflict of interest or other financial disclosures., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Aims: Presence of gallstone disease may influence outcomes in patients with nonalcoholic fatty liver disease (NAFLD). We studied the impact of gallstone disease on mortality in individuals with and without NAFLD., Methods: Prospective cohort study used the Third National Health and Nutrition Examination Survey (1988-1994) with mortality data through 2015. Gallstone disease was defined as ultrasonographic evidence of gallstones or absence of the gallbladder (prior cholecystectomy). NAFLD was defined using standardized ultrasonographic criteria., Results: Gallstone disease and cholecystectomy were independently associated with NAFLD (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.43-2.15 for gallstone disease and OR, 2.77; 95% CI, 2.01-3.83 for cholecystectomy compared with no gallstone disease). During the median follow-up of 23 years, gallstone disease was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.19; 95% CI, 1.05-1.37) and cause-specific mortality. Gallstone disease was associated with a higher risk of all-cause mortality in non-NAFLD sub-cohort (HR, 1.42; 95% CI, 1.23-1.64) but not in NAFLD (HR, 1.03; 95% CI, 0.87-1.22). Gallstone disease was associated with a higher risk of cardiovascular-related (HR, 1.40; 95% CI, 1.10-1.78) and cancer-related (HR, 1.71; 95% CI, 1.18-2.48) mortality in non-NAFLD sub-cohort. Gallstone disease was associated with increased cardiovascular mortality (HR, 1.36; 95% CI, 1.05-1.77) in NAFLD., Conclusions: Gallstone disease is an independent risk factor for NAFLD, but gallstone disease is not associated with all-cause mortality in individuals with NAFLD. Screening for gallstone disease in individuals at risk for developing NAFLD may help with risk stratification for all-cause mortality related to gallstone disease., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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.)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.)

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver conditions characterized by significant lipid deposition within hepatocytes. As an overarching diagnosis, NAFLD contains a continuum of progressive liver diseases ranging from isolated liver steatosis to necroinflammatory states leading to end-stage liver disease. Nonalcoholic fatty liver and nonalcoholic steatohepatitis are distinguished by their histologic patterns, with the former exhibiting steatosis without fibrosis or inflammation. This important distinction provides clinicians a timeline within the NAFLD staging to target appropriate interventions against modifiable risk factors. NAFLD is likely formed in response to metabolic imbalances that damage the livers adaptive capacity. Metabolic conditions leading to steatosis mirror common cardiovascular risk factors, including dyslipidemia, diabetes mellitus, and obesity. Acknowledging the common risk factors for development and progression of NAFLD, it is unsurprising the first-line management focuses on the treatment of metabolic syndrome with an emphasis on weight reduction in obese populations. The purpose of this review is to provide a detailed summary of the literature as well as outline the current treatment recommendations for patients with NAFLD with a detailed focus on pharmacologic antiobesity interventions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The impact of different types of physical activity (PA) on mortality in the context of nonalcoholic fatty liver disease (NAFLD) is not clearly defined and was investigated. This prospective study was performed using the 2007–2014 US National Health and Nutrition Examination Survey with mortality follow-up through 2019. Over a median follow-up of 8.6 years, leisure-time and transportation-related PA that fulfilled the criteria outlined in the PA guidelines (≥150 min/week) in NAFLD were associated with a risk reduction in all-cause mortality (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.59–0.98 for leisure-time PA; HR: 0.62, 95% CI: 0.45–0.86 for transportation-related PA). Leisure-time and transportation-related PA in NAFLD were inversely associated with all-cause mortality in a dose-dependent manner (p for trends <0.01). Furthermore, the risk for cardiovascular mortality was lower in those meeting the PA guidelines for leisure-time PA (HR: 0.63, 95% CI: 0.44–0.91) and transportation-related PA (HR: 0.38, 95% CI: 0.23–0.65). Increasing sedentary behavior was linked to an increased risk of all-cause and cardiovascular mortality (p for trend <0.01). Meeting PA guidelines (≥150 min/week) for leisure-time and transportation-related PA has beneficial health effects on all-cause and cardiovascular mortality among individuals with NAFLD. Sedentary behavior in NAFLD showed harmful effects on all-cause and cardiovascular mortality. [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]