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Summary: Background: Recently, a panel of multi‐society experts proposed steatotic liver disease (SLD) as an alternative terminology for metabolic dysfunction‐associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD). Aims: We compared the impact of SLD, subtype of SLD, MAFLD and NAFLD on all‐cause and cause‐specific mortality. Methods: A total of 7811 individuals in the third National Health and Nutrition Examination Survey and linked mortality through 2019 were analysed. SLD was defined based on ultrasonographic hepatic steatosis. SLD, subtype of SLD and MAFLD were defined using the proposed definitions. The Cox proportional hazard model assessed all‐cause/cause‐specific mortality. Results: During a median follow‐up of 27.1 years, individuals with SLD and MAFLD experienced approximately 13%–23% higher risk of all‐cause mortality (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.02–1.29 for SLD; HR: 1.23, 95% CI: 1.09–1.38 for MAFLD; HR: 1.13, 95% CI: 1.01–1.27 for metabolic dysfunction‐associated steatotic liver disease [MASLD]). Individuals with MetALD demonstrated a higher risk of all‐cause (HR: 1.68, 95% CI: 1.10–2.57) and cancer‐related mortality (HR: 2.40, 95% CI: 1.23–4.66). MASLD with advanced fibrosis had an increased risk of all‐cause mortality compared to MASLD without advanced fibrosis. Conclusions: SLD, especially MASLD and MetALD, is associated with increased all‐cause mortality among adults in the US. Given this significant association between SLD or subtype of SLD (MASLD and MetALD) and all‐cause mortality, adopting the proposed SLD criteria may help identify a sub‐group of individuals with SLD who are at an increased risk for all‐cause mortality. [ABSTRACT FROM AUTHOR]

Background: Depression has been associated with nonalcoholic fatty liver disease (NAFLD). Data addressing the impact of depression on NAFLD‐related mortality are evolving. We aim to study the association of depression in NAFLD and all‐cause/cause‐specific mortality in the United States. Methods: A total of 11,877 individuals with NAFLD in the 2007–2016 National Health and Nutrition Examination Survey with the availability of linked mortality through 2019 were analysed. NAFLD was defined by utilizing the hepatic steatosis index in the absence of known causes of chronic liver disease. Depression and functional impairment due to depression were assessed using the Patient Health Questionnaire. Results: During the median follow‐up of 7.6 years, individuals with depression among individuals with NAFLD had a 35% higher all‐cause mortality than those without depression (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03–1.75) after adjusting for demographic, lifestyle and clinical risk factors. NAFLD with functional impairment due to depression had a 62% higher all‐cause mortality than NAFLD without functional impairment (HR: 1.62, 95% CI: 1.10–2.39). Depression in NAFLD was associated with an approximately 50% increase in the risk for cardiovascular mortality, with a 2‐fold higher cardiovascular mortality in those with functional impairment compared to those without (HR: 2.07, 95% CI: 1.30–3.30). However, there was no significant difference in cancer‐ and accident‐related mortalities in NAFLD with or without depression. Conclusions: Depression among individuals with NAFLD was associated with a higher risk for all‐cause and cardiovascular mortality in the United States. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Patients with pre‐existing cirrhosis and exposure to coronavirus disease‐19 (COVID‐19) may portend a poor prognosis. We evaluated the temporal trends in aetiology‐based hospitalisations and potential predictors of in‐hospital mortality in hospitalisation with cirrhosis before and during the COVID‐19 pandemic. Methods: Based on the US National Inpatient Sample 2019–2020, we determined quarterly trends in aetiology‐based hospitalisations with cirrhosis and decompensated cirrhosis and identified predictors of in‐hospital mortality in hospitalisation with cirrhosis. Results: We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID‐19 era. Hospitalisation rates for alcohol‐related liver disease (ALD)‐related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%–5.1%), with a notably higher rate during the COVID‐19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)‐related cirrhosis decreased steadily with a trend of −1.4% of QPC (95% CI: −2.5% to −0.1%). Quarterly trends in the proportion of ALD‐ (QPC: 1.7%, 95% CI: 0.9%–2.6%) and nonalcoholic fatty liver disease‐related (QPC: 0.7%, 95% CI: 0.1%–1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID‐19 era and COVID‐19 infection were independent predictors of in‐hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV‐related cirrhosis, ALD‐related cirrhosis was associated with a 40% higher risk of in‐hospital mortality. Conclusion: In‐hospital mortality in cirrhosis was higher in the COVID‐19 era than in the pre‐COVID‐19 era. ALD is the leading aetiology‐specific cause of in‐hospital mortality in cirrhosis with an independent detrimental impact of the COVID‐19 infection. [ABSTRACT FROM AUTHOR]

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]

LINKED CONTENT: This article is linked to Gawrieh et al papers. To view these articles, visit https://doi.org/10.1111/apt.17849 and https://doi.org/10.1111/apt.17886 [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]

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has been associated with sarcopenia. However, mortality in the setting of NAFLD‐related sarcopenia remains undefined. We aim to determine the all‐cause and cause‐specific mortality from sarcopenia among adults with NAFLD in the USA. Methods: 11 065 individuals in the Third National Health and Nutrition Examination Survey were studied and linked mortality through 2015 was analysed. NAFLD was diagnosed based on presence of ultrasonographic hepatic steatosis without other known liver diseases. Sarcopenia was defined as skeletal muscle index determined by bioelectrical impedance analysis. The Cox proportional hazard model was used to assess all‐cause mortality and cause‐specific mortality, and hazard ratio (HR) adjusted for known risk factors. Results: During a median follow‐up of 23 years or more, sarcopenia was associated with increased all‐cause mortality (HR 1.27, 95% confidence interval [CI] 1.11‐1.44). Only in individuals with NAFLD, sarcopenia was associated with a higher risk for all‐cause mortality, while this association was absent in those without NAFLD. Individuals with both sarcopenia and NAFLD had a higher risk for all‐cause mortality (HR 1.28 95% CI 1.06‐1.55) compared with those without sarcopenia and NAFLD. Furthermore, sarcopenia was associated with a higher risk for cancer‐ and diabetes‐related mortality among those with NAFLD. This association was not noted in those without NAFLD. Conclusion: In this nationally representative sample of US adults, sarcopenia was associated with a higher risk for all‐cause, cancer‐ and diabetes‐related mortality in individuals with NAFLD. [ABSTRACT FROM AUTHOR]

We examined trends in mortality from hepatitis C virus (HCV) infection and alcoholic liver disease (ALD) in the setting of drug overdose. Using US Census and national mortality records (2009‐2018), we identified deaths with HCV infection, ALD and drug overdose. HCV‐related mortality without drug overdose increased up to 2014, followed by a marked decrease. Mortality from HCV and drug overdose increased significantly. Whereas ALD‐related mortality without drug overdose continued to rise, no significant trend from ALD with drug overdose was noted. HCV‐related mortalities reduced after the introduction of DAA agents, while drug overdose‐related mortality in HCV was constantly increased. [ABSTRACT FROM AUTHOR]

Background and Aim: The association between palatin‐like phospholipase domain‐containing 3 (PNPLA3) I148M (rs738409) polymorphism and mortality is not well understood. We investigated the impact of PNPLA3 I148M (rs738409) polymorphism on overall and cardiovascular mortality based on the presence of nonalcoholic fatty liver disease (NAFLD). Methods: The third National Health and Nutrition Examination Survey (NHANES) from 1991 to 1994 and National Health and Nutrition Examination Survey III‐linked mortality data through 31 December 2015 were utilized in this study. Results: Of 4814 participants, 50.7% were homozygous for the C‐allele and 12.6% were homozygous for the G‐allele. During a follow up of 20 years, there were a total of 1255 deaths, 422 attributed to cardiovascular disease. There was a significant association with overall mortality among those with the PNPLA3 I148M (rs738409) GG genotype (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.02–1.77) or G‐allele (HR 1.22, 95% CI 1.09–1.36) in the general population. NAFLD with homozygous PNPLA3 I148M (rs738409) GG genotype had higher overall mortality after adjusting for multiple metabolic risk factors (HR 1.45, 95% CI 1.01–2.08). The PNPLA3 I148M (rs738409) G‐allele had a tendency of increased cardiovascular mortality in the total population. This association was not noted in those with NAFLD. Conclusions: The homozygous PNPLA3 I148M (rs738409) GG genotype showed an increase in overall mortality in the general population and NAFLD independent of multiple metabolic risk factors. [ABSTRACT FROM AUTHOR]

Background & Aims: Current estimates of the population‐based disease burden of liver failure or end‐stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in‐hospital mortality among patients with ESLD in the United States (US). Methods: A retrospective analysis was performed utilizing the National Inpatient Sample from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in‐hospital mortality were analysed from 2005 to 2014. Results: Hospitalization rates for decompensated cirrhosis during this period increased from 105.3/100 000 persons to 159.9/100 000 persons. In terms of HCC, hospitalization rates increased from 13.6/100 000 to 22.1/100 000. In patients with non‐alcoholic fatty liver disease (NAFLD)‐related decompensated cirrhosis, the hospitalization rate increased from 13.4/100 000 to 32.1/100 000 with an annual incremental increase of 10.6%, a magnitude twofold higher than other aetiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (from 29.3% to 27.6% for HCV; from 39.0% to 37.4% for ALD). Although the overall in‐hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD‐related decompensated cirrhosis showed no significant change. Conclusions: Among aetiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non‐HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD‐related hospitalizations and its impact on resource utilization. [ABSTRACT FROM AUTHOR]

Summary: Background: Currently, the relationship between depression and non‐alcoholic fatty liver disease (NAFLD) is not clearly defined. Aim: To determine whether depression is associated with NAFLD and NAFLD‐related advanced fibrosis in a large population sample. Methods: We performed a cross‐sectional analysis using the 2007‐2016 National Health and Nutrition Examination Survey database among adults (20 years or older) in the United States (US). Depression and functional impairment due to depression were assessed with the Patient Health Questionnaire (PHQ‐9). NAFLD was defined by utilising the US fatty liver index (USFLI), hepatic steatosis index (HSI) and the fatty liver index (FLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD were defined by Fibrosis‐4 score. Results: Of the 10 484 subjects (mean age 47.0 years; 48.8% men), the prevalence of depression and functional impairment due to depression was higher in subjects with NAFLD than in those without. Compared to subjects without depression, those with depression were 1.6‐2.2‐fold more likely to have NAFLD. In our multivariate analyses, depression_med was associated with increased risk of NAFLD using USFLI (odds ratio [OR] 1.48 95% confidence interval [CI] 1.17‐1.87), HSI (OR 1.51 95% CI 1.04‐2.19) and FLI (OR 2.01 95% CI 1.65‐2.48), respectively. The addition of diabetes, obesity and lipid profile to the model reduced the ORs for depression, but the significance persisted. Depression was not associated with NAFLD‐related advanced fibrosis. Conclusions: In a nationally representative sample of US adults, depression was independently associated with NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aims: The relationship between bisphenol A (BPA) and non‐alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD. Methods: We performed a cross‐sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005‐2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data. Results: Of the first 7605 participants (mean age 47 years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P < 0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39‐2.04) and 1.44 (95% CI 1.19‐1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05‐1.98, P for trend = 0.012). Conclusions: High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. Smoking and diabetes mellitus (DM) have been shown to increase mortality; however, whether NAFLD adds to the detrimental effect of smoking in DM and non‐DM patients is unknown. We evaluated the possible interactive effect of NAFLD and smoking on mortality risk in a US population‐based sample. Methods: Cross‐sectional data from 11 205 participants in the third National Health and Nutrition Examination Survey were analysed. NAFLD was defined as ultrasonographic hepatic steatosis without evidence of other liver diseases. Proportional hazards regression modelling was used to test for the multiplicative interaction of NAFLD and smoking on overall mortality, controlling for DM. Results: 36.5% of the participants had NAFLD of whom 21.1% were current smokers, while among non‐NAFLD subjects, 26.2% reported current smoking. Smoking was associated with a hazard ratio (HR) of 2.23 (95% confidence interval (CI): 1.87‐2.65) among non‐NAFLD subjects, and 2.31 (95% CI: 1.33‐2.92, P < 0.01) among NAFLD patients. In contrast, the HR for NAFLD was 1.01 (95% CI: 0.78‐1.31, P = 0.96) among smokers and 0.98 (95% CI: 0.87‐1.10, P = 0.73) among non‐smokers. There was no evidence of interaction between NAFLD and smoking (HR = 1.01, 95% CI: 0.74‐1.38, P = 0.94) in the combined model. Conclusion: We found that smoking increased mortality by two‐fold among the US population. Although the magnitude of the increase in mortality did not differ from that in non‐NAFLD subjects, smoking represents a modifiable determinant of long‐term outcomes in NAFLD patients. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and 10%-20% occurs in lean individuals. There is little data in the literature regarding outcomes in an ethnically-diverse patient populations with MASLD. Thus, we aim to investigate the natural history and ethnic disparities of MASLD patients in a diverse population, and stratified by body mass index categories., Methods: We conducted a retrospective multicenter study on patients with MASLD at the Banner Health System from 2012 to 2022. Main outcomes included mortality and incidence of cirrhosis, cardiovascular disease, diabetes mellitus (DM), liver-related events (LREs), and cancer. We used competing risk and Cox proportional hazard regression analysis for outcome modelling., Results: A total of 51 452 (cross-sectional cohort) and 37 027 (longitudinal cohort) patients were identified with 9.6% lean. The cohort was 63.33% European ancestry, 27.96% Hispanic ancestry, 3.45% African ancestry, and 2.31% Native American/Alaskan ancestry. Median follow-up was 45.8 months. After adjusting for confounders, compared to European individuals, Hispanic and Native American/Alaskan patients had higher prevalence of cirrhosis and DM, and individuals of Hispanic, African, and Native American/Alaskan ancestry had higher mortality and incidence of LREs and DM. Lean patients had higher mortality and incidence of LREs compared with non-lean patients., Conclusion: Native American/Alaskan, Hispanic, and African patients had higher mortality and incidence of LREs and DM compared with European patients. Further studies to explore the underlying disparities and intervention to prevent LREs in lean patients, particularly several ethnic groups, may improve clinical outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Testosterone plays a role in predisposing individuals to cardiovascular and metabolic diseases, but its effects differ between men and women. We investigated the association between serum total testosterone and non-alcoholic fatty liver disease in adults in the US., Methods: A cross-sectional analysis of data from participants in the 2011-2012 National Health and Nutrition Examination Survey was performed. Subjects with significant alcohol consumption and those with viral hepatitis were excluded. We used the highest sex-specific quartiles of serum total testosterone as references. Suspected non-alcoholic fatty liver disease was diagnosed when serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women., Results: Of the 4758 subjects (49.4% men), the prevalence of suspected non-alcoholic fatty liver disease was inversely correlated with the sex-specific quartiles of testosterone in men and women. In a multivariate model, low total testosterone levels were associated with progressively higher odds of suspected non-alcoholic fatty liver disease in men after adjusting for age, obesity and other metabolic risk factors (P values for trends <.01). When the women were divided into 2 groups according to menopausal status, a significant correlation was observed only in the post-menopausal women (P values for trends <.01). The adjusted odds ratios for suspected non-alcoholic fatty liver disease were 1.72-1.99 in men and 2.15-2.26 in post-menopausal women (lowest quartile vs highest quartile)., Conclusions: In this nationally representative sample of adults in the US, low total testosterone levels were associated with suspected non-alcoholic fatty liver disease in men and post-menopausal women independent of known risk factors., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aim: Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood., Methods: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB-4 score., Results: Of the 6738 participants (mean age 46.3 years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20-39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high-density lipoprotein cholesterol (P for trend <.05 respectively)., Conclusions: In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)