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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., (© 2024 John Wiley & Sons Ltd.)

Background & Aims: The cost‐effectiveness to screen hepatic fibrosis in at‐risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost‐effectiveness of this screening strategy in the expanded at‐risk population recently proposed by several societies. Methods: A combined model of the decision tree and Markov models was developed to compare expected costs, quality‐adjusted life‐years (QALYs) and incremental cost‐effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease‐related health states and cardiovascular disease (CVD) states as a base‐case analysis. Screening strategy consisted of fibrosis‐4 index (FIB‐4) followed by vibration‐controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients. Results: Cost‐effectiveness analysis showed that screening the at‐risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost‐effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost‐effectiveness model, the ICER decreased by 0.85 times from the base‐case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost‐effective with the estimate below the countries' ICER threshold. Conclusions: Our study provides compelling evidence supporting the cost‐effectiveness of FIB‐4‐based screening the at‐risk population for advanced hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Sex steroid hormones and sex hormone-binding globulin (SHBG) have a role in predisposing individuals to nonalcoholic fatty liver disease (NAFLD), but their effects are known to differ between men and women. The testosterone- to-estradiol ratio (T/E2 ratio) and free androgen index (FAI) were known biomarkers for the hormonal milieu. We investigated whether sex steroid hormones, T/E2 ratio, FAI, and SHBG were associated with NAFLD in US adults. Methods: A cross-sectional analysis using the 2013--2016 National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI) and the US fatty liver index (USFLI) without other causes of chronic liver disease. Results: Out of 8687 subjects (49.5% male), low total testosterone levels were associated with progressively higher odds of NAFLD in men. Increasing T/E2 ratio was inversely associated with higher odds of NAFLD in men. Low serum SHBG levels were independently associated with an increased risk of NAFLD regardless of sex and menopausal status. Increasing FAI was independently associated with NAFLD. When we additionally adjusted for SHBG, T/E2 ratio, not total testosterone, was inversely associated with NAFLD in a dose-dependent manner. Increasing FAI was associated with higher odds of NAFLD in premenopausal women and marginally associated with NAFLD in postmenopausal women. Conclusion: The T/E2 ratio and SHBG were inversely associated with an increased risk of NAFLD in men. In women, increasing FAI was associated with NAFLD, whereas SHBG was inversely associated with NAFLD. [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]

Muscle strength in non-alcoholic fatty liver disease and all-cause and cause-specific mortality Keywords: death; handgrip strength; hepatic steatosis; nhanes; sarcopenia EN death handgrip strength hepatic steatosis nhanes sarcopenia 513 516 4 01/27/23 20230201 NES 230201 Abbreviations BMI body mass index CI confidence interval HIS hepatic steatosis index HR hazard ratio NAFLD non-alcoholic fatty liver disease NHANES National Health and Nutrition Examination Survey UCOD underlying cause of death Key points Higher muscle strength among individuals with non-alcoholic fatty liver disease is associated with a lower risk of all-cause and cardiovascular mortality independent of known demographic, clinical and metabolic risk factors. 8 Range of combined grip strength/body mass index for women: quartile 1: <1.437, quartile 2: >=1.437 and <1.712, quartile 3: >=1.712 and <2.025, quartile 4: >=2.025. First, we used a non-invasive marker to define NAFLD, which may misclassify the true prevalence of NAFLD, because NHANES 2011-2014 data lack radiological or histological information, which is considered the gold standard for the diagnosis of NAFLD. [Extracted from the article]

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]

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is known to increase the risk of adenomatous colonic polyps. However, the role of screening colonoscopy in patients with biopsy‐proven NAFLD in detecting advanced colorectal neoplasm is not clearly evidence‐based. Therefore, we investigated whether the histological severity of NAFLD is associated with advanced colorectal neoplasm. Methods: This study included patients ≥18 years old who underwent screening colonoscopy between 2013 and 2018 within a biopsy‐evaluated prospective NAFLD cohort. Advanced colorectal neoplasm was defined as an adenomatous polyp greater than 10 mm in diameter and/or with villous histology and/or with high‐grade dysplasia or adenocarcinoma. Results: Among the 476 patients with clinically suspected NAFLD, 379 patients were diagnosed with biopsy‐proven NAFLD and 97 patients had no evidence of NAFLD histologically, who were analyzed as healthy controls. The prevalence of advanced colorectal neoplasm was 11.1% (n = 53). Patients with advanced colorectal neoplasm had higher grade of steatosis (P = 0.004) and higher stage of hepatic fibrosis (P = 0.044) than those with normal colonoscopic findings or low‐grade adenomatous polyp. Multivariable logistic regression analysis revealed that the presence of nonalcoholic steatohepatitis (NASH) was an independent risk factor for both colorectal polyp (odds ratio [OR], 2.08; 95% confidential interval [CI], 1.12‐3.86; P = 0.020) and advanced colorectal neoplasm (OR, 2.81; 95% CI, 1.01‐7.87; P = 0.049). Conclusions: The presence of biopsy‐proven NASH was significantly associated with an increased risk of advanced colorectal neoplasm among patients with NAFLD. This finding may alert physicians to conduct screening colonoscopy in patients with NASH to detect advanced colorectal neoplasm early. [ABSTRACT FROM AUTHOR]

Background and Aim: We investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7-TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non-alcoholic fatty liver disease (NAFLD). Methods: We genotyped rs738409, rs58542926, and rs641738 in biopsy-proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance and adipose tissue insulin resistance were calculated. Results: The rs738409 and rs58542926 variants, but not rs641738, were associated not only with non-alcoholic steatohepatitis (NASH) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46-2.73 and OR, 1.91; 95% CI, 1.04-3.51) but also with significant fibrosis (≥ F2) (OR, 1.53; 95% CI, 1.11-2.11 and OR, 1.88; 95% CI, 1.02-3.46) in NAFLD, even after adjustment for metabolic risk factors. Of both variants, only rs738409 was associated with homeostasis model assessment of insulin resistance and adipose tissue insulin resistance even in healthy controls (P = 0.046 and 0.002, respectively) as well as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and TM6SF2 risk variants additively increased the risk of NASH and significant fibrosis (OR per risk allele, 2.03; 95% CI, 1.50-2.73 and 1.61; 95% CI, 1.19-2.17). Even in subjects with low insulin resistance, the risk of NASH or significant fibrosis increased as the number of risk alleles increased (P = 0.008 and 0.020, respectively). Conclusions: PNPLA3 and TM6SF2 determine the risk of NASH and significant fibrosis, even after adjustment for insulin resistance, and exert an additive effect on NASH and significant fibrosis. [ABSTRACT FROM AUTHOR]