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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]

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: Healthy diet has been recommended for nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent mortality. We aim to assess the impact of quality of diet on NAFLD and mortality in subjects with and without NAFLD. Methods: We performed cohort study using the Third National Health and Nutrition Examination Survey from 1988 to 1994 and linked mortality data through 2015. We used the Healthy Eating Index (HEI) scores to define diet quality, with higher HEI scores (Q4) indicating better adherence to dietary recommendations. NAFLD was defined as ultrasonographic hepatic steatosis. Results: Multivariate analysis showed that subjects with higher diet quality were inversely associated with NAFLD in a dose‐dependent manner. During the median follow‐up of 23 years, having a higher diet quality was associated with reduction in risk of all‐cause mortality in the age, sex, Race/ethnicity‐adjusted hazard ratio (HR) (Q4, HR: 0.60, 95% CI: 0.52‐0.68) and the multivariate model (Q4, HR: 0.81, 95% CI: 0.71‐0.92). Higher diet quality was associated with a lower risk for all‐cause mortality in subjects without NAFLD; however, this protective association with diet quality was not noted in those with NAFLD. Furthermore, a high diet quality was associated with a lower risk for cancer‐related mortality in the total population and among those without NAFLD. This association was not noted in those with NAFLD. Conclusions: High diet quality was inversely associated with NAFLD and was positively associated with a lower risk for cancer‐related and all‐cause mortality in those without NAFLD. [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]

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 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]

Aims: We compared (a) demographic and clinical characteristics and (b) determinants of nonalcoholic steatohepatitis and significant fibrosis in non‐obese and obese nonalcoholic fatty liver disease. Methods: A cross‐sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy‐proven nonalcoholic fatty liver disease and controls was conducted. Subjects were divided by their body mass index into obese (body mass index ≥25 kg/m2) and non‐obese (body mass index <25 kg/m2). Results: Observations in subjects with non‐obese nonalcoholic fatty liver disease were in between non‐obese controls and subjects with obese nonalcoholic fatty liver disease for body mass index, sagittal abdominal diameter, aminotransferase levels, insulin resistance and abdominal visceral adipose tissue area. There was no significant difference in histology between non‐obese and obese subjects with nonalcoholic fatty liver disease except for lower grade of hepatic steatosis in nonobese nonalcoholic fatty liver disease and higher severity of hepatic fibrosis in nonobese nonalcoholic steatohepatitis. Predictors of nonalcoholic steatohepatitis in nonobese subjects included females (odds ratio 2.49), higher alanine aminotransferase (odds ratio 1.03), lower high‐density lipoprotein cholesterol (odds ratio 0.96), higher prevalence of diabetes (odds ratio 3.65) and higher visceral adipose tissue area (odds ratio 1.63 per standard deviation increase of visceral adipose tissue area) while age (odds ratio 1.04), higher aspartate aminotransferase (odds ratio 1.02), diabetes (odds ratio 2.76) and higher visceral adipose tissue area (odds ratio 1.57 per standard deviation increase) were associated with significant fibrosis in the non‐obese. Sagittal abdominal diameter was independently associated with nonalcoholic steatohepatitis or significant fibrosis among subjects with non‐obese nonalcoholic fatty liver disease. Conclusion: While there were a few phenotypic differences from obese subjects, non‐obese subjects with nonalcoholic fatty liver disease displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non‐obese nonalcoholic fatty liver disease advances to more severe disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Background & Aims Physical activity ( PA) is inversely associated with nonalcoholic fatty liver disease ( NAFLD) prevalence. However, few studies evaluated the effect of PA on NAFLD incidence in regard to visceral adipose tissue ( VAT) and insulin resistance ( IR). We investigated whether PA at baseline and change in PA during follow-up have any effect on incident NAFLD. Methods We enrolled subjects who underwent health screenings between 2007 and 2008 and participated in voluntary follow-up between 2011 and 2013 (median 4.42 years). Incident NAFLD was defined as NAFLD absence at baseline and presence at follow-up by ultrasonography. PA was measured using a detailed questionnaire-based metabolic equivalent at baseline and follow-up; the difference during follow-up was calculated. Results Of the 1373 subjects enrolled, 288 (21.0%) developed NAFLD. Both total and leisure-time PA at baseline were inversely associated with incident NAFLD ( P for trend=.005 and .003 respectively). Decreased PA at follow-up was associated with increased incident NAFLD risk after adjusting for age, gender, body mass index, smoking, hypertension, diabetes and diet [hazard ratio ( HR) 1.45, 95% confidence interval ( CI) 1.04-2.02, 4th (most decreased PA) vs 1st quartile (increased PA), P=.028]. This relationship was attenuated but remained statistically significant after adjustment for VAT( HR 1.48, 95% CI 1.06-2.06, 4th vs 1st quartile) and IR( HR 1.59, 95% CI 1.11-2.27, 4th vs 1st quartile). Conclusions This study shows an independent protective effect of PA at baseline on incident NAFLD after 4-year follow-up. Furthermore, sustained or increased PA had a preventive effect on incident NAFLD independent of VAT and IR. [ABSTRACT FROM AUTHOR]

Background & Aims Limited evidence supports a role for physical activity ( PA) in nonalcoholic fatty liver disease ( NAFLD) independent of visceral obesity or/and insulin resistance. We investigated the association between PA and NAFLD while considering visceral adipose tissue ( VAT) and insulin resistance in a large general population. Methods Nonalcoholic fatty liver disease was diagnosed based on typical ultrasonographic findings. A detailed PA questionnaire included type, frequency, duration and length of time that the subject engaged in PA. PA was determined by a metabolic equivalent. VAT was evaluated by computed tomography taken at the umbilicus level. Results A total of 3718 subjects were enrolled in the analysis. After adjusting for age, gender, body mass index, smoking, hypertension, diabetes, soft drink and coffee consumption, the total PA was inversely associated with NAFLD [4th quartile (highest activities), odds ratio ( OR) 0.68, 95% confidence interval ( CI) 0.54-0.85; 3rd quartile, OR 0.74, 95% CI 0.59-0.93 vs. 1st quartile (lowest activities), P for trend <0.001]. After further adjusting for VAT or insulin resistance or both ( P for trend = 0.027, 0.001 and 0.040 respectively), this relationship was slightly attenuated but remained statistically significant. The leisure-time PA and weighted PA also had inverse associations with NAFLD independent of the VAT or insulin resistance or both. Conclusions This study showed an inverse association between various types of PA and the prevalence of NAFLD in a dose-dependent manner that was independent of visceral obesity and insulin resistance. This finding suggests a beneficial association between PA and NAFLD. [ABSTRACT FROM AUTHOR]