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    Trends in statin utilisation in US adults with non-alcoholic fatty liver disease. Henson Jacqueline B,Patel Yuval A,Muir Andrew J Alimentary pharmacology & therapeutics BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) has high morbidity and mortality related to cardiovascular disease (CVD), but statins have been historically underutilised in these patients due to concern for hepatotoxicity. AIMS:To characterise trends in statin use among individuals with NAFLD and to determine predictors of statin utilisation in this population. METHODS:Individuals with NAFLD were identified from 2005 to 2018 continuous National Health and Nutrition Examination Survey. Trends in statin use over time were assessed, and predictors of statin under-utilisation for primary prevention were identified. The roles of a known diagnosis of liver disease and disease severity were examined. RESULTS:We included 14 113 individuals; 34.6% had NAFLD, of whom 5.4% reported a liver disease diagnosis. There was a significant increase in statin use for primary prevention between 2005 and 2018 (18.1%-25.0%; P = 0.03), but guideline-indicated use for this purpose was low (54.5% between 2005 and 2012; 48.6% between 2013 and 2018). A known NAFLD diagnosis was a negative predictor of statin use during the earlier time period but not more recently. Utilisation did not decrease with increasing liver disease severity. CONCLUSIONS:In a nationally representative population with NAFLD, statin use for primary prevention has increased over time, but guideline-concordant use remains low. A known liver disease diagnosis was associated with lack of statin use in the earlier time period but not more recently, suggesting a changing perspective of underlying liver disease impacting statin utilisation. Further work to improve guideline-indicated statin use in this high-risk population is needed. 10.1111/apt.16646
    Association Between Diabetes Mellitus and All-Cause and Cardiovascular Mortality Among Individuals With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease. Wu Weiti,Xiang Jingjing,Chen Xiaoye Frontiers in endocrinology Objective:The influence of diabetes on mortality among patients with non-alcoholic fatty liver disease (NAFLD) in the general population has not been extensively studied. This study aimed to determine the relationship between diabetes and all-cause and cardiovascular mortality in patients with hepatic ultrasound-confirmed NAFLD using data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. Methods:Data from 4,037 adult individuals with NAFLD from the NHANES III and mortality outcomes linked to National Death Index records through December 31, 2015, were included. Cox proportional hazards models were used to calculate the hazard ratio (HR) and corresponding 95% CI for mortality from all causes and cardiovascular disease after adjusting for multiple variables. Results:Among 4,037 subjects with NAFLD (55.9% female), 483 had diabetes at baseline. During a median follow-up of 22.1 years, 1,517 (11.5%) died, including 332 (8.22%) from cardiovascular causes. Diabetes was associated with increased all-cause (HR 3.02 [95% CI 2.67-3.41]) and cardiovascular (HR 3.36 [95% CI 2.61-4.32]) mortality in an unadjusted multivariable Cox regression model. The association remained statistically significant after adjusting for a range of potential confounders (HR 2.20 [95% CI 1.90-2.55] for all-cause mortality and HR 2.47 [95% CI 1.81-3.37] for cardiovascular mortality). An additional stratified analysis did not reveal significantly altered results. Conclusion:Diabetes was associated with all-cause and cardiovascular mortality in patients with NAFLD. This link could be further characterized in future studies assessing the degree of glycemic control and its relationship with mortality in patients with diabetes and NAFLD. 10.3389/fendo.2021.773342
    Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey Data. Kabbany Mohammad Nasser,Conjeevaram Selvakumar Praveen Kumar,Watt Kymberly,Lopez Rocio,Akras Zade,Zein Nizar,Carey William,Alkhouri Naim The American journal of gastroenterology OBJECTIVES:Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of manifestations ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), fibrosis and eventually cirrhosis. The prevalence of NAFLD has been shown to be increasing over time; however, the prevalence of NASH cirrhosis and advanced fibrosis over time has not been well studied. Estimate the changes in prevalence of NASH cirrhosis and NAFLD-associated advanced fibrosis among adults in the United States. METHODS:National Health and Nutrition Examination Survey (NHANES) data obtained during the periods from 1999-2002 and 2009-2012 were analyzed to estimate the prevalence of NASH cirrhosis and NAFLD-associated advanced fibrosis in subjects aged ≥18 years at the time of enrollment. We excluded patients with viral hepatitis, excessive alcohol consumption, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >500 and patients who were pregnant. Cirrhosis was defined by AST to platelet ratio index (APRI) >2 and abnormal liver function tests. NASH cirrhosis was defined as cirrhosis that presented with at least one of the following: obesity, diabetes, insulin resistance (HOMA-IR≥3), and metabolic syndrome. Advanced fibrosis was defined by using well-established cutoff values for APRI, fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). Population weighted prevalence was calculated separately for two groups to account for complex sampling method of NHANES. RESULTS:A total of 7034 NHANES participants from 1999-2002 and 2009-2012 group were included with mean age of 46.2±0.59 and 47.3±0.51 years, respectively, at the time of screening. The prevalence of NASH cirrhosis was significantly higher in 2009-2012 group (0.178% with an estimated 417,524 American adults with NASH-associated cirrhosis) compared to 1999-2002 group (0.072%); P value<0.05. The prevalence of NAFLD with advanced fibrosis also increased from 0.84 to 1.75% during the same time period (P value<0.001) corresponding to 4,104,871 American adults. During these time periods, there were also significant increases in obesity (29.8 vs. 36.6%), diabetes (8.3 vs. 11.9%), and insulin resistance (34.7 vs. 42.1%); P value <0.005 for all of them. CONCLUSIONS:There has been a 2.5-fold and 2-fold increases in the prevalence of NASH cirrhosis and NAFLD-associated advanced fibrosis, respectively, in 2009-2012 compared to 1999-2002. Extrapolation of NHANES data suggests that in 2010, 417,524 in the US had NASH cirrhosis, and 4,104,871 had NAFLD-associated advanced fibrosis. This represents a major disease burden and suggests the need for widespread programs to identify and treat those affected, and public health efforts aimed at controlling the burden of NAFLD and its complications. 10.1038/ajg.2017.5
    Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults. Yang Chao-Qun,Shu Long,Wang Shuai,Wang Jia-Jia,Zhou Yu,Xuan Yu-Jie,Wang Su-Fang Nutrients Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45-60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day(-1) in men and 10 g day(-1) in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: "Traditional Chinese", "Animal food", "Grains-vegetables" and "High-salt" dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the "Animal food" pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063-1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the "Grains-vegetables" pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618-0.977, p < 0.05). However, the "traditional Chinese" and "high-salt" dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the "Animal food" dietary pattern was associated with an increased risk of NAFLD. 10.3390/nu7064778
    The Association between Non-Alcoholic Fatty Liver Disease (NAFLD) and Advanced Fibrosis with Serological Vitamin B12 Markers: Results from the NHANES 1999-2004. Li Li,Huang Qi,Yang Linjian,Zhang Rui,Gao Leili,Han Xueyao,Ji Linong,Zou Xiantong Nutrients BACKGROUND:There is evidence that vitamin B12 and associated metabolite levels are changed in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); however, their association has been in dispute. METHODS:We included 8397 individuals without previous liver condition or excess alcohol intake from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. NAFLD was diagnosed with Fatty Liver Index (FLI) ≥ 60 or USFLI ≥ 30, and participants with advanced fibrosis risks were identified with elevated non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 index (FIB-4), or aspartate aminotransferase (AST)/platelet ratio index (APRI). Step-wide logistic regression adjusting for confounders was used to detect the association between NAFLD or advanced fibrosis with serum vitamin B12, folate, red blood cell folate (RBC folate), homocysteine (HCY), and methylmalonic acid (MMA). RESULTS:The weighted prevalence of NAFLD was 44.2%. Compared with non-NAFLD participants, patients with NAFLD showed significantly increased RBC folate level and RBC counts, decreased serum vitamin B12 and folate, and similar HCY and MMA levels. NAFLD with advanced fibrosis risk had higher MMA and HCY, reduced serum vitamin B12, and similar serum folate and RBC folate levels than NAFLD with low fibrosis risk. Only RBC folate was independently associated with an increased risk of NAFLD (OR (95% CI): 2.24 (1.58, 3.18)). In all participants, MMA (OR: 1.41 (1.10, 1.80)) and HCY (OR: 2.76 (1.49, 5.11)) were independently associated with increased risk for advanced fibrosis. In participants with NAFLD, this independent association still existed (OR: 1.39 (1.04, 1.85) for MMA and 1.95 (1.09, 3.46) for HCY). In all participants, the area under the receiver operating characteristic curve (ROC AUC) on fibrosis was 0.6829 (0.6828, 0.6831) for MMA and 0.7319 (0.7318, 0.7320) for HCY; in participants with NAFLD, the corresponding ROC AUC was 0.6819 (0.6817, 0.6821) for MMA and 0.6926 (0.6925, 0.6928) for HCY. CONCLUSION:Among vitamin B12-associated biomarkers, RBC folate was independently associated with elevated NAFLD risk, whereas MMA and HCY were associated with increased risk for advanced fibrosis in the total population and NAFLD participants. Our study highlighted the clinical diagnostic value of vitamin B12 metabolites and the possibility that vitamin B12 metabolism could be a therapeutic target for NASH. Further studies using recent perspective data with biopsy proven NASH could be conducted to validate our results. 10.3390/nu14061224
    Nonalcoholic Fatty Liver Disease and Renal Function Impairment: A Cross-Sectional Population-Based Study on Its Relationship From 1999 to 2016. Le Michael H,Yeo Yee Hui,Henry Linda,Nguyen Mindie H Hepatology communications There is growing evidence that links nonalcoholic fatty liver disease (NAFLD) with impairment of renal function. As such, we aimed to demonstrate the trend of NAFLD, NAFLD with renal insufficiency (RI), disease awareness, and mortality over time. Patient data were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2016. A total of 14,255 adult study participants without competing liver disease or heavy drinking and with complete laboratory data were included. NAFLD was defined using the U.S. Fatty Liver Index (USFLI) and RI was defined using the Chronic Kidney Disease Epidemiology Collaboration equation and urine albumin:creatinine ratio. Death data were obtained from the National Death Index (up to December 31, 2015). Prevalence of NAFLD in participants was 31.2% (95% confidence interval [CI], 30.01-32.46); of these participants, 22.05% (95% CI, 20.34-23.85) had RI. From 1999 to 2016, prevalence of both NAFLD without RI ( 0.048) and NAFLD-RI ( 0.006) increased significantly. Among those with NAFLD-RI, awareness of kidney disease was 8.56% (95% CI, 6.69-10.89), while awareness of liver disease among all NAFLD was 4.49% (95% CI, 3.17-6.33). Among those with NAFLD, mortality incidence per 1,000 person years was highest among those with severe RI in all-cause mortality (104.4; 95% CI, 83.65-130.39) and other residual causes of mortality (mean, 50.88; 95% CI, 37.02-69.93). Prevalence of NAFLD and NAFLD-RI has increased over the past 2 decades in the United States. Low kidney disease and liver disease awareness are major public health issues as those with NAFLD-RI have significantly higher mortality than those with only NAFLD. 10.1002/hep4.1408
    Prevalence of High and Moderate Risk Nonalcoholic Fatty Liver Disease Among Adults in the United States, 1999-2016. Golabi Pegah,Paik James M,Herring Michael,Younossi Elena,Kabbara Khaled,Younossi Zobair M Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association BACKGROUND AND AIMS:Nonalcoholic fatty liver disease (NAFLD) subjects with fibrosis stage ≥2 are at high risk for mortality. We aimed to provide national estimates and temporal trends for NAFLD, based on different fibrosis severity. METHODS:Data from the National Health and Nutrition Examination Survey (NHANES) (1999-2016) and NHANES III (1988-1994) were utilized. NAFLD was determined by ultrasound showing moderate to severe steatosis. For those without ultrasound, NAFLD was determined by the U.S. Fatty Liver Index score of ≥30. Hepatic fibrosis was assessed using Fibrosis-4 (FIB-4) score (FIB-4 <1.3 = low risk; FIB-4 1.3-2.67 = moderate risk; and FIB-4 >2.67 = high risk). Annual percent change (APC) was calculated by using the joinpoint regression model. RESULTS:From NHANES III, 10,854 individuals were included (mean age 43.5 years; 47.5% male; 75.7% non-Hispanic White) and 37.7% had NAFLD. Among them, based on FIB-4, 80% had low-risk, 18.6% had moderate-risk, and 1.4% had high-risk NAFLD. NAFLD with moderate or high risk was more likely to have hypertension, hyperlipidemia, diabetes, cardiovascular disease, and metabolic syndrome than was low-risk NAFLD (all P < .02). NAFLD prevalence increased from 29.5% in 1999-2000 to 40.3% in 2015-2016 (APC, 2.78%; P < .02), moderate-risk NAFLD increased from 6.26% to 14.17% (APC, 5.34%; P < .02), and high-risk NAFLD increased from 0.49% to 1.15% (APC, 9.72%; P < .02). Independent predictors of advanced fibrosis were age (OR, 1.11; 95% CI, 1.06-1.17; P = .001) and diabetes (OR, 2.28; 95% CI, 1.03-5.05; P = .04). Compared with low-risk NAFLD, high-risk NAFLD was associated with significantly increased all-cause (HR, 1.53; 95% CI, 1.09-2.15; P = .01), cardiovascular disease-specific (HR, 1.99; 95% CI, 1.22-3.24, P < .01) and liver-specific (HR, 4.57; 95% CI, 1.03-28.79; P = .04) mortality. CONCLUSIONS:The prevalence of moderate- or high-risk NAFLD is increasing and is associated with increased all-cause, liver-related, and cardiovascular mortality. 10.1016/j.cgh.2021.12.015
    Are there outcome differences between NAFLD and metabolic-associated fatty liver disease? Hepatology (Baltimore, Md.) BACKGROUND:Given the association of NAFLD with metabolic risks, a name change to MAFLD is proposed. We compared the long-term outcomes of NAFLD and MAFLD. METHODS:We included patients with fatty liver disease (FLD) from NHANES III and NHANES 2017-2018 (FLD defined as moderate to severe hepatic steatosis by ultrasound for NHANES III and as having a controlled attenuation parameter ≥285 dB/m for NHANES 2017-2018). NAFLD was defined as FLD without other liver diseases and excess alcohol use. Metabolic-associated fatty liver disease (MAFLD) was defined as FLD and metabolic dysfunction per criteria. All NHANES III participants had linked mortality data through December 31, 2015. RESULTS:NHANES III participants (n = 12,878): mean age 43.1 years old; 49.5% male; 20.3% with FLD, 16.5% with NAFLD, and 18.1% with MAFLD. NHANES 2017-2018 participants (n = 4328): mean age 48.0 years old; 49.1% male; 36.8% with FLD, 34.2% with NAFLD, and 36.3% with MAFLD. Excellent concordance was noted between MAFLD and NAFLD diagnosis in both data sets (kappa coefficient = 0.83-0.94). Except for components of each definition (e.g., alcohol use for MAFLD), no other major differences in clinical characteristics were noted. During up to 27 years of follow-up (median of 22.8 years), no differences in cumulative all-cause and cause-specific mortality were noted. In addition to the stage of fibrosis, insulin resistance was a predictor of liver mortality in NAFLD, and alcohol-associated liver disease (ALD) was a predictor of mortality in MAFLD. CONCLUSIONS:MAFLD and NAFLD have similar clinical profiles and long-term outcomes. The increased liver-related mortality among NAFLD is driven by insulin resistance, and among MAFLD is primarily driven by ALD. 10.1002/hep.32499
    Liver fat scores predict liver disease mortality in the United States population. Unalp-Arida Aynur,Ruhl Constance E Alimentary pharmacology & therapeutics BACKGROUND:Fatty liver is a significant global public health burden, contributing to premature death. AIM:To examine whether liver fat scores were associated with increased overall and disease-specific mortality in a United States (US) population-based survey with up to 27 years of linked mortality data. METHODS:We studied 9200 fasted viral hepatitis-negative adults in the third National Health and Nutrition Examination Survey, 1988-1994. Liver fat was predicted using the US fatty liver index (US FLI), fatty liver index (FLI), non-alcoholic fatty liver disease liver fat score (NAFLD LFS), and hepatic steatosis index (HSI). Participants were passively followed up for mortality, identified by death certificate underlying or contributing causes, by linkage to National Death Index records through 2015. Mortality hazard ratios (HR) were calculated using Cox proportional hazards regression to adjust for mortality risk factors. RESULTS:During follow-up (median, 23.3 years), cumulative mortality was 31.4% overall and 1.1% with liver disease, including primary liver cancer. Elevated liver disease mortality was associated with a high US FLI (HR, 5.7; 95% confidence interval (CI), 1.3-24.5), and intermediate (HR, 3.1; 95% CI, 1.1-9.1) or high (HR, 11.4; 95% CI, 2.9-44.4) NAFLD LFS, but not with a higher FLI or HSI. Overall and cardiovascular disease mortality was unassociated with higher liver fat scores. CONCLUSIONS:In the US population, a higher US FLI and NAFLD LFS were associated with increased liver disease mortality, but not with other mortality outcomes. Liver fat scores may be useful for metabolic health surveillance and long-term liver disease risk stratification and may complement fibrosis markers for tracking. 10.1111/apt.14967
    Race/ethnicity-based temporal changes in prevalence of NAFLD-related advanced fibrosis in the United States, 2005-2016. Kim Donghee,Kim Won,Adejumo Adeyinka C,Cholankeril George,Tighe Sean P,Wong Robert J,Gonzalez Stevan A,Harrison Stephen A,Younossi Zobair M,Ahmed Aijaz Hepatology international BACKGROUND AND AIM:Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample. METHODS:Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD was determined by the NAFLD fibrosis score, FIB-4 score, and aspartate aminotransferase-to-platelet ratio index. RESULTS:The prevalence of NAFLD-related advanced fibrosis increased from 2.6% [95% confidence interval (CI) 2.1-3.1] in 2005-2008 and 4.4% (95% CI 3.7-5.1) in 2009-2012, to 5.0% (95% CI 4.2-5.9) in 2013-2016 using HSI as the NAFLD prediction model; and from 3.3% (95% CI 2.5-4.5) in 2005-2008 and 6.4% (95% CI 3.7-5.1) in 2009-2012, to 6.8% (95% 5.3-8.7) in 2013-2016 using USFLI (p < 0.01). A similar trend was observed in entire NHANES cohort regardless of NAFLD status. While the prevalence of advanced fibrosis increased steadily in non-Hispanic whites through the duration of the study, it leveled off during 2013-2016 in non-Hispanic blacks. CONCLUSIONS:Prevalence of advanced fibrosis associated with NAFLD increased steadily from 2005 to 2016. More importantly, race/ethnicity-based temporal differences were noted in the prevalence of NAFLD-related advanced fibrosis during the study. 10.1007/s12072-018-09926-z
    Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999-2016. Zou B,Yeo Y H,Nguyen V H,Cheung R,Ingelsson E,Nguyen M H Journal of internal medicine BACKGROUND:Updated prevalence and outcome data for nonobese NAFLD for the multi-ethnic US population is limited. OBJECTIVES:We aimed to investigate the prevalence, clinical characteristics and mortality of obese and nonobese individuals with NAFLD in the United Sates. METHODS:A retrospective study was conducted using the 1999-2016 NHANES databases. We determined hazard ratio stratified by obesity status in NAFLD individuals using Cox regression and log-rank test. RESULTS:Overall NAFLD prevalence was 32.3%: 22.7% were obese and 9.6% were nonobese, with increasing trend over time for obese NAFLD, but not nonobese NAFLD. Amongst those with NAFLD, 29.7% (95% CI: 27.8%-31.7%) were nonobese, of which 13.6% had lean NAFLD. Nonobese NAFLD was more common in older (40.9% if ≥ 65 vs. 24.2% if < 65 years), male (34.0% vs. 24.2%) and foreign-born Asian people (39.8% vs. 11.4%) and uncommon in black (11.5% vs 30-35% in other ethnicities, P < 0.001). Metabolic comorbidities were common in nonobese NAFLD individuals who also had more advanced fibrosis. Nonobese NAFLD individuals had higher 15-year cumulative all-cause mortality (51.7%) than obese NAFLD (27.2%) and non-NAFLD (20.7%) (P < 0.001). However, DM and fibrosis, but neither obese nor nonobese NAFLD compared to non-NAFLD was independently associated with higher mortality. CONCLUSION:Nonobese NAFLD makes up about one-third of the NAFLD in the United States (even higher in older, male and foreign-born individuals) and carries higher mortality than obese NAFLD. Screening for NAFLD should be considered in high-risk groups even in the absence of obesity. 10.1111/joim.13069
    The steatosis-associated fibrosis estimator score: A tool to detect low-risk NAFLD in primary care. Hepatology (Baltimore, Md.) BACKGROUND:NAFLD is common in primary care. Liver fibrosis stage 2 or higher (≥F2) increases future risk of morbidity and mortality. We developed and validated a score to aid in the initial assessment of liver fibrosis for NAFLD in primary care. METHODS:Data from patients with biopsy-proven NAFLD were extracted from the NASH Clinical Research Network observational study (n = 676). Using logistic regression and machine-learning methods, we constructed prediction models to distinguish ≥F2 from F0/1. The models were tested in participants in a trial ("FLINT," n = 280) and local patients with NAFLD with magnetic resonance elastography data (n = 130). The final model was applied to examinees in the National Health and Nutrition Examination Survey (NHANES) III (n = 11,953) to correlate with long-term mortality. RESULTS:A multivariable logistic regression model was selected as the Steatosis-Associated Fibrosis Estimator (SAFE) score, which consists of age, body mass index, diabetes, platelets, aspartate and alanine aminotransferases, and globulins (total serum protein minus albumin). The model yielded areas under receiver operating characteristic curves ≥0.80 in distinguishing F0/1 from ≥F2 in testing data sets, consistently higher than those of Fibrosis-4 and NAFLD Fibrosis Scores. The negative predictive values in ruling out ≥F2 at SAFE of 0 were 88% and 92% in the two testing sets. In the NHANES III set, survival up to 25 years of subjects with SAFE < 0 was comparable to that of those without steatosis (p = 0.34), whereas increasing SAFE scores correlated with shorter survival with an adjusted HR of 1.53 (p < 0.01) for subjects with SAFE > 100. CONCLUSION:The SAFE score, which uses widely available variables to estimate liver fibrosis in patients diagnosed with NAFLD, may be used in primary care to recognize low-risk NAFLD. 10.1002/hep.32545
    In patients with non-alcoholic fatty liver disease, metabolically abnormal individuals are at a higher risk for mortality while metabolically normal individuals are not. Younossi Zobair M,Otgonsuren Munkhzul,Venkatesan Chapy,Mishra Alita Metabolism: clinical and experimental BACKGROUND AND AIM:Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and is strongly associated with metabolic syndrome. The aim of this study is to compare the clinical profile and long-term outcome in NAFLD patients with or without metabolic syndrome. METHODS:The initial cohort (N=6709) was identified from National Health and Nutrition Examination Survey-III (NHANES III, 1988-94) data. Laboratory profiles, body measurement examinations, and mortality data were linked to self-reported questionnaires of demographic and health risk information. NAFLD was defined as significant steatosis on hepatic ultrasound after exclusion of other chronic liver diseases (N=1448). NAFLD patients were classified according to presence or absence of metabolic syndrome. Mortality was determined through December 31, 2006. Cox models were used to estimate hazard ratios and 95% confidence intervals for all-cause, cardiovascular and liver-specific mortality differences between two sub-cohorts of NAFLD with and without metabolic syndrome. RESULTS:NAFLD participants with metabolic syndrome were more likely to be Non-Hispanic white, older, and have higher aminotransferase levels. All-cause mortality (P<.001) and cardiovascular mortality (P<.001) were higher in NAFLD patients with metabolic syndrome. Furthermore, the presence of metabolic syndrome was independently associated with overall mortality, liver-specific mortality, and cardiovascular mortality. Age was an independent predictor of both all-cause and cardiovascular mortality. Elevated liver enzymes and obesity were two other independent predictors of liver-specific mortality. There were no differences in all-cause, liver-related, or cardiovascular mortality between groups of individuals without liver disease and individuals with NAFLD without metabolic syndrome (metabolically-normal). CONCLUSIONS:Diagnosis of NAFLD with metabolic syndrome is an independent predictor of all-cause, liver-specific, and cardiovascular mortality. In contrast, mortality of metabolically-normal NAFLD patients is similar to the cohort without liver disease. 10.1016/j.metabol.2012.08.005
    Attributable Fractions of Nonalcoholic Fatty Liver Disease for Mortality in the United States: Results From the Third National Health and Nutrition Examination Survey With 27 Years of Follow-up. Alvarez Christian S,Graubard Barry I,Thistle Jake E,Petrick Jessica L,McGlynn Katherine A Hepatology (Baltimore, Md.) BACKGROUND AND AIMS:Nonalcoholic fatty liver disease (NAFLD) encompasses a range of conditions, from simple steatosis to nonalcoholic steatohepatitis. Studies in the United States have reported an increased mortality risk among individuals with NAFLD; therefore, the population attributable fractions (PAFs) for mortality were examined. APPROACH AND RESULTS:A total of 12,253 adult individuals with ultrasound assessment of NAFLD from the Third National Health and Nutrition Examination Survey and mortality follow-up through 2015 were included in the analysis. Cox proportional hazard regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD in association with all-cause and cause-specific mortality. Overall, sex- and race/ethnicity-specific PAFs and 95% CIs were estimated. In the current study, presence of NAFLD was associated with a 20% increased risk of all-cause mortality (HR, 1.20; 95% CI, 1.08, 1.34). The overall PAF for all-cause mortality associated with NAFLD was 7.5% (95% CI, 3.0, 12.0). The PAF for diabetes-specific mortality was 38.0% (95% CI, 13.1, 63.0) overall, 40.8% (95% CI, 2.1, 79.6) in men, and 36.8% (95% CI, 6.6, 67.0) in women. The PAF for liver disease (LD)-specific mortality was notably higher in men (68.3%; 95% CI, 36.3, 100.0) than women (3.5%; 95% CI, -39.7, 46.8). In the race-specific analysis, the PAFs of NAFLD for all-cause mortality (9.3%; 95% CI, 4.0, 14.6) and diabetes-specific mortality (44.4%; 95% CI, 10.8, 78.0) were significantly greater than zero only for whites. CONCLUSIONS:In the United States, approximately 8% of all-cause mortality and more than one-third of LD- and diabetes-specific deaths are associated with NAFLD. With these high percentages, efforts are needed to reduce the burden of NAFLD in the United States. 10.1002/hep.31040
    The impact of modifiable risk factors on the long-term outcomes of non-alcoholic fatty liver disease. Paik James M,Deshpande Rati,Golabi Pegah,Younossi Issah,Henry Linda,Younossi Zobair M Alimentary pharmacology & therapeutics BACKGROUND:Cardiovascular (CV) disease is the leading cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD). The American Heart Association (AHA) developed 7 CV health metrics (poor, intermediate and ideal health) to improve CV health. AIM:To assess population-attributable fractions (PAFs) of CV health metrics to all-cause and CV mortality among NAFLD patients METHODS: We included adult participants from National Health and Nutrition Examination Survey (NHANES 1988-1994) with clinical and mortality data. NAFLD was defined as the presence of hepatic steatosis on ultrasonography in the absence of other chronic liver diseases and excessive alcohol use. RESULTS:A total of 4040 adults with NAFLD and 7515 without were included. NAFLD had fewer ideal health metrics than non-NAFLD (age-standardised prevalence: 20% vs 10% for ≤1 ideal health metric; 5.1% vs 8.7% for ≥6, all P < .001). Following median follow-up of 19.2 years (IQR: 17.5-21.0 years), 1,136 NAFLD subjects (327 CV deaths) and 1600 non-NAFLD subjects (447 CV deaths) died. Increased number of ideal health metrics (all trend P < .0001) correlated with lower risk for all-cause and CV mortality. If all NAFLD subjects achieved 7 ideal health metrics, 66% of all-cause deaths and 83% of CV deaths were preventable. Among NAFLD subjects, lack of glycaemic control (adjusted PAF = 28.3% all-cause; 38.1% CV) and hypertension (adjusted PAF of 23% all-cause; 52.8% CV) were the largest mortality contributors. Ideal physical activity level obtainment provided an adjusted PAF = 13.9% all-cause and 13.8% CV mortality. CONCLUSIONS:Attainment of ideal CV health metrics provides protection against all-cause and CV deaths in NAFLD. 10.1111/apt.15580