Nonalcoholic Fatty Liver Disease and Renal Function Impairment: A Cross-Sectional Population-Based Study on Its Relationship From 1999 to 2016.
ABSTRACT: 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 (P = 0.048) and NAFLD-RI (P = 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). Conclusion: 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.
Project description:There is a paucity of recent data about the epidemiology and long-term outcomes of nonalcoholic fatty liver disease (NAFLD) in the female population. Our aim was to assess the prevalence, risk factors, and mortality of NAFLD in female adults of the United States. Data from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014 were used. NAFLD status was determined by the U.S. Fatty Liver Index (US-FLI) in the absence of other liver diseases and excessive alcohol consumption. The prevalence rates, risk factors, and 5-year all-cause and cardiovascular mortality were determined in women with NAFLD. The most recent prevalence of NAFLD among female adults (2007-2014) in the United States was 24.4% (95% confidence interval [CI], 22.48-26.33). Prevalence was higher among women >44 years of age and those with body mass index ?30 kg/m2. In addition, the average age of the female population with NAFLD has decreased over time. The fully adjusted odds ratios in women with NAFLD compared to those without NAFLD were 1.48 (95% CI, 1.20-1.82) for cardiovascular disease (CVD), 1.89 (95% CI, 1.42-2.52) for atherosclerotic cardiovascular disease (ASCVD) score ?7.5%, and 1.76 (95% CI, 1.37-2.25) for either CVD or ASCVD ?7.5%. The 5-year mortality for female adults with NAFLD was significantly higher than for those without NAFLD (adjusted hazard ratio, 1.48; 95% CI, 1.07-2.05). Among women with NAFLD, those with ASCVD ?7.5% had significantly higher 5-year all-cause mortality and CVD mortality. Conclusion: The prevalence of NAFLD in female NHANES participants from the United States has continued over recent years. In the female population with NAFLD, ASCVD ?7.5% is an independent predictor of overall and cardiac-specific mortality.
Project description:Non-alcoholic fatty liver disease (NAFLD) is common and strongly associated with the metabolic syndrome. Though NAFLD may progress to end-stage liver disease, the top cause of mortality in NAFLD is cardiovascular disease (CVD). Most of the data on liver-related mortality in NAFLD derives from specialist liver centres. It is not clear if the higher reported mortality rates in individuals with non-cirrhotic NAFLD are entirely accounted for by complications of atherosclerosis and diabetes. Therefore, we aimed to describe the CVD burden and mortality in NAFLD when adjusting for metabolic risk factors using a 'real world' cohort. We performed a retrospective study of patients followed-up after an admission to non-specialist hospitals with a NAFLD-spectrum diagnosis. Non-cirrhotic NAFLD and NAFLD-cirrhosis patients were defined by ICD-10 codes. Cases were age-/sex-matched with non-NAFLD hospitalised patients. All-cause mortality over 14-years follow-up after discharge was compared between groups using Cox proportional hazard models adjusted for demographics, CVD, and metabolic syndrome components. We identified 1,802 patients with NAFLD-diagnoses: 1,091 with non-cirrhotic NAFLD and 711 with NAFLD-cirrhosis, matched to 24,737 controls. There was an increasing burden of CVD with progression of NAFLD: for congestive heart failure 3.5% control, 4.2% non-cirrhotic NAFLD, 6.6% NAFLD-cirrhosis; and for atrial fibrillation 4.7% control, 5.9% non-cirrhotic NAFLD, 12.1% NAFLD-cirrhosis. Over 14-years follow-up, crude mortality rates were 14.7% control, 13.7% non-cirrhotic NAFLD, and 40.5% NAFLD-cirrhosis. However, after adjusting for demographics, non-cirrhotic NAFLD (HR 1.3 (95% CI 1.1-1.5)) as well as NAFLD-cirrhosis (HR 3.7 (95% CI 3.0-4.5)) patients had higher mortality compared to controls. These differences remained after adjusting for CVD and metabolic syndrome components: non-cirrhotic NAFLD (HR 1.2 (95% CI 1.0-1.4)) and NAFLD-cirrhosis (HR 3.4 (95% CI 2.8-4.2)). In conclusion, from a large non-specialist registry of hospitalised patients, those with non-cirrhotic NAFLD had increased overall mortality compared to controls even after adjusting for CVD.
Project description:BACKGROUND:The prevalence and outcomes of non-alcoholic fatty liver disease (NAFLD) among elderly have not been well described. Our aim was to assess the prevalence, risk factors and mortality of NAFLD in individuals older than 60 years. METHODS:The data from the Third National Health and Nutrition Examination Survey with linked mortality files were utilized. NAFLD was defined by United States Fatty Liver Index in the absence of other causes of liver disease. Cox proportional hazards models were used to assess all-cause and cardiovascular (CV) mortality. All analyses were performed using SAS software. RESULTS:Three thousand two hundred seventy-one NHANES-III participants were included. The prevalence rates from NAFLD were 40.3% (95% CI: 37.2-43.5%) and 39.2% (95% CI: 34.4-44.0%) among 60-74 and > 74 years old. Among aged 60-74, the risks for 5-year and 10-year all-cause mortality were associated with presence of NAFLD [adjusted hazard ratios: 1.60 (95% CI: 1.24-1.96) for 5-year and 1.22 (95%CI: 1.01-1.49) for 10-year]. CV mortality were higher in this group were (aHR: 2.12 (95% CI: 1.20-3.75) for 5-year and 1.06 (95%CI: 0.73-1.52) for 10-year]. In contrast, in individuals > 74 years old, diagnosis of NAFLD was not associated with all-cause or CVD mortality. CONCLUSIONS:NAFLD is common among elderly population. Although NAFLD is associated with increased risk of mortality for 60-74-year-old individuals, this risk was not increased in those older than 74 years.
Project description:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully. AIM:We explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients. METHODS:This is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software. RESULTS:Among 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ? 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness. CONCLUSIONS:Our study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.
Project description:PURPOSE:Liver diseases including non-alcoholic fatty liver disease (NAFLD) and ensuing alterations to the micro-environment may affect development of liver metastasis. Mirroring the rise in obesity rates, prevalence of NAFLD is increasing globally. Our objective was to examine the association between NAFLD and mortality in colorectal cancer patients. METHODS:Colorectal Cancer-Sarcopenia and Near-term Survival (C-SCANS) is a retrospective cohort study which included 3,262 stage I-III patients, aged 18-80 years, and diagnosed between 2006 and 2011 at Kaiser Permanente Northern California. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI). RESULTS:After up to 10 years of follow-up, 879 deaths, including 451 from CRC were identified. Cases diagnosed with NAFLD before and within 1 month after CRC diagnosis (pre-existing NAFLD; n?=?83) had a HR of 1.64 (95% CI 1.06-2.54) for overall and a HR of 1.85 (95% CI 1.03-3.30) for CRC-specific mortality compared to those without NAFLD. Findings did not differ significantly by sex, stage, tumor location, and smoking status, and were also similar when restricted to obese patients only. CONCLUSIONS:Independent of body mass index and prognostic indicators, CRC patients with pre-existing NAFLD had a worse prognosis than those without NAFLD.
Project description:This study aimed to investigate the association of nonalcoholic fatty liver disease (NAFLD) and its severity with the decline in kidney function in patients with chronic kidney disease (CKD). We conducted a cohort study of 1,525 CKD patients who underwent repeated health check-up examinations from January 2003 through December 2013. NAFLD was diagnosed by ultrasonography and its severity was assessed by the NAFLD fibrosis score. At baseline, the prevalence of NAFLD was 40.9%, and the mean estimated glomerular filtration rate (eGFR) was 59.1?ml/min/1.73?m2. The average follow-up was 6.5 years. The age- and sex-adjusted decline in eGFR was greater in patients with NAFLD (-0.79% per year, 95% CI -1.31%, -0.27%) compared to those without it (0.30%, 95% CI -0.14%, 0.76%; p?=?0.002). In multivariable adjusted models, the average difference in annual percent change in decline in eGFR comparing patients with NAFLD to those without NAFLD was -1.06% (-1.73%, -0.38%; p?=?0.002). The decline in eGFR associated with NAFLD was greater in patients with higher NAFLD fibrosis score, in those with proteinuria or with low eGFR at baseline (?<45?ml/min/1.73?m2), and in those who were smokers and hypertensive. Therefore, NAFLD is independently associated with CKD progression.
Project description: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.
Project description:Background:Newer treatments for HIV and hepatitis C virus (HCV) have decreased mortality in HIV/HCV patients. Nonalcoholic fatty liver disease (NAFLD) has increased globally; therefore, the prevalence and mortality of NAFLD among HIV (+) patients was assessed. Methods:Using Medicare denominator, inpatient, and outpatient files (random 5% sample per year), serial cross-sectional analysis (2006 to 2016) was performed. Joinpoint trend analysis evaluated prevalence and mortality with average annual percent change (AAPC). HIV (+) patients and liver diseases (LDs) were identified using International Classification of Diseases 9/10 codes. NAFLD was presumed using diagnosis codes or codes for metabolic dysfunction and obesity in absence of other LDs. Liver-related HIV (+) indicated HIV (+) patients with LDs. Results:Among 28 675 887 Medicare beneficiaries, 47 062 were HIV (+) (mean [SD] age, 51.4 [11.3] years); 11 920 had liver diseases (6923 HCV, 2019 hepatitis B virus [HBV], 2472 presumed NAFLD, 278 alcoholic liver disease [ALD], and 1653 other LDs); 2882 HIV (+) patients died; 1260 had LDs. The prevalence and mortality for non-liver-related HIV (+) decreased (AAPC, -1.1% and -9.1%). Liver-related HIV (+) increased (AAPC, 1.7%; P = .007); mortality leveled off. Prevalence and mortality worsened for presumed NAFLD (AAPC, 9.7% and 10.0%) and improved for HBV and HCV (HBV: AAPC, -3.5% and -8.8%; HCV: AAPC, -0.7% and -4.9%). After adjustments, HCV (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.24-172), HBV (OR, 2.40; 95% CI, 2.09-2.77), ALD (OR, 5.70; 95% CI, 4.34-7.48), and presumed NAFLD (OR, 1.46; 95% CI, 1.24-1.72) increased 1-year mortality. Conclusions:Among HIV (+) subjects, viral hepatitis remains the leading LD for increased 1-year mortality, but the prevalence and mortality with presumed NAFLD are increasing.
Project description:Dyslipidemia is one of the common risk factors for NAFLD and is associated with cardiovascular (CV) mortality, which is the most common cause of death in NAFLD. Lipid-lowering agents (LLAs) are used to reduce CV events in the general population. Our aim was to assess whether the use of LLAs in patients with NAFLD can reduce the risk of CV mortality. We used the third National Health and Nutrition Examination Survey mortality linked files. Mortality was determined from the National Death Index records through 2011. NAFLD was diagnosed by ultrasound after exclusion of other causes of liver disease. After inclusion and exclusion, the cohort consisted of 2,566 patients with NAFLD (45.8% < 45 years of age, 52.8% male, 75.4% white). Those who were taking LLAs were more likely to be older, non-Hispanic white, and had significantly higher rates of diabetes mellitus (DM), hyperlipidemia, hypertension, metabolic syndrome, and history of CV disease (CVD) (all P< 0.01). In our multivariate analysis, DM was an independent predictor of overall mortality (adjusted hazard ratio [aHR]: 1.79 [95% confidence interval (CI): 1.40-2.30]) and CV mortality (aHR: 1.89 [95% CI: 1.08-3.30]). History of CVD was associated with both overall (aHR: 2.03 [95% CI: 1.57-2.63]) and CV mortality (aHR: 3.69 [95% CI: 2.23-6.08]). In contrast, the use of statins and other LLAs was not associated with reduction in overall (aHR = 0.95 [95% CI: 0.37-2.44] and aHR = 1.43 [95% CI: 0.99-2.07]) and CV mortality (aHR = 1.20 [95% CI: 0.26-5.54] and aHR = 1.63 [95% CI: 0.70-3.76]). Conclusion: The use of statins and other LLAs did not reduce the increased risk of overall or CV mortality in NAFLD.
Project description:Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD. Through a systematic review and meta-analysis, we identified five adult NAFLD cohort studies reporting fibrosis stage-specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRRs) with 95% confidence intervals (CIs) for all-cause and liver-related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow-up. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality, and this risk increased with increases in the stage of fibrosis: stage 1, MRR = 1.58 (95% CI 1.19-2.11); stage 2, MRR = 2.52 (95% CI 1.85-3.42); stage 3, MRR = 3.48 (95% CI 2.51-4.83); and stage 4, MRR = 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with each increase in the stage of fibrosis: stage 1, MRR = 1.41 (95% CI 0.17-11.95); stage 2, MRR = 9.57 (95% CI 1.67-54.93); stage 3, MRR = 16.69 (95% CI 2.92-95.36); and stage 4, MRR = 42.30 (95% CI 3.51-510.34). Limitations of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis without fibrosis in the reference comparison group. CONCLUSION:The risk of liver-related mortality increases exponentially with increase in fibrosis stage; these data have important implications in assessing the utility of each stage and benefits of regression of fibrosis from one stage to another. (Hepatology 2017;65:1557-1565).