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Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: a propensity-matched cohort study.

ABSTRACT: BACKGROUND:As the prevalence of nonalcoholic fatty liver disease (NAFLD) escalates, understanding its potential impact on the development of chronic kidney disease (CKD) is needed. OBJECTIVE:To determine the longitudinal association of NAFLD with the development of advanced CKD in the United States. METHODS:A retrospective cohort analysis of the Truven Health MarketScan Database (2006-2015) was conducted. We used Cox proportional hazards models to compare the risk of developing CKD stages 3-5 in patients with NAFLD versus non-NAFLD, identified by ICD-9 codes, after 1:3 propensity score (PS) matching. RESULTS:In a cohort of 262 619 newly diagnosed patients with NAFLD and 769 878 PS (1:3)-matched non-NAFLD patients, we identified 5766 and 8655 new advanced (stage 3-5) CKD cases, respectively. The crude CKD incidence rate was 8.2 and 5.5 per 1000 person-years in NAFLD and non-NAFLD groups, respectively. In multivariable Cox model, patients with NAFLD had a 41% increased risk of developing advanced CKD compared with non-NAFLD patients [adjusted hazard ratio (aHR), 1.41; 95% confidence interval (CI), 1.36-1.46]. In the sensitivity analysis adjusting for time-varying covariates after NAFLD diagnosis, NAFLD persisted as a significant CKD risk factor (aHR, 1.58; 95% CI, 1.52-1.66) and the association remained significant when stratified by age, gender and pre-existing comorbidities. The risk of CKD increased in NAFLD with compensated cirrhosis (aHR, 1.47; 95% CI, 1.36-1.59) and decompensated cirrhosis (aHR, 2.28; 95% CI, 2.12-2.46). CONCLUSION:Nonalcoholic fatty liver disease was independently associated with an increased risk of advanced CKD development suggesting renal function screening and regular monitoring are needed in this population.

SUBMITTER: Park H

PROVIDER: S-EPMC6851415 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: a propensity-matched cohort study.

Park Haesuk H Dawwas Ghadeer K GK Liu Xinyue X Nguyen Mindie H MH

Journal of internal medicine 20190823 6

<h4>Background</h4>As the prevalence of nonalcoholic fatty liver disease (NAFLD) escalates, understanding its potential impact on the development of chronic kidney disease (CKD) is needed.<h4>Objective</h4>To determine the longitudinal association of NAFLD with the development of advanced CKD in the United States.<h4>Methods</h4>A retrospective cohort analysis of the Truven Health MarketScan Database (2006-2015) was conducted. We used Cox proportional hazards models to compare the risk of develo ...[more]

PMID: 31359543

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Project description:BackgroundThe risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.MethodsThis is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).ResultsThe prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).ConclusionUsing a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.Trial registrationUcsd irb140084.FundingNational Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

Project description:Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.

Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the United States; however, few data are available about racial and ethnic variation. We investigated relationships between ethnicity, NAFLD severity, metabolic derangements, and sociodemographic characteristics in a well-characterized cohort of adults with biopsy-proven NAFLD. Data were analyzed from 1,026 adults (?18 years) in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) from 2004 to 2008, for whom liver histology data were available within 6 months of enrollment. Associations between ethnicity (i.e., Latino versus non-Latino white) and NAFLD severity (i.e., NASH versus non-NASH histology and mild versus advanced fibrosis) were explored with multiple logistic regression analysis. We also investigated effect modification of ethnicity on metabolic derangements for NAFLD severity. Within the NASH CRN, 77% (N = 785) were non-Latino white and 12% (N = 118) were Latino. Sixty-one percent (N = 628) had NASH histology and 28% (N = 291) had advanced fibrosis. Latinos with NASH were younger, performed less physical activity, and had higher carbohydrate intake, compared to non-Latino whites with NASH. Gender, diabetes, hypertension, hypertriglyceridemia, aspartate aminotransferase (AST), platelets, and the homeostasis model assessment of insulin resistance (HOMA-IR) were significantly associated with NASH. Age, gender, AST, alanine aminotransferase, alkaline phosphatase, platelets, total cholesterol, hypertension, and HOMA-IR, but not ethnicity, were significantly associated with advanced fibrosis. The effect of HOMA-IR on the risk of NASH was modified by ethnicity: HOMA-IR was not a significant risk factor for NASH among Latinos (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.85-1.02), but was significant among non-Latino whites (OR, 1.06; 95% CI: 1.01-1.11).Metabolic risk factors and sociodemographic characteristics associated with NASH differ by ethnicity. Additional insights into NASH pathogenesis may come from further studies focused on understanding ethnic differences in this disease.

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Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: a propensity-matched cohort study.

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Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: a propensity-matched cohort study.

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