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Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

ABSTRACT: BACKGROUND:With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA). AIMS:To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes. METHODS:In randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver. RESULTS:Of 2091 patients reviewed, 399 met inclusion criteria. Normal controls (n = 65) had normal liver function. The four NAFLD cohorts included: NAFL steatosis (n = 76), nonalcoholic steatohepatitis (NASH) without fibrosis (n = 68), NAFLD/NASH stage 1-3 fibrosis (n = 82), and NAFLD/NASH cirrhosis (n = 70). NAFLD with hepatocellular carcinoma (HCC) was separately identified (n = 38). Most patients were older White men. NAFLD patients with any fibrosis were on average severely obese (BMI>35 kg/m2 ). Diabetes (54.4%-79.6%) and hypertension (85.8%-100%) were more common in NAFLD with fibrosis or HCC. Across NAFLD, 12.3%-19.5% were enrolled in diet/exercise programs and 0%-2.6% had bariatric surgery. Hispanics exhibited higher rates of NASH (20.6%), while Blacks had low NAFLD rates (1.4%-11.8%), particularly NAFLD cirrhosis and HCC (1.4%-2.6%). Diabetes (OR 11.8, P < .001) and BMI (OR 1.4, P < .001) were the most significant predictors of advanced fibrosis. CONCLUSIONS:In the VHA, diabetes and severe obesity increased risk for advanced fibrosis in NAFLD. Of these patients, only a small proportion (~20%) had enrolled in diet/exercise programs or had bariatric surgery (~2%). These results suggest that providers should focus/tailor interventions to improve outcomes, particularly in those with diabetes and severe obesity.

SUBMITTER: Patel YA

PROVIDER: S-EPMC5861349 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

Patel Y A YA Gifford E J EJ Glass L M LM McNeil R R Turner M J MJ Han B B Provenzale D D Choi S S SS Moylan C A CA Hunt C M CM

Alimentary pharmacology & therapeutics 20171108 2

<h4>Background</h4>With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA).<h4>Aims</h4>To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes.<h4>Methods</h4>In randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver.<h4>Results</h4>Of 2 ...[more]

PMID: 29115682

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Project description:ObjectiveSeveral single-nucleotide polymorphisms have been identified to be disadvantageous or protective in regard to disease severity in patients with non-alcoholic fatty liver disease (NAFLD). However, it is unclear, whether including genetic risk factor(s) either alone or combined into risk stratification algorithms for NAFLD actually provides incremental benefit over clinical risk factors.DesignPatients with biopsy-proven NAFLD were genotyped for the PNPLA3-rs738409(minor allele:G), TM6SF2-rs58542926(minor allele:T) and HSD17B13- rs72613567 (minor allele:TA) variants. The NAFLD activity score (NAS) and fibrosis stage (F0-F4) were used to grade and stage all liver biopsy samples. Patients from seven centers throughout Central Europe were considered for the study.Results703 patients were included: NAS ≥ 5:173(24.6%); Fibrosis: F3-4:81(11.5%). PNPLA3 G/G genotype was associated with a NAS ≥ 5(aOR 2.23, p = 0.007) and advanced fibrosis (aOR-3.48, p < 0.001).TM6SF2 T/- was associated with advanced fibrosis (aOR 1.99, p = 0.023). HSD17B13 TA/- was associated with a lower probability of NAS ≥ 5(TA/T: aOR 0.65, p = 0.041, TA/TA: aOR 0.40, p = 0.033). Regarding the predictive capability for NAS ≥ 5, well-known risk factors (age, sex, BMI, diabetes, and ALT; baseline model) had an AUC of 0.758, Addition of PNPLA3(AUC 0.766), HSB17B13(AUC 0.766), and their combination(AUC 0.775), but not of TM6SF2(AUC 0.762), resulted in a higher diagnostic accuracy of the model. Addition of genetic markers for the prediction of advanced fibrosis (baseline model: age, sex, BMI, diabetes: AUC 0.777) resulted in a higher AUC if PNPLA3(AUC 0.789), and TM6SF2(AUC 0.786) but not if HSD17B13(0.777) were added.ConclusionIn biopsy-proven NAFLD, PNPLA3 G/-, TM6SF2 T/- and HSD17B13 TA/- carriage are associated with severity of NAFLD. Incorporating these genetic risk factors into risk stratification models might improve their predictive accuracy for severity of NAFLD and/or advanced fibrosis on liver biopsy.

Project description:Background and aimNon-alcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance (IR). While a minority of patients with NAFLD does not have evidence of IR, no detailed characterization of this specific phenotype is currently available. This study was undertaken to investigate the clinical and histological characteristics of this patient group.Materials and methodsWe retrospectively reviewed the clinical records of 263 patients with biopsy-proven NAFLD. IR was defined by a Homeostatic Model Assessment of IR (HOMA-IR) score >2.73. The histological diagnosis of non-alcoholic steatohepatitis (NASH) was performed using 1) the steatosis, activity and fibrosis score and 2) the NASH Clinical Research Network (NASH CRN) criteria. Significant fibrosis was defined by the presence of a histological fibrosis score higher than F≥2. Patients with and without evidence of IR were compared concerning clinical, laboratory, and histological characteristics.ResultsOf the 263 patients with biopsy-proven NAFLD, 53 (20.2%) patients had no evidence of IR. Patients without IR were younger [IR (-): 42 (22-65) years versus IR (+): 49 (22-71) years, p=0.001] and had a higher prevalence of men [IR (-): 39 (73.6%) versus IR (+): 113 (53.8%), p=0.009]. Moreover, they were characterized by a lower body mass index [IR (-): 30.06±3.61 kg/m2 versus IR (+): 33.19±5.06 kg/m2, p=0.000] and lower frequencies of metabolic risk factors-including the metabolic syndrome, diabetes, hypertension, hyperlipidemia, and lower waist/hip circumference. Liver histology was generally less severe in patients without IR; specifically, they showed a lower prevalence of NASH [IR (-): 38 (71.7%) versus IR (+): 190 (90.5%), p=0.000] and significant fibrosis [IR (-): 9 (17.0%) versus IR (+): 106 (50.5%), p=0.000] than did patients with IR. Multivariate analysis identified obesity [odds ratio (OR): 9.321, 95% confidence interval (CI): 1.031-84.261, p<0.05] and an international normalized ratio >1.1 (OR: 10.116, 95% CI: 1.325-77.225, p<0.05) as independent predictors of significant fibrosis in patients with NAFLD and no IR.ConclusionPatients with NAFLD and no IR has less severe liver histology than patients with IR. However, obesity appears to be independently associated with significant fibrosis in this patient group.

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Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

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Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

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