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Low Testosterone Is Associated With Nonalcoholic Steatohepatitis and Fibrosis Severity in Men.

ABSTRACT: With rising prevalence of obesity and diabetes, nonalcoholic fatty liver disease (NAFLD) is now a leading cause of chronic liver disease. One-third of obese or diabetic men have subnormal free and bioavailable testosterone concentrations.¹ Several studies have further shown low testosterone to be associated with imaging-confirmed NAFLD in men,² although it is unknown whether low testosterone confers increased risk of more clinically relevant manifestations of NAFLD, including nonalcoholic steatohepatitis (NASH) and NASH fibrosis. We therefore aimed to evaluate the association of testosterone with histologic features of NAFLD among a representative cohort of men from the multicenter NASH Clinical Research Network (NASH CRN).

SUBMITTER: Sarkar M

PROVIDER: S-EPMC7272262 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Low Testosterone Is Associated With Nonalcoholic Steatohepatitis and Fibrosis Severity in Men.

Sarkar Monika M Yates Katherine K Suzuki Ayako A Lavine Joel J Gill Ryan R Ziegler Toni T Terrault Norah N Dhindsa Sandeep S

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20191205 2

With rising prevalence of obesity and diabetes, nonalcoholic fatty liver disease (NAFLD) is now a leading cause of chronic liver disease. One-third of obese or diabetic men have subnormal free and bioavailable testosterone concentrations.<sup>1</sup> Several studies have further shown low testosterone to be associated with imaging-confirmed NAFLD in men,<sup>2</sup> although it is unknown whether low testosterone confers increased risk of more clinically relevant manifestations of NAFLD, includi ...[more]

PMID: 31812658

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Project description:Hepatocellular injury and inflammation are believed to be the primary drivers of fibrogenesis that ultimately lead to cirrhosis in patients with nonalcoholic steatohepatitis (NASH). This study sought associations between observed improvements in fibrosis with improvement in specific histologic features, nonalcoholic fatty liver disease activity score (NAS) ≥2, diagnostic category, and primary histologically based outcomes of two adult NASH treatment trials. The primary outcome for the study was fibrosis improvement from baseline to end of treatment, defined as a 1-point or more improvement in fibrosis stage. This is a retrospective analysis of biopsy data collected from the NASH Clinical Research Network Pathology Committee of Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with NASH Trial (PIVENS) and Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment Trial (FLINT) baseline and final biopsies. Treatment group-adjusted univariable and multivariable logistic regression models related improvement in fibrosis to improvements in other histologic variables, resolution of steatohepatitis, and improvement in the NAS ≥2. In PIVENS 221 subjects had baseline and 96-week biopsies, and in FLINT 200 subjects had baseline and 72-week biopsies. Improvement in fibrosis was found in 38% of PIVENS and 29% of FLINT biopsies; fibrosis improvement was more likely in treated than placebo subjects in both studies. Controlling for treatment group, fibrosis improvement was associated most strongly with resolution of NASH (PIVENS, odds ratio [OR], 3.9; 95% confidence interval [CI] 2.0-7.6; P < 0.001; FLINT, OR, 8.0; 95% CI 3.1-20.9; P < 0.001), and improved NAS by ≥2 (PIVENS, OR, 2.4; 95% CI 1.3-4.3; P = 0.003; FLINT, OR, 4.2; 95% CI 2.1-8.3; P < 0.001). Improvement in histologic features associated with improved fibrosis for both studies included steatosis, ballooning, Mallory-Denk bodies, and portal, but not lobular, inflammation. Conclusion: These findings support a strong link between histologic resolution of steatohepatitis with improvement in fibrosis in NASH.

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Low Testosterone Is Associated With Nonalcoholic Steatohepatitis and Fibrosis Severity in Men.

Publications

Low Testosterone Is Associated With Nonalcoholic Steatohepatitis and Fibrosis Severity in Men.

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