Estrogen protects women with NASH from severe liver fibrosis

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October 29, 2013

New research suggests that estrogen protects women with nonalcoholic steatohepatitis (NASH) from severe liver fibrosis. According to the study published online in Hepatology, a journal of the American Association for the Study of Liver Diseases, men are at higher risk of more severe fibrosis compared to women prior to menopause, but liver fibrosis severity is similar in men and post-menopausal women.

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver disorders from simple fatty liver to inflammation, fibrosis, and cirrhosis. With the rapid rise in obesity, diabetes and metabolic syndrome, the prevalence of NAFLD—the result of insulin resistance—has also steadily increased. In fact, studies suggest that the NAFLD prevalence is 10% to 30%, making it the most common liver disease in the U.S.

"While most NAFLD patients have a mild disease known as fatty liver or hepatic steatosis, some patients present with NASH, which is more severe and increases overall mortality," explains Dr. Ayako Suzuki with the Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences in Little Rock, the lead author of the present study. "Our study aim was to investigate whether gender and menopause significantly impact fibrosis severity among adult patients with NAFLD."

The research team analyzed data from 541 adults with NASH who were seen at Duke University Liver Clinics and the Duke Metabolic and Weight Loss Surgery Program. The mean age of subjects was 48 years, with 35% of the group being men, 28% pre-menopausal women and 37% post-menopausal women.

Findings indicate that 22% of the cohort had advanced fibrosis. After adjusting for known predictors of fibrosis, the risk for greater fibrosis severity in post-menopausal women and men vs. pre-menopausal women was 1.4-fold and 1.6-fold, respectively. Furthermore, when dividing the cohort at age 50, which is the average age at menopause in the US, the risk for greater fibrosis severity in men vs. women before age 50 was 1.8-fold, while after the age 50 the risk was reduced to 1.2-fold.

"Our findings suggest a protective effect from estrogen against development of severe fibrosis," concludes Dr. Suzuki. "Further study of the impact of estrogen on fibrosis progression in NASH patients is needed." Explore further: Cardiovascular issues up mortality rates in patients with advanced fibrosis

More information: "Gender and Menopause Impact Severity of Fibrosis Among Patients with Nonalcoholic Steatohepatitis." Ju Dong Yang, Manal F Abdelmalek, Herbert Pang, Cynthia D Guy, Alastair D Smith, Anna Mae Diehl and Ayako Suzuki. Hepatology; (DOI: 10.1002/hep.26761) Published online: October 1, 2013.

Journal reference: Hepatology

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Estrogen Modulating Therapy for HCV Infection in Postmenopausal Women

Published in Journal Watch Gastroenterology December 14, 2012

Adding raloxifene hydrochloride to standard therapy significantly increased response, but only among women with IL28B genotype TT.

Studies of hepatitis C virus (HCV) infection treatment have shown that response to interferon-based therapy is lower in postmenopausal women than in premenopausal women. This could be caused by declining estrogen levels in menopause. To test that hypothesis, investigators evaluated whether the addition of raloxifene hydrochloride (RLX) — a selective estrogen receptor modulator — improved the efficacy of standard therapy with peginterferon and ribavirin in this group.

Investigators randomized 123 postmenopausal Japanese women aged 50 to 73 years with genotype 1b HCV infection to receive 60 mg of RLX daily plus standard therapy with 180 µg of peginterferon weekly and 600 to 1000 µg of ribavirin daily or standard therapy only for 48 weeks. The primary end point was sustained virologic response (SVR), defined as undetectable serum HCV RNA after 24 weeks of treatment. The mean length of time since menopause was 10.2 years (range, 2–22 years). Baseline characteristics of the two groups did not differ.

SVR was significantly higher in the RLX group than the standard therapy group overall (61.3% vs. 34.4%; P=0.005) and in a subgroup with IL28B genotype TT (72.5% vs. 39.2%; P=0.001), but not in patients with IL28B genotype CC or TC. Only one patient discontinued RLX after developing a rash during week 2 of treatment.

Comment: These results suggest that the addition of RLX as adjuvant therapy to peginterferon and ribavirin in postmenopausal women with genotype 1b HCV infection significantly improves SVR. The improvement was limited to women with IL28B genotype TT. The mechanism by which RLX improves SVR is unclear but could involve the improvement of estradiol levels and reduction of oxidative stress or inhibition of inflammatory cytokine production. Regardless, further study of the use of RLX and other, similar agents as adjuvant therapy to HCV regimens is warranted.

— Atif Zaman, MD, MPH

Citation(s):

Furusyo N et al. Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: A randomized trial. J Hepatol 2012 Dec; 57:1186. (http://dx.doi.org/10.1016/j.jhep.2012.08.003)

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