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Early Menopause Linked to Poor Hepatitis C Treatment Response

SUMMARY: Women who enter menopause early have worse liver disease but are less likely to achieve sustained response to interferon-based therapy for chronic hepatitis C.

By Liz Highleyman

Experts have long recognized sex differences in response to therapy for chronic hepatitis C virus (HCV) infection. Women as a group tend to experience less aggressive liver disease progression and respond to treatment better than men; research indicates that estrogen influences these outcomes. Less is known about how hormonal changes at menopause might affect treatment success.

As described in the March 2011 issue of Gastroenterology, Erica Villa and colleagues from Italy looked at associations between menopause, damage, and sustained virologic response (SVR).

The investigators conducted a prospective study of 1000 consecutive treatment-naive patients age 18 and older with compensated liver disease due to chronic hepatitis C; 442 participants (44%) were women.

The research team examined liver biopsy samples for fibrosis, inflammation, and steatosis (fat accumulation) before patients started standard therapy consisting of pegylated interferon plus ribavirin.

Women provided data about timing and characteristics of their menopause. The researchers evaluated relevant hormonal and metabolic parameters and measured levels of interleukin-6 (IL-6) in the blood and tumor necrosis factor alfa (TNF-a) in the liver.


Post-menopausal women achieved SVR significantly less often than women of reproductive age (46.0% vs 67.5%, respectively; P < 0.0001).
Post-menopausal women had a sustained response rate more similar to that of men (46.0% vs 51.1%; P = 0.283).
In a multivariate analysis controlling for other factors, significant independent predictors for failure to achieve SVR included:
Early menopause: odds ratio 8.05;
Higher levels of gamma-glutamyl transpeptidase: odds ratio 2.17;
HCV genotype 1 or 4 (vs 2 or 3): odds ratio 3.86;
Lower cholesterol levels: odds ratio 0.99.
Among women with hard-to-treat HCV genotype 1, early menopause was the only independent factor that predicted lack of SVR (odds ratio 3.93).
In addition, biopsies showed that post-menopausal women had significantly worse liver inflammation, fibrosis, and steatosis than women of reproductive age, as well as higher IL-6 and TNF-a levels.

Based on these findings, the study authors concluded, "Among women with chronic hepatitis C, early menopause was associated with a low likelihood of SVR, probably because of inflammatory factors that change at menopause."

Investigator affiliations: Department of Gastroenterology, University of Modena and Reggio Emilia, Modena, Italy; Department of Gastroenterology, University of Palermo, Italy; Department of Gastroenterology, University of Bari, Italy; Department of Gastroenterology, AUSL, Modena, Italy; Department of Infectious Diseases, University of Rome "La Sapienza," Rome, Italy; Department of Internal Medicine, University of Pisa, Italy.


E Villa, A Karampatou, C Camma, and others. Early Menopause Is Associated With Lack of Response to Antiviral Therapy in Women With Chronic Hepatitis C. Gastroenterology 140(3): 818-829 (abstract). March 2011.























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