Early 
                Menopause Linked to Poor Hepatitis C Treatment Response
              
              
                 
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                        | 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. |  |  | 
                 
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              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.
                
                Results 
                 
              
                 
                  |  | 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.
                
                3/22/11
              Reference
                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.