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Menopause May Accelerate Liver Fibrosis; Perhaps Hormone Replacement Therapy Can Be Helpful


Vincent Di Martino, Pascal Lebray, Joseph Moussalli, GH Pitie-Salpetriere and Reseau VHC Paris-Sud, Paris France; Catherine Buffet, HTMpital Bicetre et Reseau VHC-Paris Sud, Kremlin-Bictre France; Thierry Poynard, GH Pitie-Salpetriere and Reseau VHC Paris-Sud, Paris France

program abstract:
During chronic hepatitis C (CHC), liver fibrosis progression is faster in males than in females. Among all the factors involved in such difference, estrogenes may be a major one since experimental data recently supported that estrogenes may have direct antifibrosing effect. The aim of this work was to evaluate the influence of pregnancies, oral contraceptives and menopause on liver fibrosis (F) and fibrosis progression rate (FPR) in HCV-infected women, taking into account confusing factors such as age, alcohol consumption, and BMI.

Patients and methods: 472 women with CHC without HBV nor HIV coinfection received an anonymous questionnaire that asked for alcohol and tobacco consumption, presence of diabetes, age at first menstruation, age at pregnancies with or without children, hormonal contraception, age at menopause and its cause if any, and hormonal substitution. These data were completed by those collected in the DOSVIRC database. Liver biopsies performed before antiviral therapy were analyzed using the METAVIR scoring system. The FPR was estimated in case of known date of HCV infection and expressed in milli METAVIR Units of fibrosis per year. Statistical analyses were performed using Kruskall-Wallis rank test and logistic and multiple linear regression models for multivariate analyses.

Results: 212 (44%) women completed the questionnaire. 192 (48±1 years old) underwent adequate liver sample, among whom 99 had 1 to 7 pregnancies (0 to 5 children) during 15±1 months, 86 received oral contraceptive(s) during 31±4 months, 95 had menopause 11±1 years before liver biopsy, and 47 received hormonal substitution during 7±1 years. Only one woman had alcohol intake more than 50g/d. In univariate analysis, F score and/or FPR were significantly lower in women who had one or more pregnancies, who received hormonal contraception, who were seen before menopause or who received hormonal substitution, whereas liver necro-inflammatory lesions(A) were not different (table). After adjustment on age and BMI, multivariate analyses showed that menopause was associated with higher F score and FPR, and that pregnancies were associated with lower FPR ; the effect of oral contraceptives was not significant.

Conclusion: in women with CHC, menopause accelerates the liver fibrosis progression. Such effect seems prevented by hormonal substitution. Pregnancies may have a long-term beneficial impact on liver fibrosis.

editorial note: a pilot study presented at the AASLD Single Conference meeting in June 2001 showed HRT could improve response to HCV therapy for postmenopausal women.


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