thanbey

This is a good question for any woman to be asking. We have very long term data now on the progression of hepatitis C in women. After 22 years, a number of women spontaneously lost not only viremia, but antibody, too!

an abstract:

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection.

Barrett S, Goh J, Coughlan B, Ryan E, Stewart S, Cockram A, O'Keane JC, Crowe J.

Centre for Liver Diseases, Mater Misericordiae Hospital, Eccles St, Dublin 7, Ireland.

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection.

METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations.

RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%.

CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present. (end of abstract)

The risks of the interferon treatment should not be considered too lightly against the low risk of progression in women who take care of themselves (no alcohol, no smoking, good nutrition and a healthy lifestyle)

We spent a lot of time talking about a treatment that has high risk for side effects, particularly bone loss, anemia, and psychiatric side effects and a low impact on the disease even with viral clearance, a result whose significance is still unclear. We do not yet have a clear picture of its possible long term effects on reproductive health in women.

Might be time to open this discussion up, particulalry in light of women who do not have the same expectation of disease progression as seen in men. So, here are some abstract to think about. Here are a couple more articles I will be offering to the NIH consensus panel next month. (The document is 32 pages and counting so far!)

1)

Low risk of cirrhosis in HCV genotype 1b infection. (Wiese M, et al. Hepatology 2000;32:91-96)

Manfred Wiese and colleagues reexamined a cohort of 1,018 women who have been followed for 20 years after exposure to anti-D immune globulin contaminated with HCV genotype 1b from a single donor. Within 6 months of exposure, 917 (90%) women had acute hepatitis C infection. After 20 years, 85% of these patients still tested positive for HCV antibodies and 55% for serum HCV RNA. However, only 4 (0.4%) women have developed overt cirrhosis.

Thus, chronic HCV infection with genotype 1b virus in previously healthy young women is associated with a low risk for progression to cirrhosis over 20 years.

(Wiese M, et al. Hepatology 2000;32:91-96)

2)

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

IMPACT OF PREGNANCIES, ORAL CONTRACEPTION AND MENOPAUSE ON LIVER FIBROSIS PROGRESSION IN WOMEN WITH CHRONIC HEPATITIS C
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

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.

thanbey



[This message has been edited by moderator1 (edited 05-21-2002).]