Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy
Open accessAbstract
Background and aims: The rates of fibrosis progression in chronic hepatitis C are significantly different between males and females. The antifibrogenic effect of oestrogen has been proposed, possibly via inhibition of stellate cells. The aim of this study was to evaluate the severity of chronic hepatitis C in women, in relation to the menopause, steatosis and hormone replacement therapy (HRT). Methods: From November 2003 to October 2004, women with chronic hepatitis C were enrolled prospectively. A questionnaire was completed prospectively and a blood sample was obtained on the day of biopsy. We identified characteristics associated with moderate/severe fibrosis using univariate and multivariate analysis. Results: 251 women were included in the study. 122 women (52%) were menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe fibrosis (F2–F4, Metavir score) had a longer known duration of infection (>15 years), a higher body mass index and presented with steatosis more frequently than 190 (76%) women with mild fibrosis (F0–F1). Women with F2–F4 were more often menopausal (67% v 47%). The probability of fibrosis F2–F4 was lower for menopausal women receiving HRT (p = 0.012). Steatosis was more frequent and more severe in menopausal women. Conclusions: Severity of fibrosis was associated with a longer duration of infection (>15 years), a higher body mass index, advanced steatosis and the menopause. Menopausal women receiving HRT presented with a lower stage fibrosis. These results reinforce the hypothesis of a protective role of oestrogens in the progression of fibrosis. Steatosis may be implicated in the progression of fibrosis after the menopause.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The beneficial anti-fibrotic effect of ER activators in hepatic tissue may explain sex differences in liver fibrosis and cirrhosis progression.
“However, the beneficial anti-fibrotic effect of ER activators in the hepatic tissue (e.g.17b-estradiol and estradiol) [200][201][202] may also explain sex differences in liver fibrosis and cirrhosis progression.[203][204][205][206]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [204]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnosis, management, and treatment of hepatitis C†
Strader, D. B., Wright, T. L., Thomas, D. L., & Seeff, L. B. (2004) · Hepatology · doi:10.1002/hep.20119 · Cited by 1,705 · see citing works
Natural history of chronic hepatitis C
Seeff, L. B. (2002) · Hepatology · doi:10.1053/jhep.2002.36806 · Cited by 1,535 · see citing works
The Emergence of the Metabolic Syndrome with Menopause
Carr, M. C. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030242 · Cited by 1,449 · see citing works
Adinolfi, L. E., Gambardella, M., Andreana, A., Tripodi, M., Utili, R., & Ruggiero, G. (2001) · Hepatology · doi:10.1053/jhep.2001.24432 · Cited by 1,052 · see citing works
American Association for the Study of Liver Diseases
Pópper, H. (1960) · Gastroenterology · doi:10.1016/s0016-5085(60)80094-7 · Cited by 905 · see citing works
A comparison of fibrosis progression in chronic liver diseases
Poynard, T., Mathurin, P., Lai, C., Guyader, D., Poupon, R. E., Tainturier, M.-H., Myers, R. P., Muntenau, M., Ratziu, V., Manns, M. P., et al. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(02)00413-0 · Cited by 472 · see citing works
Fibrosis and disease progression in hepatitis C
Marcellin, P., Asselah, T., & Boyer, N. (2002) · Hepatology · doi:10.1053/jhep.2002.36993 · Cited by 398 · see citing works
Self-citationSTEATOSIS IN CHRONIC HEPATITIS C: WHY DOES IT REALLY MATTER?
Asselah, T., Rubbia-Brandt, L., Marcellin, P., & Negro, F. (2005) · Gut · doi:10.1136/gut.2005.069757 · Cited by 394 · see citing works
Self-citationSuppressive effects of estradiol on dimethylnitrosamine-induced fibrosis of the liver in rats
Yasuda, M., Shimizu, I., Shiba, M., & Ito, S. (1999) · Hepatology · doi:10.1002/hep.510290307 · Cited by 283 · see citing works
Martino, V. D., Lebray, P., Myers, R. P., Pannier, E., Paradis, V., Charlotte, F., Moussalli, J., Thabut, D., Buffet, C., & Poynard, T. (2004) · Hepatology · doi:10.1002/hep.20463 · Cited by 277 · see citing works
Ryder, S. D. (2004) · Gut · doi:10.1136/gut.2003.021691 · Cited by 275 · see citing works
Fibrosis and disease progression in hepatitis C
Marcellin, P., Asselah, T., & Boyer, N. (2002) · Hepatology · doi:10.1002/hep.1840360707 · Cited by 267 · see citing works
Self-citationNatural history and predictors of disease severity in chronic hepatitis C
Massard, J., Ratziu, V., Thabut, D., Moussalli, J., Lebray, P., Benhamou, Y., & Poynard, T. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.11.009 · Cited by 216 · see citing works
Impact of oestrogens on the progression of liver disease
Shimizu, I. (2003) · Liver International · doi:10.1034/j.1600-0676.2003.00811.x · Cited by 207 · see citing works
U.S. Preventive Services Task Force* (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-10-200211190-00013 · Cited by 144 · see citing works
Gervais, A., Bacq, Y., Bernuau, J., et al. (2000) · Journal of Hepatology · doi:10.1016/s0168-8278(00)80075-6 · Cited by 132 · see citing works
Asselah, T., Boyer, N., Guimont, M.-C., Cazals-Hatem, D. L., Tubach, F., Nahon, K., Daïkha, H., Vidaud, D., Martinot-Peignoux, M., Vidaud, M., et al. (2003) · Gut · doi:10.1136/gut.52.11.1638 · Cited by 125 · see citing works
Self-citationEstrogen reduces CCL4- induced liver fibrosis in rats
Xu, J.-W. (2002) · World Journal of Gastroenterology · doi:10.3748/wjg.v8.i5.883 · Cited by 121 · see citing works
Bissell, M. D. (1999) · Hepatology · doi:10.1002/hep.510290351 · Cited by 114 · see citing works
Threshold effect of liver iron content on hepatic inflammation and fibrosis in hepatitis B and C
Beinker, N. K., Voigt, M. D., Arendse, M., Smit, J. L., Stander, I. A., & Kirsch, R. E. (1996) · Journal of Hepatology · doi:10.1016/s0168-8278(96)80231-5 · Cited by 93 · see citing works
Evaluation and management of non-alcoholic steatohepatitis
Ramesh, S., & Sanyal, A. J. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.11.022 · Cited by 92 · see citing works
Iron, hepatic stellate cells and fibrosis in chronic hepatitis C
Rigamonti, C., Andorno, S., Maduli, E., Morelli, S., Pittau, S., Nicosia, G., Boldorini, R. L., & Sartori, M. G. F. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2002.0320s1028.x · Cited by 45 · see citing works
Remission of autoimmune hepatitis during pregnancy: a report of two cases
Colle, I. O., & Hautekeete, M. L. (1999) · Liver International · doi:10.1111/j.1478-3231.1999.tb00010.x · Cited by 39 · see citing works
Immunopathogenesis of hepatitis C virus infection
Ferrari, C. I., Urbani, S., Penna, A., et al. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80371-7 · Cited by 31 · see citing works
Evaluation and management of non-alcoholic steatohepatitis
Reid, B. M., & Sanyal, A. J. (2004) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200411000-00005 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis
Yang, J. D., Abdelmalek, M. F., Pang, H., Guy, C. D., Smith, A. D., Diehl, A. M., & Suzuki, A. (2014) · Hepatology · doi:10.1002/hep.26761 · Cited by 374 · see citing works
Nuclear receptors in liver fibrosis
Königshofer, P., Brusilovskaya, K., Petrenko, O., Hofer, B. S., Schwabl, P., Trauner, M., & Reiberger, T. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166235 · Cited by 45 · see citing works
- Authors
- Codes, L., Asselah, T., Cazals-Hatem, D., Tubach, F., Vidaud, D., Paraná, R., Bedossa, P., Valla, D., & Marcellin, P.
- Affiliations
- Inserm (FR)
- Hôpital Beaujon (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Corresponding author
- Marcellin, Patrick
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2006-09-27
- Volume
- 56
- Issue
- 3
- Pages
- 390-395
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1856786
- OpenAlex
- W2132111161
- Cited by
- 137
- References
- 25
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 2 · 2017: 13 · 2016: 8 · 2015: 15 · 2014: 8 · 2013: 11 · 2012: 9
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- chronic hepatitis C, liver fibrosis, menopause, hormone replacement therapy, hepatic steatosis, estrogen, fibrosis progression, women, infection duration, body mass index, METAVIR score
- MeSH terms
- Adolescent, Adult, Aged, Fatty Liver, Female, Humans, Liver Cirrhosis, Menopause, Middle Aged, Prospective Studies, Risk Factors, Severity of Illness Index, Estrogen Replacement Therapy, Body Mass Index, Disease Progression, Hepatitis C, Chronic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review