Potential conflict of interest: Nothing to report.
Progression of liver fibrosis in women infected with hepatitis C: Long-term benefit of estrogen exposure†
Article first published online: 24 MAR 2005
Copyright © 2005 American Association for the Study of Liver Diseases
Volume 41, Issue 4, page 939, April 2005
How to Cite
Campbell, M., Yang, Y.-X. and Reddy, K. R. (2005), Progression of liver fibrosis in women infected with hepatitis C: Long-term benefit of estrogen exposure. Hepatology, 41: 939. doi: 10.1002/hep.20611
- Issue published online: 24 MAR 2005
- Article first published online: 24 MAR 2005
To the Editor:
We read with interest the paper by Di Martino et al. published in the December 2004 issue of HEPATOLOGY1 that examines estrogen-related effects on hepatitis C fibrosis. Specifically, progression of hepatitis C fibrosis was correlated with prior pregnancies, menopausal status, past use of oral contraceptives, and hormone replacement therapy. Hepatitis C–infected women who completed a survey and had previously undergone liver biopsy were eligible for the study. The investigators calculated a rate of progression of fibrosis, dividing fibrosis stage (in Metavir units) by years of hepatitis C infection. This approach has been used previously in a self-described cross-sectional study.2
The present study is labeled a “retrospective cohort study,” although it would be better characterized as a cross-sectional study. Information from a single survey was correlated with results from a single liver biopsy. Patients were not followed by repeated biopsies or repeated surveys over time.
The distinction between cohort and cross-sectional is not merely semantic in this case. Figures 3 and 4 are Kaplan-Meier curves for the development of significant fibrosis in “cohorts” of hepatitis C patients. Kaplan-Meier curves depend on the precise knowledge of when a patient in a cohort develops significant fibrosis. For example, a patient with a biopsy showing stage 4 fibrosis and 20 years of disease duration would be plotted on a Kaplan-Meier curve as having developed significant fibrosis (stage 2) after 20 years' disease duration. Without a prior biopsy, it is not known at what time the patient actually developed stage 2 fibrosis. To address the impossibility of accurate censoring, the authors could have back-extrapolated to estimate time to development of stage 2 fibrosis, assuming linear progression of fibrosis. The problem with that approach is that it involves using a calculated result to generate primary data—for re-analysis.
In short, even though the investigators describe a rate of progression of fibrosis, the data do not truly describe a cohort. Statistical methods generally reserved for cohort studies cannot be applied easily to cross-sectional data.
- 1Prognosis of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure. HEPATOLOGY 2004; 40: 1426–1433., , , , , , et al.
- 2Natural history of liver fibrosis progression in patients with chronic hepatitis C: the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349: 825–832., , .
Mical Campbell*, Yu-Xiao Yang* , K. Rajender Reddy*, * Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA, Department of Medicine and Clinical Center for Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.