Gastroenterology

Gastroenterology

Volume 130, Issue 6, May 2006, Pages 1636-1642
Gastroenterology

Clinical–liver, pancreas, and biliary tract
Relationship Between Steatosis, Inflammation, and Fibrosis in Chronic Hepatitis C: A Meta-Analysis of Individual Patient Data

https://doi.org/10.1053/j.gastro.2006.03.014Get rights and content

Background & Aims: Steatosis is a frequent histologic finding in chronic hepatitis C (CHC), but it is unclear whether steatosis is an independent predictor for liver fibrosis. We evaluated the association between steatosis and fibrosis and their common correlates in persons with CHC and in subgroup analyses according to hepatitis C virus (HCV) genotype and body mass index. Methods: We conducted a meta-analysis on individual data from 3068 patients with histologically confirmed CHC recruited from 10 clinical centers in Italy, Switzerland, France, Australia, and the United States. Results: Steatosis was present in 1561 patients (50.9%) and fibrosis in 2688 (87.6%). HCV genotype was 1 in 1694 cases (55.2%), 2 in 563 (18.4%), 3 in 669 (21.8%), and 4 in 142 (4.6%). By stepwise logistic regression, steatosis was associated independently with genotype 3, the presence of fibrosis, diabetes, hepatic inflammation, ongoing alcohol abuse, higher body mass index, and older age. Fibrosis was associated independently with inflammatory activity, steatosis, male sex, and older age, whereas HCV genotype 2 was associated with reduced fibrosis. In the subgroup analyses, the association between steatosis and fibrosis invariably was dependent on a simultaneous association between steatosis and hepatic inflammation. Conclusions: In this large and geographically different group of CHC patients, steatosis is confirmed as significantly and independently associated with fibrosis in CHC. Hepatic inflammation may mediate fibrogenesis in patients with liver steatosis. Control of metabolic factors (such as overweight, via lifestyle adjustments) appears important in the management of CHC.

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Patients

Collection of CHC patient data was performed at 10 centers from Italy, Switzerland, France, Australia, and the United States. Patients were recruited consecutively for clinical management of their hepatitis C virus (HCV) infection, including the assessment of the indication to antiviral therapy, but were not involved primarily in clinical treatment trials. To be included in the HCV Meta-Analysis (on) Individual patients’ Data Study Group database, patients had to fulfill the following basic

Results

The baseline characteristics of the 3068 patients included in the study population are shown in Table 1. There were 1999 men (65.2%) with a mean age of 44.7 ± 11.8 years, and an average BMI of 25.4 ± 3.9 kg/m2. According to the previously described definitions, alcohol abuse at the time of liver biopsy examination was reported by 370 persons (12.1%), whereas 737 (24.0%) had a history of long-lasting excess alcohol drinking in the past. Diabetes was present in 194 patients (6.3%). Overall, HCV

Discussion

Progression of CHC depends significantly on host and environmental factors. Given that currently available antiviral regimens induce a sustained virologic response in only approximately 60% of patients, and that individuals with advanced liver disease may not benefit from therapy, medical interventions often are limited to correcting cofactors associated with liver-related morbidity.

Steatosis has been suggested as an important cofactor for liver fibrosis. However, there is not a clear consensus

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Supported by grants 3200-63549.00 and 3200B0-103727 from the Swiss National Science Foundation, Berne, Switzerland (to F.N.); DK56402 from the National Institutes of Health, Bethesda, Maryland (to The University of Sydney Hepatitis C Pathogenesis Study Group and to J.G.); grants from the French Agency for Acquired Immune Deficiency Syndrome Research (ANRS), Paris, France (to T.A., P.M.); grant 2004061213-006 from the Ministero dell’Istruzione, Universita’ e Ricerca Scientifica, Rome, Italy (to L.E.A., G.R.); a grant from the Regione Campania, Naples, Italy (to L.E.A., G.R.); from the National Health and Medical Research Council, Canberra, Australia (to E.E.P., J.R.J.); from the Lions Medical Research Foundation, Brisbane, Australia (to J.R.J.); and R01 AA12879 from the National Institutes of Health–National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (to N.T.).

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