Hemophilic Siblings with Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-related Viral Clearance.
From: Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. mfried@med.unc.edu
Gastroenterology
- Publish Date: Sep 2006
- ISSN: 0016-5085
- Volume: 131
- Issue: 3
- Pages: 757-64
- Medium: Print
- Language: English
- Citation (JAMA): Fried Michael W, Kroner Barbara L, Preiss Liliana R, et al. Hemophilic Siblings with Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-related Viral Clearance.. Gastroenterology Sep 2006;131:757-64
Abstract
BACKGROUND & AIMS: Hemophilic siblings provide a unique population to explore the natural history of chronic hepatitis C. METHODS: From 3993 hemophilic patients with hepatitis C, 257 sibling pairs, of which both members had evidence of hepatitis C infection, were studied to evaluate the genetic contribution to spontaneous and treatment-induced clearance of hepatitis C infection and progression of liver disease. Familial aggregation was assessed by comparing observed probabilities of concordance for these disease characteristics within sibling pairs to those expected for randomly paired hemophilic subjects. Additional measures of familial aggregation, heritability, and sibling relative risk were also calculated. RESULTS: Among human immunodeficiency virus-negative subjects, concordance for spontaneous viral clearance was 2-fold higher in siblings compared with randomly paired subjects (8.8% vs 4.3%, respectively, P = .04). Similarly, the concordance rate for treatment-related viral clearance was over twice that among sibling pairs than among randomly paired hemophiliacs (31.3% vs 13.3%, respectively, P = ns). Heritability estimates for spontaneous and treatment-induced viral clearance were 0.24 +/- 0.14 (P = .04) and 0.43 +/- 0.42 (P = .10), respectively. The sibling relative risks for these respective characteristics were 1.6 and 1.7. Concordance for advanced liver disease was higher among siblings but did not reach statistical significance (4.0% vs 2.3%, respectively, P = ns). The heritability estimate was 0.29 +/- 0.13 (P = .02). CONCLUSIONS: Concordance rates and heritability estimates for spontaneous and treatment-related viral clearance indicate that genetic factors have a modest influence on the outcome of hepatitis C, although shared environmental factors cannot be excluded. Investigations to map candidate disease-susceptibility genes associated with these characteristics must be approached with caution.
Mesh Headings (Keywords): Antiviral Agents, Child, Female, Follow-Up Studies, Genetic Predisposition to Disease, Hemophilia A, Hepacivirus, Hepatitis C, Chronic, Humans, Male, Prognosis, RNA, Viral, Retrospective Studies, Risk Factors, Siblings
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