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Fibrosis in chronic hepatitis C acquired in infancy: is it only a matter of time?
Maria Guido1, Flavia Bortolotti, Gioacchino Leandro
1Dipartimento di Scienze Oncologiche and Chirurgiche, Università degli Studi di Padova, Azienda Ospedale Padova, Padova, Italy.
Insights
Chronic hepatitis C in children is a slow fibrotic disease. Predicting fibrosis progression using mathematical models is unreliable in clinical practice.
Area of Science:
- Hepatology
- Virology
- Pediatric Gastroenterology
Background:
- The natural history of chronic hepatitis C (HCV) infection acquired in infancy remains poorly understood.
- Fibrosis progression in untreated pediatric HCV patients without cofactors requires further analysis.
Purpose of the Study:
- To analyze the progression of liver fibrosis in children with chronic hepatitis C virus infection.
- To evaluate the reliability of mathematical models in predicting fibrosis progression in this population.
Main Methods:
- 112 pediatric patients with chronic HCV were studied, including 13 with paired liver biopsies.
- Fibrosis was staged using the METAVIR score; progression rates were calculated based on biopsy duration and changes.
- Estimated fibrosis progression rates were compared with observed rates from paired biopsies.
Main Results:
- Age at biopsy and infection duration correlated significantly with fibrosis stage (p < 0.002 and p < 0.0005).
- Fibrosis stage differed significantly between infections <10 years and >10 years (p < 0.0006).
- In 13 patients with paired biopsies, fibrosis increased in 7; prediction models were unreliable in 97% of cases.
Conclusions:
- Chronic hepatitis C acquired in childhood is a slow, progressive fibrotic disease.
- Mathematical models for fibrosis progression in pediatric HCV should be critically evaluated in clinical practice.
Objective:
The natural history of chronic hepatitis C acquired in infancy is not well understood. The progression of fibrosis was analyzed in untreated children with chronic hepatitis C virus infection and no other hepatotoxic cofactors.
Methods:
A total of 112 pediatric patients (13 with paired liver biopsies) were considered. Fibrosis was assessed by METAVIR score (i.e., stage F1 to F4). The ratio between the stage of fibrosis (METAVIR units) and the presumed duration of infection represented the "estimated" rate of fibrosis progression per year. In patients with paired biopsies, the "observed" rate of fibrosis progression was defined as the difference between the stage of fibrosis in the two biopsies divided by the time interval between them.
Results:
Both age of patients at biopsy and duration of infection correlated with stage of fibrosis (p < 0.002 and p < 0.0005, respectively). Stage of fibrosis differed significantly between patients with infection lasting less or more than 10 yr (p < 0.0006). Sex, hepatitis C virus genotype, and route of infection did not correlate with stage of fibrosis. Among the 13 patients with paired biopsies, stage of fibrosis increased in seven and did not change in six; the median rate of estimated fibrosis progression per year was 0.142. The difference between estimated and observed fibrosis progression rates was significant (coefficient of determination, r(2) = 0.031), which demonstrated that the prediction of the fibrosis progression was unreliable in 97% of patients.
Conclusions:
Chronic hepatitis C acquired in childhood is a progressive, slow-moving, fibrotic disease. Fibrosis progression inferred on the basis of linear mathematical models should be critically evaluated in the clinical practice.
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