We have read with interest the article of Dr. Fartoux and colleagues, 1 who assessed the factors involved in the progression of fibrosis in 135 mild chronic hepatitis C (CHC) patients who underwent paired liver biopsies after a median of 61 months. Steatosis was the only determinant of fibrosis progression in this subgroup of CHC patients.
Evidence has accumulated to suggest that steatosis is a major cause of progression of liver damage in CHC. 2 This concept is now further corroborated by the study of Fartoux at al. 1 Among patients with a low risk of fibrosis progression, such as mild CHC patients, those with steatosis were the only ones showing worsening disease. We have similar data on a series of 36 CHC patients with genotype 1 infection, no alcohol abuse, and a recognized date of infection or paired liver biopsies. Patients with steatosis developed hepatic fibrosis with a rate two times faster than those without steatosis (0.22 and 0.10 fibrosis scores per year, respectively).
We feel these data have clinical relevance as well as important therapeutic implications. Fartoux and colleagues 1 conclude that patients with mild CHC associated with steatosis should be considered for antiviral treatment due to the risk of disease progression. We believe the authors' conclusion, to treat this subgroup of patients with antivirals, is disputable. Several considerations should be made before establishing the treatment which is the most appropriate for mild CHC with steatosis. First of all, it is necessary to underscore that steatosis is mainly virus-induced in HCV genotype 3 infection while host factors play a major role in genotype non-3 infections. 3 In HCV genotype 3-infected patients, steatosis dramatically improves with interferon treatment after viral clearance. Therefore, antiviral treatment should be regarded as the first therapeutic option in genotype 3 infection. In contrast, in genotype 1-infected patients with mild CHC and steatosis, a 'metabolic' therapeutic approach appears more meaningful, since only a limited number of patients may benefit from antivirals due to the low response rate of this genotype. In addition, steatosis is a further cause of unfavourable response to interferon-based treatments, especially so in genotype 1-infected patients. On the other hand, a weight-reduction program of treatment for CHC with steatosis is highly effective in improving both biochemical and histological liver parameters. 7 Thus, we believe that achievement of normal weight should be obtained in all overweight CHC patients.
A growing body of data is being published on factors implicated in the development of HCV-related steatosis. Among them, insulin resistance, hyperhomocysteinemia and hypoadiponectinemia seem to be major determinants of steatosis in CHC. 8-10 Thus, molecules such as insulin sensitizers, folic acid and betaine, alone or in combination with antivirals, are candidate for treatment of CHC-related steatosis. Randomized clinical trials are awaited to establish their efficacy.