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Hepatitis C Virus Genotypes in the United States: Epidemiology, Pathogenicity, and Response to Interferon Therapy

Authors: Nizar N. Zein, MD; Jorge Rakela, MD; Edward L. Krawitt, MD; K. Rajender Reddy, MD; Tomonari Tominaga, MD; David H. Persing, MD, PhD; and the Collaborative Study Group*
Source: Ann Intern Med. 1996;125:634-639

To study 1) the geographic distribution and clinical significance of hepatitis C virus (HCV) genotypes in the United States and 2) the influence of HCV genotypes on response to interferon therapy.

Hepatitis Cvirus genotype was determined in 179 stored serum samples obtained from patients who were positive for antibody to HCV and for HCV RNA by using polymerase chain reaction.

Tertiary referral centers in four geographic re gions of the United States.

Patients who visited medical centers in the Mid west (50 patients), Northeast (42 patients), Southeast (35 patients), and West (52 patients).

Chaotropic lysis and isopropanol precipitation were used to extract RNA from serum. Polymerase chain reaction was done on the NS5 region and was fol lowed by automated direct sequencing and genotyping of desalted amplification products.

104 patients (58%) had subtype la; 38 (21 %) had subtype 1b; 4 (2%) had subtype 2a. 23 (13%) had subtype 2b; 8 (5%) had subtype 3a; and 2 (1%) had subtype 4a. Examination of the known risk factors for acquiring HCV showed no association between genotype and mode of acquisition (blood transfusion. injection drug use, employ ment at a health care facility) or histologic findings at presentation (mild active hepatitis, moderately active hepatitis, or cirrhosis). Sixty-eight percent of patients with genotype la, 80% of patients with genotype 1b. and 37% of patients with genotype 2a or 2b had severe hepatitis. Thirteen of 46 (28%) patients with genotype la and 4 of 15 (26%) patients with genotype 1b had a complete biochemical response after 6 months of interferon therapy. In contrast. 10 of 14 (71%) patients with genotype 2a or 2b had a complete response to interferon therapy. Five of 39 (13%) patients with genotype la, 1 of 14 (7%) patients with genotype 1b. and 2 of 11 (18%) patients with genotype 2a or 2b had a sustained biochemical response.

In the United States. HCV genotypes la and 1b are the predominant genotypes in patients with chronic hepatitis C. Genotype is not correlated with mode of virus acquisition or with histologic findings at presentation. Patients with HCV genotype la or 1b had more severe liver disease and lower rates of response to interferon therapy than did patients with HCV genotype 2a or 2b. These findings may have implications for predicting outcome and selecting patients for interferon treatment.

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