HEPATITIS-C VIRUS GENOTYPES IN THE UNITED-STATES - EPIDEMIOLOGY, PATHOGENICITY, AND RESPONSE TO INTERFERON THERAPY

Objective: To study 1) the geographic distribution and clinical signif icance of hepatitis C virus (HCV) genotypes in the United States and 2 ) the influence of HCV genotypes on response to interferon therapy. De sign: Hepatitis C virus genotype was determined in 179 stored serum sa mples obtained from patients who were positive for antibody to HCV and for HCV RNA by using polymerase chain reaction. Setting: Tertiary ref erral centers in four geographic regions of the United States. Patient s: Patients who visited medical centers in the Midwest (50 patients), Northeast (42 patients), Southeast (35 patients), and West (52 patient s). Measurements: Chaotropic lysis and isopropanol precipitation were used to extract RNA from serum. Polymerase chain reaction was done on the NS5 region and was followed by automated direct sequencing and gen otyping of desalted amplification products. Results: 104 patients (58% ) had subtype 1a; 38 (21%)had subtype 1b; 4 (2%) had subtype 2a; 23 (1 3%) 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 asso ciation between genotype and mode of acquisition (blood transfusion, i njection drug use, employment at a health care facility) or histologic findings at presentation (mild active hepatitis, moderately active he patitis, or cirrhosis). Sixty-eight percent of patients with genotype 1a, 80% of patients with genotype 1b, and 37% of patients with genotyp e 2a or 2b had severe hepatitis. Thirteen of 46 (28%) patients with ge notype 1a and 4 of 15 (26%) patients with genotype 1b had a complete b iochemical response after 6 months of interferon therapy. In contrast, 10 of 14 (71%) patients with genotype 2a or 2b had a complete respons e to interferon therapy. Five of: 39 (13%) patients with genotype 1a, 1 of 14 (7%) patients with genotype 1b, and 2 of 11 (18%) patients wit h genotype 2a or 2b had a sustained biochemical response. Conclusions: In the United States, HCV genotypes 1a and 1b are the predominant gen otypes in patients with ch ron ic hepatitis C. Genotype is not correla ted with mode of virus acquisition or with histologic findings at pres entation. Patients with HCV genotype 1a or 1b had more severe liver di sease and lower rates of response to interferon therapy than did patie nts with HCV genotype 2a or 2b. These findings may have implications f or predicting outcome and selecting patients for interferon treatment.