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