- Objective In 2003, a cluster of hepatitis C virus (HCV)-infected patients with a common history of a surgical procedure, performed during 2001 to 2003, was identified in a medical center. An epidemiologic investigation linked a physician, infected with HCV genotype 2, as the possible source of infection in 35 patients. The evaluation, therapy, and outcome of this unique cohort are presented. Design HCV-RNA was isolated from sera of all patients and the double-stranded phosphorylation homology domain region was sequenced. After a routine clinical investigation 33 patients were offered antiviral therapy. Two patients were not treatment candidates due to old age and comorbidity. Results Twenty-two (66%) were women. The mean age was 48.5±16.9 years. Alanine aminotransferase level was 117±135 IU/L. Thirty patients were treated with pegylated interferon alpha 2a, 1 with pegylated interferon alpha 2b, and 1 with standard interferon. All received ribavirin 800 mg daily. One patient refused to be treated and was lost for follow-up. Time from acquisition of disease to initiation of therapy was 14.8±4.9 month (5.5 to 26). Therapy duration was 24 weeks except for 1 patient who stopped therapy after 16 weeks. Sustained virologic response was achieved in all 32 treated patients. The sequence motif of the phosphorylation homology domain region, studied in all patients, predicted good response to interferon. Conclusions Our excellent results can be explained by a constellation of favorable viral characteristics, a short-term disease and adherence to therapy.