Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified products demonstrated that the degree of heterogeneity of two well-conserved regions of the hepatitis C virus (HCV) genome within individual plasma samples from a single patient was consistent with a quasispecies structure of HCV genomic RNA. About half of circulating RNA molecules were identical, while the remaining consisted of a spectrum of mutants differing from each other in one to four nucleotides. Mutant sequence diversity ranged from silent mutations to appearance of in-frame stop codons and included both conservative and nonconservative amino acid substitutions. From the relative proportion of essentially defective sequences, we estimated that most circulating particles should contain defective genomes. These observations might have important implications in the physiopathology of HCV infection and underline the need for a population-based approach when one is analyzing HCV genomes.

Our findings provide evidence that a cardiac surgeon with chronic hepatitis C may have transmitted HCV to five of his patients during open-heart surgery.

No abstract

Pegylated interferon (peginterferon) alfa-2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa-2b and ribavirin in 55 patients. Twenty-eight patients were randomized to receive a high once-weekly dose of peginterferon alfa-2b (3 g/kg for 1 week, 1.5 g/kg for 3 weeks, and 1.0 g/kg for 44 weeks), and 27 patients were randomized to receive a low dose (0.5 g/kg) for 48 weeks. Both groups also received 800 mg ribavirin daily. Mean baseline HCV RNA load, measured by reverse-transcription polymerase chain reaction, was similar in both groups (5.32 ؎ 0.86 log vs. 5.15 ؎ 1.04 log). The 3-g/kg dose of peginterferon alfa-2b inhibited HCV RNA more significantly than the 0.5-g/kg dose during the first 48 hours (2.08 ؎ 0.93 log vs. 1.09 ؎ 0.80 log; P < .001) and both increased at 72 hours (0.54 ؎ 0.73 log vs. 0.03 ؎ 0.36 log; P ‫؍‬ not significant [NS]), but the high dose showed a greater reduction at the end of the week (1.07 ؎ 0.99 log vs. 0.72 ؎ 0.73 log). Both doses showed a progressive, slower viral decrease throughout therapy; however, HCV RNA became undetectable faster and in more patients with the high dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63% at week 24, and 71% vs. 61.5% at the end of therapy). In conclusion, peginterferon alfa-2b/ribavirin produces an initial rapid decline in HCV RNA levels, followed by a slower, progressive decrease, similar to the biphasic kinetic profile of standard combination therapy. Higher doses of peginterferon alfa-2b also accelerate viral clearance. (HEPATOLOGY 2002;35:930-936.) See Editorial on page 967 P egylated interferons (peginterferons) represent the most recent advance in the treatment of patients with chronic hepatitis C. Peginterferon alfa-2b consists of a conjugate of straight-chain polyethylene glycol (molecular weight, 12,000 daltons) and interferon alfa-2b in a 1:1 ratio. 1,2 The main effects of pegylated proteins are to delay clearance and prolong half-life, which allows for less-frequent dosing and may be associated with increased efficacy.Studies in humans have shown peginterferon to be safe and well tolerated. [1][2][3][4] The efficacy of peginterferon alfa-2b given once weekly has been evaluated in a large, multicenter study. This study showed that peginterferon alfa-2b increases the sustained virologic response rate to 25%, compared with the 12% rate observed with standard interferon therapy. 4 Even patients infected with genotype 1, who are least responsive to interferon therapy, experienced an increase in sustained virologic response when treated with peginterferon alfa-2b. 4,5 This response appeared to be dose dependent; 11% of patients with hepatitis C virus (HCV) genotype 1 treated with 0.5 g/kg peginterferon alfa-2b achieved sustained virologic