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The objective is to assess the efficacy and safety of 24 or 28 weeks of treatment with a low or standard dose of ribavirin. It is concluded that the treatment with peginterferon-alpha2a and ribavirin is individualized by genotype and patients with hepatitis C virus (HCV) genotype 1 require treatment for 48 weeks and standard dose of ribavirin and those with HCV genotype 2 and 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.

9–27 mRNA is expressed to a high level in response to both α and γ interferons. In contrast, 6–16 mRNA Is expressed well in response to α but very poorly in response to γ interferon in human cells. The factors governing these different levels of expression were investigated. For both genes the major effect of both interferons is on transcription. A transcriptional bias in the 6–16 promoter/enhancer accounts in large part for the differential response of 6–16 to the two interferons. No single DNA element appears responsible; the smaller the 5′ region analysed the lower the absolute activity and the smaller the differential response to α and γ interferons observed. Both the 6–16 and 9–27 mRNAs are very stable and no effect of the interferons on stability was detected. Nor was any direct evidence obtained for preferential processing of the 9–27 mRNA. Nevertheless, differentials between the transcription and accumulation of mature mRNAs, particularly for 6–16 mRNA in response to γ interferon, suggest that post-transcriptional controls) must additionally operate. The 9–27 5′ promoter/enhancer Is much less active than that from 6–16 when placed 5′ of a marker gene, despite the similar response of the two genes to a interferon.

Factors induced by interferons (IFNs) bind to the IFN-stimulated response elements (ISREs) of many genes. In human cells treated with type I ( α, β) IFN, factor E is induced in about 1 min and factor M after about 1 hr. Factor G is induced after about 1 hr in cells treated with type II (γ) IFN. G and M have very similar positions in bandshift assays, sensitivities to cycloheximide, footprints on an ISRE and relative affinities for different ISREs. Four different patterns of expression were observed in different cell lines: E,M and G strongly induced; M and G strongly but E weakly; only E and M induced; only E induced. Transcription in response to IFN α is initiated by E and probably maintained by M since, in fibroblasts, M is present maximally when transcription is most active and declines together with transcription. In Bristol-8 cells, where induction of M is not detected, transcription is still induced by IFN α and still declines in its continued presence, suggesting that M is not essential for either process. A variant ISRE with two G-to-C mutations binds E especially weakly but M and G strongly. The mutations don't change the response of a reporter gene to IFN γ but do abolish its response to IFN α, suggesting that the binding of M is not sufficient for the latter. G probably acts positively, since its appearance correlates well with induction of transcription by IFN γ. A 39-bp ISRE from the 9–27 gene binds E much better than M or G. Conversely, a 39–bp ISRE from the 6–16 gene binds M and G much better than E. Different patterns of expression of E, M, and G and different affinities of these factors for alternative ISREs may play a part in modulating the relative responses of genes to type I and type II IFNs in vivo.