Based on the first decade of research on alpha interferon and improving hepatic histology. The discovery and characterization of the hepatitis C virus (HCV) led to reanalysis of in viral hepatitis, one can conclude that up to 40% of patients with compensated chronic hepatitis C and elevated alanine the early trials and design of new studies that demonstrated that the majority of patients with biochemical responses to aminotransferase (ALT) levels will respond at least transiently to interferon. Four forms of alpha interferon have been evalu-therapy, and particularly those with sustained responses (SRs), had significant decreases in viremia, and that some ated in large numbers of patients with chronic hepatitis C: alfa-2b, alfa-2a, alfa-n1, and consensus interferon (CIFN). Re-long-term responders to interferon appeared cured and no longer have HCV RNA in either serum or liver. More recent sponses are defined on the basis of biochemical (ALT) or virological (hepatitis C virus [HCV] RNA testing by polymer-studies have focused on means of improving the response rate to alpha interferon, using higher doses, longer courses ase chain reaction [PCR]) end points, and as end-of-treatment response (ETR) or sustained response (SR). Biochemical ETR of therapy, regimens tailored to responses, and combinations with other agents. Most recently, several very large multicen-rates to 6 months of therapy range from 35% to 50%, and SR rates 6 months after treatment from 8% to 21%. Although 6-ter controlled trials have directly compared various forms of alpha interferon and different regimens. This introduction month treatment courses are associated with a significant rate of relapse, 12 months of initial treatment and re-treatment provides the context and framework to evaluate current regimens of therapy of hepatitis C that will be dealt with in detail regimens markedly improve the SR rate. Long-term follow-up evaluation in patients with an SR to interferon consistently in subsequent articles. It is important to remember that the early studies were initiated before HCV was identified, and show long-lasting and significant clinical, virological, and histological improvement. Finally, baseline factors that have been that virological tests to evaluate and monitor therapy have only recently become widely available. shown to be associated with SR to 6 months of treatment are not accurate enough to predict response. Therefore, the best THERAPEUTIC AGENTS treatment strategy is a therapeutic trial. Further studies of interferon therapy of hepatitis C are needed to define better
The interferons, naturally occurring proteins secreted by virological end points useful in stopping therapy, to undermany mammalian cells, were initially identified by their abilstand and better manage significant side effects of interferon, ity to interfere with viral replication and production. 2 Alpha and to evaluate the histological effects of interferon in biointerferon, a type 1 interferon, actually represents a family chemical nonresponders. Also needed is a better understandof more than 20 subspecies of proteins and glycoproteins ing of the causes of resistance to interferon. Finally, newer produced by many cell types with diverse antiviral, antiproliftherapeutic regimens such as the use of induction therapy and erative, and immunomodulatory effects. 3,4 The precise mechcombination therapies with ribavirin, other antiviral agents, anism of action of alpha interferon in hepatitis C is unknown, cytokines, and cytokine modifiers are of primary importance but the immunoregulatory and anti-inflammatory properties in eventually developing safe and effective means of treatment as well as the antiviral properties of this cytokine may play of hepatitis C. (HEPATOLOGY 1997;26(Suppl 1):71S-77S.) an important role. 5 Four forms of alpha interferon have been evaluated in large A great deal has been learned about the treatment of hepanumbers of patients with chronic hepatitis C: alfa-2b, alfatitis C since the original report in 1986 describing the use 2a, alfa-n1, and consensus interferon (CIFN). A number of of alpha interferon in chronic non-A, non-B hepatitis. 1 This other alpha and beta interferons are under evaluation. initial report was followed by a series of randomized con-Interferon Alfa-2b. Interferon alfa-2b is produced by recomtrolled trials that demonstrated the efficacy of a 6-month binant DNA techniques using a strain of Escherichia coli bearcourse of therapy in reducing serum aminotransferase levels ing a genetically engineered plasmid containing an interferon alfa-2b gene from human leukocytes. It has been extensively tested in hepatitis C, 6 and was approved for use in hepatitis Abbreviations: HCV, hepatitis C virus; SR, sustained response; CIFN, consensus C by the Food and Drug Administration (FDA) in February interferon; FDA, Food and Drug Administration; MU, million units; SC, subcutane-1991, to be administered as 3 million units (MU) subcutaneously; IM, intramuscularly; PCR, polymerase chain reaction; ALT, alanine aminotransously (SC) three times weekly for 6 months. In