Treatment of histologically mild hepatitis C virus infection with interferon and ribavirin: a multicentre randomized controlled trial

Abstract

Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing alpha-interferon (3 MU thrice weekly) + ribavirin (1000-1200 mg/day) for 48 weeks with no treatment in treatment naive, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with alpha-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% vs 49% P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.

Cutaneous Reactions to Novel Therapeutics

“…76-78 Sarcoidosis has been described in patients with hepatitis C and with melanoma treated with Interferon-alpha. [79][80][81][82] Alopecia has been reported in 19% of patients treated with combination interferon and ribavirin, 83 including alopecia areata 84,85 and alopecia universalis. [86][87][88] Vitiligo has been reported in a number of patients who were treated for Hepatitis C with interferron.…”

An appraisal of the histopathological assessment of liver fibrosis

“…Routine scoring is done with increasing frequency under the impression that the UK National Institute for Health and Clinical Excellence (formerly known as the National Institute for Clinical Excellence) HCV treatment guidelines require this: the guidelines state that ''Interferon alpha and ribavirin as combination therapy is recommended for the treatment of moderate to severe hepatitis C (defined as histological evidence of significant scarring (fibrosis) and/ or significant necrotic inflammation), at standard doses for patients over the age of 18 years''. 13 The original guidelines (Appraisal 14,2000) suggested in a more detailed discussion (than is present in the 2003 revision) that ''Liver biopsy is undertaken, if there are no increased risks, in order to assess liver scarring and necro-inflammation according to an accepted severity scale such as the Knodell''. A later document (Appraisal 75, 2004) eliminates reference to the Knodell system.…”

Cost effectiveness of interferon or peginterferon with ribavirin for histologically mild chronic hepatitis C

“…19 Briefly, the Markov model required the natural history of the disease to be divided into a series of health states (fig 1). Two hypothetical cohorts with the characteristics of the UK mild hepatitis C trial population (summarised in box 1), 20 were entered into the model and faced annual probabilities of progression to subsequent health states (table 1).…”

“…The base case comparator was no treatment at a mild stage which was defined by the monitoring received by the control group in the UK mild hepatitis C RCT and reflected routine practice for mild hepatitis C patients in the UK. 20 The UK mild hepatitis C RCT was a pragmatic trial designed to assess the effectiveness of providing the intervention as part of routine clinical practice. The proportions of patients having a SVR following interferon a-2b and ribavirin in the mild hepatitis C RCT were 33% overall, 18% for patients with genotype 1, and 49% for patients with genotype non-1.…”