About 60% to 85% of people infected with hepatitis C virus will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions in treatment-naïve people with chronic hepatitis C infection, but without liver decompensation? What are the effects of interventions in people with chronic hepatitis C infection, but without liver decompensation, who have not responded to interferon treatment? What are the effects of interventions in people with chronic hepatitis C infection, but without liver decompensation, who relapse after interferon treatment? What are the effects of interventions in people with chronic hepatitis C infection who also have HIV? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: interferon monotherapy; interferon alfa plus ribavirin; peginterferon monotherapy; and peginterferon plus ribavirin.
Chronic hepatitis C virus (HCV) infection is defined as persistent, detectable serum HCV RNA for a period greater than 6 months, with or without derangement in liver function tests.
About 60% to 85% of people infected with HCV will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population.Complications of chronic HCV infection include cirrhosis, compensated and decompensated liver disease, and hepatocellular carcinoma.Many people chronically infected with HCV remain asymptomatic, including a significant proportion of those who progress to cirrhosis, so routine screening of people in high-risk groups is advisable.
Interferon monotherapy produces a sustained virological response in both treatment-naïve people and people with cirrhosis or advanced fibrosis compared with placebo or no treatment.
Interferon also improves liver histology, although it may not be effective in preventing hepatocellular carcinoma in people with cirrhosis.Efficacy is dependent on duration of treatment, with treatment for 12 months seeming more effective than treatment for 6 months. However, treatment for 12 months is associated with an increase in adverse effects.A dose of 6 MU of interferon three times weekly seems no more effective at achieving sustained virological response than 3 MU three times weekly, and is associated with an increased risk of adverse effects.
Adding ribavirin to interferon regimens further increases the likelihood of achieving sustained virological response, but also increases the risk of anaemia.
Efficacy of combination therapy depends on genotype, with genotype 1-infected people typically requiring longer duration of treatment compared with genotype 2- and genotype 3-infected people.
Peginterferon monotherapy increases the proportion of treatment-naïve people who achieve sustained virological response compared with standard interferon monotherapy.
Adding ribavirin to peginterferon increases the likelihood of achieving sustained virological response compared with either peginterferon alone or standard interferon plus ribavirin. This is currently the standard recommended therapeutic approach.
In people previously non-responsive to interferon monotherapy, treatment with interferon alfa plus ribavirin increases the likelihood of achieving sustained virological response compared with interferon alone.
This effect seems greater when the interferon dose is higher than 3 MU three times weekly, or the duration of the treatment is 12 months or greater.We don't know whether peginterferon as a monotherapy, or in combination with ribavirin, is effective in non-responders to interferon monotherapy. We don't know whether peginterferon plus ribavirin is more effective than interferon alfa plus ribavirin.
In people who relapse after interferon monotherapy, treatment with interferon plus ribavirin is more likely than interferon treatment alone to achieve sustained virological response (SVR).
There is general consensus that peginterferon plus ribavirin is likely to improve the probability of achieving SVR in people who relapse after interferon monotherapy.We don't know whether peginterferon alone is effective at achieving SVR in people who relapse after interferon monotherapy.
In people co-infected with HCV and HIV, peginterferon plus ribavirin seems more effective than standard interferon plus ribavirin treatment or peginterferon alone at achieving SVR.
Although interferon plus ribavirin seems less effective than peginterferon plus ribavirin, the proportion of people achieving SVR suggests that interferon plus ribavirin may be effective in people with HCV and HIV. We don't know whether interferon alone is effective in people co-infected with HCV and HIV.