Treatment of chronic hepatitis C with interferon: how long should a lasting response last if a lasting response could last?
In chronic hepatitis C infection to document spontaneous remission or response to treatment, more than one parameter is required. Both the activity of liver disease and of viral replication need to be recorded. The former is most accurately done by liver biopsy. The number of such biopsies which a patient or physician are willing to have performed is necessarily limited, such that serum-ALT has traditionally been used as surrogate marker. Viral replication can be quantified using a standardized and validated polymerase chain reaction (PCR) test system. Drawing on a database of over 2300 patients with documented chronic hepatitis C for whom data were recorded longitudinally for up to 5 years, a proposal is presented on how to document more precisely quality of response and its duration. Using both biochemical and virological parameters quantified repeatedly at regular intervals, three response patterns can be described, and less frequent histological assessments are used for confirmation: non-response, where no relevant changes are seen in either parameter; transient response that consists of a response induction, usually biochemical in nature, accompanied by a transient decrease in viral replication only. This response is subsequently lost either during (breakthrough) or after the end of treatment (relapse); finally, a durable response is defined by a rapid return to normal or fall to undetectable levels, as a rule within 2 weeks to 3 months, of serum ALT and hepatitis C virus (HCV) RNA that is sustained until the end of the follow-up period (up to 5 years).
Ryff
J C
JC
Virology Section, F. Hoffmann-LaRoche Ltd, Basel, Switzerland.
D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*
D000998:Antiviral Agents; D016898:Interferon-alpha; D000410:Alanine Transaminase