GASTROENTEROLOGY LITERATURE ALERT!
LANDMARK ARTICLE -
Required reading
Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. [To be published in the November 15, 2001 Issue of NEJM]
Major findings:
Patients with acute hepatitis C [known exposure within 4 months, seroconversion to HCV antibody, ALT >350] were treated with 5 MU interferon alfa-2b daily for 4 weeks then 5MU three times a week for 20 weeks.
44 patients were treated, 43 completed therapy. HCV-RNA became negative during therapy in all patients, the average time to negative viremia was 3.2 weeks, all were negative by 12 weeks.
Of the 43 patients completing treatment, 42/43 were still virus negative 24 weeks after completing 6 months of interferon.
ALT fell rapidly and normalized within 10.4 weeks of initiating therapy
The patient who stopped therapy at 12 weeks had a flare of the hepatitis, then cleared virus and went into long-term remission.
Response was not determined by genotype.
FACTS TO REMEMBER FOR BOARDS
Approximately 75%-85% of patients infected with hepatitis C develop chronic infection if left untreated.
The determinant of viral clearance in acute hepatitis C seems to be the strength of the CD4 and CD8 T cell response. If the viral replication overwhelms the T cell response, virus-specific CD4 and CD8 T cells are deleted by apoptosis or are rendered anergic and the disease becomes chronic.
Controlling viral load early on, allows the CD4 and CD8 response continue to be strong
Best way to assess for HCV infection after exposure is to measure HCV-RNA in 3 to 6 weeks, rather than wait for anti-HCV seroconversion or ALT elevation.
Clinical application
In most cases of acute hepatitis C infection, antiviral therapy should be offered unless there is a contraindication.
The use of pegylated interferon + ribavirin will eliminate the need for daily interferon injections.
These were symptomatic patients. It is not known if asymptomatic acute infections (detected by serial RNA measurements after exposure) will respond as well
It appears that 6 months of therapy is sufficient, regardless of genotype, it is not known if the new pegylated interferon and ribavirin combination will allow for shorter treatment duration with similar efficacy.