Ask the Experts - Continue Antiviral Therapy in the Presence of...
Ask the Experts - Continue Antiviral Therapy in the Presence of...
A 40-year-old white man presented with chronic hepatitis C and mildly elevated aminotransferases 1 year ago. At that time, biopsy showed mild disease activity with periportal fibrosis (grade 2, stage 2). After 1 year of combination therapy with interferon and ribavirin, he had normalization of serum aminotransferases and no associated side effects. Virus is still present, although at a reduced titer. Should this patient be maintained on low-dose combination therapy?
This patient has chronic hepatitis C with mild inflammation and scarring on his liver biopsy. He is a nonresponder to the current "standard" of care for treating hepatitis C virus (HCV) infection. Fortunately, he suffered few side effects from this treatment. Because the patient's viral load is lower at the end of antiviral therapy than it was at baseline, the question arises as to whether the patient would benefit from further therapy.
Currently, there is one well-conducted, relatively small study that supports the concept of continuing antiviral therapy in the presence of persisting viremia. In a series of 53 patients whose liver histology was found to improve at the end of a 6-month course of interferon monotherapy despite remaining viremic (albeit at lower titer), antiviral therapy was continued for an additional 6 months in half of patients. Liver histology continued to improve during that latter 6 months of treatment for this group of patients when compared with that of those whose treatment had been stopped. However, no long-term follow-up biopsies were performed, so we do not know if "catch-up" occurred upon cessation of therapy in those who were treated for 12 months but who remained viremic.
This well-conducted study has prompted the initiation of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial to evaluate long-term interferon (pegylated) monotherapy in nonresponders to previous antiviral therapy who had severe "background" liver disease. The results of this National Institutes of Health-supported study will not be available for many years. It was not considered appropriate to subject individuals to long-term interferon treatment combined with ribavirin "combination" therapy.
There are, nevertheless, several recommendations for those patients with chronic hepatitis C who are nonresponders to current antiviral therapy. Alcohol intake should be maintained at a minimum because even "social" drinking is associated with enhanced hepatic fibrosis if continued for long periods. And, more recently, it has been recognized that central obesity is associated with more progressive liver disease. Patients are advised to undergo vaccination against hepatitis A and B if they are not already immune. It is important to reassure individuals that the natural progression (with the avoidance of the risk factors discussed) of chronic hepatitis C is very slow. Such individuals should be encouraged to enter trials of therapy involving new agents; otherwise, ongoing treatment is not recommended.
Fortunately, this patient has only mild-to-moderately severe chronic hepatitis C and is unlikely to progress rapidly to more severe disease. It may be advisable to repeat his liver biopsy in 3 years unless at that point in time we have reliable markers of liver fibrosis not requiring biopsy.
A 40-year-old white man presented with chronic hepatitis C and mildly elevated aminotransferases 1 year ago. At that time, biopsy showed mild disease activity with periportal fibrosis (grade 2, stage 2). After 1 year of combination therapy with interferon and ribavirin, he had normalization of serum aminotransferases and no associated side effects. Virus is still present, although at a reduced titer. Should this patient be maintained on low-dose combination therapy?
This patient has chronic hepatitis C with mild inflammation and scarring on his liver biopsy. He is a nonresponder to the current "standard" of care for treating hepatitis C virus (HCV) infection. Fortunately, he suffered few side effects from this treatment. Because the patient's viral load is lower at the end of antiviral therapy than it was at baseline, the question arises as to whether the patient would benefit from further therapy.
Currently, there is one well-conducted, relatively small study that supports the concept of continuing antiviral therapy in the presence of persisting viremia. In a series of 53 patients whose liver histology was found to improve at the end of a 6-month course of interferon monotherapy despite remaining viremic (albeit at lower titer), antiviral therapy was continued for an additional 6 months in half of patients. Liver histology continued to improve during that latter 6 months of treatment for this group of patients when compared with that of those whose treatment had been stopped. However, no long-term follow-up biopsies were performed, so we do not know if "catch-up" occurred upon cessation of therapy in those who were treated for 12 months but who remained viremic.
This well-conducted study has prompted the initiation of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial to evaluate long-term interferon (pegylated) monotherapy in nonresponders to previous antiviral therapy who had severe "background" liver disease. The results of this National Institutes of Health-supported study will not be available for many years. It was not considered appropriate to subject individuals to long-term interferon treatment combined with ribavirin "combination" therapy.
There are, nevertheless, several recommendations for those patients with chronic hepatitis C who are nonresponders to current antiviral therapy. Alcohol intake should be maintained at a minimum because even "social" drinking is associated with enhanced hepatic fibrosis if continued for long periods. And, more recently, it has been recognized that central obesity is associated with more progressive liver disease. Patients are advised to undergo vaccination against hepatitis A and B if they are not already immune. It is important to reassure individuals that the natural progression (with the avoidance of the risk factors discussed) of chronic hepatitis C is very slow. Such individuals should be encouraged to enter trials of therapy involving new agents; otherwise, ongoing treatment is not recommended.
Fortunately, this patient has only mild-to-moderately severe chronic hepatitis C and is unlikely to progress rapidly to more severe disease. It may be advisable to repeat his liver biopsy in 3 years unless at that point in time we have reliable markers of liver fibrosis not requiring biopsy.
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