improvements of liver despite virologic failure of interferon (IFN)+ribavirin
therapy in 3 HIV+/HCV+ patients
said in her poster that although the usual outcomes measured for HCV treatment
in studies are HCV viral clearance
and ALT normalization, follow up biopsy
data in treatment failures in HIV- cohorts show improvements in histology in over 30%. Mitch Shiffman has
published data (Gastroenterology
1999;117:1164-1172) suggesting that maintenance
therapy may be useful in maintaining improved histology.
an ongoing treatment trial of IFN alpha, 3 million units TIW + ribavirin 800mg/d , 3 patients with virologic
failure at 6 months have received
pre- and post-therapy liver biopsies. Patients
had post-treatment liver biopsies between 1-3 weeks after discontinuing therapy.
3 (pt A, B, and C) patients were males ages 44,
47, and 50 with baseline CD4 counts 234, 202, and 779. HCV genotypes were
1a, 3a, and 2b, and HCV RNA levels of 16,000,000/ml, 10,000,000/ml,
and 250,000/ml. 2 patients had cirrhosis at baseline. None of
the 3 had a substantial change in HCV RNA with monthly monitoring.
ALT remained at least 2X normal in all patients at all time points
measured. Patient B did have a 5-fold reduction in ALT from his baseline. The other two had no significant reductions. Knodell
scores improved in all three, 11 to 9, 16 to 13, and 15 to 8.
Patient B had an apparent reduction in fibrosis as well.
Shulman concluded that As has been shown in HIV- HCV+ patients, treatment of HCV with interferon-based therapy can lead to histologic benefits despite lack of HCV clearance or ALT normalization. Biopsy outcomes should be an important part of future therapeutic trials for these patients.