Histologic improvements of liver despite virologic failure of interferon (IFN)+ribavirin therapy in 3 HIV+/HCV+ patients

Shulman 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.

In 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.

All 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.