PMO-176 Induction maintenance treatment in chronic hepatitis B; step-down from tenofovir and lamivudine to lamivudine monotherapy is effective

Abstract

Results Intrahepatic vs peripheral blood NK cells demonstrated significantly less expression of CD16 (p NKG2D and NKp30 expression was increased in PBMCs of HCV patients with a more striking down regulation of NKG2D in the liver (p. There was no difference in NKp46 or NKG2A expression between the intrahepatic and peripheral NK cells in either cohort. However, the necroinflammatory score of HCV subjects correlated with NKp46 expression (p¼0.003), CD107a expression (p¼0.05) and Introduction Stopping rules have been proposed for the early discontinuation of Pegylated-Interferon-a (PEG-IFN-a) therapy in those patients who are considered unlikely to respond. Recent studies have shown that no reduction in quantitative HBsAg and the absence of >2 log decline in HBV DNA at 12 weeks therapy can predict non-response. However, these data are almost exclusively from genotype A and D cohorts. Here we test how robust this strategy would be in clinical practice and whether this rule could be applied to a UK population of diverse HBV genotypes. Methods 49 patients (male¼35) were treated with PEG-IFNa for CHB over the course of the study. Ten patients remain on therapy and eight patients discontinued due to poor compliance or intolerance. 31 patients (male¼20), HBeAg positive (n¼24), median age 31 (range 18e55) completed 48 weeks PEG-IFNa and were included in the analysis. HBV genotype was recorded for all patients (A¼6, B¼5, C¼10, D¼9, E¼1). ALT, HBV DNA and HBsAg was quantified at baseline and longitudinally at 12-week intervals. Results Of the 31 patients, 10 were considered responders; seven were HBeAg positive and seroconverted on therapy and three were HBeAg negative pre-therapy and considered responders with sustained immune control off treatment. The decline in HBV DNA and qHBsAg by 12 weeks was 3.99 log, 0.17 log (HBeAg positive group) and 2.9 log, 0.5 log (HBeAg negative group) respectively. 16/ 31 patients were non-genotype A or D. Of the responders from this group there was a decline in HBV DNA and qHBsAg of 4.10 log and 0.58 log respectively by 12 weeks. On sub-group analysis by genotype, there was no statistically significant difference in HBV DNA and qHBsAg decline at 12 weeks across all genotypes, when comparing HBV DNA and qHBsAg between genotype A and D and non A and D patients (p¼0.40 and 1.0 respectively). More over adopting the rule of >2 log decline in HBV DNA and no decline in qHBsAg by 12 weeks, reveals we would not exclude those likely to respond; as all responders achieve the outlined viral response by 12 weeks therapy.