Simple Scoring System Predicting Genotypic Resistance During Rescue Therapy for Lamivudine-Resistant Chronic Hepatitis B

Abstract

Goal: In this study, we aimed to devise a simple scoring system predicting the risk of genotypic resistance (GR) to current rescue therapies for patients with lamivudine (LAM)-resistant chronic hepatitis B. Background: LAM and adefovir (ADV) combination therapy should be recommended for an initial rescue therapy against LAM-resistant hepatitis B virus (HBV). However, there still are many LAM-resistant patients being treated with entecavir (ETV) or ADV monotherapy. Study: This retrospective cohort study included consecutive patients treated for LAM-resistant chronic hepatitis B with ETV or ADV monotherapy, or LAM/ADV combination therapy. The cumulative probabilities of GR and virological responses and breakthrough according to clinical variables were analyzed by survival analyses and derived an index for future GR. Results: A total of 224 patients were included (median treatment duration = 117.9 wk). Using risk factors indentified on multivariable analyses, a simple index for future GR (Antiviral Resistance Prediction Index, ARPI) was developed with 3 clinical variables: the rescue therapy regimens (+0, ADV; +1, ETV; +2, LAM/ADV), HBV DNA reduction at 12 weeks (+0, < 3 log(10) copies/mL; +1, >3 log(10) copies/mL), and the initial HBV DNA level (+0, > 10(6) copies/mL; +1, < 10(6) copies/mL). No patient with ARPI >= 2 exhibited GR, whereas 47% of the patients with an ARPI < 2 developed GR by week 144 (P = 0.005). Conclusions: The results of this study suggest that the ARPI is a simple and early index that can be used to determine the risk for subsequent GR during rescue therapy for LAM-resistant chronic hepatitis B.