title: Simple scoring system predicting genotypic resistance during rescue therapy for Lamivudine-resistant chronic hepatitis B.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 log10 copies/mL; +1, >3 log10 copies/mL), and the initial HBV DNA level (+0, >10 copies/mL; +1, <10 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.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Cho
authors.forename: Hyo Joon
authors.initials: HJ
authors.lastname: Yang
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jang
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kwak
authors.forename: Sang Youn
authors.initials: SY
authors.lastname: Hwang
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Chung Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine