title: Do different lamivudine-resistant hepatitis B genotypes carry the same risk of entecavir resistance?
abstract: Entecavir switch is one of the treatment options for lamivudine-resistant hepatitis B (HBV) patients in Asia. This study examined the outcome of patients with different baseline resistance genotypes in a cohort study. In this study, 14 patients with chronic HBV were treated with entecavir 1 mg/day for 5 years. Enrolment criteria include: documented lamivudine resistant mutations, treatment with adefovir 10 mg/day for at least 24 weeks, and Child-Pugh score <7. Most had previous failed adefovir therapy and compensated cirrhosis of the liver. Clinical outcomes, liver biochemistries, and HBV DNA were monitored regularly. Patients with virologic breakthrough were rescued with add-on adefovir. At the end of the treatment period, the mean HBV DNA fell from 5.92 × 10(6) (baseline) to 3.67 × 10(1)  IU/ml. The presence of a HBV polymerase rtM204V mutation at the baseline was found to be the major risk factor for adverse outcomes. Compared to the patients with the rtM204I mutant, patients with the rtM204V mutant had increased risk of virologic breakthrough (80% vs. 0%, P = 0.010) requiring add-on adefovir, slower virologic responses (log rank test, P = 0.0011), failure to reach undetectable HBV DNA levels (60% vs. 0%, P = 0.045), and higher risk of entecavir-resistance (60% vs. 0%, P = 0.045). All the patients with rtM204I and rtA181 mutants had undetectable HBV DNA from 18th month. In summary, lamivudine-resistant HBV patients with the rtM204V mutation have the highest risk of developing entecavir resistance, and entecavir monotherapy should be avoided. Those with the rtM204I and rtA181V mutations may have lower risks, but regular surveillance for viral breakthrough is required.
authors.affiliation: Department of Gastroenterology and Hepatology, National University Health System, Singapore.
authors.forename: Guan Huei
authors.initials: GH
authors.lastname: Lee
authors.forename: Myat Oo
authors.initials: MO
authors.lastname: Aung
authors.forename: Yock Young
authors.initials: YY
authors.lastname: Dan
authors.forename: Yin Mei
authors.initials: YM
authors.lastname: Lee
authors.forename: Belinda
authors.initials: B
authors.lastname: Mak
authors.forename: How Cheng
authors.initials: HC
authors.lastname: Low
authors.forename: Kieron
authors.initials: K
authors.lastname: Lim
authors.forename: Maung Aye
authors.initials: MA
authors.lastname: Thwin
authors.forename: Poh Seng
authors.initials: PS
authors.lastname: Tan
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D001208:Asia; D001774:Blood Chemical Analysis; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D012194:RNA-Directed DNA Polymerase