Rescue Therapy for Lamivudine-resistant Chronic Hepatitis B: Adefovir Monotherapy, Adefovir Plus Lamivudine or Entecavir Combination Therapy

Abstract

Objective We aimed to compare the cumulative efficacy and resistance of ADV monotherapy, ADV add-on LAM (ADV + LAM), ADV and ETV (ADV + ETV) combination therapy in LAM-resistant patients. Methods Ninety-one adult CHB patients with LAM-resistance mutations (YMDD) were identified. Of these 91, 29 patients were treated with ADV monotherapy, 30 were treated with ADV + LAM and 32 were treated with ADV + ETV combination therapy, for at least 24 months. Results The mean serum HBV-DNA decreases from baseline at 3, 6, 12, and 24 months were -3.23, -4.41, -5.32, and -5.58 log10IU/mL in the ADV + ETV combination therapy groups, respectively; the most significant among the three treatment groups (p<0.01). The rate of HBV-DNA PCR undetectability (<60 IU/mL) at 6 months in ADV + ETV combination therapy was 78.1%; also the most significant among the three treatment groups (p=0.024). Viral breakthrough and genotypic mutations were detected in 8 (27.6%) and 4 (13.3%) patients in the ADV monotherapy and ADV+LAM therapy groups, respectively; whereas no case of viral breakthrough and genotypic resistance was detected in the ADV+ETV combination therapy group after 24 months (p<0.05). Conclusion ADV + ETV combination therapy demonstrated faster and significantly greater suppression of HBV DNA compared with ADV add-on LAM combination therapy for patients with LAM-resistance mutations. ADV + ETV was superior to ADV + LAM in achieving initial virological response and long-term suppression activity against HBV. ADV + ETV combination therapy was the most effective to refrain from selecting HBV strains with cross-resistance to three NAs (LAM, ADV and ETV) for LAM-resistance patients.

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice

“…And this superiority of ETV + ADV could be explained by the effect of ETV against ADV resistant mutation and the effect of ADV against LAM resistant mutation. In present study, we also found that ETV + ADV combination therapy showed ideal efficacy in HBV DNA suppression over 24 months in patients after LAM and ADV therapy failures, and this finding also supported the superior efficacy of ETV + ADV combination therapy in a certain degree [19]. …”

Entecavir plus adefovir combination therapy versus lamivudine add‐on adefovir for lamivudine‐resistant chronic hepatitis B: A meta‐analysis

“…By adhering to the inclusion criteria, 24 of those studies were excluded. Finally, 4 studies were chosen for inclusion in the meta‐analysis, which comprised a total of 323 patients (Figure S1).…”

“…The characteristics of the included studies including population size, age, rate of HBeAg positivity, serum alanine aminotransferase (ALT), serum HBV DNA levels and variants are summarized in Table . The study population was Asian for all four studies, with two studies composed of Chinese and two composed of Korea subjects. Two studies were randomized controlled trials and two were cohorts.…”

Entecavir plus adefovir versus adefovir plus lamivudine in hepatitis B virus e antigen‐positive, lamivudine‐resistant chronic hepatitis B

“…In both groups, the proportions of patients with HBV‐DNA < 60 IU/mL increased gradually and were comparable at week 104 (42.2% and 34.1%, respectively), with decreased levels of resistance mutants selected during second‐ or third‐line therapy, and no emergence for additional multidrug resistance mutants . In another study in LAM‐resistant patients, ADV + ETV demonstrated faster and significantly greater virologic suppression after 24 months than switch to ADV monotherapy or ADV add‐on therapy . Another small study assessed ETV + ADV as third‐line therapy after failure on initial LAM and any of the second‐line options ETV, ADV, or LAM + ADV.…”