Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis

Sheng, Yun-Jian; Liu, Junying; Tong, Shiwen; Hu, Huaidong; Zhang, Dazhi; Hu, Peng; Ren, Hong

doi:10.1186/1743-422x-8-393

Cited by 52 publications

(35 citation statements)

References 41 publications

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“…It is clear that ETV is the most potent antiviral agent when TDF is not available. Recently, Sheng et al (24) reported LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. Similarly, Kim et al (25) found ADV add-on treatment in patients with LAM-resistant CHB suppressed HBV replication more effectively than ETV or ADV monotherapy.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Diao

et al. 2012

Intern. Med.

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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.

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Section: Discussionmentioning

confidence: 99%

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

Zhang

Diao

et al. 2012

Intern. Med.

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“…Clearance of HBV DNA was seen in seven out of eight (78%) of the HBeAg negative children and five out of 22 (23%) of the HBeAg positive [112]. No safety data were presented in this pediatric study, however adverse effects of entecavir in adult studies have been minimal [105,106]. As with all the nucleos(t)ide analogues, lactic acidosis with severe hepatomegaly and steatosis has been reported [113].…”

Section: Treatmentmentioning

confidence: 99%

HIV/HBV coinfection in children and antiviral therapy

Healy

Gupta

Melvin

2013

Expert Review of Anti-infective Therapy

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Small cohort studies from countries where both HIV and HBV are endemic demonstrate prevalence rates of chronic hepatitis B in HIV-infected children of between 1 and 49%. While data on coinfected children are limited, results from studies in adults with HIV/HBV coinfection raise the concern that coinfected children may be at a higher risk of liver disease, hepatic fibrosis and cirrhosis. With the scale-up of combination antiretroviral therapy worldwide, of which lamivudine is included in most first-line regimens, coinfected children treated with lamivudine risk development of HBV resistance mutations. This article summarizes the current literature relevant to HIV/HBV coinfection in children, the options for treatment and highlights priorities for future research.

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“…A recent meta-analysis has demonstrated that a combination therapy with lamivudine and adefovir dipivoxil is more effective and produces long-lasting effects than switching to entecavir monotherapy in treating chronic hepatitis B patients with lamivudine resistance. However, taking into account the practical benefits and the limitations of adefovir dipivoxil, individualized therapy will be needed in patients with a prior history of lamivudine-resistant infections [54] . Entecavir rescue therapy for 96 wk is less efficacious in patients with lamivudine/adefovir dipivoxil-refractory HBV, particularly in those who have an initial HBV DNA of > 10 7 copies/mL.…”

Section: Nasmentioning

confidence: 99%

Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

Li-ping

Zhao²,

Du³

et al. 2012

WJV

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Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). The approved medication for the treatment of chronic HBV infection is interferon-α (IFNα) and nucleos(t)ide analogues (NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. IFNα is the most suitable for young patients with less advanced liver diseases and those infected with HBV genotype A. IFNα treatment significantly decreases the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Orally administered NAs are typically implemented for patients with more advanced liver diseases. NA treatment significantly reduces disease progression of cirrhosis and therefore HCC incidence, especially in HBV e antigen-positive patients. NA-resistance due to the mutations in HBV polymerase is a major limiting factor. Of the NA resistance-associated mutants, A181T mutant significantly increases the risk of HCC development during the subsequent course of NA therapy. It is important to initiate treatment with NAs that have a high genetic barrier to resistance, to counsel patients on medication adherence and to monitor virological breakthroughs. The recommended treatment for patients with chronic HCV infection is peg-IFN plus ribavirin that can decrease the occurrence of HCC in those who achieve a sustained virological response and have not yet progressed to cirrhosis. IFN-based treatment is reserved for patients with decompensated cirrhosis who are under evaluation of liver transplantation to reduce post-transplant recurrence of HCV. More effective therapeutic options such as direct acting antiviral agents will hopefully increase the response rate in difficult-totreat patients with HCV genotype 1. However, the risk of HCC remains in cirrhotic patients (both chronic HBV and HCV infection) if treatment is initiated after cirrhosis is established. Future research should focus on investigating new agents, especially for those patients with hepatic decompensation or post-transplantation.

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Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis

Cited by 52 publications

References 41 publications

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

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

HIV/HBV coinfection in children and antiviral therapy

Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

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