The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis

doi:10.1016/j.intimp.2016.11.022

International Immunopharmacology

Volume 42, January 2017, Pages 168-175

https://doi.org/10.1016/j.intimp.2016.11.022 Get rights and content

Highlights

•
There were significant difference of ALT norm level between TDF and ETV in the short-term period.
•
There was significant difference of undetectable HBV-DNA only in 3 months follow up period.
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There were significant difference between TDF and ETV in eGFR level and hypophosphatemia incidence.

Abstract

Background

The purpose of this study was to assess the efficacy and safety between tenofovir and entecavir in the treatment of CHB and HBV related cirrhosis through Meta-analysis. Methods

The electronic databases of PubMed, the Cochrane Library, Nature, CNKI and WanFang data were searched. The key words were: (“tenofovir”, “entecavir”) and (“Chronic Hepatitis B” or “CHB”) and “Liver cirrhosis”. Heterogeneity and report bias were analyzed.

Results

There was significant difference of ALT norm level in the short-term period of 3 months (RR = 1.43, 95%CI: 1.06–1.94, P < 0.017) and 6 months (RR = 0.89, 95%CI: 0.81–0.97, P < 0.017), and significant difference of undetectable HBV-DNA only in 3 months follow-up period (RR = 1.59, 95%CI: 1.04–2.42, P < 0.017) between TDF and ETV, but no significant difference in the long-term period. There is significant difference between TDF and ETV in eGFR level (RR = 1.601, 95%CI: 1.035–2.478, P = 0.0034) and hypophosphatemia incidence (RR = 4.008, 95%CI: 1.485–10.820, P = 0.006).

Conclusion

TDF has a better efficacy than ETV in 3 months treatment duration, but intriguingly, TDF might not better than ETV during the 6 months treatment period in the viral suppression and liver function improvement. There's no significant difference between TDF and ETV in the long-term treatment duration and in the treatment of HBV related liver cirrhosis. Both TDF and ETV could influence renal function but patients under TDF therapy may have more risk to suffer from renal damage and hypophosphatemia.

Introduction

Hepatitis B virus (HBV) infection will cause chronic hepatitis B (CHB), a difficult problem for centuries. The earliest human virus isolation known so far was obtained by laparoscopic liver biopsy from a Korean mummy in the sixteenth century [1]. And to date, HBV infection has already become a global problem. Till 2010, 248 million individuals have been reported the hepatitis B surface antigen (HBsAg) positive, and despite the availability of an effective vaccine, the virus causes about 780,000 deaths every year [1], [2]. HBV carriers present a broad spectrum ranging from asymptomatic carrier state to liver cirrhosis and hepatocellular carcinoma [3]. It's estimated that about 15% to 30% of chronic hepatitis B virus (HBV) carriers in the world are at the increasing risks for developing liver cirrhosis and complicated end-staged liver disease [4].

The approved and widely used agents to treat CHB are conventional interferon alfa and pegylated interferon-alfa-2a as well as the nucleoside analogs (lamivudine, entecavir, and telbivudine) and the nucleotide analog (adefovir, dipivoxil and tenofovir) [5]. Evidence shows that entecavir and tenofovir have low incidence of drug-resistant mutants and side effects, moreover, the current guidelines recommend that the most common potent drugs to treat CHB and liver cirrhosis are nucleoside analog entecavir (ETV) and the nucleotide analog tenofovir (TDF) [6], [7]. However, the difference of efficacy and the safety between ETV and TDF is under debating. And which one is the best to treat CHB and CHB related cirrhosis in different treatment duration remains unclear. Besides, whether there's any difference regarding the safety between TDF and ETV is not well concluded.

Therefore, the study aims to evaluate the efficacy and safety between tenofovir and entecavir in the treatment of CHB and HBV related cirrhosis through Meta-analysis.

Section snippets

Article retrieval

The retrieval sources include PubMed, the Cochrane Library, Nature, China National Knowledge Infrastructure (CNKI) and WanFang Data. The key words were the combination of (“Tenofovir” and “Entecavir”) and (“Chronic Hepatitis B” or “CHB”) and “Liver cirrhosis”. All human studies were included and no publish time lower limit (up to May 12, 2016) was taken. We also searched articles through relevant citations in related literature.

Inclusion and exclusion criteria

Any article which conforms to the under-mentioned criteria would be

Article selection

After searching the electronic databases and selecting the relevant citations, we obtained 572 reports and 17 studies respectively. 422 articles were ruled out because of irrelevance. After reading full-text of 167 articles, 141 articles were excluded due to meet the exclusion criteria. 26 articles were combined into qualitative description (12 [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22] articles evaluated TDF and ETV in CHB patients, 6 [23], [24], [25], [26], [27],

Discussion

We found that there's significant difference in comparing TDF with ETV in short-term follow up period (RR = 1.43, 95%CI: 1.06–1.94, I² = 0.0%; P < 0.017 and RR = 0.89, 95%CI: 0.81–0.97, I² = 0.0%; P < 0.017 for month 3 and month 6, respectively) but no significant difference in long-term follow up period (RR = 0.96, 95%CI: 0.90–1.02, I² = 10.4%; P > 0.017 and RR = 0.97, 95%CI: 0.92–1.02, I² = 0.0%; P > 0.017 for 12 months and 24 months, respectively) which indicated that in 3 month duration of treatment, TDF users might

Conclusion

Conflict of interests

The authors declare that they have no competing interests.

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To the best of our knowledge, four systematic reviews have compared the efficacy and safety of TDF and ETV. Among them, Ke et al. (2014) and Han et al. (2017) focused on efficacy rather than renal safety. Ke et al. (2014) did not find a significant difference in the safety between the two drugs, whereas Han et al. (2017) suggested that patients treated with TDF may have underlying renal impairment compared with those treated with ETV.
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The electronic databases of the Cochrane Library, PubMed, and Embase were searched. The keywords were: “CHB”, “tenofovir”, and “entecavir”. Heterogeneity and subgroups were analyzed.
A total of 16 studies met the inclusion criteria. There was no significant difference in serum creatinine levels between the TDF and the ETV group. There was a significant standardized mean difference (SMD) in the serum estimated glomerular filtration rate between months (12 months: SMD [95% confidence interval] = -0.07 [-0.12, -0.01]; 18-24 months: SMD [95% confidence interval] = -0.11 [-0.17, -0.05]), but no significant difference emerged in the long-term drug use for over 24 months. There was no significant difference in the incidence of osteopenia/osteoporosis (I² = 41%, risk ratio [95% confidence interval] = 1.29 [0.93, 1.77], P-value = 0.13 >0.05).
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La infección por el virus de la hepatitis B (VHB) continúa siendo un problema de salud pública mundial, en México se estima que podría haber por lo menos tres millones de personas adultas que han adquirido la hepatitis B (anticuerpo anti-antígeno central del VHB [anti-HBc] positivo), de ellos cerca de 300,000 portadores activos (antígeno de superficie del VHB [HBsAg] positivo) podrían requerir tratamiento. Al ser prevenible por vacunación, debe enfatizarse la vacunación universal. Esta infección es un factor de riesgo mayor para el desarrollo de carcinoma hepatocelular, el estudio semestral con ultrasonido hepático y alfafetoproteína sérica favorece la detección temprana de esta neoplasia y debe realizarse en todo paciente con infección crónica por VHB, independientemente de la presencia de fibrosis avanzada o cirrosis. En la actualidad, la terapia de primera línea, son análogos nucleós(t)idos con alta barrera a la resistencia.
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Many studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12–25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions.
WHO and US Centers for Disease Control and Prevention.
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View all citing articles on Scopus

View full text

The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis

Highlights

Abstract

Background

Results

Conclusion

Introduction

Section snippets

Article retrieval

Inclusion and exclusion criteria

Article selection

Discussion

Conclusion

Conflict of interests

Lancet

Clin. Liver Dis.

J. Prosthet. Dent.

J. Craniomaxillofac. Surg.

Int. J. Infect. Dis.

Gastroenterology

Clin. Gastroenterol. Hepatol.

J. Hepatol.

J. Hepatol.

Clin. Gastroenterol. Hepatol.

Natural history of chronic hepatitis B virus infection

Med. Microbiol. Immunol.

Effect of entecavir and tenofovir treatment on noninvasive fibrosis scores: which one is better?

Am. J. Ther.

Hepatitis B virus infection

Lancet

First-line treatment of chronic hepatitis B with entecavir or tenofovir in ‘real-life’ settings: from clinical trials to clinical practice

J. Viral Hepat.

Management of chronic hepatitis B: an overview of practice guidelines for primary care providers

J. Am. Board Fam. Med.

A meta-analysis comparing the efficacy of entecavir and tenofovir for the treatment of chronic hepatitis B infection

J. Clin. Pharmacol.

Efficacy comparison of tenofovir and entecavir in HBeAg-positive chronic hepatitis B patients with high HBV DNA

Biomed. Res. Int.

Virologic response and safety of tenofovir versus entecavir in treatment-naive chronic Hepatitis B patients

Saudi J. Gastroenterol.

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease

Hepatology