Compare with safety and efficacy of entecavir and adefovir dipivoxil combination therapy and tenofovir disoproxil fumarate monotherapy for chronic hepatitis B patient with adefovir-resistant

Ming-Chun Lai; Jiang-Shan Lian; Wen-Jin Zhang; Jun Xu; Lin Zhou; Shu-Sen Zheng; Ming-Chun Lai; Jiang-Shan Lian; Wen-Jin Zhang; Jun Xu; Lin Zhou; Shu-Sen Zheng

doi:10.3934/mbe.2020032

Mathematical Biosciences and Engineering

2020, Volume 17, Issue 1: 627-635. doi: 10.3934/mbe.2020032

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Research article Special Issues

Compare with safety and efficacy of entecavir and adefovir dipivoxil combination therapy and tenofovir disoproxil fumarate monotherapy for chronic hepatitis B patient with adefovir-resistant

1.
Key Laboratory of Combined Multi-Organ Transplantation Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China
2.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China

Received: 03 April 2019 Accepted: 24 September 2019 Published: 21 October 2019

Objective To compare the 2-year efficacy and safety of combination therapy with entecavir (ETV) and adefovir dipivoxil (ADV) to that of tenofovir disoproxil fumarate (TDF) monotherapy in treatment of patients with adefovir drug-resistant chronic hepatitis B.

Methods HBeAg-positive CHB patients (n = 100) with adefovir-resistance (rtA181T/V and/or rtN236T) were enrolled. Patients were treated with either ETV 0.5 mg plus ADV 10 mg per day (n = 52) or TDF 300 mg per day (n = 48) for 48 weeks. Tests for liver and kidney function, Serum Phosphorus, HBV serum markers, HBV DNA load and ultrasonography of liver were performed every 3 months. Student's t-test and χ² test were used to compare the efficacy, side effects in the two groups.

Results Fifty-two patients in ETV + ADV group and forty-eight patients in TDF group were followed-up for 96 weeks. HBV DNA undetectable rate were 76.9% versus 81.3% (P = 0.631) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV + ADV combination therapy and TDF monotherapy group respectively. Serum ALT normalized rate were 84.6% versus 87.5% (P = 0.777) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV+ADV combination therapy and TDF monotherapy group respectively. But the level of serum Phosphorus was significantly lower in ETV + ADV combination therapy group compare with TDF monotherapy group (1.13 ±0.15 versus 1.22 ±0.16, P = 0.004) at week 96.

Conclusion Both ETV + ADV combination therapy and TDF monotherapy provided effective treatments in chronic hepatitis B with adefovir-resistant. However, it was associated with poor serological responses up to week 96. The long term treatment of hepatitis B with ETV (0.5 mg/day) combination of ADV (10 mg/day) can potentially cause hypophosphatemia and renal impairment, so regular monitoring of serum phosphate, serum creatinine and evaluation of eGFR is needed.
- chronic hepatitis B,
- adefovir-resistant,
- adefovir dipivoxil,
- entecavir,
- tenofovir disoproxil fumarate,
- combination therapy,
- hypophosphatemia
Citation: Ming-Chun Lai, Jiang-Shan Lian, Wen-Jin Zhang, Jun Xu, Lin Zhou, Shu-Sen Zheng. Compare with safety and efficacy of entecavir and adefovir dipivoxil combination therapy and tenofovir disoproxil fumarate monotherapy for chronic hepatitis B patient with adefovir-resistant[J]. Mathematical Biosciences and Engineering, 2020, 17(1): 627-635. doi: 10.3934/mbe.2020032

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Abstract

Objective To compare the 2-year efficacy and safety of combination therapy with entecavir (ETV) and adefovir dipivoxil (ADV) to that of tenofovir disoproxil fumarate (TDF) monotherapy in treatment of patients with adefovir drug-resistant chronic hepatitis B.

Methods HBeAg-positive CHB patients (n = 100) with adefovir-resistance (rtA181T/V and/or rtN236T) were enrolled. Patients were treated with either ETV 0.5 mg plus ADV 10 mg per day (n = 52) or TDF 300 mg per day (n = 48) for 48 weeks. Tests for liver and kidney function, Serum Phosphorus, HBV serum markers, HBV DNA load and ultrasonography of liver were performed every 3 months. Student's t-test and χ² test were used to compare the efficacy, side effects in the two groups.

Results Fifty-two patients in ETV + ADV group and forty-eight patients in TDF group were followed-up for 96 weeks. HBV DNA undetectable rate were 76.9% versus 81.3% (P = 0.631) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV + ADV combination therapy and TDF monotherapy group respectively. Serum ALT normalized rate were 84.6% versus 87.5% (P = 0.777) at week 48, and 92.3% versus 95.8% (P = 0.679) at week 96 in ETV+ADV combination therapy and TDF monotherapy group respectively. But the level of serum Phosphorus was significantly lower in ETV + ADV combination therapy group compare with TDF monotherapy group (1.13 ±0.15 versus 1.22 ±0.16, P = 0.004) at week 96.

Conclusion Both ETV + ADV combination therapy and TDF monotherapy provided effective treatments in chronic hepatitis B with adefovir-resistant. However, it was associated with poor serological responses up to week 96. The long term treatment of hepatitis B with ETV (0.5 mg/day) combination of ADV (10 mg/day) can potentially cause hypophosphatemia and renal impairment, so regular monitoring of serum phosphate, serum creatinine and evaluation of eGFR is needed.

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