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Lumley SF, Delphin M, Mokaya JF, Tan CCS, Martyn E, Anderson M, Li KC, Waddilove E, Sukali G, Downs LO, Said K, Okanda D, Campbell C, Harriss E, Shimakawa Y, Matthews PC. A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) resistance in people treated with entecavir or tenofovir. J Clin Virol 2024; 174:105711. [PMID: 38991458 DOI: 10.1016/j.jcv.2024.105711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 06/26/2024] [Accepted: 06/27/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND As nucleos/tide analogue (NA) therapy (e.g. entecavir and tenofovir) for chronic Hepatitis B virus (HBV) infection becomes more widely indicated and available, understanding drug resistance is essential. A systematic review to quantify resistance to these agents has not previously been undertaken. METHODS We performed a systematic review and random-effects meta-analysis to estimate the risk of HBV resistance to entecavir and tenofovir. We searched nine databases up to 29-Aug-23. We included studies of HBV infection featuring >10 individuals, written in English, reporting treatment ≥48 weeks, with assessment of HBV resistance based on viral sequence data. Data were analysed according to prior exposure history to NA, and choice of NA agent. Analyses were performed in R. FINDINGS 62 studies involving a total of 12,358 participants were included. For entecavir, in treatment-naive individuals (22 studies; 4326 individuals), resistance increased over time to 0.9 % at ≥5 years (95 %CI 0.1-2.3 %), and resistance was increased in NA-experienced individuals (18 studies; 1112 individuals), to 20.1 % (95 %CI 1.6-50.1 %) at ≥5 years. For tenofovir, pooled resistance risk was 0.0 % at all time points, whether previously NA naive (11 studies; 3778 individuals) or experienced (19 studies; 2059 individuals). There was a lack of consistent definitions, poor global representation and insufficient metadata to support subgroup analysis. INTERPRETATION We have generated the first pooled estimates of HBV entecavir and tenofovir resistance over time. HBV resistance to entecavir in treatment-experienced groups in particular may represent a clinical and public health challenge. To date, tenofovir appears to have an excellent resistance profile, but due to data gaps, we caution that existing studies under-estimate the true real-world risk of resistance. Robust prospective data collection is crucial to reduce health inequities and reduce blind-spots in surveillance as treatment is rolled out more widely.
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Affiliation(s)
- Sheila F Lumley
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, UK.
| | | | | | | | - Emily Martyn
- The Francis Crick Institute, 1 Midland Road, London, UK
| | - Motswedi Anderson
- The Francis Crick Institute, 1 Midland Road, London, UK; Africa Health Research Institute, Durban, SA
| | - Ka Chun Li
- The Francis Crick Institute, 1 Midland Road, London, UK
| | | | - Gloria Sukali
- University of KwaZulu Natal, Nelson R Mandela Medical School,Durban, SA
| | - Louise O Downs
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, UK; KEMRI-Wellcome Trust, Kilifi, Kenya
| | - Khadija Said
- The Francis Crick Institute, 1 Midland Road, London, UK
| | | | - Cori Campbell
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Eli Harriss
- Bodleian Health Care Libraries, University of Oxford, UK
| | - Yusuke Shimakawa
- Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France
| | - Philippa C Matthews
- The Francis Crick Institute, 1 Midland Road, London, UK; Department of Infectious Diseases, University College London Hospitals, London, UK; Division of Infection and Immunity, University College London, Gower Street, London, UK
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Bi Z, Wang L, Hou H, Lu M, Wang W, Li Z, Liu C. Comparing the efficacy and safety of tenofovir and adefovir or combined drug treatment for the treatment of chronic hepatitis B infection: a systematic review and meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:1016. [PMID: 36267714 PMCID: PMC9577806 DOI: 10.21037/atm-22-3747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/21/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Chronic hepatitis B (CHB) affects a vast population globally. A variety of drugs are available for the treatment of CHB, including tenofovir (TDF) and adefovir (ADV). However, the efficacy of monotherapy drug treatment is inconclusive, the safety and efficacy of TDF remain unclear, more data are needed to be included and combined drug treatment is considered to exhibit higher efficacy. To explore this issue, we performed a current literature review and meta-analysis to compare the efficacy and safety of ADV vs. TDF, TDF vs. ADV + lamivudine (LAM); TDF vs. ADV + entecavir (ETV). METHODS We systematically searched China National Knowledge Infrastructure, the Cochrane Library, Embase, PubMed, Chinese VIP, and Wanfang Data, for relevant clinical trials since July 2015, all included studies were based on PICOS principles and evaluated independently by the reviewers in accordance with the Cochrane Handbook (Rob2.0). A meta-analysis was performed by using Review Manager 5.4. RESULTS We included a total of 32 studies, including 31 randomized controlled trials and one retrospective study involving 2,473 patients. The results revealed a low risk of bias in included studies, that the virologic response of TDF was superior to ADV (P<0.05). And TDF was also superior to ADV in Serum creatinine levels, Immunologic function, and safety profile. However, when ADV was combined with other medications, it was superior to TDF in alanine aminotransferase (ALT) level and Tbil level and adverse reactions, but on other indicators, TDF was superior to drug combination therapy. CONCLUSIONS Results showed that TDF was superior to ADV in the parameters of ALT, hepatitis B virus (HBV)-DNA reduction, HBeAg-negative conversion rate, safety, and total bilirubin levels in patients with CHB. However, when ADV was combined with LAM or ETV, they often showed the same therapeutic effect as TDF in parameters such as ALT level and Tbil level and combined therapy can effectively reduce the occurrence of adverse reactions. In this study, because the sample source countries were limited, a greater number of global studies are needed in the future to verify the current findings.
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Affiliation(s)
- Zeyu Bi
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan, China
| | - Ling Wang
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan, China
| | - Huixin Hou
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan, China
| | - Miao Lu
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan, China
| | - Wei Wang
- Department of outpatients, Wuhan Asian Heart Hospital, Wuhan, China
| | - Zishuo Li
- Department of outpatients, Wuhan Asian Heart Hospital, Wuhan, China
| | - Chengjiang Liu
- Department of Gastroenterology, Anhui Medical University, Hefei, China
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Liang X, Xie Q, Shang J, Tang H, Xu M, Meng Q, Zhang J, Gao P, Sheng J, Wang H, Jia J, Wang G, Wu S, Ping J, Hou J. Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: Is monotherapy enough? J Gastroenterol Hepatol 2022; 37:471-479. [PMID: 34894002 PMCID: PMC9303406 DOI: 10.1111/jgh.15757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/10/2021] [Accepted: 12/01/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs). METHODS Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA < 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed. RESULTS Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log10 IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]-positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly. CONCLUSIONS Tenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.
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Affiliation(s)
- Xieer Liang
- Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Qing Xie
- School of MedicineRuijin Hospital Affiliated to Jiaotong UniversityShanghaiChina
| | - Jia Shang
- Department of Infectious DiseasesHenan Provincial People's HospitalZhengzhouChina
| | - Hong Tang
- West China Hospital of Sichuan UniversityChengduChina
| | - Min Xu
- Guangzhou Eighth Municipal People's HospitalGuangzhouChina
| | - Qinghua Meng
- Beijing You‐An HospitalCapital Medical UniversityBeijingChina
| | - Jiming Zhang
- Huashan Hospital Affiliated to Fudan UniversityShanghaiChina
| | - Pujun Gao
- The First Hospital of Jilin UniversityChangchunChina
| | - Jifang Sheng
- Department of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
| | - Hao Wang
- Peking University People's HospitalBeijingChina
| | - Jidong Jia
- Beijing Friendship HospitalCapital Medical UniversityBeijingChina
| | | | - Shunquan Wu
- GlaxoSmithKline R&D Company LimitedShanghaiChina
| | - Jingna Ping
- GlaxoSmithKline R&D Company LimitedShanghaiChina
| | - Jinlin Hou
- Nanfang HospitalSouthern Medical UniversityGuangzhouChina
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Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Xiao L, Li C, Wu Q, Sun C, Niu J, Hou J. Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B. Aliment Pharmacol Ther 2021; 54:1134-1149. [PMID: 34587302 PMCID: PMC9292801 DOI: 10.1111/apt.16611] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/10/2021] [Accepted: 09/07/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). AIM To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). METHODS We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. RESULTS We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. CONCLUSION TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).
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Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol 2021; 9:769-791. [PMID: 34722192 PMCID: PMC8516840 DOI: 10.14218/jcth.2021.00209] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/20/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022] Open
Abstract
To achieve the goal of the World Health Organization to eliminate viral hepatitis as a major public health threat by 2030, the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology convened an expert panel in 2019 to update the guidelines for the prevention and treatment of chronic hepatitis B (CHB). The current guidelines cover recent advances in basic, clinical, and preventive studies of CHB infection and consider the actual situation in China. These guidelines are intended to provide support for the prevention, diagnosis, and treatment of CHB.
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Affiliation(s)
- Guiqiang Wang
- Center for Liver Diseases, Department of Infectious Diseases, Peking University First Hospital; Department of Infectious and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Zhongping Duan
- Center for Difficult and Complicated Liver Diseases and Artificial Liver, Beijing YouAn Hospital, Capital Medical University, Beijing, China
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Chen P, Wei W, Jin L, Kuai W, Li F, Liu H, Jiang B, Zhu Y. Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B. Exp Ther Med 2021; 22:1325. [PMID: 34630679 DOI: 10.3892/etm.2021.10760] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 08/18/2021] [Indexed: 11/06/2022] Open
Abstract
Tenofovir alafenamide fumarate (TAF) is a first-line drug for the antiviral treatment of patients with chronic hepatitis B (CHB) in China. In the present study, the efficacy and renal safety of TAF were evaluated in treatment-naive patients with CHB. Patients with CHB who had not been previously treated with nucleoside analogues (NAs) were recruited before TAF treatment was initiated. Changes in the levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were analyzed at 24 and 48 weeks using immunoassays. In addition, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were analyzed using transient elastography, while alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels, calcium (Ca) and inorganic phosphorus (IP) levels were measured using biochemistry assay. In addition, the estimated glomerular filtration rate (eGFR) was calculated. After 48 weeks, the ALT normalization rate was 95.24% (40/42), the complete virological response (HBV DNA <20 IU/ml) rate was 69.05% (29/42) and the HBeAg seroconversion rate was 8.57% (3/35). The levels of HBV DNA and HBsAg were significantly decreased from the baseline at 5.49±1.95 to 1.26±0.66 log10 IU/ml and from 3.59±0.81 to 3.32±0.55 log10 IU/ml after 48 weeks of treatment, respectively. Compared with that in the baseline measurements, LSM at 48 weeks was significantly decreased from 13.00±8.15 to 8.66±4.45 kPa. No significant differences were observed in the TG, TC, LDL-C, CAP, eGFR, Ca and IP measurements. According to the baseline ALT levels, patients were divided into group A [ALT ≤1 x upper limit of normal (ULN); ULN=50 U/l; n=21], group B (1 x ULN < ALT <2 x ULN; n=22) and group C (ALT ≥2 x ULN; n=18). A significant decrease in HBsAg levels was observed in group B (3.63±0.68 vs. 3.53±0.63 log10 IU/ml) and group C (4.15±0.57 vs. 3.66±0.48 log10 IU/ml) at 24 weeks compared with the baseline. In conclusion, TAF was found to be effective and safe in NA treatment-naive patients with CHB. Moreover, the higher the ALT levels, the more prominent the curative effect from TAF treatment. Therefore, NA treatment-naive CHB patients could benefit from TAF treatment in real world.
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Affiliation(s)
- Peng Chen
- Department of Chronic Liver Disease, Tianjin Second People's Hospital, Tianjin Medical Institute of Hepatology, Tianjin 300192, P.R. China
| | - Wei Wei
- Postgraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China.,Department of Severe Hepatitis, Tianjin Second People's Hospital, Tianjin Medical Institute of Hepatology, Tianjin 300192, P.R. China
| | - Li Jin
- Postgraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China
| | - Wentao Kuai
- Department of Chronic Liver Disease, Tianjin Second People's Hospital, Tianjin Medical Institute of Hepatology, Tianjin 300192, P.R. China
| | - Fei Li
- Department of Chronic Liver Disease, Tianjin Second People's Hospital, Tianjin Medical Institute of Hepatology, Tianjin 300192, P.R. China
| | - Huan Liu
- Department of Chronic Liver Disease, Tianjin Second People's Hospital, Tianjin Medical Institute of Hepatology, Tianjin 300192, P.R. China
| | - Bei Jiang
- Department of Chronic Liver Disease, Tianjin Second People's Hospital, Tianjin Medical Institute of Hepatology, Tianjin 300192, P.R. China
| | - Yu Zhu
- Department of Clinical Laboratory, Tianjin Haihe Hospital, Tianjin 300351, P.R. China
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Li G, Xu M, Yue T, Gu W, Tan L. Life-long passion for antiviral research and drug development: 80th birthday of Prof. Dr. Erik De Clercq. Biochem Pharmacol 2021; 185:114485. [PMID: 33617841 PMCID: PMC7895689 DOI: 10.1016/j.bcp.2021.114485] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/17/2021] [Accepted: 02/17/2021] [Indexed: 12/15/2022]
Abstract
Since the 1950s, great efforts have been made to develop antiviral agents against many infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and varicella-zoster virus (VZV). Among the list of nearly 106 antiviral agents approved in the past five decades, Prof. Erik De Clercq has contributed to the development of 7 antiviral drugs: tenofovir disoproxil fumarate (Viread®) for HIV and HBV treatment, tenofovir alafenamide (Vemlidy®) for HIV and HBV treatment, brivudine (Zostex®) for HSV-1 and VZV treatment, valacyclovir (Valtrex®) for HSV and VZV treatment, adefovir dipivoxil (Hepsera®) for HBV treatment, stavudine (Zerit®) for HIV treatment, and cidofovir (Vistide®) for treating HCMV retinitis in AIDS patients. In addition to the above antiviral drugs, his contributions include two anti-cancer drugs: rabacfosadine (Tanovea®-CA1) for canine lymphoma and plerixafor (Mozobil®) for multiple myeloma and non-Hodgkin's lymphoma. These achievements are driven by his life-long passions for antiviral research and successful collaborations worldwide. To honor the 80th birthday of Prof. Erik De Clercq, this study highlights his scientific achievements and the importance of life-long passions and collaborations in the success of antiviral research and drug development.
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Affiliation(s)
- Guangdi Li
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Ming Xu
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Tingting Yue
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, China
| | - Weijie Gu
- Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Leuven 3000, Belgium
| | - Li Tan
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
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Con D, Goodwin T, Majeed A, Roberts S, Kemp W. Comparison of 48-week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta-analysis. J Viral Hepat 2021; 28:40-50. [PMID: 32893921 DOI: 10.1111/jvh.13400] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 08/15/2020] [Accepted: 08/17/2020] [Indexed: 02/06/2023]
Abstract
Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first-line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta-analysis of randomized trials. The secondary aim was to additionally include propensity-matched cohort studies in a conventional meta-analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English-language randomized and propensity-matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48 weeks. We excluded patients who had co-infection or significant prior treatment with antivirals. 13 517 participants from 16 studies (11 RCTs, n = 2675; five propensity-matched cohort studies, n = 10 842) were included. Virological response at 48 weeks was higher in patients receiving TDF compared to ETV using both the network meta-analytic approach (OR 1.69, P < .001) and the conventional meta-analysis including propensity-matched cohort studies (OR 1.40, P < .001). On subgroup analysis, this difference was only significant in HBeAg-positive patients (OR 1.81, P = .037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P = .07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48 weeks in treatment-naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.
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Affiliation(s)
- Danny Con
- Department of General Medicine, Eastern Health, Melbourne, Victoria, Australia
| | - Thomas Goodwin
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Stuart Roberts
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia
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Ji TT, Tan N, Lu HY, Xu XY, Yu YY. Early renal injury indicators can help evaluate renal injury in patients with chronic hepatitis B with long-term nucleos(t)ide therapy. World J Clin Cases 2020; 8:6306-6314. [PMID: 33392311 PMCID: PMC7760448 DOI: 10.12998/wjcc.v8.i24.6306] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 10/06/2020] [Accepted: 11/02/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Patients with chronic hepatitis B (CHB) with long-term nucleos(t)ide therapy may experience renal insufficiency. Traditional renal function indicators, such as urine protein, serum urea nitrogen (BUN), and serum creatinine, are normal when early mild lesions occur. Therefore, more sensitive renal function indicators are needed.
AIM To investigate the significance of early renal injury indicators in evaluating renal injury in patients with CHB with long-term nucleos(t)ide therapy.
METHODS We collected the clinical data of 69 outpatients with CHB at Peking University First Hospital from March 2018 to January 2020 who had been treated with long-term nucleos(t)ide therapy and analyzed the results of early renal injury indicators. Continuous normal distribution data were analyzed by the t-test to determine the difference between two groups. Continuous non-normally distributed data were analyzed by the Mann-Whitney U-test between two groups. The Kruskal-Wallis H test was used to determine the differences among multiple groups. Enumeration data were analyzed by the chi-square test. The related factors of early renal injury indicators were analyzed by logistic regression analysis.
RESULTS The average treatment duration with nucleos(t)ide analogs of the 69 patients with CHB was 99.7 ± 28.7 mo. The cases of patients with elevated BUN and hypophosphatemia were 6 (8.7%) and 13 (18.8%), respectively; 31 (44.9%) patients had abnormal early renal injury indicators, including 9 patients with abnormal urine microalbumin, 7 patients with abnormal urine immunoglobulin, 6 patients with abnormal urine transferrin, and 19 patients with abnormal α1 microglobulin. There were no significant differences in the mean values of age, sex, BUN, estimated glomerular filtration rate (eGFR), serum uric acid, serum calcium, or serum phosphorus between the two groups of patients with and without early renal injury indicators. However, the mean levels of serum creatinine and urine creatinine, N-acetyl-β-D-glucosidase enzyme, α1 microglobulin, and urine immunoglobulin in the former group of patients were significantly higher than those in the latter group of patients (P < 0.05). The incidence of early renal injury in patients with eGFR ≥ 90, 60-89, and 30-59 mL/(min·1.73 m2) was 36.4% (8/22), 47.6% (20/42), and 60% (3/5), respectively. Logistic regression analysis results showed that gamma-glutamyl transpeptidase [odds ratio (OR) = 1.05 (1.008-1.093), P = 0.020], direct bilirubin [OR = 1.548 (1.111-2.159), P = 0.010], serum creatinine [OR = 1.079 (1.022-1.139), P = 0.006], and age [OR = 0.981 (0.942-1.022), P = 0.357] were independent predictors of early renal injury.
CONCLUSION Patients with CHB treated with long-term nucleos(t)ide analog therapy had a high probability of early renal injury, and early renal injury indicators were highly sensitive and could be used to monitor early renal impairment.
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Affiliation(s)
- Tong-Tong Ji
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Ning Tan
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Hai-Ying Lu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Xiao-Yuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Yan-Yan Yu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
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Chou R, Blazina I, Bougatsos C, Holmes R, Selph S, Grusing S, Jou J. Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2020; 324:2423-2436. [PMID: 33320229 DOI: 10.1001/jama.2020.19750] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Importance A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited. Objective To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF. Data Sources Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection Randomized clinical trials (RCTs) on screening and antiviral therapy; cohort studies on screening, antiviral therapy clinical outcomes, and the association between achieving intermediate outcomes after antiviral therapy and clinical outcomes. Data Extraction and Synthesis One investigator abstracted data; a second investigator checked accuracy. Two investigators independently assessed study quality. Random-effects profile likelihood meta-analysis was performed. Results Thirty trials and 20 cohort studies, with a total of 94 168 participants, were included. No study directly evaluated the effects of screening for HBV infection vs no screening on clinical outcomes such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high-prevalence countries and demographic and behavioral risk factors would identify nearly all HBV infection cases. In 1 study (n = 21 008), only screening immigrants from high-prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (n = 2972), antiviral therapy compared with placebo or no treatment was associated with greater likelihood of achieving intermediate outcomes, such as virologic suppression and hepatitis B e-antigen (HBeAg) or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virologic suppression to 17 for HBeAg seroconversion. Based on 12 trials (n = 4127), first-line antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (n = 4809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (n = 3893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes but were heterogeneous (hazard ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events vs placebo or no antiviral therapy. Conclusions and Relevance There was no direct evidence for the clinical benefits and harms of HBV screening vs no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes.
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Affiliation(s)
- Roger Chou
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Division of General Internal Medicine and Geriatrics; Oregon Health & Science University, Portland
| | - Ian Blazina
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Christina Bougatsos
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Rebecca Holmes
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Shelley Selph
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Department of Family Medicine, Oregon Health & Science University, Portland
| | - Sara Grusing
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Janice Jou
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Division of Gastroenterology and Hepatology; Oregon Health & Science University, Portland
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11
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Sbarigia U, Vincken T, Wigfield P, Hashim M, Heeg B, Postma M. A comparative network meta-analysis of standard of care treatments in treatment-naïve chronic hepatitis B patients. J Comp Eff Res 2020; 9:1051-1065. [PMID: 32945178 DOI: 10.2217/cer-2020-0068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective: Published network meta-analyses of chronic hepatitis B (CHB) treatments are either out-of-date or excluded key treatments. Therefore, we aimed to comprehensively update the efficacy evidence for the following end points: Hepatitis B surface antigen (HBsAg) loss, hepatitis B early antigen (HBeAg) seroconversion and hepatitis B virus DNA (HBV DNA) suppression. Materials & methods: Approved treatments in CHB and their combinations were evaluated. A systematic literature review was conducted to identify all randomized controlled trials in treatment-naïve CHB patients. Included studies reported at least one of the end points of interest. A frequentist probability network meta-analysis was performed for each end point. The choice of fixed effect or random-effect model was based on the I-square statistic, a measure of variation in study outcomes between studies. The analyses were performed separately for HBeAg-positive and HBeAg-negative patients. For the primary analyses, end points measured 48 ± 4 weeks after treatment initiation were considered. Results: A total of 47 randomized controlled trials (13,826 patients), covering 23 unique treatment regimens, were included: a total of 29 reported HBsAg loss, 36 reported HBeAg seroconversion and 37 reported HBV DNA suppression. For both HBsAg loss and HBeAg seroconversion, pegylated interferon-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. On the other hand, for HBV DNA suppression, nucleosides-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. Conclusion: Our findings confirm available evidence around the comparative efficacy of available CHB treatments. Therefore, they can be used to update relevant cost-effectiveness analyses and clinical guidelines.
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Affiliation(s)
| | - Talitha Vincken
- Ingress-Health, Weena 316 Rotterdam, 3012NJ, The Netherlands
| | - Peter Wigfield
- Ingress-Health, Weena 316 Rotterdam, 3012NJ, The Netherlands
| | - Mahmoud Hashim
- Ingress-Health, Weena 316 Rotterdam, 3012NJ, The Netherlands
| | - Bart Heeg
- Ingress-Health, Weena 316 Rotterdam, 3012NJ, The Netherlands
| | - Maarten Postma
- Unit of PharmacoEpidemiology & PharmacoEconomics, Rijksuniversiteit Groningen - Pharmacy, Groningen, The Netherlands.,Institute of Science in Healthy Aging & healthcaRE (SHARE), Universitair Medisch Centrum Groningen, Groningen, The Netherlands.,Epidemiology, Universitair Medisch Centrum Groningen, Groningen, The Netherlands
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12
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Yu HC, Lin KH, Tsay FW, Tsai TJ, Wu PC, Chen YH, Chen YH. Kinetics of hepatitis B surface antigen and estimated glomerular filtration rate in telbivudine-treated hepatitis B patients with different rescue strategies. PLoS One 2020; 15:e0237586. [PMID: 32785260 PMCID: PMC7423127 DOI: 10.1371/journal.pone.0237586] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 07/29/2020] [Indexed: 01/09/2023] Open
Abstract
This study investigated the kinetics of estimated glomerular filtration rate (eGFR) and quantitative hepatitis B surface antigen (qHBsAg) in telbivudine (LdT)-treated chronic hepatitis B (CHB) patients whose treatment was subsequently adjusted with the adding on adefovir or by switching to tenofovir disoproxil fumarate (TDF) as rescue. Of 295 CHB patients initially treated with LdT, 102 of them who subsequently receiving either adding-on adefovir (group A, n = 58) or switching to TDF (group B, n = 44) for more than 24 months were enrolled. Serial eGFR and qHBsAg levels (3 to 6 monthly) in both LdT monotherapy and rescue therapy periods were analyzed retrospectively. Subsequent decline of qHBsAg especially in rescue therapy period were noted (p<0.001 and p = 0.068 in group A and B). However, patients in group B achieved a significant increase of eGFR (p = 0.010) in LdT monotherapy period but had a significant decline of eGFR (p<0.001) in rescue therapy period. In contrast, patients in group A maintained eGFR levels in both periods. Meanwhile, switch to TDF (hazard ratio: 3.036; 95% confidence interval: 1.040-8.861; p = 0.042) was the sole factor related to the decrease of eGFR>20% from baseline. Both rescue therapies achieved subsequent declines of qHBsAg over time but caused different changes in eGFR. LdT-based rescue therapy maintained eGFR but TDF switching therapy descended eGFR. Therefore, it is essential to monitor patient's renal function intensively when switching from LdT to TDF as a rescue strategy.
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Affiliation(s)
- Hsien-Chung Yu
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Chung Shan Medical University, Taichung, Taiwan
- Institute of Health Care Management, Department of Business Management, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Kung-Hung Lin
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Feng-Woei Tsay
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Chung Shan Medical University, Taichung, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Chung Shan Medical University, Taichung, Taiwan
| | - Pin-Chieh Wu
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yu-Hsun Chen
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yan-Hua Chen
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- * E-mail:
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13
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Wang Y, Wang M, Zhang G, Ou X, Ma H, You H, Jia J. Control of Chronic Hepatitis B in China: Perspective of Diagnosis and Treatment. China CDC Wkly 2020; 2:596-600. [PMID: 34594716 PMCID: PMC8428426 DOI: 10.46234/ccdcw2020.159] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 07/18/2020] [Indexed: 01/01/2023] Open
Affiliation(s)
- Yu Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Min Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Guanhua Zhang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Xiaojuan Ou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Hong Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
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14
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Pang X, Zhang L, Liu N, Liu B, Chen Z, Li H, Chen M, Peng M, Ren H, Hu P. Combination of pegylated interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients. Clin Exp Immunol 2020; 202:80-92. [PMID: 32638357 DOI: 10.1111/cei.13486] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/07/2020] [Accepted: 06/11/2020] [Indexed: 02/06/2023] Open
Abstract
A combination of pegylated interferon-alpha (peg-IFN-α) and nucleos(t)ides analogue (NA) therapy can effectively reduce hepatitis B surface antigen (HBsAg), especially in NA-experienced chronic hepatitis B (CHB) patients. However, the immune mechanism of this therapy is unclear. Forty NA-experienced CHB patients were enrolled into this study. The frequencies of peripheral blood natural killer (NK) cells, dendritic cells (DCs), CD4+ T cells, CD8+ T cells, T helper (Th) cells, regulatory T cells (Treg ), B cells and follicular T helper (Tfh) cells were evaluated by flow cytometry. Seven of the 40 patients converted to peg-IFN-α combined with NA treatment, while the other 33 continued to NA therapy. The decrease in HBsAg was more pronounced in the combination treatment group, and only patients receiving combination treatment achieved HBsAg loss. The frequency and absolute number of CD56bright NK cells in the combination treatment group increased significantly compared with the NA treatment group, whereas the CD56dim NK cells were decreased. In the NA treatment group, the proportions of CD4+ TN , CD8+ TN , CD19+ B and cytotoxic T lymphocyte antigen-4 (CTLA-4)+ CD4+ T cells were increased, while the proportions of CD4+ TEM , CD8+ TEM , CD25+ CD4+ Treg , CD25high CD4+ Treg , CD127low CD25+ Treg , programmed cell death 1 (PD-1)+ CD4+ T, PD-1+ CD8+ T, CTLA-4+ CD8+ T, CCR4+ CD25+ Treg and CCR4+ CD25high Treg cells were decreased after therapy. For NA-experienced CHB patients who achieved low HBsAg levels, combination treatment is more likely to result in HBsAg decline and HBsAg clearance by increasing the activity of CD56bright NK cells.
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Affiliation(s)
- X Pang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - L Zhang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - N Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - B Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Z Chen
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - H Li
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - M Chen
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - M Peng
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - H Ren
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - P Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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15
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Geng J, Bao H, Chen Y, Shi L, Geng J, Wang Q, Yu H. Nucleos(t)ide analogues for the treatment of chronic hepatitis B: a systematic review with network meta-analysis. Expert Rev Anti Infect Ther 2020; 18:823-834. [PMID: 32329638 DOI: 10.1080/14787210.2020.1760843] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVES Chronic hepatitis B (CHB) is a major global health problem caused by hepatitis B virus (HBV) infection, and can put patients at high risk of death from cirrhosis and liver cancer. However, CHB can be treated with nucleos(t)ide analogues. We aimed to evaluate the effectiveness and safety of nucleos(t)ide analogues for the treatment of CHB patients. METHODS A systematic literature search was performed. Direct comparison meta-analyses and network meta-analysis (NMA) were carried out. RESULTS Thirty-six randomized controlled trials (RCTs) met inclusion criteria. Compared with placebo, the nucleos(t)ide analogues were all effective in HBeAg seroconversion, HBeAg loss, and achieving undetectable HBV DNA. Telbivudine was associated with higher HBeAg seroconversion compared with entecavir. For HBeAg loss rate and proportion of achieving undetectable HBV DNA, tenofovir ranked as the best. Entecavir might be the most potent in the normalization of alanine aminotransferase (ALT). The nucleos(t)ide analogues did not have higher serious adverse events rate as compared with placebo. CONCLUSION The nucleos(t)ide analogues are all effective for HBeAg seroconversion, HBeAg loss, undetectable HBV DNA, and most are effective for ALT normalization in adults with CHB. RCTs of multi-center, low risk of bias, and long-term follow-up are still needed.
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Affiliation(s)
- JinSong Geng
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - HaiNi Bao
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - YaLan Chen
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - LiLi Shi
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - Jing Geng
- Department of Gastroenterology, Lianyungang No 1 People's Hospital , Jiangsu, China
| | - Qing Wang
- Department of Infectious Disease, Ningxiang People's Hospital , Hunan, China
| | - Hao Yu
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston, MA, USA
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16
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Shen Y, Jia Y, Zhou J, Ji J, Xun P. Bayesian Network Meta-Analysis for Assessing Adverse Effects of Anti-hepatitis B Drugs. Clin Drug Investig 2020; 39:835-846. [PMID: 31228017 DOI: 10.1007/s40261-019-00802-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVE Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their adverse events. Therefore, a Bayesian network meta-analysis (NMA) was performed to evaluate the relative safety of five NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate) in CHB treatment among adults. METHODS Eligible randomized clinical trials (RCTs) and prospective cohort studies were systematically and thoroughly searched until May 1, 2019. Poisson-prior-based Bayesian NMA was performed to synthesize both direct and indirect evidence with reporting hazard ratios (HRs) and 95% credible intervals (CrIs) for serious adverse events (SAEs) and hepatic/renal impairments. RESULTS Thirty-three RCTs and 11 prospective cohort studies were identified. As to SAEs, no statistically significant difference was found of any comparison among five NAs. In terms of hepatotoxicity, lamivudine was safer than telbivudine (HR 0.45; 95% CrI 0.21, 0.85), and entecavir increased the risk by 102% (entecavir vs lamivudine: HR 2.02; 95% CrI 1.19, 3.27). CONCLUSIONS The findings from this large NMA could influence clinical practice, and the methodological framework of this study could provide evidence-based support to analyze sparse safety data in the field.
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Affiliation(s)
- Yi Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, China
| | - Yulong Jia
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, China
| | - Jie Zhou
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, China
| | - Juling Ji
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, China.
- Medical School of Nantong University, No. 19, Qixiu Rd, Nantong, Jiangsu, 226001, China.
| | - Pengcheng Xun
- Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, 1025 E 7th Street C103, Bloomington, IN, 47405, USA.
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17
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Adverse events of nucleos(t)ide analogues for chronic hepatitis B: a systematic review. J Gastroenterol 2020; 55:496-514. [PMID: 32185517 PMCID: PMC7188775 DOI: 10.1007/s00535-020-01680-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 02/26/2020] [Indexed: 02/04/2023]
Abstract
Nucleos(t)ide analogues (NAs) are the main drug category used in chronic hepatitis B (CHB) treatment. Despite the fact that NAs have a favourable safety profile, undesired adverse events (AEs) may occur during the treatment of CHB. Given the eminent number of patients currently receiving NAs, even a small risk of any of these toxicities can represent a major medical issue. The main objective of this review was to analyse information available on AEs associated with the use of NAs in published studies. We choose the following MesH terms for this systematic review: chronic hepatitis B, side effects and treatment. All articles published from 1 January 1990 up to 19 February 2018 in MEDLINE of PubMed, EMBASE, the Cochrane Library and LILACS databases were searched. A total of 120 articles were selected for analysis, comprising 6419 patients treated with lamivudine (LAM), 5947 with entecavir (ETV), 3566 with tenofovir disoproxil fumarate (TDF), 3096 with telbivudine (LdT), 1178 with adefovir dipivoxil (ADV) and 876 with tenofovir alafenamide (TAF). The most common AEs in all NAs assessed were abdominal pain/discomfort, nasopharyngitis/upper respiratory tract infections, fatigue, and headache. TAF displays the highest density of AEs per patient treated among NAs (1.14 AE/treated patient). In conclusion, treatment of CHB with NAs is safe, with a low incidence of AEs. Despite the general understanding TAF being safer than TDF, the number of patients treated with TAF still is too small in comparison to other NAs to consolidate an accurate safety profile. PROSPERO Registration No. CRD42018086471.
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18
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Lee SH, Cheon GJ, Kim HS, Kim SG, Kim YS, Jeong SW, Jang JY, Kim BS, Jun BG, Don Kim Y, Jun DW, Sohn JH, Kim TY, Lee BS. Tenofovir disoproxil fumarate monotherapy is superior to entecavir-adefovir combination therapy in patients with suboptimal response to lamivudine-adefovir therapy for nucleoside-resistant HBV: a 96-week prospective multicentre trial. Antivir Ther 2019; 23:219-227. [PMID: 28436380 DOI: 10.3851/imp3169] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/07/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND A complete virological response is closely related to the long-term outcome of patients with chronic hepatitis B and prevention of emerging HBV mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy compared to entecavir-adefovir dipivoxil (ETV-ADV) combination therapy in patients with suboptimal responses to long-term lamivudine-adefovir dipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis B. METHODS Patients (n=60) were randomized to TDF monotherapy or ETV-ADV combination therapy for 96 weeks. All patients had the rt204I/V mutation and serum HBV DNA was measured (>60 IU/ml) during LAM-ADV therapy. The primary end point was a complete virological response (HBV DNA <20 IU/ml) at week 96. RESULTS The median duration of prior LAM-ADV rescue therapy was 43 (7-108) months. A complete virological response was achieved in 86.6% and 53.3% of patients in the TDF and ETV-ADV groups, respectively, at week 96 (P=0.005). Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV-ADV group (-3.2 ±1.2 versus -2.6 ±1.2; P=0.01). Hepatitis B e antigen loss (22.2% versus 16.6%; P=0.731) and biochemical responses (76.7% versus 73.3%; P=0.766) were not different between the TDF and ETV-ADV groups. No newly emerged mutations were detected. Both therapies demonstrated favourable safety profiles. CONCLUSIONS TDF therapy achieved a better complete virological response than ETV-ADV therapy in chronic hepatitis B patients with suboptimal response to long-term LAM-ADV rescue therapy. (KCT0000627).
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Affiliation(s)
- Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Gab Jin Cheon
- Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Boo Sung Kim
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Korea
| | - Young Don Kim
- Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Tae Yeob Kim
- Institute of Medical Science, Hanyang University, Seoul, Korea
| | - Byung Seok Lee
- Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea
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19
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Wong WWL, Pechivanoglou P, Wong J, Bielecki JM, Haines A, Erman A, Saeed Y, Phoon A, Tadrous M, Younis M, Rayad NZ, Rac V, Janssen HLA, Krahn MD. Antiviral treatment for treatment-naïve chronic hepatitis B: systematic review and network meta-analysis of randomized controlled trials. Syst Rev 2019; 8:207. [PMID: 31426837 PMCID: PMC6699129 DOI: 10.1186/s13643-019-1126-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 08/04/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main goal of current therapy is to improve survival and quality of life by preventing disease progression to cirrhosis and liver failure, and consequently hepatocellular carcinoma development. The objective of this review is to provide a contemporary and comprehensive evaluation of the effectiveness of treatment options. METHODS We performed a systematic review of peer-reviewed literature for randomized controlled trials involving treatment-naïve CHB adult population who received antiviral therapy. The endpoints were virologic response (VR), normalization of alanine aminotransferase (ALT norm), HBeAg loss, HBeAg seroconversion, and HBsAg loss for the HBeAg-positive population; and VR and ALT norm for the HBeAg-negative population. Network meta-analysis (NMA) was performed to synthesize evidence on the efficacy of treatment. RESULTS Forty-two publications were selected. Twenty-three evaluated HBeAg-positive population, 13 evaluated HBeAg-negative population, and six evaluated both. We applied NMA to the efficacy outcomes of the two populations separately. Treatment strategies were ranked by the probability of achieving outcomes, and pairwise comparisons calculated from NMA were reported in odds ratios (OR). For HBeAg-positive population, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) were the best for VR; OR vs adefovir = 14.29, 95% CI 7.69-25 and 12.5, 95% CI 4.35-33.33 respectively. TAF was the best for achieving ALT norm (OR vs placebo = 12.5, 95% CI 4.55-33.33), HBeAg loss, and seroconversion (OR vs entecavir/TDF combination = 3.03, 95% CI 1.04-8.84 and 3.33, 95% CI 1.16-10 respectively). In the HBeAg-negative population, TDF and TAF were the best for VR (OR vs adefovir = 9.79, 95% CI 2.38-42.7 and 11.71, 95% CI 1.03-150.48 respectively). Telbivudine and TAF were the best for ALT norm. Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes. CONCLUSIONS Our results are consonant with current clinical guidelines and other evidence reviews. For both HBeAg-positive and HBeAg-negative populations, TDF and TAF are the most effective agents for virologic suppression, and TAF is effective across all outcomes.
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Affiliation(s)
- William W L Wong
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada. .,University of Waterloo, School of Pharmacy, Waterloo, ON, Canada. .,University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON, Canada.
| | - Petros Pechivanoglou
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada.,The Hospital for Sick Children, Toronto, ON, Canada
| | - Josephine Wong
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada
| | - Joanna M Bielecki
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada
| | - Alex Haines
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada
| | - Aysegul Erman
- University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON, Canada
| | - Yasmin Saeed
- University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON, Canada
| | - Arcturus Phoon
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada
| | - Mina Tadrous
- University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON, Canada.,The Ontario Drug Policy Research Network, St. Michael's Hospital, Toronto, ON, Canada
| | - Mona Younis
- University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON, Canada
| | - Noha Z Rayad
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada.,BioPharma Services Inc, Toronto, ON, Canada
| | - Valeria Rac
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada.,Ted Rogers Centre for Heart Research at Peter Munk Cardiac Centre, Toronto General Hospital Research Institute (TGHRI), University Health Network (UHN), Toronto, Canada.,Institute of Health Policy, Management and Evaluation (IHPME), Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.,Diabetes Action Canada, CIHR SPOR Network, Toronto, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
| | - Murray D Krahn
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto and University Health Network, Toronto, ON, Canada.,University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON, Canada
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20
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Liang X, Gao Z, Xie Q, Zhang J, Sheng J, Cheng J, Chen C, Mao Q, Zhao W, Ren H, Tan D, Niu J, Chen S, Pan C, Tang H, Wang H, Mao Y, Jia J, Ning Q, Xu M, Wu S, Li J, Zhang X, Zhang W, Xiong C, Hou J. Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results. Hepatol Int 2019; 13:260-269. [PMID: 30977033 PMCID: PMC6529393 DOI: 10.1007/s12072-019-09943-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 03/13/2019] [Indexed: 02/05/2023]
Abstract
Background and aim Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection. Methods Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF–TDF and ADV–TDF groups) for additional 192 weeks. Results Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF–TDF and ADV–TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF–TDF than in ADV–TDF group, respectively. Only one HBeAg-positive patient in TDF–TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF–TDF, 56.4% vs. ADV–TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL). Conclusion In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648. Electronic supplementary material The online version of this article (10.1007/s12072-019-09943-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xieer Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Zhiliang Gao
- 3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Qing Xie
- Ruijin Hospital Affiliated to Jiaotong University, School of Medicine, Shanghai, China
| | - Jiming Zhang
- Huashan Hospital Affiliated to Fudan University, Shanghai, China
| | - Jifang Sheng
- 1st Affiliated Hospital of ZheJiang University, Hangzhou, China
| | - Jun Cheng
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Chengwei Chen
- Shanghai the 85th Hospital Affiliated to Nanjing Military, Shanghai, China
| | - Qing Mao
- Southwest Hospital, Army Medical University, Chongqing, China
| | - Wei Zhao
- 2nd Hospital of Nanjing, Nanjing, China
| | - Hong Ren
- 2nd Affiliated Hospital Chongqing Medical University, Chongqing, China
| | - Deming Tan
- Xiangya Hospital Central-South University, Changsha, China
| | - Junqi Niu
- 1st Affiliated Hospital of Jilin University, Changchun, China
| | - Shijun Chen
- Jinan Hospital for Infectious Disease, Jinan, China
| | - Chen Pan
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian Sheng, China
| | - Hong Tang
- West China Hospital, Sichuan University, Chengdu, China
| | - Hao Wang
- Peking University People's Hospital, Beijing, China
| | - Yimin Mao
- RenJi Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital University, Beijing, China
| | - Qin Ning
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Xu
- Guangzhou Eighth Municipal People's Hospital, Guangzhou, China
| | - Shanming Wu
- Shanghai Public Health Clinical Center, Shanghai, China
| | - Jun Li
- The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xinxin Zhang
- Ruijin Hospital Affiliated to Jiaotong University, School of Medicine, Shanghai, China
| | - Wenyan Zhang
- GlaxoSmithKline R&D Company Limited, Shanghai, China
| | - Cui Xiong
- GlaxoSmithKline R&D Company Limited, Shanghai, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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21
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Sarkar J, Saha D, Bandyopadhyay B, Saha B, Chakravarty R, Guha SK. Lamivudine plus tenofovir versus lamivudine plus adefovir for the treatment of hepatitis B virus in HIV-coinfected patients, starting antiretroviral therapy. Indian J Med Microbiol 2018; 36:217-223. [PMID: 30084414 DOI: 10.4103/ijmm.ijmm_17_37] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and efavirenz (EFV) is preferred in the treatment of HIV/hepatitis B virus (HBV) coinfection. We postulated that a HBV active nucleoside reverse transcriptase (RT) inhibitor/nucleotide RT inhibitor backbone of adefovir dipivoxil (ADV) +3TC would be as effective as TDF +3TC for the Indian population. Objective ADV + 3TC could be an alternative option for these HIV/HBV coinfected individuals, preserving the dually active TDF + 3TC as second-line nucleoside backbone following failure of the first-line ART. Materials and Methods This randomised control trial (CTRI/2012/03/002471) was carried out at the ART Centre of Calcutta School of Tropical Medicine, India. Seventy-eight (39 on each arm) treatment-naïve HIV/HBV coinfected patients were randomised to receive either the combination of lamivudine + tenofovir + EFV or lamivudine + adefovir + zidovudine + EFV and followed up for 120 weeks. Results Median age of the study participants was 36 years (21-62), majority were male (61/78; 78.2%) and heterosexually (39/78; 50%) infected. Baseline characteristics were identical in both arms. There was no statistically significant difference in median aspartate aminotransferase (37 vs. 29.5 U/L), alanine aminotransferase (ALT) (36 vs. 34.5 U/L), ALT normalisation rate (80 vs. 70%), AST to platelet ratio index (0.45 vs. 0.33), CD4 count (508 vs. 427 cells/mm3), HBV DNA suppression (81.8 vs. 70%), hepatitis B e antigen loss (9 vs. 5%), hepatitis B surface antigen seroclearance rate (6.06 vs. 18.75%) and death (3 vs. 3) at 120 weeks between TDF (n = 33) and ADV (n = 32), respectively. Conclusions Adefovir plus lamivudine is an effective alternative of tenofovir plus lamivudine in long-term HBV treatment outcome in HIV/HBV coinfected patients.
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Affiliation(s)
- Jayeeta Sarkar
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
| | - Debraj Saha
- Department of Virology ICMR Virus Unit, ID and BG Hospital Campus, Kolkata, West Bengal, India
| | - Bhaswati Bandyopadhyay
- Department of Microbiology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
| | - Bibhuti Saha
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
| | - Runu Chakravarty
- Department of Virology ICMR Virus Unit, ID and BG Hospital Campus, Kolkata, West Bengal, India
| | - Subhasish Kamal Guha
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
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22
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Wong RJ, Nguyen MT, Trinh HN, Chan C, Huynh A, Ly MT, Nguyen HA, Nguyen KK, Torres S, Yang J, Liu B, Garcia RT, Bhuket T, Baden R, Levitt B, da Silveira E, Gish RG. Hepatitis B surface antigen loss and sustained viral suppression in Asian chronic hepatitis B patients: A community-based real-world study. J Viral Hepat 2017; 24:1089-1097. [PMID: 28581644 DOI: 10.1111/jvh.12736] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 05/09/2017] [Indexed: 12/19/2022]
Abstract
Community-based real-world outcomes on effectiveness of antiviral therapies for chronic hepatitis B virus (CHB) in Asians are limited. Whether hepatitis B surface antigen (HBsAg) loss correlates with undetectable virus and alanine aminotransferase (ALT) normalization on treatment or what predicts risk of seroreversion or detectable virus after stopping therapy is unclear. We aim to evaluate rates and predictors of HBsAg loss, seroconversion, ALT normalization and undetectable HBV DNA, including HBsAg seroreversion or re-emergence of HBV DNA among Asian CHB patients. We retrospectively evaluated 1072 CHB adults on antiviral therapy at two community gastroenterology clinics from 1997 to 2015. Rates of HBsAg loss, ALT normalization, achieving undetectable HBV DNA and developing surface antibody (anti-HBs) were stratified by HBeAg status. Following HBsAg loss, HBsAg seroreversion or re-emergence of detectable HBV DNA was analysed. With median treatment of 76.7 months, the overall rate of HBsAg loss was 4.58%, with similar HBsAg loss rates between HBeAg-positive and HBeAg-negative patients (4.44% vs 4.71%, P=.85) in a predominantly Asian population (98.1%). Among HBsAg loss patients, 33.3% developed anti-HBs, 95.8% achieved undetectable virus and 66.0% normalized ALT. No significant baseline or on-treatment predictors of HBsAg loss were observed. While six patients who achieved HBsAg loss had seroreversion with re-emergence of HBsAg positivity, viral load remained undetectable, demonstrating the sustainability of viral suppression. Among a large community-based real-world cohort of Asian CHB patients treated with antiviral therapy, rate of HBsAg loss was 4.58%. Despite only 33.3% of HBsAg loss patients achieving anti-HBs, nearly all patients achieved sustained undetectable virus.
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Affiliation(s)
- R J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - M T Nguyen
- Silicon Valley Research Institute, San Jose, CA, USA
| | - H N Trinh
- San Jose Gastroenterology, San Jose, CA, USA
| | - C Chan
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - A Huynh
- Silicon Valley Research Institute, San Jose, CA, USA
| | - M T Ly
- Silicon Valley Research Institute, San Jose, CA, USA
| | - H A Nguyen
- San Jose Gastroenterology, San Jose, CA, USA
| | - K K Nguyen
- San Jose Gastroenterology, San Jose, CA, USA
| | - S Torres
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - J Yang
- San Jose Gastroenterology, San Jose, CA, USA
| | - B Liu
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - R T Garcia
- San Jose Gastroenterology, San Jose, CA, USA
| | - T Bhuket
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - R Baden
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - B Levitt
- San Jose Gastroenterology, San Jose, CA, USA
| | | | - R G Gish
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA.,Hepatitis B Foundation, Doylestown, PA, USA
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23
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Zeng N, Zou C, He Z, Ma H, Ou X, You H, Kong Y, Jia J. Systematic review on the reporting quality of randomized controlled trials in patients with hepatitis B or C in China. Int J Infect Dis 2017; 67:58-64. [PMID: 29138012 DOI: 10.1016/j.ijid.2017.11.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 10/31/2017] [Accepted: 11/03/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The numbers of articles reporting randomized controlled trials (RCTs) on viral hepatitis in China have been increasing, but there have been few systematic studies evaluating the reporting quality of RCTs in this field. This study was performed to assess the reporting quality of RCTs on the treatment of hepatitis B and C in China from 1991 to 2015. METHODS Articles published between January 1991 and December 2015 were identified via the PubMed, MEDLINE, and Embase databases using the key words "randomized clinical trials", "treatment", "therapy", "hepatitis B", "HBV", "hepatitis C", "HCV", "China", and "Chinese". The reporting quality was assessed against the Consolidated Standards of Reporting Trials (CONSORT) checklist. RESULTS In total, 211 RCTs on the treatment of hepatitis B or C were included. The number of articles focusing on these RCTs increased rapidly over time, while the reporting quality improved steadily over time. Overall, compliance with the key components of the CONSORT checklist was low, with only 8.5%, 3.8%, and 11.4% of the articles fulfilling the reporting requirements of randomization, allocation concealment, and blinding, respectively. CONCLUSIONS Both the number and the quality of RCT articles were found to have increased steadily over the last two decades. However, compliance with the key components of the CONSORT checklist still needs improvement. It is hoped that the results of this study will lead to improvements in the reporting quality of clinical trials on hepatitis B and C in China.
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Affiliation(s)
- Na Zeng
- Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing, China
| | - Cailun Zou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing, China
| | - Zhiying He
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing, China
| | - Hong Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing, China
| | - Xiaojuan Ou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing, China.
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing, China.
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24
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Yu YJ. Tenofovir dipivoxil for treatment of chronic hepatitis B patients with gastric ulcer: Efficacy and impact on host immune response. Shijie Huaren Xiaohua Zazhi 2017; 25:1079-1082. [DOI: 10.11569/wcjd.v25.i12.1079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the clinical efficacy of tenofovir dipivoxil in chronic hepatitis B (CHB) patients with gastric ulcer and its effect on host immune response.
METHODS From January 2015 to October 2015, 60 CHB patients with gastric ulcer were randomly divided into a control group (n = 30) and an observation group (n = 30). The control group was treated with adefovir dipivoxil, and the observation group was treated with tenofovir dipivoxil. The immune levels before and after treatment were measured by flow cytometry. The clinical efficacy and the effect on the host immune response were compared between the two groups.
RESULTS There was no significant difference in the rate of viral breakthrough between the two groups (P > 0.05). The ALT normalization rate, HBV DNA negative convsersion rate and HBeAg seroconversion rate in the observation group were significantly higher than those in the control group (P < 0.05). The percentages of CD4+ and CD8+ cells and CD4+/CD8+ ratio in the observation group were significantly higher than those in the control group (P < 0.05). The incidence of adverse reactions was 10.00% in the observation group and 13.33% in the control group. There was no significant difference in the incidence of adverse drug reactions between the two groups (P > 0.05).
CONCLUSION Tenofovir dipivoxil has good efficacy in CHB patients with gastric ulcer and can be used to regulate immunity.
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25
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Cost-Effectiveness Comparison Between the Response-Guided Therapies and Monotherapies of Nucleos(t)ide Analogues for Chronic Hepatitis B Patients in China. Clin Drug Investig 2017; 37:233-247. [PMID: 27928739 DOI: 10.1007/s40261-016-0486-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVE Nucleos(t)ide analogue (NA) monotherapies are typically used as the primary treatment for chronic hepatitis B (CHB) patients, including lamivudine (LAM), telbivudine (TBV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF). For high-resistance NAs (LAM, TBV, ADV), they can generate excellent clinical outcomes by using response-guided therapy; however, their pharmacoeconomic profiles remain unclear in China. We aimed to evaluate the cost effectiveness between response-guided therapies and monotherapies of NAs for Chinese hepatitis B e-antigen (HBeAg)-positive and -negative CHB patients. METHODS We constructed a Markov model to simulate CHB progression associated with 12 treatment strategies using effectiveness and cost data from the published literature. We measured the lifetime costs, quality adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity (especially to extend the range of the TDF price) and probabilistic sensitivity analyses were used to explore the uncertainties of the model. RESULTS For both HBeAg-positive and -negative patients, no treatment strategy generated the lowest lifetime costs (US$31,185-US$31,338) and QALYs (7.54-7.58). ETV and TDF monotherapies were not dominated by other treatments, whereas, the ICER of ETV monotherapy was the lowest (US$6112/QALY-US$8533/QALY). For each high-resistance NA, compared with its monotherapy, the ICERs of its response-guided therapies were below the willingness-to-pay threshold of US$22,833/QALY. Additionally, TDF monotherapy was the preferred treatment when its price dropped to US$1820/year or lower. CONCLUSION Among 12 treatment strategies evaluated, ETV monotherapy is the most cost-effective treatment for treatment-naive CHB patients in China. The response-guided therapies of high-resistance NAs are more cost-effective than their monotherapies.
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26
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Xing T, Xu H, Cao L, Ye M. HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis. PLoS One 2017; 12:e0169444. [PMID: 28107377 PMCID: PMC5249087 DOI: 10.1371/journal.pone.0169444] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 12/17/2016] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND HBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide analogs (NAs) on HBeAg seroconversion in treating CHB with lamivudine, adefovir, telbivudine, entecavir, and tenofovir. METHODS Network meta-analysis of NA treatment-induced HBeAg seroconversion after 1-2 years of treatment was performed. In addition, NA treatment-induced HBeAg seroconversion after 3-5 years of treatment was systematically evaluated. RESULTS A total of 31 articles were included in this study. Nine and five studies respectively reporting on 1- and 2-year treatment were included in our network meta-analysis. In addition, 6, 5, and 5 studies, respectively reporting on 3-, 4-, and 5-year treatment were included in our systematic evaluation. Telbivudine showed a significantly higher HBeAg seroconversion rate after a 1 year treatment period compared to the other NAs (odds ratio (OR) = 3.99, 95% CI 0.68-23.6). This was followed by tenofovir (OR = 3.36, 95% CI 0.70-16.75). Telbivudine also showed a higher seroconversion rate compared to the other NAs after a 2 year treatment period, (OR = 1.38, 95% CI 0.92-2.22). This was followed by entecavir (OR = 1.14, 95% CI 0.72-1.72). No significant difference was observed between spontaneous induction and long-term telbivudine treatment-induced HBeAg seroconversion. However, entecavir and tenofovir treatment-induced HBeAg seroconversions were significantly lower than spontaneous seroconversion. CONCLUSION Long-term treatment with potent anti-HBV drugs, especially tenofovir and entecavir, may reduce HBeAg seroconversion compared with spontaneous HBeAg seroconversion rate. Telbivudine treatment, whether short term or long term, is associated with higher HBeAg seroconversion compared with the other NAs. However, the high rates of drug resistance likely limit the application of telbivudine.
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Affiliation(s)
- Tongjing Xing
- Department of Infectious Diseases, Taizhou People’s Hospital, Taizhou, Jiangsu Province, China
| | - Hongtao Xu
- Department of Infectious Diseases, Taizhou People’s Hospital, Taizhou, Jiangsu Province, China
| | - Lin Cao
- Department of Infectious Diseases, Taizhou People’s Hospital, Taizhou, Jiangsu Province, China
| | - Maocong Ye
- Department of Infectious Diseases, Taizhou People’s Hospital, Taizhou, Jiangsu Province, China
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27
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Song BC. Switch to tenofovir-based therapy or to continue adefovir-based therapy in CHB patients with suboptimal response to adefovir-based combination? Clin Mol Hepatol 2016; 22:439-442. [PMID: 28081595 PMCID: PMC5266348 DOI: 10.3350/cmh.2016.0108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 12/01/2016] [Indexed: 11/16/2022] Open
Affiliation(s)
- Byung-Cheol Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
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Zhang L, Zhang FK. Treatment of chronic hepatitis B with tenofovir. Shijie Huaren Xiaohua Zazhi 2016; 24:4279-4287. [DOI: 10.11569/wcjd.v24.i31.4279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Tenofovir (TDF) is a potent hepatitis B virus (HBV) inhibitor with a high barrier to drug resistance, and it has been recommended as one of the first-line drugs to treat chronic hepatitis B (CHB). This paper reviews the recent advances in the treatment of CHB with TDF, especially in terms of its efficacy as first-line and second-line antiviral therapies as well as its role in the prevention of mother-to-child HBV transmission.
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Ke W, Zhang C, Liu L, Gao Y, Yao Z, Ye X, Zhou S, Yang Y. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China. Hepatol Int 2016; 10:924-936. [PMID: 27271357 DOI: 10.1007/s12072-016-9741-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 05/17/2016] [Indexed: 12/26/2022]
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. METHODS Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. RESULTS In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. CONCLUSIONS For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained.
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Affiliation(s)
- Weixia Ke
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China
| | - Chi Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China
| | - Li Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China
| | - Yanhui Gao
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China
| | - Zhenjiang Yao
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China
| | - Xiaohua Ye
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China
| | - Shudong Zhou
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China
| | - Yi Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, Guangdong, China.
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Banerjee S, Gunda P, Drake RF, Hamed K. Telbivudine for the treatment of chronic hepatitis B in HBeAg-positive patients in China: a health economic analysis. SPRINGERPLUS 2016; 5:1719. [PMID: 27777855 PMCID: PMC5052247 DOI: 10.1186/s40064-016-3404-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Accepted: 09/28/2016] [Indexed: 01/13/2023]
Abstract
BACKGROUND Nucleos(t)ide analogs (NUCs) are the standard of care for chronic hepatitis B (CHB). The present analysis aimed to determine the cost effectiveness of NUCs in Chinese healthcare settings. METHODS A Markov model was used to simulate two therapeutic strategies for a hypothetical patient cohort diagnosed with hepatitis B e antigen-positive CHB, unwilling or unable to receive interferon therapy, and about to start treatment with any NUC. The first strategy included NUC monotherapy without sequencing (telbivudine [LDT], entecavir [ETV], tenofovir [TDF], lamivudine [LAM], adefovir dipivoxil [ADV], and combination therapies of either LDT and ADV or LDT and TDF, followed by best supportive care [BSC]). The second strategy included sequential therapies of individual NUCs: LAM → ADV, ADV → LAM, LDT → ADV, and ETV → ADV, followed by BSC. The analysis included two scenarios: with and without costs due to nephrotoxicity. Renal impact was quantified as costs alone, without consideration for quality of life decrements. RESULTS When renal impact was not considered, without treatment sequencing, LDT was cost effective compared with other NUCs. Amongst the strategies with sequencing, LDT → ADV was cost effective. The results were similar when renal impact was considered. However, LDT strategy demonstrated better cost effectiveness. In probabilistic sensitivity analysis, in both scenarios, LDT → ADV sequence was cost effective with 51 % probability even at willingness to pay of $20,000. CONCLUSION Use of LDT, as compared with other NUCs, is cost effective in CHB treatment in Chinese healthcare settings. Considering the detrimental renal impact, overall costs for all treatment options were increased. However, the increase for LDT was comparatively small.
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Affiliation(s)
- S Banerjee
- Novartis Healthcare Pvt. Ltd., Hyderabad, India
| | - P Gunda
- Novartis Healthcare Pvt. Ltd., Hyderabad, India
| | - R F Drake
- Novartis Pharma AG, Basel, Switzerland
| | - K Hamed
- Novartis Pharmaceuticals Corporation, East Hanover, NJ USA
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Zhang C, Ke W, Liu L, Gao Y, Yao Z, Ye X, Zhou S, Yang Y. Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients. Drug Des Devel Ther 2016; 10:897-910. [PMID: 27041994 PMCID: PMC4780199 DOI: 10.2147/dddt.s98200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND/AIM Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). METHODS To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. RESULTS In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. CONCLUSION ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.
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Affiliation(s)
- Chi Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
| | - Weixia Ke
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
| | - Li Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
| | - Yanhui Gao
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
| | - Zhenjiang Yao
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
| | - Xiaohua Ye
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
| | - Shudong Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
| | - Yi Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
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Al-hamoudi WK. Hepatitis B management: it is time to change the strategy. Saudi J Gastroenterol 2014; 20:331-2. [PMID: 25434312 PMCID: PMC4271006 DOI: 10.4103/1319-3767.145313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Waleed K. Al-hamoudi
- Associate Professor, Gastroenterology and Hepatology Unit (59), Department of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia E-mail:
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