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Fonseca MA, Ling JZJ, Al-Siyabi O, Co-Tanko V, Chan E, Lim SG. The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta-analysis. J Viral Hepat 2020; 27:650-662. [PMID: 32170983 DOI: 10.1111/jvh.13283] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 11/20/2019] [Accepted: 01/13/2020] [Indexed: 02/06/2023]
Abstract
Current therapies for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) and interferon (IFN), but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence, we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination. We searched PubMed, EMBASE and abstracts from EASL, Asia Pacific Association for study of the Liver and American Association for the Study of Liver Disease for randomized controlled trials of CHB patients, comparing NA, IFN or the combination. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, IFN dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata, and HBsAg loss was measured at the end-of-study (EOS), end-of-treatment (EOT) or end-of-follow-up (EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random-effects model. Forty-five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination vs IFN, RD = 1%, 95%CI-1%, 2%; combination vs NA, RD = 5%, 95%CI 3%,7%; IFN vs NA, RD = 3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose vs nonstandard; IFN duration ≥48 weeks vs <48 weeks, and loss of efficacy >2 years of follow-up. Similar findings were seen in HBsAg seroconversion, but only three studies reported HBsAg seroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48 weeks of therapy, although this effect faded over time.
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Affiliation(s)
- Mariana Alves Fonseca
- Hospital DivinaProvidência, Porto Alegre, Brazil.,Hospital Moinhos de Vento, Porto Alegre, Brazil
| | - Joanna Zhi Jie Ling
- Royal Melbourne Institute of Technology, Melbourne, Vic., Australia.,Singapore Clinical Research Institute, Singapore City, Singapore
| | - Omar Al-Siyabi
- Division of Gastroenterology and Hepatology, Department of Medicine, Royal Hospital, Oman Muscat, Oman
| | - Vanessa Co-Tanko
- Division of Gastroenterology and Hepatology, Department of Medicine, UP-Philippine General Hospital, Manila, Philippines
| | - Edwin Chan
- Singapore Clinical Research Institute, Singapore City, Singapore.,Duke-NUS Medical School, Singapore City, Singapore
| | - Seng Gee Lim
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore City, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
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Zhu F, Zhang Q, Zhang Q, Zhang D. Effects of IFN monotherapy versus combined therapy on HBeAg seroconversion or seroclearance in HBeAg-positive chronic hepatitis B patients: A meta-analysis. Microb Pathog 2019; 139:103912. [PMID: 31816402 DOI: 10.1016/j.micpath.2019.103912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 12/01/2019] [Accepted: 12/03/2019] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive chronic hepatitis B (CHB) patients. To evaluate the effect of combination therapy [interferon (IFN) plus nucleos(t)ide analogues (NAs)] versus IFN monotherapy on HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. METHODS All available controlled clinical studies, published from Jan 2000 to Sep 2018, with CHB receiving IFN and NA combination therapy or IFN monotherapy were included. Risk ratio (RR) and their 95% confidence intervals (CIs) was estimated with a fixed-effects model when I2 <50% for the test for heterogeneity. Publication bias was measured using Egger's test. RESULTS Twelve studies were included. Our meta-analysis demonstrated that IFN and NA combination therapy had a superior HBeAg seroconversion rate or clearance rate compared with IFN monotherapy at the end of treatment (EOT). Sub-analysis showed IFN plus adefovir dipivoxi (ADV) therapy had a better HBeAg seroconversion or seroclearance rate at EOT or at the end of follow-up (EOF). CONCLUSION Compared with IFN monotherapy, the combined therapy had a higher e-antigen serological response at EOT, but failed to improve the sustained response at EOF. Only combination therapy with IFN and ADV is superior to IFN monotherapy at the EOT or EOF for HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. The effect of other combination therapies is not superior to IFN monotherapy.
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Affiliation(s)
- Feng Zhu
- Department of Infectious Disease, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Qiongfang Zhang
- Department of Infectious Disease, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Qiongyue Zhang
- Department of Infectious Disease, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Dazhi Zhang
- Department of Infectious Disease, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
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Cannizzo ES, Tincati C, Binda F, Ronzi P, Cazzaniga FA, Antinori S, d'Arminio Monforte A, Marchetti G, Milazzo L. Unconventional T cells in chronic hepatitis B patients on long-term suppressive therapy with tenofovir followed by a Peg-IFN add-on strategy: A randomized study. J Viral Hepat 2018; 25:381-390. [PMID: 29091327 DOI: 10.1111/jvh.12820] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 09/19/2017] [Indexed: 12/21/2022]
Abstract
HBV eradication in chronic hepatitis B (CHB) subjects is rarely achieved with either nucleos(t)ide analogues (NA) or pegylated interferon (Peg-IFN), which both have a limited effect in restoring immune responses. Thirty CHB subjects on long-term treatment with tenofovir (TDF) and HBV suppression were enrolled and randomized 1:2 to either receive Peg-IFN-α-2a add-on therapy or continue TDF alone. We studied γδ T and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment. A higher reduction in qHBsAg occurred in the add-on group compared with the NA group at W12 (P = .016) and at W24 (P = .012). A decline of qHBsAg ≥0.5 log10 at week 24 occurred in 4 of 10 patients in the add-on arm and 1 of 20 in the NA arm, respectively (P = .03). HBsAg loss was seen in 20% of subjects in the add-on group and in none of the NA group. Compared to HBV negative, CHB on TDF showed lower frequency of iNKT (P = .03) and γδ T cells (P = .03) as well as fewer γδ T cells expressing Vδ2 T-cell receptors (P = .005). No changes in unconventional T-cell frequency and function were shown in both add-on and NA patients nor were differences detected between the two treatment groups. We report persistent impairment of unconventional T cells in CHB. Despite a greater qHBsAg decline of add-on patients, our data failed to detect any effect of Peg-IFN treatment on unconventional T cells.
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Affiliation(s)
- E S Cannizzo
- Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
| | - C Tincati
- Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
| | - F Binda
- Department of Clinical and Biomedical Sciences Luigi Sacco, III Division of Infectious Diseases, University of Milan, Milan, Italy
| | - P Ronzi
- Department of Clinical and Biomedical Sciences Luigi Sacco, III Division of Infectious Diseases, University of Milan, Milan, Italy
| | - F A Cazzaniga
- Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
| | - S Antinori
- Department of Clinical and Biomedical Sciences Luigi Sacco, III Division of Infectious Diseases, University of Milan, Milan, Italy
| | - A d'Arminio Monforte
- Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
| | - G Marchetti
- Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy
| | - L Milazzo
- Department of Clinical and Biomedical Sciences Luigi Sacco, III Division of Infectious Diseases, University of Milan, Milan, Italy
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Wong GLH, Wong VWS, Chan HLY. Combination therapy of interferon and nucleotide/nucleoside analogues for chronic hepatitis B. J Viral Hepat 2014; 21:825-34. [PMID: 25402543 DOI: 10.1111/jvh.12341] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 09/09/2014] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis B is one of the leading causes of cirrhosis and hepatocellular carcinoma globally. At present, seven drugs, including two interferons and five oral nucleos(t)ide analogues (NAs), have been approved for the treatment of chronic hepatitis B. Interferon works by immunomodulation, but is successful in less than a third of treated patients and is a relatively weak antiviral. NAs directly suppress the hepatitis B virus but have limited durability. Based on current data, combination of NA and interferon results in greater viral suppression but does not translate to off-treatment sustained response. Concomitant or sequential treatment also does not make a difference. Combining telbivudine and interferon also runs the risk of severe peripheral neuropathy. On the other hand, interferon switch or additional therapy in patients well controlled with NAs appears to improve the durability of off-treatment response. This article reviews current data on interferon and NA combination and discusses potential future developments.
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Affiliation(s)
- G L-H Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
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Zhang Q, Lapalus M, Asselah T, Laouénan C, Moucari R, Martinot-Peignoux M, Bieche I, Estrabaud E, De Muynck S, Boyer N, Bedossa P, Vidaud M, Marcellin P, Lada O. IFNL3 (IL28B) polymorphism does not predict long-term response to interferon therapy in HBeAg-positive chronic hepatitis B patients. J Viral Hepat 2014; 21:525-32. [PMID: 24118626 DOI: 10.1111/jvh.12177] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Accepted: 08/01/2013] [Indexed: 01/03/2023]
Abstract
UNLABELLED The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN) treatment in patients infected with hepatitis B virus (HBV) is controversial. We aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long-term response of chronic hepatitis B (CHB) treatment to conventional IFN. DESIGN Ninety-seven HBeAg-positive patients treated with IFN were evaluated in this study. Associations were investigated between IFNL3 genotypes and (i) HBeAg seroconversion at the end of treatment (EOT), (ii) sustained virological response (SVR) and (iii) HBsAg seroconversion through long-term follow-up (LTFU). Patients were followed for a median of 14 years. The majority of patients were infected with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety-five patients were genotyped at rs12979860. Similar IFNL3 distribution was observed among the different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70). Thirty-six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9 and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80). HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR, nor with HBeAg seroconversion and long-term HBsAg seroconversion in HBeAg-positive CHB patients responding to IFN therapy.
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Affiliation(s)
- Q Zhang
- Service d'Hépatologie and Univ Paris Diderot, Sorbonne Paris Cité, CRB3, UMR 773, Inserm, Clichy, France
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Wiens A, Lenzi L, Venson R, Pedroso MLA, Correr CJ, Pontarolo R. Economic evaluation of treatments for chronic hepatitis B. Braz J Infect Dis 2013; 17:418-26. [PMID: 23849851 PMCID: PMC9428064 DOI: 10.1016/j.bjid.2012.12.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2012] [Accepted: 12/10/2012] [Indexed: 12/22/2022] Open
Abstract
The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.
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Affiliation(s)
- Astrid Wiens
- Universidade Federal do Paraná, Curitiba, PR, Brazil
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Shamliyan TA, Johnson JR, MacDonald R, Shaukat A, Yuan JM, Kane RL, Wilt TJ. Systematic review of the literature on comparative effectiveness of antiviral treatments for chronic hepatitis B infection. J Gen Intern Med 2011; 26:326-39. [PMID: 21203860 PMCID: PMC3043173 DOI: 10.1007/s11606-010-1569-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2010] [Revised: 10/07/2010] [Accepted: 10/20/2010] [Indexed: 12/19/2022]
Abstract
OBJECTIVES To evaluate the comparative effectiveness of antiviral drugs in adults with chronic hepatitis B monoinfection for evidence-based decision-making. METHODS A systematic review of randomized controlled clinical trials (RCTs) published in English. Results after interferon and nucleos(t)ides analog therapies were synthesized with random-effects meta-analyses and number needed to treat (NNT). RESULTS Despite sustained improvements in selected biomarkers, no one drug regimen improved all intermediate outcomes. In 16 underpowered RCTs, drug treatments did not reduce mortality, liver cancer, or cirrhosis. Sustained HBV DNA clearance was achieved in one patient when two were treated with adefovir (NNT from 1 RCT=2 95%CI 1;2) or interferon alpha-2b (NNT from 2 RCTs=2 95%CI 2;4), 13 with lamivudine (NNT from 1 RCT=13 95%CI 7;1000), and 11 with peginterferon alpha-2a vs. lamivudine (NNT from 1 RCT=11 95%CI 7;25). Sustained HBeAg seroconversion was achieved in one patient when eight were treated with interferon alpha-2b (NNT from 2 RCTs=8 95%CI 5;33) or 10--with peginterferon alpha-2b vs. interferon alpha-2b (NNT from 1 RCT=10 95%CI 5;1000). Greater benefits and safety after entecavir vs. lamivudine or pegylated interferon alpha-2b vs. interferon alpha-2b require future investigation of clinical outcomes. Adverse events were common and more frequent after interferon. Treatment utilization for adverse effects is unknown. CONCLUSIONS Individual clinical decisions should rely on comparative effectiveness and absolute rates of intermediate outcomes and adverse events. Future research should clarify the relationship of intermediate and clinical outcomes and cost-effectiveness of drugs for evidence-based policy and clinical decisions.
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Affiliation(s)
- Tatyana A Shamliyan
- Division of Health Policy and Management, Minnesota Evidence-based Practice Center, University of Minnesota School of Public Health, 420 Delaware Street SE, D330-5 Mayo (MMC 729), Minneapolis, MN 55455, USA.
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Brunetto MR, Lok AS. New approaches to optimize treatment responses in chronic hepatitis B. Antivir Ther 2011; 15 Suppl 3:61-8. [PMID: 21041905 DOI: 10.3851/imp1625] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Substantial advances have been made in the treatment of chronic hepatitis B in the past decade. Currently, there are seven approved agents including two forms of interferon (conventional and pegylated), and five oral nucleoside/nucleotide analogues (lamivudine, adefovir, entecavir, telbivudine and tenofovir disoproxil fumarate). The availability of these multiple treatment options has led to expansion of treatment indications. However, the need for a long duration of treatment with some therapies, the high costs of HBV medications, the side effects associated with some treatments and the risks of drug resistance during long-term use of oral antiviral medications necessitate the careful assessment of the risk-benefit ratio prior to initiating treatment, and the evaluation of better strategies to optimize response once treatment is initiated. In this article, we review the current approaches to optimize treatment response to nucleoside/nucleotide analogue- and interferon-based therapies for chronic hepatitis B.
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Interferon and nucleoside analog combination therapy for hepatitis B. Clin J Gastroenterol 2010; 3:69-72. [DOI: 10.1007/s12328-010-0135-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2009] [Accepted: 12/25/2009] [Indexed: 11/25/2022]
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Luo J, Li J, Chen RL, Nie L, Huang J, Liu ZW, Luo L, Yan XJ. Autologus dendritic cell vaccine for chronic hepatitis B carriers: a pilot, open label, clinical trial in human volunteers. Vaccine 2010; 28:2497-2504. [PMID: 20117267 DOI: 10.1016/j.vaccine.2010.01.038] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2009] [Revised: 12/23/2009] [Accepted: 01/17/2010] [Indexed: 01/07/2023]
Abstract
Antigen-presenting autologous dendritic cells (ADCs), primed with antigen, have been used in immunotherapy. We evaluated ADCs for treatment of chronic hepatitis B (CHB). ADCs were administered to 380 CHB patients. Virological, biochemical, and serological responses were evaluated in each patient over the course of 48 weeks. Undetectable levels of HBV DNA were reported in 46.36% of patients negative for the hepatitis B "e" antigen (HBeAg) and 3.13% HBeAg-positive patients. Normalization of alanine aminotransferase levels occurred in both HBeAg-positive (P=0.007) and HBeAg-negative (P=0.003) patients. It appears that ADC vaccination effectively reconstructed the immunity and elicited virological, serological, and biochemical improvements in some patients with chronic HBV. No side effects were observed.
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Affiliation(s)
- Jin Luo
- Institute of Genetic Diagnosis, Department of Pharmacogenomics, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, Shaanxi, China
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Treatment of chronic hepatitis B: are we ready for combination therapy? Curr Gastroenterol Rep 2009; 11:22-7. [PMID: 19166655 DOI: 10.1007/s11894-009-0004-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Treatment of chronic hepatitis B virus (HBV) infection currently involves the use of immunomodulators such as interferon and nucleoside or nucleotide analogues. Treatment aims to suppress levels of HBV DNA and induce clearance of the hepatitis B e antigen (HBeAg) or surface antigen (HBsAg) and seroconversion. At present, no single treatment has been shown to reliably suppress HBV DNA and induce durable HBsAg loss. Nucleoside or nucleotide analogues induce the production of HBV-resistant mutations that may lead to virologic and clinical breakthrough. Combination therapy, using either immunomodulators in combination or with nucleoside or nucleotide analogues, represents an emerging strategy for treating chronic HBV infection. The theoretical benefits of combining agents with varying mechanisms of action include more efficacious viral suppression and potentially durable HBsAg loss. Although combination therapy has proven successful in chronic hepatotropic viral infections and in chronic, noninfectious medical conditions, its benefits must be weighed against risks such as increased toxicity, resistance, and cost.
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Kumar M, Sarin SK. Pharmacology, clinical efficacy and safety of lamivudine in hepatitis B virus infection. Expert Rev Gastroenterol Hepatol 2008; 2:465-95. [PMID: 19072396 DOI: 10.1586/17474124.2.4.465] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Lamivudine was the first nucleoside analog for the treatment of chronic hepatitis B (CHB). It is well-tolerated and induces a decrease in serum HBV DNA levels associated with normalization of serum alanine aminotransferase levels. However, a sustained response with hepatitis B 'e' antigen to anti-hepatitis B e seroconversion is obtained in a smaller proportion of patients and hepatitis B surface antigen loss is exceptional. The response is maintained during therapy, and needs to be continued indefinitely in the majority of patients since withdrawal of treatment is generally followed by a rapid reappearance of the virus. However, mutations can be induced in long-term treatment.
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Affiliation(s)
- Manoj Kumar
- Department of Gastroenterology, Academic Block, GB Pant Hospital, New Delhi-110002, India.
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Kumar M, Sarin SK. Systematic review: combination therapies for treatment-naïve chronic hepatitis B. Aliment Pharmacol Ther 2008; 27:1187-209. [PMID: 18373730 DOI: 10.1111/j.1365-2036.2008.03695.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND There is a renewed interest in use of combination therapies in treatment-naïve chronic hepatitis B (CHB) because of limitations of monotherapies. AIM To discuss the current status of combination therapies in treatment-naïve CHB. METHODS PubMed search was done using 'combination', 'sequential' and 'chronic hepatitis B' as the search terms. RESULTS The two most popular combination therapies include 'combination of nucleos(t)ide analogues' and 'combination of interferons and nucleos(t)ide analogues'. Combination therapies using two nucleos(t)ide analogues do not lead to higher long-term efficacy. However, addition of a nucleos(t)ide analogue with a good resistance profile to a nucleos(t)ide analogue with a lower genetic barrier to resistance decreases the risk of emergent resistance to the latter. Greater sustained virological, biochemical and seroconversion rates are observed with addition of lamivudine to conventional interferon, but pegylated-interferon monotherapy is equally effective as combination with lamivudine. Again, resistance to lamivudine is lower with its combination with interferons. CONCLUSIONS The answer to the question whether hepatitis B can be treated better with combination or monotherapy remains largely unknown. Additional trials are warranted of combination therapies of peginterferon and potent nucleos(t)ide analogues or therapies with the combined use of nucleos(t)ide analogues or immunomodulators.
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Affiliation(s)
- M Kumar
- Department of Gastroenterology, G.B. Pant Hospital, Affiliated to the University of Delhi, New Delhi, India
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Rudin D, Shah SM, Kiss A, Wetz RV, Sottile VM. Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials. Liver Int 2007; 27:1185-93. [PMID: 17919229 PMCID: PMC2156150 DOI: 10.1111/j.1478-3231.2007.01580.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
AIMS To compare interferon monotherapy with its combination with lamivudine for hepatitis B e antigen (HBeAg)-positive hepatitis B treatment. METHODS Two independent researchers identified pertinent randomized controlled trials. The trials were evaluated for methodological quality and heterogeneity. Rates of sustained virological and biochemical responses, and HBeAg clearance and seroconversion were used as primary efficacy measures. Quantitative meta-analyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. RESULTS Greater sustained virological, biochemical and seroconversion rates were observed with addition of lamivudine to conventional [odds ratio (OR)=3.1, 95% confidence intervals (CI) (1.7-5.5), P<0.0001, OR=1.8, 95% CI (1.2-2.7), P=0.007 and OR=1.8, 95% CI (1.1-2.8), P=0.01 respectively], although not pegylated [OR=1.1, 95% CI (0.5-2.3), P=0.8, OR=1.0, 95% CI (0.7-1.3), P=0.94, and OR=0.9, 95% CI (0.6-1.2), P=0.34 respectively] interferon-alpha, with no significant affect on HBeAg clearance rates [OR=1.6, 95% CI (0.9-2.7), P=0.09, and OR=0.8, 95% CI (0.6-1.1), P=0.26 respectively]. Excluding virological response (P<0.001), pegylated interferon monotherapy and conventional interferon and lamivudine combination therapy were similarly efficacious (P>0.05), with the former studied in harder to treat patients, as evidenced by the superior virological response observed with conventional as compared with pegylated interferon monotherapy (P<0.0001). CONCLUSION In comparable populations, pegylated interferon monotherapy is likely to be equally or more efficacious than conventional interferon and lamivudine combination therapy, thus constituting the treatment of choice, with no added benefit with lamivudine addition. However, when conventional interferon is used, its combination with lamivudine should be considered.
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Affiliation(s)
- Dan Rudin
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, USA.
| | - Sooraj M Shah
- Department of Internal Medicine, Staten Island University HospitalStaten Island, NY, USA
| | - Alexander Kiss
- Department of Research Design and Biostatistics, Sunnybrook Health Sciences CenterToronto, ON, Canada,Institute for Clinical Evaluative SciencesToronto, ON, Canada
| | - Robert V Wetz
- Department of Internal Medicine, Staten Island University HospitalStaten Island, NY, USA
| | - Vincent M Sottile
- Department of Gastroenterology, Staten Island University HospitalStaten Island, NY, USA
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Fehér J, Lengyel G. [Interferon in the treatment of viral hepatitis. The interferon was discovered 50 years ago]. Orv Hetil 2007; 148:1539-43. [PMID: 17686671 DOI: 10.1556/oh.2007.28194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The interferons are heterogenic glycoproteins which are produced on the effect of virus infection, as immune answer, by the living cells. They were discovered half a century ago. They have antineoplastic, antiviral and immunomodulator effect. The names of interferons used in the therapy are nominated with Greek letters. This nomination shows their origins: the interferon-alpha originates from leucocytes, the interferon-beta does from fibroblasts and the interferon-gamma is produced as immune interferon by lymphocytes. In human medicine both natural and recombinant interferons are applied. The connection of polyethyleneglycol to interferons ensures their sustained effect. Nowadays they are applied in the therapy of chronic hepatitis B or C as well as in oncology to inhibit the neoplasm progression.
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Affiliation(s)
- János Fehér
- Semmelweis Egyetem, Altalános Orvostudományi Kar II. Belgyógyászati Klinika Budapest Szentkirályi u. 46. 1088.
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Rudin D. Lamivudine and interferon versus lamivudine monotherapy for HBeAg-positive hepatitis B treatment: a meta-analysis of randomized, controlled trials. Adv Ther 2007; 24:784-95. [PMID: 17901027 DOI: 10.1007/bf02849971] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The suboptimal outcomes of current chronic hepatitis B treatments have prompted the notion of combination therapy as a means of augmenting the therapeutic response. In this study, investigators compared lamivudine monotherapy versus its combination with conventional or pegylated interferon-alpha, pooling data from all pertinent randomized controlled studies into the meta-analysis. The studies were evaluated for methodologic quality and heterogeneity. Rates of sustained virologic and biochemical responses and of hepatitis B e antigen clearance and seroconversion were used as primary efficacy measures. Quantitative metaanalyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall. Analysis yielded greater sustained virologic, biochemical, and seroconversion rates with the addition of conventional (odds ratio [OR]=4.5, 95% confidence interval [CI]=2.2-9.4, P<.001; OR=2.1, 95% CI=1.3-3.2, P=.002; and OR=2.6, 95% CI=1.4-4.8, P=.001, respectively) and pegylated (OR=2.0, 95% CI=1.1-3.6, P=.02; OR=1.8, 95% CI=1.3-2.6, P<.001; and OR=1.6, 95% CI=1.1-2.3, P=.03, respectively) interferon-alpha to lamivudine, with the former also yielding greater hepatitis B e antigen clearance rates (OR=2.6, 95% CI=1.3-5.2, P=.008). As previous studies suggested that pegylated interferon monotherapy and its combination with lamivudine were comparable, the use of this combination is not justified. In contrast, when conventional interferon-a is used, its combination with lamivudine should be considered.
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Affiliation(s)
- Dan Rudin
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, New York 10305, USA.
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Abstract
Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.
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Affiliation(s)
- Steven-Huy B Han
- David Geffen School of Medicine at UCLA, Los Angeles, California 90095-7302, USA.
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Sarin SK, Sood A, Kumar M, Arora A, Amrapurkar D, Sharma BC, Konar A, Chawla YK, Jain RK, Nanda V, Kumar A, Hissar S, Lavate P, Lahoti D. Effect of lowering HBV DNA levels by initial antiviral therapy before adding immunomodulator on treatment of chronic hepatitis B. Am J Gastroenterol 2007; 102:96-104. [PMID: 17266689 DOI: 10.1111/j.1572-0241.2006.01006.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Lower hepatitis B virus DNA (HBV DNA) levels are associated with better responses in chronic hepatitis B (CHB). It is unclear whether an initial phase of antiviral treatment to lower HBV DNA levels before adding immunomodulator therapy is more effective than the strategy of using immunomodulators from the beginning. AIM The aim of the study was to compare the efficacy of lamivudine followed by pegylated-interferon (peg-IFN) therapy with placebo followed by peg-IFN therapy in HBeAg-positive CHB patients. PATIENTS AND METHODS Sixty-three treatment-naive HBeAg-positive patients with histologically proven CHB and alanine aminotransferase (ALT) > 1.2 x upper limit of normal (ULN) received placebo for 4 wk followed by peg-IFN 1.0 mug/kg/wk for next 24 wk (group A, N = 27; age 32 +/- 11 yr; M:F = 25:2) or lamivudine 100 mg per day for 4 wk followed by peg-IFN 1.0 mug/kg/wk for next 24 wk (group B, N = 36; age 32.5 +/- 10.5 yr; M:F = 31:5). Patients were followed for next 24 wk after completion of treatment. Biochemical and virologic responses were assessed at weeks 4, 28, and 52 and analysis was done on intention-to-treat basis. RESULTS At wk 4, mean +/- SD of log change in DNA from baseline was 0.2594 +/- 1.7873 in group A and 1.2186 +/- 1.6347 in group B, respectively (P = 0.032). At week 28, undetectable HBV DNA was seen in eight (29.6%) and 16 (44.4%) patients in groups A and B, respectively (P= 0.298). At week 28, HBeAg loss occurred in eight (29.6%) in group A and 15 (41.7%) in group B (P = 0.43). Six months posttherapy, at week 52, undetectable HBV DNA was seen in four (14.8%) and 18 (50%) in groups A and B, respectively (P = 0.028) and HBeAg loss was maintained in four (14.8%) and 14 (38.9%) (P = 0.05) patients. Normal ALT was seen in five (18.5%) and 10 (27.8%) at week 28 (P = 0.552) and five (18.5%) and 13 (36.1%) at week 52 (P = 0.159) in groups A and B, respectively. There was a significant correlation among achievement of HBeAg loss, anti-HBe appearance, and undetectable HBV DNA levels at week 28 (P = 0.008) and 52 (P < 0.001) and HBV DNA levels at week 4. CONCLUSIONS The strategy of using an antiviral initially to decrease HBV DNA levels before adding an immunomodulatory agent leads to improved sustained virological response as compared with using immunomodulator from the start.
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Affiliation(s)
- Shiv Kumar Sarin
- Department of Gastroenterology and Hepatology, G.B. Pant Hospital, New Delhi, India
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Manesis EK, Papatheodoridis GV, Hadziyannis SJ. A partially overlapping treatment course with lamivudine and interferon in hepatitis B e antigen-negative chronic hepatitis B. Aliment Pharmacol Ther 2006; 23:99-106. [PMID: 16393286 DOI: 10.1111/j.1365-2036.2006.02731.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Treatment of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHBe-) with interferon or lamivudine alone is inefficient and reports of combination treatment with both drugs, equivocal so far. AIM To investigate the efficacy of a lamivudine-interferon combination therapy in 36 patients HBeAg-negative CHBe-. METHODS Lamivudine was administered from 1 to 12 months and interferon-alpha2b from 7 to 18 months. A historical control group of 36 CHBe- patients, matched for age and sex and treated with the same dosage of interferon-alpha2b was used. All patients were followed up for > or =12-month post-treatment. RESULTS The biochemical response rate at the end of treatment was 78% in lamivudine-interferon and 52.8% in interferon-control group (P = 0.026) and at 12-month post-treatment 38.9% and 22.2%, respectively (P = 0.125). Alanine aminotransferase normalization and serum HBV-DNA levels < or =30 000 cp/mL were observed in 50.0% of lamivudine-interferon-treated and 30.6% of interferon-treated patients at the end of treatment (P =0.093) and in 22.2% and 13.9% of patients, respectively, at 12-month post-treatment (P = 0.358). Moreover, alanine aminotransferase normalization and undetectable serum HBV-DNA (<400 cp/mL) was observed in 30.6% of lamivudine-interferon-treated and 8.3% of interferon-treated patients at the end of treatment (P = 0.017) and in 8.3% and 0% of patients, respectively, at 12-month post-treatment (P = 0.076). CONCLUSIONS In CHBe-, 12 months after ending a lamivudine-interferon partially overlapping 18-month combination course, 22% of patients still maintain normal alanine aminotransferase and HBV-DNA levels < or =30 000 cp/mL. However, a 12-month interferon monotherapy course may achieve similar responses.
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Affiliation(s)
- E K Manesis
- Academic Department of Medicine, Hippokration General Hospital, Athens, Greece
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Sarin SK, Kumar M, Kumar R, Kazim SN, Guptan RC, Sakhuja P, Sharma BC. Higher efficacy of sequential therapy with interferon-alpha and lamivudine combination compared to lamivudine monotherapy in HBeAg positive chronic hepatitis B patients. Am J Gastroenterol 2005; 100:2463-71. [PMID: 16279901 DOI: 10.1111/j.1572-0241.2005.00247.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Monotherapy with interferon (IFN) or lamivudine is effective in a limited proportion of chronic hepatitis B (CHB) patients. A sequential combination may have better therapeutic effects by sustained viral suppression combined with immunomodulation. AIM To compare the efficacy of sequential lamivudine and IFN therapy versus lamivudine monotherapy in HBeAg positive CHB patients. PATIENTS AND METHODS Seventy-five treatment naïve HBeAg positive patients with histologically proven CHB and alanine aminotransferase (ALT) >1.5 x ULN received lamivudine 100 mg per day for 52 wks with IFN 5 MIU per day added for 16 wks after the first 8 wks (group A, n = 38; age 30 +/- 12 yr; M:F = 35:3) or lamivudine 100 mg per day for 52 wks (group B, n = 37; age 30 +/- 16 yr; M:F = 31:6). Biochemical and virologic responses were assessed at weeks 52 and 76 and analysis was done on intention-to-treat. Serial samples were studied for the emergence of lamivudine-resistant YM552I/VDD mutations by direct sequencing. RESULTS At week 52, HBeAg loss occurred in 15 (39.5%) in group A and 14 (37.8%) in group B (p= 1.00). HBeAg loss, anti-HBe appearance, and undetectable DNA levels were seen in 26.3% and 13.5% (p= 0.249), respectively. Nine of 10 (90%) patients in group A and 1 of 5 (20%) in group B maintained the response through week 76 (p= 0.017). At week 76, 5 additional patients in group A and 3 in group B further achieved the primary end point and the overall HBeAg loss was observed in 44.7% and 18.9% (p= 0.025) and HBeAg loss, anti-HBe appearance, and undetectable hepatitis B virus (HBV) DNA levels in 36.8% and 10.8% in group A and group B, respectively (p= 0.026). At week 76, undetectable HBV DNA was seen in 39.5% and 16.2% in groups A and B, respectively (p= 0.039). Normal ALT was seen in 47.7% and 40.5% at week 52 (p= 0.489) and ALT was normal in 39.5% and 13.5% at week 76 (p= 0.018) in groups A and B, respectively. YM552I/VDD-resistant mutants emerged in 6 of 38 (15.5%) patients in group A, and 3 of 37 (8.1%) in group B (p= ns). The rate of histological improvement was comparable in the two groups. CONCLUSIONS Our results demonstrate that sequential therapy is superior to lamivudine monotherapy in achieving sustained seroconversion, ALT normalization, and HBV DNA loss. Compared to 80% with sequential therapy, only 20% Indian patients with CHB did not relapse after stopping lamivudine monotherapy.
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Affiliation(s)
- Shiv Kumar Sarin
- Department of Gastroenterology, G.B. Pant Hospital, Affiliated to the University of Delhi, India
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Chen M, Li YG, Zhang DZ, Wang ZY, Zeng WQ, Shi XF, Guo Y, Guo SH, Ren H. Therapeutic effect of autologous dendritic cell vaccine on patients with chronic hepatitis B: A clinical study. World J Gastroenterol 2005; 11:1806-8. [PMID: 15793869 PMCID: PMC4305879 DOI: 10.3748/wjg.v11.i12.1806] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the therapeutic effect of autologous HBsAg-loaded dendritic cells (DCs) on patients with chronic hepatitis B.
METHODS: Monocytes were isolated from fresh peripheral blood of 19 chronic HBV-infected patients by Ficoll-Hypaque density gradient centrifugation and cultured by plastic-adherence methods. DCs were induced and proliferated in the culture medium with recombinant human granulocyte-macrophage-colony- stimulating factor (rhGM-CSF) and human interleukin-4 (rhIL-4). DCs pulsed with HBsAg for twelve hours were injected into patients subcutaneously twice at intervals of two weeks. Two patients received 100 mg oral lamivudine daily for 12 mo at the same time. HBV-DNA and viral markers in sera of patients were tested every two months.
RESULTS: By the end of 2003, 11 of 19 (57.9%) patients had a clinical response to DC-treatment. HBeAg of 10 (52.6%) patients became negative, and the copies of HBV-DNA decreased 101.77±2.39 averagely (t = 3.13, P<0.01).Two cases co-treated with DCs and lamivudine had a complete clinical response. There were no significant differences in the efficient rate between the cases with ALT level lower than 2×ULN and those with ALT level higher than 2×ULN before treatment (χ2 = 0.0026).
CONCLUSION: Autologous DC-vaccine induced in vitro can effectively suppress HBV replication, reduce the virus load in sera, eliminate HBeAg and promote HBeAg/anti-HBe transformation. Not only the patients with high serum ALT levels but also those with normal ALT levels can respond to DC vaccine treatment, and the treatment combining DCs with lamivudine can eliminate viruses more effectively.
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Affiliation(s)
- Min Chen
- Research Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, China.
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Abstract
PURPOSE OF REVIEW Hepatitis B and C infections are prevalent around the world and a major health burden due to the associated complications of hepatic fibrosis, cirrhosis and hepatocellular carcinoma which occur in the context of chronic infection. Significant advances are being made in assessing and treating infected patients and recent studies are now targeting patients who have failed to respond to previous treatments or who have associated co-morbidities. The purpose of this article to review the recent literature on the subject of hepatitis B and C infections with particular focus on new treatment options, new approaches in patients who have previously failed therapy and in those who have co-morbidity. RECENT FINDINGS A large number of studies have been carried out investigating the roles of varying doses, targeting treatment in particular groups and new treatment options in patients infected with hepatitis B and C. Several key findings such as the value of prolonging treatment in patients with genotype 1 hepatitis C infection, the use of pegylated interferon in chronic hepatitis B infection and the emergence of new treatments such as adefovir for resistant hepatitis B infection, as well as treatment of patients co-infected with hepatitis C and human immunodeficiency virus, have dominated the recent literature. Patients in particular groups such as those who have had liver transplantation or who are immunosuppressed have also received added attention. SUMMARY Hepatitis B and C infections are the focus of much current attention with particular regard to new and emerging treatment options which are becoming increasingly focused on varying patient groups.
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Gjørup IE, Skinhøj P. New aspects on the natural history of chronic hepatitis B infection: implication for therapy. ACTA ACUST UNITED AC 2004; 35:808-13. [PMID: 14723354 DOI: 10.1080/00365540310017168] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
The incidence and sequelae of chronic hepatitis B (HBV) infection appear to have been overestimated previously, especially in areas outside Asia where neonatal infection predominates. A high rate of spontaneous HBeAg seroconversion is found in children as well as adults, and 40 to 50 y of replicative infection seems to be the most important risk factor for cirrhosis and hepatocellular carcinoma necessitating a cautious attitude towards antiviral treatment. Of concern, however, HBeAg seroconversion, which usually predicts a good outcome, is not always an irreversible event. Low grade replication of HBV may continue in anti-HBe positive individuals and shift in HBe status does occur in up to 10% of viral carriers with evidence of an increased risk of complications. Viral replication (HBV DNA positivity) is also found in HBeAg negative mutant infection and is an important parameter to note. To date, the data do not suggest any different prognosis for patients with this kind of infection. Also the various viral genotypes might have different prognoses partly due to the association with precore mutations, but the present knowledge does not allow different therapeutic management as in the case of hepatitis C. Treatment is available with a number of safe antiviral agents. However, all of them are mainly suppressive with low cure rates after 1 y. Initiation of therapy should therefore mainly be considered in symptomatic chronic infection and in cases with high risk of complications i.e. patients with ongoing viral replication and age above 40 y or bridging necroses verified by liver biopsy.
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Affiliation(s)
- Ida E Gjørup
- Department of Internal Medicine Q, Herlev Hospital, University of Copenhagen, Denmark
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