|
1
|
Cuenca-Gómez JÁ, Lozano-Serrano AB, Cabezas-Fernández MT, Soriano-Pérez MJ, Vázquez-Villegas J, Estévez-Escobar M, Cabeza-Barrera I, Salas-Coronas J. Chronic hepatitis B genotype E in African migrants: response to nucleos(t)ide treatment in real clinical practice. BMC Infect Dis 2018; 18:568. [PMID: 30428845 PMCID: PMC6236963 DOI: 10.1186/s12879-018-3469-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 10/31/2018] [Indexed: 12/18/2022] Open
Abstract
Background Hepatitis B virus (HBV) genotype E is a poorly studied genotype that almost exclusively occurs in African people. It seems to harbour intrinsic potential oncogenic activity and virological characteristics of immune scape but a paucity of information is available on clinical and virological characteristic of HBV genotype E-infected patients as well as on the efficacy of anti-HBV drugs for such patients. The increasing flow of migrants from high endemic HBV sub-Saharan Africa, where genotype E is the predominant one, to Western countries makes improving such knowledge critical in order to deliver proper medical care. Methods Prospective observational study of naïve patients of sub-Saharan origin treated for chronic HBV genotype E infection at a Tropical Medicine clinic sited in Spain from February 2004 to January 2018. The aim of the study was to describe the response of chronic HBV genotype E infection to nucleos(t)ide analogues (NA), entecavir or tenofovir, in real clinical practice. Results During the study period, 2209 sub-Saharan patients were assisted at our Tropical Medicine Unit and 609 (27.6%) had chronic HBV (CHB) infection. Genotype information was available for 55 naïve patients initiating treatment with NA (entecavir or tenofovir), 43 (84.3%) of them being genotype E, although 15 were excluded because they did not meet study inclusion criteria. Thus, a total of 28 CHB genotype E patients were included and followed for 24 months at least. Twenty-one patients were in HBeAg-negative chronic hepatitis phase and 7 patients in HBeAg-positive chronic hepatitis phase. After one year of treatment, among those with good adherence, 89.4% (17/19) of the HBeAg-negative patients and 80% of the HBeAg-positive ones had undetectable viral loads. Response rates reached 100% in both groups after 15–18 months of follow-up. Out of the 7 HBeAg-positive patients, 6 (85.7%) presented HBeAg loss in a median time of 31.8 months. Neither serious adverse effects nor hepatocarcinoma cases happened during the study period. Conclusions HBV genotype may influence disease progression and antiviral response. Our study provides precious information on the efficacy and safety of NA treatment for CHB genotype E infection, a fairly unknown genotype with and increasing epidemiological impact.
Collapse
Affiliation(s)
- José Ángel Cuenca-Gómez
- Tropical Medicine Unit, Hospital de Poniente, Carretera de Almerimar s/n, PD: 07400, Almería, El Ejido, Spain.
| | - Ana Belén Lozano-Serrano
- Tropical Medicine Unit, Hospital de Poniente, Carretera de Almerimar s/n, PD: 07400, Almería, El Ejido, Spain
| | | | - Manuel Jesús Soriano-Pérez
- Tropical Medicine Unit, Hospital de Poniente, Carretera de Almerimar s/n, PD: 07400, Almería, El Ejido, Spain
| | | | | | - Isabel Cabeza-Barrera
- Tropical Medicine Unit, Hospital de Poniente, Carretera de Almerimar s/n, PD: 07400, Almería, El Ejido, Spain
| | - Joaquín Salas-Coronas
- Tropical Medicine Unit, Hospital de Poniente, Carretera de Almerimar s/n, PD: 07400, Almería, El Ejido, Spain
| |
Collapse
|
|
2
|
The human C-type lectin 18 is a potential biomarker in patients with chronic hepatitis B virus infection. J Biomed Sci 2018; 25:59. [PMID: 30055605 PMCID: PMC6064175 DOI: 10.1186/s12929-018-0460-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 07/11/2018] [Indexed: 12/14/2022] Open
Abstract
Background Hepatitis B virus (HBV) infection is a common disease worldwide and is known to cause liver disease. C-type lectin 18 (CLEC18) is a novel secretory lectin highly expressed in human hepatocytes. Because the liver is the major target of HBV infection, we investigated whether the expression of CLEC18 can be used as a biomarker for HBV infection. Methods The expression level of CLEC18 in human liver chimeric mice with/without HBV infection was measured by quantitative real time polymerase chain reaction (qPCR) assay. Baseline plasma CLEC18 levels in 271 treatment-naive patients with chronic hepatitis B (CHB) undergoing nucleos(t)ide analogue (NUC) therapy and 35 healthy donors were measured by enzyme-linked immunosorbent assay, and the relationships to other clinical data were analyzed. Results The expression of CLEC18 was down-regulated in the human liver chimeric mice after HBV infection. Plasma CLEC18 levels were lower in the patients with CHB compared to the healthy donors and positively correlated with HBV DNA and HBsAg levels (P < 0.05). Multivariate Cox proportional hazard regression analysis identified a baseline plasma CLEC18 level of 320–2000 pg/mL to be an independent predictor of HBeAg loss (hazard ratio (HR): 2.077, P = 0.0318), seroconversion (HR: 2.041, P = 0.0445) and virological response (HR: 1.850, P = 0.0184) in 101 HBeAg-positive patients with CHB undergoing NUC therapy. Conclusions Plasma CLEC18 levels were correlated with the stage of HBV infection and could predict HBeAg loss and seroconversion in the patients with CHB undergoing NUC therapy. Electronic supplementary material The online version of this article (10.1186/s12929-018-0460-2) contains supplementary material, which is available to authorized users.
Collapse
|
|
3
|
Wang Q, Li H, Ding D, Peng M, Ren H, Hu P. Upgrade Combination Response Is Limited by Prolonged Nucelos(t)ide Analogue Therapy in HBeAg-positive Chronic Hepatitis B: A Real-life Study. J Clin Transl Hepatol 2018; 6:11-17. [PMID: 29577027 PMCID: PMC5862994 DOI: 10.14218/jcth.2017.00020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 08/04/2017] [Accepted: 08/21/2017] [Indexed: 12/16/2022] Open
Abstract
Background and Aims: Few previous studies have reported on a combination response (hepatitis B virus (HBV) DNA undetected, alanine aminotransferase normalization and hepatitis B e antigen (HBeAg) seroconversion) following nucleos(t)ide analogue (NAs) long-term therapy in patients with chronic hepatitis B (CHB). This study aimed to investigate the combination response on long-term NAs therapy in patients with HBeAg-positive CHB and to determine whether prolonged therapy is beneficial for combination response, particularly in optimal patients (baseline alanine aminotransferase level ≥5 upper limit of normal and HBV DNA level <109 copies/mL). Methods: In total, 280 HBeAg-positive CHB patients were enrolled in this study. Among them, 190 were treated with entecavir and 90 were treated with telbivudine. Results: The cumulative rates of combination response in the total number of patients were 8.6% at 1 year, 13.2% at 2 years, 19.1% at 3 years, 24.2% at 4 years and 26.0% at 5 years. In optimal patients, the cumulative rate of combination response was significantly higher than that in the non-optimal patients at 3 years (p = 0.043); the trend of the cumulative rate was not strong at the later time. Interestingly, in optimal patients, combination response mainly occurred in the first 3 years. Multivariate analysis identified HBeAg/anti-HBe seroconversion at 1 year as the only factor for combination response in optimal patients (hazard ratio: 16.321; p = 0.000). During the 3 years, the proportion with aspartate aminotransaminase to platelet ratio index ≤0.5 increased from 15.6% at baseline to 71.3% at year 3. Conclusions: Upgrading the rate of combination response is limited by prolonging the treatment duration of NAs from 3 years to 5 years in HBeAg-positive CHB patients; a new switch treatment strategy modification should be considered, particularly in optimal patients.
Collapse
Affiliation(s)
- Qiaohe Wang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Disease, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hu Li
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Disease, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Daohai Ding
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Disease, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingli Peng
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Disease, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hong Ren
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Disease, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Disease, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- *Correspondence to: Peng Hu, Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing 400010, China. Tel: +86-23-63693289, Fax: +86-23-63703790, E-mail:
| |
Collapse
|
|
4
|
Using Population Pharmacokinetic and Pharmacodynamic Analyses of Entecavir in Pediatric Subjects to Simplify Dosing Recommendations. Clin Pharmacokinet 2017; 55:1559-1572. [PMID: 27319000 DOI: 10.1007/s40262-016-0420-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Entecavir is an orally administered guanosine nucleoside analog with activity against hepatitis B virus (HBV) polymerase, which is approved for the treatment of chronic hepatitis B (CHB) infection in adults and children ≥2 years old (USA and EU). OBJECTIVE To develop simplified entecavir dosing recommendations for young children infected with CHB. METHODS Data from recent clinical trials were used to develop a population pharmacokinetic (PPK) model, which allowed us to estimate entecavir exposures in children and compare them to ranges known to be efficacious in adults. A population pharmacodynamic (PPD) model was generated to describe the concentration/effect relationship for entecavir in lamivudine treatment-naïve children. The PPK dataset comprised three pediatric cohorts: 2 to <6 years (n = 36); 6 to <12 years (n = 43); and 12 to <18 years (n = 74). Data from 177 adults were also included to enhance model stability and to aid in the covariate search. RESULTS Entecavir concentration-time profiles were well-described by a two-compartment model with first-order absorption and first-order elimination. Age was not a statistically significant covariate after accounting for weight. For the PPD model, the HBV DNA concentration following entecavir exposure was adequately described using a direct effect inhibitory maximum effect (E max) model with additive residual error. CONCLUSION Model-estimated, steady-state entecavir area under the concentration-time curve, in both the original (15 weight groups) and simplified (eight weight groups) pediatric dosing regimens, provided entecavir exposures consistent with those observed to be efficacious in adults, and resulted in the simplified dose algorithm for pediatric patients that is approved for the current entecavir label.
Collapse
|
|
5
|
Abstract
OBJECTIVE As the efficacy of a direct antiviral agent is reduced in cirrhotic chronic hepatitis C patients, prolonged duration of treatment or addition of ribavirin is recommended to improve the rates of sustained virological response. However, the impact of cirrhosis on the efficacy of antiviral treatment for chronic hepatitis B (CHB) remained unclear. PATIENTS AND METHODS This retrospective cohort study screened entecavir (ETV)-treated CHB patients in Taipei Tzu Chi Hospital from January 2007 till October 2014. The diagnosis of cirrhosis was made on the basis of clinical/imaging or histologic findings. The primary endpoints were hepatitis B e antigen (HBeAg) loss in HBeAg-positive patients and undetectable hepatitis B virus (HBV) DNA in the overall study population. Initial virological response is defined as undetectable HBV DNA at 1-year ETV treatment. RESULTS A total of 381 (262 men; mean age: 49.6±12.9 years) CHB patients were recruited for the final analysis. Of these, 138 were cirrhotic. In 143 HBeAg-positive patients, there was no difference in the rates of 1- and 2-year HBeAg loss between cirrhotic and noncirrhotic patients (P=0.226 and 0.729, respectively). In the overall population, the rate of 1-year undetectable HBV DNA was higher in patients with cirrhosis than those without cirrhosis (76.1 vs. 64.2%, P=0.016). The rate of 2-year undetectable HBV DNA was not different between these two groups. Using multivariate logistic regression analysis, baseline HBV DNA levels (P=0.006) and HBeAg status (P=0.007), were associated with initial virological response, but not cirrhosis. CONCLUSION Therapeutic responses of ETV are not decreased in cirrhotic CHB patients. Thus, cirrhotic CHB patients can be treated with ETV without the need for dose adjustment.
Collapse
|
|
6
|
Predictors of HBeAg seroconversion after long-term nucleos(t)ide analogues treatment for chronic hepatitis B: a multicenter study in real clinical setting. Braz J Infect Dis 2017; 21:213-218. [PMID: 28351603 PMCID: PMC9427966 DOI: 10.1016/j.bjid.2017.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Revised: 03/10/2017] [Accepted: 03/10/2017] [Indexed: 12/26/2022] Open
Abstract
Aims To evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). Methods 251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100 mg daily), adefovir (ADV, 10 mg daily), telbivudine (LDT, 600 mg daily), entecavir (ETV, 0.5 mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. Results In real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p < 0.001, Hazard Ratio (HR) = 2.203), elevated alanine aminotransferase (ALT) levels (p < 0.001, HR = 2.049), and non-vertical transmission (p = 0.006, HR = 1.656) were predictors of HBeAg seroconversion. Conclusion Adherence, elevated ALT, and non-vertical transmission are predictors of HBeAg seroconversion in CHB patients treated with NAs.
Collapse
|
|
7
|
Wang CC, Tseng KC, Hsieh TY, Tseng TC, Lin HH, Kao JH. Assessing the Durability of Entecavir-Treated Hepatitis B Using Quantitative HBsAg. Am J Gastroenterol 2016; 111:1286-94. [PMID: 27045923 DOI: 10.1038/ajg.2016.109] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 02/02/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVES This study aims to assess whether quantitative HBsAg can predict durability of chronic hepatitis B (CHB) patients stopping entecavir (ETV) treatment. METHODS We conducted a multicenter study on non-cirrhotic CHB patients who discontinued ETV treatment. The primary end points were clinical relapse and sustained viral response (SVR), which was defined as undetectable serum hepatitis B virus (HBV) DNA levels (<6 IU/ml) at 12 months off-therapy. RESULTS A total of 117 consecutive CHB patients were enrolled. Among them, 93 patients who received more than 1-year off-therapy follow-up were included for the final analysis. The duration of off-therapy follow-up was 24.8±11.6 months. All 12 patients who did not achieve therapeutic end points had clinical relapse. In 81 patients who achieved therapeutic end points, clinical relapse and SVR were observed in 44 (54.3%) and 11 (13.6%) patients, respectively. The serum HBV DNA at 3 months and 6 months off-therapy were associated with clinical relapse over time, whereas quantitative hepatitis B surface antigen (qHBsAg) level at 6 months off-therapy had a marginal effect. Furthermore, end-of-treatment qHBsAg levels were associated with SVR (P=0.009). CONCLUSIONS The serum qHBsAg level off-therapy can predict durability of ETV-treated CHB patients. It may guide clinicians to select which patients can maintain sustained viral suppression or need retreatment after discontinuing ETV treatment.
Collapse
Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Kuo-Chih Tseng
- Department of Hepatology, Da-Lin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Tsai-Yuan Hsieh
- Department of Gastroenterology, Tri-service General Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hans Hsienhong Lin
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| |
Collapse
|
|
8
|
Tseng KC, Tseng CW, Hsieh TY, Peng CY, Lin CL, Su TH, Tseng TC, Lin HH, Wang CC, Kao JH. Efficacy of entecavir therapy for hepatitis B e-antigen positive chronic hepatitis B patients with prior exposure to interferon or nucleoside/nucleotide analogues. Hepatol Res 2016; 46:642-9. [PMID: 26422680 DOI: 10.1111/hepr.12600] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Revised: 09/01/2015] [Accepted: 09/23/2015] [Indexed: 01/06/2023]
Affiliation(s)
- Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi and School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chih-Wei Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi and School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Tsai-Yuan Hsieh
- Department of Gastroenterology, Tri-Service General Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Taipei City Hospital, Ren-Ai branch, Taipei, Taiwan
| | - Tung-Hung Su
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hans Hsienhong Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| |
Collapse
|
|
9
|
Pereira CV, Tovo CV, Grossmann TK, Mirenda H, Dal-Pupo BB, de Almeida PRL, de Mattos AA. Efficacy of entecavir and tenofovir in chronic hepatitis B under treatment in the public health system in southern Brazil. Mem Inst Oswaldo Cruz 2016; 111:252-257. [PMID: 27074254 PMCID: PMC4830114 DOI: 10.1590/0074-02760150390] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 03/11/2016] [Indexed: 02/07/2023] Open
Abstract
There are about 350 million hepatitis B virus (HBV) carriers worldwide and chronic HBV is considered a major public health problem. The objective of the present study was to assess the effectiveness of the nucleos(t)ide analogues tenofovir (TDF) and entecavir (ETV) in the treatment of chronic HBV. A cross-sectional study was carried out from March-December 2013, including all patients with chronic HBV, over 18 years of age, undergoing therapy through the public health system in southern Brazil. Only the data relating to the first treatments performed with TDF or ETV were considered. Retreatment, co-infection, transplanted or immunosuppressed patients were excluded. Six hundred and forty patients were evaluated, of which 336 (52.5%) received TDF and 165 (25.8%) ETV. The other 139 (21.7%) used various combinations of nucleos(t)ide analogues and were excluded. The negativation of viral load was observed in 87.3% and 78.8% and the negativation of hepatitis B e antigen was achieved in 79% and 72% of those treated with ETV or TDF, respectively. Negativation of hepatitis B surface antigen was not observed. There was no occurrence of adverse effects. This is a real-life study demonstrating that long-term treatment with ETV and TDF is both safe and effective.
Collapse
Affiliation(s)
| | - Cristiane Valle Tovo
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de
Pós-Graduação em Hepatologia, Porto Alegre, RS, Brasil
| | | | | | | | | | | |
Collapse
|
|
10
|
Xu Y, Wu XN, Shi YW, Wei W, Yang AT, Sun YM, Zhao WS, You H. Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3 (rd) Month Virological Response to Entecavir Therapy: A Study of Strict Defined Hepatitis B virus Induced Cirrhosis. Chin Med J (Engl) 2016; 128:1867-72. [PMID: 26168824 PMCID: PMC4717924 DOI: 10.4103/0366-6999.160488] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Cirrhosis is a common complication of chronic hepatitis B. It remains unclear if viral and biochemical parameters at baseline affect virological response to entecavir and therefore warrant investigation. In the present study, we aimed to evaluate the efficacy of entecavir therapy by monitoring virological response at the end of the 3 rd month of treatment and try to figure out whether baseline factors could help predict it in a cohort of hepatitis B virus (HBV) compensated cirrhosis patients and to determine the cut-off value of a predicting parameter. METHODS A total of 91 nucleos(t)ide-naïve patients with HBV induced cirrhosis (compensatory stage) were enrolled in a prospective cohort. HBV DNA and alanine aminotransferase (ALT) were tested at baseline and monitored every 3-6 months after starting therapy. RESULTS Of all 91 patients, the median follow-up time was 12 (9-24) months. Overall, 64 patients (70.3%) achieved virological response in the 3 rd month. Univariate analysis showed that the 3 rd month virological response can be predicted by baseline HBV DNA levels (P < 0.001, odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.44-3.15), ALT value (P = 0.023, OR: 1.01, 95% CI: 1.00-1.01) and hepatitis B e antigen (HBeAg) negativity (P = 0.016, OR: 0.30, 95% CI: 0.11-0.80). Multiple regression analysis showed baseline HBV DNA level was the only parameter related to full virological response. Higher baseline HBV DNA strata indicated a higher probability that HBV DNA remains detectable at the 3 rd month (P = 0.001). Area under receiver operating characteristic curve for determining the 3 rd month virological response by baseline HBV DNA was 77.6% (95% CI: 66.7-85.2%), with a best cut-off value of 5.8 log 10 . CONCLUSIONS Baseline HBV DNA, HBeAg negativity, and ALT were independent factors contributing to virological response at the 3 rd month. Further, multiple regression showed that HBV DNA level was the only parameter predicting full virological response as early as the 3 rd month, in this cirrhosis cohort.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Hong You
- Department of Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, China
| |
Collapse
|
|
11
|
Wang CC, Kao JH. How have the recent advances in antiviral therapy impacted the management of virus-related hepatocellular carcinoma? Expert Opin Pharmacother 2016; 17:911-9. [PMID: 26831361 DOI: 10.1517/14656566.2016.1149165] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Whether the recent advances in antiviral therapy including nucleos(t)ide analogue (NA) or interferon (IFN) impacts the management of patients with virus-related hepatocellular carcinoma (HCC) remains unclear. AREA COVERED The beneficial effects of antiviral therapy on HCC patients receiving curative treatment, transhepatic arterial chemoembolization (TACE), or radiotherapy are reviewed and discussed. EXPERT OPINION For patients with HCV-related HCC after curative treatment, interferon (IFN)-based therapy has been shown to improve the survival and reduces the risk of HCC recurrence. However, it carries the risk of adverse effects, especially in cirrhotic patients. Therefore, the benefit of IFN should be weighted against its risk in each individual. For patients with HBV-related HCC after curative treatments, antiviral treatment with NA has been found to improve liver function, overall survival, and possibly reduce the risk of HCC recurrence. In contrast, these benefits were not consistently observed in those receiving IFN treatment. In HCC patients receiving palliative TACE or radiotherapy, HBV reactivation occurs in a small proportion of them, and preemptive NA treatment can reduce the risk of hepatitis flare due to viral reactivation. Therefore, NA treatment after curative treatments or TACE is strongly recommended for HCC patients with high viral load (HBV DNA> 2000 IU/mL).
Collapse
Affiliation(s)
- Chia-Chi Wang
- a Department of Gastroenterology and Hepatology, Taipei Tzu Chi Hospital , Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University , Hualien , Taiwan
| | - Jia-Horng Kao
- b Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital , Taipei , Taiwan
| |
Collapse
|
|
12
|
Treatment Outcomes With First-line Therapies With Entecavir and Tenofovir in Treatment-Naive Chronic Hepatitis B Patients in a Routine Clinical Practice. J Clin Gastroenterol 2016; 50:169-74. [PMID: 26018133 DOI: 10.1097/mcg.0000000000000345] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Given their high efficacy, entecavir (ETV) and tenofovir (TDF), are the recommended first-line therapies for chronic hepatitis B, but it is not clear whether the efficacy reported from pivotal trials is similar to the outcomes seen in routine practice. GOALS Our goal was to examine the treatment outcomes of antiviral therapy in such setting. PATIENTS AND METHODS We conducted a retrospective study of 557 consecutive treatment-naive patients who started either ETV (n=443) or TDF (n=114) at 3 US liver clinics between January 2005 and 2012. Primary study endpoint was complete viral suppression (CVS) rate (hepatitis B virus DNA<40 IU/mL). RESULTS The majority of patients in both ETV and TDF groups were Asians, hepatitis B e antigen (HBeAg) negative, male, and with similar pretreatment alanine aminotransferase and hepatitis B virus DNA levels. Similar proportions of patients in the ETV and TDF groups achieved CVS at 24 months: 87.7% versus 87.0%, respectively. Cumulative rates of virological breakthrough in the ETV and TDF groups were 1.0% versus 4.8% (P=0.26) and 3.7% versus 9.8% (P=0.04) at month 12 and 24, respectively; and all were associated with medication nonadherence. Cumulative rate of medication nonadherence was lower in the ETV than TDF group: 4.6% versus 7.8% at month 12 and 8.9% versus 16.9% at month 24, respectively. CONCLUSIONS Patients treated with either ETV or TDF achieve a similar rate of CVS at 24 months. The primary contributor to suboptimal response was medication nonadherence. Attention to medication adherence is needed in a routine clinical setting.
Collapse
|
|
13
|
Ahn J, Lee HM, Lim JK, Pan CQ, Nguyen MH, Ray Kim W, Mannalithara A, Trinh H, Chu D, Tran T, Min A, Do S, Te H, Reddy KR, Lok AS. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study. Aliment Pharmacol Ther 2016; 43:134-144. [PMID: 26510638 PMCID: PMC4926997 DOI: 10.1111/apt.13440] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2015] [Revised: 08/12/2015] [Accepted: 10/03/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection. AIM To determine the safety and effectiveness of ETV in 'real-world' HBV patients in the United States (US). METHODS Treatment-naïve HBV patients ≥18 years old who received ETV for ≥12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated. RESULTS Of 841 patients, 658 [65% male, 83% Asian; median age 47 years] met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg- patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five-year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%. CONCLUSION Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.
Collapse
Affiliation(s)
- J Ahn
- Division of Gastroenterology & Hepatology, Oregon Health & Science University, Portland, OR, USA
| | - H M Lee
- Gastroenterology/Hepatology Division, Tufts Medical Center, Boston, MA, USA
| | - J K Lim
- Digestive Diseases, Yale University, New Haven, CT, USA
| | - C Q Pan
- Department of Medicine, NYU Langone, New York, NY, USA
| | - M H Nguyen
- Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA
| | - W Ray Kim
- Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA
| | - A Mannalithara
- Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA, USA
| | - H Trinh
- San Jose Gastroenterology, San Jose, CA, USA
| | - D Chu
- Albert Einstein College of Medicine, New York, NY, USA
| | - T Tran
- Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - A Min
- Division of Gastroenterology, Mount Sinai Beth Israel, New York, NY, USA
| | - S Do
- Digestive Health Associates of Texas, Plano, TX, USA
| | - H Te
- Digestive Disease Center, University of Chicago, Chicago, IL, USA
| | - K R Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
| | - A S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| |
Collapse
|
|
14
|
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1933] [Impact Index Per Article: 214.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Collapse
Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
15
|
Liu F, Zou F, Wang X, Hu H, Hu P, Ren H. A model with combined viral and metabolic factors effectively predicts HBeAg status under long term entecavir therapy: a prospective cohort study. Virol J 2015; 12:179. [PMID: 26527281 PMCID: PMC4630878 DOI: 10.1186/s12985-015-0409-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 10/23/2015] [Indexed: 12/24/2022] Open
Abstract
Background & Aim The aim was to extract factors from virologic and biochemical profiles at baseline and 24 weeks of treatment to predict HBeAg seroconversion in patients treated with ETV. Methods HBeAg positive chronic hepatitis B patients receiving ETV naïve-treatment were enrolled. HBV DNA, ALT, and serological markers were prospectively monitored every 6 months for 240 weeks. The cumulative rates of virologic response (VR), biochemical response (BR), and HBeAg seroconversion were determined, and potential predictors for HBeAg seroconversion were identified through uni/multivariate analysis. Result Two hundred twenty nine patients were eligible for this study. The cumulative rates of VR, BR, and HBeAg seroconversion at 240 weeks were 88.4 %, 100 %, and 36.7 %, respectively. Multivariate analysis showed that HBV DNA (OR, 2.8, p = 0.003), ALT (OR, 2.6, p = 0.005) at baseline, undetectable HBV DNA within 24 weeks (OR = 3.2, p < 0.001), and body mass index (BMI) ≥24kg/m2 (OR = 0.038, p = 0.013) were associated with HBeAg seroconversion. A prediction model for probability of HBeAg seroconversion was constructed. Patients can be classified into high (>40 %), intermediate (20–40 %), or low (≤20 %) groups based on the calculated probability of HBeAg seroconversion. The cumulative rates of HBeAg seroconversion were different among the three groups (p < 0.001). About 58 % patients in the high probability group achieved HBeAg seroconversion while almost 90 % patients within the low group remained HBeAg positive. Conclusion A combination of HBV DNA, ALT and BMI values at baseline, and undetectable HBV DNA level within 24 weeks can predict HBeAg seroconversion. Both viral and metabolic factors likely determine HBeAg status with ETV treatment. Trial registration CTR20132358
Collapse
Affiliation(s)
- Fen Liu
- Department of Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China.
| | - Feng Zou
- Department of Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China.
| | - Xiwei Wang
- Department of Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China. .,Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China.
| | - Huaidong Hu
- Department of Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China. .,Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China.
| | - Peng Hu
- Department of Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China. .,Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China.
| | - Hong Ren
- Department of Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China. .,Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Linjiang Road, Yuzhong District, Chongqing, China.
| |
Collapse
|
|
16
|
Boettiger DC, Kerr S, Ditangco R, Chaiwarith R, Li PC, Merati TP, Pham TTT, Kiertiburanakul S, Kumarasamy N, Vonthanak S, Lee CK, Van Kinh N, Pujari S, Wong WW, Kamarulzaman A, Zhang F, Yunihastuti E, Choi JY, Oka S, Ng OT, Kantipong P, Mustafa M, Ratanasuwan W, Durier N, Law M. Tenofovir-based antiretroviral therapy in
HBV-HIV coinfection: results from the TREAT Asia HIV Observational Database. Antivir Ther 2015; 21:27-35. [PMID: 26069150 DOI: 10.3851/imp2972] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2015] [Indexed: 01/13/2023]
Abstract
BACKGROUND The World Health Organization recommends HBV-HIV-coinfected individuals start antiretroviral therapy containing tenofovir. Here we describe first-line tenofovir use and treatment outcomes in coinfected patients in Asia. METHODS HBV surface antigen positive patients enrolled in the TREAT Asia HIV Observational Database who started first-line antiretroviral therapy were included. Logistic regression adjusted for period of treatment initiation was used to determine factors associated with tenofovir use. Generalized estimating equations were used to evaluate factors associated with alanine transaminase levels and CD4(+) T-cell count on treatment. RESULTS There were 548 eligible patients, of whom 149 (27.2%) started tenofovir. Patients treated in high/high-middle income countries (odds ratio 4.4 versus low/low-middle, 95% CI 2.6, 7.4; P<0.001) and those with elevated baseline alanine transaminase (odds ratio 4.2 versus normal, 95% CI 2.4, 7.2; P<0.001) were more likely to receive tenofovir. Hepatitis C antibody positive patients (odds ratio 0.4 versus negative, 95% CI 0.2, 0.8; P=0.008) were less likely. In those starting antiretroviral therapy with elevated alanine transaminase, mean reduction after tenofovir initiation was 11.2 IU/l (95% CI 0.9, 21.6; P=0.034) lower compared with those using a non-tenofovir-based regimen although this did not significantly increase the chance of alanine transaminase normalization. Tenofovir use was not associated with a superior CD4(+) T-cell response. CONCLUSIONS HBV-HIV-coinfected patients in Asia are most likely to receive tenofovir if they are treated in a high/high-middle income country, have elevated alanine transaminase levels and are hepatitis C antibody negative. Compared to other antiretroviral therapies, tenofovir-based regimens more effectively reduce liver inflammation in HBV-HIV-coinfection but do not result in superior CD4(+) T-cell recovery.
Collapse
|
|
17
|
Rybicka M, Stalke P, Bielawski K. Dynamics of hepatitis B virus quasispecies heterogeneity in association with nucleos(t)ide analogue treatment determined by MALDI-TOF MS. Clin Microbiol Infect 2015; 21:288.e1-4. [DOI: 10.1016/j.cmi.2014.10.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 09/25/2014] [Accepted: 10/05/2014] [Indexed: 01/04/2023]
|
|
18
|
Abstract
Chronic hepatitis B virus (HBV) infection is a global health problem, leading to cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Universal hepatitis B vaccination is the most cost-effective way to eradicate HBV infection with the remarkable reduction of chronic carriage, neonatal fulminant hepatitis and childhood HCC. The introduction of highly effective antiviral agents, including lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir disoproxil fumarate and pegylated interferons further improve short-, medium- and long-term outcomes of chronic HBV infection, such as ALT normalization, HBV DNA suppression, HBeAg seroconversion, HBsAg seroclearance, fibrosis regression, reduction of cirrhosis, HCC, liver-related deaths and the need for liver transplantation. Above all, sustained and profound viral suppression is the key to improve the clinical outcomes of chronic hepatitis B.
Collapse
Affiliation(s)
- Tung-Hung Su
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan
| | | |
Collapse
|
|
19
|
Su WC, Hsieh TC, Hsieh TY, Tseng KC, Peng CY, Lin CL, Su TH, Hsiao TH, Tseng TC, Lin HH, Wang CC, Kao JH. Younger age and female sex predict a better therapeutic response in HBeAg-positive chronic hepatitis B patients to entecavir therapy. ADVANCES IN DIGESTIVE MEDICINE 2014. [DOI: 10.1016/j.aidm.2014.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
|
|
20
|
Ridruejo E. Treatment of chronic hepatitis B in clinical practice with entecavir or tenofovir. World J Gastroenterol 2014; 20:7169-7180. [PMID: 24966587 PMCID: PMC4064062 DOI: 10.3748/wjg.v20.i23.7169] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 11/20/2013] [Accepted: 01/02/2014] [Indexed: 02/07/2023] Open
Abstract
Results from phase III clinical trials clearly demonstrate the efficacy and safety of entecavir and tenofovir in the controlled environment of randomized clinical studies. There are several studies with both drugs performed in clinical practice (also called "real life studies"). Despite the pros and cons, studies performed in real life conditions represent everyday practice and add important information about long term treatment effectiveness and safety in this clinical setting. This review shows that patients treated with first line nucleos(t)ide analogs at referral centres, with good clinical follow-up and adherence to international guidelines, can achieve high treatment response rates with a very low rate of adverse events.
Collapse
|
|
21
|
Ridruejo E, Marciano S, Galdame O, Reggiardo MV, Muñoz AE, Adrover R, Cocozzella D, Fernandez N, Estepo C, Mendizabal M, Romero GA, Levi D, Schroder T, Paz S, Fainboim H, Mandó OG, Gadano AC, Silva MO. Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice. Ann Hepatol 2014; 13:327-336. [DOI: 10.1016/s1665-2681(19)30861-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
|
|
22
|
Wang J. Clinical utility of entecavir for chronic hepatitis B in Chinese patients. DRUG DESIGN DEVELOPMENT AND THERAPY 2013; 8:13-24. [PMID: 24376343 PMCID: PMC3865082 DOI: 10.2147/dddt.s41423] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The People's Republic of China has one of the highest rates of hepatitis B virus (HBV) infection. This review summarizes recent data from studies of entecavir, one of the recommended first-line oral therapies for treating chronic hepatitis B, in Chinese HBV-infected patients. Long-term treatment with entecavir is efficacious and well tolerated, and studies comparing entecavir with other nucleos(t)ide therapies, such as lamivudine, adefovir, and telbivudine, demonstrate superior antiviral effects for entecavir therapy and comparable safety profiles. Entecavir monotherapy and combination treatment with other nucleos(t) ide analogs has been shown to be efficacious in the treatment of lamivudine-resistant and adefovir-resistant patients with HBV infection, as well as in patients with multidrug-resistant disease. Entecavir has also been shown to be effective in patients with HBV-associated clinical morbidity, including cirrhosis and liver failure, as well as in preventing recurrence of HBV following liver transplantation and in preventing reactivation of HBV after immunosuppres-sive therapy. Although the cost of anti-HBV therapy is a particular concern in the People's Republic of China, a number of studies have recently demonstrated that entecavir (particularly long-term therapy) represents a more cost-effective treatment strategy compared with other nucleos(t)ide therapies. Further research is required to assess the effects of entecavir combination therapy on hepatitis B surface antigen clearance, and in drug-resistant patients in the People's Republic of China.
Collapse
Affiliation(s)
- Jiyao Wang
- Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Medical, Molecular Virology of MOE/MOH, Shanghai, People's Republic of China
| |
Collapse
|
|
23
|
|