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Martin P, Nguyen MH, Dieterich DT, Lau DTY, Janssen HLA, Peters MG, Jacobson IM. Treatment Algorithm for Managing Chronic Hepatitis B Virus Infection in the United States: 2021 Update. Clin Gastroenterol Hepatol 2022; 20:1766-1775. [PMID: 34329775 DOI: 10.1016/j.cgh.2021.07.036] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/15/2021] [Accepted: 07/21/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chronic hepatitis B (CHB) infection remains the most frequent etiology of hepatocellular carcinoma globally as well as a major cause of cirrhosis. Despite vaccination, substantial numbers of persons have already been infected with hepatitis B virus and remain at risk of progressive liver disease. METHODS In 2004, a CHB management algorithm was developed by a panel of North American hepatologists, which was subsequently updated in 2006, 2008, and 2015. Since the most recent version, several developments have altered the management of CHB. Tenofovir alafenamide, with a more favorable safety profile than tenofovir disoproxil fumarate, has been introduced as an initial antiviral choice as well as an alternative for long-term therapy. Quantitation of hepatitis B surface antigen is becoming more widely available in clinical practice, with implications for monitoring response to treatment. Additionally, there has been a shift in how the natural history of CHB is perceived, as newer evidence has challenged the concept that during the immunotolerant phase of infection disease progression is not a concern. Finally, recent analyses indicate that in the United States, the average age of patients with CHB has increased, implying that the presence of comorbidities, including metabolic liver disease, increasing use of biologics associated with aging will increasingly affect disease management. RESULTS This updated algorithm is intended to serve as a guide to manage CHB while new antiviral strategies are developed. CONCLUSIONS Recommendations have been based on evidence from the scientific literature, when possible, as well as clinical experience and consensus expert opinion. Points of continued debate and areas of research need are also described.
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Affiliation(s)
- Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, Florida.
| | - Mindie H Nguyen
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California
| | | | - Daryl T-Y Lau
- Liver Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Harry L A Janssen
- Toronto Centre for Liver Diseases, University Health Network, Toronto, Canada
| | - Marion G Peters
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Ira M Jacobson
- Division of Gastroenterology, NYU Langone Health, New York, New York
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Lee J, Cho S, Kim HJ, Lee H, Ko MJ, Lim YS. High level of medication adherence is required to lower mortality in patients with chronic hepatitis B taking entecavir: A nationwide cohort study. J Viral Hepat 2021; 28:353-363. [PMID: 33051945 DOI: 10.1111/jvh.13418] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 07/11/2020] [Accepted: 09/07/2020] [Indexed: 02/06/2023]
Abstract
It is unclear whether suboptimal adherence contributes to adverse clinical outcomes in patients with chronic hepatitis B (CHB). Moreover, there is no consensus regarding the optimal level of drug adherence. This was a population-based historical cohort study including 51 975 adult CHB patients treated with entecavir (0.5 mg/d orally). Data were obtained from the Korean national health insurance service claims database, which covers >99% of the entire population, between 2007 and 2015. Medication adherence was categorized as high (proportion of days covered [PDC], ≥90%; n = 32 089), intermediate (PDC, 80%-89%; n = 10 197) and low (PDC, <80%; n = 9689). During a median 4.5 years (maximal 9 years) of follow-up in 51 975 CHB patients treated with entecavir, multivariable analyses revealed that the risk of mortality/transplantation was significantly greater in the low-adherers (adjusted hazard ratio [HR], 1.38; P < .001) and intermediate-adherers (adjusted HR, 1.44; P < .001) than the high-adherers (P for trend < 0.001). The risk of renal failure in the low- and intermediate-adherence groups was also significantly higher than the high-adherence group (P for trend < 0.001). By contrast, the risk of hepatocellular carcinoma (HCC) was not significantly different between groups (P for trend = 0.70). The higher risk of mortality/transplantation and renal failure but similar risk of HCC for low- and intermediate-adherers compared with high-adherers was consistent in inverse probability treatment weighting analysis of the entire cohort and subcohorts with or without cirrhosis. In conclusion, high medication adherence (≥90%) is required to significantly lower risk of mortality and renal failure in patients with CHB during long-term treatment with entecavir.
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Affiliation(s)
- Jayoun Lee
- Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Songhee Cho
- Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Hyo Jeong Kim
- Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Hangil Lee
- Seoul-Gangwon Regional Headquarters, National Health Insurance Service, Seoul, Republic of Korea
| | - Min Jung Ko
- Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Young-Suk Lim
- Division for Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea.,Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Li Y, Chen A, Wang H, Han L, Wang R, Zhang G, Yuan Y. Treatment Adherence to Nucleos(t)ide Analogs in Chinese Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: A Single-Center Cross-Sectional Study. Patient Prefer Adherence 2021; 15:1729-1738. [PMID: 34408406 PMCID: PMC8364380 DOI: 10.2147/ppa.s317250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 07/20/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Chronic hepatitis B virus (HBV) infection is a crucial risk factor in the occurrence and development of hepatocellular carcinoma (HCC). Antiviral therapy is very important for patients with HBV-related HCC. To maintain undetectable level of HBV DNA, patients must take nucleos(t)ide analogues (NUCs) appropriately and regularly. We explored the adherence of Chinese patients with HBV-related HCC to antiviral treatment. PATIENTS AND METHODS One-hundred and eighty-one patients were included in a cross-sectional study between August 2020 and February 2021. A structured questionnaire was used to interview patients, and a form was applied to collect data from electronic medical records. Medication adherence was measured using a visual analog scale. Data of the adherent group and non-adherent group were compared using Student's t-test and the chi-square test. Multivariate logistic regression analysis was employed to explore independent risk factors that affected adherence behavior. RESULTS High adherence was reported in 46.4% of patients with HBV-related HCC. Patients with high adherence were more likely to be women (P = 0.02), shun alcohol (P = 0.01), take NUCs other than entecavir (P = 0.04), and pay attention to their titer of HBV DNA (P = 0.05). Sex, alcohol consumption, and taking entecavir were independent risk factors for low adherence (P < 0.05). The prevalence of virological breakthrough was lower in patients who adhered to NUC therapy than in those who did not, but the difference was not significant (P = 0.31). CONCLUSION The adherence of patients with HBV-related HCC to NUC therapy was low. More attention should be paid to adherence of antiviral therapy in patients with HBV-related HCC.
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Affiliation(s)
- Yueyue Li
- Department of Pharmacy, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Anni Chen
- Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai, 200438, People’s Republic of China
| | - Hui Wang
- Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai, 200438, People’s Republic of China
| | - Lu Han
- Department of Pharmacy, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Rong Wang
- Department of Pharmacy, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Guoqing Zhang
- Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai, 200438, People’s Republic of China
| | - Yongfang Yuan
- Department of Pharmacy, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, People’s Republic of China
- Correspondence: Yongfang Yuan Department of Pharmacy, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, People’s Republic of ChinaFax +86 21 5678 6907 Email
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Persistence and adherence to nucleos(t)ide analogues in chronic hepatitis B: a multicenter cohort study. Eur J Gastroenterol Hepatol 2020; 32:635-641. [PMID: 31688309 DOI: 10.1097/meg.0000000000001558] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Adherence and persistence to long-term therapy with nucleos(t)ides analogues are crucial to the outcome of treatment in chronic hepatitis B. Our aim was to determine the persistence and adherence rates to nucleos(t)ides analogues in chronic hepatitis B patients under maintenance therapy and to identify relative to prediction of adherence factors. METHODS We retrospectively analyzed electronic prescription data of patients (2011-2016; n = 400) with chronic hepatitis B treated with nucleos(t)ides analogues at 4 tertiary liver centers in Greece. RESULTS Two hundred ninety-six of 400 patients were under or initiated treatment in 2011-2012 (existing patients), while the remainder initiated or switched medication from January 2013 and onward (new patients). The median adherence rate was 99%, with 89.7% achieving adherence >80% during a mean follow-up of 28 ± 14 months. The overall 12-month persistence rate was 57%, with no difference between patients receiving tenofovir, entecavir or double therapy (57.8%, 52.8% and 68.4%, respectively, P = 0.399). The decline in persistence was more pronounced during the first 3 months of follow-up and in existing patients (P = 0.057). Overall, 80% and 55.1% of nonpersistent patients succeeded adherence to nucleos(t)ides analogues >80% and >90%, respectively. Multivariate analyses showed that existing (vs. new) patients were less likely to have >80% adherence (odds ratio: 0.324, P = 0.44) and persistence (odds ratio: 0.562, P = 0.057) to nucleos(t)ides analogues therapy. CONCLUSION In this real-world cohort of chronic hepatitis B patients, high adherence to nucleos(t)ides analogues was coupled with suboptimal persistence with prescribing the medication. Our data indicate that persistence and adherence are distinct measures that should be approached separately in educational programs targeting to improve medication-taking behavior in chronic hepatitis B.
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Abstract
Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.
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Wu Z, Gong Y, Peng J, Zhang X, Tang L. Correlation Between Serum Entecavir Concentration and Virological Response in Patients with Chronic Type B Hepatitis. Med Sci Monit 2019; 25:6998-7004. [PMID: 31530794 PMCID: PMC6765337 DOI: 10.12659/msm.916553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background This study was conducted to investigate the relationship between trough concentrations of serum entecavir and the virological response of patients with chronic type B hepatitis (CHB). Material/Methods A total of 59 CHB patients who had been receiving antiviral therapy with entecavir for >3 months were included in this study. Serum entecavir concentrations, HBV DNA levels, and other biochemical indicators were determined after drug treatments. Results The serum entecavir concentrations in the good response and poor response groups were 0.58±0.38 and 0.43±0.15 ng/mL, respectively. The antiviral efficacy was 52.38%, 65.63%, and 100% in low, middle, and high entecavir groups, respectively. The baseline HBV DNA level among the patients with poor response was significantly higher than in the group with good response. Among the 14 patients with a high viral load, 5 patients showed a good response and had a higher entecavir concentration than the other 9 patients with poor response. Entecavir in patients with cirrhosis was higher than in those without cirrhosis (0.63±0.45 ng/mL vs. 0.46±0.16 ng/mL), and the virological response rate in patients with cirrhosis was higher than in those without cirrhosis (83.33 vs. 51.43%). Cirrhosis progression was reversed in 3 patients with high serum entecavir concentration. Conclusions Serum entecavir concentrations vary among individuals, and higher serum entecavir concentration is correlated with more efficient viral clearance. Therefore, for patients with poor response, high doses may be beneficial for viral clearance.
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Affiliation(s)
- Zhengjie Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Yiwen Gong
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Jun Peng
- Hangzhou Biozon Medical Institute, Hangzhou, Zhejiang, China (mainland)
| | - Xiao Zhang
- Hangzhou Biozon Medical Institute, Hangzhou, Zhejiang, China (mainland)
| | - Lingling Tang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
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Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
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Desalegn H, Aberra H, Berhe N, Mekasha B, Stene-Johansen K, Krarup H, Pereira AP, Gundersen SG, Johannessen A. Treatment of chronic hepatitis B in sub-Saharan Africa: 1-year results of a pilot program in Ethiopia. BMC Med 2018; 16:234. [PMID: 30554571 PMCID: PMC6296040 DOI: 10.1186/s12916-018-1229-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 11/30/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia. METHODS At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data. RESULTS Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04-5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33-8.88). CONCLUSIONS This pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa. TRIAL REGISTRATION NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
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Affiliation(s)
- Hailemichael Desalegn
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Hanna Aberra
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Nega Berhe
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.,Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, 0424, Oslo, Norway
| | - Bitsatab Mekasha
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | | | - Henrik Krarup
- Section of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark
| | | | - Svein Gunnar Gundersen
- Research Unit, Sørlandet Hospital HF, Kristiansand, Norway.,Department of Global Development and Planning, University of Agder, Kristiansand, Norway
| | - Asgeir Johannessen
- Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, 0424, Oslo, Norway. .,Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway.
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Xu K, Liu LM, Farazi PA, Wang H, Rochling FA, Watanabe-Galloway S, Zhang JJ. Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B. Glob Health Action 2018; 11:1433987. [PMID: 29447614 PMCID: PMC5827725 DOI: 10.1080/16549716.2018.1433987] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background: Globally, of the 248 million people chronically infected with the hepatitis B virus (HBV), 74 million reside in China. Five oral nucleot(s)ide analogs (NUCs) have been approved for the treatment of chronic hepatitis B (CHB) in China. Objectives: The aims of this study were to determine rates of adherence to NUC therapy in patients with CHB, to identify the self-perceived barriers to adherence, and to examine the factors associated with adherence. Methods: Questionnaire-based interviews were administered among Chinese patients with CHB at hepatology clinics of a tertiary hospital in the city of Wuhan, China. Adults aged 18 years or older prescribed with NUCs were recruited and interviewed to complete a 27-item questionnaire in a private setting, and adherence was measured using the Morisky Medication Adherence Scale (MMAS-8). Results: Among 369 participants, only 16.5% had high adherence (score of 8), 32.2% had medium adherence (score of 6 to <8), and 51.2% were measured with low adherence (score of <6). A logistic regression model was used to determine the factors associated with medication adherence. Significant predictors of high adherence consisted of urban residency, non-cirrhotic status, not using prescribed pills other than HBV medications, and reminders from family members. The five most common reasons for skipping NUCs were that medication(s) are expensive (48.7%), forgetfulness (45.1%), have experienced or worry about potential side effects (19.8%), do not want others to know about my medication(s) usage (18.5%), and ran out of pills and do not have time to refill (15.9%). Conclusions: This study revealed that adherence rates to oral antiviral therapy were far from optimal. This finding should generate public attention, and it would be beneficial for interventional programs to target Chinese patients from rural regions, as well as patients with low socioeconomic status, cirrhosis, and taking multiple medications.
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Affiliation(s)
- Kerui Xu
- a Department of Epidemiology, College of Public Health , University of Nebraska Medical Center , Omaha , NE , USA
| | - Li-Ming Liu
- b Department of Hepatology , Hubei Third People's Hospital , Wuhan , Hubei , China
| | - Paraskevi A Farazi
- a Department of Epidemiology, College of Public Health , University of Nebraska Medical Center , Omaha , NE , USA
| | - Hongmei Wang
- c Department of Health Services Research & Administration, College of Public Health , University of Nebraska Medical Center , Omaha , NE , USA
| | - Fedja A Rochling
- d Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine , University of Nebraska Medical Center , Omaha , NE , USA
| | - Shinobu Watanabe-Galloway
- a Department of Epidemiology, College of Public Health , University of Nebraska Medical Center , Omaha , NE , USA
| | - Jian-Jun Zhang
- b Department of Hepatology , Hubei Third People's Hospital , Wuhan , Hubei , China
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Kim DY, Park JY. Step-down strategy in antiviral resistant chronic hepatitis B patients who achieved viral suppression with rescue combination therapy. Future Virol 2018. [DOI: 10.2217/fvl-2018-0078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In the treatment of chronic hepatitis B (CHB) patients with drug resistance, rescue combination therapy leads to viral suppression in almost all patients. However, once it is achieved, lifelong maintenance especially, by using combination therapy is not always possible in a significant proportion of patients. At present, there is no consensus on whether it is possible to switch to monotherapy from combination therapy. However, there is robust evidence to support step-down therapy, which involves switching from combination therapy to monotherapy in antiviral resistant CHB patients who achieve complete viral response from combination therapy. We review the evidence in favor of switching to monotherapy in antiviral resistant CHB patients who achieve complete viral response by combination therapy.
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Affiliation(s)
- Dong Yun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Ford N, Scourse R, Lemoine M, Hutin Y, Bulterys M, Shubber Z, Donchuk D, Wandeler G. Adherence to Nucleos(t)ide Analogue Therapies for Chronic Hepatitis B Infection: A Systematic Review and Meta-Analysis. Hepatol Commun 2018; 2:1160-1167. [PMID: 30288470 PMCID: PMC6167073 DOI: 10.1002/hep4.1247] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 07/15/2018] [Indexed: 01/06/2023] Open
Abstract
Successful treatment outcomes for chronic hepatitis B virus (HBV) infection requires high levels of adherence to treatment. We searched three databases and abstracts from two conferences up to January 2018 for studies reporting the proportion of patients who were adherent to HBV antiviral therapy and pooled data using random effects meta-analysis. We included 30 studies, providing data for 23,823 patients. Overall, adherence to treatment was 74.6% (95% confidence interval [CI] 67.1%-82.1%). Adherence was similar in high-income settings (75.1%; 95% CI, 65.4%-85.0%) and in low-income and middle-income settings (72.9%; 95% CI, 57.8%-88.0%). Reported barriers to adherence included forgetting, limited understanding of the importance of adherence, and change to routine. Conclusion : There is a need to reinforce assessment and reporting of adherence as a routine part of HBV care and to assess the extent to which evidence-based interventions to improve adherence to medication for human immunodeficiency virus [HIV] and other chronic diseases are effective for HBV infection.
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Affiliation(s)
- Nathan Ford
- Department of HIV and Global Hepatitis Program World Health Organization Geneva Switzerland
| | - Roz Scourse
- Médecins Sans Frontières Access Campaign Geneva Switzerland
| | - Maud Lemoine
- Department of Surgery and Cancer St Mary's Hospital, Imperial College London London United Kingdom
| | - Yvan Hutin
- Department of HIV and Global Hepatitis Program World Health Organization Geneva Switzerland
| | - Marc Bulterys
- Department of HIV and Global Hepatitis Program World Health Organization Geneva Switzerland
| | - Zara Shubber
- Department of Infectious Disease Epidemiology Imperial College London London United Kingdom
| | | | - Gilles Wandeler
- Department of Infectious Diseases and Institute of Social and Preventive Medicine University of Berne Berne Switzerland
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12
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Su Q, Liu Y, Li J. Combined effect of pegylated interferon α with adefovir on renal function in Chinese patients with chronic hepatitis B. Medicine (Baltimore) 2018; 97:e12089. [PMID: 30142868 PMCID: PMC6113016 DOI: 10.1097/md.0000000000012089] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) and/or interferon alfa (IFN-α) therapies have previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos (t)ide analogues (NAs) and IFN-α. The aim of this analysis was to assess the renal function during combined therapy with pegylated interferon α-2b (PEG-IFN-α-2b) and ADV versus PEG-IFN-α-2b alone in patients with chronic hepatitis B (CHB). METHODS We performed a multicenter, prospective, open-label, randomized-controlled trial of renal function data to investigate the efficacy of 48 weeks of therapy with PEG-IFN-α-2b and ADV versus PEG-IFN-α-2b alone in 102 patients with CHB in Anhui, China. Glomerular filtration rates (GFRs) were calculated by Cockcroft-Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and were tested by repeated-measures 1-way analysis of variance within groups. A linear mixed effects model for repeated measures was also used to evaluate the association between baseline information and estimated glomerular filtration rate (eGFR) changes overtime in all enrolled patients. The model considered the baseline age, sex, HBV DNA, aminotransferase, treatment group, time, and group-by-time interaction as fixed effects and incorporated random effects for individual subjects. RESULTS After 48 weeks of therapy and further 24 weeks of follow-up, the eGFR decreased both in patients given PEG-IFN-α-2b single therapy and combined therapy. Age, HBV DNA, and combined therapy were significant negative predictive factors for eGFR changes. CONCLUSION The incidence of renal adverse events in both groups was low, and the combination therapy may have delayed, but reversible renal impairment.
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Affiliation(s)
- Qian Su
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University
| | - Yanyan Liu
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University
| | - Jiabin Li
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University
- Department of Infectious Diseases, Chaohu Affiliated Hospital of Anhui Medical University, Hefei, China
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Kim DY, Lee HW, Song JE, Kim BK, Kim SU, Kim DY, Ahn SH, Han KH, Park JY. Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance. J Med Virol 2018; 90:497-502. [PMID: 29077211 DOI: 10.1002/jmv.24986] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 09/27/2017] [Indexed: 12/30/2022]
Abstract
It is unclear whether chronic hepatitis B (CHB) patients with antiviral resistance, who achieve a complete virologic response (CVR) with tenofovir disoproxil fumarate (TDF) and nucleoside analogue (NUC) combination therapy, maintain CVR if switched to TDF monotherapy. We investigated the persistence of CVR after cessation of NUC in virologically suppressed antiviral resistant CHB patients using TDF+NUC combination therapy. This study recruited 76 antiviral-resistant CHB patients showing CVR on TDF+entecavir (ETV) (n = 52), TDF+lamivudine (LAM; n = 14), and TDF+telbivudine (LdT; n = 10) combination therapy, who were switched to TDF monotherapy as step-down therapy. At baseline, 47 patients were male and the median age was 53.0 years (range: 30-78 years); 72.3% cases were hepatitis B e antigen-positive (HBeAg+) and 23.7% were of liver cirrhosis. The median duration of TDF+NUC combination therapy was 20.8 months (range: 3-46 months). At a median follow-up of 24.7 months (range: 12-48 months) after switching to TDF monotherapy, all 76 patients maintained CVR, regardless of the duration of combination therapy and the type of prior NUC and antiviral resistance. Renal dysfunction was not observed during the treatment period. The step-down strategy of switching from TDF+NUC combination therapy to TDF monotherapy in virologically suppressed CHB patients with antiviral resistance should be considered.
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Affiliation(s)
- Dong Yun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Jeong Eun Song
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
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Entecavir Combined With Adefovir Ameliorates Patients With Chronic Hepatitis B Who Fail to Respond to Nucleotide (Acid) Analog Monotherapy. Am J Ther 2018; 24:e250-e258. [PMID: 25923228 DOI: 10.1097/mjt.0000000000000262] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The aim of this study was to evaluate the efficacy and safety of entecavir (ETV) combined treatment with adefovir (ADV) on chronic hepatitic B (CHB) patients who failed to respond to nucleotide (acid) analog (NA) treatment. On this basis, the possible factors in the combined treatment of these patients will be analyzed. The safety, biochemical index, and the possible factors that might affect the ETV and ADV combined treatment at different points in time were retrospectively analyzed. The biochemical index included the following: virological response, hepatitis B virus (HBV) DNA decline, primary nonresponse, biochemical response, and the hepatitis B virus E antigen/hepatitis B virus E antibody seroconversion rate. There were 94 CHB patients and compensated liver cirrhosis patients who received ETV plus ADV treatment for over 12 weeks after failure of treatment with NAs. The authors have also investigated 76 CHB patients (80.9%) and 18 hepatitis B cirrhosis patients (19.1%) in this study. The HBV DNA baseline was 4.4 ± 1.4 log10 IU/mL, and the positive rate of HBeAg before salvage treatment was 78.7% (74/94). The sample sizes were 94, 78, 42, 10, 6, and 1 for follow-up of 24, 48, 96, 144, 192, and 240 weeks, respectively. The virological responses (HBV DNA < 2 log10 IU/mL) and biochemical responses were 52.1%, 74.3%, and 90.4% and 63.1%, 61.6%, and 81.1%, respectively, at 24, 48, and 96 weeks, which showed significant differences (P < 0.001 and P < 0.005, respectively). The HBV DNA decline was presented as mean ± SEM, which were 1.53 ± 1.23, 1.75 ± 1.37, 2.07 ± 1.54, and 2.39 ± 1.77 log10 IU/mL at 12, 24, 48, and 96 weeks, respectively. They showed significant differences compared with the baseline (χ = 8.084, P < 0.05). The rate of primary nonresponse was 30.9% (29/94), and the primary treatment failure rates were 26.6% (25/94), 24.4% (19/78), and 4.8% (2/42) at 24, 48, and 96 weeks, respectively. They all have statistical difference (P = 0.011 < 0.05). There were 23 patients who experienced virological breakthrough after the HBV DNA levels were undetectable, whereas after follow-up for 12-24 weeks, the HBV DNA levels were back to undetectable again. ETV plus ADV treatment is an efficient and safe treatment for CHB and compensated liver cirrhosis patients who experienced NA treatment failure. The high quantity of baseline HBV DNA level is a risk factor for poor efficacy of salvage treatment.
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Clinical Course of Partial Virologic Response with Prolonged Tenofovir Therapy in Nuclos(t)ides-Naïve Patients with Chronic Hepatitis B. Dig Dis Sci 2017; 62:2908-2914. [PMID: 28871337 DOI: 10.1007/s10620-017-4737-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Accepted: 08/24/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS The clinical course of chronic hepatitis B (CHB) patients with partial virologic response (PVR) during tenofovir disoproxil fumarate (TDF) therapy remains unclear. METHODS We retrospectively investigated the long-term clinical outcomes of TDF treatment in nucleos(t)ides-naïve CHB patients, particularly in those with PVR. RESULTS A total of 391 patients treated with TDF therapy for more than 12 months were included. Virologic response (VR) was achieved in 341 patients (87.2%). PVR was evident in 127 (45.3%) of the 391 patients. Multivariate logistic regression analysis using selected baseline factors identified absolute HBV DNA levels at baseline (OR 0.496; 95% CI 1.369-1.969) and HBeAg positivity (OR 0.622; 95% CI 1.096-3.167) as factors significantly associated with PVR. During continuous prolonged TDF therapy, 127 (71.8%) of 177 patients with PVR achieved VR. The cumulative rates of VR in patients with PVR at 12, 24, and 36 months were 42.4, 79.7, and 90.2%, respectively. Serum HBV DNA level at week 24 was significantly associated with VR in patients with PVR. CONCLUSIONS The vast majority of CHB patients with PVR achieved VR through prolonged TDF therapy, although the time to achieve VR was delayed in those with PVR. This suggests that adjustment of TDF therapy in patients with PVR is unnecessary.
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Lin D, Yang HI, Hoang J, Nguyen MH. Letter: reduction in chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low-risk patients - more questions than answers. Authors' reply. Aliment Pharmacol Ther 2017; 45:186-187. [PMID: 27910142 DOI: 10.1111/apt.13859] [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: 12/08/2022]
Affiliation(s)
- D Lin
- Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
| | - H-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - J Hoang
- Division of GI and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - M H Nguyen
- Division of GI and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
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Nguyen LH, Hoang J, Nguyen NH, Vu VD, Wang C, Trinh HN, Li J, Zhang JQ, Nguyen MH. Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real-life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection. Aliment Pharmacol Ther 2016; 44:390-9. [PMID: 27363288 PMCID: PMC5316284 DOI: 10.1111/apt.13709] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Revised: 03/26/2016] [Accepted: 06/07/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from US patients are limited. AIM To determine the incidence of HBsAg seroclearance in a real-life US cohort. METHODS In total, 4737 patients with chronic hepatitis B from five primary care, gastroenterology and multispecialty centres, and a university medical centre were retrospectively enrolled between 2001 and 2014 with data obtained by manual review of individual patient medical records. Seroclearance was determined by loss of HBsAg seropositivity. Persistent HBsAg was confirmed by direct serology or by proxy with positive hepatitis B e-antigen (HBeAg) or HBV DNA levels. RESULTS HBsAg seroclearance occurred in 52 patients over 16 844 person-years (0.31% annually, 1.2% overall). Median follow-up was 32 months, and mean age 45 ± 14 years. Incidence of HBsAg seroclearance was higher in non-Asians, age >45, males, and those with baseline HBV DNA ≤10 000 IU/mL. On multivariate Cox proportional modelling, non-Asian ethnicity (HR 2.8), male sex (HR 2.1), baseline HBVDNA ≤10 000 (HR 2.0) and age >45 (HR 1.8) were significant independent predictors of seroclearance. CONCLUSION HBsAg seroclearance rates were lower than previously described in this real-life cohort of patients with chronic hepatitis B, especially among Asian, female and younger patients.
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Affiliation(s)
- Long H. Nguyen
- Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.,Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Joseph Hoang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Nghia H. Nguyen
- Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Vinh D. Vu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Christina Wang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | | | - Jiayi Li
- Department of Gastroenterology, Palo Alto Medical Foundation, Mountain View, CA, USA
| | | | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
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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.
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Abreu RM, da Silva Ferreira C, Ferreira AS, Remor E, Nasser PD, Carrilho FJ, Ono SK. Assessment of Adherence to Prescribed Therapy in Patients with Chronic Hepatitis B. Infect Dis Ther 2016; 5:53-64. [PMID: 26757720 PMCID: PMC4811839 DOI: 10.1007/s40121-015-0101-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Indexed: 01/28/2023] Open
Abstract
Introduction Evidence shows that treatment for hepatitis B virus (HBV) can suppress viral load. Among the factors directly linked to therapeutic success is adherence to the treatment. Several instruments to assess adherence are available, but they are not validated for use in chronic hepatitis B. The purpose of this paper was to adapt and validate the “Assessment of Adherence to Antiretroviral Therapy Questionnaire—HIV” (CEAT-VIH) for patients with chronic hepatitis B (referred to herein as CEAT-HBV). Methods The validity of the adapted questionnaire evidence was established through concurrent, criterion, and construct validities. Results We found negative and significant correlation between the domain “degree of compliance to antiviral therapy” assessed by CEAT-HBV and the Morisky test (r = −0.62, P < 0.001) and between the domain “barriers to adherence” and HBV viral load (r = −0.42, P < 0.001). In terms of the construct’s discriminative capacity, scores greater than or equal to 80 detected antiviral therapy success, which are necessary for the prediction of an undetectable HBV viral load. Thus, a cutoff value of 80.5 was set with a value of 81% for sensitivity and 67% for specificity. Conclusion The CEAT-HBV identified 43% (n = 79) non-adherent patients and was shown to be a useful tool in clinical practice. Electronic supplementary material The online version of this article (doi:10.1007/s40121-015-0101-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Rodrigo Martins Abreu
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | - Camila da Silva Ferreira
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | - Aline Siqueira Ferreira
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | - Eduardo Remor
- Faculty of Psychology, Universidad Autónoma de Madrid, Madrid, Spain
| | - Paulo Dominguez Nasser
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | - Flair José Carrilho
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | - Suzane Kioko Ono
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of Sao Paulo School of Medicine, São Paulo, Brazil.
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Martin P, Lau DTY, Nguyen MH, Janssen HLA, Dieterich DT, Peters MG, Jacobson IM. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update. Clin Gastroenterol Hepatol 2015; 13:2071-87.e16. [PMID: 26188135 DOI: 10.1016/j.cgh.2015.07.007] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 07/01/2015] [Accepted: 07/09/2015] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis B (CHB) continues to be an important public health problem worldwide, including in the United States. An algorithm for managing CHB was developed by a panel of United States hepatologists in 2004 and subsequently updated in 2006 and 2008. Since 2008, additional data on long-term safety and efficacy of licensed therapies have become available and have better defined therapeutic options for CHB. The evidence indicates that potent antiviral therapy can lead to regression of extensive fibrosis or even cirrhosis, thus potentially altering the natural history of CHB. In addition, appropriate choice of antiviral agent can minimize the risk of resistance. This updated algorithm for managing CHB is based primarily on evidence from the scientific literature. Where data were lacking, the panel relied on clinical experience and consensus expert opinion. The primary aim of antiviral therapy for CHB is durable suppression of serum hepatitis B virus (HBV) DNA to low or undetectable levels. CHB patients who have HBV DNA >2000 IU/mL, elevated alanine aminotransferase level, and any degree of fibrosis should receive antiviral therapy regardless of their hepatitis B e antigen status. CHB patients with HBV DNA >2000 IU/mL and elevated alanine aminotransferase level but no evidence of fibrosis may also be considered for antiviral therapy. Approved antiviral therapies for CHB are interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir, entecavir, telbivudine, and tenofovir, although the preferred first-line treatment choices are peginterferon alfa-2a, entecavir, and tenofovir. In determining choice of therapy, considerations include efficacy, safety, rate of resistance, method of administration, duration, and cost.
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Affiliation(s)
- Paul Martin
- Division of Hepatology, University of Miami School of Medicine, Miami, Florida.
| | - Daryl T-Y Lau
- Liver Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California
| | - Harry L A Janssen
- Toronto Centre for Liver Diseases, University Health Network, Toronto, Canada
| | | | - Marion G Peters
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Ira M Jacobson
- Department of Medicine, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, New York
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Qiu Q, Duan XW, Li Y, Yang LK, Chen Y, Li H, Duan ZP, Wang L. Impact of partial reimbursement on hepatitis B antiviral utilization and adherence. World J Gastroenterol 2015; 21:9588-9597. [PMID: 26327766 PMCID: PMC4548119 DOI: 10.3748/wjg.v21.i32.9588] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 04/28/2015] [Accepted: 06/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the impact of partial reimbursement for antivirals on antiviral utilization and adherence for chronic hepatitis B patients. METHODS This was a retrospective cohort study. Two separate cohorts were enrolled, including 14163 and 16288 chronic hepatitis B outpatients, respectively. These patients were referred to Beijing You'an Hospital before and after the new partial reimbursement for antivirals, which was implemented on July 1, 2011. Demographic characteristics (including medical insurance status), routine biochemical, virological and serology laboratory test results, and antiviral agents' prescription information were collected from an electronic database. Patients were also defined as new and existing patients according to treatment history. Antiviral utilization, medication possession ratio and persistence rate were calculated and compared among the patients with different characteristics. A questionnaire survey was conducted among 212 randomly sampled outpatients from the same hospital to confirm the validity of the electronic database. Propensity score matching was used to adjust the distribution of patient's characteristics which may influence the antiviral utilization. χ(2) test or ANOVA was adopted and multivariate logistic regression was used to determine the factors associated with antiviral utilization and good adherence. RESULTS A total of 13364 outpatients from each cohort were enrolled after the propensity score matching. The antiviral utilization rate for the insured patients increased from 57.4% to 75.9% (P < 0.0001) after the reimbursement, and the rate among those who paid out-of-pocket increased from 54.9% to 56.7% (P = 0.028). Approximately 71% of the patients had a medication possession ratio of more than 80% in each cohort before reimbursement. This increased to 79.2% and 73.1% for insured patients and those who paid out-of-pocket, respectively (P < 0.0001). Insured patients and those who paid out-of-pocket had the similar persistence rates before reimbursement. But after reimbursement, insured patients had higher persistence rates than those who paid out-of-pocket at 6 (86.5% vs 81.5%, P < 0.0001), 9 (79.7% vs 69.9%, P < 0.0001), 12 (73.4% vs 61.9%, P < 0.0001), and 15 mo (66.6% vs 53.1%, P < 0.0001). The reimbursement could significantly improve adherence for the insured patients than those who paid out-of-pocket even after adjusting other covariates, with an interaction odds ratio of 1.422 (95%CI: 1.220-1.657, P < 0.0001). The questionnaire survey supported the validity of the electronic database. CONCLUSION The reimbursement policy shows a positive impact on antiviral utilization as well as adherence for insured chronic hepatitis B patients.
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Lu L, Yip B, Trinh H, Pan CQ, Han SHB, Wong CC, Li J, Chan S, Krishnan G, Wong CC, Nguyen MH. Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir. J Viral Hepat 2015; 22:675-81. [PMID: 25417914 PMCID: PMC4442074 DOI: 10.1111/jvh.12368] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Accepted: 10/18/2014] [Indexed: 12/22/2022]
Abstract
Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore, our aim was to compare the effectiveness of two alternate therapies--tenofovir (TDF) monotherapy and combination therapy of ETV+TDF--in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n = 25) or ETV+TDF (n = 43). Patients were seen in seven US liver/community-based clinics and started on ETV between 2005 and 2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pretreatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs 83%, P = 0.23) and 12 months (86% vs 84%, P = 0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR = 1.19, P = 0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs two pills (ETV+TDF) could lead to lower nonadherence rates and better treatment outcomes.
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Affiliation(s)
- Louis Lu
- Medical School, University of Michigan Medical School, Ann Arbor, MI, USA
,Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Benjamin Yip
- Medical School, Eastern Virginia Medical School, Norfolk, VA, USA
| | - Huy Trinh
- San Jose Gastroenterology, San Jose, CA, USA
| | - Calvin Q. Pan
- Division of Gastroenterology and Hepatology, NYU Langone Medical Center, NYU School of Medicine, New York, NY, USA
| | - Steven-Huy B. Han
- Pfleger Liver Institute, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA
| | | | - Jiayi Li
- Palo Alto Medical Foundation, Mountain View, CA, USA
| | | | - Gomathi Krishnan
- Stanford Center for Clinical Informatics, Stanford University School of Medicine, Stanford, CA, USA
| | | | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
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Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy. Eur J Gastroenterol Hepatol 2015; 27:871-6. [PMID: 25919771 DOI: 10.1097/meg.0000000000000368] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV. Our goal was to examine virologic outcomes in such patients. METHODS This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy, who were switched back to monotherapy with either ETV (n=16) or TDF (n=18), or continued on combination therapy (n=23). The majority of patients were Asian (91%) and male (65%), with a mean age of 41±12 years. RESULTS The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs. 39%, P=0.004). Patients who remained on ETV+TDF also had virologic breakthrough, due to either confirmed or suspected nonadherence. On multivariate analysis inclusive of age, sex, and hepatitis B virus DNA levels at initiation of combination therapy, ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 112.7, P=0.03), as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 60.2, P=0.03). CONCLUSION TDF monotherapy, especially in those who have had CVS for at least 12 months on combination therapy, may be considered for some ETV partial responders who have achieved CVS with combination therapy, given the financial advantage and convenience of monotherapy.
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van Vlerken LG, Arends P, Lieveld FI, Arends JE, Brouwer WP, Siersema PD, Janssen HL, van Erpecum KJ. Real life adherence of chronic hepatitis B patients to entecavir treatment. Dig Liver Dis 2015; 47:577-83. [PMID: 25936691 DOI: 10.1016/j.dld.2015.03.024] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Revised: 03/24/2015] [Accepted: 03/28/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Real-life prospective data on adherence to nucleos(t)ide analogues in chronic hepatitis B patients are scarce. AIMS We investigated adherence to entecavir in relation to virological response. METHODS In this prospective study, we provided 100 consecutive chronic hepatitis B patients with a medication dispenser that monitored entecavir intake during 16 weeks therapy. Hepatitis B virus (HBV) DNA was measured at baseline and after 16 weeks. Beliefs about medicines were evaluated using a questionnaire. RESULTS Adherence over 16 weeks averaged 85 ± 17%, with 70% of patients exhibiting good (i.e. ≥ 80%) adherence. Patients with poor (i.e. <80%) adherence were significantly younger (p=0.01), with more often indifferent attitudes towards entecavir (p=0.03) Viral breakthrough did not occur during the study. Adherence in patients with HBV DNA after 16 weeks > 20 IU/mL (n=18) and ≤ 20 IU/mL (n=81) averaged 83% and 91% respectively (p=0.19). In multivariate analysis, adherence was not a significant predictor of HBV DNA negativity (adjusted OR 1.02; p=0.34), after adjustment for duration of entecavir treatment (p<0.001) and HBe-status (p=0.001). CONCLUSIONS 70% of chronic hepatitis B patients exhibited good adherence to entecavir, with younger age and an indifferent attitude being risk factors for poor adherence. Poor adherence was not an independent predictor of virological response.
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Affiliation(s)
- Lotte G van Vlerken
- Department of Gastroenterology and Hepatology, University Medical Centrum Utrecht, Utrecht, The Netherlands
| | - Pauline Arends
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Faydra I Lieveld
- Department of Gastroenterology and Hepatology, University Medical Centrum Utrecht, Utrecht, The Netherlands; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Joop E Arends
- Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Willem Pieter Brouwer
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, University Medical Centrum Utrecht, Utrecht, The Netherlands
| | - Harry L Janssen
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands; Liver Clinic, Toronto Western and General Hospital, University Health Network, Toronto, Canada
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Centrum Utrecht, Utrecht, The Netherlands.
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Seto WK, Hui AJ, Wong VWS, Wong GLH, Liu KSH, Lai CL, Yuen MF, Chan HLY. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut 2015; 64:667-72. [PMID: 24833635 DOI: 10.1136/gutjnl-2014-307237] [Citation(s) in RCA: 172] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVE The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in predicting off-treatment durability has not been well investigated. METHODS Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥ 2 years with undetectable HBV DNA levels on ≥ 3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6-12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA >2000IU/mL). RESULT 184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11000 (range 2115 to >1.98×10(8)) IU/mL. 42 (25.8%) patients had elevated alanine aminotransferase (median level 97 U/L, range 37-1058 U/L) during virologic relapse. Mean rate of off-treatment HBsAg decline was 0.018 (± 0.456) log IU/mL/year. No patients cleared HBsAg. There was no correlation between off-treatment serial HBsAg and HBV DNA levels (r=-0.026, p=0.541). HBsAg levels at the time of entecavir commencement, entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse (all p>0.05). CONCLUSIONS Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance.
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Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Aric Josun Hui
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong
| | | | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | | | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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Peng J, Yin J, Cai S, Yu T, Zhong C. Factors associated with adherence to nucleos(t)ide analogs in chronic hepatitis B patients: results from a 1-year follow-up study. Patient Prefer Adherence 2015; 9:41-5. [PMID: 25609925 PMCID: PMC4293917 DOI: 10.2147/ppa.s71510] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Little is known about the factors associated with patient compliance with nucleos(t)ide analog (NUC) treatment for chronic hepatitis B (CHB). The purpose of this study was to examine the association between sociodemographic and clinical characteristics and adherence to NUCs among patients with CHB. A total of 211 CHB patients receiving NUC monotherapy were asked to report the number of prescribed doses of medication they had taken during the last 90 days. A total of four 3-month adherence scores were averaged to obtain a combined rate of NUC adherence during a 1-year follow up period. The mean age of the patients was 29.6 years, 79% were men, and 68% had no prior NUC treatment for CHB. Females, patients without a previous NUC treatment, and those who had NUC drug resistance showed better adherence to NUC treatment, and compliance was better with telbivudine than with lamivudine and entecavir.
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Affiliation(s)
- Jie Peng
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
- Correspondence: Jie Peng, Nanfang Hospital, Southern Medical University, No 1838, Guangzhou Avenue North, Guangzhou, Guangdong Province 510515, People’s Republic of China, Tel +86 20 6278 7428, Fax +86 20 8771 9653, Email
| | - Junhua Yin
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Shaohang Cai
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Tao Yu
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Chunxiu Zhong
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
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28
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Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, Tang H, Sheng J, Zhao M. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol 2014; 61:777-84. [PMID: 24915612 DOI: 10.1016/j.jhep.2014.05.044] [Citation(s) in RCA: 192] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 05/16/2014] [Accepted: 05/30/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Durable post-treatment response is uncommon in chronic hepatitis B (CHB) patients on nucleos(t)ide analogue therapy. Response, response predictors and safety were assessed in patients who switched from long-term entecavir (ETV) to peginterferon alfa-2a. METHODS Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9-36 months, with HBeAg <100 PEIU/ml and HBV DNA ⩽1000 copies/ml, were randomised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48 (ClinicalTrials.gov: NCT00940485). RESULTS 200 patients were randomised; 197 received ⩾1 study drug dose. Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population (peginterferon alfa-2a, n = 94; ETV, n = 98). Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV (14.9% vs. 6.1%; p = 0.0467). Only patients receiving peginterferon alfa-2a achieved HBsAg loss (8.5%). Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg <1500 IU/ml at randomisation, 33.3% and 22.2% achieved HBeAg seroconversion and HBsAg loss, respectively. Early on-treatment HBsAg decline predicted response at week 48; highest rates were observed in patients with week 12 HBsAg <200 IU/ml (HBeAg seroconversion, 66.7%; HBsAg loss, 77.8%). Alanine aminotransferase elevations were not associated with viral rebound (n = 38). Peginterferon alfa-2a was well-tolerated. CONCLUSIONS For patients who achieve virological suppression with ETV, switching to a finite course of peginterferon alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss. A response-guided approach may identify patients with the greatest chance of success.
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Affiliation(s)
- Qin Ning
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Meifang Han
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yongtao Sun
- Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - Jiaji Jiang
- The First Hospital, Fujian Medical University, Fuzhou, China
| | - Deming Tan
- Xiangya Hospital, Central South University, Changsha, China
| | - Jinlin Hou
- Nanfang Hospital, Nanfang Medical University, Guangzhou, China
| | - Hong Tang
- West China Hospital, Sichuan University, Chengdu, China
| | - Jifang Sheng
- The First Hospital, Zhejiang University, Hangzhou, China
| | - Mianzhi Zhao
- Shanghai Roche Pharmaceutical Co., Ltd, Shanghai, China
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A Randomized, Open-Label Clinical Study of Combined Pegylated Interferon Alfa-2a (40KD) and Entecavir Treatment for Hepatitis B "e" Antigen-Positive Chronic Hepatitis B. Clin Infect Dis 2014; 59:1714-23. [DOI: 10.1093/cid/ciu702] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Ha NB, Ha NB, Chaung KT, Trinh HN, Nguyen HA, Nguyen KK, Nguyen MH. Similar response to entecavir 0.5 and 1.0 mg in treatment-naïve chronic hepatitis B patients: a case-control study. Dig Dis Sci 2014; 59:168-73. [PMID: 24248420 DOI: 10.1007/s10620-013-2940-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2013] [Accepted: 10/29/2013] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS The dose recommendation for entecavir (ETV) is 0.5 mg daily for treatment-naïve chronic hepatitis B (CHB) patients and 1.0 mg daily for lamivudine-refractory patients; however, few data are available for the efficacy of a 1.0-mg daily dose in treatment-naïve CHB patients. Our goal is to examine the treatment outcome of treatment-naïve patients placed on ETV 0.5 mg or ETV 1.0 mg daily through week 48. METHODS Cases were 40 consecutive hepatitis B e antigen (HBeAg)-positive CHB patients treated with ETV 1.0 mg daily between January 2005 and September 2010, and controls were 40 consecutive CHB patients treated with ETV 0.5 mg daily between January 2005 and September 2010 at three US gastroenterology/liver clinics. Controls were matched for age (±5 years), sex, HBeAg, and baseline hepatitis B virus (HBV) DNA (±0.5 log10 IU/ml). Complete viral suppression was defined as undetectable HBV DNA by polymerase chain reaction (<100 IU/ml). RESULTS Both groups had similar distributions of age (38 ± 11 years), male patients (55 %), and mean HBV DNA (7.7 ± 1.1 log10 IU/ml). The complete viral suppression rate was similar in both cases and controls through week 24 (15 vs. 15 %, p = 1.00) and week 48 (22 vs. 36 %, p = 0.17). Non-adherence was reported in three patients in the ETV 1.0 mg daily cohort at week 48. CONCLUSIONS There were no significant differences in the proportion of patients with complete viral suppression in patients treated with ETV 0.5 mg daily or the higher daily dose of 1.0 mg.
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Affiliation(s)
- Nghiem B Ha
- School of Medicine, University of California, Davis, Sacramento, CA, USA
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31
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Bang SJ, Kim BG, Shin JW, Ju HU, Park BR, Kim MH, Kim CJ, Park JH, Jeong ID, Jung SW, Park NH. Clinical course of patients with insufficient viral suppression during entecavir therapy in genotype C chronic hepatitis B. Dig Liver Dis 2013; 45:600-5. [PMID: 23333665 DOI: 10.1016/j.dld.2012.12.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2012] [Revised: 12/10/2012] [Accepted: 12/19/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS The clinical course of patients with insufficient virologic suppression diagnosed with chronic hepatitis B undergoing entecavir therapy is unclear. METHODS We retrospectively investigated the long-term clinical outcomes of entecavir treatment for more than 12 months in 355 nucleos(t)ide-naïve chronic hepatitis B patients, particularly those with primary non-response or partial virologic response. RESULTS The median duration of entecavir therapy was 40 months (range, 12-64 months). Virologic response was achieved in 315 patients (88.7%). One hundred forty-four (96.6%) of 149 HBeAg-negative patients achieved virologic response. Among 206 HBeAg-positive patients, 52 (25.2%) achieved HBeAg seroconversion. Virologic breakthrough was observed in 7 patients (2.0%). Of these 7 patients, 5 (1.4%) had genotypic resistance to entecavir. Primary non-response and partial virologic response were evident in 6 (1.7%) and 63 (17.7%) patients, respectively. During continuous prolonged entecavir therapy, virologic response of patients with primary non-response and partial virologic response was achieved in 6 (100%) and 28 (44.4%) patients, respectively. CONCLUSION The vast majority of chronic hepatitis B patients in this study achieved virologic response through prolonged entecavir therapy, with only 1.4% chance of viral resistance. Furthermore, all patients with primary non-response were able to achieve virologic response without adjustment of antiviral therapy.
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Affiliation(s)
- Sung-Jo Bang
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
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Lin B, Ha NB, Liu A, Trinh HN, Nguyen HA, Nguyen KK, Ahmed A, Keeffe EB, Garcia RT, Garcia G, Nguyen MH. Low incidence of hepatitis B e antigen seroconversion in patients treated with oral nucleos(t)ides in routine practice. J Gastroenterol Hepatol 2013; 28:855-60. [PMID: 23278507 DOI: 10.1111/jgh.12108] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2012] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIM Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates. METHODS We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development. RESULTS The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA < 7.5 log10 IU/mL (hazard ratio [HR] = 2.59 [1.04-6.44]), P = 0.041) and alanine transaminase (ALT) > 1.5 × upper normal limit (HR = 2.86 [1.05-7.81], P = 0.040), but not the choice of nucleos(t)ides. CONCLUSIONS The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.
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Affiliation(s)
- Brian Lin
- Pacific Health Foundation, California, USA
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Kamezaki H, Kanda T, Arai M, Wu S, Nakamoto S, Chiba T, Maruyama H, Fujiwara K, Kanai F, Imazeki F, Nomura F, Yokosuka O. Adherence to medication is a more important contributor to viral breakthrough in chronic hepatitis B patients treated with entecavir than in those with Lamivudine. Int J Med Sci 2013; 10:567-574. [PMID: 23533048 PMCID: PMC3607242 DOI: 10.7150/ijms.5795] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Accepted: 03/13/2013] [Indexed: 12/16/2022] Open
Abstract
Viral breakthrough is related to poor adherence to medication in some chronic hepatitis B patients treated with nucleos(t)ide analogues (NAs). Our study aimed to examine how adherence to medication is associated with viral breakthrough in patients treated with NAs. A total of 203 patients (135 ETV and 68 LAM) were analyzed in this retrospective analysis. Physical examination, serum liver enzyme tests, and hepatitis B virus marker tests were performed at least every 3 months. We reviewed medical records and performed medical interviews regarding to patients' adherence to medication. Adherence rates <90% were defined as poor adherence in the present study. Cumulative viral breakthrough rates were lower in the ETV-treated patients than in the LAM-treated patients (P<0.001). Seven ETV-treated (5.1%) and 6 LAM-treated patients (8.8%) revealed poor adherence to medication (P=0.48). Among ETV-treated patients, 4 (3.1%) of 128 patients without poor adherence experienced viral breakthrough and 3 (42.8%) of 7 patients with poor adherence experienced viral breakthrough (P<0.001). Only 3 of 38 (7.8%) LAM-treated patients with viral breakthrough had poor adherence, a lower rate than the ETV-treated patients (P=0.039). Nucleoside analogue resistance mutations were observed in 50.0% of ETV- and 94.1% of LAM-treated patients with viral breakthrough (P=0.047). Viral breakthrough associated with poor adherence could be a more important issue in the treatment with especially stronger NAs, such as ETV.
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Affiliation(s)
- Hidehiro Kamezaki
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Tatsuo Kanda
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Makoto Arai
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Shuang Wu
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Shingo Nakamoto
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Tetsuhiro Chiba
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Hitoshi Maruyama
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Keiichi Fujiwara
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Fumihiko Kanai
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Fumio Imazeki
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Fumio Nomura
- 2. Departments of Molecular Diagnosis, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
| | - Osamu Yokosuka
- 1. Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
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Low hepatitis B envelope antigen seroconversion rate in chronic hepatitis B patients on long-term entecavir 0.5 mg daily in routine clinical practice. Eur J Gastroenterol Hepatol 2013; 25:338-43. [PMID: 23169311 DOI: 10.1097/meg.0b013e32835b3677] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44-90 patients from centers in Asia, Europe, and South America. MATERIALS AND METHODS In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion. RESULTS Sixty-one percent of HBeAg-positive patients were men, mean age 39 ± 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10 IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV. CONCLUSION In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.
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Pan CQ, Hu KQ, Tsai N. Long-term therapy with nucleoside/nucleotide analogues for chronic hepatitis B in Asian patients. Antivir Ther 2012; 18:841-852. [PMID: 23178555 DOI: 10.3851/imp2481] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2012] [Indexed: 12/14/2022]
Abstract
Of the estimated 400 million patients with chronic hepatitis B (CHB) globally, approximately 75% are Asians, representing a clinically important subgroup with a higher risk of cirrhosis and hepatocellular carcinoma than Caucasian patients. This review summarizes recent data from clinical long-term and real-life studies of entecavir and tenofovir, the recommended first-line oral therapies for treating CHB, in nucleoside/nucleotide-naive Asian CHB patients with compensated or decompensated liver disease. Long-term treatment with entecavir or tenofovir achieved profound and durable virological suppression, and led to improved liver histology and function. The data presented in this review will help physicians in making evidence-based decision choices regarding first-line antiviral therapy and long-term management in Asian CHB patients.
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Affiliation(s)
- Calvin Q Pan
- Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA.
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Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy for entecavir partial responders. Dig Dis Sci 2012; 57:3011-6. [PMID: 23010744 DOI: 10.1007/s10620-012-2402-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 08/31/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients. METHODS We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir). RESULTS All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir. CONCLUSIONS Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.
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He J, Bowen JM, Xie F, Goeree R. Cost-effectiveness analysis of antiviral treatments for HBeAg-positive chronic hepatitis B in Canada. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2012; 15:894-906. [PMID: 22999140 DOI: 10.1016/j.jval.2012.06.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2011] [Revised: 05/15/2012] [Accepted: 06/13/2012] [Indexed: 06/01/2023]
Abstract
OBJECTIVE To conduct a cost-effectiveness analysis of currently available nucleos(t)ide antiviral treatments (lamivudine, telbivudine, entecavir, and tenofovir) for chronic hepatitis B in Canada. METHODS Markov modeling was used to project the lifetime health benefits and costs associated with the antiviral treatments. The hypothetical patient population was hepatitis B e antigen-positive chronic hepatitis B-infected patients aged 34 years. Quality-adjusted life-years were used as a measure of effectiveness. Long-term cumulative incidence of liver complications was also projected. Treatment effectiveness data were derived from the literature; meta-analysis was conducted when there was a large variance in reported effectiveness data. Costs were obtained from a cost analysis of treating chronic hepatitis B-related complications in Canada. Stochastic parameter uncertainty was examined in probabilistic sensitivity analysis by using second-order Monte Carlo simulation. Alternative modeling assumptions were assessed in scenario analysis. One-way sensitivity analysis was used to explore each parameter's impact on the uncertainty of the results. RESULTS In the base-case analysis, telbivudine was dominated by entecavir and tenofovir. Tenofovir strictly dominated lamivudine, telbivudine, and entecavir. Over the 72-year period of the model, the expected life expectancy (undiscounted) of lamivudine, telbivudine, entecavir, and tenofovir was 35.71, 36.94, 37.65, and 37.99 years, respectively. Tenofovir had the highest expected quality-adjusted life-years at 11.86 (discounted) in all comparisons. Scenario and sensitivity analyses proved the robustness of the base-case results. The projected 10-year cumulative incidence of cirrhosis and hepatocellular carcinoma was 11.40% and 3.05%, respectively, for tenofovir, which is significantly lower than that for lamivudine. CONCLUSION Tenofovir generated the best results compared with all other therapies under evaluation.
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Affiliation(s)
- Jing He
- Canadian Institute for Health Information, Toronto, ON, Canada.
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Pol S, Lampertico P. First-line treatment of chronic hepatitis B with entecavir or tenofovir in 'real-life' settings: from clinical trials to clinical practice. J Viral Hepat 2012; 19:377-86. [PMID: 22571899 PMCID: PMC3489060 DOI: 10.1111/j.1365-2893.2012.01602.x] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are potent nucleos(t)ide analogues (NUCs) recommended as first-line monotherapies for chronic hepatitis B. In Phase III trials, ETV and TDF demonstrated superior efficacy, and comparable safety compared with other NUCs. In long-term clinical studies, both drugs achieved virologic response rates of around 95%, with very low rates of resistance development and good safety profiles. Clinical trials are conducted under standardized conditions with strict enrolment criteria that limit the heterogeneity of study populations. 'Real-life' populations tend to be composed of a wider range of patients, often older and with different morbidities, comorbidities that may impact treatment efficacy and co-factors, such as smoking and alcohol intake, which can have a direct impact on disease progression. Real-life studies provide better representations of everyday clinical practice and are important to confirm the results reported in clinical studies and to identify rare or late-emerging adverse events. In five 'real-life' studies of ETV in more than 1000 patients, up to 4 years of treatment resulted in virologic responses in 76-96% of patients. Two real-life studies of TDF reported response rates of 71-92% after up to 21 months of treatment. Low incidences of drug resistance and favourable tolerabilities were reported for both drugs, thus confirming the results from registration trials.
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Affiliation(s)
- S Pol
- Unité d’Hépatologie, Hôpital Cochin, Université Paris DescartesAPHP, INSERM U.1016, Paris, France
| | - P Lampertico
- First Gastroenterology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Università di MilanoMilan, Italy
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Partial Response to Entecavir and Tenofovir in Naïve Patients with Chronic Hepatitis B: Clinical Relevance and Management. ACTA ACUST UNITED AC 2012. [DOI: 10.1007/s11901-012-0127-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Sogni P, Carrieri MP, Fontaine H, Mallet V, Vallet-Pichard A, Trabut JB, Méritet JF, Pol S. The Role of Adherence in Virological Suppression in Patients Receiving Anti-HBV Analogues. Antivir Ther 2012; 17:395-400. [DOI: 10.3851/imp1944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2011] [Indexed: 10/15/2022]
Abstract
Background Although adherence is of major importance in long-term treatments, few studies have been published regarding the use of anti-HBV analogues in clinical practice. The aim of this study was to evaluate adherence to anti-HBV analogues and associated virological suppression. Methods A cross-sectional study was performed between 1 January 2009 and 15 July 2009 in Cochin Hospital, Paris, France. It included all patients being treated with anti-HBV analogues for at least three months, who were without coinfection (HIV, HCV or HDV) and who had not received organ transplants. At the time of enrolment, HBV viral load, analogue regimen and self-reported adherence were collected prospectively. Patients were classified as non-adherent, or moderately or totally adherent using a score based on analysis of self-reports. Other data were obtained retrospectively. Results Among the 190 patients meeting the inclusion criteria, 33% were initially hepatitis B e antigen-positive and 50% had extensive fibrosis or cirrhosis. Pretreatment viral load was 6.0 log IU/ml (median). The median duration of treatment was 52 months. At enrolment, 61%, 32% and 7% of patients were classified as totally adherent, moderately adherent and non-adherent, respectively. Complete virological suppression (HBV DNA<12 IU/ml) was observed in 83% of patients at enrolment. In the multivariate analysis, lack of virological suppression was associated with an increased pretreatment viral load, with no change in analogue regimen and is classified as non-adherent. Conclusions Adherence seems to be an independent factor associated with virological suppression during anti-HBV analogue treatment. Therapeutic education and a systematic evaluation of adherence using self-reports should be promoted to assure long-term anti-HBV analogue efficacy in clinical practice.
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Affiliation(s)
- Philippe Sogni
- Institut Cochin, Université Paris-Descartes, CNRS (UMR 8104), INSERM U-1016, Paris, France
- Assistance Publique – Hôpitaux de Paris, Service d'Hépatologie, Hôpital Cochin, Paris, France
| | - Maria Patrizia Carrieri
- INSERM U-912 (SE4S), Marseille, France
- Université Aix Marseille, IRD, UMR-S912, Marseille, France
- ORS PACA, Observatoire Régional de la Santé Provence Alpes Côte d'Azur, Marseille, France
| | - Hélène Fontaine
- Institut Cochin, Université Paris-Descartes, CNRS (UMR 8104), INSERM U-1016, Paris, France
- Assistance Publique – Hôpitaux de Paris, Service d'Hépatologie, Hôpital Cochin, Paris, France
| | - Vincent Mallet
- Institut Cochin, Université Paris-Descartes, CNRS (UMR 8104), INSERM U-1016, Paris, France
- Assistance Publique – Hôpitaux de Paris, Service d'Hépatologie, Hôpital Cochin, Paris, France
| | - Anaïs Vallet-Pichard
- Institut Cochin, Université Paris-Descartes, CNRS (UMR 8104), INSERM U-1016, Paris, France
- Assistance Publique – Hôpitaux de Paris, Service d'Hépatologie, Hôpital Cochin, Paris, France
| | - Jean-Baptiste Trabut
- Assistance Publique – Hôpitaux de Paris, Service d'Hépatologie, Hôpital Cochin, Paris, France
| | - Jean-François Méritet
- Assistance Publique – Hôpitaux de Paris, Laboratoire de Virologie, Hôpital Cochin, Paris, France
| | - Stanislas Pol
- Institut Cochin, Université Paris-Descartes, CNRS (UMR 8104), INSERM U-1016, Paris, France
- Assistance Publique – Hôpitaux de Paris, Service d'Hépatologie, Hôpital Cochin, Paris, France
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Hayashi N, Kiyosawa K, Tsubouchi H, Okanoue T, Kumada H. Efficacy and safety of treatment with peginterferon alfa-2a for chronic hepatitis B patients. ACTA ACUST UNITED AC 2012. [DOI: 10.2957/kanzo.53.135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Lee M, Keeffe EB. Hepatitis B: modern end points of treatment and the specter of viral resistance. Gastroenterol Clin North Am 2011; 40:495-505. [PMID: 21893270 DOI: 10.1016/j.gtc.2011.06.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The goal of antiviral treatment of chronic hepatitis B is to prevent the complications of cirrhosis, hepatic decompensation, HCC, and death. Because these clinical outcomes may take a long period of time to develop, it is important to use intermediate or surrogate end points to evaluate the efficacy and response to antiviral treatment, and to determine whether treatment can be safely stopped, especially given concern for the development of antiviral resistance with NUC therapy. Although normalization of ALT and suppression of HBV DNA viral replication are associated with favorable outcomes, the durability of their response is low, and these end points are insufficient markers for stopping treatment. HBeAg seroconversion is currently used to discontinue NUC treatment in patients with HBeAg-positive chronic hepatitis B, whereas the stopping rule for HBeAg-negative disease relies on HBsAg loss. However, HBsAg loss occurs very infrequently and is not a practical end point for clinical use, although quantitative HBsAg levels may be useful in identifying patients who could achieve a sustained virologic response to treatment.
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Affiliation(s)
- Maximilian Lee
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, 300 Pasteur Drive, Alway Building M211, Palo Alto, CA 94305-5187, USA
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