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      A Novel Estimation of the Relative Economic Value in Terms of Different Chronic Hepatitis B Treatment Options

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          Abstract

          Background

          Prescribers, payors and healthcare decision-makers are increasingly examining the value of treatments. This study aims at analyzing economic value of chronic hepatitis B (CHB) treatment options, which are available in Korea.

          Methods

          CHB infection was simulated using a health-state transition model with disease states defined as mild disease (Ishak F0/F1), fibrosis (F2/F3/F4), advanced fibrosis/cirrhosis (>F4), and complicated disease states (decompensated cirrhosis, hepatocellular carcinoma, liver transplant and death) based on available natural history data. The value of treatment-specific attributes on disease progression/regression was estimated based on published data in terms of events and costs avoided. 5-year treatment duration was assumed except for treatment initiation. Primary model output is the estimated cost savings of entecavir per patient per day of treatment versus the comparator in question for a given CHB patient.

          Results

          The simulation of treating with entecavir versus no treatment predicted improved clinical outcomes for entecavir-treatment patients. In the long term, these clinical benefits translate into cost savings of $3.10 per day of treatment. In naive patient treatment, daily cost savings of using entecavir versus lamivudine or telbivudine was estimated at $2.89 and $1.72, respectively. In the case of suboptimal responders who pre-treated with lamivudine, daily cost saving for patients switching to entecavir was $1.38 per day of treatment compared to patients maintaining on lamivudine.

          Conclusions

          Entecavir exhibits characteristics of a favourable CHB treatment, which directly translates into economic and therapeutic value as opposed to either no treatment or alternative strategies.

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          Most cited references14

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          Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy.

          Patients with chronic hepatitis B virus (HBV) infection who develop antiviral resistance lose benefits of therapy and may be predisposed to further resistance. Entecavir (ETV) resistance (ETVr) results from HBV reverse transcriptase substitutions at positions T184, S202, or M250, which emerge in the presence of lamivudine (LVD) resistance substitutions M204I/V +/- L180M. Here, we summarize results from comprehensive resistance monitoring of patients with HBV who were continuously treated with ETV for up to 5 years. Monitoring included genotypic analysis of isolates from all patients at baseline and when HBV DNA was detectable by polymerase chain reaction (> or = 300 copies/mL) from Years 1 through 5. In addition, genotyping was performed on isolates from patients experiencing virologic breakthrough (> or = 1 log(10) rise in HBV DNA). In vitro phenotypic ETV susceptibility was determined for virologic breakthrough isolates, and for HBV containing novel substitutions emerging during treatment. The results over 5 years of therapy showed that in nucleoside-naïve patients, the cumulative probability of genotypic ETVr and genotypic ETVr associated with virologic breakthrough was 1.2% and 0.8%, respectively. In contrast, a reduced barrier to resistance was observed in LVD-refractory patients, as the LVD resistance substitutions, a partial requirement for ETVr, preexist, resulting in a 5-year cumulative probability of genotypic ETVr and genotypic ETVr associated with breakthrough of 51% and 43%, respectively. Importantly, only four patients who achieved < 300 copies/mL HBV DNA subsequently developed ETVr. Long-term monitoring showed low rates of resistance in nucleoside-naïve patients during 5 years of ETV therapy, corresponding with potent viral suppression and a high genetic barrier to resistance. These findings support ETV as a primary therapy that enables prolonged treatment with potent viral suppression and minimal resistance.
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            Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients.

            The aim of this study was to compare the prognosis of patients with hepatitis B surface antigen (HBsAg) positive and those with antibody to hepatitis C (anti-HCV) positive cirrhosis. This was a retrospective cohort study of 297 untreated Western European patients with compensated viral cirrhosis (Child class A; 161 patients with hepatitis type B and 136 with type C) who were followed for a median period of 6.6 yr. At diagnosis, median age was lower (48 vs 58 yr, respectively) in HBsAg-positive cirrhotic patients. The Kaplan-Meier 5-yr probability of hepatocellular carcinoma (HCC) was 9% and 10% in HBsAg and anti-HCV-positive cirrhotic patients, respectively; the corresponding figures for decompensation unrelated to HCC were 16% and 28% and for survival were 86% and 84%, respectively. After adjustment for clinical and serological differences at baseline, the relative risk (95% CI) for HCC, decompensation and mortality was 1.53 (CI = 0.81-2.89), 0.59 (CI = 0.37-0.94), and 1.44 (CI = 0.85-2.46) respectively, in HBsAg-positive patients compared with anti-HCV-positive cirrhotic patients. Among HBsAg-positive cirrhotic patients, the relative risk for HCC, decompensation, and mortality was 0.89 (CI = 0.30-2.63), 4.05 (CI = 1.09-15.1), and 5.9 (CI = 1.64-21.3), respectively, in HBV-DNA positive (HBeAg positive or negative) compared with HBV-DNA negative (HBeAg negative) patients at entry. Patients with HBV infection may present with cirrhosis about 10 yr earlier than those with HCV infection. HCV infection tends to be associated with a higher risk of decompensation, but these data should take into consideration the heterogeneity of HBV-related cirrhosis in terms of viremia levels and risk of hepatic failure. Survival shows no significant differences according to HBV or HCV etiology in Western European cirrhotic patients.
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              Epidemiology of hepatitis B virus infection in the Asia-Pacific region.

              There is a wide variation of hepatitis B virus (HBV) infection in the Asia-Pacific region. The prevalence of chronic HBV infection is lowest (<1%) in North America, Australia and New Zealand, 2-4% in Japan, 5-18% in China and highest (15-20%) in Taiwan as well as several other countries in South East Asia. Perinatal transmission is common in HBV-hyperendemic areas. Geographical clusters of horizontal HBV infection have been reported in both high- and low-risk countries. Common sources of infection, including iatrogenic and sexual transmission, have been implicated. Migrant studies indicate the importance of childhood environments in the determination of HBV infection. Rural urban and ethnic differences in the prevalence of HBV infection have also been reported. There has been a decrease in the prevalence of HBV infection after mass HBV vaccination programmes in some Asia-Pacific countries, which may be due to the intervention of possible transmission routes through the use of disposable syringes and needles, screening of HBV infection markers in blood banks, and prevention of high-risk tattooing, acupuncture, ear-piercing and sexual contact. A striking decrease in the incidence of HBV infection and hepatocellular carcinoma has been observed among children in Taiwan and other areas where mass vaccination programmes have been implemented.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                11 March 2013
                : 8
                : 3
                : e57900
                Affiliations
                [1 ]Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
                [2 ]Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
                [3 ]Seoul National University School of Public Health & Institute, Seoul, Korea
                [4 ]Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
                [5 ]Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
                [6 ]Monitor Group Korea, Seoul, Korea
                [7 ]Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea
                Mahidol-Oxford Tropical Medicine Research Unit, Thailand
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JYP SHA MSL. Performed the experiments: JYP JH HJY JEY YL MJS SHA MSL. Analyzed the data: JYP TJL MJS SHA MSL. Contributed reagents/materials/analysis tools: JYP JH HJY JEY YL SHA MSL. Wrote the paper: JYP MJS.

                Article
                PONE-D-12-31485
                10.1371/journal.pone.0057900
                3594204
                23536775
                6d903744-1063-46d3-b31f-95a4a423c749
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 October 2012
                : 28 January 2013
                Page count
                Pages: 9
                Funding
                This study was sponsored by Bristol-Myers Squibb (BMS). The funders had no role in data interpretation, decision to publish or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Clinical Research Design
                Modeling
                Drugs and Devices
                Pharmacoeconomics
                Gastroenterology and Hepatology
                Liver Diseases
                Infectious Hepatitis
                Hepatitis B
                Infectious Diseases
                Viral Diseases
                Non-Clinical Medicine
                Health Economics
                Socioeconomic Aspects of Health
                Social and Behavioral Sciences
                Economics
                Human Capital
                Economics of Health
                Health Economics

                Uncategorized
                Uncategorized

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