The quest for a cure for chronic hepatitis B from an HTA perspective:lessons learned from chronic hepatitis c

Despite the availability of treatments and vaccines, chronic hepatitis B (CHB) is among the world's deadliest infectious diseases and a global public health concern. This thesis focuses on the quest for curative treatments for CHB from a Health Technology Assessment (HTA) perspective and the evidence/data required by HTA and reimbursement bodies to evaluate new products. New direct antivirals have recently been introduced for hepatitis C and this experience can be built on in hepatitis B, although there are both similarities and differences between hepatitis C and B viruses and related chronic diseases. The second and third chapters focus on hepatitis C with possible directions for future research and development on CHB. Chapter 4 concerns an analysis of data on US Veterans patients, showing the high clinical and economic burden of CHB in this population. Chapter 5 highlights that self-stigma and social stigma are common among patients living with CHB. Chapter 6 addresses patient preferences and shows that one of the main desired attributes of new treatments is limited duration and the ability to achieve sustained HBsAg loss. Chapters 7 and 8 describe a network meta-analysis of clinical trials in CHB, and a systematic review of the literature about health economics models; these findings can be used to adapt cost-effectiveness models. Adequate collection and provision of the data required by HTA agencies and payers and learning from experience in hepatitis C will optimize patient access to new treatments for HBV and accelerate WHO's ambitious goal of eliminating viral hepatitis

Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants

Abstract Introduction The aim of this study was to assess the cost-utility of palivizumab versus no prophylaxis in the prevention of respiratory syncytial virus infection among high-risk preterm infants. Methods We used and adapted a pre-existent model in which two cohorts of patients received palivizumab or no prophylaxis. The patients were followed for their expected lifetimes. The economic evaluation was conducted from the perspective of the Italian National Health Service. We considered Life-Years Gained (LYGs), Quality-Adjusted Life-Years (QALYs) and direct medical costs (pharmacological treatment, hospitalization, recurrences for wheezing, etc.). LYGs and QALYs were based on the results of a double blind cohort study with prospective follow-up and direct medical costs were based on Italian treatment patterns. Benefits and costs were discounted at 3%. Costs were assessed in 2007 Euros. Sensitivity and threshold analysis on key clinical and economic parameters were performed. Result For the two cohorts, the expected life-years (per patient) with palivizumab versus no prophylaxis were 29.842 and 29.754 years, respectively. Quality-adjusted life years (per patient) with palivizumab were 29.202, and for no prophylaxis were 29.043. The expected cost (per patient) was € 6,244.20 with palivizumab and € 4,867.70 with no prophylaxis. We calculated for palivizumab versus no prophylaxis the incremental cost per LYG and per QALY gained. It was € 15,568.65 and € 8,676.74, respectively. Conclusion This study suggests that, compared with no prophylaxis, palivizumab is cost-effective in the prevention of respiratory syncytial virus infection among high risk preterm infants.</p

A comparative network meta-analysis of standard of care treatments in treatment-naive chronic hepatitis B patients

Objective:Published network meta-analyses of chronic hepatitis B (CHB) treatments are either out-of-date or excluded key treatments. Therefore, we aimed to comprehensively update the efficacy evidence for the following end points: Hepatitis B surface antigen (HBsAg) loss, hepatitis B early antigen (HBeAg) seroconversion and hepatitis B virus DNA (HBV DNA) suppression.Materials & methods:Approved treatments in CHB and their combinations were evaluated. A systematic literature review was conducted to identify all randomized controlled trials in treatment-naive CHB patients. Included studies reported at least one of the end points of interest. A frequentist probability network meta-analysis was performed for each end point. The choice of fixed effect or random-effect model was based on the I-square statistic, a measure of variation in study outcomes between studies. The analyses were performed separately for HBeAg-positive and HBeAg-negative patients. For the primary analyses, end points measured 48 +/- 4 weeks after treatment initiation were considered.Results:A total of 47 randomized controlled trials (13,826 patients), covering 23 unique treatment regimens, were included: a total of 29 reported HBsAg loss, 36 reported HBeAg seroconversion and 37 reported HBV DNA suppression. For both HBsAg loss and HBeAg seroconversion, pegylated interferon-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. On the other hand, for HBV DNA suppression, nucleosides-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients.Conclusion:Our findings confirm available evidence around the comparative efficacy of available CHB treatments. Therefore, they can be used to update relevant cost-effectiveness analyses and clinical guidelines

Real-World Epidemiology, Clinical and Economic Burden of Chronic Hepatitis B in Japan: A Retrospective Study Using JMDC Claims Database

Abstract Introduction Chronic hepatitis B (CHB) is one of the world's major healthcare problems, especially in the Western Pacific regions. This study describes the prevalence, incidence, treatment profiles and clinical and economic burden of chronic hepatitis B patients in Japan using the Japan Medical Data Center (JMDC) Claims Database. Methods This is a retrospective observational study. Prevalence cases were identified as patients with ≥ 1 inpatient or ≥ 2 outpatient CHB diagnoses and ≥ 2 records for hepatitis B tests or ≥ 1 prescription for CHB treatment between January 2010 and December 2019. Newly diagnosed CHB patients were defined as patients diagnosed from 2010 to 2018 with no history of the disease up to 2 years prior to the diagnosis. The index date is defined as the first CHB diagnosis day. We only used patients’ data with ≥ 1-year post-index date. Results We identified 13,061 CHB prevalent cases (2010–2019), yielding a crude period prevalence of 0.32%. Newly diagnosed CHB patients (n = 1973; median age 52 years) were followed for a median period of 3.1 years, during which 15% received a CHB treatment. Entecavir was the most common first treatment (66%). During this period, 3.4% of the patients developed compensated cirrhosis (CC), 1.5% decompensated cirrhosis (DC) and 3.0% hepatocellular carcinoma (HCC). Around 43.3% of CHB patients were hospitalized at least once. Hospitalizations, treatment rates, serologic testing and screening for liver diseases increased as the severity of the disease progressed. The average total healthcare cost was 870,568 JPY (7779 USD) per person per year. DC and HCC resulted in the highest management costs. Conclusions Chronic hepatitis B represents a high clinical and economic burden for patients and caregivers, given its morbidity and associated costs

Clinical Outcomes and Quantitative HBV Surface Antigen Levels in Diverse Chronic Hepatitis B Patients in Canada: A Retrospective Real-World Study of CHB in Canada (REVEAL-CANADA)

Background: Hepatitis B surface antigen (HBsAg) loss is associated with improved clinical outcomes for individuals with chronic hepatitis B (CHB); however, the effects of varying HBsAg levels on clinical outcomes in diverse cohorts are understudied. Methods: In this cross-sectional, multicentre, retrospective study, the data on adult subjects enrolled in the Canadian HBV Network with CHB seen from 1 January 2012 to 30 January 2021 with the treatment and virologic data within 1 year of HBsAg testing were analyzed. Patients were tested for HBsAg using qualitative (for HBsAg-negative samples) and/or commercial quantitative assays. Fibrosis or hepatic necroinflammation was determined by the liver stiffness measurement (LSM). The baseline data were summarized using descriptive statistics and compared by using univariable/multivariable analyses. Results: This study included 844 CHB patients, with a median age of 49.6 years (IQR 40.1&ndash;60.5), and 37% were female. In total, 751 patients (78.6%) had known ethnicity data, and 76.7% self-reported as Asian, 11.4% as Black, 6.8% as White, and 4.8% as other. Among the 844 patients, 237 (28.0%) were HBsAg (&minus;) (&lt;LLOQ), 190 (22.5%) had qHBsAg 1&ndash;100, 91 (10.8%) had qHBsAg 100&ndash;500, 54 (6.4%) had qHBsAg 500&ndash;1000, and 272 (32.2%) had qHBsAg &gt;1000 IU/mL. Overall, 80% (682) had known HBeAg status at the last follow-up, and the majority (87.0%) were HBeAg-negative. In addition, 54% (461/844) had prior antiviral therapy, 19.7% of which (16.3, 23.7, n = 91) were HBsAg (&minus;). The treated patients had a lower risk of cirrhosis (16.46, 95% CI 1.89&ndash;143.39, p = 0.01) or HCC (8.23, 95% CI 1.01&ndash;67.39, p = 0.05) than the untreated patients. A lower proportion of the HBsAg-loss group had cirrhosis (5.7% vs. 10.9%, p = 0.021) and HCC (0.9% vs. 6.2%, p = 0.001). Conclusion: In this retrospective, ethnically diverse cohort study, CHB patients who received antiviral therapy and/or had HBsAg loss were less likely to develop cirrhosis and HCC, confirming the results of the studies in less diverse cohorts. No association was found between the qHBsAg level and fibrosis determined with LSM. Individuals who achieved HBsAg loss had low-level qHBsAg within 1 year of seroclearance

Experience and impact of stigma in people with chronic hepatitis B: a qualitative study in Asia, Europe, and the United States

Abstract Background People with chronic hepatitis B (CHB) commonly experience social and self-stigma. This study sought to understand the impacts of CHB-related stigma and a functional cure on stigma. Methods Adults with CHB with a wide range of age and education were recruited from 5 countries and participated in 90-minute qualitative, semi-structured interviews to explore concepts related to CHB-associated stigma and its impact. Participants answered open-ended concept-elicitation questions regarding their experience of social and self-stigma, and the potential impact of reduced CHB-related stigma. Results Sixty-three participants aged 25 to 71 years (15 from the United States and 12 each from China, Germany, Italy, and Japan) reported emotional, lifestyle, and social impacts of living with CHB, including prejudice, marginalization, and negative relationship and work experiences. Self-stigma led to low self-esteem, concealment of CHB status, and social withdrawal. Most participants stated a functional cure for hepatitis B would reduce self-stigma. Conclusions CHB-related social and self-stigma are widely prevalent and affect many aspects of life. A functional cure for hepatitis B may reduce social and self-stigma and substantially improve the health-related quality of life of people with CHB. Incorporating stigma into guidelines along with infectivity considerations may broaden the patient groups who should receive treatment