Antiviral drug utilization and annual expenditures for patients with chronic HBV infection in Guangzhou, China, in 2008-2015.

BACKGROUND: The aims of this study were to describe antiviral drug (AD) utilization and costs in patients with chronic HBV infection. METHODS: We conducted a retrospective study of patients in the hospital and calculated annual proportions of AD utilization and costs among patients. A two-part model was used to estimate adjusted odds ratio (OR) for antiviral therapy and cost ratios for antiviral costs associated with demographics. RESULTS: Of a total of 14,920 records, 143,658 records were involved in the analysis. The annual proportions of AD utilization were 56.99% (45.65%) for inpatients (outpatients) during 2008-2015 and increased annually. Entecavir (ETV), in particular, increased from 11.08% to 70.26% (11.05% to 49.35%) for inpatients (outpatients). The patients with medical insurance were more likely to use AD than patients without insurance, and the adjusted OR was 1.11 (95% CI: 1.03, 1.19) for inpatients and 1.66 (1.59, 1.73) for outpatients. With the disease progressing, the proportion of antiviral costs in total direct medical costs decreased from 13.91% to 4.07% (71.29% to 49.29%) for inpatients (outpatients). CONCLUSIONS: The use of AD for chronic HBV infection was less than expected based on established guidelines, and only half of patients received antiviral treatment. However, the AD utilization, especially ETV, increased annually. Reimbursement policy was the most important factor affecting antiviral treatment. Antiviral therapy was an important part of the direct medical costs, especially in the early stage of disease.

Chapter 6.1. Pediatric Chronic Hepatitis B and C: 30 Years of ESPGHAN Clinical Research and Recommendations.

The expression of hepatitis B and C virus infections in children differs from that in adults and requires specific paediatric expertise. The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has been a pioneer in this field, having stressed the need for straightforward recommendations since the mid-1980s. Following much observation, surveillance, and research, a panel of ESPGHAN experts was able to develop such recommendations on hepatitis B infection in children in 2009, which was then followed in June 2013 by proper guidelines. In the field of Chronic Hepatitis C, in 2011 ESPGHAN experts published also the Guidance for Clinical Trials for Children and Adolescents, and approved in 2012 the NASPGHAN guidelines for treatment. The ESPGHAN Society is to be commended for its pioneering work in furthering our understanding of chronic hepatitis B and C disease presentations in infants, children, and adolescents.

Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination Policy, China.

China's hepatitis B virus (HBV) prevention policy has been evaluated through nationally representative serologic surveys conducted in 1992 and 2006. We report results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in the context of program policy. The 2014 survey used a 2-stage sample strategy in which townships were selected from 160 longstanding, nationally representative, county-level disease surveillance points, and persons 1-29 years of age were invited to participate. The 2014 sample size was 31,713; the response rate was 83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen prevalence declined 46% by 2006 and by 52% by 2014. Among children <5 years of age, the decline was 97%. China's HBV prevention program, targeted toward interrupting perinatal transmission, has been highly successful and increasingly effective. However, this progress must be sustained for decades to come, and elimination of HBV transmission will require augmented strategies.

A historical perspective on the discovery and elucidation of the hepatitis B virus.

The discovery in 1965 of the "Australia antigen," subsequently identified as the hepatitis B virus surface antigen (HBsAg), was such a watershed event in virology that it is often thought to mark the beginning of hepatitis research, but it is more accurately seen as a critical breakthrough in a long effort to understand the pathogenesis of infectious hepatitis. A century earlier, Virchow provided an authoritative explanation of "catarrhal jaundice," which did not consider an infectious etiology, but the transmission of jaundice by human serum was clearly identified in two outbreaks in 1885, and the distinction between "infectious" and "serum" hepatitis was recognized by the early 1920s. The inability to culture a virus or reproduce either syndrome in laboratory animals led to numerous studies in human volunteers; by the end of World War II, it was known that the diseases were caused by different filterable agents, and the terms "hepatitis A" and "B" were introduced in 1947 (though some long-incubation cases then designated B must in retrospect have been hepatitis C). The development of a number of liver function tests during the 1950s led to the recognition of anicteric infections and the existence of chronic carriers, but little more could be done until an infectious agent had been identified. Once Blumberg and colleagues had found a specific viral marker, the vast amount of accumulated epidemiologic and clinical data, together with huge numbers of stored serum samples, enabled rapid progress in understanding hepatitis B, and revealed the existence of a vast population of chronically infected people in Asia, Oceania and Africa. In this article, we place the identification of the Australia antigen within the historical context of research on viral hepatitis. Following a chronological review from 1865 to 1965, we summarize how the discovery led to improved safety of blood transfusion, the development of a highly effective vaccine and the eventual identification of the hepatitis C, D and E viruses. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for chronic hepatitis B."

Then and now: the progress in hepatitis B treatment over the past 20 years.

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this review, we will examine the antiviral drugs and the progresses that have been made with antiviral treatments in the field of CHB.

Tracing hepatitis B virus to the 16th century in a Korean mummy.

UNLABELLED: A rare find of a mummified child from the 16th century AD, in Korea, with relatively preserved organs, enabled a search for ancient hepatitis B virus (aHBV) DNA sequences from laparoscopic-derived liver biopsies. Analysis of the complete aHBV genome (3,215 base pairs) revealed a unique HBV genotype C2 (HBV/C2) sequence commonly spread in Southeast Asia, which probably represents an HBV that infected the Joseon Dynasty population in Korea. Comparison of the aHBV sequences with contemporary HBV/C2 DNA sequences revealed distinctive differences along four open reading frames. Genetic diversity between contemporary and recovered aHBV/C2 DNA may be the result of immunologic, environmental, and/or pharmacologic pressures. The calculated time of most recent common ancestor suggests that the Korean HBV sequence origin dates back at least 3,000 years and possibly as long as 100,000 years. This isolate most likely represents the earliest human HBV sequence that colonized Southeast Asia by human migration. CONCLUSION: This study describes the complete sequence of the oldest HBV isolate and the most ancient full viral genome known so far.

Natural history of chronic hepatitis B in Euro-Mediterranean and African countries.

Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic infection. Perinatal HBV infection is rare while the vast majority of chronic infections originate from horizontal HBV transmission to infants and children. HBeAg loss and seroconversion to anti-HBe occur in a few years time, usually during the second decade of life. HBeAg-negative/anti-HBe-positive chronic hepatitis B (CHB), predominates in these countries being 7-9 times more frequent than HBeAg-positive CHB. The predominance of HBeAg-negative CHB is largely linked to the molecular characteristics of HBV genotype D prevailing in European and African countries of the Mediterranean basin and of genotype E and subgenotype A1 that prevail in the other parts of Africa. The molecular characteristics of the African subgenotype A1 differ from those of European subgenotype A2 explaining the fact that patients infected subgenotype A1 demonstrate an earlier loss of HBeAg and seroconversion to anti-HBe during the natural course of HBV infection compared to those infected with subgenotype A2. It is proposed that the molecular characteristics of HBV genotypes and subgenotypes prevailing in Euro-Mediterranean and African countries acting in concert with host and environmental factors largely determine the natural history of chronic HBV infection and its significant differences from countries of HBV genotype C and B and of subgenotype Ae predominance. The knowledge of the natural history of chronic HBV infection in Euro-Mediterranean and African countries combined with wide screening programs for prompt recognition and treatment of chronic HBV infection both in its HBeAg-positive and -negative immune reactive phases can be expected to increase the efficacy of current and future therapeutic strategies.

[Interferon in the treatment of viral hepatitis. The interferon was discovered 50 years ago]. / Interferon a vírushepatitis kezelésében. 50 éve fedezték fel az interferont.

The interferons are heterogenic glycoproteins which are produced on the effect of virus infection, as immune answer, by the living cells. They were discovered half a century ago. They have antineoplastic, antiviral and immunomodulator effect. The names of interferons used in the therapy are nominated with Greek letters. This nomination shows their origins: the interferon-alpha originates from leucocytes, the interferon-beta does from fibroblasts and the interferon-gamma is produced as immune interferon by lymphocytes. In human medicine both natural and recombinant interferons are applied. The connection of polyethyleneglycol to interferons ensures their sustained effect. Nowadays they are applied in the therapy of chronic hepatitis B or C as well as in oncology to inhibit the neoplasm progression.

[Give all children vaccine against hepatitis B!]. / Vaccinera alla barn mot hepatit B! Invandring från högendemiska länder har gjort att risken för smittspridning ökar.

The number of individuals with chronic hepatitis B in Sweden has increased, mainly due to new immigrant groups. A safe and effective hepatitis B vaccine exists which allows a flexible dosing schedule. Most countries in the world adheres to the WHO recommendations to include this vaccine in the childhood vaccination regimen. This has led to a substantial drop in morbidity and mortality from hepatitis B virus infections in high endemic regions such as Taiwan. Sweden should consider changing its vaccination policy, including the vaccination of high risk groups only, and consider vaccination of all infants.