Reimbursement policies in the Asia-Pacific for chronic hepatitis B.

BACKGROUND: There is considerable variation in reimbursement policies in Asian countries and this is likely to have an impact on treatment practice for chronic hepatitis B (CHB). Consequently a survey of leading hepatologists was performed to evaluate such policies and their impact on management of CHB in the Asia Pacific region. METHODS: A questionnaire was sent to key hepatologists in Asia Pacific for information on CHB reimbursement policy-its nature, coverage, funding source, duration, review strategy and impact on Asia Pacific Association for the Study of the Liver (APASL) CHB guidelines. The results were analysed and described. RESULTS: Leading hepatologists from 16 Asia Pacific countries responded. Almost all of the countries have reimbursement policies but eligibility varied from only a limited group (e.g. civil servants only) to universal access. In most instances reimbursement was from the central government (except China, Pakistan and Hong Kong). Reimbursement policies were usually created by Ministry of Health committees, who received input from medical professionals, although they may not be aware of the APASL guidelines. Policies were limited by available resources, funds and prioritization. Where there was a regular review this occurred between 1 and 5 years. The quantum of reimbursement varied from 50% in Singapore to 100% in the majority of other countries. The criteria for treatment reimbursement were based on doctor's opinion alone (Bangladesh, India, Pakistan, Philippines, Singapore and Vietnam) or specific clinical/laboratory criteria in the rest of the countries. In general, most countries offered unlimited duration for reimbursement except Taiwan, Indonesia and Pakistan. Monitoring tests for treatment response were reimbursed in all countries other than Vietnam. Viral resistance was diagnosed by viral or biochemical breakthrough, and viral resistance testing was uncommon. The main rescue therapy was adefovir. CONCLUSION: Reimbursement policies differed from country to country, the quantum and the proportion of patients who received reimbursement also varied significantly. Asia Pacific countries were able to follow APASL guidelines with variable success based on their reimbursement policies.

Prevalence of hepatitis B virus subgenotypes and basal core promoter, precore variants in patients with acute hepatitis B in central Vietnam.

OBJECTIVE: Hepatitis B virus (HBV) has been classified into 8 genotypes that have different geographic distributions. The clinical outcomes of acute hepatitis are dependent on genotype. The aim of this study was to investigate the distribution of HBV subgenotypes and basal core promoter (BCP)/precore (PC) regions in acute hepatitis patients in Central Vietnam to clarify the distributions and the clinical and virological differences. METHODS: 27 patients with acute hepatitis B were studied. HBV subgenotypes and BCP/PC variants were determined by direct sequencing of the preS, BCP/PC regions, respectively. RESULTS: HBV subgenotypes B4/Ba (n = 22) and C1/Cs (n = 5) were detected. Of the 27 patients, 3 developed fulminant hepatic failure, and all were infected with B4/Ba. Three patients had a BCP mutation, and 10 patients had a PC mutation in subgenotype B4/Ba. Three patients with C1/Cs had a BCP mutation. Two of 3 patients who progressed to fulminant hepatic failure had T1762, A1764, and A1896 simultaneously. None of the patients with acute, self-limited hepatitis carried these triple mutations. CONCLUSION: The prevalent HBV subgenotypes in patients with acute hepatitis B in Central Vietnam were B4/Ba and C1/Cs. BCP/PC variants have an association with the development of fulminant hepatic failure in subgenotype B4/Ba.

Genotyping of hepatitis B virus--genotypes a to g by multiplex polymerase chain reaction.

OBJECTIVES: Eight genotypes (A-H) of hepatitis B virus (HBV) are known with variations in nucleotide sequences greater than 8%. Several recent publications found that the clinical course and outcome of antiviral therapy depended on the genotype of the infecting HBV strain. Large epidemiological studies will require the availability of a system which is rapid, reliable and can be performed on a large number of samples. METHODS: To establish a simple and accurate genotyping method, the study collected 369 HBV complete genomic sequences from the GenBank database. Type-specific primers were also designed that separated HBV genotypes A to G by multiplex polymerase chain reaction. RESULTS: By comparison with the traditional restriction fragment length polymorphism method, over 93% of 441 samples were accurately genotyped by current assay, with a higher detection rate and sensitivity to detect mixed HBV infections. CONCLUSIONS: This methodology can be applied only to areas prevalent with HBV genotypes A to G. However, it provides an efficient alternative for clinical diagnosis and large-scale studies.

Five subgenotypes of hepatitis B virus genotype B with distinct geographic and virological characteristics.

Several hepatitis B virus (HBV) subgenotypes, HBV/A1, A2, Bj and Ba, have been reported with respect to clinical differences among patients infected with these subgenotypes. The population genetics and phylogeography of HBV were investigated based on the complete genome sequences of 484 isolates with 108 from our chronic hepatitis B patients and the remaining from the GenBank database. Besides genotypes A-H (HBV/A-H), five subgenotypes were identified among 169 HBV/B isolates by phylogenetic analysis and nucleotide divergence. There were 27 isolates of subgenotype B(1) (HBV/B(1)) restricted to Japan, 104 isolates of HBV/B(2) with the widest distribution in most Asian countries, 4 isolates of HBV/B(3) restricted to Indonesia, 32 isolates of HBV/B(4) restricted to Vietnam, and 7 isolates of HBV/B(5) restricted to Philippines. HBV/B(2)-B(5) isolates carried a recombination with HBV/C over the precore and core genes. In addition to the characteristics of HBV/B(1)-B(5) at some cis-acting elements, the precore stop-codon mutant (G1896A) was significantly different among HBV/B(1), HBV/B(2), and HBV/B(4) (70.3%, 31.7%, 53.0%, P=0.001), while no such mutation was found in HBV/B(3) and B(5). Among characteristics of the HBV/B(1)-B(5) amino acid sequences, serotype adw (K(122)) was exclusive among HBV/B(1), HBV/B(2), and HB V/B(3) isolates, while serotype ayw (R(122)) was among the HBV/B(4) and HBV/B(5) isolates. Furthermore, distinct variations of T cell and B cell recognition epitopes within surface and core proteins were also found among these subgenotypes. In conclusion, subgenotypes HBV/B(1)-B(5) exhibited distinct geographical distributions, virologic characteristics, and probable clinical implications.

Practical difficulties in the management of hepatitis B in the Asia-Pacific region.

The Asia-Pacific Expert Committee on Hepatitis B Management recently reviewed the impact of hepatitis B in the region and assessed the differences and similarities observed in the practical management of the disease in individual Asia-Pacific countries. Hepatitis B is a major health concern in the Asia-Pacific region, and of all chronically infected carriers worldwide, approximately 75% are found in Asia. The disease poses a considerable burden on healthcare systems, and is likely to remain a cause of substantial morbidity and mortality for several decades. Disease prevention activities, including screening and vaccination programs, have been implemented successfully in some Asia-Pacific countries and similar measures are being established in other parts of the region. The management of hepatitis B in the Asia-Pacific varies throughout the region, with each country confronting different issues related to treatment options, disease monitoring and duration of therapy. The influence of cost, availability of diagnostic equipment, and patient awareness and compliance are of additional concern. Although guidelines such as those developed by the Asian Pacific Association for the Study of the Liver have been created to address problems encountered in the management of hepatitis B, many physicians in the region still find it difficult to make satisfactory management decisions because of the treatment choices available. This article examines the different approaches to hepatitis B management in a number of Asia-Pacific countries, and highlights the difficulties that can arise when adhering to treatment guidelines and disease prevention solutions that have proved to be successful in the region.