Hepatitis B virus genotypes in precision medicine of hepatitis B-related hepatocellular carcinoma: Where we are now.

Hepatitis B virus (HBV) infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma (HCC). HBV genetics are diverse where it is classified into at least 9 genotypes (A to I) and 1 putative genotype (J), each with specific geographical distribution and possible different clinical outcomes in the patient. This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC, related to different pathogenicity of the virus and host response. This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine, in addition to the recent advances in cellular and molecular biology technologies.

Progress towards elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission update.

The top 20 highest burdened countries (in disability-adjusted life years) account for more than 75% of the global burden of viral hepatitis. An effective response in these 20 countries is crucial if global elimination targets are to be achieved. In this update of the Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis, we convene national experts from each of the top 20 highest burdened countries to provide an update on progress. Although the global burden of diseases is falling, progress towards elimination varies greatly by country. By use of a hepatitis elimination policy index conceived as part of the 2019 Commission, we measure countries' progress towards elimination. Progress in elimination policy has been made in 14 of 20 countries with the highest burden since 2018, with the most substantial gains observed in Bangladesh, India, Indonesia, Japan, and Russia. Most improvements are attributable to the publication of formalised national action plans for the elimination of viral hepatitis, provision of publicly funded screening programmes, and government subsidisation of antiviral treatments. Key themes that emerged from discussion between national commissioners from the highest burdened countries build on the original recommendations to accelerate the global elimination of viral hepatitis. These themes include the need for simplified models of care, improved access to appropriate diagnostics, financing initiatives, and rapid implementation of lessons from the COVID-19 pandemic.

A cautionary note to hepatitis B e antigen (HBeAg)-negative test results in pregnant women in an area prevalent of HBeAg-negative chronic hepatitis B.

Maternal hepatitis B e Antigen (HBeAg) positivity poses a risk for hepatitis B virus (HBV) mother-to-child transmission (MTCT). In resource-constrained settings, HBeAg testing is recommended as an alternative to HBV DNA testing to establish antiviral prophylaxis eligibility. Nevertheless, the high prevalence of HBeAg-negative chronic hepatitis B (e-CHB) in many countries should not be overlooked. We studied HBV characteristics and explored the potential MTCT risk among HBeAg-negative/HBsAg-positive expectant mothers in an area prevalent of e-CHB. Among 1348 pregnant mothers screened for HBV infection, 81 (6.0%) were HBsAg-positive. These women were examined for HBeAg, HBV DNA, and cord blood HBV DNA. Sixteen (19.8%) of the HBsAg-positive mothers were HBeAg-positive, whereas 65 (80.2%) were HBeAg-negative, including eight inactive carriers (HBsAg <100 IU/ml, HBV DNA ≤ 2000 IU/ml, and ALT < 40 IU/L). Of the remaining 57 HBeAg-negative mothers, ten revealed HBV Basal Core Promoter or Precore mutations, with three having high viremia (HBV DNA > 200 000 IU/mL), which is associated with a high MTCT risk and therefore qualifies them for antiviral prophylaxis. This pilot study provides a cautionary note to the interpretation of negative HBeAg test results when determining eligibility for MTCT antiviral prophylaxis in situations with limited resources and in regions where e-CHB is prevalent.

Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants.

Background: The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. Methods: A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. Results: No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067-4.578, P = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316-18.310, P < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010-14.858, P = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605-11.023, P = 0.004). Conclusions: Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.

Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy.

Hepatitis B virus (HBV) infection still remains a major public health issue in the Asia-Pacific region. Most of the burden of HBV-related disease results from infections acquired in infancy through perinatal or early childhood exposure to HBV in Asia-Pacific. Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These APASL guidelines provide a comprehensive review and recommendations based on available evidence in the literature, for the management of females with HBV infection through every stage of pregnancy and postpartum. These also address the concerns, management challenges, and required follow-up of children born to hepatitis B-positive mothers.

Convalescent plasma therapy in patients with moderate-to-severe COVID-19: A study from Indonesia for clinical research in low- and middle-income countries.

BACKGROUND: We explored the outcome of convalescent plasma (CP) treatment in patients with moderate and severe coronavirus disease 2019 (COVID-19) and investigated variables for the design of further trials in Indonesia. METHODS: Hospitalised patients with moderate (n = 5) and severe (n = 5) COVID-19 were recruited and transfused with CP from donors who recovered from mild (n = 5), moderate (n = 5), or severe (n = 1) COVID-19. Neutralising antibodies (NAbs) to the virus were measured at the end of the study using a surrogate virus neutralisation test as an alternative to the plaque reduction assay. Clinical improvement was assessed based on the modified World Health Organization Research and Development Blueprint six-point scale, Brixia Chest-X-Ray scoring, and laboratory parameters. The study was registered at ClinicalTrials.gov (NCT04407208). FINDINGS: CP transfusion in three doses of 3 mL/kg of recipient body weight at 2-day intervals was well tolerated. Good clinical improvement was achieved in all patients with moderate disease and in two patients with severe disease. Most patients at baseline had detectable NAbs with median inhibition rates comparable to those of the donors (90·91% vs. 86·31%; p = 0·379). This could be due to the unavailability of pre-donation NAb testing and postponed CP administration that required communal consent. INTERPRETATION: This study highlights the safety of CP therapy. Although improvements were observed, we could not conclude that the outcomes were solely due to CP treatment. Further randomised controlled trials that cover different disease stages with pre-donation NAb measurements using locally applicable strategies are warranted. FUNDING: The study was supported by PT Bio Farma, Indonesia.

Genetic and antigenic characterization of influenza A/H5N1 viruses isolated from patients in Indonesia, 2008-2015.

Since the initial detection in 2003, Indonesia has reported 200 human cases of highly pathogenic avian influenza H5N1 (HPAI H5N1), associated with an exceptionally high case fatality rate (84%) compared to other geographical regions affected by other genetic clades of the virus. However, there is limited information on the genetic diversity of HPAI H5N1 viruses, especially those isolated from humans in Indonesia. In this study, the genetic and antigenic characteristics of 35 HPAI H5N1 viruses isolated from humans were analyzed. Full genome sequences were analyzed for the presence of substitutions in the receptor binding site, and polymerase complex, as markers for virulence or human adaptation, as well as antiviral drug resistance substitutions. Only a few substitutions associated with human adaptation were observed, a remarkably low prevalence of the human adaptive substitution PB2-E627K, which is common during human infection with other H5N1 clades and a known virulence marker for avian influenza viruses during human infections. In addition, the antigenic profile of these Indonesian HPAI H5N1 viruses was determined using serological analysis and antigenic cartography. Antigenic characterization showed two distinct antigenic clusters, as observed previously for avian isolates. These two antigenic clusters were not clearly associated with time of virus isolation. This study provides better insight in genetic diversity of H5N1 viruses during human infection and the presence of human adaptive markers. These findings highlight the importance of evaluating virus genetics for HPAI H5N1 viruses to estimate the risk to human health and the need for increased efforts to monitor the evolution of H5N1 viruses across Indonesia.

Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission.

The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.

International Liver Transplantation Society Asian Consensus on the Management of Hepatitis C Virus Infection in Resource Limited Setting-From Noncirrhotic to Decompensated Disease and After Liver Transplantation.

BACKGROUND: The population of Asia exceeds 4.4 billion people. Chronic hepatitis C virus (HCV) infection in Asia is characterized by specific distribution of genotypes, lack of access to specific therapeutic agents, relatively high cost of treatment, and lack of experienced healthcare providers. Clear consensus on the diagnosis, management, and monitoring of HCV infection specific to the Asian region is a major unmet need. The consensus guidelines documents that have been published to date by major medical societies presume access to an array of direct acting antiviral agents and diagnostic tests that are not broadly applicable to resource limited settings, including Asia. METHODS: To address the lack of an Asia-specific set of HCV treatment guidelines, we assembled a panel of 15 HCV experts in the field of hepatology from India, Indonesia, Myanmar, Vietnam, Pakistan, Philippines, and Mongolia convened in April 2017 to review the updated literature and provide recommendations on the diagnosis and management of chronic HCV infection that reflects local conditions. RESULTS: An evidence-based comprehensive compilation of the literature supported by the graded recommendations from the expert panel for the optimization of the diagnosis, pretreatment, on treatment, and posttreatment assessments, and management of chronic HCV infection has been presented in this article. CONCLUSIONS: With the evolving treatment landscape and addition of several new direct-acting antiviral agents and combination regimens into the therapeutic armamentarium, the current article may serve as a guide to the clinicians in optimizing the diagnosis and treatment selection for the management of chronic HCV infection in resource-limited settings.

Seroepidemiology of HBV infection among health-care workers in South Sulawesi, Indonesia.

BACKGROUND: Hepatitis B virus (HBV) infection is a world health problem with an estimated 257 million chronically infected people. Indonesia, with 7.1% prevalence of hepatitis B surface antigen (HBsAg), is classified as a moderately endemic country. Healthcare workers (HCWs) are at high occupational risk for HBV infection and potentially becoming transmitters for further infections. In Indonesia, the extent of hepatitis B among HCWs and specific control strategy are not available. This study evaluated the seroprevalence of HBV infection and associated risk factors in HCWs from four areas in South Sulawesi, Indonesia. METHODS: A total of 467 HCWs (median age 28 years, male/female 89/378) were recruited. All HCWs were classified into three age groups (< 20-29, 30-39, and ≥ 40 years old), three work types (administration, non-intervention, and intervention), and three service periods (< 5, 5-9, and ≥ 10 years). Data on socio-demographic characteristics and risk factors were obtained by questionnaire and serum samples were tested for HBV markers (HBsAg, its antibody [anti-HBs], and antibody to core antigen [anti-HBc]. Chi-square or Fisher's exact test was used to determine differences in categorical variables, while risk factors were reported as odds ratios (OR). RESULTS: The prevalence of current HBV infection (HBsAg+), exposure to HBV (anti-HBc+), and immunity to HBV (anti-HBs+) was 6.2, 19.2, and 26.1%, respectively. Two thirds (66.17%) of all HCWs did not express any of HBV markers. In relation to the age groups, intervention work-type, and service period of HCWs, increasing trends were observed in the exposure to HBV (p < 0.001, p < 0.001, and p < 0.010, respectively) and the immunity to HBV by natural infection (HBsAg-, anti-HBc+, anti-HBs+) (p = 0.004, p < 0.001, and p < 0.010, respectively). Needlestick injury contributed the highest risk factor (OR = 1.71; 95% CI: 1.05-2.77; p = 0.029) for infection acquisition, which mostly occurred in the intervention group (p = 0.046). CONCLUSION: Exposure to HBV showed significant association with HCWs' age, work type, and service period. Needlestick injury was the highest risk factor for the acquisition of HBV, with highest events in the intervention work-type. Two thirds of HCWs were still susceptible to HBV infection. Intervention strategies at the national level are required to mount prevention, control, and management of HBV infection in HCWs.

Exploring contacts facilitating transmission of influenza A(H5N1) virus between poultry farms in West Java, Indonesia: A major role for backyard farms?

Highly pathogenic avian influenza virus (HPAIV) H5N1 has been reported in Asia, including Indonesia since 2003. Although several risk factors related to the HPAIV outbreaks in poultry in Indonesia have been identified, little is known of the contact structure of farms of different poultry production types (backyard chickens, broilers, layers, and ducks). This study aims to quantify the contact rates associated with the movement of people, and movements of live birds and products and equipment that affect the risk of HPAIV H5N1 transmission between poultry farms in Indonesia. On 124 poultry farms in 6 districts in West Java, logbooks were distributed to record the movements of farmers/staff and visitors and their poultry contacts. Most movements in backyard chicken, commercial native chicken, broiler and duck farms were visits to and from other poultry farms, whilst in layer farms visits to and from poultry companies, visits to egg collection houses and visit from other poultry farms were most frequent. Over 75% of persons visiting backyard chicken and duck farms had previously visited other poultry farms on the same day. Visitors of backyard chicken farms had the highest average contact rate, either direct contact with poultry on other farms before the visits (1.35 contact/day) or contact during their visits in the farms (10.03 contact/day). These results suggest that backyard chicken farms are most at risk for transmission of HPAIV compared to farms of the other poultry production types. Since visits of farm-to-farm were high, backyard farms could also a potential source for HPAIV transmission to commercial poultry farms.

Hepatitis B virus infection in children of HBV-related chronic liver disease patients: a study of intra-familial HBV transmission.

BACKGROUND: HBV-infected patients are potential sources of intra-familial transmission. We studied HBV transmission and molecular characteristics within families of HBV-related chronic liver disease (CLD) patients. METHODS: Family members [index cases (ICs), spouses, and 1-18-year-old children] of HBV-related CLD patients were tested for HBsAg, anti-HBc, and anti-HBs. HBsAg-positive subjects were tested for HBeAg/anti-HBe. Anti-HBc-positive children together with their family members were further investigated for HBV DNA. Sequences of positive isolates were analyzed over surface, precore (PC) and basal core promoter (BCP) regions. RESULTS: Among 94 children of 46 ICs, the prevalence of HBsAg, anti-HBc, and anti-HBs was 10 (10.6 %), 19 (20.2 %), and 46 (48.9 %), respectively. Thirty-eight (40.4 %) children were seronegative, indicating susceptibility to HBV infection. HBV DNA was identified in all ICs, 4 spouses, and 16 children. Having both parents with HBsAg positive and at least two HBV carriers in the households were significant risk factors of intra-familial transmission. HBV genotype/subtype distributions were comparable between children and ICs/spouses, with predominance of genotype B. The majority of HBV DNA sequences found in children were identical to their corresponding ICs-particularly mothers-including mutation patterns in the surface, PC, and BCP regions. Recognized mutations associated with HBsAg detection and/or vaccination failure, T140I, T143S/M, G145R, and Y161F, were identified in 20 subjects; while mutations linked to HBeAg-defective variants, PC G1896A and BCP A1762T/G1764A, were found in 7 and 11 subjects, respectively. CONCLUSIONS: Children of HBV-related CLD patients were at increased risk of HBV infection through multi-modal transmission routes despite negative parental HBsAg and HBeAg status.

Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, and DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.

Hepatitis B and hepatitis C in southeast and southern Asia: challenges for governments.

In 2015, the Coalition to Eradicate Viral Hepatitis in Asia Pacific gathered leading hepatitis experts from Bangladesh, India, Indonesia, Malaysia, Pakistan, the Philippines, and Thailand to discuss common challenges to the burden posed by hepatitis B virus (HBV) and hepatitis C virus (HCV), to learn from each other's experience, and identify sustainable approaches. In this report, we summarise these discussions. Countries differ in their policy responses to HBV and HCV; however, substantial systemic, cultural, and financial barriers to achievement of elimination of these infections persist in all countries. Common challenges to elimination include limited availability of reliable epidemiological data; insufficient public awareness of risk factors and modes of transmission, leading to underdiagnosis; high rates of transmission through infected blood products, including in medical settings; limited access to care for people who inject drugs; prevailing stigma and discrimination against people infected with viral hepatitis; and financial barriers to treatment and care. Despite these challenges, promising examples of effective programmes, public-private initiatives, and other innovative approaches are evident in all countries we studied in Asia Pacific. The draft WHO Global Health Sector Strategy on Viral Hepatitis 2016-21 provides a solid framework upon which governments can build their local strategies towards viral hepatitis. However, greater recognition by national governments and the international community of the urgency to comprehensively tackle both HBV and HCV are still needed. In all countries, strategic plans and policy goals need to be translated into resources and concrete actions, with national governments at the helm, to enable a sustainable response to the rising burden of hepatitis B and C in all countries.

Chronic hepatitis B in pregnant women: is hepatitis B surface antigen quantification useful for viral load prediction?

BACKGROUND: New cases of hepatitis B virus (HBV) infection continue to occur worldwide. Most of these are due to mother-to-child transmission (MTCT), with maternal viraemia as the most important contributing factor. The hepatitis B surface antigen (HBsAg) level, which correlates positively with viral load, has been used for treatment monitoring in chronic hepatitis B. This study evaluated the usefulness of quantitative HBsAg for viral load prediction in HBsAg-positive pregnant women. METHODS: A total of 943 pregnant women in Makassar, Indonesia, were screened for HBsAg. Sixty-four women were HBsAg-positive and investigated. HBsAg level and hepatitis B e antigen (HBeAg)/hepatitis B e antibody (anti-HBe) status were determined serologically. Viral load was measured by real-time PCR. HBV DNA was sequenced and analysed for identification of genotype and basal core promoter (BCP)/precore (PC) mutations. RESULTS: Of 64 subjects, 12 (18.8%) were HBeAg-positive and 52 (81.3%) were HBeAg-negative. HBsAg and HBV DNA levels were significantly higher in the HBeAg-positive group (p<0.001). HBsAg and HBV DNA levels were positively correlated in the HBeAg-positive group (r = 0.659; p=0.02), but not in the HBeAg-negative group (r=0.194; p=0.168). Low HBsAg levels (<3.0 log10 IU/ml) corresponded with HBV DNA levels<6.0 log10 IU/ml (r=0.404; p=0.001), a recognized threshold for MTCT. Genotype C was more prevalent than genotype B, but not associated with HBsAg level, viral load, or HBeAg status. Two-thirds of HBeAg-negative subjects with high HBV DNA levels harboured BCP (A1762T/G1764A) and/or PC (G1896A) variants. CONCLUSIONS: HBsAg levels provide a good viral load predictor in HBeAg-positive but not HBeAg-negative pregnant women. The HBeAg-negative group had a frequent occurrence of BCP/PC variants, which may have contributed to the lack of correlation observed. Samples with a low HBsAg level, which is associated with a low risk of MTCT, do not require HBV DNA measurement.

High Prevalence of Hepatitis B Virus Infection in Young Adults in Ternate, Eastern Indonesia.

The incidence of hepatitis B virus (HBV) infection has been declining thanks to the universal hepatitis B infant immunization program. Nevertheless, young adults born before the program implementation might have acquired HBV in early childhood or remain susceptible to infection. This study aimed to evaluate hepatitis B epidemiology in asymptomatic young adult population in Ternate, eastern Indonesia. Serum samples of 376 subjects (aged 17-25, mean 19.82 ± 1.69 years; male/female 138/238) were screened for HBV parameters serologically (HBV surface antigen [HBsAg]; its antibody [anti-HBs]; anti-core antigen [anti-HBc]), and molecularly (HBV DNA). HBsAg, anti-HBc, anti-HBs, and HBV DNA prevalence were 15.7%, 36.2%, 24.2%, and 27.9%, respectively, with male predominance. Of all subjects, 13.0% were HBsAg negative with detectable HBV DNA (occult hepatitis B [OHB]), and 56.4% showed negativity for all seromarkers. This population showed high hepatitis B prevalence with substantial occurrence of OHB. However, a high percentage of the population were still susceptible and at risk of HBV infection. This study emphasizes the necessity to improve prevention strategies to screen and manage HBV carriers, including the adoption of catch-up or booster vaccination targeted to young adult populations. Investigations on the roles of host-virus interactions associated with OHB and its implications are warranted.

Current prevalence of hepatitis B infection among parturient women in Jakarta, Indonesia.

AIM: to determine the current prevalence of hepatitis B infection among parturient women in Jakarta, Indonesia. METHODS: a cross-sectional study was conducted in women giving birth between May and July 2009, recruited by consecutive sampling technique in 2 hospitals and 13 public health centers in Jakarta. Mothers with history of chronic liver disease were excluded. Data were collected by questionnaires including obstetric history, hepatitis B immunization history, and the presence of jaundice; maternal venous blood samples were taken before parturition for HBsAg determination that was performed by ELISA. RESULTS: of 1,009 parturient women screened for hepatitis B infection, 22 were found positive, giving an overall hepatitis B prevalence of 2.2%, previous 5.2% in 1985. None of the subjects had any symptoms of HBV infection. The highest HBsAg prevalence was found in the East Jakarta study site, with predominance in mothers aged <20 years and those with multi-parities. CONCLUSION: present prevalence of HBsAg among Indonesian parturient women in Jakarta was 2.2% and markedly reduced compared with prevalence in 1985.

Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors.

BACKGROUND: Selection of hepatitis B virus (HBV) by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the 'a' determinant of the surface antigen (HBsAg), the main target of antibody neutralization and diagnostic assays. However, there have never been successful attempts to provide evidence for this hypothesis, partly because the 3 D structure of HBsAg molecules has not been determined. Tertiary structure prediction of HBsAg solely from its primary amino acid sequence may reveal the molecular energetic of the mutated proteins. We carried out this preliminary study to analyze the predicted HBsAg conformation changes of HBV variants isolated from Indonesian blood donors undetectable by HBsAg assays and its significance, compared to other previously-reported variants that were associated with diagnostic failure. RESULTS: Three HBV variants (T123A, M133L and T143M) and a wild type sequence were analyzed together with frequently emerged variants T123N, M133I, M133T, M133V, and T143L. Based on the Jameson-Wolf algorithm for calculating antigenic index, the first two amino acid substitutions resulted in slight changes in the antigenicity of the 'a' determinant, while all four of the comparative variants showed relatively more significant changes. In the pattern T143M, changes in antigenic index were more significant, both in its coverage and magnitude, even when compared to variant T143L. These data were also partially supported by the tertiary structure prediction, in which the pattern T143M showed larger shift in the HBsAg second loop structure compared to the others. CONCLUSIONS: Single amino acid substitutions within or near the 'a' determinant of HBsAg may alter antigenicity properties of variant HBsAg, which can be shown by both its antigenic index and predicted 3 D conformation. Findings in this study emphasize the significance of variant T143M, the prevalent isolate with highest degree of antigenicity changes found in Indonesian blood donors. This highlights the importance of evaluating the effects of protein structure alterations on the sensitivity of screening methods being used in detection of ongoing HBV infection, as well as the use of vaccines and immunoglobulin therapy in contributing to the selection of HBV variants.