Pattaratida Sa-nguanmoo

Low pretreatment serum HBsAg level and viral mutations as predictors of response to PEG-interferon alpha-2b therapy in chronic hepatitis B.

BACKGROUND Viral genomic mutations have become increasingly recognized as being associated with the outcome of chronic HBV infection. However, the role of viral mutations as a predictor of response to pegylated-interferon (PEG-IFN) therapy has so far remained unclear. STUDY DESIGN Viral mutations in the enhancer II/basal core promoter (BCP)/precore and the pre-S regions were characterized by direct sequencing in pretreatment serum samples of 50 patients with chronic hepatitis B (33 HBeAg-positive and 17 HBeAg-negative), who were treated for 48 weeks with PEG-IFN alpha-2b. RESULTS Sustained virological response at 48 weeks post treatment, defined as HBeAg seroconversion and HBV DNA<2000IU/mL for HBeAg-positive patients, and HBV DNA<200IU/mL for HBeAg-negative patients, was achieved in 12 (36.4%) and 6 (35.3%) of HBeAg-positive and HBeAg-negative patients, respectively. Response to PEG-IFN therapy correlated to low pretreatment HBsAg level but did not correlate with HBV genotype, pretreatment alanine transaminase and HBV DNA levels. In HBeAg-positive hepatitis, PEG-IFN response correlated with the appearance of double BCP mutations (A1762T/G1764A) at baseline (P=0.041). In the HBeAg-negative group, response to PEG-IFN therapy was associated with the presence of pre-S mutation/deletions (P=0.028). Multivariate analysis identified low pretreatment HBsAg level as an independent factor associated with SVR in both groups. CONCLUSIONS Pretreatment quantitative HBsAg determination is useful for predicting response to PEG-IFN therapy. The presence of double BCP and pre-S mutation/deletions at entry may be associated with a high rate of antiviral response in HBeAg-positive and HBeAg-negative hepatitis, respectively.

Comparison between quantitative hepatitis B surface antigen, hepatitis B e-antigen and hepatitis B virus DNA levels for predicting virological response to pegylated interferon-α-2b therapy in hepatitis B e-antigen-positive chronic hepatitis B

Aim:  The aim of this study was to compare the clinical applicability of quantitative serum hepatitis B surface antigen (HBsAg), hepatitis B e‐antigen (HBeAg) and hepatitis B virus (HBV) DNA for predicting virological response (VR) to pegylated interferon (PEG‐IFN) therapy.

Molecular epidemiological study of hepatitis B virus among migrant workers from Cambodia, Laos, and Myanmar to Thailand.

Although hepatitis B virus (HBV) infection is endemic in Southeast Asia, molecular epidemiological data on HBV circulating in some countries are limited. The aims of this study were to evaluate the seroprevalence of HBV and its genetic variability among migrant workers from Cambodia, Laos, and Myanmar in Thailand. Sera collected from 1,119 Cambodian, 787 Laotian, and 1,103 Myanmarese workers were tested for HBsAg. HBV DNA was amplified and the pre‐S/S region was sequenced for genotyping and genetic mutation analysis. HBsAg was detected in 282 (9.4%). The prevalence of HBsAg among migrant workers from Cambodia, Laos, and Myanmar was 10.8%, 6.9%, and 9.7%, respectively. Of 224 subjects positive for HBV DNA, 86% were classified as genotype C (99% were sub‐genotype C1) and 11.6% were genotype B (30.8%, 34.6%, and 30.8% were sub‐genotypes B2, B3, and B4, respectively). Various point mutations in the “a” determinant region were detected in approximately 18% of these samples, of which Ile126Ser/Asn was the most frequent variant. Sequencing analysis showed that 19.1% of samples had pre‐S mutations, with pre‐S2 deletion as the most common mutant (7.7%) followed by pre‐S2 start codon mutation (3.8%) and both pre‐S2 deletion and start codon mutation (3.3%). High prevalence of HBV infection (approximately 7–11%) was found among migrant workers from Cambodia, Laos, and Myanmar, which may reflect the current seroprevalence in their respective countries. The data also demonstrated that HBV sub‐genotype C1 was the predominant strain and various mutations of HBV occurring naturally were not uncommon among these populations. J. Med. Virol. 82:1341–1349, 2010.

Increased risk of developing chronic HBV infection in infants born to chronically HBV infected mothers as a result of delayed second dose of hepatitis B vaccination.

This two-stage study (cross-sectional and case-control) assessed the effects of delayed second dose HB vaccination on the risk of developing chronic HBV infection in infants born to chronically HBV infected mothers. 521 infants enrolled received the first vaccination by the end of the day after birth, without HBIG. 15 of these infants were chronically HBV infected. In the case-control comparison, controlling for HBeAg in the mother, the risk of an infant becoming chronically infected was 3.74 times (95% CI=0.97-14.39) higher if the interval between the first and the second doses exceeded 10 weeks. This finding suggests it is important that immunization programs ensure timely second dose vaccination to infants born to mothers with chronic HBV infection. Nevertheless, due to the small sample size, these findings should be verified by larger studies.

Hepatitis E virus infection: Epidemiology and treatment implications

Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable.

Molecular analysis of hepatitis B virus associated with vaccine failure in infants and mothers: A case–control study in Thailand

Perinatal transmission of hepatitis B virus (HBV) has been controlled incompletely despite adequate immunoprophylaxis in infants. The aim of this study was to characterize virological factors of HBV associated with vaccine failure in Thailand. Sera of 14 infected infants (13 HBeAg‐positive and one HBeAg‐negative) with vaccine failure and their respective mothers (group M1) were tested quantitatively for HBV DNA by real‐time PCR, HBV genotypes and mutations were characterized by direct sequencing. Sera collected from 15 HBeAg‐positive (group M2) and 15 HBeAg‐negative (group M3) mothers whose infants had been vaccinated successfully served as controls. The results showed that group M1 and group M2 mothers had equal titers of HBV DNA but higher titers than group M3. All infected infants and their respective mothers had the same HBeAg status and HBV genotypes. DNA analysis in a pair of HBeAg‐negative infant and mother revealed that both were infected with an HBV precore mutant (G1896A). Escape mutants in the “a” determinant region (residues 144 and 145) were detected in two (14%) infected infants. The prevalence of BCP mutations/deletions in groups M2 and M3 was higher significantly than in group M1 (P = 0.022 and P < 0.001, respectively). In conclusion, instead of the HBeAg status, a high titer of HBV DNA in mothers was the major contributor to perinatal transmission of HBV. Escape mutants might be associated with vaccine failure in some infants. BCP mutations/deletions in mothers might contribute to the prevention of mother‐to‐infant transmission of HBV. J. Med. Virol. 84: 1177–1185, 2012.

The Success of a Universal Hepatitis B Immunization Program as Part of Thailand's EPI after 22 Years' Implementation.

Hepatitis B vaccination for newborns was introduced in two provinces in 1988 as part of Thailand’s Expanded Program on Immunization (EPI), and extended to the whole country in 1992. Our previous studies showed that children and adolescents who were born after the implementation of this program had a carrier rate of less than 1%, compared with 5–6% before implementation. In 2014 we performed hepatitis B serosurveys among 5964 subjects in the different geographic regions of the country to evaluate the long-term immunogenicity and impact of universal hepatitis B vaccination in newborns as part of the 22-year EPI program, by assessing HBsAg, anti-HBc and anti-HBs seropositivity status. The number of HB virus (HBV) carriers, both children and young adults, who were born after universal HB vaccination was markedly reduced. The carrier rates among the age groups 6 months to 5 years, 5–10, 11–20, 21–30, 31–40, 41–50 and >50 years were respectively 0.1, 0.29, 0.69, 3.12, 3.78, 4.67 and 5.99%. The seropositivity rate for HBsAg in the post-EPI group was 0.6%, whereas in the pre-EPI group it was as high as 4.5% (p<0.001). HBV infection by means of detectable anti-HBc had also drastically declined in the population born after the HB vaccine was integrated into the EPI program. We estimated that the total number of HBV carriers amounted to 2.22 million, or 3.48% of the total population, most of whom are adults. The HB vaccine is the first vaccine shown to be effective in preventing the occurrence of chronic liver disease and hepatocellular carcinoma. Universal vaccination campaign will contribute to the eventual eradication of HBV-associated disease.

Prevalence, whole genome characterization and phylogenetic analysis of hepatitis B virus in captive orangutan and gibbon.

Background  Hepatitis B virus (HBV) is a public health problem worldwide and apart from infecting humans, HBV has been found in non‐human primates.

Hepatitis B Virus Genetic Variation and TP53 R249S Mutation in Patients with Hepatocellular Carcinoma in Thailand

Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factors for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variation and the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infected with HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249S mutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP) in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basal core promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group. R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was not significantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations was independently associated with the risk of HCC in Thai patients.

HIV and Hepatitis B coinfection among perinatally HIV-infected Thai adolescents.

Objectives: This study aimed to determine the prevalence of hepatitis B virus (HBV) coinfection and HBV seropositivity in perinatally HIV-infected adolescents. A secondary objective was to describe the clinical characteristics of adolescents with chronic HBV/HIV coinfection. Materials and Methods: Multicenter cross-sectional study of perinatally HIV-infected adolescents aged 12–25 years. HBV surface antigen, surface antibody (anti-HBs) and core antibody (anti-HBc) were measured. Coinfection was defined as having persistently positive HBV surface antigen. Seroprotective antibody from immunization was defined as having anti-HBs ≥10 mIU/mL with negative anti-HBc. HBV DNA quantitation and rtM204V/I mutation analysis (lamivudine resistance–associated mutation) were performed in adolescents with chronic HBV infection. Results: From November 2010 to March 2011, 521 patients were enrolled. Mean (SD) of CD4 lymphocyte count was 685 (324) cells/&mgr;L. The prevalence of HBV/HIV coinfection was 3.3% (95% confidence interval: 1.9–5.2%). Protective antibody against HBV was found in 18% of population, and this was significantly higher among adolescents who received than those who did not receive HBV revaccination after receiving antiretroviral therapy (93% versus 6%, P < 0.01). Among adolescents with chronic HBV infection, 88% have received lamivudine; however, 69% have HBV DNA >105 copies/mL and 75% had the rtM204V/I mutation. Conclusions: The prevalence of HBV coinfection in HIV-infected Thai adolescents was 3.3%. Most HIV-infected adolescents had no HBV protective antibody; therefore, revaccination with HBV vaccine is encouraged. The high prevalence of HBV-lamivudine resistance underscores the importance of HBV screening prior to antiretroviral therapy initiation to guide the selection of optimal regimen for coinfected children.