Voranush Chongsrisawat

Hepatitis B seroprevalence in Thailand: 12 years after hepatitis B vaccine integration into the national expanded programme on immunization

Objectives  To evaluate the impact of the universal hepatitis B (HB) vaccination programme on the prevalence of hepatitis B surface antigen (HBsAg) carriers and immunity to HB virus infection among children <18 years and to determine the HB seroprevalence in the Thai population.

Persistence of antibodies and immune memory to hepatitis B vaccine 20 years after infant vaccination in Thailand

Booster vaccination against hepatitis B (HBV) is not currently recommended, although debate continues on the duration of protection after priming. We assessed antibody persistence and immune memory to hepatitis B 20 years after priming with a recombinant HBV-vaccine during infancy. Infants were vaccinated at birth, 1, 2 and 12 months of age. A subset received a booster dose at Year 5. Antibody persistence was measured approximately yearly until Year 20. Immune memory was assessed by administration of HBV booster dose. At Year 20, anti-HBs seroprotection rates and GMCs tended to be higher in Year 5 boosted than unboosted recipients (83.9% versus 60.5%). After the Year 20 booster dose, anti-HBs anamnestic responses were within the same range 95.8% of subjects in both groups. Primary and booster vaccination with HBV-vaccine in infants induces sustained seroprotection and immune memory against hepatitis B for up to 20 years. Higher persisting seroprotection rates in subjects boosted at Year 5 did not translate into apparent differences in immune memory in a high endemic country.

Evidence of protection against clinical and chronic hepatitis B infection 20 years after infant vaccination in a high endemicity region

Summary.  Vaccination against hepatitis B virus (HBV) immediately after birth prevents neonatal infection by vertical transmission from HBV carrier mothers. There is an ongoing debate whether infant vaccination is sufficient to protect against infection when exposed to HBV later in life. We studied 222 Thai infants born to HBsAg −/+ and HBeAg −/+ mothers who were vaccinated with recombinant hepatitis B vaccine at 0‐1‐2‐12 months of age. A subset of 100 subjects received a booster dose at age 5 years. Blood samples collected yearly for 20 years were examined for anti‐HBs antibodies and serological markers of hepatitis B infection (anti‐HBc, HBsAg, and in selected cases HBeAg, anti‐HBe, HBV DNA). During the 20‐year follow‐up, no subject acquired new chronic HBV infection or clinical hepatitis B disease. During the first decade, possible subclinical breakthrough HBV infection (anti‐HBc seroconversion) was only observed in subjects born to HBsAg +/HBeAg + mothers (6/49 [12.2%]). During the second decade, breakthrough HBV infections were detected in all groups (18/140 [12.8%]). Increases in anti‐HBs concentrations that were unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects in each decade. Primary infant vaccination with a recombinant hepatitis B vaccine confers long‐term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure. (http://www.clinicaltrials.gov NCT00240500 and NCT00456625)

Dengue virus infection: a major cause of acute hepatic failure in Thai children

Abstract Background: Acute hepatic failure (AHF) can be caused by a variety of viruses, drugs, toxins and metabolic disorders. Aims: A prospective study was conducted to determine the aetiology and outcome of AHF in Thai children aged 1–15 years. Methods: All serum samples were tested for anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, anti-HEV IgM and anti-dengue IgG and IgM. Further individual investigations were done according to the clinical impression. Results: Forty subjects were enrolled from 14 centres during February 2000 to December 2001. Five cases were excluded owing to a lack of evidence of encephalopathy. The causes of AHF were dengue infection in 12 (34.3%), Wilson disease in 2 (5.7%), T-cell lymphoma in 2 (5.7%), ischaemic hepatitis in two (5.7%), haemophagocytic syndrome in one (2.8%), CMV in 2 (5.7%), Reye syndrome in one (2.8%) and unknown in 13 (37.1%) patients. The fatality rate was 68.6%. Eight of 24 (33.3%) deaths were caused by dengue infection. Conclusions: Improvements in sanitation and socio-economic status as well as the implementation of hepatitis B vaccine in the Extended Programme on Immunization (EPI) are likely to be the reasons for the observed absence of AHF caused by hepatitis A and B. The study showed that dengue infection, on the other hand, was a major cause of AHF in Thailand.

Epidemiology and prophylaxis of viral hepatitis: a global perspective.

Viral hepatitis with various forms of acute and chronic liver disease as potential and ultimately fatal sequelae presents a public health problem worldwide.

Association between serum hepatocyte growth factor and survival in untreated hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is a common hepatic malignancy worldwide. Its nature of rapid growth results in a grave prognosis. Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, responsible for their proliferation. The aim of the present study was to investigate the prognostic roles of serum HGF in untreated HCC patients.MethodsFifty-five patients with inoperable HCC were studied. The diagnosis of HCC was based on either liver histopathology or imaging evidence of a liver mass, together with elevated serum alpha-fetoprotein. Serum HGF levels of the patients, at the time of diagnosis, were compared to those of 28 healthy controls. All patients received only palliative treatments and were followed up until they died. Comparison of survival curves between patients with a serum HGF level of 1.0 ng/ml or more and those with lower serum HGF was performed, using the log-rank test. Data values are expressed as means and SD.ResultsFifty-one men and four women with inoperable HCC were recruited. The mean age was 54.15 ± 15.34 years. The serum HGF levels in the inoperable HCC patients were significantly higher than those in the controls (0.58 ± 0.43 vs 0.14 ± 0.04 ng/ml; P < 0.001). The patients’ mean survival time was 5.28 ± 6.73 months (range, 0.1–33 months). Serum HGF levels exhibited a negative correlation with the survival time (P = 0.032). In addition, HCC patients with serum HGF levels of 1.0 ng/ml or more had a shorter survival time than the other HCC patients (P = 0.0025).ConclusionsPatients with inoperable HCC had higher levels of serum HGF than the healthy controls, and serum HGF was negatively correlated with the survival time. Serum HGF levels of 1.0 ng/ml or more in HCC patients are suggestive of a grave prognosis, indicating that HGF plays important and active roles in the disease progression. The detailed mechanisms need to be further investigated.

Transient elastography for predicting esophageal/gastric varices in children with biliary atresia.

BackgroundTransient elastography (TE) is an innovative, noninvasive technique to assess liver fibrosis by measuring liver stiffness in patients with chronic liver diseases. The purpose of this study has been to explore the accuracy of TE and clinical parameters in predicting the presence of esophageal/gastric varices in children with biliary atresia (BA) following portoenterostomy.MethodsPatients with BA status post portoenterostomy and normal children were recruited. Splenomegaly and presence of EV/GV were determined by physical examination and endoscopy, respectively. Aspartate transaminase to platelet ratio index (APRI) was used as a serum fibrosis marker. TE was performed by using FibroScan. Data was expressed as mean ± SD.ResultsSeventy-three BA patients (male:female = 32:41; age 9.11 ± 5.64 years) and 50 normal controls (male:female = 19:31; age 11.00 ± 3.31 years) were enrolled. The liver stiffness score of BA patients was significantly higher than that of normal controls (27.37 ± 22.48 and 4.69 ± 1.03 kPa; p < 0.001). Patients with EV/GV had significantly higher liver stiffness score and APRI than those without EV/GV. As for EV/GV diagnosis, the areas under the receiver operating characteristic curve were 0.89 (95% CI 0.80 to 0.98) for TE and 0.87 (95% CI 0.78 to 0.96) for APRI, respectively. The sensitivity (and specificity) of TE (using a cut-off value of 12.7 kPa) and APRI (using a cut-off value of 1.92) in predicting EV/GV were 84% (77%) and 84% (83%), respectively, whereas the sensitivity (and specificity) of splenomegaly in predicting EV/GV were 92% (85%).ConclusionsTransient elastography is a useful tool for predicting the presence of EV/GV. In addition, basic physical examination, routine biochemical and hematological tests, are still worthwhile and correlate well with the presence of EV/GV in patients with BA post portoenterostomy.

Long‐Term Benefit of Hepatitis B Vaccination among Children in Thailand with Transient Hepatitis B Virus Infection Who Were Born to Hepatitis B Surface Antigen–Positive Mothers

BACKGROUND Transmission of hepatitis B virus (HBV) from carrier mothers to their babies appears to be one of the most important factors influencing the prevalence of chronic HBV infection in areas of high hepatitis B endemicity. METHODS Infants born to HBV surface antigen (HBsAg)-positive mothers who were or were not positive for HBV e antigen (HBeAg) or to mothers who were negative for both HBsAg and HBeAg have been followed for 17 years for serological evidence of HBV infection. These infants were divided into 2 groups on the basis of their hepatitis B vaccination protocols: group 1 received vaccine at birth and 1, 2, and 12 months later, and group 2 received vaccine at birth and 1 and 6 months later. Follow-up involved annual clinic visits, during which a blood sample was taken and analyzed for the presence of HBsAg, antibody to HBsAg, and antibody to HBV core antigen (HBcAg). Selected blood samples that tested positive for HBV markers during 2 consecutive visits separated by a long interval were further investigated by polymerase chain reaction to detect HBV DNA. RESULTS Transient presence of HBsAg or transient and/or long-term presence of antibody to HBcAg suggested that this population was heavily exposed to HBV during the follow-up period. Despite these findings, no new cases of chronic HBV infection were observed. None of the subjects with transient presence of HBsAg had any clinical symptoms of liver disease. CONCLUSIONS This study demonstrates the efficacy of the HBV vaccine and its ability to protect against symptomatic disease.

Molecular epidemiological study of hepatitis B virus in Thailand based on the analysis of pre-S and S genes.

Aims:  This study was undertaken to determine the prevalence and characteristics of hepatitis B virus (HBV) genotypes, antigen subtypes, “a” determinant variants and pre‐S gene mutations circulating on a large scale in Thailand.

Long-term anti-HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response A 20-year follow-up study in Thailand

Hepatitis B vaccine has been available worldwide since the mid-1980s. This vaccine was evaluated in a clinical trial in Thailand, conducted on subjects born to hepatitis B surface antigen positive and hepatitis B e-antigen positive mothers and vaccinated according to a 4-dose schedule at 0, 1, 2 and 12 mo of age and a single dose of hepatitis B immunoglobulin concomitantly at birth. All enrolled subjects seroconverted and were followed for 20 y to assess the persistence of antibody to the hepatitis B surface antigen (anti-HBs) (NCT00240539). At year 20, 64% of subjects had anti-HBs antibody concentrations ≥ 10 milli-international units per milli liter (mIU/ml) and 92% of subjects had detectable levels (≥ 3.3 mIU/ml) of anti-HBs antibodies. At year 20, subjects with anti-HBs antibody titer < 100 mIU/ml were offered an additional dose of hepatitis B virus (HBV) vaccine to assess immune memory (NCT00657657). Anamnestic response to the challenge dose was observed in 96.6% of subjects with an 82-fold (13.2 to 1082.4 mIU/ml) increase in anti-HBs antibody geometric mean concentrations. This study confirms the long-term immunogenicity of the 4-dose regimen of the HBV vaccine eliciting long-term persistence of antibodies and immune memory against hepatitis B for up to at least 20 y after vaccination.