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Chronic hepatitis B (HBV) and C (HCV) are major health challenges in Thailand, with Phetchabun province, a known HCV-endemic area, being a key target for elimination efforts. This study aimed to assess HBV prevalence and identify associated risk factors in this province. Data was collected from three cross-sectional population studies: (1) adults in 2015 (n = 1,667, age 30-64 years), (2) young adults in 2017 (n = 1,453, age 18-30 years), both from high HCV-endemic districts, and (3) a province-wide study in 2018 (n = 4,769, age 35-64 years). Plasma samples were tested for HBsAg using the ARCHITECT assay. Results showed HBsAg seropositivity in 3.1 % of young adults in high-endemic districts, with significant associations with age, education, injecting drug use, and MSM behavior. Among adults, HBsAg prevalence was 5.9 %, linked to age and family liver disease history. Province-wide, 6.3 % of adults tested positive, with factors like gender and history of blood donation playing significant roles. Notably, age and blood donation were protective factors against HBV in adults. Analysis revealed a moderate HBV prevalence in those born before Thailand Expanded Program on Immunization (EPI) program, while those born after had rates below 1 %. The findings emphasize distinct HBV transmission patterns in different age groups, influenced by social and behavioral shifts. This knowledge is crucial for effective hepatitis elimination strategies in the Phetchabun province and nationwide., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Hepatitis C virus (HCV) is a viral pathogen that causes chronic hepatitis, which can lead to cirrhosis and hepatocellular carcinoma. Detection of HCV RNA is the standard method used to diagnose the disease and monitor antiviral treatment. A quantification assay for the HCV core antigen (HCVcAg) has been proposed as a simplified alternative to the HCV RNA test for predicting active HCV infection, with the aim of achieving the global goal of eliminating hepatitis. The objective of this study was to determine the correlation between HCV RNA and HCVcAg, as well as the impact of amino acid sequence heterogeneity on HCVcAg quantification. Our findings demonstrated a strong positive correlation between HCV RNA and HCVcAg across all HCV genotypes (1a, 1b, 3a, and 6), with correlation coefficients ranging from 0.88 to 0.96 (p < 0.001). However, in some cases, samples with genotypes 3a and 6 exhibited lower HCVcAg levels than expected based on the corresponding HCV RNA values. Upon the core amino acid sequence alignment, it was observed that samples exhibiting low core antigen levels had an amino acid substitution at position 49, where threonine was replaced by either alanine or valine. Core mutation at this position may correlate with one of the epitope regions recognized by anti-HCV monoclonal antibodies. The present findings suggest that the utilization of HCVcAg as a standalone marker for HCV RNA might not provide adequate sensitivity for the detection of HCV infection, especially in cases where there are variations in the amino acid sequence of the core region and a low viral load of HCV RNA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hansoongnern et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The World Health Organization envisions the elimination of viral hepatitis by 2030 through reducing prevalence and transmission, increasing diagnostic screening, and expanding treatment coverage. Efforts to micro-eliminate hepatitis in Phetchabun province in Thailand, a region where the prevalence of hepatitis C virus (HCV) infection and liver cancer is higher than elsewhere in the country, began with evaluating the province-wide burden of HCV. Here, we describe a feasibility study to assess active HCV infection by screening Phetchabun residents ages 35 to 69 years for anti-HCV antibodies by using a rapid diagnostic test (RDT) at the point of care. Positive anti-HCV results were further evaluated for active infection using qualitative HCV RNA assay, followed by quantitative HCV viral load determination in a subset of samples. Currently, we have identified 6.2% (10,621/170,163) anti-HCV positive individuals, of whom 74.9% (3,930/5,246) demonstrated detectable viral RNA. Quantitative test found that 97.5% (1,001/1,027) had HCV viral load ≥5,000 IU/mL. Thus, primary screening with anti-HCV RDT followed by qualitative HCV RNA evaluation could identify active and chronic HCV infection in almost all individuals with a viral load ≥5,000 IU/mL, which is the current threshold for treatment dictated by Thailand's National Health Security Office. Our data suggest that qualitative HCV RNA evaluation may obviate the need for the more expensive quantitative HCV viral load test and reduce a significant barrier toward HCV elimination in a middle-income country., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pratedrat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To identify novel host genetic variants that predispose to hepatitis B virus (HBV) persistence, we performed the first genome-wide association study in the Thai population involving 318 cases of chronic hepatitis B and 309 healthy controls after quality control measures. We detected the genome-wide significant association of the HLA class II region ( HLA-DPA1/DPB1 , rs7770370, p -value = 7.71 × 10 -10 , OR = 0.49) with HBV chronicity. Subsequent HLA allele imputation revealed HLA-DPA1*01:03 ( Pc = 1.21 × 10 -6 , OR = 0.53), HLA-DPB1*02:01 ( Pc = 2.17 × 10 -3 , OR = 0.50), and HLA-DQB1*06:09 ( Pc = 2.17 × 10 -2 , OR = 0.07) as protective alleles, and HLA-DPA1*02:02 ( Pc = 6.32 × 10 -5 , OR = 1.63), HLA-DPB1*05:01 ( Pc = 1.13 × 10 -4 , OR = 1.72), HLA-DPB1*13:01 ( Pc = 4.68 × 10 -2 , OR = 1.60), and HLA-DQB1*03:03 ( Pc = 1.11 × 10 -3 , OR = 1.84) as risk alleles for HBV persistence. We also detected suggestive associations in the PLSCR1 (rs35766154), PDLIM5 (rs62321986), SGPL1 (rs144998273), and MGST1 (rs1828682) loci. Among single-nucleotide polymorphisms in the PLSCR1 locus, rs1061307 was identified as the primary functional variant by in silico/in vitro functional analysis. In addition to replicating the association of the HLA class II region, we detected novel candidate loci that provide new insights into the pathophysiology of chronic hepatitis B., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ashouri, Khor, Hitomi, Sawai, Nishida, Sugiyama, Kawai, Posuwan, Tangkijvanich, Komolmit, Tsuiji, Shotelersuk, Poovorawan, Mizokami and Tokunaga.)

Asymptomatic hepatitis C virus (HCV) infection without treatment is associated with chronic liver diseases including hepatocellular carcinoma. A major obstacle to hepatitis C diagnosis leading to antiviral treatment in some developing countries is the complicated HCV testing required before treatment. To simplify an HCV test-to-treat strategy, which could lead to timely diagnosis and treatment at the point-of-care, we evaluated the performance of four anti-HCV rapid diagnostic tests (RDTs) (Abon, Blue Cross, Healgen, and SD Bioline). They yielded comparable sensitivity (80-83%), specificity (99-100%), and accuracy (90-91.5%). When we field-tested Abon in 4,769 residents of an HCV-endemic province in Thailand, 306 seropositive individuals (6.4%) were identified. In comparison, laboratory test using an automated commercial chemiluminescent microparticle immunoassay (Abbott ARCHITECT) identified slightly more seropositives (327% or 6.9%). Field implementation suggests that Abon was sensitive (88.7%), specific (99.6%), and accurate (98.9%). Furthermore, 82% (250/306) of Abon-positive samples had detectable HCV RNA as determined by nucleic acid test (Roche cobas). The same 250 samples out of 327 reactive in Abbott immunoassay also had detectable HCV RNA (mean RNA level: log 6.28 IU/mL, range: log 3.06- 7.78 IU/mL). The use of RDT followed by qualitative nucleic acid test can cost-effectively identify the majority of HCV seropositive individuals with active infection, which will obviate the need for expensive viral load quantification tests when simplifying HCV diagnosis for the test-to-treat program at the point-of-care.

A high prevalence of hepatitis B (HepB) antibody loss after liver transplantation (LT) and de novo HepB infection (DNH) was documented, hence revaccination to prevent DNH is crucial. This study aimed to compare the safety and immunogenicity of two HepB vaccine regimens in liver-transplanted children. Liver-transplanted children who were previously immunised but showed HepB surface antibodies (anti-HBs) ≤ 100 mIU/mL were randomised to receive a standard three-dose (SD) and double three-dose (DD) vaccine intramuscularly in months 0-1-6. Anti-HBs and T-cell-specific response to the HepB antigen were assessed. A total of 61 children (54.1% male, aged 1.32 ± 1.02 years) completed the study without any serious adverse reaction. The seroprotective rate was 69.6% vs. 60% ( p = 0.368) and 91.3% vs. 85% ( p = 0.431) in SD and DD after the first and third 3-dose vaccinations, respectively. The geometric mean titre (95% confidence interval) of anti-HBs in SD and DD were 443.33 (200.75-979.07) vs. 446.17 (155.58-1279.50) mIU/mL, respectively, at completion. Numbers of interferon-γ-secreting cells were higher in hyporesponders/responders than in nonresponders ( p = 0.003). The significant factors for the immunologic response to HepB vaccination were anti-HB levels prevaccination, tacrolimus trough levels, and time from LT to revaccination. SD and DD had comparative immunogenicity and were safe for liver-transplanted children who were previously immunised.

This study monitored the long-term immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in patients who had recovered from coronavirus disease (COVID)-19. Anti-nucleocapsid immunoglobulin G (anti-N IgG) titer in serum samples collected at a single (N = 302) or multiple time points (N = 229) 3-12 months after COVID-19 symptom onset or SARS-CoV-2 detection in respiratory specimens was measured by semiquantitative chemiluminescent microparticle immunoassay. The 531 patients (966 specimens) were classified according to the presence or absence of pneumonia symptoms. Anti N IgG was detected in 87.5% of patients (328/375) at 3 months, 38.6% (93/241) at 6 months, 23.7% (49/207) at 9 months, and 26.6% (38/143) at 12 months. The anti-N IgG seropositivity rate was significantly lower at 6, 9, and 12 months than at 3 months (P < 0.01) and was higher in the pneumonia group than in the non-pneumonia/asymptomatic group at 6 months (P < 0.01), 9 months (P = 0.04), and 12 months (P = 0.04). The rate started to decline 6-12 months after symptom onset. Anti-N IgG sample/cutoff index was positively correlated with age (r = 0.192, P < 0.01) but negatively correlated with interval between symptom onset and blood sampling (r =  - 0.567, P < 0.01). These findings can guide vaccine strategies in recovered COVID-19 patients., (© 2021. The Author(s).)

Background: Efficient monitoring and control of coronavirus disease 2019 (COVID-19) require access to diagnostic tests, and serological diagnostic testing is desirable. In the current study, antibodies were investigated in patients recently diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: Cross-sectional data were obtained from 245 patients in whom SARS-CoV-2 infection had been confirmed via real-time reverse transcriptase-polymerase chain reaction between March and October 2020. Serum samples were acquired between 2 and 60 days following the onset of COVID-19 symptoms or the first detection of SARS-CoV-2 in asymptomatic patients. All specimens were tested simultaneously using an IgM/IgG rapid diagnostic test (RDT), IgG nucleocapsid protein-based chemiluminescent microparticle immunoassay (CMIA), IgG, and IgA spike protein-based enzyme-linked immunosorbent assays (ELISAs). Blood donor samples obtained in 2018 were used as negative controls., Results: The sensitivity and specificity of the RDT IgG were compared with the IgG immunoassays as standards. The RDT IgG exhibited 97.5% sensitivity and 89.4% specificity compared with a CMIA IgG, 98.4% sensitivity, and 78.8% specificity compared with an ELISA IgG. IgM, IgG, and IgA seropositivity rates were low between 1 and 2 weeks after COVID-19 symptom onset or the detection of SARS-CoV-2 RNA. IgM seropositivity rate began decreasing after 4 weeks, whereas IgG and IgA seropositivity rate remained at appreciable levels over the 8-week study period. No cross-reactivity with seasonal coronaviruses was detected., Conclusions: IgG RDT alone or combined with molecular diagnostic tests may be useful for identifying recent SARS-CoV-2 infection.

Background: Human rotavirus A (RVA) infection is the primary cause of acute gastroenteritis (AGE) in infants and young children worldwide, especially in children under 5 years of age and is a major public health problem causing severe diarrhea in children in Thailand. This study aimed to investigate the prevalence, genotype diversity, and molecular characterization of rotavirus infection circulating in children under 15 years of age diagnosed with AGE in Thailand from January 2016 to December 2019., Methods: A total of 2,001 stool samples were collected from children with gastroenteritis (neonates to children <15 years of age) and tested for RVA by real-time polymerase chain reaction (RT-PCR). Amplified products were sequenced and submitted to an online genotyping tool for analysis., Results: Overall, 301 (15.0%) stool samples were positive for RVA. RVA occurred most frequently among children aged 0-24 months. The seasonal incidence of rotavirus infection occurred typically in Thailand during the winter months (December-March). The G3P[8] genotype was identified as the most prevalent genotype (33.2%, 100/301), followed by G8P[8] (10.6%, 32/301), G9P[8] (6.3%, 19/301), G2P[4] (6.0%, 18/301), and G1P[6] (5.3%, 16/301). Uncommon G and P combinations such as G9P[4], G2P[8], G3P[4] and G3P[9] were also detected at low frequencies. In terms of genetic backbone, the unusual DS-1-like G3P[8] was the most frequently detected (28.2%, 85/301), and the phylogenetic analysis demonstrated high nucleotide identity with unusual DS-1-like G3P[8] detected in Thailand and several countries., Conclusions: A genetic association between RVA isolates from Thailand and other countries ought to be investigated given the local and global dissemination of rotavirus as it is crucial for controlling viral gastroenteritis, and implications for the national vaccination programs., Competing Interests: The authors declare that they have no competing interests., (© 2021 Pasittungkul et al.)

Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis and hepatocellular carcinoma. To eliminate HCV infection in an endemic area, an epidemiological baseline of the current HCV infection in the population is required. We therefore aimed to evaluate the HCV burden in the Thai Province of Phetchabun, which has the highest HCV infection rate in the country. Toward this, a province-wide district-based representative sampling of 4,769 individuals ages 35-64 years previously shown to represent high-risk age-groups were tested for anti-HCV antibodies using the automated chemiluminescent microparticle assays. Active HCV infection and subsequent genotyping were determined from serologically reactive samples by amplification of the HCV core gene. We found that 6.9% (327/4,769) were anti-HCV positive, of which 75.8% (248/327) had detectable HCV RNA and 5.8% (19/327) were in the presence of hepatitis B virus coinfection. Nucleotide sequencing and phylogenetic analysis revealed that HCV genotype 6 was the most prevalent (41%, 101/248), followed by genotype 3 (31%, 78/248), and genotype 1 (28%, 69/248). Socioeconomic and demographic factors including male gender, education, and agricultural work were associated with HCV seropositivity. From these results, we defined the regional HCV genotypes and estimated the HCV burden necessary toward the implementation of pan-genotypic direct-acting antivirals, which may be appropriate and effective toward the diversity of genotypes identified in this study. Micro-elimination of HCV in Phetchabun may serve as a model for a more comprehensive coverage of HCV treatment in Thailand.

Viral hepatitis is a global problem with mortality comparable to HIV, tuberculosis and malaria. The WHO aims to eliminate hepatitis B (HBV) and hepatitis C (HCV) by 2030. Improved socioeconomic status of developing countries such as Thailand has reduced the incidence and morbidity associated with hepatitis A. Since the beginning of hepatitis B vaccination in all Thai newborns in 1992, at least 95% of one-year-olds are currently receiving 3-4 hepatitis B doses. The second vaccination of newborns of carrier mothers at 1 month of age has contributed to an effective reduction in mother-to-child transmission. Universal vaccination, blood donation screening, and decreasing needle sharing have reduced hepatitis B infection. Under the test and treat model, cost-effective screening at the point-of-care (health center or village hospital) is recommended for adults >30 years-old. Following referral to a tertiary healthcare center for a treatment plan in developing disease management plan, its implementation by trained healthcare professionals is preferably administered at the point-of-care. Hepatitis C prevalence is also decreasing as a result of blood-borne pathogen awareness. Current hepatitis C infection is highest for adults >35 years who were born prior to 1983, with screening is recommend once in their lifetime. Treatment strategy recommendation follows that of hepatitis B. The availability of direct antiviral agents with high cure rates is expected to contribute to the reduction in hepatitis C transmission and mortality as set forth by the WHO policy. Thus, ensuring the successful planning of hepatitis elimination in Thailand requires pilot regional assessment prior to national implementation., (© 2020 The Author(s).)

High hepatitis E (HEV) seroprevalence has been reported in the general population and in post-liver transplant (LT) cases in several regions, including Thailand, with genotype 3 being a predominant genotype. We hypothesized that HEV might persist at a subclinical level and might pose clinical risks in the post-LT period. We performed a cross-sectional study with 108 post-LT patients and found an IgG seroprevalence of 55.6%. Subsequently, 91 cases without clinical evidence of HEV-related hepatitis were enrolled in 1 year of prospective follow-up to determine clinical status, serologies and serum/feces HEV RNA every 4 months. HEV RNA was detected, indicating subclinical infections in patients with or without seropositivity, with an annual incidence of 7.7%. Our results suggest that subclinical HEV infection exists among LT patients in this high-prevalence area. Thus, clinicians should be aware of the possibility of disease reemergence and HEV viral transmission in LT patients.

Background: Owing to a declining birth rate and longer lifespan, the number of elderly people (≥ 60 years) in Thailand has grown rapidly. However, the elderly are at significant risk of infectious diseases because they have never been immunized, because they have not been completely immunized, or because their immunity has waned. Immunity against infectious diseases in the elderly is an important means of controlling diseases in the community. Our objective was to evaluate the seroprotective rate against diphtheria, tetanus, and pertussis in the elderly Thai population., Methods: In total, 430 healthy individuals from the northeastern region of Thailand were enrolled in this study and stratified into five age groups: 60-65, 66-70, 71-75, 76-80, and > 80 years. Serum samples were collected and quantitatively analyzed for diphtheria, tetanus, and pertussis IgG antibody by using commercial ELISA kits. For anti-diphtheria toxoid and anti-tetanus toxoid ELISA, values < 0.01 IU/ml were interpreted as seronegative, and for anti-Bordetella pertussis toxin ELISA, values < 5 IU/ml were interpreted as seronegative; these definitions were in accord with previous studies., Results: For diphtheria toxoid Ab, the majority of the population had antibody levels > 0.01 IU/ml. For tetanus anti-toxoid Ab, the majority of the population had antibody levels of > 0.01 IU/ml, of which approximately 34% had durable antibody protection levels (DAPL) of ≥ 1 IU/ml. Meanwhile, nearly 45% of the population had an Ab level against pertussis lower than the protectivity level., Conclusions: In total, 97.2%, 83.5%, and 55.8% of the population had a higher antibody level than the minimal protective level for diphtheria, tetanus, and pertussis, respectively. In order to prevent an outbreak of these diseases in the future, the elderly should be administered with Tdap revaccination to provide diphtheria herd immunity in the population; this will increase cocoon phenomenon for pertussis and protect the population from tetanus-prone injury.

Hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) viruses are hepatotropic viruses responsible for acute/chronic hepatitis associated with liver failure, cirrhosis, and hepatocellular carcinoma. Due to the limited data on the prevalence of hepatitis in the older population in Thailand, this study aimed to evaluate the seroprevalence of these viruses in elderly Thais. Using an automated immunoassay, serum samples from individuals older than 60 years of age in Chum Phae district of Khon Kaen province in northeast Thailand were analyzed for anti-HAV ( n  = 93), HBV markers ( n  = 460, HBsAg, anti-HBs, and anti-HBc), and anti-HCV ( n  = 460). Samples were classified into five age groups (61-65, 66-70, 71-75, 76-80, and >80 years). The overall seroprevalence of anti-HAV, HBsAg, anti-HBc, anti-HBs, and anti-HCV was 98.9%, 4.6%, 51.5%, 32.4%, and 1.3%, respectively. When samples were stratified into three groups representing three generations (children/young adults aged 6 months-30 years and middle-aged adults between 31-60 years old from a previous survey, and older adults aged >60 years from the current study), the highest levels of anti-HAV and anti-HBc were found in older adults. Children/young adults had the lowest levels of HBsAg and anti-HCV, and the highest level of anti-HBs. These findings are consistent with the integration of HBV vaccination into the Expanded Program on Immunization (EPI) in 1992 and coincide with increased awareness of blood-borne viral transmission in Thailand. Extrapolating from our data, the estimated numbers of cases of chronic HBV and HCV infection in Thailand in 2017 were 2.2 and 0.79 million, respectively. Thus, effective treatments for viral hepatitis B and C for middle-aged and elderly Thais are needed. This seroprevalence survey could be used to help formulate policies and possible guidelines for treatment and prevention in specific age groups, which is recommended to facilitate the elimination of viral hepatitis by 2030., Competing Interests: The authors declare there are no competing interests.

Objective: This study aimed to determine the seroprevalence of anti-HAV IgG in Thai medical students in 2016 compared with the previous data and to demonstrate the cross-effective strategy to screen HAV seropositivity., Results: Sera from 176 first-year medical students (age 19.07 ± 0.59 years; 50% female) at a university hospital in Thailand were tested for anti-HAV IgG. Data from HAV vaccination records and questionnaires were also collected. HAV seropositivity was unexpectedly high (62.5%, n = 110). 37.5% (n = 66) had an HAV vaccination record. Of these, 60.6% received the full HAV vaccination series, 4.5% received one HAV vaccination, 34.8% did not receive HAV vaccination, and 3.0% had natural HAV immunity. The long-term efficacy of HAV vaccination was at least 97.5% over a mean of 15.55 ± 2.44 years. There was a significant difference in immunity between students with (66.7%) and without (50.9%) vaccination records (P = 0.028). Most of the student's parents had a bachelor's degree or higher (87.9%; n = 272) and above average income (mean 17,000.76 ± 194.22 USD/person/year). Parental education and socioeconomic status influenced vaccination accessibility in these medical students. Screening of vaccination records instead of routine anti-HAV IgG testing is a cost-effective and reliable strategy to determine HAV immunity in medical students in Thailand.

The World Health Organization aims to eliminate HCV infection worldwide by 2030. A targeted HCV screening policy is currently unavailable in Thailand, but a decrease in HCV infection has been observed in the country. However, a previous study showed that there was a higher HCV seroprevalence in adults aged between 30-64 years in the Phetchabun province (15.5%), as compared to the Khon Kaen province (3.6%). It was hypothesized that young adults had a lower rate of HCV seropositivity; this was determined by the age distribution of anti-HCV in Phetchabun and with the identification of high seroprevalence birth cohorts. In order to compare the provincial findings to the national level, anti-HCV birth cohorts were further analyzed in Khon Kaen (averaged-HCV prevalence) as well as the Thai data set that was derived from the previous literature. Thai individuals aged between 18-30 years residing in Phetchabun (n = 1453) were recruited, tested for the presence of anti-HCV antibodies and viral RNA and completed questionnaires that were designed to identify HCV exposure risks. Data was collected and compiled from previously published articles (n = 1667, age 30-64 years). The HCV seropositivity in Phetchabun by age group (18-64, at 5-year intervals) and the birth year were tabulated parallel to the Khon Kaen data set (n = 2233) in conjunction with data from the national survey 2014 (n = 5964) representing the Thai population. Factors such as age, male gender, agricultural work, blood transfusion, intravenous drug use and having a tattoo were associated with anti-HCV positivity in Phetchabun. HCV seroprevalence was less than 4.0% (ranging from 0.0-3.5%) from the age of 18-34 years. A dramatic increase of 15.1% was found in adults aged greater than or equal to 35 years, whereas, the age group in Khon Kaen and the national population with increasing prevalence of HCV were older (≥40). The HCV seropositivity cohort accumulated for those born between 1951-1982 accounted for 71.4-100.0% of all seropositive individuals. Subsequently, new cases occurred sporadically. This finding provides evidence that there is a disproportionately high HCV seroprevalence among people born before 1983 (or aged ≥35). This cohort should be targeted for priority screening as part of the national HCV screening policy. Incorporating this birth cohort with other risk factors could improve HCV diagnostic rates, resulting in overall improvements in parallel to those given by novel antiviral treatment., Competing Interests: The authors have declared that no competing interests exist.

Universal hepatitis B (HB) vaccination among Thai newborns was initiated in 1992. The first dose of the monovalent HB vaccine was given at birth, then at months 2 and 6 simultaneously with the diphtheria-tetanus-pertussis whole-cell (DTPw) vaccine. In 2008, Thailand replaced the monovalent HB vaccine at months 2 and 6 with a combined DTP-HB given at months 2, 4, and 6, with an added monovalent HB vaccine at month 1 for infants whose mothers were HBV carriers. Despite this rigorous HB vaccination schedule, vaccinated infants who are now adolescents do not possess a protective level of anti-HB surface antigen (anti-HBs) (≥10 mIU/ml). Thus, many young adults may be rendered susceptible to HB infection. Our objective was to determine how HB booster vaccination may benefit high-risk adolescents. We evaluated the serological records of a cohort of medical students (n = 291), which showed that 271 students (93.1%) possessed anti-HBs less than the accepted protective level (<10 mIU/ml) and subsequently received the HB vaccine booster prior to medical school enrollment. We then examined the anti-HB surface antibody (anti-HBs) in 216 individuals six weeks after they were immunized. We found that 61%, 88%, and 94% of individuals with pre-booster anti-HBs of <1 mIU/ml, 1-<3 mIU/ml, and 3-<10 mIU/ml achieved protective anti-HBs, respectively. Post-booster geometric mean titers were 305, 513, and 1,929 mIU/ml in these groups and correlated with pre-booster anti-HBs titers. These data suggest that medical students with known anti-HBs <1 mIU/ml will benefit from 3 doses of HB vaccine at 0, 1, and 6 months. Students with anti-HBs 1-<10 mIU/ml would benefit from an HB vaccine booster without further anti-HBs evaluation., Competing Interests: The authors have declared that no competing interests exist.

We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10 -4 located within the HLA class I region and three SNPs were genotyped in three independent population-based replication sets. Meta-analysis confirmed the association of the three SNPs (rs2523961: OR = 1.73, P = 7.50 × 10 -12 ; rs1110446: OR = 1.79, P = 1.66 × 10 -13 ; and rs3094137: OR = 1.73, P = 7.09 × 10 -9 ). We then performed two-field HLA genotype imputation for six HLA loci using genotyping data to investigate the association between HLA alleles and HCC. HLA allele association testing revealed that HLA-A * 33:03 (OR = 1.97, P = 4.58 × 10 -4 ) was significantly associated with disease progression to HCC. Conditioning analysis of each of the three SNPs on the HLA class I region abolished the association of HLA-A * 33:03 with disease progression to HCC. However, conditioning the HLA allele could not eliminate the association of the three SNPs, suggesting that additional genetic factors may exist in the HLA class I region.

The prevalence of hepatitis C virus (HCV) infection has been decreasing globally, but the growing effects of HCV-related morbidity and mortality remain of concern. Advances in curative medicine, involving direct-acting antivirals (DAAs), have led many countries to aim to eradicate HCV. Information on epidemiology and disease burden is essential for national policy development. Thus, this study aimed to determine the HCV-related hepatic disease burden in areas of Thailand with high and average HCV prevalence in order to extrapolate the viral burden across Thailand. Patients previously diagnosed as positive for anti-HCV antibodies were recruited to assess chronic HCV infection (CHC) status, liver function, HCV-RNA level and hepatic fibrosis. The number of patients eligible for Universal Health Coverage (UC) scheme and the approximately required expenditure on interferon (IFN)-based treatment were estimated. In areas of both high (12%) and average (2%) HCV viremic prevalence, over half of the patients (52.2% to 62.5%) had advanced liver fibrosis (F3 and F4). A striking percentage of patients with F4 (38.9%) were found in the high-prevalence area, while comparable proportions of advanced liver fibrosis presented in the two areas and disease burden peaked at 50-59 years. Under the current UC program treatment scenario, 78-83% of CHC patients with stage F2-F4 fibrosis were eligible for treatment. The estimated expenditure required for overall CHC treatment across the whole country was 1,240 million USD at this current status, but the declining cost of generic DAA-based therapy may reduce the requirement to <90 million USD. This study provides information on the estimated number of CHC patients, liver disease burden and expenditure requirements for Thailand. To eliminate HCV by 2030, proactive government strategies raising public health to minimize transmission and emphasizing targeted screen-and-treatment programs, novel therapeutic guideline development for decentralizing treatment, and effective budget allocation are urgently needed.

Aim: To assess the seroprevalence of hepatitis B virus (HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation., Methods: This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss., Results: In total, 50 children were recruited. The mean time from liver transplantation to anti-HBs testing was 2.53 ± 2.11 years. The mean anti-HBs levels before and after liver transplantation were 584.41 ± 415.45 and 58.56 ± 6.40 IU/L, respectively. The rate of non-immunity (anti-HBs < 10 IU/L) in the participants was 46% ( n = 26) at one year, 57% ( n = 7) at two years and 82% ( n = 17) at > three years following liver transplantation. The potential factors relating to HBV immunity loss after liver transplantation were identified as anti-HBs ( P = 0.002), serum albumin ( P = 0.04), total bilirubin ( P = 0.001) and direct bilirubin ( P = 0.003) before liver transplantation. A five-year-old boy with biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of > 1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was the donor. After liver transplantation, the boy had stenosis of the hepatic artery up to the inferior vena cava anastomosis and underwent venoplasty three times. He also received subcutaneous injections of enoxaparin for 5 mo and 20 transfusions of blood components. Three years and ten months after the liver transplantation, transaminitis was detected with positive tests for HBsAg, HBeAg, and anti-HBc (2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an HBV viral load of 33212320 IU/mL., Conclusion: The present study showed that loss of hepatitis B immunity after liver transplantation is unexpectedly common. In our case report, despite high levels of anti-HBs prior to transplantation, infection occurred at a time when, unfortunately, the child had lost immunity to hepatitis B after liver transplantation., Competing Interests: Conflict-of-interest statement: None of the authors has any potential conflict to declare.

Improved awareness of the hepatitis C virus (HCV) transmission has contributed to the overall decline in the HCV infection rate in some developing countries including Thailand. Chronic HCV infection in some rural Thai communities, however, presents a challenge in the efforts to treat and manage HCV-related diseases. Published and unpublished studies have suggested an unusually high incidence of HCV infection in a Thai province of Phetchabun compared to elsewhere in Thailand. To determine the magnitude of HCV infection and identify potential factors contributing to the higher rate of HCV infection in this province, we performed a population-based study in Phetchabun (n = 1667) and the neighboring Khon Kaen province (n = 1410) where HCV prevalence is much lower. Individuals between 30 and 64 years old completed detailed questionnaires designed to identify HCV risk factors and provided blood samples for anti-HCV antibody screening. The anti-HCV seropositive rates were 15.5% (259/1667) in Phetchabun and 3.6% (51/1410) in Khon Kaen. Positive samples were subsequently genotyped for HCV core gene sequence and assessed for the hepatitis B virus surface antigen (HBsAg) and human immunodeficiency virus antigen/antibody (HIV Ag/Ab). More individuals in Phetchabun possessed the combined presence of HBsAg (5.0%) and HIV Ag/Ab (0.4%) than those in Khon Kaen (3.9% HBsAg and 0.0% HIV Ag/Ab). While male gender, intravenous drug use (IVDU) and tattoos were significant HCV risk factors in both provinces (p <0.05), education less than high school and agriculture-related occupation were additionally associated with HCV in Phetchabun. HCV genotypes 6, 3, and 1 were identified in similar frequency in both provinces. We estimated that prevalence of HCV seropositivity and viremic carriers were higher in Phetchabun (143 and 111 per 1000) than in Khon Kaen (34 and 22 per 1000). Finally, we derived a simple risk factor-based scoring system as a useful preclinical tool to screen individuals at risk of chronic HCV infection prior to intervention. Knowledge gained from this study will assist in HCV screening and promote access to anti-viral treatment in high-risk groups.

Hepatitis A virus (HAV) is transmitted via the fecal-oral route from contaminated food or water. As part of the most recent survey of viral hepatitis burden in Thailand, we analyzed the current seroprevalence of HAV in the country and compared with data dating back to 1971. From March to October, 2014, a total of 4,260 individuals between one month and 71 years of age from different geographical regions (North = 961; Central = 1,125; Northeast = 1,109; South = 1,065) were screened for anti-HAV IgG antibody using an automated chemiluminescent microparticle immunoassay. Overall, 34.53% (1,471/4,260) possessed anti-HAV IgG antibody, and the age-standardized seroprevalence was 48.6%. Seroprevalence rates were 27.3% (North), 30.8% (Central), 33.8% (Northeast) and 45.8% (South) and were markedly lower than in the past studies especially among younger age groups. The overall trend showed an increase in the age by which 50% of the population were anti-HAV IgG antibody: 4.48 years (1971-1972), 6 (1976), 12.49 (1990), 36.02 (2004) and 42.03 (2014).This suggests that Thailand is transitioning from low to very low HAV endemicity. Lower prevalence of HAV correlated with improved healthcare system as measured by decreased infant mortality rate and improved national economy based on increased GDP per capita. The aging HAV immuno-naïve population may be rendered susceptible to potential HAV outbreaks similar to those in industrialized countries and may benefit from targeted vaccination of high-risk groups.

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.

Hepatitis C virus (HCV) infection affects ≥ 180 million individuals worldwide especially those living in developing countries. Recent advances in direct-acting therapeutics promise effective treatments for chronic HCV carriers, but only if the affected individuals are identified. Good treatment coverage therefore requires accurate epidemiological data on HCV infection. In 2014, we determined the current prevalence of HCV in Thailand to assess whether over the past decade the significant number of chronic carriers had changed. In total, 5964 serum samples from Thai residents between 6 months and 71 years of age were obtained from 7 provinces representing all 4 geographical regions of Thailand and screened for the anti-HCV antibody. Positive samples were further analyzed using RT-PCR, sequencing, and phylogenetic analysis to identify the prevailing HCV genotypes. We found that 56 (0.94%) samples tested positive for anti-HCV antibody (mean age = 36.6±17.6 years), while HCV RNA of the core and NS5B subgenomic regions was detected in 23 (41%) and 19 (34%) of the samples, respectively. The seropositive rates appeared to increase with age and peaked in individuals 41-50 years old. These results suggested that approximately 759,000 individuals are currently anti-HCV-positive and that 357,000 individuals have viremic HCV infection. These numbers represent a significant decline in the prevalence of HCV infection. Interestingly, the frequency of genotype 6 variants increased from 8.9% to 34.8%, while the prevalence of genotype 1b declined from 27% to 13%. These most recent comprehensive estimates of HCV burden in Thailand are valuable towards evidence-based treatment coverage for specific population groups, appropriate allocation of resources, and improvement in the national public health policy.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in developing countries are associated with contaminated food or water. Although Thailand is non-endemic for HEV, sporadic infections may occur from zoonotic transmission. Individuals between 7 months to 69 years (mean age = 32.8) from predominantly Islamic Narathiwat (n = 305) and swine farm-dense Lop Buri (n = 416) provinces were screened for anti-HEV and anti-HAV antibodies by commercial enzyme-linked immunosorbent assay and automated chemiluminescent microparticle immunoassay, respectively. Seroprevalence and relative antibody titers were analyzed according to age groups. HAV IgG antibody positive rates in Lop Buri and Narathiwat residents were 39.9% and 58%, respectively (p < 0.001). Greater than 90% of individuals >50 years old in both provinces possessed anti-HAV IgG. In contrast, seroprevalence for anti-HEV IgG was much higher in Lop Buri (37.3%) than in Narathiwat (8.9%) (p < 0.001). Highest anti-HEV IgG prevalence was found among 21-30 year-olds (50%) in Lop Buri and 41-50 year-olds (14.1%) in Narathiwat. In summary, fewer individuals possessed anti-HEV IgG in Narathiwat where most residents abstained from pork and fewer swine farms are present. Therefore, an increased anti-HEV IgG seroprevalence was associated with the density of swine farm and possibly pork consumption. Adults were more likely than children to have antibodies to both HEV and HAV.

Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ∶ 01 (P = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ∶ 01 (P = 5.22 × 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ∶ 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 × 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.

Background: Previous studies showed that single nucleotide polymorphisms (SNPs) in the HLA-DP, TCF19 and EHMT2 genes may affect the chronic hepatitis B (CHB). To predict the degree of risk for chronicity of HBV, this study determined associations with these SNPs., Methods: The participants for this study were defined into 4 groups; HCC (n = 230), CHB (n = 219), resolved HBV infection (n = 113) and HBV uninfected subjects (n = 123). The HLA-DP SNPs (rs3077, rs9277378 and rs3128917), TCF19 SNP (rs1419881) and EHMT2 SNP (rs652888) were genotyped., Results: Due to similar distribution of genotype frequencies in HCC and CHB, we combined these two groups (HBV carriers). The genotype distribution in HBV carriers relative to those who resolved HBV showed that rs3077 and rs9277378 were significantly associated with protective effects against CHB in minor dominant model (OR = 0.45, p<0.001 and OR = 0.47, p<0.001). The other SNPs rs3128917, rs1419881 and rs652888 were not associated with HBV carriers., Conclusions: Genetic variations of rs3077 and rs9277378, but not rs3128917, rs1419881 and rs652888, were significantly associated with HBV carriers relative to resolved HBV in Thai population.

Hepatitis B virus (HBV) infection can become chronic and if left untreated can progress to hepatocellular carcinoma (HCC).Thailand is endemic for HBV and HCC is one of the top five cancers, causing deaths among Thai HBV-infected males. A single nucleotide polymorphism (SNP) at the KIF1B gene locus, rs17401966, has been shown to be strongly associated with the development of HBV-related HCC. However, there are no Thai data on genotypic distribution and allele frequencies of rs17401966. Thai HBV patients seropositive for HBsAg (n=398) were therefore divided into two groups: a case group (chronic HBV with HCC; n=202) and a control group (HBV carriers without HCC; n=196). rs17401966 was amplified by polymerase chain reaction (PCR) and analyzed by direct nucleotide sequencing. The genotypic distribution of rs174019660 for homozygous major genotype (AA), heterozygous minor genotype (AG) and homozygous minor genotype (GG) in the case group was 49.5% (n=100), 40.1% (n=81) and 10.4% (n=21), respectively, and in controls was 49.5% (n=97), 42.3% (n=83) and 8.2% (n=16). Binary logistic regression showed that rs17401966 was not statistically associated with the risk of HCC development in Thai chronic HBV patients (p-value=0.998, OR=1.00 and 95% CI=0.68-1.48). In conclusion, the KIF1B gene SNP (rs174019660) investigated in this study showed no significant association with HBV-related HCC in Thai patients infected with HBV, indicating that there must be other mechanisms or pathways involved in the development of HCC.

Polyomavirus (PyV) infection usually persists without any symptoms in normal individuals. In immunocompromised patients including patients with systemic lupus erythematosus (SLE), PyV reactivation occurs with a high prevalence and can cause severe clinical complications. In this study, reactivation of six PyV [JC, BK, WU, KI, merkel cell (MC) and trichodysplasia spinulosa (TS)] was investigated in terms of prevalence, clinical implications and correlation with urine transforming growth factor (TGF)-β1 expression in 50 SLE patients aged less than 18 years. Clinical characteristics were obtained from medical record review. PyV viruria was assessed by nested polymerase chain reaction. Urine TGF-β1 was measured with ELISA. The mean age was 13 ± 2.8 years. The prevalence of JC and BK viruria was 16% and 32%, respectively. WU, KI, MC and TS were not isolated from any urine specimens. Co-reactivation of 2 PyV was not detected. Urine TGF-β1 levels in patients with JC viruria, with BK viruria and without PyV viruria were 0.27 ± 0.09, 0.10 ± 0.05 and 0.13 ± 0.09 ng/mg of urine creatinine, respectively. Cumulative doses of cyclophosphamide per body weight and urine TGF-β1 levels were higher in JC viruria than in other groups (p < 0.05). The prevalence of JC and BK reactivation was higher in pediatric patients with SLE than in the normal population. JC reactivation in pediatric patients with SLE was correlated with the administration of high-dose cyclophosphamide and increased urine TGF-β1 levels. Surveillance of JC reactivation is recommended in pediatric patients with chronic and severe SLE receiving high-dose cyclophosphamide.