Flea-Borne Rickettsioses and Scrub Typhus in Patients with Suspected Arbovirus Infection in Bangkok, Thailand.

Background: In urban Thailand, arboviral infections dominate diagnoses of acute undifferentiated fevers (AUFs) owing to their well-defined epidemiology and characteristic clinical presentations. However, rickettsial diseases, also endemic in this setting, remain under-recognized owing to challenges in early detection. Objective: This study aimed to identify potential rickettsial infections among patients with AUF in Bangkok and vicinity utilizing leftover nucleic acid extracted from serum samples from patients initially suspected of but negative for arbovirus infections. Materials and Methods: A total of 609 nucleic acid samples were screened for rickettsial bacteria using real-time PCR, targeting the 17-kDa common antigen gene of Rickettsia spp. and the 47-kDa gene of Orientia tsutsugamushi. Results: Nine samples were positive for Rickettsia spp. and two were positive for O. tsutsugamushi. DNA sequence and phylogenetic analyses based on partial 17-kDa antigen and citrate synthase (gltA) genes identified the Rickettsia-positive samples as R. typhi in eight cases and R. felis in one case. Analysis of the 56-kDa type-specific antigen gene identified the two O. tsutsugamushi isolates as Gilliam-related genotypes. Although rickettsial diseases typically present with mild symptoms, two patients with R. typhi infection (murine typhus) developed respiratory distress syndrome, highlighting the potential for rare but serious complications. Conclusion: This study underscores the critical importance of differential diagnosis and prompt, effective intervention to prevent complications in suspected cases.

Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci.

BACKGROUND AND AIMS: Brugada syndrome (BrS) is an inherited arrhythmia with a higher disease prevalence and more lethal arrhythmic events in Asians than in Europeans. Genome-wide association studies (GWAS) have revealed its polygenic architecture mainly in European populations. The aim of this study was to identify novel BrS-associated loci and to compare allelic effects across ancestries. METHODS: A GWAS was conducted in Japanese participants, involving 940 cases and 1634 controls, followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3760 cases and 11 635 controls). The novel loci were characterized by fine-mapping, gene expression, and splicing quantitative trait associations in the human heart. RESULTS: The Japanese-specific GWAS identified one novel locus near ZSCAN20 (P = 1.0 × 10-8), and the cross-ancestry meta-analysis identified 17 association signals, including six novel loci. The effect directions of the 17 lead variants were consistent (94.1%; P for sign test = 2.7 × 10-4), and their allelic effects were highly correlated across ancestries (Pearson's R = .91; P = 2.9 × 10-7). The genetic risk score derived from the BrS GWAS of European ancestry was significantly associated with the risk of BrS in the Japanese population [odds ratio 2.12 (95% confidence interval 1.94-2.31); P = 1.2 × 10-61], suggesting a shared genetic architecture across ancestries. Functional characterization revealed that a lead variant in CAMK2D promotes alternative splicing, resulting in an isoform switch of calmodulin kinase II-δ, favouring a pro-inflammatory/pro-death pathway. CONCLUSIONS: This study demonstrates novel susceptibility loci implicating potentially novel pathogenesis underlying BrS. Despite differences in clinical expressivity and epidemiology, the polygenic architecture of BrS was substantially shared across ancestries.

Correction: The association between vitamin D receptor polymorphism and phases of chronic hepatitis B infection in HBV carriers in Thailand.

[This corrects the article DOI: 10.1371/journal.pone.0277907.].

Characterization of antibody response to SARS-CoV-2 Orf8 from three waves of COVID-19 outbreak in Thailand.

A dynamic of virus adaptation and a mass vaccination campaign could significantly reduce the severity of clinical manifestations of COVID-19 and transmission. Hence, COVID-19 may become an endemic disease globally. Moreover, mass infection as the COVID-19 pandemic progressed affected the serology of the patients as a result of virus mutation and vaccination. Therefore, a need exists to acquire accurate serological testing to monitor the emergence of new outbreaks of COVID-19 to promptly prevent and control the disease spreading. In this study, the anti-Orf8 antibodies among samples collected in Thailand's first, fourth, and fifth waves of COVID-19 outbreaks compared with pre-epidemic sera were determined by indirect ELISA. The diagnostic sensitivity and specificity of the anti-Orf8 IgG ELISA for COVID-19 samples from the first, fourth, and fifth waves of outbreaks was found to be 100% compared with pre-epidemic sera. However, the diagnostic sensitivity and specificity of the anti-Orf8 IgG ELISA for a larger number of patient samples and controls from the fifth wave of outbreaks which were collected on day 7 and 14 after an RT-PCR positive result were 58.79 and 58.44% and 89.19 and 58.44%, respectively. Our data indicated that some of the controls might have antibodies from natural past infections. Our study highlighted the potential utility of anti-Orf8 IgG antibody testing for seroprevalence surveys but still warrants further investigations.

Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines.

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

Transplacental transfer of maternal antibodies following immunization with recombinant pertussis vaccines during pregnancy: Real-world evidence.

AIM/OBJECTIVE: This study investigates placental antibody transfer following recombinant pertussis vaccination in pregnancy in a real-world setting. METHODS: This postmarketing observational study recruited pregnant women vaccinated with monovalent recombinant acellular pertussis (aP) vaccine (aPgen; n = 199) or combined to tetanus-diphtheria (TdaPgen; n = 200), or Td-vaccine only (n = 54). Pregnancy, delivery, and neonatal outcomes were assessed. Cord blood was collected postdelivery and pertussis toxin (PT)-IgG, filamentous hemagglutinin (FHA)-IgG, and PT-neutralizing antibodies (PT-Nab) were assessed. RESULTS: No adverse pregnancy, delivery, or neonatal outcomes attributed to aPgen, TdaPgen, or Td vaccination were reported. High anti-PT antibody levels were detected in cord samples from women vaccinated with aPgen (geometric mean concentration [GMC] PT-IgG 206.1 IU/ml, 95% confidence intervals [CI]: 164.3-258.6; geometric mean titer [GMT] PT-Nab 105.3 IU/ml, 95% CI: 81.7-135.8) or TdaPgen (GMC PT-IgG 153.1 IU/ml, 95% CI: 129.1-181.5; GMT PT-Nab 81.5 IU/ml, 95% CI: 66.4-100.0). In the Td-only group, anti-PT antibodies were low (GMC PT-IgG 6.5 IU/ml, 95% CI: 4.9-8.8; GMT PT-Nab 3.8 IU/ml, 95% CI: 2.8-5.1). The same was found for FHA-IgG. Recombinant pertussis vaccination at <27 or 27-36 weeks gestation induced similar cord pertussis antibody levels. CONCLUSION: This first real-world study confirms that recombinant pertussis vaccination in the second or third trimester of pregnancy results in high levels of passive immunity in infants. Thai Clinical Trial Registry: TCTR20200528006.

Identification of Bacteria and Viruses Associated with Patients with Acute Febrile Illness in Khon Kaen Province, Thailand.

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93-97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness.

Bacterial DNA Translocation Is Associated With Overt Hepatic Encephalopathy and Mortality in Patients With Cirrhosis.

INTRODUCTION: Data on the relationship between bacterial translocation, hepatic encephalopathy (HE), and mortality are scarce. This study aimed to assess the association between bacterial DNA (bactDNA) translocation, inflammatory response, ammonia levels, and severity of HE in patients with cirrhosis, as well as the role of bactDNA translocation in predicting mortality. METHODS: Cirrhotic patients without bacterial infection were prospectively enrolled between June 2022 and January 2023. Grading of HE was classified by the West Haven Criteria and Psychometric Hepatic Encephalopathy Score ≤ -5. RESULTS: Overall, 294 cirrhotic patients were enrolled, with 92 (31.3%) and 58 (19.7%) having covert and overt HE, respectively. BactDNA translocation was detected in 36.1% of patients (n = 106). Patients with overt HE had more bactDNA translocation and higher serum lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, interleukin-6 (IL-6), and ammonia levels than those without HE. Patients with detectable bactDNA had higher white cell counts and serum LBP and IL-6 levels than those without. By contrast, bactDNA, serum LBP, and soluble CD14 levels were comparable between patients with covert HE and those without HE. The multivariate Cox regression analysis revealed that bactDNA translocation (hazard ratio [HR] = 2.49, 95% confidence interval [CI]: 1.22-5.11), Model for End-Stage Liver Disease score (HR = 1.12, 95% CI: 1.09-1.16), age (HR = 1.05, 95% CI: 1.000-1.002), and baseline IL-6 (HR = 1.001, 95% CI: 1.000-1.002) were independent factors associated with 6-month mortality. DISCUSSION: Apart from hyperammonemia, bactDNA translocation is a possible factor associated with overt HE in cirrhotic patients. BactDNA translocation and IL-6 are independent factors associated with 6-month mortality.

Human Enterovirus B Is a Significant Cause of Aseptic Meningitis and Sepsis-Like Illness in Young Infants in Thailand.

Human enterovirus (EV) and Parechovirus (PeV) infections are major causes of sepsis-like illness in infants < 90 days of age. Enterovirus species B (EV-B) was found to be the leading cause of aseptic meningitis in young infants. In Thailand, EV and PeV are not part of the routine screening of blood or cerebrospinal fluid (CSF) of children with suspected aseptic meningitis and sepsis-like illness. Consequently, data on EV and PeV epidemiology are limited. This study tested clinical samples from hospitalized young infants with suspected aseptic meningitis or sepsis-like illness between 2013 and 2022 for EV, PeV, and Herpes simplex virus (HSV). Of 95 specimens, 10 were positive for EV, representing 10.5%. These positive samples included eight CSF and two stool samples. No samples were positive for PeV and HSV. Of these positive cases, EV-B was detected in eight, and EV-A was detected in two cases. The species of EV-B detected include echovirus-18 (E18) (n=2), E21 (n=2), E4(n=1), E5 (n=1), E9 (n=1), and E11 (n=1). Our report demonstrates the significant role of EV-B, and less frequently EV-A, in Thai infants with aseptic meningitis and sepsis-like illness.

Long-Term Dynamic Changes in Hybrid Immunity over Six Months after Inactivated and Adenoviral Vector Vaccination in Individuals with Previous SARS-CoV-2 Infection.

Numerous studies have largely focused on short-term immunogenicity in recovered individuals post mRNA vaccination. However, understanding the long-term durability, particularly in inactivated and adenoviral vectored vaccines, remains limited. We evaluated antibody responses, omicron variant neutralization, and IFN-γ responses in 119 previously infected individuals vaccinated with CoronaVac or ChAdOx1 up to six months post-vaccination. Both vaccines elicited robust immune responses in recovered individuals, surpassing those who were infection-naïve, and these persisted above pre-vaccination levels for six months. However, antibody levels declined over time (geometric mean ratio (GMR) = 0.52 for both vaccines). Notably, neutralizing activities against omicron declined faster in ChAdOx1 (GMR = 0.6) compared to CoronaVac recipients (GMR = 1.03). While the first dose of ChAdOx1 adequately induced immune responses in recovered individuals, a second dose demonstrated advantages in omicron variant neutralization and slower decline. Although both vaccines induced T cell responses, the median IFN-γ level at six months returned to pre-vaccination levels. However, more individuals exhibited reactive T cell responses. Extending the interval (13-15 months) between infection and vaccination could enhance antibody levels and broaden neutralization. Together, these findings demonstrate a robust humoral and cellular response that was sustained for at least six months after vaccination, thus guiding optimal vaccination strategies based on prior infection and vaccine platforms.

Inadvertent Platelet Transfusion from Monkeypox Virus-Infected Donor to Recipient, Thailand, 2023.

In Thailand, platelet product from a blood donor was transfused to a recipient who had dengue. Two days later, the donor was confirmed to have monkeypox virus infection. Monkeypox virus DNA was undetectable in recipient specimens up to 2 weeks after transfusion. The recipient remained asymptomatic at 4 weeks of monitoring.

Comparable detection of HPV using real-time PCR in paired cervical samples and concentrated first-stream urine collected with Colli-Pee device.

We compared high-risk human papillomavirus (HPV) detection on first-stream urine from self-sampled collection device (Colli-Pee) and same-day clinician-collected cervical swab in 240 women. Testing with automated cobas 4800 system showed 96.7 % concordance (198 concordant-negative, 34 concordant-positive, Cohen's kappa=0.87). HPV testing on Colli-Pee urine offers advantages for acceptable non-invasive HPV screening.

Antibody persistence of standard versus double three-dose hepatitis B vaccine in liver transplant children: a randomized controlled trial.

Rapid hepatitis B (HB) surface antibody (anti-HBs) loss is prevalent after liver transplantation (LT). Herein, we evaluated anti-HBs persistence after HB vaccination using two regimens in LT children. We recruited 66 previously immunized LT children with anti-HBs level of < 100 mIU/mL. Participants were randomly reimmunized with standard-three-dose (SD) and double-three-dose (DD) intramuscular HB vaccination at 0, 1, and 6 months. Anti-HBs were assessed at every outpatient visit. Antibody loss defined as anti-HBs levels < 100 mIU/mL after three-dose vaccination. After three-dose vaccination, 81.8% and 78.7% of participants in the SD and DD groups, had anti-HBs levels > 100 mIU/mL, with a geometric mean titer (GMT) of 601.68 and 668.01 mIU/mL (P = 0.983). After a mean follow-up of 2.31 years, the anti-HBs GMT was 209.81 and 212.61 mIU/mL in the SD and DD groups (P = 0.969). The number of immunosuppressants used and an anti-HBs level < 1 mIU/mL at baseline were independently associated with anti-HB loss. The DD regimen strongly increased the risk of anti-HBs loss (adjusted hazard ratio, 2.97 [1.21-7.31]; P = 0.018). The SD HB reimmunization regimen effectively maintained protective anti-HBs levels in children undergoing LT, making it the preferred regimen for such children with anti-HB loss.Trial registration: TCTR20180723002.

Immunogenicity and durability against Omicron BA.1, BA.2 and BA.4/5 variants at 3-4 months after a heterologous COVID-19 booster vaccine in healthy adults with a two-doses CoronaVac vaccination.

Background: Several countries have authorized a booster vaccine campaign to combat the spread of COVID-19. Data on persistence of booster vaccine-induced immunity against new Omicron subvariants are still limited. Therefore, our study aimed to determine the serological immune response of COVID-19 booster after CoronaVac-priming. Methods: A total of 187 CoronaVac-primed participants were enrolled and received an inactivated (BBIBP), viral vector (AZD1222) or mRNA vaccine (full-/half-dose BNT162B2, full-/half-dose mRNA-1273) as a booster dose. The persistence of humoral immunity both binding and neutralizing antibodies against wild-type and Omicron was determined on day 90-120 after booster. Results: A waning of total RBD immunoglobulin (Ig) levels, anti-RBD IgG, and neutralizing antibodies against Omicron BA.1, BA.2, and BA.4/5 variants was observed 90-120 days after booster vaccination. Participants who received mRNA-1273 had the highest persistence of the immunogenicity response, followed by BNT162b2, AZD1222, and BBIBP-CorV. The responses between full and half doses of mRNA-1273 were comparable. The percentage reduction of binding antibody ranged from 50 % to 75 % among all booster vaccine. Conclusions: The antibody response substantially waned after 90-120 days post-booster dose. The heterologous mRNA and the viral vector booster demonstrated higher detectable rate of humoral immune responses against the Omicron variant compared to the inactivated BBIBP booster. Nevertheless, an additional fourth dose is recommended to maintain immune response against infection.

Genomic epidemiology and evolutionary analysis during XBB.1.16-predominant periods of SARS-CoV-2 omicron variant in Bangkok, Thailand: December 2022-August 2023.

The growing occurrence of novel recombinants, such as XBB.1.16, has emerged and become predominant, raising concerns about the impact of genomic recombination on the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the molecular epidemiological trends and evolution of the Omicron XBB.1.16 epidemic in Bangkok between December 2022 and August 2023. Partial spike and complete genome sequencing of SARS-CoV-2 samples collected from collaborating hospitals were performed. The analysis of 491 partial spike sequences identified 15 distinct lineages, with XBB.1.16 dominating the lineages beginning in March 2023. Phylogenetic analysis revealed at least four distinct XBB.1.16 lineages, suggesting multiple independent introductions into Bangkok. The estimated emergence of XBB.1.16 occurred approximately in January 2022, with an evolutionary rate of 0.79 × 10-3 substitutions per site per year. Monitoring the genomic epidemiology and evolution of XBB.1.16 is vital for the early detection of new strains or emerging variants, which may guide vaccine design and the inclusion of new vaccine strains.

Impact of Subgroup Distribution on Seasonality of Human Respiratory Syncytial Virus: A Global Systematic Analysis.

BACKGROUND: Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We aimed to further understand the association by conducting a global-level systematic analysis. METHODS: We compiled published data on RSV seasonality through a systematic literature review, and unpublished data shared by international collaborators. Using annual cumulative proportion (ACP) of RSV-positive cases, we defined RSV season onset and offset as ACP reaching 10% and 90%, respectively. Linear regression models accounting for meteorological factors were constructed to analyze the association of proportion of RSV-A with the corresponding RSV season onset and offset. RESULTS: We included 36 study sites from 20 countries, providing data for 179 study-years in 1995-2019. Globally, RSV subgroup distribution was not significantly associated with RSV season onset or offset globally, except for RSV season offset in the tropics in 1 model, possibly by chance. Models that included RSV subgroup distribution and meteorological factors explained only 2%-4% of the variations in timing of RSV season. CONCLUSIONS: Year-on-year variations in RSV season onset and offset are not well explained by RSV subgroup distribution or meteorological factors. Factors including population susceptibility, mobility, and viral interference should be examined in future studies.

Prevalence and the impact of hepatitis E infection in pediatric liver transplanted recipients with hepatitis in Thailand.

BACKGROUND: The hepatitis E virus (HEV) infection typically causes acute and self-limiting hepatitis. However, chronic infection can occur in immunocompromised hosts. This study determined the prevalence and impact of HEV infection in liver transplanted (LT) children who had transaminitis. METHODS: The demographic data, anti-HEV IgM/IgG, serum/stool HEV RNA, and management for LT children with acute or persistent transaminitis from 2003 to 2020 were retrospectively reviewed. HEV serology was tested by ELISA, and HEV RNA was detected by semi-nested PCR. RESULTS: Seventy-two children with LT with persistent transaminitis with a median age of 4.41 (1.32, 9.14) years (55.6% female) and one with acute hepatitis were investigated for HEV infection. Anti-HEV IgM, anti-HEV IgG, serum, or stool HEV RNA was investigated in 95.8% (N = 69), 93.1% (N = 67), 43.1% (N = 31), and 37.5% (N = 27) of patients, respectively. The prevalence of HEV infection was 37.5% (N = 27). There was no significant difference in characteristics between the HEV-infected and HEV-non-infected patients. Moreover, 22.2% (N = 16) and 15.3% (N = 11) of patients had past HEV infection and HEV-related acute or chronic infection, respectively. Most of the patients had primary treatment as the presumed graft rejection without improvement. In two patients, detectable HEV RNA in serum turned undetectable in approximately 2 weeks and 2 months, and liver enzyme levels normalized after reducing immunosuppressive therapy. CONCLUSIONS: The prevalence of HEV infection among pediatric LT recipients with hepatitis was high. Chronic HEV infection was evidenced in two patients. Investigations of HEV infection in pediatric LT recipients with persistent transaminitis should guide proper management.

Acute Gastroenteritis Associated with Norovirus GII.8[P8], Thailand, 2023.

Acute gastroenteritis associated with human norovirus infection was reported in Phuket, Thailand, in June 2023. We amplified GII.8[P8] from the outbreak stool specimens. Retrospective sample analysis identified infrequent GII.8[P8] in the country beginning in 2018. In all, the 10 whole-genome GII.8[P8] sequences from Thailand we examined had no evidence of genotypic recombination.

Elevated serum IL-34 is correlated with disease severity in patients with biliary atresia following Kasai portoenterostomy.

BACKGROUND: Biliary atresia (BA) is a severe congenital disorder with progressive obstructive cholangiopathy in young children. The inflammatory process has been recognized as one of the pathological mechanisms driving bile duct injury. Since interleukin-34 (IL-34) has been reportedly linked to several pathological liver disorders, including inflammation, the current study aimed to analyze circulating IL-34 and the association of circulating IL-34 with hepatic deterioration and clinical outcomes in post-Kasai BA children. METHODS: Circulating IL-34 levels were analyzed in 89 post-Kasai BA subjects and 45 healthy individuals using an ELISA. Liver stiffness (hardness) was measured by ultrasound elastography. RESULTS: Circulating IL-34 was substantially higher in BA children than in control individuals, particularly those with unfavorable outcomes including hepatic dysfunction, jaundice, and portal hypertension. In BA group, circulating IL-34 was positively correlated with liver stiffness (r = 0.515, p < 0.001), AST (r = 0.403, p < 0.001), ALT (r = 0.279, p = 0.008), total bilirubin (r = 0.224, p = 0.03), ALP (r = 0.255, p = 0.016), and serum IL-6 (r = 0.590, p < 0.001) but inversely correlated with albumin (r = -0.417, p < 0.001). Kaplan-Meier survival analysis showed that higher circulating IL-34 levels were significantly associated with reduced survival rates in BA subjects (p = 0.002). CONCLUSION: Higher circulating IL-34 values were directly associated with hepatic impairment and the BA severity, implicating thatserum IL-34 could be applied as a noninvasive marker for the monitoring of the severity in BA subjects following Kasai portoenterostomy and therapeutic efficacy.