A randomized clinical trial of peginterferon alpha-2b with or without entecavir in patients with HBeAg-negative chronic hepatitis B: Role of host and viral factors associated with treatment response.

Combining peginterferon (PEG-IFN) and a potent nucleoside/nucleotide analogue might improve treatment response in patients with chronic hepatitis B (CHB). The aims of this study were to compare the efficacy of PEG-IFN alpha-2b with or without entecavir in HBeAg-negative CHB and to investigate predictors of response. A total of 126 treatment-naïve patients were randomly assigned to receive monotherapy (n = 63) or combination therapy (n = 63) for 48 weeks. Virological response (VR) was defined as HBV DNA level <2000 IU/mL at week 96. Baseline factors including polymorphisms in the IFNL3 (rs12979860) and HLA-DPA1 (rs3077) genes and on-treatment viral kinetics were determined. At week 48, rates of undetectable HBV DNA were lower in the monotherapy than combination groups, but rates of HBsAg clearance and decline were comparable. At week 96, there was no difference between the corresponding groups regarding virological response (41.3% vs 38.1%, P = 0.856), HBsAg clearance (9.5% vs 4.8%, P = 0.491) and HBsAg decline. Baseline HBsAg level [odds ratio (OR): 3.14 (1.34-7.69), P = 0.012] and rs3077 polymorphism [OR: 2.78 (1.27-6.11), P = 0.011] were independent predictors of response. Patients carried GG genotype of rs3077 with low baseline HBV (<1000 IU/mL) had high probability of achieving VR (76.5%) and HBsAg clearance (29.4%). None of the patients without decrease in HBsAg combined with <2 log10 HBV DNA decline at week 12 achieved a virological response. In conclusion, the combination therapy lead to greater on-treatment HBV DNA suppression but did not improve virological response and HBsAg clearance/decline over monotherapy. Host and viral factors could help optimize decision-making at baseline and during PEG-IFN-based therapy.

Cytokine levels as biomarkers for leptospirosis patients.

Inflammatory mediators were suggested to be biomarkers for prediction of disease severity. In this study, we investigated the levels of IL-6, IL-8, IL-10 and TNF-α in leptospirosis patients with mild or severe illnesses. Sera samples were divided into two groups. The OI group and NOI groups included sera from patients with and without organ involvement, respectively. Each group consisted of 20 pairs of sera. Twenty-five sera from healthy individuals were included as controls. Cytokine levels were compared. Although IL-6, IL-8 and IL-10 levels in acute sera from the OI group were significantly higher than NOI group, only IL-8 level was significantly higher in the OI group when cytokine levels in convalescent sera were compared. TNF-α, an inflammatory cytokine widely studied in leptospirosis was not significantly different between two groups of patients. Our data suggested that IL-6, IL-8 and IL-10 were involved in disease severity. However, time of specimen collection could affect the significant levels of cytokines especially as biomarkers for monitoring disease severity.

Epidemic outbreak of acute haemorrhagic conjunctivitis caused by coxsackievirus A24 in Thailand, 2014.

Acute haemorrhagic conjunctivitis outbreaks are often attributed to viral infection. In 2014, an unprecedented nationwide outbreak of infectious conjunctivitis occurred in Thailand, which affected >300 000 individuals over 3 months. To identify and characterize the virus responsible for the epidemic, eye swab specimens from 119 patients were randomly collected from five different provinces. Conserved regions in the enteroviral 5'-UTR and adenovirus hexon gene were analysed. Enterovirus was identified in 71·43% (85/119) of the samples, while no adenovirus was detected. From enterovirus-positive samples, the coxsackievirus A24 variant (70·59%, 84/119) and echovirus (0·84%, 1/119) were identified. Additional sequencing of full-length VP1 and 3C genes and subsequent phylogenetic analysis revealed that these clinical isolates form a new lineage cluster related to genotype IV-C5. In summary, the coxsackievirus A24 variant was identified as an aetiological agent for the recent acute haemorrhagic conjunctivitis outbreak in Thailand.

Compound heterozygosity of a novel exon 3 frameshift (p.R357P fs*24) mutation and Y486D mutation in exon 5 of the UGT1A1 gene in a Thai infant with Crigler-Najjar syndrome type 2.

Mutations in the UGT1A1 gene cause Crigler-Najjar syndrome (CN), which causes non-hemolytic unconjugated hyperbilirubinemia, and is categorized as CN1 and CN2 according to the severity of bilirubin levels. The UGT1A1 gene is responsible for encoding the liver enzyme uridine diphosphate-glucuronosyltransferase, UGT1A1. This protein adds glucuronic acid to unconjugated bilirubin in bilirubin metabolism to form conjugated bilirubin. CN2 occurs when UGT1A1 activity is low, while CN1 is the absence of UGT1A1 activity; therefore, the CN2 phenotype is not as severe as that of CN1. Here, we report a novel allele of compound heterozygous mutations in UGT1A1 in a Thai male infant with clinical symptoms of CN2. The patient's compound heterozygosity was composed of a novel mutation, c.1069-1070insC, and the c.1456T>G mutation. The novel c.1069-1070insC mutation generated a premature stop codon in exon 4 (p.R357Pfs*24). The healthy parents were heterozygous for the c.1069-1070insC mutation (father) and c.1456T>G missense mutation (mother). Our results suggest that compound heterozygosity of the novel c.1069-1070insC and c.1456T>G (c211 G >A) missense mutation in the UGT1A1 gene played a primary role in the development of CN2 unconjugated hyperbilirubinemia.

A novel stop codon mutation in exon 1 (558C>A) of the UGT1A1 gene in a Thai neonate with Crigler-Najjar syndrome type I.

Human uridine 5'-diphosphate-glucuronosyltransferases play a critical role in detoxification by conjugating bilirubin with glucoronic acid. Impaired or reduced enzymatic activity causes a spectrum of clinical disorders such as Crigler-Najjar syndrome type I (CN1), Crigler-Najjar syndrome type II, and Gilbert's syndrome. CN1 is a severe form of unconjugated hyperbilirubinemia caused by homozygous or compound heterozygous mutations in the gene for uridine 5'-diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1), resulting in complete loss of enzyme function. Here, we report a novel homozygous mutation of UGT1A1 in a female Thai infant who was diagnosed with CN1, and her parents were found to be heterozygous carriers. The patient was homozygous for the c.558C>A mutation, which resulted in a premature stop codon in exon 1. Her asymptomatic parents were carriers of the nonsense c.558C>A mutation. Our result suggests an important role for homozygous c.558C>A mutations in the UGT1A1 gene in the development of severe unconjugated hyperbilirubinemia.

Molecular epidemiology and genetic history of hepatitis C virus subtype 3a infection in Thailand.

OBJECTIVE: Among all hepatitis C virus (HCV) infections, subtype 3a is the most common genotype in Thailand. This study investigates the molecular epidemiology and epidemic history of HCV subtype 3a in Thailand. METHODS: Three hundred and fifty-six serum samples were collected from HCV-infected Thai patients. The virus was isolated, after which the core and NS5B regions were sequenced. Subsequently, the HCV genotype was classified by phylogenetic analysis based on the core and NS5B regions. Molecular evolution analysis of HCV subtype 3a was estimated using BEAST (Bayesian Evolutionary Analysis by Sampling Trees) v.1.5.4. RESULTS: Based on our phylogenetic analyses, subtype 3a (38.5%) was the most prevalent, followed by 1a (21%), 1b (13.8%), genotype 6 (19.9%) [comprised of subtypes 6e (0.3%), 6f (11%), 6i (1.9%), 6j (1.9%) and 6n (4.8%)] and 3b (5.6%). Our phylogenetic tree indicates the existence of a specific group of HCV subtype 3a strains in the Thai population. Molecular evolutionary analysis dated the most recent common ancestor of the Thai HCV subtype 3a strains as existing approximately 200 ago, and a Bayesian skyline plot showed that this particular strain spread to Thailand during the mid-1970s and early 1980s. This period overlaps with the Vietnam War (1955-1975) and the widespread use of injection stimulants introduced by the US Army during this time. CONCLUSION: The estimated history of HCV subtype 3a infection in Thailand may help to predict the future burden of HCV-related diseases and facilitate better public health control and surveillance.

Role of a homozygous A(TA)7TAA promoter polymorphism and an exon 1 heterozygous frameshift mutation UGT1A1 in Crigler-Najjar syndrome type II in a Thai neonate.

Crigler-Najjar syndrome is a rare autosomal recessive disease caused by mutations in the UGT1A1 gene. These mutations result in the deficiency of UGT1A1, a hepatic enzyme essential for bilirubin conjugation. This report describes the case of a 4-month-old boy with the cardinal symptoms of Crigler-Najjar syndrome type II. Molecular genetic analysis showed a homozygous UGT1A1 promoter mutation [A(TA)7TAA] and a heterozygous insertion of 1 adenosine nucleotide between positions 353 and 354 in exon 1 of UGT1A1 that caused a frameshift with a premature stop codon.

Fatal Balamuthia amebic encephalitis in a healthy child: a case report with review of survival cases.

Balamuthia mandrillaris is one of the 4 amebas in fresh water and soil that cause diseases in humans. Granulomatous amebic encephalitis (GAE), caused by B. mandrillaris, is a rare but life-threatening condition. A 4-year-old, previously healthy, Thai girl presented with progressive headache and ataxia for over a month. Neuroimaging studies showed an infiltrative mass at the right cerebellar hemisphere mimicking a malignant cerebellar tumor. The pathological finding after total mass removal revealed severe necrotizing inflammation, with presence of scattered amebic trophozoites. Cerebrospinal fluid (CSF) obtained from lumbar puncture showed evidence of non-specific inflammation without identifiable organisms. A combination of pentamidine, sulfasalazine, fluconazole, and clarithromycin had been initiated promptly before PCR confirmed the diagnosis of Balamuthia amebic encephalitis (BAE). The patient showed initial improvement after the surgery and combined medical treatment, but gradually deteriorated and died of multiple organ failure within 46 days upon admission despite early diagnosis and treatment. In addition to the case, 10 survivors of BAE reported in the PubMed database were briefly reviewed in an attempt to identify the possible factors leading to survival of the patients diagnosed with this rare disease.

Response-guided therapy for patients with hepatitis C virus genotype 6 infection: a pilot study.

The optimal duration of treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) in patients with hepatitis C virus (HCV) genotype 6 is unknown. This study was aimed at determining treatment response on the basis of rapid virological response (RVR) of HCV genotype 6 in comparison with genotypes 1 and 3. Sixty-six treatment naïve patients were treated with PEG-IFN-α2a (180 µg/week) plus weight-based RBV (1000-1200 mg/day). Patients with genotype 1 n = 16) and genotype 3 (n = 16) were treated for a fixed duration of 48 and 24 weeks, respectively. Patients with genotype 6 (n = 34) who achieved RVR were treated for 24 weeks (response-guided therapy) and the remaining patients were treated for 48 weeks (standard therapy). The mean baseline HCV RNA levels were not statistically different between groups (6.4 ± 0.8, 6.0 ± 1.0 and 6.5 ± 0.8 Log(10) IU/mL for genotypes 1, 3 and 6, respectively). Patients with genotypes 1, 3 and 6 achieved RVR in 43.8%, 87.5% and 73.5% of cases, respectively. One patient with genotype 1 and 3 with genotype 6 were considered nonresponders and discontinued therapy. Sustained virological response (SVR) was achieved in 62.5%, 81.3% and 76.5% of patients with genotypes 1, 3 and 6, respectively. The SVR rate in patients with genotype 6 who underwent response-guided therapy was 88%. This pilot study suggested that the SVR rate of HCV genotype 6 was at an intermediate level between those of genotypes 3 and 1. Treatment with PEG-IFN plus RBV for 24 weeks may be sufficient for patients with genotype 6 who achieve RVR. Prospective randomized trials are required to evaluate this response-guided strategy in a larger number of patients with genotype 6.

Piperine inhibits cytokine production by human peripheral blood mononuclear cells.

Piperine, an amide isolated from Piper species (Piperaceae), has been reported to exhibit central nervous system depression, anti-pyretic and anti-inflammatory activity. Immunomodulatory and anti-tumor activity of piperine has been demonstrated in mouse carcinomas. However, there is little information available concerning the effect of piperine on humans. We evaluated the immunopharmacological activity of this compound in human immune cells. Human peripheral blood mononuclear cells (PBMCs) were exposed to piperine, and cell proliferation was determined by the MTS assay. Piperine significantly inhibited phytohemagglutinin-stimulated human PBMC proliferation after exposure for 72 h. This compound inhibited PBMC activity, with an IC(50) of 100.73 ± 11.16 µg/mL. Production of interleukin-2 (IL-2) and interferon-γ (IFN-γ) was measured using an ELISA assay and RT-PCR. Piperine inhibited IL-2 and IFN-γ production in the PBMCs. RT-PCR data indicated that IL-2 and IFN-γ mRNA expression in PBMCs is suppressed by piperine. This compound significantly inhibited the production of these two cytokines by activated PBMCs in a dose-dependent manner. In conclusion, piperine appears to have potential as an immunomodulatory agent for immune system suppression.

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

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.

Recombination dynamics of human parechoviruses: investigation of type-specific differences in frequency and epidemiological correlates.

Human parechoviruses (HPeVs) are highly prevalent RNA viruses classified in the family Picornaviridae. Several antigenically distinct types circulate in human populations worldwide, whilst recombination additionally contributes to the genetic heterogeneity of the virus. To investigate factors influencing the likelihood of recombination and to compare its dynamics among types, 154 variants collected from four widely geographically separated referral centres (UK, The Netherlands, Thailand and Brazil) were typed by VP3/VP1 amplification/sequencing with recombination groups assigned by analysis of 3Dpol sequences. HPeV1B and HPeV3 were the most frequently detected types in each referral region, but with marked geographical differences in the frequencies of different recombinant forms (RFs) of types 1B, 5 and 6. HPeV1B showed more frequent recombination than HPeV3, in terms both of evolutionary divergence and of temporal/geographical indicators of population separation. HPeV1 variants showing between 10 and 20% divergence in VP3/VP1 almost invariably fell into different recombination groups, compared with only one-third of similarly divergent HPeV3 variants. Substitution rates calculated by beast in the VP3/VP1 region of HPeV1 and HPeV3 allowed half-lives of the RFs of 4 and 20 years, respectively, to be calculated, estimates fitting closely with their observed lifespans based on population sampling. The variability in recombination dynamics between HPeV1B and HPeV3 offers an intriguing link with their markedly different seasonal patterns of transmission, age distributions of infection and clinical outcomes. Future investigation of the epidemiological and biological opportunities and constraints on intertypic recombination will provide more information about its influence on the longer term evolution and pathogenicity of parechoviruses.

Increased level of hepatocyte growth factor in children with dengue virus infection.

BACKGROUND: Evidence of hepatocellular damage is common in dengue-infected individuals. Hepatocyte growth factor (HGF), a key cytokine responsible for liver regeneration, may play a prognostic role in dengue virus infection. AIM: To determine the relationship between serum HGF level and disease severity in patients with dengue virus infection. METHODS: Serum samples from 27 children [17 dengue fever (DF), ten dengue haemorrhagic fever (DHF)] with serologically confirmed dengue virus infection during the febrile, toxic stages and at follow-up were analysed for HGF. Serum samples obtained from nine healthy children served as the control group. RESULTS: In dengue-infected patients, serum HGF was significantly higher at the febrile and toxic stages than at follow-up (p<0.05). In comparison with DF, patients with DHF had a greater level of HGF at the febrile stage (p<0.05). A cut-off HGF level of 1220 pg/mL obtained during the febrile stage showed a sensitivity of 90% and a specificity of 53% for predicting clinical progression to DHF (area under the ROC curve 0.75). CONCLUSION: Serum HGF level at the early stage of dengue virus infection is elevated and may be a useful predictor for clinical progression to DHF.

Molecular characteristics of the human pandemic influenza A virus (H1N1).

The outbreak of the human pandemic influenza A (H1N1) has caused a considerable public concern. The aim of this review was to improve our understanding of this novel virus by analyzing the relationships between its molecular characteristics and pathogenic properties. Results of this analysis indicate that the human pandemic influenza A (H1N1) virus is a new re-assorted virus, which combines genetic materials from the avian flu (H1N1) virus, classical swine flu (H1N1) virus, human flu (H3N2) virus, and Eurasian swine flu (H1N1) virus. Analysis of the sequences for receptor-binding and cleavage sites of hemagglutinin (HA), stalk region of neuraminidase (NA), non-structural protein 1 (NS1), polymerase basic protein 2 (PB2), and polymerase basic protein 1 (PB1) suggested that (i) the human pandemic influenza A (H1N1) virus is a low virulent and low pathogenic virus, (ii) its replication is restricted to the cells of upper respiratory tract, so it does not lead to a systemic infection, (iii) it spreads among humans only, (iv) its replication could be inhibited by oseltamivir, zanamivir, interferon (IFN), and tumor necrosis factor alpha (TNF-alpha). A potential application of amantadine might be complicated by the drug-resistant virus strains.

Hepatitis B virus infection in non-human primates.

Hepatitis B viruses (HBVs) represent a serious public health problem affecting 350 to 400 million HBV carriers worldwide. The virus does not exclusively infect humans, but can also be found in non-human primates as in the families Hominidae (chimpanzee, gorilla, orangutan) and Hylobatidae (gibbon), which are distributed over Africa (chimpanzee and gorilla) and Southeast Asia (orangutan and gibbon), the endemic areas of human HBV. The prevalence of asymptomatic HBV carriers reaches in gibbons 23-33% and in orangutans 15%. The genome organization of non-human primate HBVs is nearly identical to that of human HBVs. Because of this close similarity, the question of cross-transmission of HBV between species has arisen. There are many data on cross-transmission of human HBVs to the non-human primates. However, a cross-transmission of HBVs from non-human primates to humans has not been reported yet. Using more advanced diagnostic methods, the non-human primates have increasingly been identified as a reservoir of several viruses such as lymphocryptoviruses, Cercopithecine herpesvirus 1 (CeHV-1), Simian immunodeficiency virus (SIV), Simian foamy virus (SFV), and HBVs. Thus veterinarians, zookeepers, or people in close contact with non-human primates may potentially become infected with those viruses causing severe diseases. Enhanced awareness of prevalence, genetic relatedness and evolution of non-human primate HBVs will help prevent further spread and cross-transmission of these viruses between humans and non-human primates.

Prevalence, clinical presentations and complications among hospitalized children with influenza pneumonia.

Viral respiratory tract infections are a major cause of hospitalization in children. Influenza is common but often not laboratory proven. We report a prospective study of children admitted with a clinical diagnosis of pneumonia. Infants and children (ages 1 month-15 years) who were hospitalized with community-acquired pneumonia were enrolled in the study. Their nasopharyngeal aspirated samples were analyzed for common respiratory viruses, including influenza virus, by reverse transcription-polymerase chain reaction (RT-PCR) or PCR. Out of 257 patients, we identified 127 (49.4%) cases with respiratory viruses, and influenza was found in 32 of these cases (12.5%). Other common respiratory viruses included respiratory syncytial virus in 42 (16.3%), human metapneumovirus in 24 (9.3%), adenovirus in 17 (6.6%) and parainfluenza virus in 12 (4.7%). The median age of the influenza group was 2 years and 3 months, and 27 (84%) of children in this group were under the age of 5. Asthma was the most common co-morbidity (4/32, 12.5%). Common clinical presentations were fever and cough (100%) with crepitations (90%). The median length of hospitalization was 6 days. Three patients developed respiratory failure, with one mortality (3.1%). One child developed infection-associated hemophagocytic syndrome. Our study demonstrated that young children had a high risk of hospitalization due to influenza pneumonia, which contributed to a significant morbidity.

Serum transforming growth factor-beta1 and epidermal growth factor in biliary atresia.

BACKGROUND AND AIM: Biliary atresia (BA) is a serious liver disease in children. Since transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) are involved in the hepatic reparative process, our objective was to investigate whether serum TGF-beta1 and serum EGF levels were associated with therapeutic outcomes in BA. METHODS: Serum levels of TGF-beta1 and EGF were determined with the ELISA method in 67 postoperative BA patients with a median age of 7 years and in 10 age-comparable healthy children. The BA patients were then divided into two groups depending on their therapeutic outcome: good outcome (jaundice-free) and poor outcome (persistent jaundice). Clinical data, serum TGF-beta1 and serum EGF levels were compared between the two groups of BA patients. Correlation analysis of serum TGF-beta1 with serum EGF was carried out. Data are expressed as mean +/- SD. RESULTS: Serum TGF-beta1 levels of BA patients were higher than those of controls (86.6 +/- 15.7 vs. 75.7 +/- 8.8 ng/ml, p = 0.0362). However, there was no difference in serum EGF between BA patients and controls (133.1 +/- 66.6 vs. 125.4 +/- 88.9 pg/ml, p = 0.744). Further subgroup analysis showed that patients with good outcomes (n = 40) had higher serum TGF-beta1 and serum EGF levels than patients with poor outcomes (TGF-beta1: 91.2 +/- 16.5 vs. 79.6 +/- 11.7 ng/ml, p = 0.002; EGF: 148.5 +/- 65.0 vs. 110.3 +/- 63.4 pg/ml, p = 0.02). In addition, serum TGF-beta1 was positively correlated with serum EGF (Pearson's r = 0.3418, p = 0.0046). CONCLUSION: Elevated serum TGF-beta1 and serum EGF levels were associated with a good outcome in BA patients. There was a positive correlation between serum TGF-beta1 and serum EGF. This suggests that the resultant TGF-beta1 and EGF pathways may be involved in the pathophysiological process in postoperative BA.

Elevated serum soluble E-selectin is associated with poor outcome and correlated with serum ALT in biliary atresia.

BACKGROUND AND AIM: Biliary atresia (BA) is a serious liver disease. Our objective was to investigate possible roles of serum soluble E-selectin (sE-selectin) in BA. METHODS: During their annual follow-up, the serum levels of sE-selectin were determined by ELISA in 53 postoperative BA patients and 10 healthy children. The patients were categorized into two groups according to their jaundice status. Comparisons of demographic data and serum sE-selectin levels between jaundice-free patients and jaundice patients were performed. Correlation analysis was carried out of serum E-selectin with serum ALT and serum GGT. Data are expressed as mean and SD (ng/mL). RESULTS: The serum sE-selectin of BA patients was higher than that of controls (114.1 +/- 44.0 vs. 88.7 +/- 22.2; p = 0.01). Further subgroup analysis showed that there was an increase in serum sE-selectin levels of BA patients with jaundice (n = 21) compared to those without jaundice (n = 32) (129.7 +/- 48.6 vs. 103.9 +/- 38.1; p = 0.035). Also, serum E-selectin was positively correlated with serum ALT, a marker for liver injury (Pearson r = 0.355, p = 0.009), but not with serum GGT (Pearson r = 0.223, p = 0.12). CONCLUSION: Elevated serum sE-selectin was associated with a poor outcome of BA. There was a positive correlation between serum sE-selectin and serum ALT. E-selectin probably plays a role in the pathophysiology of liver injury in postoperative BA.

Predictive role of serum HBsAg and HBcrAg kinetics in patients with HBeAg-negative chronic hepatitis B receiving pegylated interferon-based therapy.

OBJECTIVES: To investigate the role of serum hepatitis B core-related antigen (HBcrAg) kinetics in predicting long-term outcome of pegylated interferon (PEG-IFN)-based therapy in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). METHODS: A total of 121 Thai patients with HBeAg-negative CHB recruited from a previous randomized trial of 48-week PEG-IFN alone or combined with entecavir were enrolled. Hepatitis B surface antigen (HBsAg) and HBcrAg levels were serially examined. Paired biopsy samples taken at baseline and after treatment were assessed for intrahepatic covalently closed circular DNA (cccDNA). RESULTS: Persistent virologic remission (PVR, defined by persistent hepatitis B virus (HBV) DNA <2000 IU/mL) and HBsAg clearance at 3 years after treatment were 29% (35/121) and 9% (11/121) respectively. Baseline HBcrAg correlated with HBV DNA and cccDNA but not with HBsAg. Baseline HBsAg, as well as HBsAg and HBcrAg, declines were associated with PVR, while HBsAg decline was predictive of HBsAg clearance. High baseline antigen levels (HBsAg ≥3.4 log10 IU/mL plus HBcrAg ≥3.7 log10 U/mL) yielded high negative predictive values of PVR (45/50, 90%) and HBsAg clearance (50/50, 100%). At week 12, declines of HBsAg, HBcrAg and both antigens combined of <0.5 log10 yielded negative predictive values for PVR of 90% (71/79), 82% (61/74) and 96% (48/50) respectively. CONCLUSIONS: Quantitative HBcrAg was significantly associated with cccDNA in HBeAg-negative CHB. This novel antigen, together with HBsAg, could identify patients with low probability of PVR and HBsAg clearance in long-term follow-up.

Epstein-Barr viral DNA in serum of patients with nasopharyngeal carcinoma.

This study evaluated Epstein-Barr virus (EBV) DNA in sera of 42 patients with nasopharyngeal carcinoma (NPC) and 82 healthy individuals who had been infected previously with EBV. Thirteen of 42 NPC samples were positive for EBV DNA in their sera, whereas all 82 normal controls were negative. In addition, EBV typing between primary tumors and sera showed identical results, suggesting that serum EBV DNA represented tumor DNA. To evaluate the importance of the serum NPC DNA, clinical data and tumor phenotypes including age, sex, WHO type, EBV type, stage, tumor invasion, metastasis, and apoptosis were correlated with serum EBV DNA, and only apoptosis was found statistically significant. In conclusion, EBV DNA was detectable in the serum of some patients with NPC, represented tumor DNA, and might have clinical implications in the future.