Liver function test results and outcomes in children with acute liver failure due to dengue infection.

This retrospective study compared the liver function test results and outcomes between children with acute liver failure (ALF) due to dengue hemorrhagic fever (DHF) and due to other causes. We retrospectively reviewed patients less than 15 years old with a diagnosis of ALF admitted to 13 participating centers from different parts of Thailand for the years 2000 and 2001, and those admitted to King Chulalongkorn Memorial Hospital for the year 1997 to 2004. The diagnosis of ALF was based on prothrombin time (PT) prolongation to greater than 2 times the normal control value and the presence of encephalopathy without pre-existing liver disease. The patients were divided into 2 groups: group I (n=16) had DHF with ALF and group II (n=37) had ALF due to other causes. DHF patients had AST levels significantly higher than ALT levels. The mortality rate in group I (50%) was lower than in group II (72.9%), although the difference was not statistically significant. The non-DHF patients who died had a significantly longer duration of jaundice before the onset of encephalopathy and a significantly higher PT ratio compared to survivors. There were no significant differences in the duration of jaundice before the onset of encephalopathy and liver function between dengue patients who died and those who survived.

Seroprevalence of tetanus antibody in the Thai population: a national survey.

Tetanus is a disease with high mortality and the most important measure for effective prevention is vaccination. Tetanus immunization has been introduced to Thailand's national immunization program for 30 years. Yet, the coverage and seroprevalence of tetanus antibody in vast parts of the population has not been assessed. This study has been performed on 1,277 subjects aged between 6 months and 60 years or above from four geographically distinct provinces of Thailand. Tetanus antibody levels were measured using a commercially available ELISA kit. Most of the Thai population had immunity against tetanus. The level of antibodies to tetanus, as demonstrated by the geometric mean titer of antibody (GMT) (and 95% confidence interval) was 2.62 (2.34-2.91) IU/ml. The highest and lowest GMT was found in subjects aged between 5 and 9 years, and above 60 years of age with GMT (and 95% confidence intervals) of 3.64 (3.34-3.96) and 1.24 (0.67-2.29) IU/ml respectively. The minimum protective level of antitoxin (>0.01 IU/ml) was detected in 99.7 % of subjects. More than 90% of subjects displayed durable antibody protection levels (DAPL) (> or = 1.0 IU/ml), except for subjects above the age of 60 years (82%). According to this study, the majority of the population expresses tetanus antibody levels that can confer long term protection. Yet, considering the lowest GMT and the highest incidence of tetanus cases found in subjects aged above 60 years, re-immunization should be targeted at this age group especially if they had sustained any tetanus-prone injury.

Dynamics of HBV DNA levels, HBV mutations and biochemical parameters during antiviral therapy in a patient with HBeAg-negative chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection leads to long-term sequelae such as cirrhosis and hepatocellular carcinoma. Antiviral therapy aims at controlling the viral replication and thus, decreasing the likelihood of such complications. In this study, we evaluated the dynamics of biochemical and virological parameters over 10 years of antiviral therapy in a Thai patient with chronic HBeAg-negative HBV infection, who had relapsed after two courses of interferon alfa treatment. Lamivudine administration initially led to a significant reduction in alanine aminotransferase (ALT) and HBV DNA levels, but a subsequent emergence of YIDD mutants caused an ALT flare and a virus breakthrough. A 4-log HBV DNA decrease and normalization of the ALT level were achieved within 3 months of adefovir monotherapy without any relapse during follow-up exceeding 20 months. Thus, careful monitoring during treatment and knowledge of cross-resistance to antiviral salvage therapy are crucial for the management of patients with chronic hepatitis B.

Seroepidemiology and genotypes of hepatitis C virus in Thailand.

HCV can be classified into 6 major genotypes based on the phylogenetic analysis of the genomic sequences. The 3 major genotypes found in Thailand are 3, 1 and 6, respectively. In 2004, an epidemiological survey was carried out to evaluate the seroprevalence of HCV infections among populations aged 2-60 years in four provinces of Thailand, representing the North, Northeast, Center and South of the country, respectively. One hundred and twenty five out of 5,825 serum samples (2.15%) were positive for anti-HCV by ELISA. Fifty eight out of 100 anti-HCV positive samples (58.0%) were positive by RT-PCR of the 5'UTR. The core region of 45 representative samples was sequenced allowing classification into genotype variants 1a (6.7%), 1b (26.7%), 2a (2.2%), 2c (2.2%), 3a (51.1%), 3b (2.2%) and 6 (8.9%). This information might be crucial for public health surveillance and prevention of HCV infection.

Analysis of connective tissue growth factor promoter polymorphism in Thai children with biliary atresia.

OBJECTIVE: Connective tissue growth factor (CTGF) has been proposed to play a key role in the pathogenesis of hepatic fibrosis in biliary atresia (BA). The aim of the present study was to determine the single nucleotide polymorphism (SNP) in the promoter region of CTGF gene in a Thai population, and to investigate the possible role of CTGF promoter polymorphism in the susceptibility of BA. MATERIAL AND METHOD: Genomic DNA was obtained from 84 patients with BA and 142 healthy controls. The -447 G/C and -132 C/G in CTGF promoter were amplified and examined by amplification-refractory mutation system (ARMs) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. The test of Hardy-Weinberg equilibrium (HWE) was performed using HWE program of SNPAnalyzer. Statistical analysis was carried out with SPSS and Epi Info. RESULT: According to the previous experiment, there were two SNPs, which were at position -447 and -132 on the promoter. However, there was only one SNP at the position -447 in the Thai population. No significant differences in genotype and allele frequency were observed between BA and controls or with BA subgroups. CONCLUSION: The present study demonstrated that CTGF polymorphism at -447 G/C was not associated with BA and the jaundice status of the postoperative BA patients.

Association of serum levels of tissue inhibitors of metalloproteinase-1 with clinical outcome in children with biliary atresia.

The purpose of this study was to determine the possible role of serum levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) in the pathogenesis of the progressive inflammation and fibrosis in biliary atresia (BA). Serum concentrations of TIMP-1 were measured in 57 BA patients and 15 healthy controls using commercially available enzyme-linked immunosorbent assays. The mean ages of the BA patients and the controls were 6.1 +/- 0.6 and 6.7 +/- 1.1 years, respectively. The patients were categorized into two groups according to their clinical outcomes: patients with jaundice (total bilirubin > or = 2 mg/dl) and patients without jaundice (total bilirubin < 2 mg/dl). In our study, serum levels of TIMP-1 were significantly higher in the BA patients than in healthy subjects (4.8 +/- 0.4 vs. 3.5 +/- 0.3 ng/ml, respectively; p < 0.05). Additionally, serum levels of TIMP-1 significantly increased in the BA patients with jaundice in comparison to those without jaundice (6.3 +/- 0.7 vs. 3.1 +/- 0.3 ng/ml, respectively; p = 0.001). Patients with persistent jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Furthermore, patients with portal hypertension (PH) had higher TIMP-1 levels than those without PH (5.3 +/- 0.4 vs. 1.9 +/- 0.3 ng/ml, respectively; p < 0.001). It is concluded that serum levels of TIMP-1 increased in patients with BA. The significant increase in TIMP-1 levels is related to the presence of PH and the severity of jaundice. The elevated TIMP-1 levels may reflect the degree of hepatic fibrosis and development of PH. The data suggest that TIMP-1 may play a role in the pathophysiology of post-Kasai BA.

Pregnancy in biliary atresia after kasai operation complicated by portal hypertension.

Hepatic portoenterostomy or Kasai operation has been widely accepted as the standard therapy for biliary atresia. Recently, more female patients have grown up and reached adulthood; therefore, pregnancy in women with biliary atresia is sometimes inevitable. The authors report a 17-year-old woman with biliary atresia post Kasai operation at 3 months of age. After the operation, she became jaundice-free but developed portal hypertension with abnormal liver function. She had several episodes of esophageal variceal bleeding and was treated by beta-blocker and endoscopic sclerotherapy. Since then, she was lost to follow up for nearly 2 years. She came back again with 12 weeks of gestation with no symptoms of gastrointestinal bleeding for antenatal care. At 32 weeks of gestation, she presented with severe hematemesis from variceal bleeding and had thrombocytopenia from hypersplenism. She was treated with somatostatin analogue, fluid and blood component replacement and other supportive treatments. Cesarean section was performed when she was stable at 33 weeks of gestation. After the operation, her clinical status was improved and had no other complications. Her baby experienced complications of prematurity but improved after treatment. Pregnancy may affect the natural course of portal hypertension and worsen the clinical outcome. Pregnancy should be avoided in patients with portal hypertension, however it is not contraindicated. Pregnancy in biliary atresia patients needs intensive prenatal care.

Incidence and clinical manifestations of rotavirus infection among children with acute diarrhea admitted at Buri Ram Hospital, Thailand.

To study the incidence and clinical manifestations of rotavirus among children at Buri Ram Hospital, admitted with the diagnosis of acute diarrhea between November 2005 and February 2006. In the course of a cross sectional descriptive study, 103 stool samples obtained from inpatients below the age of 5 years were examined for rotavirus by RT- PCR. Data on clinical manifestations, complications, administration of antibiotics, length of admission and hospital cost were obtained by means of questionnaires distributed among physicians. The statistics used were presented as percentage, mean and 95% confidence interval, while chi-square and unpaired t-test were used to establish significant differences at p < 0.05. Rotavirus was detected in 45 of 103 stool samples (43.68%, 95%CI = 33.93, 53.81). No significant differences were found between clinical manifestations of children with rotavirus infection and non-rotavirus infection as both groups displayed acute watery diarrhea (p = 0.33), fever (p = 0.80), nausea or vomiting (p = 0.08), predominant lymphocytes (p = 0.54), absence of red blood cells (p = 0.63) or white blood cells (p = 0.57) in the stool examination, moderate or severe dehydration (p = 0.06), lactose intolerance (p = 0.41), hypokalemia (p = 0.55), metabolic acidosis (0.18) Administration of antibiotics was significantly reduced for treatment of rotavirus acute diarrhea (31.1% vs 63.8%, p = 0.001). Hospital cost and length of admission were significantly reduced in rotavirus acute diarrhea (1,845.04 baht vs 2,297.00 baht, p < 0.01) (2.09 days vs 2.81 days, p < 0.001). Compared to previous studies, no differences were found in the percentage of rotavirus acute diarrhea. Rotavirus infection is a major cause for hospitalization of children below the age of 5 years with acute diarrhea. Clinical characteristics of rotavirus acute diarrhea were not significantly different from those due to other etiologies. Diagnosis of rotavirus infection should be based on various clinical manifestations and specific laboratory methods. Further studies on the cost benefit of rotavirus vaccine in Thailand ought to be performed before implementing a universal vaccination program.

An evidence of intestinal mucosal injury in dengue infection.

The aim of this study was to determine whether there is an association between dengue infection and intestinal mucosal injury. Serum levels of intestinal fatty acid binding protein (I-FABP) were used as a specific marker for mucosal injury. The diagnosis of all patients was serologically confirmed by anti-dengue IgG or IgM. Serum I-FABP levels of 120 patients were determined and compared to those of 25 controls using ELISA. In order to investigate serum I-FABP among dengue patients, they were categorized into 5 groups according to disease severity: dengue fever (DF), dengue hemorrhagic fever (DHF) grade I through DHF grade IV. The dengue patients had higher levels of serum I-FABP compared to 25 controls (408.0 +/- 499.3 vs 124.72 +/- 147.81 pg/ml, p=0.006). The patients with DHF grade IV had the highest levels of serum I-FABP, ALT, and AST compared to the other groups. However, there were no differences in serum I-FABP, ALT, and AST levels among patients with DF, DHF grade I, grade II, and grade III. Evidence of intestinal mucosal injury in patients with dengue infection was demonstrated. Patients with DHF grade IV had high serum I-FABP levels and had associated liver injury.

Serum nitric oxide in children with dengue infection.

One hundred and ten patients (M/F = 67/43) from King Chulalongkorn Memorial Hospital and the provincial hospitals of Uttaradit, Ayudhaya, and Sakonnakorn, who were clinically diagnosed with dengue infection and serologically confirmed by ELISA anti-Dengue IgM and IgG were recruited. Their serum NO level was measured using commercially available assay kits to investigate its correlation with the severity of the dengue infection: dengue fever (DF), DHF I/II, and DHF III/IV or dengue shock syndrome (DSS). Serum NO levels were also measured in 38 healthy controls (M/F = 19/19). Serum NO levels in dengue patients were lower than those of the controls (control = 168.18 +/- 24.10 micromol/l, DF = 124.94 +/- 36.79 micromol/l, DHF I/II = 99.69 +/- 33.42 micromol/l, and DHF III/IV = 120.63 +/- 46.26 micromol/l; p < 0.05). Serum NO levels in patients with DHF I/II were significantly lower than in those with DHF III/IV. These preliminary data revealed that levels of serum NO in dengue patients were significantly lower than those of normal controls. Patients with DSS had higher NO levels than those with DHF I/II. The decreased NO in dengue patients could be due to endothelial damage rendering the endothelium incapable of producing NO. Endothelial function seems to play a role in the pathogenesis of dengue infection. Further studies are required to see whether serum NO levels could play a role in the course of the disease and could help predict the severity of dengue infection.

Prevalence of hepatitis A virus infection in children with biliary atresia.

This study aimed at identifying the prevalence of hepatitis A virus (HAV) infection in children with biliary atresia (BA). Blood samples were collected from children with BA whom had undergone portoenterostomy and attended the pediatric liver clinic, King Chulalongkorn Memorial Hospital between May 2002 and May 2003. Seventy-seven patients, 45 females and 32 males, ages ranging from 0.2-19 years (mean +/- SD = 5.9 +/- 4.6 years) were enrolled in the study. The HAV seropositivity rate of patients aged <10 years and > or =10 years were 13.1% and 25%, respectively. The seropositivity rate of patients with favorable outcomes (total bilirubin level < or =2 mg/dl) and unfavorable outcome (total bilirubin level >2 mg/dl) were 17.5% and 13.5%, respectively, which were not statistically different (p = 0.6). Children suffering from BA with failed portoenterostomy are at risk of developing severe liver damage at an early age. In these patients a superimposed acute liver infection due to a hepatitis virus, including HAV, may affect liver function and lead to particularly severe disease. The effectiveness of HAV immunization in this particular group of children merits further study.

Hospital-based epidemiology of childhood cholera: a 6-year review in a university hospital in Bangkok, Thailand.

BACKGROUND: Cholera is the cause of severe acute watery diarrhea. Without proper fluid therapy, severe cholera kills half of the affected patients. In terms of epidemiology and surveillance, up-to-date information of this disease in each country is essential. OBJECTIVES: To evaluate 1) prevalence, serogroups, serotypes and antimicrobial susceptibility pattern of V cholerae, and 2) demographic data and clinical manifestation of pediatric patients with cholera. MATERIAL AND METHOD: Microbiogical records of children aged 0-15 years with cholera, who were treated at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 1995 and December 2000 were retrospectively reviewed Serogroups, serotypes, and antimicrobial susceptibility of V. cholerae were studied Medical records of children with positive stool cultures for V. cholerae were reviewed in terms of demographic data, clinical manifestation of the patients. RESULTS: Of 11,709 stool culture specimens, pathogenic bacteria were found in 1,745 specimens and 95 specimens (5.4%) were positive for V. cholerae. V. cholerae O1 and non-O1/non-O139 were found in 52.6% and 47.4%, respectively. Common serotypes of V. cholorae O1 were Ogawa. Antimicrobial susceptibility of the pathogens to co-trimoxazole, ampicillin, ceftriaxone, ciprofloxacin and gentamicin were 55.0%, 56.4%, 91.4%, 92.5% and 94.9%, respectively. Age distribution of the patients ranged from 2 months to 15 years with an average age of 2.92 years. Clinical manifestations included acute watery diarrhea (92.8%), vomiting (56.4%), fever (37.5%), hypotension (19.6%) and abdominal pain (3.8%). Stool leukocytes were microscopically detected in 20% of the patients. No patients died in the present study. CONCLUSION: Childhood cholera in Thailand still exists. Most patients presented with acute watery diarrhea. Regarding antimicrobial susceptibility pattern, ceftriaxone and quinolones are appropriate drugs of choice.

Rectal prolapse associated with cytomegalovirus pseudomembranous colitis in a child infected by human immunodeficiency virus.

We report a newly recognized presentation of cytomegalovirus (CMV) enterocolitis in a 4-year-old girl with newly diagnosed HIV disease who presented with rectal prolapse. Gross findings showed multiple whitish punctate lesions. An endoscopic examination revealed multiple shallow ulcers and pseudomembranes along the colon. A biopsy from colonic tissues demonstrated CMV-like inclusion bodies. A direct immunofluorescence assay using specific CMV monoclonal antibody was positive for CMV-infected cells in specimens from the rectal smear.

The effect of phenobarbital on the accuracy of technetium-99m diisopropyl iminodiacetic acid hepatobiliary scintigraphy in differentiating biliary atresia from neonatal hepatitis syndrome.

Biliary atresia (BA) and neonatal hepatitis syndrome (NHS) are major causes of cholestatic jaundice in infancy. Technetium-99m diisopropyl iminodiacetic acid hepatobiliary scintigraphy (99mTc-DISIDA scan) is widely used in the differentiation of these two entities. The objective of this study was to evaluate the effect of phenobarbital premedication on the accuracy of 99mTc-DISIDA scan. Ninety-five cholestatic infants (38 females and 57 males) with an age range of 2 weeks to 4 months (mean 2.1 mo) who underwent 99mTc-DISIDA scan testing were retrospectively reviewed. The patients were divided into 3 groups according to the history of phenobarbital administration prior to 99mTc-DISIDA scan examination. Group 1 (n = 48), group 2 (n = 29), and group 3 (n = 18) received phenobarbital at the dosage of 5 mg/kg/day for at least 5 days, less than 5 mg/kg/day or less than 5 days, and no premedication, respectively. The accuracy of 99mTc-DISIDA scan in differentiating BA from NHS in group 1, 2, and 3 was 72.92 per cent, 89.66 per cent, and 100 per cent, respectively. No significant difference was seen between the patients who received and did not receive phenobarbital in terms of age at presentation, age at onset of jaundice, and liver function tests. In conclusion, phenobarbital therapy may not be necessary prior to 99mTc-DISIDA scan examination in the evaluation of cholestatic infants and thus a delay in diagnosis and surgical therapy of BA can be avoided.

Gastrointestinal manifestations of cow's milk protein allergy during the first year of life.

BACKGROUND: Cow's milk protein sensitive enteropathy (CMPSE) is a common condition in the first year of life. Clinically CMPSE usually presents with symptoms like vomiting, chronic diarrhea, mucous bloody diarrhea and hematemesis. More unusual symptoms associated with CMPSE are infantile colic, gastroesophageal reflux and chronic constipation. The objective of this study was to assess the gastrointestinal manifestations and allergic march in CMPSE patients. METHOD: The authors reviewed the records of 10 CMPSE patients observed by the Gastrointestinal Unit at King Chulalongkorn Memorial Hospital from 1997-2001 including patient characteristics, laboratory investigations, endoscopy and follow-up outcome. RESULTS: Of 10 CMPSE patients, the median age of CMPSE onset was 3.5 months. The gastrointestinal manifestations were hematemesis (n = 6), mucous bloody diarrhea (n = 3) and chronic watery diarrhea (n = 2). Exclusively breast-fed infants seemed to have more delayed onset of symptoms than those who were not. Anemia (n = 3), high serum IgE (n = 4) and positive skin prick test for cow's milk (n = 5) were found. Neither peripheral eosinophilia nor hypoalbuminemia was found. Endoscopy revealed acute and chronic gastritis. Treatment was successful by changing to soy or extensive hydrolysate formula with mean duration of cow's milk intolerance of 24 months. In 2-year follow-up, three of ten patients who had high serum IgE level developed allergic rhinitis and eczema. CONCLUSION: CMPSE can be manifested in various symptoms. Exclusive breast feeding for more than 4 months can postpone the onset of CMPSE. Serum IgE or specific IgE level to cow's milk protein may identify the atopic career of CMPSE individuals.

Resident recruitment: what are good predictors for performance during pediatric residency training?

The authors evaluated the value of the Cumulative Grade Point Average (GPAX), letters of recommendation and personal interview in predicting performance of first year residents at the Department of Pediatrics, Faculty of Medicine, Chulalongkorn University. The pre-residency data of 25 first year pediatric residents were compared to the results of the Pediatric In-training Examination (PIE) and clinical evaluation by faculty during the first 7 months of training. The Clinical Performance Rating Score (CPRS) developed by the Royal College of Pediatricians of Thailand was used for clinical performance evaluation. GPAX correlated strongly with PIE score (r = 0.69, p < 0.001) while letters or recommendation and interview score were not predictive. For the majority of residents who graduated from Chulalongkorn University, including the undergraduate program into the regression model improved this association (r = 0.90, p < 0.001). Interview score correlated moderately (r = 0.49, p = 0.02) with clinical performance measured by CPRS which entailed the evaluator to assess a resident in 6 specific areas. GPAX and letters of recommendation showed a trend toward positive correlation with clinical performance, but these associations were weak (r = 0.32-0.39). Further analysis of letters of recommendation found a significant difference between the score given by evaluators in community hospital settings compared to the score given by medical school faculty or evaluators in large regional or provincial hospitals. The authors conclude that the cognitive function of pediatric resident candidates can be assessed reliably by GPAX. Research on how to adjust for the variability of GPAX given by an individual undergraduate program will improve the residency selection process. A structured interview may correlate better with global clinical performance than GPAX or letters of recommendation but all methods are at best moderately predictive of clinical performance. Improvement can be made by continuous evaluation and adjustment of the selection process.

Declining hepatitis A seroprevalence among medical students in Bangkok, Thailand, 1981-2001.

The severity of clinical symptoms following hepatitis A virus (HAV) infection is age dependent. Hepatitis A in children is mostly an asymptomatic disease while adolescents and adults usually show symptoms of clinical hepatitis. Improved personal hygiene and environmental sanitation has led to a decline in natural immunity acquired in childhood, creating a population of susceptible adults. In the past decade, the incidence and prevalence of hepatitis A disease in Thailand have decreased significantly. In this study, we used enzyme-linked immunosorbent assay to determine the prevalence of anti-HAV antibodies among medical students at two different time points in 1996 and 2001. We then compared these results with data from previous studies in 1981 and 1992. The seroprevalence was 73.01%, 30.23%, 16.67% and 6.67% in 1981, 1992, 1996 and 2001, respectively. A significant decline has happened over the past two decades (p < 0.001). Considering the decreasing immunity to HAV in the younger generations, more cases of symptomatic HAV infection could be anticipated. Further seroprevalence studies in other adolescence groups from different socioeconomic status are needed to elucidate the current situation of HAV infection in the young generation more comprehensively and to develop an appropriate prevention program.

Management of chronic hepatitis B and C virus infections.

Hepatitis B and C virus (HBV and HCV) infections present an important health problem causing significant morbidity and mortality on a worldwide scale. The younger the subjects infected, the higher the risk predisposing to progression towards chronic infection. Treatment of chronic HBV and HCV infections is aimed at reducing hepatic inflammation and thus improving the symptoms, decreasing the likelihood of long-term sequelae such as hepatocellular carcinoma, and increasing the survival rate. Interferon accelerates the spontaneous course of chronic HBV infection in children with greater disease activity and lower levels of replication. There is limited information on the use of lamivudine and its long-term benefit in children with chronic HBV infection. The response of combination therapy with IFN and ribavirin in children with chronic HCV infection is still under investigation. The long-term clinical and virological effects of various drugs used in chronic HBV and HCV infections on children remain to be evaluated.