Clinical Predictors of Liver Fibrosis in Patients With Chronic Hepatitis B Virus Infection From Children to Adults.

Background: This study aimed to elucidate predictors of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection. Methods: Transient elastography was performed to define liver stiffness in 533 patients with chronic HBV infection (mean age ± standard deviation, 30.72 ± 0.57 years). Protein array was performed on serum samples and lysates of Huh7 cells transfected with HBV mutants; the results were confirmed by enzyme-linked immunosorbent assay. Single-nucleotide polymorphisms in the gene encoding interleukin 1ß (IL-1ß) were examined in patients with chronic HBV infection with and without liver fibrosis. Results: Male sex, age ≥18 years, and serum α-fetoprotein level >3.6 ng/mL were independent predictors of a liver stiffness measurement of ≥7 kPa (P = .005, .019, and <.001, respectively). HBV e antigen (HBeAg)-negative hepatitis is associated with increased liver stiffness (P < .001). Elevation of the serum IL-1ß level was demonstrated in subjects with liver fibrosis. IL-1ß was upregulated in Huh7 cells transfected with HBV mutants associated with HBeAg-negative hepatitis. The AA genotype at rs16944 and the CC genotype at rs1143627 in the gene encoding IL-1ß were associated with higher serum IL-1ß levels and liver fibrosis. Conclusions: Male sex, age ≥18 years, elevated α-fetoprotein level, and HBeAg-negative hepatitis are risk factors for liver fibrosis. IL-1ß is involved in the progression of liver fibrosis in subjects with HBeAg-negative hepatitis.

Gastrointestinal complications and extraintestinal manifestations of inflammatory bowel disease in Taiwan: A population-based study.

BACKGROUND: Despite a rising incidence of inflammatory bowel disease (IBD) in Taiwan, the clinical presentation of IBDs in this population has yet to be well characterized. Therefore, the aim of our study was to identify and describe the clinical features of gastrointestinal (GI) complications and extraintestinal manifestations (EIMs) of IBDs in the Taiwanese population. METHODS: We conducted a retrospective study between 1998 and 2011, with relevant medical information extracted from the National Health Insurance Research Database. The diagnoses of IBD, GI complications, and EIMs were defined from the health registry using the appropriate International Classification of Diseases 9 codes. RESULTS: A total of 3153 patients with IBDs were identified: 611 with Crohn's disease (CD) and 2542 with ulcerative colitis, with GI complications and EIMs identified in 22.2% and 11.9% of cases, respectively. CD was associated with an increased incidence of intestinal fistula, perforation, obstruction, peritonitis and perianal disease, and ulcerative colitis with benign neoplasm of the colon. Colorectal cancer developed in 0.35% of patients. Children with CD characteristically have more complex intestinal complications. The prevalence of EIMs was higher in females and in CD, with peripheral arthritis identified as the most common EIMs, overall. The rate of major EIMs affecting the articular, cutaneous, and visual systems was lower than the rate reported in Western countries. CONCLUSION: Our study found that CD had a more complicated course, with a higher incidence of GI complications and EIMs. However, the prevalence of intestinal complications, perianal disease, and major EIMs was less common than in Western countries. This study provided a distinct clinical feature of IBD in Taiwan.

Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer.

BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. METHODS: We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. RESULTS: Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P < .001 and 1986-1992 vs 1984-1986; P < .002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC. CONCLUSIONS: Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer.

Induced pluripotent stem cells without c-Myc reduce airway responsiveness and allergic reaction in sensitized mice.

BACKGROUND: Allergic disorders have increased substantially in recent years. Asthma is characterized by airway damage and remodeling. Reprogramming induced pluripotent stem cells (iPSCs) from adult somatic cells transfected by Oct-4/Sox-2/Klf-4, but not c-Myc, has shown the potential of embryonic-like cells. These cells have potential for multilineage differentiation and provide a resource for stem cell-based utility. However, the therapeutic potential of iPSCs without c-Myc (iPSC-w/o-c-Myc) in allergic diseases and airway hyperresponsiveness has not been investigated. The aim of this study was to evaluate the therapeutic effect of iPSC-w/o-c-Myc transplantation in a murine asthma model. METHODS: BALB/c mice were sensitized with alum-adsorbed ovalbumin (OVA) and then challenged with aerosolized OVA. Phosphate-buffered saline or iPSC-w/o-c-Myc was then intravenously injected after inhalation. Serum allergen-specific antibody levels, airway hyperresponsiveness, cytokine levels in spleen cells and bronchoalveolar lavage fluid (BALF), and cellular distribution in BALF were then examined. RESULTS: Treatment with iPSC-w/o-c-Myc effectively suppressed both Th1 and Th2 antibody responses, which was characterized by reduction in serum allergen-specific IgE, IgG, IgG1, and IgG2a levels as well as in interleukin-5 and interferon-γ levels in BALF and in OVA-incubated splenocytes. Meanwhile, regulatory cytokine, interleukin-10, was enhanced. Transplantation of iPSC-w/o-c-Myc also significantly attenuated cellular infiltration in BALF and allergic airway hyperresponsiveness. However, no tumor formation was observed 6 months after transplantation. CONCLUSIONS: Administration of iPSC-w/o-c-Myc not only inhibited Th1 inflammatory responses but also had therapeutic effects on systemic allergic responses and airway hyperresponsiveness. iPSC-w/o-c-Myc transplantation may be a potential modality for treating allergic reactions and bronchial asthma.

Prevalence of functional gastrointestinal disorders in Taiwan: questionnaire-based survey for adults based on the Rome III criteria.

Functional gastrointestinal disorders (FGID) are a group of disorders of the digestive system in which the chronic or recurrent symptoms cannot be explained by the presence of structural or tissue abnormality. This survey used a modified Rome III questionnaire on the health and nutrition status of a general population in Taiwan during 2005-2008. A total of 4,275 responders completed the questionnaire. The sample was evenly distributed for men (n=2,137) and women (n=2,138). The prevalence of FGID was 26.2%. Unspecified functional bowel disorder was the most prevalent (8.9%). The second was functional dyspepsia (5.3%), and the third were irritable bowel syndrome (4.4%) and functional constipation (4.4%). Women had a greater prevalence than males (33.2% compared to 22.4%, p<0.05) with regards to total FGID. Most categories of FGID were significantly prominent in women, except functional diarrhea. The FGID groups took fewer servings of vegetables and fruits than the non-FGID group each day (vegetables 2.51 vs 2.70, p<0.001; fruits 0.82 vs 0.91, p<0.001). Smoking, alcohol consumption, and betel nut chewing had no significant impaction on prevalence of FGID. The mean BSRS (brief-symptom rating scale) for screening depression and suicide ideation was higher in the FGID group (2.86 vs 1.63, p<0.001). In conclusion, FGID diagnosed with Rome III criteria are not uncommon in Taiwan's general population. Subjects who met the Rome III criteria for FGID in Taiwan were younger, had less vegetables and fruits intake, higher BSRS scores and were of greater female predominance.

Pediatric gastrointestinal endoscopic sedation: a 2010 nationwide survey in Taiwan.

BACKGROUND: There is insufficient data on pediatric endoscopic sedation practices worldwide. This study aimed to assess nationwide data on the current pediatric endoscopic sedation practices in Taiwan. METHODS: Members of the Taiwan Society of Pediatric Gastroenterology Hepatology and Nutrition in 2010 were asked to participate in an 18-item questionnaire survey regarding current sedation practices for diagnostic esophagogastric-duodenoscopy (EGD). RESULTS: A total of 22 of 32 questionnaires were returned for a response rate of 68.8%. A majority (86.4%) of the respondents practiced in a medical center hospital setting, and 72.7% preferred sedation during EGD. The proportions of respondents applying sedative methods in cases aged < 1, 1∼12, and > 12 years old were 85.7%, 100%, and 23.7% respectively. Ketamine (27.8%) and midazolam with meperidine (22.2%) were the most commonly applied sedation agents, while the percentage of respondents using regimens that included propofol was 11.2%. Comparing complications between EGD with and without sedation, only hypoxia (Wilcoxon statistics=347.00, p=0.003) was significantly more common in sedated patients. The endoscopists' satisfaction rating was greater among respondents using sedation compared to those without (visual analog scale 9 vs. 7; p=0.0001). CONCLUSION: A majority of pediatric EGD in Taiwan was performed under sedation and applied more often to younger children. Endoscopists were more satisfied during EGD when practicing sedation. This survey should help formulate updated practice guidelines and policies regarding endoscopic sedation.

Suppression of furin by interferon-γ and the impact on hepatitis B virus antigen biosynthesis in human hepatocytes.

The roles of furin and intrahepatic cytokines in chronic heptatitis B virus (HBV) infection remain largely unknown. Here, we examined the relations between furin, IL-10, IL-12ß, interferon (IFN)-γ, programed death (PD)-1, programed death ligand (PD-L)1, and the suppression of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) biosynthesis. Liver biopsies were performed on 20 chronically HBV-infected (15 HBeAg-positive and 5 HBeAg-negative) patients to assess liver inflammation/fibrosis, and mRNA levels of furin, IL-10, IL-12ß, IFN-γ, PD-1, and PD-L1 were assessed by quantitative real-time PCR. IFN-γ mRNA abundance was associated with lower furin mRNA levels and higher PD-1 and PD-L1 mRNA levels in liver tissue from HBeAg-positive patients. IL-10 and IL-12ß mRNA levels positively correlated with IFN-γ expression levels (P < 0.05). PD-L1 and furin mRNA levels were further assessed in IFN-γ-stimulated hepatoma cell lines with (HepG2.2.15 cells) and without (HepG2 and Huh7 cells) HBV replication. IFN-γ enhanced PD-L1 expression in hepatoma cells. In HepG2.2.15 cells, IFN-γ further suppressed furin and HBeAg expression. Furin inhibition and knockdown in HepG2.2.15 cells also down-regulated HBeAg and HBsAg biosynthesis. These data suggest that IFN-γ modulates the inflammatory response to avoid excessive hepatocyte damage through the enhancement of PD-1/PD-L1 expression, whereas furin suppression may contribute to a reduction in HBeAg/HBsAg biosynthesis.

Profile of nucleotides and nucleosides in Taiwanese human milk.

BACKGROUND: Human milk-borne nucleotides and their related metabolic products have been reported to have important physiological roles in breast-fed infants. The purpose of this study was to measure the concentrations of free nucleotides and nucleosides in human milk from Taiwanese women. METHODS: A total of 24 individual milk specimens were collected from women in Taipei and Kaohsiung, at four stages of lactation. Vegetarian or non-vegetarian dietary patterns were recorded. The samples were analyzed for nucleotides and nucleosides by high-performance liquid chromatography. RESULTS: The mean (±standard deviation) free nucleotide and nucleoside concentrations in Taiwanese human milk were 213.13 ± 76.26 µmol/L and 16.38 ± 7.11 µmol/L. The predominant nucleotide was cytidine diphosphate for almost all samples, regardless of the location, stage of lactation, or dietary status of the subjects. Overall, the mean concentrations of cytidine diphosphate, cytidine monophosphate, uridine monophosphate, guanosine monophosphate, adenosine monophosphate, and inosine monophosphate, in milk samples were 129.86 µmol/L, 49.10 µmol/L, 5.60 µmol/L, 0.82 µmol/L, 2.96 µmol/L, and 25.25 µmol/L, respectively (equivalent to 61.0%, 23.1%, 2.6%, 0.4%, 1.0%, and 11.9% of free nucleotide composition). In free nucleosides, cytidine and uridine were predominant during all stages of lactation. The average concentrations of cytidine, uridine, adenosine, guanosine, and inosine, in milk samples were 9.25 µmol/L, 6.33 µmol/L, 0.18 µmol/L, 0.36 µmol/L, and 0.23 µmol/L, respectively (equivalent to 56.5%, 38.7%, 1.1%, 2.2%, and 1.4% of free nucleoside composition). Comparing vegetarian and non-vegetarian statuses, it was found that the total free nucleotide concentration was high in the vegetarian group (p=0.037). CONCLUSION: Our data showed a wide range of concentrations of individual nucleotides and nucleosides in Taiwanese human milk. Unique dietary status could affect the nucleotide and nucleoside levels in human milk, especially the nucleotides in our study. However, the mechanism of modulation of nucleotide and nucleoside levels in human milk is not clear.

Delirium due to scopolamine patch in a 4-year-old boy.

The scopolamine patch is usually used to reduce postoperative nausea and vomiting associated with anesthesia and/or surgery. It is also commonly used for the prevention of motion sickness. Transdermal scopolamine patches have been used for decades and there are few reports in the literature of toxic psychosis associated with the product. Most documented cases of acute psychosis following administration of scopolamine or other anticholinergic agents have been from the adult population. Here we present a 4-year-old boy with deteriorated cognitive function and changed mental status acutely. Besides flushing skin and psychotic behaviors including bizarre actions, hallucinations, aggressive behavior, hyperactivity, and incoherent speech were also noticed. Symptoms and signs were resolved after removal of scopolamine patch and conservative management. This case is possibly one of the youngest patients to exhibit such toxic effects. We hope to relay information about common agents with anticholinergic effects to clinical practitioners and remind that drug-induced psychosis should be considered in children with acute changes in behavior.

Effects of the infant stool color card screening program on 5-year outcome of biliary atresia in Taiwan.

UNLABELLED: In Taiwan, a screening system using an infant stool color card to promote the early diagnosis of biliary atresia (BA) was established in 2002. This study aimed to investigate the 5-year outcome of BA before and after using the screening program. BA patients were divided into three cohorts according to their birth dates. The patients in cohort A (n = 89) were born before the stool card screening program (1990-2000); those in cohort B (n = 28) were screened by the stool card regional screening program (2002-2003); and those in cohort C (n = 74) were screened by the stool card universal screening program (2004-2005). The relative odds ratios were computed using logistic regression to compare the different factors affecting survival time. The rate of age at Kasai operation <60 days was 49.4% and 65.7% in cohorts A and B+C, respectively (P = 0.02). The jaundice-free (total serum bilirubin <2.0 mg/dL) rate 3 months after surgery was 34.8% and 60.8% in cohorts A and B+C, respectively (P < 0.001). The 3-year jaundice-free survival rate with native liver was 31.5% in cohort A and 56.9% in cohort B+C (P < 0.001), whereas the 3-year overall survival rates were 64.0% and 89.2%, respectively (P < 0.001). The 5-year jaundice-free survival rate with native liver was 27.3% in cohort A and 64.3% in cohort B (P < 0.001), and the 5-year overall survival rates were 55.7% and 89.3%, respectively (P < 0.001). CONCLUSION: The stool color card screening program for BA allows for earlier Kasai operation, which increases the jaundice-free rate at 3 months postsurgery. With higher surgical success rates, the 3- and 5-year outcome of BA patients in Taiwan improves remarkably.

Hepatic steatosis: an experimental model for quantification.

Non-alcoholic fatty liver disease (NAFLD) has gained extensive research attention, and the relationship with cardiovascular disease is of great clinical interest. Traditionally, diagnosis of NAFLD is dependent on liver biopsy, but the heterogeneous fatty infiltration may confound the diagnosis. The main purpose of this study was to introduce an experimental method to quantify hepatic steatosis in rats, and to provide an alternative experimental model in following researches. Twenty male Sprague-Dawley rats (6-week-old) randomly divided into two groups and were fed by the commercial chow diet and the choline/methionine deficient (CMD) diet for 2 weeks. All rats underwent a complete morphological measurements and blood biochemistry studies at the beginning of study and 2 weeks later. Two Chinese acupuncture needles were inserted percutaneously into the liver of each rat under general anesthesia for bioelectric impedance analysis (BIA). The acupuncture needles were carefully wrapped by non-conducting sheathes, and were inserted at left subcostal margin and the lower limb of the left rib with the depth of 0.5 cm. All rats were sacrificed with their livers isolated, sampled, sliced and well prepared after BIA measurements were completed. All pathological specimens were interpreted by one single hepatopathologist. With similar weight in the beginning of study, CMD rats were significantly lighter in weight, but had significantly higher liver weight/body weight ratio (5.5% (4.5-6.7%) vs. 4.6% (4.2-5.7%), p=0.015) 2 weeks later. Serum levels of ALT: 77 (64-125) vs. 53 (40-167) IU/ml, p=0.019, and AST: 370 (324-420) vs. 282 (217-365) IU/ml, p<0.001, were significantly higher in CMD rats, but not the lipid profile. Hepatic steatosis was more advanced: 3 (0-3) vs. 0 (0-0), p<0.001, in pathological staging, and the BIA readings were significantly lower: 15.3 (12-25) vs. 30.5 (14-66) mΩ, p=0.004, in CMD rats. Steatosis score was significantly correlated with BIA readings (p<0.001, γ=-0.52). In conclusion, this experimental model enables researchers to quantify hepatic steatosis with less concern of heterogeneous fatty infiltration, and providing a continuous but not categorical measurement of hepatic steatosis.

An uncommon cause of abdominal pain and diarrhea-gastrinoma in an adolescent.

Gastrinoma is a hormone-secreting tumor associated with the Zollinger-Ellison syndrome. It is quite rare among children, and it is also uncommon in locations other than the pancreas and the duodenum in the pediatric group. Here, we describe an adolescent male, presenting with recurrent secretory diarrhea and abdominal cramping pain, who had a solitary gastrinoma in the lesser sac, close to the stomach. The prognosis was good after complete resection.

Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study.

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts. METHODS: Data on 1958 patients with hepatocellular carcinoma who were aged 6-29 years at diagnosis in Taiwan between 1983 and 2004 were collected from two national hepatocellular carcinoma registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analyzed by using Poisson regression models. All statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination program were compared for HBV immunization characteristics during infancy and prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) serostatus. RESULTS: Hepatocellular carcinoma incidence was statistically significantly lower among children aged 6-19 years in vaccinated compared with unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709 304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person-years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for persons vaccinated at birth). The risk of developing hepatocellular carcinoma for vaccinated cohorts was statistically significantly associated with incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with prenatal maternal HBeAg seropositivity (with administration of hepatitis B immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR = 9.43, 95% CI = 3.54 to 25.11). CONCLUSION: The prevention of hepatocellular carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure to prevent hepatocellular carcinoma results mostly from unsuccessful control of HBV infection by highly infectious mothers.

Universal screening for biliary atresia using an infant stool color card in Taiwan.

UNLABELLED: Biliary atresia is the most common cause of death from liver disease in children. Although the Kasai operation before 60 days of age can significantly improve prognosis, delay in referral and surgery remains a formidable problem worldwide because of difficulties in differentiating it from benign prolonged neonatal jaundice. We established a universal screening system using an infant stool color card to promote the early diagnosis and treatment of biliary atresia. After a pilot regional study in 2002-2003, a national stool color screening system was established by integrating the infant stool color card into the child health booklet given to every neonate in Taiwan since 2004. Within 24 hours of the discovery of an abnormal stool color, this event is reported to the registry center. The annual incidence of biliary atresia per 10,000 live births in 2004 and 2005 was 1.85 (40/216,419) and 1.70 (35/205,854), respectively. The sensitivity of detecting biliary atresia using stool cards before 60 days of age was 72.5% in 2004, which improved to 97.1% in 2005. The national rate of the Kasai operation before 60 days of age increased from 60% in 2004 to 74.3% in 2005. The jaundice-free rate (<2 mg/dL) at 3 months after the Kasai operation among infants with biliary atresia in 2004-2005 was 59.5% (44 of 74), significantly higher than the historical data of 37.0% in 1976-2000 before the stool card screening program (P = 0.002). CONCLUSION: Universal screening using the stool color cards can enhance earlier referral, which may ultimately lead to timely performance of the Kasai operation and better postoperative outcome in infants with biliary atresia.

Childhood functional abdominal pain and Helicobacter pylori infection.

BACKGROUND/AIMS: Like functional gastrointestinal disorders in adults, the exact etiology of childhood functional abdominal pain (FAP) is unclear. Among those proposed etiologies, chronic Helicobacter pylori (HP) infection plays an important role. Therefore, we conducted this study to investigate the relationship of childhood FAP and chronic HP infection. METHODOLOGY: From 1998 to 2000, pediatric patients referred to our outpatient department under the impression of recurrent abdominal pain were carefully evaluated, and only subjects with FAP were recruited for study. Endoscopic examinations for rapid urease test and histology were performed in each patient, and [13C]-urea breath test was also performed in each patient. Twelve months later, all the procedures were repeated again for follow-up study. Status of FAP and HP infection of each subject was re-evaluated again for further comparisons. RESULTS: In total, 135 patients participated in the primary survey, and 114 of them were successfully followed 12 months later. The results of primary endoscopic examinations were as follows: 43.7% normal results, 19.3% esophagitis, 15.6% gastroduodenitis, 13.3% peptic ulcer diseases (PUD), and 7.4% nodular gastritis. The overall prevalence of HP infection was 23.7% (32/135) at the primary survey. At the follow-up study, 77 (67.5%) patients still suffered from FAP. Persistence of FAP was noted among 59 of 84 (70.2%) non-HP infected patients, and in 13 (86.7%) of the 15 HP-infected, non-eradicated patients in the follow-up study, which did not show statistical significance (P=0.13). CONCLUSIONS: Aside from subjects with PUD, 72.7% of FAP children suffered from similar symptoms during the 12-month follow-up, and HP infection status did not significantly influence the disease courses.

The diagnostic value of serum interleukins 6 and 8 in children with acute gastroenteritis.

OBJECTIVES: Early identification of the pathogen causing acute gastroenteritis in children helps the physicians managing the disease and prevents unnecessary antibiotic treatment. C-reactive protein (CRP), interleukin (IL) 6 and IL-8 play a major role in immune responses and have been studied in a large number of infectious and noninfectious inflammatory diseases. The purpose of this study was to determine the serum IL-6 and IL-8 concentrations early in the course of acute gastroenteritis to see if these cytokines were useful diagnostic markers in differentiating viral from bacterial gastroenteritis. METHODS: Interleukin 6, IL-8 and CRP were measured in 18 patients with bacterial gastroenteritis, 21 patients with viral gastroenteritis and 17 healthy children. RESULTS: Interleukin 6 and CRP concentrations in patients with bacterial gastroenteritis were significantly higher than those in patients with viral gastroenteritis and healthy controls (P < 0.001). IL-8 concentrations in patients with viral and bacterial gastroenteritis were both increased and were not statistically different. IL-6 and IL-8 levels had diagnostic sensitivities of 79% and 50% and specificities of 86% and 67%, respectively. The combination of IL-6 and CRP had a sensitivity of 94%, specificity of 71%, a positive predictive value of 74% and a negative predictive value of 93.75%. CONCLUSIONS: Serum IL-6 may be a useful marker for early differentiation of viral and bacterial gastroenteritis in children, especially in combination with CRP.

Screening for biliary atresia by infant stool color card in Taiwan.

OBJECTIVE: We aimed to detect biliary atresia (BA) in early infancy to prevent additional liver damage because of the delay of referral and surgical treatment and to investigate the incidence rate of BA in Taiwan. METHODS: A pilot study to screen the stool color in infants for the early diagnosis of BA was undertaken from March 2002 to December 2003. We had designed an "infant stool color card" with 7 numbers of different color pictures and attached it to the child health booklet. Parents were then asked to observe their infant's stool color by using this card. The medical staff would check the number that the parents chose according to their infant's stool color at 1 month of age during the health checkup and then send the card back to the stool color card registry center. RESULTS: The average return rate was approximately 65.2% (78,184 infants). A total of 29 infants were diagnosed as having BA, and 26 were screened out by stool color card before 60 days of age. The sensitivity, specificity, and positive predictive value were 89.7%, 99.9%, and 28.6%, respectively. Seventeen (58.6%) infants with BA received a Kasai operation within 60-day age period. The estimated incidence of BA in screened newborns was 3.7 of 10,000. CONCLUSIONS: The stool color card was a simple, efficient, and applicable mass screening method for early diagnosis and management of BA. The program can also help in estimating the incidence and creating a registry of these patients.

Prevention of hepatocellular carcinoma by universal vaccination against hepatitis B virus: the effect and problems.

PURPOSE: In spite of the success of hepatitis B immunization, still a significant proportion of childhood hepatocellular carcinoma (HCC) failed to be prevented by the hepatitis B immunization program. This study is aimed to investigate the problems in the HCC prevention in children. EXPERIMENTAL DESIGN: All HCC children ages 6 to 14 diagnosed between 1981 and 2000 in Taiwan were collected from two national childhood HCC registry systems. We analyzed the causes of HCC prevention failure and the risk ratio of HCC among hepatitis B carriers born before versus after the vaccination program. RESULTS: The incidence of HCC per 100,000 children declined from 0.54 to 0.20 in those born before versus after the vaccination program (risk ratio, 0.36). Vaccine failure (33.3-51.4%) and failure to receive hepatitis B immunoglobulin at birth (42.4-57.5%) were the main causes of HCC prevention failure. Mother-to-child transmission of hepatitis B virus infection is an important risk factor of HCC development. This is evidenced by the very high hepatitis B surface antigen seropositive rate in our HCC children (97%) and their mothers (96%). Hepatitis B carrier children born after the vaccination program had a higher risk of developing HCC than those born before the program (risk ratio, 2.3-4.5). CONCLUSIONS: Vaccine failure and failure to receive hepatitis B immunoglobulin are the main problems preventing eradication of HCC. Hepatitis B carrier children born after the immunization program have a higher risk of developing HCC than those born before.

Tumor necrosis factor-alpha and interleukin-10 in viral and bacterial gastroenteritis in children.

BACKGROUND: Gastroenteritis is a common cause of hospitalization and is associated with high morbidity in children. C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) are primary mediators of inflammation, and have been implicated in many infectious and non-infectious inflammatory diseases. The main objective of this study was to identify serum markers in viral and bacterial gastroenteritis. METHODS: Thirty-one patients admitted to a pediatric infection ward with gastroenteritis and definite pathogens were enrolled in the study: 17 patients had viral gastroenteritis and 14 bacterial gastroenteritis. Serum levels of TNF-alpha, IL-10 and CRP were measured in these 31 patients, and in a control group of 15 healthy children. RESULTS: Serum concentrations of TNF-alpha and CRP were significantly greater in patients with bacterial gastroenteritis than in patients with viral gastroenteritis and healthy controls (p < 0.001). Concentrations of IL-10 were increased, but not significantly, in patients with viral or bacterial gastroenteritis (p = 0.577 vs controls). Regarding diagnosis, the measurement of TNF-alpha and CRP levels was 78.6% and 92.0% sensitive, respectively; and 88.2% and 58.8% specific, respectively. CONCLUSION: Serum TNF-alpha concentration may be a useful marker for distinguishing between viral and bacterial gastroenteritis.