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Biomedical subjects

Mei-Hwei Chang

Publications and source records attributed to Mei-Hwei Chang.

At least 37 records · Page 2Linked to original sources

Differential integration rates of hepatitis B virus DNA in the liver of children with chronic hepatitis B virus infection and hepatocellular carcinoma.

BACKGROUND AND AIM: Integration of hepatitis B virus-DNA (HBV-DNA) into the host genome, a phenomenon found frequently in hepatocellular carcinomas (HCC) and causally linked to oncogenesis, has not been well characterized in children. The aim of the present study was to determine the prevalence of HBV integration more accurately and to decide whether the integration rate varies at different stages of chronic HBV infection in children. METHODS: Of 13 children with chronic hepatitis, 14 liver biopsy tissues were analyzed. One liver tissue with pure liver cirrhosis, nine non-tumor, and nine tumor liver tissues from children with HCC were analyzed by a very sensitive method, inverse polymerase chain reaction (IPCR). RESULTS: Thirteen genuine viral-host junctional sequences from 23 patients were successfully isolated and proved that IPCR is a useful method in this context. The results also indicated that the detection rate of HBV-DNA integration increased in parallel with the progress of liver histology towards the neoplastic transformation, with 0% in the liver of chronic hepatitis, 22.2% in non-tumor livers of HCC patients, and 66.7% in tumor liver tissues of HCC patients. CONCLUSION: The present results indicate that integration of HBV-DNA into the host genome was rarely confirmed at the early stage of chronic hepatitis in children until the stage of HCC formation.

Carcinoma, Hepatocellular↗

Factors affecting the mortality of pediatric fulminant hepatic failure in relation to hepatitis B virus infection.

AIM: To investigate the factors affecting the outcome of fulminant hepatic failure (FHF) in children in relation to hepatitis B virus (HBV) infection. METHODS: Retrospective review of a total of 94 cases (61 males and 33 females, aged from 1 month to 15 years) recruited from nine tertiary referral centers in Taiwan from 1985 to 1999. RESULTS: The overall mortality rate was 75%. Patients in the mortality group were of an older age, had higher peak total bilirubin levels, a longer prothrombin time, and a lower percentage of HBV positivity (P < 0.001, P = 0.003, P = 0.0027 and P = 0.042, respectively). Mortality was 65% in the HBV positive (n = 42) and 83% in the HBV negative (n = 52) group (P = 0.05). In the HBV positive group, the prothrombin time was noted to be the single factor affecting outcome (P = 0.036). In the HBV negative group, older age and higher peak value of total serum bilirubin were suggestive of poor survival rate (P < 0.001 and P = 0.006, respectively). Multivariate analysis revealed that total bilirubin was the single factor affecting outcome in the HBV-negative group. The mortality rate of HBV positive children in three consecutive time periods without liver transplantation (1985-1989, 1990-1994, 1995-1999) decreased gradually (91, 67 and 38%, respectively, with P = 0.027). This change was not observed in HBV-negative cases. CONCLUSIONS: Hepatitis B virus positive FHF had a lower mortality rate than HBV negative FHF, with each group having different factors affecting mortality.

Acute Disease↗

Lamivudine treatment in maternally transmitted chronic hepatitis B virus infection patients.

BACKGROUND: Lamivudine treatment in chronic carriers who acquired hepatitis B virus through maternal transmission were investigated. METHODS: A total of 29 subjects (Male:Female, 24:5; mean age, 14.7 +/- 5.6 years) who were hepatitis B e antigen (HBeAg) seropositive for >6 months, alanine aminotransferase (ALT) was >1.3 times of upper limit of normal value, and receiving a 52 week-long treatment, received open-label lamivudine (3 mg/kg per day, maximum 100 mg/day). Another 29 subjects matched for gender, age, liver function, and HBeAg status followed up before the introduction of lamivudine served as the control group. The control group did not receive any treatment and were evaluated at week 52 after the onset of abnormal ALT. Mothers of all study subjects were hepatitis B surface antigen (HBsAg) carriers. A successful treatment response at week 52 was defined as: (i) undetectable hepatitis B virus DNA by real time polymerase chain reaction; (ii) normal ALT; and (iii) HBeAg/anti-HBe seroconversion. Lamivudine-resistant YMDD mutants were checked at week 52. RESULTS: The lamivudine group did not reach a better successful treatment response rate than the control group (17 vs 10%, P = 0.44), except in patients with a baseline ALT >5 times of the upper limit of normal value. YMDD mutants developed in 34% of patients in the lamivudine group. CONCLUSION: Lamivudine treatment is effective for maternally transmitted subjects with high ALT.

Adolescent↗

Clinical implication of hiatal hernia in patients with right isomerism.

OBJECTIVE: Despite a reported association between hiatal hernia in patients with heterotaxy syndrome, the clinical significance has remained unclear. Based on large patient cohorts, this study specifically aimed at defining the implication of hiatal hernia in patients with right isomerism. METHODS: From 1994 to 2002, 143 patients were identified as having right isomerism. Among them, 119 received ultrafast computed tomography (CT) to determine the presence of hiatal hernia as well as any cardiovascular anomalies. RESULTS: Hiatal hernia was found in 17 patients (seven females and 10 males, 14.3%). The upper gastrointestinal (GI) series in six patients confirmed the diagnosis of hiatal hernia in all and revealed severe gastro-oesophageal reflux in four. The most common symptom of hiatal hernia was vomiting (47%), followed by recurrent bronchiolitis or pneumonia (41.2%) and upper gastrointestinal bleeding (11.8%). Three patients with hiatal hernia underwent fundoplication for medically refractory vomiting. Seven patients were found to have midgut malrotation (5.9%), and four of these had both hiatal hernia and malrotation. Pulmonary atresia was closely associated with the presence of hiatal hernia (p=0.02). One patient with hiatal hernia died suddenly at 6 mo. However, overall mortality was similar between those patients with hiatal hernia and those without. CONCLUSIONS: The incidence of hiatal hernia was considerably high in patients with right isomerism, especially in those with pulmonary atresia, and it is this that may have led to vomiting and recurrent airway infections. While an association between sudden death and hiatal hernia may well exist, this does require further clarification.

Abnormalities, Multiple↗

Long-term follow-up of Hepatitis B Surface antibody levels in subjects receiving universal Hepatitis B vaccination in infancy in an area of hyperendemicity: correlation between radioimmunoassay and enzyme immunoassay.

The aims of the present study were to determine (i) the long-term immunogenicity and the decay rate of hepatitis B virus (HBV) surface antibody (anti-HBs) from universal hepatitis B vaccination at infancy for a healthy population in an area of hyperendemicity and (ii) whether the anti-HBs levels measured by enzyme immunoassay (EIA) were closely correlated with those assayed by radioimmunoassay (RIA) methods during long-term monitoring. A total of 1,337 apparently healthy children (696 boys and 641 girls) who were vaccinated against HBV at infancy and monitored for anti-HBs annually from 7 to 16 years of age entered the study. Serum samples were analyzed for anti-HBs by RIA at 7 to 15 years of age and were also analyzed by EIA at 13 to 16 years of age. Antibody titers were quantified in mIU/ml by EIA as well as by the ratio of the count in the sample to the count for a negative control (S/N) by RIA. In non-boosted children, the average decay of anti-HBs from 7 to 16 years of ages indicated that approximately 20% of the geometric mean titer decays per year. There was a good correlation between serum anti-HBs levels measured by the RIA and the EIA methods (r=0.91; P<0.0001). An equation for RIA to EIA level conversion was established: log EIA titer=-0.12+ (1.31 . log RIA S/N). The anti-HBs titers measured by EIA correlate well with the S/N assayed by RIA. The annual decay rate of the log anti-HBs level may help in planning booster immunizations for hypo-responders or individuals at risk in adolescence.

Adolescent↗

Intussusception in Taiwanese children: analysis of incidence, length of hospitalization and hospital costs in different age groups.

BACKGROUND AND PURPOSE: This study investigated the characteristics of intussusception in Taiwanese children of different age groups, including the incidence, length of hospitalization and hospital costs. METHODS: Children with a diagnosis of intussusception who were hospitalized from 1999 through 2001 were identified from a nationwide health insurance claims database. The incidence of intussusception was calculated by age, gender, and season. Length of hospitalization and hospital costs were also analyzed. RESULTS: A total of 6988 cases of intussusception were identified in Taiwan from 1999 to 2001. Among them, 4859 cases occurred in children below 15 years of age. The average incidence among children below age 15 years was 34.5 per 100,000, with a peak incidence of 118.8 per 100,000 observed among children younger than 24 months old. The highest incidence of intussusception in Taiwanese children occurred between 12 and 24 months of age. According to the data for patients below 15 years of age hospitalized for intussusception in year 2000, males were more likely to be affected than females (61.3% vs 38.7%). Intussusception-related hospitalizations were rare in infants in the first few months of life, increased in those 6 to 12 months old, and peaked among children 1 to 3 years old. Among the 952 patients with intussusception admitted to hospitals in 2000, 297 (31.2%) received surgery, incurring higher median medical costs (New Taiwan Dollars [NT dollars] 42,265 or US dollars 1234) and longer median hospital stay (6.2 days) than the 655 patients who did not require surgery (NT dollars 6290 or US dollars 185 for hospitalization of 2.4 days). CONCLUSIONS: The study found that the incidence of intussusception peaked in the second year of life in Taiwanese children. There was also a male predominance and lack of seasonal variation in incidence.

Adolescent↗

Viral infections and prolonged fever after liver transplantation in young children with inborn errors of metabolism.

BACKGROUND AND PURPOSE: Liver transplantation could be a useful treatment for selected inborn errors of metabolism. This study evaluated the outcome and viral infections after liver transplantation in young children and infants with these diseases. METHODS: The outcome of liver transplantation and clinical characteristics of the following 4 patients were assessed: 1 infant with ornithine transcarbamylase deficiency (OTCD) who received liver transplant aged 3 years and 4 months; 1 infant with carbamyl phosphate synthetase I deficiency (CPSID) who received liver transplant at 14 months of age; and 2 infants with methylmalonic acidemia (MMA) who received liver transplant at 8 months and 11 months of age, respectively. All donors, except the 8-month-old infant with MMA, showed serologic evidence of previous cytomegalovirus (CMV) infection before transplantation. All 4 of these donors showed serologic evidence of previous infection of Epstein-Barr virus (EBV). None of the recipients had previous CMV infection. Both the infant with OTCD and the 8-month-old infant with MMA had previous EBV infection, while the other 2 patients did not. Preoperative hemodialysis was performed in both infants with MMA. Postoperative follow-up included metabolic stability, disability degree, and viral infections. RESULTS: None of the patients developed severe metabolic decompensation after transplantation and all increased protein intake postoperatively. Symptomatic viral infections, however, were present in all patients postoperatively, including CMV infection in the infant with OTCD and the 11-month-old infant with MMA, reactivation of EBV infection in the infant with OTCD and the 8-month-old infant with MMA, and primary EBV infection in the infant with CPSID. CONCLUSIONS: Liver transplantation was an effective treatment for all 4 of these patients with inborn errors of metabolism. The risk of symptomatic viral infections for these patients was high. This was likely associated with conditions including immunosuppression, young age, endemic nature of CMV and EBV infections, and lack of CMV prophylaxis.

Carbamoyl-Phosphate Synthase I Deficiency Disease↗

RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts.

The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNA-binding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein. The RBMY transcripts, expressed exclusively in the testis of normal people, were detected by reverse transcription-polymerase chain reaction in 36% of HCCs from 90 males and in 67% of hepatoblastoma from six boys. The nontumor liver counter parts, cirrhotic liver tissues from children with biliary atresia, and other types of cancers, such as bile duct, colon, stomach, lung, prostate, and kidney, were all negative for RBMY expression. One to four types of RBMY transcripts, including wild type and variants with N-terminal RRM deletion, C-terminal SRGY (serine-arginine-glycine-tyrosine) boxes deletion, or deletion of both domains, were found in the testis and liver cancer tissues. The wild-type RBMY protein was expressed in the nucleus and demonstrated its tumorigenicity by transformation of mouse fibroblast NIH3T3 cells and in vivo tumor formation. The RBMY variant protein with deletion of C-terminal exons 9-12 was trapped in the cytoplasm and showed decreased tumorigenicity. Our results suggest that RBMY is a new candidate oncogene specific for male liver cancer.

3T3 Cells↗

Longitudinal study on mutation profiles of core promoter and precore regions of the hepatitis B virus genome in children.

Precore nucleotide 1896 and core promoter mutations may account for hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B virus (HBV) infection, yet the mutational profiles of the core promoter are largely unknown in children. An age-matched, case-control study enrolled 110 chronic HBV-infected children, including 55 HBeAg seroconverters and 55 nonseroconverters. Precore and core promoter genes of HBV were sequenced and the serum viral genomes were genotyped from three serial serum samples of the seroconverters and from one serum sample of the nonseroconverters. Higher frequency of A1775G and G1799C mutation rates and lower frequency of A1752G mutation rate were found in the seroconverters. Precore 1896 mutation appeared more in seroconverters than in nonseroconverters (45.5% versus 10.9%; p < 0.001). 1762 + 1764 mutation rates were not different between the seroconverters (9.1%) and the nonseroconverters (5.5%). Genotype B was the major type. Genotype C was associated with core promoter 1762 + 1764 mutations in the seroconverter group (p = 0.023). The conclusions of this study include the following: 1) mutations of core promoter at nucleotide position 1752, 1775, and 1799 have significant correlations with HBeAg seroconversion; 2) core promoter 1762 + 1764 mutations play a minimal role in HBeAg seroconversion; 3) precore 1896 mutant accounted for half of childhood HBeAg seroconversion; 4) genotype C is associated with 1762 + 1764 mutations during the process of HBeAg seroconversion.

Adolescent↗

Corrosive esophagitis in children.

We evaluated the outcome and optimal management of corrosive esophagitis in 24 children (male:female=8:16, mean age 5.0+/-5.4 years old, ranged from 15 months to 18 years of age) from January 1984 to July 2001. In 20 patients this was the result of accidental ingestion, 4 were suicide attempts and 15 patients (63%) were below 3 years of age. The ingested substances included alkali (n=17, 71%), acid (n=6, 25%), and neutral detergent (n=1, 4%). The "dumpling alkaline oil", a traditional food additive used in Taiwan, was the most common culprit in this study. A total of 9 patients ingested the dumpling alkaline oils, which comprised 38% of the total 24 patients and 53% of the 17 alkaline ingestion accidents. Of the patients 21 (88%) suffered from esophageal injury, and 15 among these 21 patients developed esophageal strictures. Esophageal strictures occurred in all patients with second or third-degree burns. Of these 15 patients with esophageal strictures, 9 (60%) received endoscope-associated dilatation and 6 (40%) underwent an operation (esophagectomy and intestinal interposition). The 9 patients who did not develop esophageal strictures had good body weight gain without feeding difficulty (functionally normal recovery). On the other hand, among the 15 patients with esophageal strictures, 9 patients had functionally subnormal recovery and 6 patients had poor recovery with either frequent feeding difficulty or growth retardation. In conclusion, accidental ingestion of alkaline oil is the most common cause of corrosive esophagitis in Taiwan. The degree of burns correlated with stricture formation.

Acids↗

Pediatric fulminant hepatic failure in endemic areas of hepatitis B infection: 15 years after universal hepatitis B vaccination.

To investigate the role of hepatitis B virus (HBV) infection in pediatric fulminant hepatic failure (FHF) after the launch of universal HBV vaccination, the authors analyzed the data from patients with FHF collected from a nationwide collaborative study group. Children aged 1 month to 15 years who were diagnosed with FHF (62 males and 33 females) between 1985-1999 were included. HBV infection (hepatitis B surface antigen [HBsAg] and/or immunoglobulin M hepatitis B core antibody [IgM anti-HBc] seropositive) accounted for 46% (43 of 95 cases) of all the cases of FHF. The average annual incidence of FHF in the time period 1985-1999 was 0.053/100,000 in the group of patients ages 1-15 years and 1.29/100,000 in those patients age < 1 year. Approximately 61% (58 of 95 cases) of all FHF cases were infants. The percentage of HBV infection was found to be higher in infants (57%) compared with children ages 1-15 years (27%) (P = 0.004). The incidence rate ratio of those patients age < 1 year to those ages 1-15 years was 54.2 for HBV-positive FHF and 15.2 for HBV-negative FHF. Maternal HBsAg was found to be positive in 97% of the infants with HBV-positive FHF, and hepatitis B e antigen (HBeAg) was found to be negative in 84% of these infants. Approximately 74% of all HBV-positive FHF patients and 81% of the infantile HBV-positive patients had been vaccinated. In conclusion, within the first 15 years of universal vaccination, HBV was found to rarely cause FHF in children age > 1 year but remained a significant cause of FHF in infants. HBV-positive FHF was prone to develop in infants born to HBeAg-negative, HBsAg-carrier mothers; these infants had not received hepatitis B immunoglobulin according to the vaccination program in place.

Adolescent↗

Waning immunity to plasma-derived hepatitis B vaccine and the need for boosters 15 years after neonatal vaccination.

Neonatal immunization with hepatitis B (HB) vaccine is highly effective; however, more needs to be learned about the duration of protection and indications for boosters. We measured antibody to HB core antigen (anti-HBc), HB surface antigen (HBsAg), and pre- and postbooster titers of HBsAg antibody (anti-HBs) 15 years after primary neonatal immunization with plasma-derived HB vaccines in 2 cohorts of 15-year-old children. Group A consisted of 78 children who were born to HB e antigen-positive HBsAg carrier mothers and had developed protective levels of anti-HBs antibodies (> or =10 mIU/mL) following HB immunization. Group B consisted of 113 apparently healthy children whose anti-HBs titers after vaccination were unknown. Anti-HBs was undetectable (antibody titer <10 mIU/mL) in 29.9% in group A and 62.4% in group B (P < .001). Anti-HBc was detected in 33.3 % in group A and 4.4 % in group B (P < .001). After a single booster dose of HB vaccine, 2.7% in group A and 3.3% in group B remained anti-HBs-negative. A blunted serological response was noted in approximately 20% in both groups. One HBsAg carrier was detected in group A (1.3%) and 4 in group B (3.5%). Fifteen years after neonatal immunization with plasma-derived HB vaccine, a large proportion of children exhibited waning immunity. This poses the risk of breakthrough infection. A single booster augmented the serological response to the vaccine in most but not all subjects. In conclusion, our findings suggest that one or more booster immunizations are needed in seronegative subjects by at least 15 years following neonatal immunization with plasma-derived HB vaccine.

Adolescent↗

The development of hepatocellular carcinoma among prospectively followed children with chronic hepatitis B virus infection.

We prospectively followed 426 children with chronic hepatitis B virus infection. During 6250 person-years, 2 boys developed hepatocellular carcinoma, with an incidence of 32 per 100,000 person-years. Both had e antigen seroconversion in early childhood and cirrhosis. Early e antigen seroconversion and/or cirrhosis may be risk factors for hepatocellular carcinoma.

Adolescent↗

Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis.

OBJECTIVE: To determine the effect of ursodeoxycholic acid (UDCA) in very-low-birth-weight (VLBW) infants with parenteral nutrition-associated cholestasis (PNAC). STUDY DESIGN: A retrospective study of all VLBW infants with PNAC who were admitted to a tertiary referral center was conducted. Patients were classified as treatment group (receiving UDCA within 14 days after onset of cholestasis) or control group (no medical treatment). Patients who received abdominal surgery were excluded. RESULTS: A total of 30 patients were recruited, including 12 in the treatment group and 18 in the control group. The demographic data, total fasting duration, onset of cholestasis, age to tolerance of full feeds, and the duration of parenteral nutrition (PN) before the onset of cholestasis were comparable between the two groups. There was a trend in the control group to later onset of cholestasis. The patients who received UDCA therapy with doses of 10 to 30 mg/kg/day had a shorter duration of cholestasis than the control group (62.8 vs 92.4 days, P=.006). Furthermore, the peak serum levels of direct bilirubin also was significantly lower in the treatment group. CONCLUSION: UDCA can improve the course of PNAC in VLBW infants.

Bilirubin↗

Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma.

BACKGROUND & AIMS: The aim of this study was to investigate the influence of hepatitis B virus (HBV) genotypes on the clinical outcome of chronic childhood HBV infection and hepatocellular carcinoma (HCC). METHODS: A total of 460 HBV carrier children were followed-up for 15 years and 26 children with HBV-related HCC were recruited. HBV genotyping was examined at enrollment and the latest follow-up of these carrier children and at diagnosis in HCC children. Viral load was checked at enrollment for the carrier children. These carriers were grouped based on their initial hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) status. The HBeAg positive (+) group was divided further into an HBeAg(+/+) group and HBeAg(+/-) group, depending on whether spontaneous HBeAg seroconversion occurred during the follow-up period. RESULTS: Genotype B constituted 73%, 86%, and 76% in the HBeAg(+/+), HBeAg(+/-), and anti-HBe(+) groups, respectively. Genotype C was found in 27%, 8%, and 6% in the HBeAg(+/+), HBeAg(+/-), and anti-HBe(+) group, respectively. Genotype C carriers were more prevalent in the HBeAg(+/+) group than the other 2 groups (P = .01), and had a delayed HBeAg seroconversion compared with the genotype B carriers (P < .001). Changes of genotype during the follow-up period were rare (2.8%). In those with HCC, genotype B was also the major type (74%). There was no difference in the baseline viral load between genotypes B and C. CONCLUSIONS: Although HBV genotype B dominates in children with chronic HBV infection and HCC in Taiwan, genotype C delays HBeAg seroconversion in pediatric chronic HBV infection.

Carcinoma, Hepatocellular↗

Portal hypertension and duodenal ulcer in children.

OBJECTIVES: The prevalence of duodenal ulcer (DU) in adult patients with portal hypertension is higher than in patients without portal hypertension. This study investigates the prevalence and characteristics of DU in children with portal hypertension. PATIENTS AND METHODS: From January 1997 to December 2001, 80 children with portal hypertension who had undergone upper intestinal endoscopic examinations were enrolled. Possible factors contributing to the development of DU including severity of liver disease, portal hypertension, H. pylori, and serum gastrin level were studied. The control group consisted of 80 age-and sex-matched children with gastrointestinal symptoms but no liver disease and who underwent endoscopic examination during the same period. RESULTS: The prevalence of DU was significantly higher in children with portal hypertension than in children with digestive symptoms only (22.5%v 8.8%; P =0.017). DU was more common and appeared earlier in children with a history of variceal bleeding. The presence of DU was independent of the severity of liver disease, H. pylori infection and serum gastrin level. CONCLUSION: DU occurs commonly in children with portal hypertension, especially in those who have had variceal bleeding. It is mandatory to screen a patient with gastrointestinal bleeding for DU even in the presence of esophageal varices. Elevated portal pressure might be a factor contributing to the development of DU.

Adolescent↗