Comparison of two transcutaneous bilirubinometers--Minolta AirShields Jaundice Meter JM103 and Spectrx Bilicheck--in Thai neonates

Transcutaneous bilirubin (TcB) has been reported to have a high correlation with serum bilirubin. The objectives of this study were: (1) to compare the accuracy of two transcutaneous bilirubinometer (Minolto AirShields Jaundice Meter, JM103 (JM) and SpectRx, Bilicheck (BC) in estimating total serum bilirubin (TSB) levels; and (2) to assess the predictive ability of transcutaneous bilirubin in relation to specific selected TSB levels. A total of 154 measurements of TcB, using JM and BC, and TSB were recruited from 134 term and near-term infants. Postnatal ages ranged from 19 to 160 hours (x = 64.7, SD = 25.6). TSB levels ranged from 4.5 to 17.5 mg/dl (x = 10.4, SD = 2.5). The correlation coefficients between TcB (JM and BC) and TSB measurements were significant and similar (r 0.80 and 0.82, respectively). The errors of distribution were, for TSB and TcB-JM, the mean difference of 0.7 mg/dl (SD 1.6 mg/dl and 95% confidence interval of the mean (CI) 0.4 and 1.0]; and, for TSB and TcB-BC, the mean difference of -0.6 mg/dl (SD 1.5 mg/dl and 95% CI -0.4 and -0.8). TcB-JM had a tendency to underestimate TSB levels, and TcB-BC had a tendency to overestimate TSB levels. The sensitivity of BC was higher, but specificity was lower, than JM in corresponding to different TSB levels, except at a TSB level of 15 mg/dl when both instruments yielded 100% sensitivity. The accuracy of JM in predicting TSB was higher than BC at all TSB levels. Operating the JM was simple and uncomplicated. It would be suitable for clinical use when a number of personnel perform the measurement.     

Liver tumors in children with chronic liver diseases

Liver tumors are rare in children, but the incidence may increase in some circumstances and particularly in chronic liver diseases. Most liver tumors consequent to chronic liver diseases are malignant hepatocellular carcinoma. Other liver tumors include hepatoblastoma, focal nodular hyperplasia, adenoma, pseudotumor, and nodular regenerative hyperplasia. Screening of suspected cases is beneficial. Imaging and surrogate markers of alpha-fetoprotein are used initially as noninvasive tools for surveillance. However, liver biopsy for histopathology evaluation might be necessary for patients with inconclusive findings. Once the malignant liver tumor is detected in children with cirrhosis, liver transplantation is currently considered the preferred option and achieves favorable outcomes. Based on the current evidence, this review focuses on liver tumors with underlying chronic liver disease, their epidemiology, pathogenesis, early recognition, and effective management.     

Delta-like ligand 4 in hepatocellular carcinoma intrinsically promotes tumour growth and suppresses hepatitis B virus replication

AIM To investigate the role of Delta-like ligand 4(DLL4) on tumour growth in hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC) in vivo.METHODS We suppressed DLL4 expression in an HBV expressing HCC cell line, HepG2.2.15 and analysed the growth ability of cells as subcutaneous tumours in nude mice. The expression of tumour angiogenesis regulators, VEGF-A and VEGF-R2 in tumour xenografts were examined by western blotting. The tumour proliferation and neovasculature were examined by immunohistochemistry. The viral replication and viral protein expression were measured by quantitative PCR and western blotting, respectively.RESULTS Eighteen days after implantation, tumour volume in mice implanted with sh DLL4 HepG2.2.15 was significantly smaller than in mice implanted with control HepG2.2.15(P 0.0001). The levels of angiogenesis regulators, VEGF-A and VEGF-R2 were significantly decreased in implanted tumours with suppressed DLL4 compared with the control group(P 0.001 and P 0.05, respectively). Furthermore, the suppression of DLL4 expression in tumour cells reduced cell proliferation and the formation of new blood vessels in tumours. Unexpectedly, increased viral replication was observed after suppression of DLL4 in the tumours.CONCLUSION This study demonstrates that DLL4 is important in regulating the tumour growth of HBV-associated HCC as well as the neovascularization and suppression of HBV replication.     

Long term efficacy of hepatitis B vaccine in infants born to hepatitis B e antigen-positive mothers.

The long term protective efficacy of recombinant hepatitis B vaccine, administered alone or concomitantly with hepatitis B immunoglobulin, was assessed in 263 healthy neonates of hepatitis B e antigen-positive mothers. Infants received the first dose of vaccine at birth; additional doses were given at either Months 1, 2 and 12 or Months 1 and 6. During the follow-up period, which ranged from 2 to 4 years, protective titers (> or = 10 mIU/ml) of anti-hepatitis B surface antibodies were found in virtually all infants who had responded to the primary course of vaccination. "Natural boosts," without persistent infection, were observed in only a small number of children. All children who were shown to have become chronic carriers were infected within the first year of life. No statistical difference in long term protective efficacy could be shown between the two vaccination schedules used or between the use of vaccine alone or vaccine plus hepatitis B immunoglobulin for either schedule.     

Comparison study of combined DTPw-HB vaccines and separate administration of DTPw and HB vaccines in Thai children.

The safety, immunogenicity and tolerability of two different DTPw-HBV combination vaccines, containing 5 and 10 microg of HBsAg; were investigated in comparison with separate administration of DTPw and HBV (10 microg of HBsAg). A three dose primary vaccination course at 2, 4 and 6 months of age was followed by a booster dose at 18 months. All vaccines were safe and well tolerated. The DTPw-HBV combination vaccine containing 10 microg of HBsAg elicited significantly higher anti-HBs titres than the other two vaccines after the primary and booster vaccination course. All vaccines elicited a high response against the other components. Based on these results, DTPw-HBV (10 microg HBsAg) was the most effective vaccine at this schedule.     

Oxidative stress indicated by elevated expression of Nrf2 and 8-OHdG promotes hepatocellular carcinoma progression

Reactive oxygen species (ROS) is excessively generated in tumors creating an oxidative stress in tumor microenvironment. We investigated hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and 8-hydroxydeoxyguanosine (8-OHdG) in hepatocellular carcinoma (HCC) patients, and asked if ROS epigenetically upregulated Nrf2 and enhanced aggressiveness in HCC cells. Expression of Nrf2 (n = 100) and 8-OHdG (n = 53) was remarkably increased in HCC tissues compared with the noncancerous hepatic tissues. Elevated expression of 8-OHdG was associated with poor survival in HCC patients. H₂O₂, as ROS representative, provoked oxidative stress in HepG2 cells, indicated by increased protein carbonyl content and decreased total antioxidant capacity. Nrf2 expression and 8-OHdG formation were markedly increased in the H₂O₂-treated cells compared with the untreated control. Co-treatment with antioxidants, tocopheryl acetate (TA) and S-adenosylmethionine (SAM) effectively attenuated expression of Nrf2 and 8-OHdG in H₂O₂-treated cells. HepG2 cells treated with H₂O₂ had significantly higher migration and invasion capabilities than the untreated control cells, and this aggressiveness was significantly inhibited by TA and SAM. Bisulfite sequencing revealed that CpG dinucleotides in Nrf2 promoter were unmethylated in the H₂O₂-treated cells similar to the untreated control. In conclusion, robust histological evidence of increased antioxidative response and oxidative DNA damage in human HCC tissues was demonstrated. Elevated oxidative DNA lesion 8-OHdG was associated with shorter survival. Experimentally, ROS enhanced Nrf2 expression, 8-OHdG formation and tumor progression in HCC cells. These effects were inhibited by antioxidants. Therefore, oxidative stress-reducing regimens might be beneficial to diminish the ROS-induced HCC progression.     

Cytomegalovirus infection in liver-transplanted children

Cytomegalovirus (CMV) infection is a common complication of liver trans-plantation in children. The CMV serostatus of recipients and donors is the primary risk factor, and prophylaxis or pre-emptive strategies are recommended for high-risk patients. Graft rejection, coinfection and Epstein-Bar virus reactivation, which can lead to post-transplant lymphoproliferative disease, are indirect effects of CMV infection. Assessment of CMV infection viral load should be routinely performed upon clinical suspicion. However, tissue-invasive CMV disease is not associated with CMV viraemia and requires confirmation by tissue pathology. Oral valganciclovir and intravenous ganciclovir are equivalent treatments, and the duration of treatment depends on factors including CMV viral load, tissue pathology, and clinical response. Risk stratification by donor and recipient status prior to transplantation and post-transplantation antiviral prophylaxis or pre-emptive therapy are recommended. Adult guidelines have been established but additional study of the effectiveness of the preventive guidelines in children is needed. This review summarizes the burden, risk factors, clinical manifestations, laboratory evaluation, treatment, and prevention of CMV infection in children after liver transplantation.     

Necrotizing non-granulomatous lymphadenitis: a clinicopathologic study of 40 Thai patients

The purpose of this study was to describe the clinicopathological features of 40 cases of necrotizing non-granulomatous lymphadenitis in Thai patients. The clinical features, histomorphology and special stains were evaluated in 40 Thai patients from the pathology records of King Chulalongkorn Memorial Hospital from January 2001 to December 2003 in those diagnosed as having necrotizing non-granulomatous lymphadenitis. Of the 40 patients, 17 cases (42.5%) had Kikuchi-Fujimoto disease (KFD), 8 cases (20%) had tuberculosis (TB) lymphadenitis and 1 case (2.5%) had systemic lupus erythematosus (SLE) with associated lymphadenitis. Fourteen cases (35%) did not have a specific diagnosis due to a lack of follow-up data. KFD most commonly occurs in young women, and is characterized by the presence of coagulative necrosis and karyorrhexis often centered in the paracortex, an absence of neutrophils and plasma cells, proliferation of various cells composed of lymphocytes, histiocytes, immunoblasts and plasmacytoid monocytes and the absence of a granuloma. Tuberculous lymphadenitis usually occurs in women with a mean age of 34.25 years. The lymph nodes reveal extensive coagulative necrosis involving the cortex, paracortex and medulla, proliferation of mixed inflammatory cells, including neutrophils, lymphocytes and plasma cells in the necrotic area and the presence of proliferating histiocytes at the periphery of the necrotic area. The lymph nodes of SLE-associated lymphadenitis reveal large numbers of plasma cells and hematoxylin bodies. We suggest that necrotizing non-granulomatous lymphadenitis is not specific for any disease, but rather a common histologic change found in diseases, such as TB, SLE, and KFD. Further investigation to obtain a definite diagnosis should be done for appropriate treatment.