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BACKGROUND Maternal anti-viral treatment prevents mother-to-infant transmission of hepatitis B virus (HBV), but the role of neonatal viremia on subsequent HBV infection is not clear. AIMS To investigate the effect of maternal anti-viral treatment on neonatal serum HBV DNA and hepatitis B surface antigen (HBsAg) in infants born to highly viremic mothers and the roles of neonatal markers in predicting chronic HBV infection in children. METHODS Serum HBV DNA and HBsAg were tested in children. Of the 201 pregnant mothers, 110 received tenofovir during the third trimester. Chronic infection in children was defined by HBsAg seropositivity at 6 or 12 months lasting more than 6 months. RESULTS The maternal HBV viral loads from baseline to delivery were 8.25 ± 0.48 to 4.29 ± 0.98 log10 IU/mL; and 8.29 ± 0.49 to 8.12 ± 0.68 log10 IU/mL in the tenofovir and control group respectively. Of the 208 children, those in the tenofovir group had a lower rate of neonatal HBV DNA seropositivity at birth (5.22% vs 30.11%, P

Background and aim To compare the long term efficacy of infant recombinant yeast hepatitis B vaccine (Recombinant group) and infant plasma-derived one (Plasma group) in Taiwanese freshers. Methods Recruited were a total of 38,377 freshmen who underwent university entrance health examinations from 2003 to 2015. Subjects were assigned into two groups–plasma type and recombinant type, according to the national neonatal hepatitis B immunization program. The seroprevalences of hepatitis B surface antigen, antibody against hepatitis B surface antigen, and antibody against hepatitis B core antigen in each group and gender were calculated. Multivariate logistic regression analysis was performed to compare the efficacy of two groups. Results The HBsAg-positive rates in the plasma group and recombinant group were 1.5% and 0.3%, respectively. The anti-HBs positive rates were 43.6% and 30.9%. The hepatitis B viral natural infection rates were 3.6% and 1.3%. Taking those who were born in July 1986-April 1992 as baseline group after adjustment for gender and age at hepatitis B markers checkup time, the efficacy of recombinant group in decreasing HBsAg positive rate, and decreasing hepatitis B virus natural infection rate was 71.0% (95% C.I.: 59.0-79.0%, P

The differentiation between biliary atresia (BA) and idiopathic neonatal hepatitis (INH) is challenging with many histological overlaps especially in the first weeks of life. This study aimed to investigate the role of immunohistochemical staining of CK7, Ki67, CD34, and vimentin in addition to other clinicopathological features in the differentiation between BA and INH. Cases included 30 infants with BA and 30 infants with INH. The diagnosis was based on clinical, laboratory, and liver biopsy examination. Female gender and elevated serum gamma glutamyle transferase were in favor of BA. Portal tract changes, such as bile ductular proliferation documented by CK7, Ki67 immunostaining and angiogenesis documented by CD34 immunostaining, favored the diagnosis of BA. Copper associated protein was positive in 70% of BA cases, but not detected in INH cases. Parenchymatous changes, such as giant cell transformation and positive iron deposition and Kupffer cell proliferation documented by vimentin immunostaining, favored the diagnosis of INH.CK7, Ki67, CD34, and vimentin are helpful adjuvant immunostaining in the differentiation between BA and INH.

Background: Measurement of urinary sulfated bile acid (USBA) is a non-invasive method to detect bile congestion. Our aim was to evaluate the feasibility of USBA analysis for the early detection of biliary atresia (BA). Methods: We determined the USBA-to-creatinine ratio (USBA/cr) in 1148 infants at 10–40 days after birth. All infants were followed until the 3- to 4-month postnatal routine health check. The cutoff value for USBA/cr was 55.0 µmol/g creatinine. Results: Among the infants tested, 47 (4.10%) had USBA/cr ratios that exceeded the cutoff value. Two of these 47 infants had liver disease; one was diagnosed with neonatal hepatitis syndrome, and the other was diagnosed with BA. The BA patient underwent USBA analysis for the first time on day 18 after birth and hepatoportoenterostomy on day 49. No other infants were diagnosed with hepatobiliary disease during the follow-up period. Conclusion: This USBA analysis provided the correct assessment without fail and identified a case of BA. This approach could be used for the screening and early detection of BA when the false-positive rate is decreased by improving the methods for sample collection and urine storage.

This study aimed to examine the application of hepatitis B surface antigen (HBsAg) confirmatory testing when diagnosing hepatitis B infection among young persons in Taiwan with a low prevalence rate of hepatitis B infection. HBsAg status, the presence of antibodies against HBsAg (anti-HBs), and the presence of antibodies against hepatitis B core antigen (anti-HBc) were compared among 403 graduate students (mean age 22.8 ± 0.7 years) and 1,745 undergraduate students (18.6 ± 1.0 years) from one university, and 367 adult subjects (41.1 ± 15.8 years) in 2008. Any HBsAg-positive subjects were tested with an HBsAg confirmatory test. Chi-square tests for trend and predictive values of positivity (PVP) when using HBsAg-positive only for determining confirmed cases of hepatitis B infection were compared across the three cohorts. The prevalence of HBsAg positivity among subjects decreased from 16.3% in the adults to 5.2% in the graduate students and then to 2.8% for the undergraduate students (P = 0.0007). The PVP of HBsAg testing when determining cases of hepatitis B decreased from 0.97 for the adults to 0.81 for the graduate students and then to 0.56 for the undergraduate students (P < 0.0001). Thus, a significant decrease in the true-positive rate of HBsAg among the students born after the introduction of hepatitis B vaccination was observed only when HBsAg testing was applied. Additional neutralization tests may therefore become mandatory for persons with a positive HBsAg test result who were born after the commencement of the universal neonatal hepatitis B vaccination program in Taiwan.

Aim: To study the accuracy of various clinical and investigational parameters to differentiate biliary atresia (BA) from neonatal hepatitis (NH). Methods: It was a prospective study, conducted in a tertiary care hospital. A total 101 infants with neonatal cholestasis (NCS) were included in this study. Following a baseline hepatobiliary scintigraphic study (HBS), it was repeated after giving UDCA (40 mg/kg/day for 48–72 h). The sensitivity and specificity of clinical and investigational parameters were calculated with peroperative cholangiogram as gold standard. Results: The mean age was 2.8 ± 1.7 months and 82 were male. Of these, 35 were diagnosed to have BA and 66 had NH (idiopathic 25, sepsis/UTI 20, galactosaemia 11, TORCH 2 and others 8). Persistently clay stool was found to have modest accuracy (79%) and the accuracy of HBS improved significantly following UDCA therapy (91% from 77%, p < 0.01) whereas liver biopsy was 100% accurate in differentiating BA from NH. The outcome of BA cases with ductal plate malformation (DPM) was worse. Conclusion: One-third of all NCS in India is due to BA and among the intrahepatic causes acquired infection and galactosaemia are common. Liver biopsy is the best method to differentiate NH from BA.

The longest open reading frame of PKHD1 (polycystic kidney and hepatic disease 1), the autosomal recessive polycystic kidney disease (ARPKD) gene, encodes a single-pass, integral membrane protein named polyductin or fibrocystin. A fusion protein comprising its intracellular C-terminus, FP2, was previously used to raise a polyclonal antiserum shown to detect polyductin in several human tissues, including liver. In the current study, we aimed to investigate by immunohistochemistry the detailed polyductin localization pattern in normal (ductal plate [DP], remodelling ductal plate [RDP], remodelled bile ducts) and abnormal development of the primitive intrahepatic biliary system, known as ductal plate malformation (DPM). This work also included the characterization of polyductin expression profile in various histological forms of neonatal and infantile cholestasis, and in cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC). We detected polyductin expression in the intrahepatic biliary system during the DP and the RDP stages as well as in DPM. No specific staining was found at the stage of remodelled bile ducts. Polyductin was also detected in liver biopsies with neonatal cholestasis, including mainly biliary atresia and neonatal hepatitis with ductular reaction as well as congenital hepatic fibrosis. In addition, polyductin was present in CCC, whereas it was absent in HCC. Polyductin was also co-localized in some DP cells together with oval stem cell markers. These results represent the first systematic study of polyductin expression in human pathologies associated with abnormal development of intrahepatic biliary tree, and support the following conclusions: (i) polyductin expression mirrors developmental properties of the primitive intrahepatic biliary system; (ii) polyductin is re-expressed in pathological conditions associated with DPM and (iii) polyductin might be a potential marker to distinguish CCC from HCC.

Background and Aim: A major challenge in neonatal cholestasis (NC) is to differentiate biliary atresia (BA) from other non-atretic causes. In developing countries there are considerable problems of late referral of NC cases and performing surgery without prelaparotomy liver biopsy that contributes to a high proportion of negative laparotomy and increased morbidity. We evaluated the hepatic histopathology for presence of features that correlate best with the diagnosis of BA and assessed the accuracy of percutaneous liver biopsy. Methods: Fifty-five cases of NC that fulfilled the selection criteria and had liver biopsy available were analyzed. Among the 49 adequate liver biopsies, 28 cases were diagnosed as BA, 15 neonatal hepatitis (NH) and 6 were due to other causes. Validity of percutaneous liver biopsy diagnoses was compared with confirmed cases by laparotomy findings and 1-year follow up. Twelve histological parameters of confirmed cases of BA and NH were evaluated by logistic regression analyses. Results: Ductular proliferation (P = 0.0002), bile duct and ductular bile plugs (P = 0.009), and portal fibrosis (P = 0.002) were the best indicators of BA and among them ductular proliferation was the most important in distinguishing BA from NH. Ductal plate malformation was observed in 17.9% cases of BA. Sensitivity and specificity of percutaneous liver biopsy for diagnosing BA was 88.2% each. Conclusion: Percutaneous liver biopsy is highly accurate (88.2%) in diagnosing BA. In developing countries. This investigation should be done to decrease the frequency of negative laparotomy and to achieve cost–benefit with reduced morbidity.

UNLABELLED Hepatic technetium-99m-mebrofenin iminodiacetate (99mTc-mebrofenin IDA) scans and serum gamma-glutamyl transpeptidase (GGTP) have high sensitivity for extrahepatic biliary atresia (EHBA). This study was based on the hypothesis that the interpretation of results of 99mTc-mebrofenin IDA scans and serum GGTP levels in series would result in a reduction of the false positivity observed with these tests individually. The aetiology of neonatal cholestasis in 132 study patients was: 25% (33/132) EHBA, 45.5% (60/132) neonatal hepatitis (NH) with an identifiable cause and 19.7% (26/132) idiopathic NH. Of the various clinical, biochemical and imaging parameters that were significantly different between patient groups, sensitivity for EHBA was: serum GGTP > or = 150 IU l(-1) (100%), 99mTc-mebrofenin IDA scans (100%), pale stools (82.8%) and total serum bilirubin > or = 12 mg dl(-1) (66%). However, specificity ranged from 48.5 to 79%. Of the 63 patients who had non-excreting IDA scans, operative cholangiograms could be avoided on the basis of a specific aetiological diagnosis of NH, made concurrently, in only 9 infants. The rest (54) underwent operative cholangiograms; 21 (39%) of these had patent biliary trees and therefore underwent the procedure unnecessarily. If serum GGTP (< 150 IU l(-1)) had been used as a screen after IDA scanning in these 54 patients, operative cholangiograms could have been avoided in another 12 patients and thereafter only 9/42 (21%) of the operative cholangiograms would have been considered unnecessary. CONCLUSION A diagnostic algorithm is proposed wherein serum GGTP level (at a cut-off level that maintains 100% sensitivity for EHBA) is used in series with non-excreting 99mTc-mebrofenin IDA scans (for patients with no specific aetiological label). This strategy reduces the false positivity of individual tests.

UNLABELLED Congenital hypopituitarism is a recognized cause of neonatal hepatitis, but the diagnosis may be difficult to establish even if clinically suspected. In order to determine the natural history of this disorder, the outcome of 12 infants with neonatal hepatitis secondary to hypopituitarism is reviewed. The clinical diagnosis of hypopituitarism was established on a combination of features, which include dysmorphism (4 infants), optic nerve hypoplasia (8 infants), micropenis (5 male infants) and recurrent hypoglycaemia (blood glucose < 2.4 mmol/l (8 infants)). Endocrine investigation revealed low free thyroxine (T4) levels (< 10 pmol/l), with normal thyroid stimulating hormone (TSH) levels (0.4-4.5 mU/l) (11 infants), and serum cortisol levels which were inappropriately low (< 200 nmol/l). In 9 of 12 infants, liver disease resolved within 6 wk following treatment with thyroxine, hydrocortisone and, where appropriate, growth hormone, including Cases 9 and 1 in whom diagnosis and treatment were delayed until 3 mo and 3 y of age, respectively. Liver disease resolved spontaneously in two infants prior to starting hormone replacement therapy (Cases 11, 12), and one male infant (Case 10), in whom the diagnosis and hormone replacement therapy were delayed until 5 y of age, developed cirrhosis and portal hypertension and later underwent liver transplantation. CONCLUSION The diagnosis of hypopituitarism should always be considered in infants with unexplained neonatal hepatitis. Delay in diagnosis and appropriate treatment was associated with persistently abnormal liver function tests and may lead to irreversible liver disease.

Aim: Alpha 1-antitrypsin (AAT) deficiency is the most common genetic cause of liver disease in children. The Pi*S carrier rate among Filipinos is 20% of the total were recruited. Only one patient (1 month old, male) was positive for Pi*S allele and 95 were negative for Pi*S and Pi*Z alleles, with an annual incidence of 0.7%. Of the 96, 49 infants underwent diagnostic percutaneous liver biopsy. All liver biopsy specimen were subjected to PAS stain and two infants, 2 and 4 months old, both with idiopathic neonatal hepatitis, had suspicious findings of AAT globules that was confirmed on immunostain. Both infants were negative for Pi*S alleles. The only patient positive for Pi*S allele was negative for PAS globule on liver biopsy. Conclusion: Our results showed a low incidence of AAT deficiency caused by the Pi*S and Pi*Z alleles among Filipino infants presenting with neonatal cholestasis, similar to the low carrier rate in the population.

Dehydrated hereditary stomatocytosis (DHSt) is an inherited haemolytic anaemia associated with increased red cell membrane permeability to Na(+) and K(+). It is increasingly recognized that a syndrome of self-limiting perinatal ascites can accompany the haemolysis. The cause of the perinatal ascites is unknown, and it has been argued that this could be due to cardiovascular, hepatic or lymphatic problems. We describe the case of a 16-year-old girl who presented neonatally with abnormal liver function tests and ascites. She was extensively investigated at that time. A liver biopsy showed hepatitis and fatty changes. Her ascites resolved within 6 months. At the age of 15 years, she developed an episode of acute haemolysis and was re-investigated. A diagnosis of DHSt was made. Pseudohyperkalaemia, due to ex vivo loss of K(+) from red cells, was present. This study confirms the previously noted association of DHSt, pseudohyperkalaemia and perinatal ascites, and suggests that the latter is of predominantly hepatic origin.

Type II citrullinaemia (CTLN2) is an adult- or late childhood-onset liver disease characterized by a liver-specific defect in argininosuccinate synthetase protein. The enzyme abnormality is caused by deficiency of the protein citrin, which is encoded by the SLC25A 13 gene. Until now, however, few cases with SLC25A13 mutations have been reported in children with liver disease. We describe an infant who presented with neonatal hepatitis in association with hypergalactosaemia detected by neonatal mass screening. DNA analysis of SLC25A13 revealed that the patient was homozygous for a IVS11+1GA mutation. This case suggests that SLC25A13 mutant should be suspected in neonatal patients with hypergalactosaemia of unknown cause.

This report describes a patient with neonatal lupus erythematosus (NLE) in whom there was multisystem involvement including neonatal hepatitis. The hepatitis, defined pathologically as a giant cell hepatitis, presented with severe cholestasis, was unrelated to other known causes of neonatal hepatitis and resolved spontaneously by 6 months of age. Both mother and infant were positive for Sjögren syndrome A+B antibodies (SS-A[Ro] and SS-B[La]) as well as having high titres of antinuclear antibody (ANA). Three of the four cases described in the one previous report of this association were also ANA positive. This antibody may be a marker for the development of the hepatitis. Maternal and infant ANA status should be determined in cases labelled as idiopathic neonatal hepatitis to exclude undiagnosed maternal SLE as a cause of neonatal cholestasis.

Endoscopic retrograde cholangiopancreatography (ERCP) has long been used in children. The usefulness of ERCP in paediatric patients with various biliary disorders, however, has not been well documented. Thirty-two sessions of ERCP performed in 29 paediatric patients ranging in age from 1 month to 15 years were evaluated. Endoscopic retrograde cholangiopancreatography was to confirm diagnosis or to obtain detailed information about their pancreaticobiliary system. Cannulation was successful in all patients. Opacification of the biliary tracts was also successful in all except for three patients with extrahepatic biliary atresia. Endoscopic retrograde cholangiopancreatography was assessed to be successful in making a differential diagnosis of neonatal hepatitis from extrahepatic biliary atresia, and in having a confirmed diagnosis of anomalous arrangement of the pancreaticobiliary ductal system associated with choledochal cyst. The procedure was also useful for obtaining detailed information on the pancreaticobiliary system in the other children. No accidents occurred during the endoscopic procedures in any of the paediatric patients. When a confirmed diagnosis or detailed information is needed in paediatric patients with biliary disorders, ERCP is a useful and safe technique.

In order to investigate the possibility of early discrimination of extrahepatic biliary atresia from other cholestatic diseases, a series of results of liver function tests in infants with cholestatic diseases were reviewed. The results of routine liver function tests (LFT) recorded in patients' charts were reviewed within 12 weeks after birth in 47 infants with extrahepatic biliary atresia (BA), 10 infants with neonatal hepatitis (NH) and 130 age-matched control infants (CO) without cholestatic diseases. The mean of each test value for each week after birth was derived from the actual data examined in each infant. No differences were observed between BA and CO in the levels of aminotransferases within 2 weeks after birth. Total bilirubin and direct bilirubin levels were significantly different between BA and CO within 1 week after birth (16.1 +/- 3.2 mg/dL vs 11.1 +/- 4.5 mg/dL, 4.6 +/- 2.6 mg/dL vs 0.7 +/- 0.3 mg/dL, respectively). The direct bilirubin-total bilirubin ratio exceeded 25% within the first week in BA. The individual values of direct bilirubin (DB) exceeded 2 mg/dL within the first week in all infants with BA, while none of the individual values exceeded 1.6 mg/dL in CO. Gamma-glutamyl transpeptidase levels were significantly different between BA and CO at 4 weeks (432 +/- 272 IU/L vs 79 +/- 43 IU/L) and thereafter; and were significantly different between BA and NH at 6 weeks (314 +/- 232 IU/I vs 69 +/- 58 IU/L) and thereafter. These data suggest that the determination of direct bilirubin within 1 week after birth can detect extrahepatic biliary atresia patients from those with physiologic jaundice, and gamma-glutamyl transpeptidase levels may discriminate BA from NH at no later than 6 weeks of age.

To clarify the relationship between idiopathic neonatal hepatitis and feeding type, that is, formula-milk feeding and breast-milk feeding, the medical records of 100 patients (68 male and 32 female babies) with idiopathic neonatal hepatitis of non-familial form referred to the medical centers of Akita University and Tohoku University during the past 18 years were reviewed. The patients were divided into two 9 year periods (1975–83 and 1984–92), and their clinical features were analyzed in terms of feeding type and sex. The number of patients enrolled decreased from 69 in the first half to 31 in the second half. The number of male patients dropped from 53 to 15, although the number of female patients (n = 16) remained the same in both 9 year periods. The frequency of formula-milk feeding significantly decreased in the second half (42/69 to 6/31, P < 0.01). Compared with the expected numbers of patients in the second half, calculated on the changes in the live birth population and feeding modality between the two halves, the actually enrolled numbers of patients in the second half were less in both the male and the formula-milk fed groups (× 0.35 and × 0.22), whereas the numbers of female and breast-milk feeding groups were close to the expected values (× 1.26 and × 1.08). When sex and feeding modality were combined, the formula-milk fed male group showed the lowest value (× 0.10), and the breast-milk fed female group showed the highest value (× 2.85). In conclusion, feeding type, especially in combination with gender, might be one causative factor in the occurrence of idiopathic neonatal hepatitis.

Idiopathic neonatal hepatitis (INH) is a syndrome characterized clinically and histologically but there is little information concerning the relationship between the clinical features and histological findings. In the present study, sixty-two patients clinically diagnosed as non-familial INH were histologically classified into four groups according to a provisional definition based on predominant lesions and examination of their clinical features. Patients of cholestasis (n = 23) and giant cell hepatitis (GCH, n = 21) were most frequent (37% and 33%, respectively), and patients of fatty liver (n = 10) and hepatitis (n = 8) were less common (16% and 13%). The GCH group showed a dominance of male, low birthweight, older and breast-fed babies. The cholestasis group demonstrated a dominance of male, low birthweight, younger and bottle-fed babies. The hepatitis group had the highest frequencies of high-grade hepatomegaly and splenomegaly. Fifty six cases completely recovered. Two died of hepatic failure in early infancy and four had chronic liver diseases at the age of 12 months. The fatty liver group had the worst outcome. Histological features in non-familial INH were variable and typical giant cell hepatitis was seen in only one-third of patients. Characteristic clinical features in each histologically classified group may suggest heterogenous etiologies underlying non-familial INH.

The purpose of this study was to establish the incidence of carcinomas in children, changes in incidence over a 30-year period, and to identify features of possible aetiological significance. A total of 173 cases were identified, but after review of the histopathology, 30 patients were excluded because they were considered to have benign epithelial tumours or malignant tumours of nonepithelial origin. Seven other cases were excluded because pathology material was not available. Overall, in 28% of cases, the diagnoses were changed by pathology review. Thus, 136 children in the West Midlands Region diagnosed 1957–1986 were included, with carcinoid tumours (44) and tumours of skin (22), nasopharynx (14), salivary gland (13), adrenal cortex (13), thyroid (9), large bowel (5), other (16). Excluding carcinoids, the age-standardised incidence rate was 2.4 × 106 per year. Male:female ratio was 0.7:1 and 66% were aged >10 years. Incidence increased from 1.5 to 3.3 × 106 per year. Genetic factors predisposing to carcinoma included tyrosinosis, MEN II and III, congenital adrenal hyperplasia and basal cell naevus syndrome. There was a case of Li-Fraumeni syndrome and several other patients had relevant family histories. Probable “environmental” causes included antenatal exposure to stilboestrol or hydroxyprogesterone hexanoate, stilboestrol given for premature menarche, neonatal hepatitis and prior radiotherapy. The aetiology of carcinomas in children is multifactorial, both genetic and environmental factors being important. The incidence is increasing. © 1993 Wiley-Liss, Inc.

The gallbladder wall changes were observed on ultrasonography during the course of a patient with neonatal hepatitis. The gallbladder was not detected at 53 days of age, but on the next day its wall was observed to be markedly thickened and without contraction following the administration of cerulein. It had a thinner wall at 57 days of age and reacted to cerulein. The wall thickness and contractility went together with the improvement of jaundice and liver function tests. Histological diagnosis was compatible with neonatal hepatitis. Ultrasonographic detection of the gallbladder has been helpful to differentiate neonatal hepatitis from biliary atresia. It is reported to be compatible with neonatal hepatitis to detect a normal-sized gallbladder or its contraction following cerulein administration or feeding. Since this case did not meet these criteria initially, thickened wall of the gallbladder may be an additional finding indicating neonatal hepatitis. The importance of repeated ultrasonography and clinical correlation was stressed.

It has become apparent that with sophisticated technology we are now able to recognize defective bile acid metabolism in a wide variety of disease states. Recognition of specific aberrations, such as inborn errors in bile acid metabolism manifesting as neonatal cholestasis, offers new opportunities for therapeutic intervention. Future studies should determine the incidence of inborn errors in patients with enigmatic and unexplained liver diseases such as idiopathic neonatal hepatitis.

From 1985 to 1988 14,938 newborns were screened during the first days of life to determine their protease inhibitor phenotype (Pi) and 467 PiMZ and 456 PiMS were identified. Of these 101 PiMZ and 135 PiMS were followed-up and their clinical, biochemical and, in selected cases, histological data were recorded at two, five and twelve months of age. Nineteen out of 101 PiMZ infants showed hepatic dysfunction at two months, eight at five, and one at twelve months of age, respectively. In 20 of 135 PiMS infants, liver function tests were abnormal at two months, in ten at five and in none at twelve months. It appears that PiMZ and PiMS phenotypes can be associated with hepatic dysfunction during the first six months of life. The marked variability of serum levels of alpha-1-antitrypsin in heterozygotes, make Pi-typing in all cases of neonatal hepatitis advisable. This should also be done for screening purpose.

Following immunization with hepatitis B vaccine, 39 infants were followed prospectively for hepatitis B surface antigen (HBsAg). A total of 69.2% of the infants tested positive for antigenemia at least once. Antigenemia was identified most often at 2-3 days (43.5%) and 5-6 days (43.5%) after immunization. The longest documented duration of antigenemia was 21 days. In all cases the antigenemia was transient and cleared by the 28th day post-vaccination.

Serum gastrin levels were measured radioimmunologically in 123 patients with various gastrointestinal diseases to study the pathophysiological role in the diseases. 1) In winter diarrhea, mean fasting gastrin level tended to be slightly higher in the severer patients but the difference from the control level were not statistically significant. After test meal, however, mean serum gastrin level increased rapidly and reached a peak by after 10 minutes followed by levelling off for 20 minutes. This result may suggest that a feedback mechanism between the secretion of gastrin and secretin is disturbed in the disease. 2) In bacillary dysentery, mean fasting serum gastrin levels in the acute stage did not differ from that of controls. 3) Mean fasting serum gastrin levels in neonatal hepatitis and chronic hepatitis of school children were significantly lower but the level in congenital biliary atresia was not different as compared to those of age-matched controls. Further investigation of gastrin metabolism in liver may be needed. 4) In duodenal ulcer, mean fasting serum gastrin level was not different statistically from the control value but mean gastrin response to feeding was significantly greater and longer than that of controls. This abnormality of gastrin release in children with duodenal ulcer may have a significant role in the pathogenesis of the disease. 5) In superior mesenteric artery syndrome, mean fasting gastrin level was significantly lower than that of controls and mean serum gastrin responses to test meal both in sitting and prone positions were significantly lower than those of controls. No statistical difference was found when the response were compared between in a sitting and prone positions. The hypogastrinemic response to meal in patients with this order was probably considered to be due to impaired function of G-cells which was caused by dilatation of the stomach and/or duodenum resulting in the mucosal damage. 6) The increment of gastrin secretion following glucocorticoid administration was found in children with anaphylactoid purpura and the effect was confirmed in rats. This results suggest that the so-called steroid ulcer may partly be caused by steroid induced gastrin hypersecretion.

To elucidate the enterohepatic circulation of bile acids in hepatobiliary disorders, the present author measured the fasting cholic acid levels in serum and followed up the changes of the levels after MCT milk administration. The subjects were 17 cases of neonatal hepatitis, 24 cases of congenital biliary atresia (CBA), 19 cases of other hepatobiliary disorders and 117 normal children. The serum cholic acid levels in the neonatal period were significantly high, which suggested a physiological cholestasis in neonates which gradually decreased with age. The mean level in CBA was rather higher than that in neonatal hepatitis but showed overlap of the levels. The patterns of changes of serum cholic acid levels in MCT milk test were classified into 6 types which were respectively characteristic of each disorders according to varied disturbance of the enterohepatic circulation of bile acids. This MCT milk test may be useful in making a differential diagnosis of various hepatobiliary disorders, especially neonatal hepatitis and CBA.

Serum alpha-fetoprotein levels were measured using a sensitive radioimmunoassay in 77 infants presenting with persistent conjugated hyperbilirubinaemia. A breed range of alpha-fetoprotein concentrations occurred in both the 23 infants with extrahepatic biliary atresia and the 35 with idiopathic neonatal hepatitis but the 13 with alpha-1-antitrypsin deficiency had uniformly low levels. High alpha-fetoprotein concentrations (above 10 000 mug/1) favoured the diagnosis of neonatal hepatitis especially in the first ten weeks of life, but the overlap between neonatal hepatitis and extrahepatic biliary atresia was large and alpha-fetoprotein determination cannot be recommended as a reliable method for distinguishing the two conditions. Serial alpha-fetoprotein values showed no consistent relationship with standard liver function tests and gave no guide to prognosis. There was an association between alpha-fetoprotein production and needle biopsy evidence of hepatic giant cell transformation. The uniformly low alpha-fetoprotein levels in alpha-1-antitrypsin deficient infants with neonatal hepatitis is a new observation and possible mechanisms for disordered glycoprotein release are discussed.

To investigate possible involvement of immune responses in the pathogenesis of obstructive jaundice in infancy we measured antibody to liver specific lipoprotein (LSP) by radio immunoassay and immune complexes by their ability to bind Clq in sera from 16 patients with extrahepatic biliary atresia and 16 with neonatal hepatitis and 13 age matched controls. Anti-LSP was present in 6 of 16 with preoperative biliary atresia and 6 of 16 with hepatitis. Mean percentage Clq bound was higher in hepatitis (22 SD 15 %) than preoperative biliary atresia (11.1 SD 2.3 %). Nine of 16 hepatitis patients had elevated Clq binding as compared with 1 of 16 with biliary atresia. The highest value for anti-LSP and Clq binding were found in sera from patients with histologically severe hepatitis and hepotitis associated with specific viral or bacterial causes. Anti-LSP was significantly raised 5 months post-operatively in all of 6 patients with biliary atresia and poor biliary drainage but only 2 of 5 survivors. Elevated Clq binding was detected in 6 of 7 with poor drainage and 1 of 7 survivors at the same stage. Anti-LSP and Clq binding fell in 4 patients with neonatal hepatitis on recovery. These findings suggest that immunological mechanisms, possibly involving antibody to hepatocyte membrane components and immune complexes, may be involved in the pathogenesis of progressive liver disease in biliary atresia.

The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D2 for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5 +/- 3.7 (S.E.) ng/ml to 34.0 +/- 6.8 (S.E.) ng/ml after administration of vitamin D2 in controls (p less than 0.05). The mean plasma level of 25-OH-D also increased from 8.0 +/- 2.1 (S.E.) ng/ml to 22.1 +/- 2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group (p less than 0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect eh plasma levels of 25-OH-D.

Fetal blood sampling for the diagnosis of alpha-1-antitrypsin deficiency using protein isoelectric focusing was carried out in the period 1980–1985. The results of 25 cases from 18 mothers are reported. All had a previous history of a PiZ child affected by liver disease. The method was found to be technically satisfactory and the fetal results were subsequently confirmed in all 18 cases where follow-up was possible. The fetus was found to be PiZ in nine cases and all these pregnancies were terminated. Of the remaining pregnancies three cases aborted or were delivered prematurely and 13 proceeded to term without complications.

SYNOPSIS Seventy-six newborn infants with significant jaundice, caused by other than foetomaternal blood group incompatibility, have been studied by simple but systematic methods. Bacterial infection emerged as the most common cause. Blood culture and microscopy of urine proved to be the most rewarding routine tests and these are advocated in all newborn babies in whom jaundice gives rise to concern. ‘Neonatal hepatitis’ and biliary atresia were the main causes of jaundice which persisted for more than one month, and investigation of their aetiology is briefly reported.

Atresia and hypoplasia of the bile ducts are the most common congenital biliary anomalies of clinical importance. Surgical correction can help about 10% of these infants. However, surgery should be performed within the first month of life to avoid irreversible liver parenchymal changes. It is difficult to separate the surgical condition, biliary atresia, from conditions in which the trauma of laparotomy should be avoided, such as neonatal hepatitis and other clinically indistinguishable causes of obstructive jaundice. Radionuclide imaging with the 99mTc-labeled N-substituted iminodiacetic acids (HIDA, PIDIDA, DISIDA, etc) have been helpful in the differential diagnosis of biliary atresia.

Hepatoblastoma differs from the adult type of hepatoma in clinical and pathologic features. The ratio of fucosylation of serum alpha-fetoprotein (AFP) was determined in seven patients with hepatoblastoma and in 21 infants and children with otherwise elevated serum AFP, using the improved technique of lentil agglutinin-affinity immunoelectrophoresis. The clinical data for the seven patients with hepatoblastoma were also reviewed. The ratio of fucosylation of AFP was significantly higher in all seven patients with hepatoblastoma, whereas it was minimal in all other cases of benign hepatic conditions such as neonatal hepatitis or biliary atresia, as well as in normal newborns. The ratio of fucosylation in hepatoblastoma, however, definitely decreased with the age of the patient at presentation. This finding suggests a correlation between fucosylation and a rapid rate of tumor growth, because all hepatoblastomas are believed to originate early in fetal life.