Utility of liver biopsy culture in pediatric liver transplant recipients

Abstract: The purpose of our study was to determine the utility of the practice of culturing percutaneous liver biopsy specimens obtained from pediatric LT recipients for evaluation of fever and/or elevated serum aminotransferases. Accordingly, a retrospective analysis was done of the 101 liver biopsies obtained during an eight-year period which had been submitted for bacterial, fungal and/or viral culture (out of a total of 174 biopsies in 38 patients). The purpose of the analysis was to ask three questions. (1) What organisms were cultured? (2) Were there clinical profiles that were characteristic of the type of organism? (3) Was the practice cost-effective? The analysis indicated that 34/86 biopsy cultures were positive for bacteria, 4/75 for fungus and 2/81 for virus. Clinical and laboratory data for children with cultures positive for enteric flora (n = 9) were compared to those with cultures positive for Gram-positive organisms (n = 17), laboratory contaminants (n = 8), and those with negative cultures (n = 52). Children with biopsies positive for enteric flora had a ‘cholestatic profile’: mean direct bilirubin 7 mg/dl, ALT 78 IU/l, direct bilirubin/ALT 0.09, in comparison to children with biopsies positive for Gram-positive flora. These children had a ‘hepatocellular profile’: mean direct bilirubin 4 mg/dl, ALT 332 IU/l, direct bilirubin/ALT 0.01 (p = 0.04 versus the enteric flora values) and a high percentage of polymorphonuclear leukocytes (mean 69% versus 38% for those with negative cultures, p = 0.001.) The charge for performing each bacterial culture was $28 (total $28 × 86 = $2408: $268 per enteric flora-positive biopsy; $93 per biopsy positive for either enteric flora or Gram-positive flora). The charge for each fungal culture was also $28 (total $28 × 75 = $2100: $525 per positive culture), while the cost for each viral culture was $140 (total $140 × 81 = $11 340: $5670 per positive culture). Thus, discounting the eight cultures positive for laboratory contaminants, a total of $15 848 was spent for 32 positive cultures. Given the high cost of liver transplantation, this information suggests that discretion should be used in submission of liver biopsy samples for culture in pediatric transplant patients. We recommend that when liver biopsies are performed for evaluation of elevated serum aminotransferases and/or fever, culture of biopsy specimens for bacteria should be considered in children with a ‘cholestatic profile’: direct bilirubin ≥ 7 mg/dl and direct bilirubin/ALT > 0.08, or a ‘hepatocellular profile’: direct bilirubin ≤ 4 mg/dl and direct bilirubin/ALT < 0.05, together with polymorphonuclear leukocytes > 70%. Following these guidelines might provide valuable information pertinent to patient management (especially since Gram-negative organisms can sometimes be cultured from the liver and not from blood) while reducing costs. Fungal cultures should be restricted to critically ill children. However, our data suggest that the practice of obtaining fungal and viral cultures of the liver in most pediatric transplant patients has an unacceptably high cost/benefit ratio, particularly since recovery of the organism from the peripheral blood is likely.     

Cytomegalovirus DNA detection on Guthrie cards in patients with neonatal cholestasis.

AIM: To time the onset of cytomegalovirus (CMV) infection in patients (n = 39) with CMV associated neonatal cholestasis by analysing CMV DNA on Guthrie cards sampled at 3 days of age. METHODS: CMV infection was diagnosed by serology/urine isolation or by CMV DNA detection (polymerase chain reaction) in liver biopsy specimens. In order to time the infection dry blood filter paper discs were punched out from stored Guthrie cards. After phenol-choloroform extraction CMV DNA was detected by nested polymerase chain reaction. RESULTS: All cards from control children (n = 8) with congenital CMV tested positive; none of the negative controls (n = 4) did so. Two of 39 cholestatic infants were CMV DNA positive; their mothers had serological signs compatible with infection during the second half of the pregnancy. All other cholestatic infants tested negative. CONCLUSIONS: CMV DNA was not detected in most of the children using Guthrie cards, suggesting that infection developed at or soon after birth.     

alpha1-Antitrypsin deficiency is not an important cause of childhood liver diseases in a multi-ethnic Southeast Asian population

AIM: We conducted a prospective study to determine the role of alpha1-antitrypsin (alpha1AT) deficiency in the pathogenesis of neonatal cholestasis and other childhood liver diseases in a multi-ethnic Southeast Asian population. METHODS: Prospective patients with neonatal cholestasis (group 1), other liver diseases (group 2) and children with other medical conditions (group 3) referred to the Paediatric Unit, University of Malaya Medical Centre, Malaysia, from May 2002 to June 2005, were screened for alpha1AT level and phenotype. alpha1AT level below 80 mg/dL was considered as low. RESULTS: Of the 114 patients (group 1, n = 53; group 2, n = 42; group 3, n = 19) screened, seven patients (6% of total; group 1, n = 1; group 2, n = 4; group 3, n = 2) had a alpha1AT level below 80 mg/dL. All had marginally low level (range 57-79 mg/dL), but none had a clinical diagnosis of alpha1AT deficiency. One patient had PiZ- heterozygous phenotype (alpha1AT level 217 mg/dL) while another patient had PiMS heterozygous. CONCLUSIONS: alpha1AT deficiency is not an important cause of neonatal cholestasis and childhood liver diseases in Malaysian children. In Malaysian children with neonatal cholestasis or other liver diseases, routine assay for alpha1AT phenotype is not recommended if there is no family history of neonatal cholestasis of uncertain aetiology, or if alpha1AT level is above 80 mg/dL.     

Niemann-pick disease type C in neonatal cholestasis at a North American Center

OBJECTIVE: To determine the frequency of Niemann-Pick disease type C (NPC) among children being evaluated for neonatal cholestasis during a 2-year period. METHODS: Medical records were reviewed from all infants with cholestasis and all patients with NPC evaluated at our center from January 1997 through December 1998. RESULTS: Forty neonates with cholestasis were evaluated, including three patients diagnosed with NPC (age at diagnosis, 5-21 months) who were originally labeled as having idiopathic neonatal cholestasis (INH). Two adolescents (ages 14 and 16 years) were also diagnosed with NPC during this period, one who originally had neonatal hepatitis and cirrhosis, and the other who had hepatosplenomegaly throughout childhood. Three of the patients with NPC were Hispanic. At time of NPC diagnosis, infants had mildly delayed motor development and persistent splenomegaly with or without hepatomegaly, and the adolescents had ataxia, dysarthria, hepatosplenomegaly, and paresis of vertical gaze. The diagnosis of NPC was established by demonstrating defective cellular cholesterol esterification in cultured skin fibroblasts in three patients and a specific genetic mutation in three patients. Niemann-Pick disease type C was found in 27% of infants initially diagnosed with INH and 8% of all infants evaluated for cholestasis. CONCLUSION: Niemann-Pick disease type C should be considered in all infants with cholestasis, particularly those with splenomegaly or who are of Hispanic descent. Electron microscopy and lipid analysis of liver biopsy specimens obtained during the evaluation of neonatal cholestasis may suggest this diagnosis.     

Hyaluronic acid: Additional biochemical marker in the diagnosis of biliary atresia

BACKGROUND: The purpose of the present paper was to evaluate the value of biochemical markers, including conventional liver function tests, gamma-glutamyl transferase (GGT), and hyaluronic acid (HA), in the diagnosis of neonatal cholestasis. METHODS: Infants with neonatal jaundice were consecutively enrolled during 1 year period. The patients were diagnosed as having biliary atresia (BA) if there was either bile ductular proliferation in the portal tracts, atretic common bile duct/gallbladder, or evidence of bile duct obstruction demonstrated by liver pathology or intraoperative cholangiography, respectively. Serum HA was measured using an enzyme-linked immunosorbent assay-based test. RESULTS: A total of 25 patients diagnosed as having BA (n = 10), neonatal hepatitis (NH; n = 9), choledochal cyst (n = 3) and parenteral nutrition-induced cholestasis (n = 3), were studied. The age at diagnosis was not significantly different between groups. Only GGT and HA were significantly elevated in the patients with BA when compared to NH (P = 0.02, P = 0.03, respectively). In BA, the median value of serum HA was 514 ng/mL (range 19-4476 ng/mL), compared to 50 ng/mL (range 19-315 ng/mL) in NH. Additionally, the serum HA level was much higher in children with choledochal cyst. CONCLUSION: HA could be considered as a complementary biochemical marker for evaluating infants with prolonged jaundice.     

Long-term outcome after partial external biliary diversion for intractable pruritus in patients with intrahepatic cholestasis

BACKGROUND: Chronic intrahepatic cholestasis is associated with severe pruritus that is often refractory to maximal medical management and leads to significantly impaired quality of life. The hypothesis in this study was that partial external biliary diversion (PEBD) can substantially improve intractable pruritus secondary to intrahepatic cholestasis with subsequent improvement of functional quality of life. METHODS: Parents' and/or patients' clinical rating of pruritus, growth percentiles, biochemical parameters, and liver biopsies performed before and after surgery were compared in a retrospective medical record review. RESULTS: Eight children underwent PEBD from 1990 through 1997. Complete follow-up data were available for seven patients. Before surgery, all patients had intense pruritus, which was not responsive to maximal medical therapy. Specimens obtained in preoperative liver biopsies showed moderate (n = 1), minimal (n = 6), or no (n = 1) portal fibrosis. After PEBD, all patients received ursodeoxycholic acid (10-15 mg/kg/dose two to three times daily) until resolution of pruritus. Of the seven patients with complete follow-up data, six had complete resolution of pruritus and sustained resolution up to 8 years after surgery. The patient with mild to moderate residual pruritus was the youngest to undergo PEBD. Growth improved from below the 5th percentile before surgery to the 5th through the 25th percentiles for five of six patients with more than 6 years' follow-up. All families reported improved quality of life, defined by school attendance and ability to resume normal activity with peers. There has been no clinical evidence of progression of liver disease. CONCLUSION: Partial external biliary diversion is effective in the long-term treatment of pruritus refractory to medical therapy and provides a favorable outcome in a select group of patients with chronic intrahepatic cholestasis without cirrhosis.     

Laparoscopic liver biopsy using cup-shaped punch biopsy forceps and argon beam coagulator in children

Needle liver biopsy is insufficient for measuring enzyme activity in liver tissue in child cases of intrahepatic cholestasis because the biopsy specimen obtained is too small. This study was undertaken to validate the feasibility of a new, relatively non-invasive laparoscopic liver biopsy technique combining the use of laparoscopic cup-shaped punch biopsy forceps (CPBF) and an argon beam coagulator (ABC™) handpiece for the diagnosis and examination of liver enzyme activity in cases of intrahepatic cholestasis in children. The authors performed laparoscopic liver biopsy with the combined use of laparoscopic CPBF and an ABC™ handpiece in 10 children aged 4 months to 9 years old. Two 5-mm trocars were inserted in each patient after their abdomens had been filled with carbon dioxide gas at a pressure of 8 mmHg. Four to five specimens (each: 0.5 cm³ in size) were taken at the anterior edge of the left lobe of the liver using laparoscopic CPBF. ABC™ was sprayed on to the cut liver surface to achieve hemostasis. The duration of the laparoscopic procedure ranged from 25 to 64 (44 ± 12.8) min. The maximum intraoperative hemorrhage from the biopsied liver bed was 30 ml. The bleeding was easily controlled using ABC™ for about 1 min. There were no cases of postoperative bleeding, bile leakage from the cut surface, nor intraabdominal infection. There were also no death cases, and only one complication (hydrocele testis) was recorded. Examination by microscopy and assays of enzyme activities were performed using these biopsy specimens, which were sufficient for diagnosis in all patients. Laparoscopic liver biopsy combining the use of laparoscopic CPBF and an ABC™ handpiece can be performed safely, is less invasive, and provides sufficient samples for examination both by microscopy and enzyme activity assays.     

Comparison between prenatally diagnosed choledochal cyst and type-1 cystic biliary atresia by CD56-immunostaining using liver biopsy specimens.

Because it is difficult to distinguish preoperatively between a prenatally diagnosed choledochal cyst (CC) and type-1 cystic biliary atresia (BA) by ultrasound scanning or magnetic resonance imaging, some mode of discriminating between the 2 entities is required. The aim of this study was to investigate the immunohistological differences between prenatally diagnosed CC and type-1 cystic BA, using liver biopsy specimens immunostained for CD56. Five children with prenatally diagnosed CC and two children with prenatally diagnosed type-1 cystic BA were identified by fetal ultrasonography between 1985 and 2004. The control group included two children who were operated on at an earlier period due to postnatally diagnosed BA. Liver wedge biopsy in the right lobe was performed at the time of the radical operation. Histological findings of the CD56-stained liver biopsy specimens were classified into 4 categories each, with particular focus on staining distribution and intensity. The staining distribution was classified according to the scale 0 = no staining; 1 = some staining of bile ducts/ductules but staining in less than one-third of portal tracts; 2 = staining in one-third to less than two-thirds of portal tracts; and 3 = staining in more than two-thirds of portal tracts. Staining intensity was scored as follows: 0 = no staining, 1 = weak staining, 2 = moderate staining, and 3 = strong staining. The staining intensity and distribution in the CC group was zero in all 5 cases. The type-1 cystic BA group consisted of patients with scale 1 or 3 staining distribution and score 1 or 2 staining intensity. In the control group, staining distribution was 1 or 3, and staining intensity was 1 or 3. These results indicate that CD56-positive biliary duct cells are present in prenatally diagnosed type-1 cystic BA. The authors suggest that exploratory laparotomy might be avoided and, instead, immunohistological examination using liver biopsy specimens may be a reliable test for the differential diagnosis of CC and type-1 cystic BA in prenatally diagnosed neonates.     

Transient elastography for non‐invasive evaluation of post‐transplant liver graft fibrosis in children

As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow‐up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non‐invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non‐invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100‐fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval ‐0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non‐invasive, reliable tool for the assessment of graft fibrosis in the follow‐up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.     

Renal Biopsy and Family Studies in 65 Children with Isolated Hematuria

ABSTRACT. We have investigated 65 children with isolated hematuria persisting for at least a year. Renal biopsy specimens were studied by light microscopy, electron microscopy and immunofluorescence with antisera specific against basement membrane components. The majority of the biopsies (62/65) showed variable histologic abnormalities. Four categories could be distinguished on combined histological and clinical criteria: Alport syndrome (n=8), benign hematuria (n=33, familial in 23), IgA nephropathy (n = 16) and increase in mesangial cells and matrix (n=5). On the basis of our results, we suggest that a renal biopsy can establish diagnosis and prognosis in those children with isolated hematuria where the family history is negative. If the family has adult male individuals with isolated hematuria, a biopsy can usually be avoided, since this family history effectively excludes Alport syndrome. The use of antisera against basement membrane components did not allow a differentiation between Alport syndrome and benign hematuria. Goodpasture serum immunofluorescence was variable in the former and normally present in the latter.     

The constipated child: how likely is Hirschsprung's disease?

The incidence of Hirschsprung's disease (HD) was determined in children who presented with constipation to a specialist paediatric surgical unit. During a 5-year period, 355 rectal biopsies were performed on 182 neonates, infants and children presenting with chronic constipation or intestinal obstruction: 25 (14%) were diagnosed HD. One hundred and four patients had suction and 78 had full-thickness rectal biopsies. Haematoxylin-eosin (HE) staining and acetylcholinesterase (AChE) histochemistry was used. In 13 cases (8%) of suction and 2 cases (2.5%) of full thickness rectal biopsies, specimens were inadequate to diagnose HD. The mean age of all patients was 2.9 years and that of patients diagnosed with HD was 3.64 months. Nineteen patients with HD were diagnosed in the first month, 5 in 1-12 months and 1 at 4 years of age (Fig. 1). The authors found that along with onset of constipation convincing indications for rectal biopsy to exclude HD were as follows: those infants and children who do not pass meconium within 48 hours, have low intestinal obstruction of unknown cause, severe constipation, chronic abdominal distension and failure to thrive. A diagnostic accuracy of 94% was achieved with AChE histochemistry for suction rectal biopsy. After this review, referring paediatricians were advised that screening of other common organic causes of constipation with the least invasive investigations, including laboratory, dietary and paediatric gastroenterology advice, should be undertaken to avoid unnecessary rectal biopsy to exclude HD and related disorders.     

Rectal biopsy: what is the optimal procedure?

Rectal suction biopsy (RSB) is a well-known diagnostic procedure for disorders of bowel motility such as Hirschsprung's disease (HD). However, there are few reports about the optimal method of obtaining rectal tissue. We introduce a new technique using Gruenwald's nasal cutting forceps (NCF). From 1986 to 1999, we performed 130 sets of rectal biopsies in patients suspected of having HD. In group I (1986 to 1994), 68 sets of three-site biopsies (2, 3, and 5 cm above the dentate line) were performed using a conventional blind RSB technique. In group II (1995 to 1999), 62 sets of one-site biopsies (2 cm above the dentate line) were performed using Gruenwald's NCF after anal dilatation during general anesthesia. Hematoxylin-eosin staining and acetylcholinesterase histochemistry were used to examine all specimens. Biopsy specimens in group II (4.39 +/- 1.07 mm(2)) were larger than in group I (1.59 +/- 0.39 mm(2)) ( P < 0.01). In 18 cases (26 %) in group I, normal and HD bowel could not be differentiated because the specimens were too small to detect ganglion cells (i.e., only lamina propria [9 cases] or a small area of submucosa [9 cases] was present). These cases required repeat biopsy. All cases of HD diagnosed in group I (n = 20) were based on the findings of biopsies taken at 2 cm; biopsies from 3 and 5 cm did not provide additional information. There were 2 cases of post-biopsy hemorrhage in group I. In group II, 18 subjects were diagnosed with HD and 39 were confirmed to have normal bowel. There were no complications and repeating the biopsy was unnecessary. Three cases of hypoganglionosis (1 in group I and 2 in group II) were missed because the myenteric plexus abnormalities could not be detected by RSB. Intestinal neuronal dysplasia (IND) was diagnosed in 5 cases (2 in group I by repeat full-thickness biopsy and 3 in group II by rectal biopsy). We conclude that our new technique is advantageous and safe to differentiate between normal bowel, HD, and even IND on the basis of a single biopsy taken 2 cm above the dentate line. The biopsy can be taken under direct vision and is histopathologically accurate.     

Acute hemorrhagic edema of infancy: the experience of a large tertiary pediatric center in Israel

Background:Acute hemorrhagic edema of infancy (AHEI) is a rare leukocytoclastic vasculitis of the small vessels occurring at a young age and considered as a benign self-limited disease.Due to its low prevalence,there are limited data on the presentation and complications of this disease.Methods:All computerized files of children who were hospitalized at a tertiary pediatric center due to AHEI over a 10 year period were reviewed.Clinical,laboratory and histopathological data were collected.Results:Twenty-six patients were included in our study,accounting for 0.7 cases per 1000 admissions of children aged 2 years or less.Mean age was 12.9 months.More than two thirds of the children had preceding symptoms compatible with a viral infection.Upon admission,all patients presented with typical findings of a rash and edema.Edema was most profound over the lower extremities (73％).Concomitant viral or bacterial infections were found in six children.Skin biopsy was performed in six patients revealing leukocytoclastic vasculitis.Thirteen children (50％) had systemic involvement including joint involvement (n=9),gastrointestinal hemorrhage (n=4),microscopic hematuria (n=1) and compartment syndrome of the limb (n=1).The latter was diagnosed in a patient with familial Mediterranean fever.Conclusions:Our largest data series highlighted what is known regarding clinical and histological findings in children with AHEI.However,contrary to what was previously reported,we found a higher rate of systemic involvement.Although AHEI is a rare entity,pediatricians should be familiar with its presentation,management and our reported complications.     

Ursodeoxycholic acid treatment in children with Byler disease

BACKGROUND: There have been a few reports of patients with Byler disease and the best medical treatment is not known. The aim of the present study is to show the effect of ursodeoxycholic acid (UDCA) on clinical, laboratory and histologic findings in children with Byler disease. METHODS: Nine children aged between 1.5 and 9 years with Byler disease were administered UDCA orally at doses of 15-20 mg/kg per day. They were followed for at least 12 months. Clinical, laboratory and histologic outcomes were evaluated after 12 months of treatment. RESULTS: Seven children presented in the first 6 months of life with itching and/or jaundice. Gamma-glutamyl transpeptidase and cholesterol levels were normal in all patients, despite severe cholestasis. With UDCA therapy, pruritus disappeared/diminished in four (44.4%) patients. The mean serum concentrations of alanine aminotransferase, aspartate aminotransferase (AST), total and conjugated bilirubin decreased, although it was significant only for AST (P = 0.01). Before treatment, all biopsy materials showed cellular/canalicular cholestasis and fibrosis. After UDCA therapy cholestasis was ameliorated. Two patients died during follow up. CONCLUSIONS: The results suggest that administration of UDCA leads to clinical and biochemical improvement in children with Byler disease. The UDCA ameliorates symptoms partially, improves the life quality of patients and may be given for as long as the disease continues.     

The significance of isolated elevation of serum aminotransferases in infants and young children.

INTRODUCTION: The aim of this study was to assess the clinical significance and prognosis of a prolonged isolated elevation of serum aminotransferases without cholestasis (>3 months) in infants and young children, investigated for a variety of conditions, and to determine a protocol for their follow-up and investigation. METHODS: A combined prospective-retrospective analysis of apparently healthy babies and young children with isolated elevation of serum aminotransferases of at least 1.5 times above the norm for age which persisted for at least 3 months and whose creatine phosphokinase (CK), gamma glutamyltransferase (GGT), alkaline phosphatase and bilirubin levels remained normal throughout the study duration. The children underwent the following investigations: abdominal ultrasound and infectious, metabolic and/or immunological investigation depending on the duration of the abnormality. RESULTS: Six children were eliminated following the finding of positive cytomegalovirus (CMV) antigen in the urine. 72 children were investigated (47 males and 25 females). The duration of serum aminotransferases elevation was 3-36 months (average 12.4, median 11.5 months). The initial, maximal and final alanine aminotransferase (ALT) values were 85.5, 140.5 and 39.8 IU/l, respectively. Of seven children who had liver biopsies performed, three (42.8%) were suspected of having a glycogen storage disease which was not confirmed enzymatically. Four biopsies revealed non-specific histological changes. CONCLUSIONS: Isolated elevation of serum aminotransferases in healthy looking young children is mostly a benign condition that usually resolves within a year. If no pathology is found during routine investigation, these children can be followed conservatively. Liver biopsy does not contribute much to the diagnosis and is probably unnecessary.     

Analiza wskazań do biopsji wątroby u dzieci w doświadczeniu referencyjnego ośrodka hepatologii dziecięcej

Histopathological examination of the liver is used to diagnose, stage, prognose and monitore many liver diseases. Indications to the liver biopsy in children may vary. Percutaneous and surgical biopsies are the most frequently performed procedures in native or in transplanted liver, in explanted and partially resected organs. The aim of this study is to review all of histopathological liver examinations performed in Children's Memorial Health Institute (the main centre of pediatric hepatology in Poland) with division of biopsy types and indications in various age groups.

Renal biopsy and family studies in 65 children with isolated hematuria

We have investigated 65 children with isolated hematuria persisting for at least a year. Renal biopsy specimens were studied by light microscopy, electron microscopy and immunofluorescence with antisera specific against basement membrane components. The majority of the biopsies (62/65) showed variable histologic abnormalities. Four categories could be distinguished on combined histological and clinical criteria: Alport syndrome (n = 8), benign hematuria (n = 33, familial in 23), IgA nephropathy (n = 16) and increase in mesangial cells and matrix (n = 5). On the basis of our results, we suggest that a renal biopsy can establish diagnosis and prognosis in those children with isolated hematuria where the family history is negative. If the family has adult male individuals with isolated hematuria, a biopsy can usually be avoided, since this family history effectively excludes Alport syndrome. The use of antisera against basement membrane components did not allow a differentiation between Alport syndrome and benign hematuria. Goodpasture serum immunofluorescence was variable in the former and normally present in the latter.     

Clinical and pathological characteristics of Alagille syndrome in Chinese children

Background  Alagille syndrome (AS) is regarded as the most common cause of chronic cholestasis in childhood associated with specific phenotypic features in western countries. This study was undertaken to investigate the significance of AS in Chinese children with chronic cholestasis and to describe its clinical and histological features. Methods  From October 2004 to January 2007, 157 children who presented with conjugated jaundice from less than 3 months of age were admitted to a tertiary hospital in Shanghai. Investigations of the heart, spine, eyes and kidneys were conducted in 13 children who experienced prolonged cholestasis beyond 1 year of age after exclusion of biliary atresia and familial progressive intrahepatic cholestasis type 1 or 2. In patients with interlobular bile duct paucity, AS was diagnosed if 3 or more of the following 5 major features were present: cardiac murmur, posterior embryotoxon, butterfly-like vertebrae, renal abnormalities and characteristic faces. In patients without interlobular bile duct paucity or who did not receive liver biopsy, 4 or more features were required for the diagnosis. Results  Of the 13 children, 6 were diagnosed with AS at ages ranging from 1 year and 7 months to 3 years and 11 months. Jaundice was noticed in early infancy and then pruritus developed in all the 6 patients, of whom 5 presented with acholic stool and 4 had been misdiagnosed as having presumed biliary atresia by hepatobiliary scintigraphy or laparoscopic cholangiography. Biochemical examinations demonstrated increased concentration of total bile acid and hyperlipidemia. Interlobular bile duct paucity was demonstrated histologically in 5 patients who received liver biopsy. Vertebral abnormalities, heart murmur, characteristic faces and failure to thrive were found in all the 6 patients. Two patients had evidence of renal involvement. Micropenis, empty scrotum, and gall stone were seen in 1 patient. Conclusion  AS is also an important cause of prolonged cholestasis in Chinese children. It is difficult to differentiate AS from biliary atresia. Liver biopsy and spine X-ray may be helpful in the early detection of AS.     

Disease of the liver following bone marrow transplantation in children: incidence, clinical course and outcome in a long-term perspective

Sixty-four consecutive cases of allogeneic ( n = 16), autologous ( n = 47) or syngeneic ( n = 1) bone marrow transplantation (BMT) in children with haematological or lymphoid malignancy, aplasia or metabolic disease were reviewed to assess the incidence, clinical presentation and outcome of liver disease. Median follow-up time was 5 y (1.0-10). No liver diagnosis was established at the pre-transplant check-up. During the first 100d post-transplant, 81% of the patients had impaired liver function as documented by various biochemical parameters. Three of 64 patients (5%) met diagnostic criteria for veno-occlusive disease. Four (25%) of the 16 receiving allografts were diagnosed as having acute graft vs host disease (GVHD) with liver involvement (grades II-III). No patient died of liver disease. During the late post-transplant follow-up, one patient developed HCV hepatitis after packed erythrocyte transfusion. Four patients were diagnosed as having chronic GVHD with liver involvement; three of them also had an episode of CMV hepatitis. At their latest follow-up, the patients with chronic GVHD had aminotransferase values 1.5–3 times the normal, whereas all other long-term survivors had normal or near-normal liver function tests. We conclude that the incidence of serious liver disease was low in this paediatric population of bone marrow recipients.     

Histological differentiation between prenatally diagnosed choledochal cyst and type I cystic biliary atresia using liver biopsy specimens.

Because it is difficult to distinguish preoperatively between prenatally diagnosed choledochal cyst (CC) and type I cystic biliary atresia (BA) by ultrasound scanning or magnetic resonance imaging (MRI), some modality of discrimination for the 2 entities is required. The aim of this study was to investigate the histological differences between prenatally diagnosed CC and type I cystic BA using liver biopsy specimens. Four children with prenatally diagnosed CC and two children with prenatally diagnosed type I cystic BA were identified by fetal ultrasonography between 1985 and 2003. The control group included two children who were operated on at an earlier period due to postnatally diagnosed BA. Liver wedge biopsy in the right lobe was performed at the time of the radical operation. Histological findings of the H & E-stained liver biopsy specimens were classified into 4 grades (Grade 0, no abnormality; Grade 1, ductular proliferation without bridging fibrosis; Grade 2, ductular proliferation with bridging fibrosis; and Grade 3, liver cirrhosis). The CC group consisted of one case of Grade 0 and three cases of Grade 1. The type I cystic BA group consisted of one case each of Grade 2 and Grade 3. In the control group, both cases were Grade 2. The authors suggest that exploratory laparotomy might be avoided and, instead, histologic examination using liver biopsy specimens can be a reliable test for the differential diagnosis of CC and type I cystic BA in prenatally diagnosed neonates.