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Mucopolysaccharidosis (MPS) IIIB (Sanfilippo syndrome, OMIM 252920) is a lysosomal storage disorder caused by the deficiency of α-N-acetylglucosaminidase (NAGLU), a lysosomal hydrolase involved in the degradation of heparan sulphate (HS) (1). MPS IIIB is characterized by multisystem involvement and a complex phenotype. The most debilitating manifestations of the disease are those related to central nervous system disease, with severe and progressive mental retardation, hyperactivity, and behavioral problems. Skeletal and visceral manifestations are less prominent, as compared with other MPS. Gastrointestinal manifestations, including diarrhea and constipation, have occasionally been described in patients with MPS IIIB, but they have been poorly characterized and their pathophysiology is not known. Although gastrointestinal symptoms are often overshadowed by the severe neurological phenotype, they may affect the quality of life of patients and of their families. We describe a case of MPS IIIB, referred to our hospital because of chronic diarrhea, in which abnormalities of intestinal endoscopy, histology, and scintigraphy with Tc-99m-labeled human serum albumin were found, partially overlapping with the features of intestinal lymphangiectasia. In this patient, a low-fat diet and supplementation of medium-chain triglycerides were started, leading to persisting improvement of diarrhea. These results add information on the pathophysiology of intestinal manifestations in MPS IIIB patients and possibly in other MPS patients with a history of chronic diarrhea.

We report the case of a girl affected by giant cell hepatitis associated with autoimmune haemolytic anaemia. Both conditions were severe with a number of life-threatening episodes of liver failure and anaemia unresponsive to several immunosuppressant drugs but cyclophosphamide. After a low-dose long-term treatment with this drug the patient is stably well without any therapy. A review of therapeutical options in this condition is also presented.

Aim The observation of bright liver echo pattern on ultrasound is commonly considered a sign of hepatic steatosis. However, the interference of liver fibrosis on sensitivity and specificity of bright liver echo pattern has caused many to question its effectiveness as a diagnostic tool. The objective of this study was to evaluate the sensitivity, specificity and predictive values of bright liver echo pattern for liver steatosis. Patients and methods We studied 235 consecutive patients suspected of having liver disease of various aetiologies. Median age was 52 years (range, 17–72 years), and there was a male/female ratio of 1:18. All patients underwent ultrasound examination before liver biopsy and was performed by two operators. The presence or absence of bright liver echo pattern and posterior attenuation or areas with different patterns of fat infiltration were noted. Histologic evaluation was performed and graded by Ishak score. Steatosis was categorised as absent, 0–2%, 3–29% to 30–49% or >50%. Results Interobserver concordance was high. Bright liver echo pattern was found in 67% of patients with steatosis of any degree and 89% of patients with steatosis of ≥30%. Only three patients without steatosis, who had a low Ishak score, demonstrated bright liver echo pattern on ultrasonography. The sensitivity, specificity, positive predictive value and negative predictive value of bright liver echo pattern for steatosis were 64%, 97%, 96.0% and 65%, respectively. Among the subgroup of patients who had steatosis of ≥30%, the sensitivity, specificity, positive predictive value and negative predictive value of bright liver echo pattern were 91%, 93%, 89% and 94%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of posterior attenuation and/or skip areas associated with bright liver echo pattern for steatosis were 89.7%, 100%, 100% and 92.3%, respectively. Univariate analysis showed bright liver echo pattern to be associated only with steatosis and not with fibrosis. Conclusion We concluded that the presence of bright liver echo pattern is a sign of liver steatosis and that liver fibrosis does not interfere with ultrasound measurements. Posterior attenuation and/or skip areas are closely related to steatosis of ≥30%.

Background/Aims : Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. Methods : We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). Results : Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. Conclusions : Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.

We retrospectively studied 42 liver biopsy specimens from 39 patients who met serologic and histologic criteria of autoimmune liver diseases. We found 10 cases of overlap syndrome (OLS), 10 autoimmune cholangitis (AIC), 10 primary biliary cirrhosis (PBC), and 9 autoimmune hepatitis (AIH) type 1. The following results were obtained: (1) Granulomas and biliary duct lesions were more prominent in PBC and AIC than in OLS and AIH. (2) Bile duct loss was not observed in AIH cases. (3) Features of hepatocellular damage such as piecemeal necrosis, spotty lobular necrosis, and confluent necrosis, were much more prevalent in OLS and AIH than in PBC and AIC. (4) HLA-DR antigen expression by hepatocytes was more frequent in AIH and OLS, whereas the expression of the same antigen by the bile duct epithelium was more frequent in PBC and AIC. We conclude there is a morphologic spectrum in autoimmune liver diseases, in which PBC forms one end of the spectrum, AIH the other, OLS the middle but closer clinically and histologically to AIH than to PBC, and AIC, which seems to be an antimitochondrial antibody-negative subtype of PBC.

Objective: To report, to our knowledge, the first case of a patient with nodular regenerative hyperplasia of the liver (NRHL) associated with portal hypertension in whom ursodeoxycholic acid (UOCA) therapy had a therapeutic effect on liver enzymes and was associated with nonprogression of portal hypertension. Case Summary: A symptom-free 13-year-old boy was hospitalized for splenomegaly and thrombocytopenia identified during a routine check-up. Infectious, autoimmune, and neoplastic causes were ruled out. Two years later, laboratory findings revealed high levels of aminotransferases and γ-glutamyltransferase (GGT), thrombocytopenia, and neutropenia. Ultrasound scanning of the abdomen confirmed portal hypertension. Results of liver pathology studies showed diagnostic features of NRHL Given the biochemical evidence of cholestasis, UDCA was administered, with an initial dosage of 10 mg/kg/day that was progressively increased to 20 mg/kg/day (1800 mg/day). After 5 months of treatment, GGT and then aminotransferase levels normalized and remained within normal limits in the following months. With arbitrary withdrawal of UDCA after 30 months of therapy, a rapid increase in transaminase levels was observed. Prompt reinstitution of UOCA was followed by sustained normalization of liver enzymes. Laboratory and sonographic signs of portal hypertension remained stable and tended to improve during UDCA therapy, as demonstrated by regularization of the mean portal vein flow velocity, reduction of the congestion index, progressive increase of the platelet count, and improvement of the esophagogastroscopy pattern. Discussion: NRHL is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma that may lead to noncirrhotic portal hypertension. No specific treatment is available, and management of patients with a primary form of NRHL consists mainly of treating the complications of portal hypertension. In our patient, UDCA therapy was followed by a prompt reduction and sustained normalization of liver enzyme levels and no progression of portal hypertension throughout the follow-up period. Conclusions: Since in this patient with primary NRHL, ongoing UDCA administration resulted in improved biochemical and portal hypertension markers, this therapy can be considered in cases of NRHL associated with abnormalities of liver enzymes.

Objective To evaluate the efficacy of triple eradication therapy versus symptomatic therapy in children with Helicobacter pylori –associated chronic active gastritis ( H pylori -ACAG). Study design Symptomatic patients with H pylori -ACAG (n = 31) were randomly assigned into two groups: (1) patients infected with H pylori who were treated with triple eradication therapy (n = 16); and (2) patients infected with H pylori who were treated with symptomatic therapy (n = 15). Results After 1 year of follow-up, macroscopic appearance was significantly different in group B ( P = .023), and chronic inflammation, H Pylori density, and activity were significantly higher in group B than in group A ( P = .022, .007, and .002, respectively); however, we did not find a significant difference in the symptoms comparing both groups ( P = .287). After 1 year of follow-up, we observed the persistence of the H pylori infection in all children who had not received eradication treatment. Conclusions There is no correlation between eradication of H pylori infection and improvement of dyspeptic symptoms. Self-eradication does not occur within 1 year of follow-up. A trend toward a higher rate of chronic inflammation in noneradicated children at 1 year limited the time of our study.

Background Differently from chronic hepatitis C, factors associated with hepatic steatosis in children with chronic hepatitis B are not clearly elucidated. Objective Aim of this study was to investigate prevalence of steatosis at liver biopsy in HBV-infected children. Study design A retrospective study including 56 children with chronic hepatitis B undergoing liver biopsy at median age of 8.1 years. In all patients demographic, anthropometric, clinical and laboratory data were evaluated at the time of liver biopsy. Results Steatosis was present in 2 (4%) children. BMI was significantly higher in 2 patients with steatosis compared with those without steatosis. Demographic, biochemical and virological parameters did not differ between children with and those without steatosis. Conclusions Liver steatosis in HBV-infected children seems to be related to obesity and metabolic factors rather than to viral factors. Detection of steatosis in non-obese children with HBV infection requires a careful investigation to rule out other causes of fatty liver.

Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. (HEPATOLOGY 2007;45:725–734.)

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Lathosterolosis (LS) is a defect of cholesterol biosynthesis due to the deficiency of the enzyme sterol-C5-desaturase. Only two patients have been described to date, both presenting with multiple malformations, mental retardation, and liver involvement. In addition in one of them pathological examination revealed mucolipidosis-like inclusions on optic microscopy analysis, and peculiar lysosomal lamellar bodies on electron microscopy analysis. This study is focused on a better characterization of the clinical phenotype of LS. We describe a further case in a fetus, sibling of the first patient reported, presenting with neural tube defect, craniofacial and limb anomalies, and prenatal liver involvement. The fetal phenotype suggests the possible occurrence of significant intrafamilial variability in LS, and expands the phenotypic spectrum of the disease. Histological examination of autopsy samples from the fetus and skin fibroblasts from the living sibling suggested that the mucolipidosis-like picture previously reported is not a constant feature of LS, being possibly associated with the most severe biochemical defects, but confirmed the ultrastructural finding of lamellar inclusions. The LS phenotype appears to be characterized by the distinctive association of a recognizable pattern of congenital anomalies, involving axial and appendicular skeleton, liver, central nervous and urogenital systems, and lysosomal storage. This condition partially overlaps with other defects of sterol metabolism, suggesting intriguing pathogenic links among these conditions.

OBJECTIVE: Both arterial hypertension and chronic hepatitis are common disorders. The relationship between arterial pressure and liver cirrhosis has been extensively studied, but no studies are available in chronic hepatitis (CH). Recently, a few studies have reported that treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs), commonly used in arterial hypertension, reduce hepatic fibrosis in patients with viral CH and in nonalcoholic steatohepatitis. This study was aimed at comparing the evolution of post-viral CH in patients with/without concomitant essential hypertension. Methods: Two sets of observations were carried out: a) a cross-sectional cohort study of 95 patients with viral CH, to compare the severity of histological and biochemical data at diagnosis, in relation to pharmacologically-treated essential hypertension; and b) a retrospective study with the observation of 254 patients with CH of viral etiology, followed up from 2 to 20 years, to establish the natural history of viral CH in relation to treated essential hypertension. Results: In the cross-sectional analysis, patients with treated hypertension had a significantly older age at diagnosis of CH (51.4 ± 8.4 years vs. 46.2 ± 12.2 in normotensive; P

Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine aminotransferase (ALT) levels (PNAL). Patients with PNAL experience significantly milder disease. In order to understand the differences between CHC patients with elevated ALT levels compared with those with PNAL better, we compared epidemiological, immunological and histological findings, in particular, the value of proliferating hepatocyte activity (PCNA) between the two groups of patients. We studied 40 chronic hepatitis C virus (HCV) carriers with increased ALT who underwent liver biopsy for histological diagnosis and determination of clinical prognosis, and 24 PNAL patients under follow-up for 10 years. Immunological response to different HCV genomic epitopes was tested in both the control group and in PNAL subjects. PCNA values from liver specimens of all patients as well as liver biopsies of PNAL patients at time points 0 and 5 years were calculated according to Hall et al.Age, sex and body mass index (BMI) were not significantly different between the two groups. The median liver histology stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2-6 vs 1.5, range = 1-2; P < 0.01). Among PNAL patients, histological stage was not statistically different at the three time points considered. Interferon (IFN)-gamma production was comparable in the two groups. PCNA was significantly higher in the group with elevated ALT levels vs the PNAL group (8%, range = 4-15%vs 5% range = 3-8%; P < 0.05) and no statistically significant differences were found in PNAL patients at time points 0, 5 and 10 years. This study confirms that progression to cirrhosis is slow or absent in PNAL patients after 10 years of follow-up. Accordingly, the hepatic proliferative activity index is low and seems to be stable over time.

We investigated the metabolic defect(s) of four children who presented with isolated cryptogenic chronic liver disease, coagulopathy, and abnormalities of several unrelated serum glycoproteins. Analysis of the patients' serum glycoproteins and fibroblasts suggest they have a novel congenital disorder of glycosylation (CDG). All had abnormal transferrin (Tf) isoelectric focusing (IEF) profiles. More detailed analysis of Tf by electrospray ionization mass spectrometry (ESI-MS) showed a plethora of abnormal glycosylations that included loss of 1-2 sialic acids and 1-2 galactose units, typical of Group II defects. Tf from two patients also lacked 1-2 entire oligosaccharide chains, typical of Group One disorders. Total serum N-glycans were analyzed by HPLC and matrix-assisted laser desorption/ionization mass spectrometry and also showed increased proportion of neutral glycan chains lacking sialic acids and galactose units. Analysis of patient fibroblasts eliminated CDG-Ia, through CDG-Ih, -IL and CDG-IId. Our results suggest that a subset of children with clinically asymptomatic, cryptogenic hypertransaminasemia and/or liver steato-fibrosis may represent a novel type of CDG-X with an unknown defect(s). Clinicians are encouraged to test such patients for abnormal Tf glycosylation by ESI-MS.

BACKGROUND/AIMS: Prevalence and significance of steatosis in children with chronic hepatitis C are not well defined. We analysed the prevalence of steatosis in children with chronic hepatitis C and its relationship with clinical, laboratory features and response to interferon. METHODS: Sixty-four consecutive children with CHC undergoing liver biopsy were retrospectively evaluated. RESULTS: Twenty-five percent of children showed mild to moderate steatosis. Only one child was infected by genotype 3. Body mass index did not significantly differ between children with and without steatosis. Although no significant difference in necroinflammatory and fibrosis scores between children with and without steatosis was found, 3 (18.7%) of 16 patients with steatosis and only one (2.1%) of 48 patients without steatosis had a fibrosis score >2 (P

Background. The long-term outcome of chronic hepatitis C (CHC) has not been well studied, both for untreated and interferon-treated children. The aim of this study was to evaluate the long-term outcome of disease in a large series of children with CHC.Methods. Clinical, biochemical, virological, and histological features were evaluated in all children (age, 2–18 years) with CHC who did not have concomitant disease and who attended at our hospital's liver unit during the period of 1986–2004.Results. One hundred twenty-five children with CHC were studied. All patients remained free of symptoms throughout the period of observation. On the basis of transaminase levels during the first year of positivity for antibodies to hepatitis C virus (HCV), children were divided into 2 groups: patients with hypertransaminasemia (100 patients, all of whom had detectable HCV RNA), and those with normal transaminases (25 patients; 16 had viremia and 9 did not have viremia). Sustained clearance of viremia was achieved in 38% of the patients treated with interferon, compared with 12% of untreated children (P < .05). A sustained response to therapy was obtained in 64.7% of children infected with an HCV genotype other than genotype 1 and in 24.2% of those infected with HCV genotype 1 (P < .05). Histological lesions were mild in all 64 patients who underwent liver biopsy. No linear correlation was found between duration of disease and progression of fibrosis. Examination of a follow-up liver biopsy specimen revealed cirrhosis only in 1 (4.7%) of 21 children.Conclusions. Children with CHC were symptom free and had a morphologically mild liver disease. Interferon therapy may be effective for patients infected with HCV genotypes other than genotype 1, whereas lower response rates are expected for HCV genotype 1–infected children. The real impact of therapy on long-term outcome remains to be established.

Background/Aims We studied the prevalence of non-alcoholic fatty liver disease and non-alcoholic-steatohepatitis in patients with metabolic-syndrome but normal liver enzymes. The histological findings of patients with normal liver enzymes and non-alcoholic-steatohepatitis were compared with those of a control-group with persistently abnormal liver enzymes. Methods Patients presenting with normal liver enzymes were enrolled in the study and underwent liver biopsy. Prevalence of non-alcoholic-steatohepatitis and risk factors for fibrosis and cirrhosis were evaluated. Data from a control-group with non-alcoholic-steatohepatitis and abnormal liver enzymes were used to compare the histological findings. Results Fifty-eight of the 80 patients enrolled had varying degrees of non-alcoholic steatohepatitis, of these 26 had fibrosis and 8 silent cirrhosis. The association of metabolic-syndrome, female-sex, a long-history of obesity and body mass index>45 were considered to be independent risk-factors for fibrosis. Comparing the histological findings of cases and controls we found a similar severity of steatosis and fibrosis, with a greater prevalence of ballooning degeneration and glycogenated-nuclei rather than lobular-inflammation. Conclusions In the subjects selected according to our criteria, liver enzyme levels could not be used as surrogate markers of non-alcoholic-steatohepatitis. Histological hallmarks of patients with metabolic-syndrome, normal liver enzymes and non-alcoholic-steatohepatitis consist to a lesser degree of lobular-inflammation and a more severe ballooning and glycogenated-nuclei.

Objectives. The aim of this study was to define the features of chronic cryptogenic hepatitis (CCH) in childhood and to investigate whether it is related to hepatitis G virus infection. Methods. Forty-six children (24 males; age range, 1.5 to 17 years) with CCH were studied. CCH was diagnosed when serum alanine aminotransferase concentrations were more than 1.5 times normal for longer than 6 months without any apparent cause of liver disease. Results. No patient had acute symptomatic onset or had received a blood transfusion. Three had undergone minor surgical procedures. All appeared to be healthy during follow-up (median, 4.2 years; range, 1 to 10 years). Hypertransaminasemia was the only aberrant liver function test. Elevated serum alanine aminotransferase values alternated with normal values in 40 children (86.9%). Five children (10.8%) had a spontaneous sustained (>12 months) remission of hypertransaminasemia. Twelve (26%) had laboratory signs of autoimmunity, but none fulfilled the criteria for autoimmune hepatitis. Of 20 children who underwent liver biopsy, 13 (65%) had minimal chronic hepatitis, 4 (20%) had mild chronic hepatitis and 3 (15%) had moderate chronic hepatitis. Serum hepatitis G virus RNA was detected in 2 girls (4%) whose risk factor was a hepatitis G virus-infected mother and a minor surgical procedure, respectively. In 12 families at least 1 other member had chronic liver disease. Conclusions. Childhood CCH seems to be a symptomless disease characterized by isolated hypertransaminasemia with onset during the first 4 years of life and mild to moderate histologic liver lesions. Although the frequency of spontaneous remissions is low, childhood CCH seems, in the short run, to be a nonprogressive disease. Hepatitis G virus does not play a major role in CCH.

To determine the safety and advantages of laparoscopic liver biopsy in pediatric liver disorders, we reviewed the medical records of 80 children affected by liver disease of various etiologies who underwent this procedure from 1986 to 1996. The main indicators for laparoscopic biopsy were increased risk of bleeding (i.e., mild to moderate coagulation abnormalities in patients probably affected by cirrhosis) and/or previous poorly informative blind needle liver biopsy (65 cases), and the need for a large amount of liver tissue for biochemical assays (10 cases). After inspection of the liver surface, at least two core biopsies were performed using a Tru-cut needle. We encountered difficulties with the biopsy in only four cases, due to a hard consistency of the liver. Bleeding time from the liver orifice was greatly reduced by positioning a fibrin plug (50-120 s vs 5-10 s, on average). In 15 patients, a large excisional biopsy was also successfully performed. Our results confirm an important role for laparoscopy in the diagnosis of cirrhosis (30% of bioptic false negative diagnoses in this series) and show that in selected cases laparoscopy-guided needle or excisional biopsy is an easy, useful and safe alternative to percutaneous blind liver biopsy.

Background. There is no generally accepted treatment for chronic hepatitis B (HB) infection in children. Objectives. To evaluate the efficacy of a prolonged course of high dose interferon alone or after prednisone priming in children with chronic HB infection. Methods. The outcome of 31 children with HB e antigen (HBeAg)-positive chronic hepatitis who randomly received either no treatment (n = 9) or 10 million units of interferon alpha-2b/m 2 , alone (n = 13) or after prednisone priming (n = 9), three times weekly for 1 year was studied. Results. One patient withdrew from treatment. By the end of the first year treatment induced a loss of HB virus DNA and HBeAg from serum in 10 of 21 patients (48%), and a loss of HB surface antigen (HBsAg) in 4 (19%). Alanine aminotransferase values became normal in one patient (4.8%). Response rates in the two groups of treated patients were similar. In controls only one patient lost HBeAg and HBV DNA (11% ; P = 0.05), and none lost HBsAg or showed alanine aminotransferase normalization (P = 0.21 and 0.70, respectively). After a posttreatment 2-year follow-up there were still no differences in the response rates of the two treatments ; of the 21 pooled treated patients, 61% lost HBeAg and DNA and 67% normalized alanine aminotransferase (vs. 33 and 44% of controls, respectively ; P = 0.32 and 0.40). Reversion to HBeAg and HBV DNA negativity in treated patients occurred significantly earlier (P = 0.02 and 0.006, respectively) than in controls. No further patient lost HBsAg, but one reacquired HBsAg. Treated patients had posttreatment histologic scores better than controls (P = 0.03). Conclusions. Our medium term follow-up results indicate that a prolonged course of high dose interferon in children with chronic HB infection, regardless of prednisone priming, poorly affects response rates but significantly speeds termination of active viral replication.

The analysis of the literature on limb body wall complex reveals a varied and rather confused spectrum of cases. However, we noticed the presence of at least 2 clearly distinguishable phenotypes. The first phenotype shows craniofacial defects and amniotic bands and/or adhesion; the second--without craniofacial defects--presents urogenital anomalies, anal atresia, and abdominal placental attachment, together with a persistence of the extra-embryonic coelom. We think these 2 phenotypes are the consequence of different pathogenetic mechanisms. The pathogenesis of the first type can be related to an early vascular disruption, while the pathogenesis of the second one is attributable to an intrinsic embryonal maldevelopment. Eight cases of the second phenotype were identified and the pathological findings proving this maldevelopmental origin are described.

Six children in whom long-standing hypertransaminasemia of unknown cause led to an initial diagnosis of chronic or protracted cryptogenic hepatitis were found to have asymptomatic celiac disease. Administration of a gluten-free diet caused a prompt improvement of both hepatic and intestinal biochemical/histologic abnormalities. Hepatic damage may be another "atypical" form of celiac disease in children.

We describe the first case of renal tubular dysgenesis in a newborn female who survived 15 days. The immunohistochemical and lectin binding studies confirmed the lack of proximal tubule differentiation. Electron microscopy showed undifferentiated tubular epithelium. Widely patent cranial fontanels were present in the proposita. The father and sister showed acrocephalosyndactyly Saethre-Chotzen type. The parents were not related and there was no familial history of renal pathology.

Percutaneous liver biopsy (PLB) is the golden standard for diagnosing chronic liver disease (CLD) even if it is still debated if and how much a single liver specimen might represent the histological status of the entire liver. A study was conducted to determine the diagnostic value of PLB comparing the histological score of two liver specimens collected in the same patient on the hepatic right and left lobe. The role of PLB for diagnosing CLD is confirmed.

It is a well-known fact that thymic tissue enclosed in millipore diffusion chambers is capable of restoring both lymphopoiesis and immunological reactivity. Attempts to restore leukemogenesis by the same technique have so far proved unsuccessful. It seemed worthwhile to use the thymic tissue culture technique in order to obtain a quantitatively greater number of epithelial reticular cells. These cells were transplanted intramuscularly in the thigh of 40–50 day old W/Fu rats, thymectomized at birth and injected with Gross virus at 3–4 days of age. In 5 out of 11 animals a lymphoma appeared 6–8 months later at the site of implantation of thymic cells. In control animals (not injected with virus), islands of more or less morphologically normal thymus developed from the grafted cells. The findings suggest that, whereas reticular cells can restore lymphopoiesis and immunological reactivity, the presence of a whole thymus is essential for leukemogenesis to occur.

We report a case of a 19-month-old infant with congenital hepatic fibrosis. The clinical features consisted of portal hypertension with massive gastrointestinal bleeding, recurrent cholangitis, and cystic dysplasia of the kidneys, without im pairment of renal function. The dramatic course of the disease required surgical treatment. Congenital hepatic fibrosis with life-threatening gastrointestinal bleed ing is extremely rare below three years of age. The purpose of the present report is to stress the need of looking for varices in all cases of congenital hepatic fibrosis, even when occurring in early infancy.

CORRELATION OF SERUM HYALURONIC ACID (HA) AND lAMININ (LAM) WITH STANDARD LIVER HISTOLOGYAND HISTOMORPHOMETRY-PROVEN LIVER FIBROSIS IN CHILDREN AFFECTED BY CHRONIC HEPATITIS B VIRUS (HBV) INFECTION