Gastrointestinal immune responses in HIV infected subjects

Biliary atresia (BA) is characterized by luminal obstruction of the extrahepatic bile duct with fibrous remnants. The authors reviewed ultrasonographic examinations of the fibrous tissue in the bifurcation of the portal vein at the porta hepatis and identified the triangular- or tubular-shaped echogenic density, the so-called "triangular cord" (TC), in the vicinity of the portal vein on a transverse or longitudinal scan. In this prospective study, the authors investigated whether TC was useful in the noninvasive diagnosis of biliary atresia in 18 infants who had persistent neonatal jaundice. This was done by comparing the ultrasonographic examination with the histopathologic examination (HPE) of liver specimens obtained from a needle biopsy. The TC was identified in nine patients, all of whom were confirmed to have BA by HPE. The TC was not observed in the other nine patients, who had neonatal hepatitis (NH). The mean size of the TC was 13 mm (wide) x 6 mm (thick) (width range, 5 to 21 mm; thickness range, 4 to 12 mm). The diagnosis of BA was confirmed at the time of Kasai hepatoportojejunostomy in eight of the nine patients whose TC was noted by ultrasonography (US). The other patient was discharged because his parents refused the operation; he died of liver failure at 15 months of age. The nine patients with absent TC were treated medically for NH. Eight of them improved clinically. The other, diagnosed to have NH by needle and wedge liver biopsies, was reexamined 40 days after the initial examination because of worsening jaundice. A 18 x 12-mm TC was visualized ultrasonographically. Additionally, a percutaneous liver biopsy specimen showed BA with severe portal fibrosis and ductal proliferation. The patient underwent a Kasai hepatoportoenterostomy. On the basis of these results, the authors conclude that TC is a very specific ultrasonographic finding, representing the fibrous cone at the porta hepatis, and is a useful tool in the noninvasive diagnosis of BA. However, early exploration or close US follow-up is recommended for any patient suspected of having BA clinically, even if a liver biopsy confirms the NH.     

Laparoscopy-guided biopsy in diagnosis of liver disorders in children

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.     

Neonatal cholestasis syndrome: an appraisal at a tertiary center

OBJECTIVE: To know the magnitude, etiology and clinical profile, the efficacy of various investigations and the outcome in patients with neonatal cholestasis syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants with NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years. SETTING: Tertiary level referral gastroenterology center in North India. METHODS: Liver function tests, urine examination, serum antibodies against Cytomegalovirus (CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done. In appropriate setting, laparotomy and surgical corrections were done for biliary tract disorders. RESULTS: NCS constituted 19% of pediatric liver diseases. Considerable delay in presentation was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0 months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%) infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract infection and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%) were of indeterminate etiology. Liver biopsy was the most accurate (96.4%) investigation in discriminating between EHBA and NH. Of the 18 operated infants with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive (mean follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic. CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian children. (ii) It requires prompt referral, quick investigative approach and targeted management. (iii) Liver biopsy is highly accurate in differentiating EHBA and NH. (iv) infants with EHBA and compensated status of liver should undergo corrective surgery irrespective of age at presentation.     

Fine needle aspirative biopsy of the liver in HBsAG-positive patients with end-stage renal failure

HBsAg-positive patients with end-stage renal failure have a high prevalence of asymptomatic chronic hepatitis. In order to determine the usefulness of hepatic cytology in the diagnosis of liver disease, the findings of hepatic needle core biopsy (NCB) and fine needle aspirative biopsy (FNAB) were compared in 15 HBsAg-positive uremic patients. The patients, aged 42 +/- 12 years, 14 males, were on hemodialysis for periods ranging from 13 to 105 months. The NCB was processed by standard histologic and immunohistochemical techniques and FNAB by the conventional technique, using the total corrected increment score (TCI). Plasma samples were collected for evaluation of hepatic function and for viral serologic tests. In 15 patients a diagnosis was made by NCB: normal, 7 cases; chronic persistent hepatitis, 4 cases; and chronic active hepatitis, 4 cases. When the patients were allocated into two groups according to the severity of the liver histologic findings [group I--minor changes (normal+chronic persistent hepatitis), 11 patients; group II--major changes (chronic active hepatitis), 4 patients], statistically higher values were found in the major changes group for alanine aminotransferase (49 +/- 33 vs. 24 +/- 11, p = 0.04), gamma-glutamyl transpeptidase [148 +/- 53 vs. 38 +/- 28, p < (minor) 0.02] and TCI (3.7 +/- 1.2 vs. 2.5 +/- 0.8, p = 0.04). In conclusion, liver FNAB can be useful as a screening procedure for the identification of liver histologic changes (minor or major) in uremic HBsAG-positive patients.     

Magnetic resonance cholangiography for evaluation of cholestatic jaundice in neonates and infants

Distinguishing extrahepatic biliary atresia from other causes of cholestasis in neonates and infants is important because surgical intervention before 2 months of age allows for long-term survival. The purpose of this prospective study was to evaluate the usefulness of magnetic resonance (MR) cholangiography in differentiating biliary atresia from other causes of cholestatic jaundice in neonates and infants. Nine anicteric infants (control group) aged 10 to 224 days (mean +/- SD, 8 +/- 65 days) and 15 neonates and infants with cholestatic jaundice, aged 22 to 142 days (mean +/- SD, 71 +/- 37) underwent MR cholangiography. The final diagnosis of extrabiliary atresia (6 patients) was based on laparotomy findings (4 patients) or autopsy (2 patients), while neonatal hepatitis (9 patients) was diagnosed according to the liver biopsy findings and clinical recovery during follow-up. Percutaneous liver biopsies were performed in all 15 patients. Results showed that the gall bladder and common bile duct (CBD) could be visualized using MR cholangiography in all patients in the control group. Nonvisualization of the CBD (6/6 patients) and demonstration of a small gall bladder (6/6 patients) characterized MR cholangiography findings in patients with biliary atresia. MR cholangiography failed to depict the CBD in one infant with hepatitis. We conclude that demonstration of the CBD by MR cholangiography in neonates and infants with cholestasis can be used to exclude the diagnosis of biliary atresia. In patients with cholestatic jaundice considered for exploratory laparotomy, preoperative MR cholangiography is recommended to avoid unnecessary surgery.     

Sacral rectopexy-sigmoidectomy in the treatment of rectal prolapse syndrome. Anatomical and functional results

BACKGROUND/AIM: Quantitative measurement of hepatic iron by biochemical analysis of liver biopsy samples is required to assess hepatic iron stores accurately. Cirrhotic livers, however, contain variable amounts of fibrous tissue and the distribution of iron within the hepatic parenchyma is not always uniform. The aim of this study was to assess the variability in hepatic iron concentration measurement from needle-biopsy specimens. METHODS: The livers from eight patients with cirrhosis selected because of elevated serum ferritin were obtained at the time of liver transplantation (n = 6) or at autopsy (n = 2). Multiple needle biopsies were done, and hepatic iron concentration was measured by atomic absorption spectroscopy. The hepatic iron index was calculated as iron concentration divided by age. RESULTS: Four cases had a mean hepatic iron index above 2.0, in the range of that reported in patients with homozygous genetic hemochromatosis, whereas the other four had an hepatic iron index of less than 2.0. The intra-individual coefficient of variation for hepatic iron concentration ranged from 11.3 to 43.7%, averaging 24.9%. The coefficient of variation was smaller in biopsy samples > 4 mg dry weight than in samples < 4 mg (19.8% vs 28.6%, p < 0.05). Histological examination of surgical biopsies from these livers showed large amounts of fibrous tissue, and inhomogeneous distribution or iron in the hepatic parenchyma. CONCLUSIONS: This study demonstrates an important variability in the measurement of hepatic iron content from needle biopsy specimens in patients with severe cirrhosis.     

Needle track seeding of primary and secondary liver carcinoma after percutaneous liver biopsy

Seeding of tumour in the needle track following percutaneous needle biopsy of liver neoplasms is rarely reported. We describe two such cases following the needle biopsy of an hepatocellular carcinoma and secondary colorectal carcinoma respectively. The risk of needle track recurrence of liver tumours should not be regarded as insignificant. The diagnosis of liver neoplasms may be achieved by non-invasive modalities, and their needle biopsy should be reserved for cases not amenable to surgical resection.     

Evaluation of mebrofenin hepatoscintigraphy in neonatal-onset jaundice

BACKGROUND: The prognosis of infants with prolonged neonatal jaundice is dependent on early diagnosis because of the need for prompt surgical management of biliary atresia. OBJECTIVE: To evaluate the usefulness of 99 mTcm-trimethylbromo-iminodiacetic acid (TBIDA, mebrofenin) in the investigation of infantile jaundice. MATERIALS AND METHODS: A retrospective study was undertaken of 58 patients with unexplained prolonged neonatal jaundice. Sixty-eight scans were reviewed. RESULTS: Mebrofenin scintigraphy confirmed the presence of a choledochal cyst in three of the four cases with that diagnosis. There were no false negative results in the nine patients with extrahepatic biliary atresia (EHBA). Three further infants had an incorrect histological diagnosis of EHBA. A gall bladder was identified by US in each case and in one of these, scintigraphy showed gut excretion. In the 16 patients with no gut excretion by 24 h, the final diagnoses were intrahepatic cholestasis (n = 7), Alagille's syndrome (n = 3), neonatal hepatitis (n = 3), alpha-1-antitrypsin deficiency (n = 2) and juvenile xanthogranuloma (n = 1). Seven infants had repeat scintigraphy after the administration of ursodeoxycholic acid (URSO). This changed five non-excretors with hepatitis into excretors. Two infants with hepatitis continued to show non-excretion after URSO, but a gallbladder was identified by US in both. CONCLUSIONS: Mebrofenin scintigraphy is accurate in confirming the presence of a choledochal cyst and in refuting the diagnosis of EHBA. While histology and scintigraphy are each 100 % sensitive for the diagnosis of EHBA, neither, individually, is accurate and the investigation of prolonged neonatal jaundice requires a multi-modality imaging strategy.     

Reducing the addictiveness of cigarettes. Council on Scientific Affairs, American Medical Association

Biliary atresia is a disorder of infants in which there is obliteration or discontinuity of the extrahepatic biliary system, resulting in obstruction of bile flow. Untreated, the resulting cholestasis leads to progressive conjugated hyperbilirubinemia, cirrhosis, and hepatic failure. Biliary atresia has an incidence of approximately one in 10,000 live births worldwide. Evidence to date supports a number of pathogenic mechanisms for the development of biliary atresia. An infectious cause, such as by a virus, would seem most pausible in many cases. The clinical observation that biliary atresia is rarely encountered in premature infants would support an agent acting late in gestation. However, no infectious or toxic agent has been conclusively implicated in biliary atresia. Genetic mechanisms likely play important roles, even regarding susceptibility to other specific causes, but no gene whose altered function would result in obstruction or atresia of the biliary tree has been identified. The variety of clinical presentations support the notion that the proposed mechanisms are not mutually exclusive but may play roles individually or in combination in certain patients. Biliary atresia, when untreated, is fatal within 2 years, with a median survival of 8 months. The natural history of biliary atresia has been favorably altered by the Kasai portoenterostomy. Approximately 25 to 35% of patients who undergo a Kasai portoenterostomy will survive more than 10 years without liver transplantation. One third of the patients drain bile but develop complications of cirrhosis and require liver transplantation before age 10. For the remaining one third of patients, bile flow is inadequate following portoenterostomy and the children develop progressive fibrosis and cirrhosis. The portoenterostomy should be done before there is irreversible sclerosis of the intrahepatic bile ducts. Consequently, a prompt evaluation is indicated for any infant older than 14 days with jaundice to determine if conjugated hyperbilirubinemia is present. If infectious, metabolic, endocrine disorders are unlikely and if the child has findings consistent with biliary atresia, then exploratory laparotomy and intraoperative cholangiogram should be done expeditiously by a surgeon who has experience doing the Kasai portoenteostomy. Biliary atresia represents the most common indication for pediatric liver transplantation, representing more than 50% of cases in most series. Transplantation is indicated when symptoms of end stage liver disease occur, including recurrent cholangitis, progressive jaundice, portal hypertension complications, ascites, decreased synthetic function, and growth/nutritional failure.     

Dissociation between anxiolytic and hypomnestic effects for combined extracts of zingiber officinale and ginkgo biloba, as opposed to diazepam

Extrahepatic biliary atresia is a severe neonatal liver disease resulting from a sclerosing cholangiopathy of unknown etiology. Although biliary obstruction may be surgically corrected by a "Kasai" hepatoportoenterostomy, most patients still develop progressive hepatic fibrosis, although the source of increased collagen deposition is unclear. This study examined the role of hepatic stellate cells (HSCs) and assessed the source of transforming growth factor-beta (TGF-beta) production in hepatic fibrogenesis in patients with biliary atresia. Liver biopsies from 18 biliary atresia patients (including 5 pre- and post-Kasai) were subjected to immunohistochemistry for alpha-smooth muscle actin and in situ hybridization for either procollagen alpha1 (I) mRNA or TGF-beta1 mRNA. Sections were also subjected to immunohistochemistry for active TGF-beta1 protein. The role of Kupffer cells in TGF-beta1 production was assessed by immunohistochemistry for CD68. Procollagen alpha1 (I) mRNA was colocalized to alpha-smooth muscle actin-positive HSCs within the region of increased collagen protein deposition in fibrotic septa and surrounding hyperplastic bile ducts. The number of activated HSCs was decreased in only one post-Kasai biopsy. TGF-beta1 mRNA expression was demonstrated in bile duct epithelial cells and activated HSCs and in hepatocytes in close proximity to fibrotic septa. Active TGF-beta1 protein was demonstrated in bile duct epithelial cells and activated HSCs. This study provides evidence that activated HSCs are responsible for increased collagen production in patients with biliary atresia and therefore play a definitive role in the fibrogenic process. We have also shown that bile duct epithelial cells, HSCs, and hepatocytes are all involved in the production of the profibrogenic cytokine, TGF-beta1.     

A new diagnostic approach to biliary atresia with emphasis on the ultrasonographic triangular cord sign: comparison of ultrasonography, hepatobiliary scintigraphy, and liver needle biopsy in the evaluation of infantile cholestasis

BACKGROUND/PURPOSE: The authors evaluated prospectively the utility of ultrasonography, Tc-99m-DISIDA hepatobiliary scintigraphy, and liver needle biopsy in differentiating biliary atresia (BA) from intrahepatic cholestasis in 73 consecutive infants who had cholestasis. METHODS: Sixty three ultrasonographic examinations of 61 infants with 7.0-MHz transducer were carried out, focusing on the fibrous tissue at the porta hepatis. The authors defined the triangular cord (TC) as visualization of a triangular or tubular shaped echogenic density just cranial to the portal vein bifurcation on a transverse or longitudinal scan. RESULTS: Although 17 of 20 ultrasonographic examinations from infants who had BA denoted TC, 43 ultrasonographic examinations from infants with either neonatal hepatitis (NH) or other causes of cholestasis denoted no TC, showing a diagnostic accuracy of 95% with 85% sensitivity and 100% specificity. Investigation with Tc-99m-DISIDA hepatobiliary scintigraphy showed that 24 of 25 infants who had BA had no gut excretion, and 16 of 46 infants who had either NH or other causes of cholestasis had gut excretion, showing a diagnostic accuracy of 56% with 96% sensitivity and 35% specificity. Therefore, gut excretion of tracer excluded BA, but no gut excretion of tracer needed further investigations as liver needle biopsy. Forty-four liver needle biopsies were carried out in 19 infants who had BA and 24 infants who had either NH or other causes of cholestasis. Although 18 of 20 biopsy findings in infants who had BA were correctly interpreted as having BA, 23 of 24 biopsy results in infants who had either NH or other causes of cholestasis were correctly diagnosed, showing a diagnostic accuracy of 93% with 90% sensitivity and 96% specificity. CONCLUSIONS: Since the introduction of ultrasonographic TC sign in the diagnosis of BA by our institution, we have found that it seemed to be a simple, time-saving, highly reliable, and non-invasive tool in the diagnosis of BA from other causes of cholestasis. The authors propose a new diagnostic strategy in the evaluation of infantile cholestasis with emphasis on ultrasonographic TC sign as first priority of investigations. When the TC is visualized, prompt exploratory laparotomy is mandatory without further investigations. When the TC is not visualized, hepatobiliary scintigraphy is the next step. Excretion of tracer into the small bowel actually rules out BA. Liver needle biopsy is reserved only for the infants with no excretion of tracer. The authors believe that a correct decision regarding the need for surgery can be made in almost all cases with infantile cholestasis by this multidisciplinary approach.     

Comparative profitability of hepatic biopsy and microbiological tests in patients with HIV infection

OBJECTIVES: Diagnostic liver biopsy is proposed in HIV-positive patients who present unexplained fever. This invasive procedure is truly useful if it allows establishing a difficult diagnosis or improves survival rate. We conducted a retrospective study to determine the diagnostic and prognostic power of liver biopsy in HIV-positive patients with fever. METHODS: One hundred thirty-eight liver biopsies were performed in 129 patients. Utility was defined as demonstration of the pathogen or identification of a tumoral process. RESULTS: The liver biopsy met the utility criteria in 27 cases showing mycobacterial infections (n = 22) and herpes hepatitis, type 1 herpes simplex virus, cytomegalovirus and cryptococcosis infections (n = 1 each). These last 4 diagnoses were also possible with other tests. Comparing non-contributive liver biopsies (n = 111) with those demonstrating hepatic mycobacterial infection (n = 22) showed that the two groups were not different in terms of demographic data. Splenomegalia was more frequent in the non-contributive group (68% vs 37%, p = 0.007) as was superficial lymph node enlargement (45% vs 12%, p < 10(-3)). Laboratory tests were not discriminating. Mycobacterial infection was diagnosed in 22 patients in the non-contributive group. Bacteriological samples were positive for mycobacterium in 20 of the 22 patients in the contributive group. The mean delay to the first positive test for mycobacterium was 15 +/- 8 days compared with 30 +/- 10 days for liver tissue cultures. Mean survival after liver biopsy was 10 months: patients with a positive Ziehl-Neelson stain on the liver biopsy did not have a longer survival (9.7 +/- 7.6 vs 10.2 +/- 10.4 months). CONCLUSION: In most cases, liver biopsy in HIV-positive patients with fever provides a diagnosis which can be obtained with non-invasive techniques without improving prognosis.     

Medical informatics in perinatology project AGUSTINA in Argentina

Biliary atresia, a progressive obliterative process involving the bile ducts, has its onset in the newborn period. It is characterized by worsening cholestasis, hepatic fibrosis, and cirrhosis, which lead to portal hypertension and a decline in hepatic synthetic function. Untreated, the outcome is uniformly fatal. The two major milestones toward improved treatment of this disease have been the Kasai portoenterostomy and orthotopic liver transplantation. There has been discussion regarding transplantation as primary therapy, but portoenterostomy remains the standard of care as first-line intervention. Hepatic transplantation, done more frequently for biliary atresia than for any other cause of liver failure in the pediatric population, offers improved survival and quality of life to those for whom the Kasai operation fails. The etiology of biliary atresia remains poorly understood. Working toward a better understanding of this disease, recent investigations target more precise characterization of the hepatic pathology and seek to identify possible causative agents and predictors of favorable outcome. Recent advances in the understanding of biliary atresia published between December 1995 and November 1996 are the focus of this review.     

Biliary ductal shave biopsy with use of the Simpson atherectomy catheter

PURPOSE: The authors performed percutaneous biliary ductal shave biopsy through an existing transhepatic biliary drainage tract with use of the Simpson atherectomy catheter. The technical feasibility, sensitivity, and complications of this endoluminal biopsy method were studied when used for diagnosis of biliary ductal and pancreatic neoplasm. PATIENTS AND METHODS: Nineteen bile duct shave biopsies were performed in 18 patients with symptomatic biliary obstruction by using a 9-F Simpson directional atherectomy catheter. Seven of the 18 patients underwent nine negative percutaneous needle biopsies prior to undergoing percutaneous biliary drainage. Results of previous transcatheter brush biopsies performed through the transhepatic tract were negative in all patients. RESULTS: A histologic diagnosis was obtained in 15 of the 19 procedures (sensitivity, 0.79) and included cholangiocarcinoma (n = 7), pancreatic carcinoma (n = 5), metastatic carcinoma (n = 2), and primary sclerosing cholangitis (n = 1). Two complications occurred in the 19 procedures (10.5%), both transient but significant hemorrhage, one of which necessitated transfusion. CONCLUSIONS: Percutaneous biliary ductal shave biopsy with the Simpson atherectomy catheter can be performed successfully through the transhepatic approach and is a sensitive endoluminal biopsy technique, particularly in patients with tumors of the biliary tree that are not diagnosed by means of percutaneous needle biopsy or endoscopic methods. Disadvantages of this method include the high cost of the device and risk of hemorrhage. Atherectomy shave biopsy should be used cautiously and only after more conventional biopsy methods have been employed.     

Mechanical removal of the smear layer

Complications after nonoperative management of hepatic trauma are rare but include persistent biliary fistula in 4% of cases. Therapy usually involves surgical drainage or hepatic resection to control the fistula. The authors present a case of hepatic biliary fistula treated nonoperatively with percutaneous drainage and endoscopic sphincterotomy. A 16-year-old girl suffered a grade III parenchymal liver fracture to the right lobe in an automobile accident. She was hemodynamically stable with no coexistent injuries and was treated nonoperatively. Over 2 weeks her total bilirubin rose to 3.2 mg/dL, and alkaline phosphatase was 463 U/L. Ultrasound showed free intraperitoneal fluid, and 2 L of bilious fluid were retrieved by paracentesis. A radionuclide scan confirmed massive extravasation of isotope from the right lobe. Two drains percutaneously placed over the parenchymal fracture produced 500 to 600 mL of bile daily. Endoscopic retrograde cholangiopancreatography (ERCP) 1 week later showed a normal extrahepatic biliary system. A 1-cm sphincterotomy was performed without difficulty. Within 72 hours, percutaneous drains produced only 35 mL per day. The follow-up radionuclide scan showed no evidence of extrahepatic biliary extravasation, and 3 weeks later the drains were removed. Six months after the accident, results of the computerized tomography scan and liver function tests were normal. It was believed that endoscopic sphincterotomy reduced fistula output by decreasing the intrabiliary pressure caused by the ampulla, thus favoring internal drainage. This case demonstrates the effectiveness of endoscopic sphincterotomy as an alternative to direct surgical intervention for the management of posttraumatic biliary fistula.     

Using ethnography to investigate life scientists'' information needs

Although several liver diseases of childhood, particularly biliary atresia (BA) and cystic fibrosis (CF) liver disease (CFLD) are characterized by hepatic fibrosis, the pathogenesis of this process is incompletely understood. The cytokine transforming growth factor-beta1 (TGF-beta1) has been implicated in hepatic fibrosis in experimental animals, in which both the hepatic expression and plasma concentration of this cytokine are increased. The objective of our study was to determine whether there are similar alterations of TGF-beta1 in patients with hepatic fibrosis secondary to either BA and/or CFLD. The study design was as follows. In study 1, plasma TGF-beta1 was assessed by ELISA in 9 children with BA undergoing liver transplantation, 11 patients with CFLD, and appropriate control subjects. In study 2, hepatic expression of TGF-beta1 protein (assessed immunohistochemically) and hepatic fibrosis were scored semiquantitatively, on a 1-3 scale, by blinded investigators, in archival liver biopsy specimens from 10 children with BA, 10 with CFLD, and from 10 older children with normal hepatic histology, as well as in 4 patients with liver diseases of various etiologies. Simultaneous plasma and liver TGF-beta1 studies were performed in 8 patients with liver disease. Results were as follows. Plasma TGF-beta1 values were inversely correlated with age in healthy subjects (r=-0.54, p < 0.0001). The plasma TGF-beta1 protein of children with BA was decreased (13+/-2 ng/mL) compared with values for healthy children (42+/-6 ng/mL, n=10, p < 0.005). Similarly, the plasma TGF-beta1 concentration in patients with CFLD was also decreased compared with values for children with CF and normal serum liver profiles (n=14) (2+/-1 ng/mL versus 12+/-1, p < 0.05). However, the plasma TGF-beta1 concentration was increased in two patients with other types of liver disease. The hepatic expression of TGF-beta1 was increased in the presence of hepatic fibrosis in all types of liver diseases studied. Forty-six percent of patients had both marked hepatic fibrosis and marked TGF-beta1 labeling; 86% of samples without fibrosis showed no TGF-beta1 labeling, p=0.007. In conclusion, these studies have established the association of hepatic TGF-beta1 protein and hepatic fibrosis in several common liver diseases of childhood. Our data also suggest that, in children, plasma TGF-beta1 does not appear to be a useful marker of hepatic expression of this cytokine.     

Percutaneous biopsy of operable liver lesions: is it necessary or advisable?

AIM: The necessity and desirability of performing percutaneous biopsy of potentially resectable liver tumours is called into question. METHODS: Two cases are reported in which percutaneous biopsy of resectable liver tumours was performed unnecessarily and resulted in needle track seeding. RESULTS: In both instances patients who underwent potentially curative liver resection were rendered incurable because of biopsy track recurrence. CONCLUSION: The common practice of performing percutaneous ultrasound or CT guided biopsy of potentially resectable lesions in the liver is generally neither necessary nor desirable.     

Total anomalous pulmonary venous return complicating portoenterostomy for biliary atresia

Cardiovascular anomalies such as absent inferior vena cava and preduodenal portal vein are reported in cases of biliary atresia and make hepatic portoenterostomy a technical challenge. The authors present the case of a severe cardiac anomaly that significantly altered the functional outcome of a Kasai procedure. Baby M., an 8-week-old boy born with total anomalous pulmonary venous return (TAPVR), underwent hepatic portoenterostomy for biliary atresia. Over the next 3 months he remained icteric and febrile, and failed to gain weight. After multiple antibiotic treatments for suspected cholangitis, he underwent reexploration of the portoenterostomy, with no improvement in his overall condition. His prognosis was considered dismal because correction of the cardiac anomaly is associated with a high mortality rate (> 90%). The cardiac surgeon agreed to attempt a cure of the TAPVR, provided liver transplantation is contemplated if the patient survived. Within 48 hours postoperatively, his hepatic function had improved drastically. He became afebrile, had an improved appetite and weight gain, and was finally discharged 203 days after admission. One year later, he is thriving and remains anicteric. The exact reason for this drastic improvement is not well understood, but the right-sided cardiac failure caused by the TAPVR had a significant effect on the functional outcome of the portoenterostomy.     

Solute focusing techniques for bioseparations

BACKGROUND: Hepatic lesions in sickle cell disease have been studied essentially in autopsy series. Previous reports on living patients are rare and concern a limited number of cases. The aim of the present study is to report the clinical, biochemical, and hepatic histological findings in 26 living patients with sickle cell disease and hepatobiliary disease. PATIENTS AND METHODS: Twenty-six of 510 patients with sickle cell disease, in whom liver tissue was available for histological analysis, were selected. In 21 patients, biopsy was obtained during laparotomy for cholecystectomy; 5 patients underwent needle biopsy for hepatomegaly and/or liver test abnormalities. RESULTS: Twenty of the 21 cholecystectomized patients, as well as the 5 other patients, had liver vascular lesions consisting of sinusoidal dilatation (23 cases), perisinusoidal fibrosis (19 cases), and acute ischemic necrosis (5 cases). It is of interest that the 21 cholecystectomized patients had clinical signs of complicated cholelithiasis, and that 20 of them had gallbladder stones, with common bile duct lithiasis in only 1 case. In the 25 patients without common bile duct obstruction, symptoms might have been due to vascular lesions, but it must also be noted that in the cholecystectomized patients they did not persist or recur following surgery. In one cirrhotic patient, marked sinusoidal lesions might have favored severe hepatocellular failure that led to liver transplantation. In another patient, fatal hepatocellular insufficiency was possibly due to ischemia. The nonvascular lesions that were observed, ie, chronic persistent or mildly active hepatitis (11 cases) and cirrhosis (2 cases), were always associated with vascular lesions. CONCLUSION: These results suggest that in sickle cell disease: (1) hepatic lesions are mainly vascular; (2) these lesions can be responsible for acute and/or chronic ischemia that may be severe; (3) symptoms suggestive of acute cholecystitis and/or biliary tract obstruction might be, at least in part, explained by vascular lesions; and (4) biliary tract surgery indications should be considered more carefully.