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.     

Current concept of the treatment of biliary atresia

Hepatic portoenterostomy (Kasai operation) for the patient with biliary atresia (BA) can restore the bile flow in approximately 80% of children operated on before 60 days of life [1]. However, in terms of long-term survival, according to a recent nationwide survey among the major pediatric centers in Japan, only 325 of 2013 patients had more than 10 years' survival, and only 157 patients (7.8%) remained jaundice-free with normal liver function [2]. About 20% of BA cases without jaundice are generally able to survive for long periods; and most of those patients have portal hypertension or abnormal liver function [3-5]. As the results of liver transplantation have improved, controversy has arisen over the optimal care of these children [4, 6, 7]. Some investigators have claimed that transplantation is the favored primary therapy for most patients with BA [8]. We are thus at a turning point concerning the primary therapy of BA, which makes it necessary to determine the exact indications for the Kasai portoenterostomy and the timing of liver transplantation. This paper describes our strategy for the optimal treatment of BA patients based on our 117 patients who have had various form of portoenterostomy.     

Clinical significance of c-erbB2 oncoprotein expression in stomach carcinoma

We report a patient having a non-diagnosed small cell lung cancer, presenting with a clinical picture comprising emaciation, hepatomegaly, progressive jaundice, bilirubinuria and clay-colored stools. Computed tomography showed intrahepatic and extrahepatic biliary duct dilatation. The cause was compression of the common bile duct by metastatic enlarged lymph nodes in the porta hepatis. Clinical suspicion arose because of a mass found on the chest X-ray film and a positive cytologic sputum examination. The definitive diagnosis was obtained by bronchoscopy and biopsy.     

Hyaline cartilage at porta hepatis in extrahepatic biliary atresia

Hyaline cartilage was found on microscopy of sections of the extrahepatic biliary tree in two infants with extrahepatic biliary atresia (EHBA). Respiratory epithelium was not present, and the cartilage did not seem to block the bile duct lumen. Hyperbilirubinemia was manifest in one infant on the second postnatal day, but clinical courses were otherwise unremarkable. In neither infant was the ductal plate malformation found on light microscopy of liver biopsy specimens, and in neither infant was visceral topography abnormal. Hyaline cartilage at the porta hepatis appears to be a novel finding in EHBA. Its significance remains to be defined.     

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.     

Surgical treatment of biliary atresia in the liver transplantation era

Biliary atresia (BA) still remains one of the most intractable gastrointestinal diseases in infancy despite the concerted efforts of pediatric surgeons all over the world. The introduction of liver transplantation has revolutionized the protocols for the treatment of this condition. In this editorial, the role of hepatic portoenterostomy (the Kasai procedure) in the surgical treatment of BA in the "transplantation era" will be discussed.     

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.     

Plasma cell leukemia 3 months after autologous blood cell transplantation for multiple myeloma

A case of an amebic liver abscess with unusual clinical manifestations is presented. A middle-aged male with an abscess in both lobes of the liver presented with obstructive jaundice due to pressure on the porta hepatis with stasis of the bile in the intrahepatic biliary radicals. The patient did not respond to repeated needle aspirations and thus required open drainage. Subsequently, the patient developed a biliary leak through the drainage sites, and an injection of contrast dye into the cavity revealed a communication between the abscess cavities and the biliary tree. The biliary leak stopped spontaneously, and the large cavities also closed completely during the followup period.     

A comparison of regular with intermittent bronchodilators in asthma patients on inhaled steroids

A 73 year old lady developed abdominal pain, anaemia and obstructive jaundice 18 days after a road traffic accident. The jaundice was due to compression of the biliary confluence by a haematoma which was caused by a laceration of the left portal vein. The portal vein was repaired (lateral venorrhaphy) and post-operative recovery was uncomplicated. Porta hepatis injuries are difficult to diagnose and delayed presentation is not uncommon. Significant morbidity and mortality may ensue if aggressive management is not adopted.     

Periportal adenitis secondary to abdominal tuberculosis. A CT study

Isolated periportal tuberculous adenitis is rare. Computed tomography (TC) is the primary modality for its detection and evaluation. Although not definitive, in the presence of an appropriate clinical history and a positive purified protein derivative test, a diagnosis of periportal tuberculous lymphadenopathy may be suggested by CT by the presence of low-density enlarged porta hepatis lymph nodes with immediate postcontrast peripheral rim enhancement.     

Systemic amyloidosis presenting as cholestatic jaundice

We present a case of a 68 year old man with general deterioration and recent onset of jaundice that was admitted for clinical evaluation. Previous records were: treated bone tuberculosis, hypertrophic myocardiopathy and ischemic cardiopathy. Physical examination showed liver enlargement without evidence of chronic liver disease. Laboratory studies and other explorations such as abdominal ultrasound, CAT and ERCP did not leed to an objective diagnosis. Therefore, a liver biopsy was performed, showing liver amyloidosis AA type with amyloid deposits in portal spaces. The patient died three months later. The rarity of this clinical presentation is discussed and its poor prognosis outlined. Some peculiarities of liver deposits are reviewed.     

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.     

What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy

BACKGROUND/AIMS/METHODS: The diagnosis of cirrhosis is currently based on percutaneous liver biopsy, although this procedure may give rise to false negative results. This prospective study blindly investigates the accuracy of an ultrasonographic score, derived from liver, spleen and portal vein features, in predicting the final diagnosis in 212 patients with compensated chronic liver disease undergoing percutaneous liver biopsy. RESULTS: Taking biopsy as the standard, the ultrasonographic score differed significantly between chronic hepatitis (39+/-33) and cirrhosis (100+/-35) (p<0.0001). Discriminant analysis with stepwise forward selection of the variables identified liver surface nodularity and portal flow velocity as independently associated with the diagnosis of cirrhosis (p<0.005), and a score based on these two variables correctly identified cirrhosis in 82.2% of cases. One or both of these abnormalities were also found in 27/32 patients who were diagnosed as having cirrhosis at ultrasound, but were not cirrhotic histologically. Eight of these 32 cases developed signs of decompensated liver disease and/or portal hypertension in the subsequent 6-month follow-up, thus supporting the diagnosis of cirrhosis. CONCLUSIONS: Our data suggest that ultrasound is accurate in predicting the final diagnosis in patients with compensated chronic liver disease and may identify cirrhosis even in the absence of a typical histopathological pattern. However, neither percutaneous liver biopsy nor ultrasonography can be assumed to be the definitive criterion for the diagnosis of compensated cirrhosis.     

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.     

Intrahepatic cholestasis due to systemic mastocytosis: a case report and review of literature

A 35-yr-old female presented with symptoms of obstructive jaundice. Liver biopsy, bone marrow aspiration, and biopsy revealed systemic mastocytosis and acute myeloid leukemia. The liver biopsy specimen showed infiltration of mast cells within portal tracts with periductal and portal edema, irregularity of interlobular duct epithelium, and centrizonal cholestasis. Endoscopic retrograde cholangiography was normal. Following chemotherapy treatment with idarubicin and cytarabine for seven days for AML, the bilirubin levels continued to increase for two weeks and then decreased, reaching normal levels in two months. Infiltration of mast cells in the liver leads to hepatomegaly, liver function abnormality and rarely portal hypertension. Intrahepatic cholestasis due to systemic mastocytosis has never been reported. We report a rare case of systemic mastocytosis causing intrahepatic cholestasis that resolved with remission of AML following chemotherapy.     

Usefulness of liver biopsy in the study of the pediatric patient. Review of 145 cases

There were reviewed 145 cases of children in which hepatic biopsy was done at the Hospital Infantil del Estado de Sonora, from 1978 to 1990. The larger age group were infants and preschool children (74.3 percent) males being predominant; signs and symptoms were related with hepatic illness, as well as the admission diagnoses. The indication of biopsy was for confirmation of liver disease in more than 50 percent, 37.1 percent for unknown diagnoses and 20.6 percent to look for liver disease by a systemic illness. The most usual procedure was percutaneous biopsy with Vim-Silverman needle in 111 cases (76.5 percent), in 23 percent, the biopsy was done by major surgical method. Nine percent of the children needed open surgical method after percutaneous biopsy. The time from the admission to biopsy performance in patients with neonatal hepatitis vs biliary atresia was 14 days. In other type of illness the time was 25 days. The morbidity was 1 percent. There was no mortality. The histopathologic diagnosis of liver diseases was done in 96 cases (66.7 percent) by this method in 31 children (21.3 percent) with investigation of jaundice (neonatal hepatitis vs biliary atresia). The diagnostic mistake in tissues obtained by percutaneous needle, was statistically significant (p < 0.05). Average hospitalization stay was less than two months in 70 percent of the cases.     

Liver perfusion studied with ultrafast CT

OBJECTIVE: Our goal was to quantify absolute hepatic arterial and portal venous perfusion noninvasively in patients with and without liver disease using ultrafast CT. MATERIALS AND METHODS: A single slice through the porta hepatis was repeatedly scanned after bolus injection of 25 ml of iohexol 300 mg I/ml, followed by a 25 ml saline "chaser" intravenously at 10 ml/s. Thirty-nine controls, 7 cirrhotic patients, and 5 patients with known metastases on the slice plane were studied; hepatic arterial perfusion was determined in 41 patients and portal venous perfusion in 24. Time-attenuation curves from regions of interest drawn over the liver, spleen, aorta, and portal vein were analysed. Hepatic arterial perfusion was calculated by dividing the peak gradient of the liver time-attenuation curve prior to the time of peak splenic attenuation by the peak aortic CT number increase. Splenic perfusion was calculated by dividing the peak gradient of the splenic time-attenuation curve by the peak aortic CT number increase. Portal perfusion was derived by scaling the splenic time-attenuation curve by the ratio of hepatic arterial/splenic perfusion. This scaled curve was subtracted from the liver time-attenuation curve to give a portal curve. The peak up-slope of this curve was divided by the peak rise in splenic or portal vein density. RESULTS: Hepatic arterial perfusion averaged 0.19 ml/min/ml (n = 31) in controls and was raised in cirrhosis to 0.25 ml/min/ml (n = 6) and metastases 0.43 ml/min/ml (n = 4). Portal venous perfusion was 0.93 ml/min/ml (n = 19) in controls and 0.43 ml/min/ml (n = 4) in cirrhosis. Reproducibility has been confirmed. CONCLUSION: Dynamic ultrafast CT shows potential in quantifying arterial and portal hepatic perfusion. The technique may be adaptable to dynamic bolus MRI.     

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.     

Chronic liver failure induced by long-term administration of tegafur: a case report

A 55 year-old man was admitted with massive ascites. Although the laboratory data on admission were compatible with hepatic cirrhosis and remarkable esophageal varices were observed during endoscopy, the imaging findings such as computed tomography and ultrasonographic examination did not confirm hepatic cirrhosis. The patient had no history of alcohol abuse, blood transfusions or acute hepatitis. Serological markers related to viral and autoimmune hepatitis were all negative. Seven years ago, the patient had undergone an operation for colon cancer and has been taking tegafur since then for a total of 55 months. Tegafur was suspected as the causative agent for the liver dysfunction of this patient and the administration of tegafur was stopped. His laboratory data improved gradually and the ascites vanished. The first liver biopsy performed 6 months after discontinuation of tegafur still revealed chronic active hepatitis. However, at the liver biopsy performed 18 months after withdrawal of tegafur, inflammatory activity had subsided and the third liver biopsy, performed 34 months thereafter, revealed further improvement of the pathological changes that had occurred in the liver. We therefore conclude that the administration of tegafur may have caused chronic active liver injury with portal hypertension manifested as ascites and esophageal varices.     

Treatment of sleep apnoea in spinal cord injured patients

Nine patients with biliary atresia (BA) were investigated from the aspect of biliary bilirubin conjugates. They were classified arbitrarily into the good prognostic group in which jaundice disappeared (serum total bilirubin equal or below 1.0 mg/dl), and the poor prognostic group in which persistent jaundice was observed for more than 12 months. The ratio of biliary bilirubin diconjugate (BDC) increased in all patients of the two groups by the first month after operation. Although there was no significant difference in daily bilirubin excretion within 1-3 postoperative days, the BDC ratio in the good prognostic group was significantly higher than that in the poor prognostic group (p < 0.01). The study indicated that the ratio of BDC was an early prognostic determinant of BA patients. The prognosis of BA patients was much influenced by the ability of bilirubin conjugation in the early postoperative days.