Biliary tract abnormalities in patients with arteriohepatic dysplasia

Arteriohepatic dysplasia is a congenital syndrome associated with life-long cholestasis. Because of symptoms suggesting extrahepatic biliary tract obstruction, we studied three patients with this syndrome by endoscopic retrograde cholangiopancreatogram (ERCP). All patients showed a decrease in the number of intrahepatic ducts. In addition, the intrahepatic ducts show attenuation with focal areas of dilatation. In one subject, this latter finding appeared to be a localized process. The extrahepatic ducts were also narrowed. One patient in this series was found to have gallstones and another cirrhosis. Although the relationship of these anomalies to the cholestasis seen in these patients is unclear, arteriohepatic dysplasis can be added to the list of processes associated with biliary tract abnormalities.     

Thin needle cholangiography: experience with 50 patients

Thin needle cholangiography (TNC) was performed in 50 patients with obstructive jaundice or jaundice of obscure origin. The purpose of this study was to assess the diagnostic accuracy and safety of this procedure. TNC was performed by the technique described by Redeker et al. using the Chiba needle (JAMA 231:386, 1975). Obstructed ducts were successfully demonstrated in 100% of cases (29/29). Non-obstructed ducts were opacified in 12/21 (57%). Overall success was 82% (41/50). Two septic complications occurred. It is concluded that 1) TNC is a highly reliable, easy to perform and safe procedure in the evaluation of the jaundiced patient; 2) Accurate demonstration of the biliary anatomy by TNC provided important information which often in (10/50 = 20%) led to a change in diagnosis, avoidance of unnecessary procedures, and shortening of hospitalization; 3) Failure to visualize patients with non-dilated biliary ducts occurred with advanced chronic liver disease or fatty liver.     

Intrahepatic cholestasis in childhood

The apparent well-being of some children who as neonates were believed to have obstructive jaundice prompted us to study the clinical course, histologic features and possible etiologic factors in 17 children with cholestasis in the neonatal period. During a follow-up period of five months to 22 years, all had signs of chronic cholestasis, but only four died (two from nonhepatic causes); the others live remarkably normal lives. Serial hepatic biopsies in 11 showed a variety of initial lesions, which progressed to hypoplasia of the intrahepatic bile ducts, increasing portal fibrosis and eventual cirrhosis. Although evidence of possible viral infection was found in only 10 cases, a hepatitis, beginning either before or after birth, appears to be a likely original cause. The histologic changes seen may represent different stages of one process, starting as cholestasis with or without evidence of hepatitis and progressing to obliteration or failure of normal growth of the intrahepatic bile ducts.     

Intrahepatic vascular lesions following nonsurgical percutaneous transhepatic bile duct intubation

Hepatic angiography was performed following nonsurgical percutaneous transhepatic intubation of the bile ducts in patients with extrahepatic cholestasis. Vascular lesions of the liver (aneurysm, hematoma, arterioportal venous fistula, arteriohepatic venous fistula) were demonstrated in 27 of 83 patients. No clinical complications were observed in 22 of these cases. One patient with an arterioportal venous fistula developed marked hemobilia necessitating blood transfusion. In four patients with severe hemorrhage from an intrahepatic aneurysm, transcatheter embolization was performed. Two of these patients died within 72 h because of liver insufficiency.     

Histopathological diagnosis of intra- and extrahepatic neonatal cholestasis

The histopathology of the liver is fundamental for the differential diagnosis between intra- and extrahepatic causes of neonatal cholestasis. However, histopathological findings may overlap and there is disagreement among authors concerning those which could discriminate between intra- and extrahepatic cholestasis. Forty-six liver biopsies (35 wedge biopsies and 11 percutaneous biopsies) and one specimen from a postmortem examination, all from patients hospitalized for neonatal cholestasis in the Pediatrics Service of Hospital de Clínicas de Porto Alegre, were prospectively studied using a specially designed histopathological protocol. At least 4 of 5 different stains were used, and 46 hepatic histopathological variables related to the differential diagnosis of neonatal cholestasis were studied. The findings were scored for severity on a scale from 0 to 4. Sections which showed less than 3 portal spaces were excluded from the study. Sections were examined by a pathologist who was unaware of the final diagnosis of each case. Bile tract permeability was defined by scintigraphy of the bile ducts and operative cholangiography. The F test and discriminant analysis were used as statistical methods for the study of the hepatic histopathological variables. The chi-square method with Yates correction was used to relate the age of the patients on the date of the histopathological study to the discriminatory variables between intra- and extrahepatic cholestasis selected by the discriminant function test. The most valuable hepatic histopathological variables for the discrimination between intra- and extrahepatic cholestasis, in decreasing order of importance, were periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules, foci of myeloid metaplasia, and portal-portal bridges. The only variable which pointed to the diagnosis of intrahepatic cholestasis was myeloid metaplasia. Due to the small number of patients who were younger than 60 days on the date of the histopathological study (N = 6), no variable discriminated between intra- and extrahepatic cholestasis before the age of 2 months and all of them, except for the portal expansion, were discriminatory after this age. In infants with cholestasis, foci of myeloid metaplasia, whenever present in the liver biopsy, suggested intrahepatic cholestasis. Periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules, portal cholestasis and portal-portal bridges suggested extrahepatic obstructive cholestasis.     

Cholestasis secondary to Hodgkin's disease: report of 2 cases of vanishing bile duct syndrome

Only a small percentage of patients with Hodgkin's disease become clinically Jaundiced during their disease. This Jaundice may be secondary to biliary obstruction, hemolysis, direct hepatic infiltration by the disease, drug toxicity or viral hepatitis. Vanishing bile duct syndrome secondary to Hodgkin's disease is a rare cause of cholestasis in these patients, only 13 cases having been reported so far. The authors describe 2 patients who developed severe Jaundice secondary to Hodgkin's disease due to vanishing bile duct syndrome affecting small intrahepatic bile ducts.     

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.     

Segmental hyperintensity on T1-weighted MRI of the liver: indication of segmental cholestasis

The purpose of this study was to determine the relationship between segmental hyperintensity of the liver on T1-weighted images and segmental cholestasis in patients with obstructive jaundice. T1-weighted and T2-weighted MR images were obtained of 73 patients with obstructive jaundice caused by various diseases. Fat-suppressed T1-weighted images were also obtained of 10 patients. Eleven patients with segmental intrahepatic bile duct dilatation (cholestasis) showed segmental hyperintensity on T1-weighted images and/or fat-suppressed T1-weighted images and no signal intensity difference on T2-weighted images. Sixty-two patients with widespread intrahepatic bile duct dilatation showed no intensity difference on T1-weighted and T2-weighted images (P < .01). Segmental hyperintensity on T1-weighted images was correlated with intrahepatic cholestasis.     

Multicentre evaluation of a commercial test for the rapid diagnosis of Clostridium difficile-mediated antibiotic-associated diarrhoea

Although histologic studies of mucin distribution in the peribiliary glands have been conducted, a quantitative study of mucin content in intrahepatic bile ducts has yet to be reported. In an attempt to evaluate the mucin content in stone-containing intrahepatic bile ducts, we conducted a study on 25 surgically resected livers with hepatolithiasis. Specimens from 10 livers without stones served as controls. All specimens were fixed in 10% formalin and sectioned for periodic acid Schiffalcian blue double-stain (PAS-AB; pH 2.5) to evaluate the epithelial mucin content of the intrahepatic bile ducts. The PAS-AB positive area and the total epithelial area were measured with a computerized image analyzer and the PAS-AB index was calculated as the proportion of the PAS-AB positive to the total epithelial area. The histochemical study showed that epithelial cells in both the intramural glands and extramural glands of stone-containing intrahepatic bile ducts stained heavily and homogeneously with PAS-AB, while those of controls stained weakly. The PAS-AB indexes in stone-containing intrahepatic bile ducts were 51.8 +/- 15.88% for mucous cells of intramural glands, 52.86 +/- 9.85% for mucous cells of extramural glands, and 77.29 +/- 21.59% for serous cells of extramural glands. These values were all significantly higher than those of control specimens. However, the PAS-AB index of the epithelial lining in both hepatolithiasis and control specimens were similarly low, indicating the epithelial lining does not secrete much mucous glycoprotein. The results of this study led us to conclude that stone-containing intrahepatic bile ducts contain an abundant amount of mucous glycoprotein, and mucin is secreted from the peribiliary glands, not from the epithelial lining of the bile ducts.     

Unexpected clinical remission of cholestasis after rifampicin therapy in patients with normal or slightly increased levels of gamma-glutamyl transpeptidase

OBJECTIVE: Rifampicin is an effective drug against pruritus in intrahepatic cholestasis. However, there is no specific hepatic disease in which its use could cause undoubtedly biochemical improvement. The aim of this study was to describe patients with complete remission of cholestatic symptoms after rifampicin therapy. METHODS: We reported three female patients with intrahepatic cholestasis with no evidence of viral, metabolic, or autoimmune liver diseases. Total bilirubin levels ranged from 13.2 to 27.2 mg/dl (before the first treatment with rifampicin), and in all of them gamma-glutamyl transpeptidase values were within the normal range or slightly increased. Rifampicin therapy was administered orally, without any concomitant drug, with an effective dosage of 5-17 mg/kg/day. RESULTS: In all patients, pruritus ceased completely and bilirubin returned to normal values. The symptoms recurred after rifampicin withdrawal on, at least, three occasions in each patient, and these symptoms were always eliminated after its reintroduction. The patients had a total of 16 cholestatic episodes during a follow-up of 8 yr, with a complete clinical recovery in all of them. Undergoing therapy with a suitable dosage of rifampicin, none of the patients had a cholestatic crisis even during a period for as long as 12 months. The diagnosis of two patients was consistent with benign recurrent intrahepatic cholestasis, and it was not well defined in the remaining. CONCLUSION: Rifampicin may induce clinical remission, and perhaps prevent clinical relapses of intrahepatic cholestasis with normal or slightly increased levels of gamma-glutamyl transpeptidase.     

Evidence for a luteinizing hormone surge center in the hypothalamus of the pig

Lipoprotein-X (Lp-X) is an abnormal low-density lipoprotein frequently found in liver disease. It is regarded as the most sensitive and specific biochemical parameter for the diagnosis of intra- and extrahepatic cholestasis. Moreover, Lp-X is supposed to contribute to the development of hypercholesterolemia in cholestatic liver disease, because it fails to inhibit de novo cholesterol synthesis. This investigation will focus on the relationship between the presence of Lp-X and serum lipid concentrations in cirrhosis. The significance of Lp-X in the diagnosis of cholestasis, compared with alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), and bilirubin levels, will be assessed as well. The present cross-sectional study includes 212 patients with histopathologically proven cirrhosis. The detection of Lp-X and the quantification of -, beta-, and pre-beta-cholesterol was based on agar gel electrophoresis and polyanion precipitation. For the characterization of liver function, the concentrations of albumin and bilirubin, the activities of liver enzymes, and coagulation times were assessed. In a subgroup of 40 individuals, liver biopsies were re-evaluated to confirm or exclude intrahepatic cholestasis. As a result, there was no association between the appearance of Lp-X and total cholesterol concentrations. While all patients with Lp-X showed intrahepatic cholestasis (predictive value of the positive test = 1), only 16 of 28 patients with cholestasis formed Lp-X (sensitivity = 0.57). The activities of AP and of GGT, as well as the concentrations of bilirubin, were strongly elevated in most patients, with and without cholestasis. The predictive values of AP, GGT, and bilirubin were 0.77, 0.69, and 0.74 for the positive test and 0.5, 0, and 0.6 for the negative test, respectively. We conclude that Lp-X is not related to hypercholesterolemia in cirrhosis. The positive, but not the negative, Lp-X test has high predictive value for the diagnosis of cholestasis in cirrhosis. The biochemical parameters traditionally used for the assessment of extrahepatic cholestasis, AP, GGT, and bilirubin, do not support the diagnosis of intrahepatic cholestasis caused by cirrhosis.     

Elevated levels of bile acids in colostrum of patients with cholestasis of pregnancy are decreased following ursodeoxycholic acid therapy [see comemnts

BACKGROUND/AIMS: Intrahepatic cholestasis of pregnancy is characterised by increased levels of serum bile acids. Ursodeoxycholic acid therapy corrects the serum bile acid profile. The aims of this study were: (i) to investigate bile acid excretion into colostrum of women with intrahepatic cholestasis of pregnancy; (ii) to compare concentrations of bile acids in serum and colostrum of non-treated and ursodeoxycholic acid-treated patients; and (iii) to clarify whether ursodeoxycholic acid is eliminated into colostrum following treatment. METHODS: Bile acids were assessed by gas chromatography and high-performance liquid chromatography in serum collected at delivery, and in colostrum obtained at 2+/-1 days after labour, from patients with intrahepatic cholestasis of pregnancy, non-treated (n=9) and treated (n=7) with ursodeoxycholic acid (14 mg/kg bw per day, for 14+/-7 days) until parturition. RESULTS: The concentration of total bile acids in colostrum from patients with intrahepatic cholestasis of pregnancy was higher than in normals (23.3+/-14.8 micromol/l vs. 0.7+/-0.2 micromol/l, p<0.01) and cholic acid was a major species (19.0+/-13.1 micromol/l), reflecting the elevated concentrations in maternal serum (48.9+/-21.0 micromol/l, total bile acids; 33.9+/-16.7 micromol/l, cholic acid. Following ursodeoxycholic acid administration, total bile acids and cholic acid levels in colostrum diminished to 5.7+/-2.5 micromol/l and 3.6+/-1.5 micromol/l, respectively; the proportion of cholic acid decreased (60.6+/-8.0% vs. 76.8+/-5.0%, p<0.05). The ursodeoxycholic acid concentration in colostrum was maintained following treatment; its increased percentage (9.4+/-3.2% vs. 1.0+/-0.2%, p<0.01) was still lower than in maternal serum (20.8+/-3.6%, p<0.05). Only a small proportion (<1%) of lithocholic acid was found in colostrum following therapy. CONCLUSIONS: Bile acid concentrations are elevated and cholic acid is the major species accumulating in colostrum, reflecting serum bile acid profiles in intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid therapy decreases endogenous bile acid levels in colostrum.     

Seasonal variations in sperm abnormalities in bulls in a tropical climate

A case of anicteric idiopathic intrahepatic cholestasis in association with ankylosing spondylitis is described. No primary cause for the cholestatic syndrome was found and the liver histology was repeatedly normal. Results of treatment with clofibrate (2 g daily) were very satisfactory, as the symptoms and signs of cholestasis had gradually subsided. Discontinuation of the treatment was followed rapidly by a recurrence of the cholestasis with a new improvement after restarting treatment. The beneficial mechanism of action of clofibrate on the intrahepatic cholestasis in the case described remains speculative.     

Intrahepatic cholestasis due to biochemical errors of bile acids. II. Clinical and therapeutic aspects

Within the "primary" cholestasis we can discriminate "essential" forms due to an endogenous biochemical error of bile acid metabolism and/or secretion and "conditioned" forms, in which a known precipitating factor is required to elicit the functional disorder responsible for cholestasis. Among the essential forms of cholestasis must be included benign recurrent intrahepatic cholestasis or Summerskill-Walshe disease, Aagenaes disease, progressive familial intrahepatic cholestasis or Byler's disease, and forms due to disorders of the peroxisomes. Benign recurrent intrahepatic cholestasis, the best known form, is characterized by recurrent episodes of itching and jaundice with an acute onset separated by symptom-free intervals, which shows no tendency to progress to liver failure. The conditioned cholestasis group comprises cholestasis of pregnancy and drug-induced cholestasis. Benign recurrent cholestasis of pregnancy is a form induced "by" pregnancy and not a form occurring "in" pregnancy, such as cholestasis due to hepatitis, to primary biliary cirrhosis, to cholelithiasis. Drug-induced cholestasis is a chapter of great clinical relevance: forms due to steroid hormones and due to phenothiazines are discussed.     

Lung changes by experimentally induced cholesterol atheromatosis (author''s transl)

A family study was prompted by the presence of benign recurrent intrahepatic cholestasis in three members and probably in a fourth. Pruritus and/or jaundice occurred during pregnancy in nine members. Two additional members suffered from pruritus while using oral contraceptives. The literature on benign recurrent intrahepatic cholestasis since 1959 describes at least 57 cases. A familial form of this condition proved to be fairly common. There seems to be a relation to the intrahepatic cholestasis sometimes seen during pregnancy and during oral contraceptive use. The data of the family study are suggestive for an interrelation of the three types of intrahepatic cholestasis, although a common denominator remains obscure.     

A case of benign recurring intrahepatic cholestasis (Tygstrup-Summerskill and Walshe syndrome)

The case of a 23-year-old male patient with benign intrahepatic recurrent cholestasis of Summerskill-Tygstrup and Walshe type is presented. The patient had suffered 9 attacks up to 1974. The clinical and histological data of this patient were compared with those in the 65 cases described previously. The most characteristic signs were that the disease began before puberty and the attacks of jaundice with direct hyper bilirubmemia were induced by infections. Histology obtained in acute phase of the disease revealed intrahepatic cholestasis, and there were signs of a non-specific mesenchymal reaction of the liver tissue while the patients were asymptomatic. The serum activity of alkaline phosphatase was increased, gamma-glutamyltranspeptidase and transaminases being normal or close to normal. The pattern of the biochemical findings was characteristic and the patient was recognized among 19,035 other patients hospitalized from 1972-1975 by means of a special computer program. This program may be helpful in detecting patients with this disease from computerized data of hospitalized patients and avoiding unnecessary surgical intervention.     

Transvenous cholangiography and percutaneous transhepatic fine needle cholangiography (author's transl)

The comparison of transvenous cholangiography (TVC) in 82 patients with percutaneous transhepatic fine needle cholangiography (PTFC) in 84 patients showed that TVC must be considered obsolete due to the complicated procedure with low success rate (56.9%). In one case it led to septicaemia followed by death. The total success rate was 84.5% in PTFC performed with an ultrathin needle (0.5 mm diameter); congested biliary ducts were successfully punctured in 87.9% and noncongested ducts in 72.2%. Severe complications consisted of one case of intraabdominal bleeding and one biliary extravasation. As shown in animal experiments, the superficial parenchymal lesion has not always the shape of a point. High accuracy also in noncongested biliary tracts and low mortality make PTFC superior to TVC and conventional percutaneous transhepatic cholangiography.     

Conversational maxims and scaffolded learning in children with learning disabilities: is the flying buttress a better metaphor?

BACKGROUND: To compare half-Fourier acquisition single-shot turbo spin-echo spin-echo (HASTE) magnetic resonance cholangiopancreatography (MRCP) with two-dimensional turbo spin-echo (2D TSE) MRCP for imaging pancreatobiliary diseases. METHODS: Twenty-seven patients with biliary or pancreatic disease underwent MRCP on a 1.0-T scanner with a body phased-array coil. A T2-weighted HASTE sequence (18 s) and a T2-weighted 2D TSE sequence (45 s) were used during a breath-hold by the patient. The source images and maximum intensity projection images of both sequences were reviewed independently by two radiologists. RESULTS: Motion artifacts were more severely pronounced with 2D TSE sequences than with HASTE sequences (p < 0.001). All obstructions and their sites were accurately identified with both sequences. Filling defects (calculi) in bile ducts were identified in all 22 segments (100%) with HASTE-MRCP, whereas calculi in 19 of 22 segments (86%) were identified with 2D TSE-MRCP (p = 0.25). Three missed sites on 2D TSE-MRCP were intrahepatic bile ducts. CONCLUSIONS: HASTE-MRCP is superior to 2D TSE-MRCP in terms of detecting motion artifacts and visualization of the pancreatic ducts. HASTE-MRCP is comparable to 2D TSE-MRCP for visualization of the biliary ducts and their obstruction and is superior to 2D TSE-MRCP for identification of calculi in intrahepatic bile ducts.     

Hypermethioninemia in the differential diagnosis of infantile obstructive jaundice (author's transl)

In 7 infants suffering from obstructive jaundice we found transient high levels of methionine in serum. All cases had only intrahepatic cholestasis, especially with intrahepatic biliary hypoplasia, whereas other patients with extrahepatic biliary atresia and/or combination of extra- and intrahepatic obstructive jaundice always showed normal levels of methionine. Therefore hypermethioninemia seems to be helpful in differentiating the various causes of infantile obstructive jaundice.     

Usefulness of fine needle aspiration cytology in the diagnosis of prostate cancer

The efficacy of aspiration cytology, using Franzen method and echo-guided aspiration for prostate cancer was examined to 102 patients under saddle-block anesthesia in urological clinic of Chiba University Hospital. Between 1990 and 1993, 77 cases out of 102 patients were diagnosed histologically as prostate cancer by needle biopsy and 90% of them were coincidental with findings of aspiration cytology. Looking at histological grades, well differenciated cancer was shown to yield low positivity compared with moderately and poorly differentiated cancer. Positive rate showed similar when grade of specimens from needle biopsy was classified with Gleason pattern. Neither T category nor method of aspiration between Franzen and echo-guided methods influenced positive rate of aspiration cytology. On aspiration cytology, its grading revealed 60% of coincidence with that obtained by histological method. When counting more than 300 scattered cells, 90% of coincidence was achieved with histological grading. It is concluded that aspiration cytology is efficient for diagnosis of prostate cancer.