[Condition of lipid peroxidation and antioxidant system in patients with non-alcoholic fatty liver disease].

The article presents research results which made it possible to reveal processes of lipoperoxidation of neutral lipids featuring oxidative stress in patients with non-alcoholic fatty liver disease and biliary tract pathology. All the patients demonstrated contra-directed changes in the antioxidant system enzymes activity requiring therapeutic correction including pathogenetic preparations with antioxidant properties.

EUS yield in evaluating biliary dilatation in patients with normal serum liver enzymes.

The finding of common bile duct (CBD) dilatation on abdominal imaging frequently results in additional testing. It has been our impression that endoscopic ultrasound (EUS) evaluation of a dilated CBD is a low-yield examination in the setting of normal serum liver enzymes. We therefore sought to evaluate the EUS yield in evaluating CBD dilatation in patients with normal as compared to elevated serum liver enzymes. A retrospective review was performed to identify patients referred for EUS evaluation of a dilated CBD in the absence of obvious pathology on prior imaging. Charts were reviewed for patient symptoms, presence of elevated serum liver enzymes, imaging studies before EUS, and EUS findings. Exclusion criteria included clinical jaundice, known biliary stricture, mass lesion or stone, and previously sphincterotomy and/or stent placement. Forty-seven patients were identified: 32 with normal and 15 with elevated serum liver enzymes. There was no difference in mean CBD diameter between these two groups (8.51 vs. 8.79 mm, p=0.854). Of the entire group, 15 patients had undergone prior magnetic resonance cholangiopancreatography (MRCP); an additional 7 patients had undergone prior endoscopic retrograde cholangiopancreatography (ERCP). EUS findings to explain CBD dilatation were found more commonly in patients with elevated compared with normal serum liver enzymes (53% vs. 6%, p=0.001). Periampullary diverticula and choledocholithiasis were the most common findings; of 32 patients with normal serum liver enzymes, one periampullary diverticulum and one CBD stone were found, respectively. The CBD stone had been missed by prior MRCP examination. Of 15 patients with elevated serum liver enzymes, there were 3 cases of choledocholithiasis, 4 periampullary diverticula, and 1 ampullary tumor. EUS should be the test of choice for further evaluation of CBD dilatation when index imaging is normal. Although the EUS yield is low in cases of biliary dilatation in the setting of normal serum liver enzymes, its preferential use would potentially avoid unnecessary MRCP and ERCP.

Gamaglutamil transpeptidasa: interpretación y valor diagnóstico / Gammaglutamyl transpeptidase: interpretation and diagnostic value

La gamaglutamil transpeptidasa es una enzima elaborada por los hepatocitos y de muy amplia distribución en el organismo, lo que reduce su especificidad y su utilidad diagnóstica. La evaluación de sus valores séricos se observa en el 90 por ciento de las afecciones hepato-biliares pero también alrededor del 5 por ciento de los sujetos sanos. Para tener utilidad diagnóstica, se recomienda no determinarla ni utilizarla aisladamente si no que en conjunto con la clínica y con las fosfatasas alcalinas y las transaminasas. En el campo del alcoholismo crónico, la GGT se encuentra elevada en alrededor del 75 por ciento de los casos pero como herramienta de despistaje no tiene más valor que la macrocitosis de los hematíes. En cambio, tiene utilidad en el control y monitorización de la abstinencia dado que sus valores séricos se reducen fuertemente ya al cabo de 15 días de suprimida la ingesta. Algunos medicamentos tales como los antidepresivos, los anticonvulsivantes, el fenobarbital y los inductores enzimáticos provocan alzas de la GGT.

Clinical importance of gamma glutamyltransferase in the Ankara-Pursaklar region of Turkey.

OBJECTIVE: The aim of this study is to determine the etiologies of serum gamma glutamyltransferase (GGT) elevation and relations between multiple etiologies prevalent in the Pursaklar region of Ankara in Turkey. PATIENTS AND METHODS: The patients referred to the Family Medicine and Internal Medicine departments with various complaints from the Pursaklar region of Ankara between July 2000 and July 2002 were evaluated, and values for GGT, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) levels were determined. GGT elevation was classified as being associated with hepatic, biliary, and other origins. RESULTS: For GGT elevation, hepatobiliary etiologies were more prevalent. The most prevalent hepatic etiology was nonalcoholic steatohepatitis, followed by biliary etiologies. The most prevalent etiology of biliary origin was cholelithiasis. Other etiologies, in order of prevalence, were drug exposure and urinary infection. There were no gender-related differences for distribution of GGT elevation; however, the GGT values for women were higher than those for men.

Clinical value of biliary alkaline phosphatase in non-jaundiced cholangiocarcinoma.

PURPOSE: Measurement of the activities of alkaline phosphatase isoenzyme has been used for the identification and monitoring of diseases associated with the isoenzyme. Biliary alkaline phosphatase (BALP), an isoform of liver-ALP, has been found in the serum of patients with biliary obstruction and metastatic liver cancer. This study compared the BALP isoform in the serum of patients with cholangiocarcinoma (CCA) with that of non-jaundiced benign hepatobiliary disease, other cancers, and healthy persons. METHODS: ALP isoforms were separated using cellulose acetate electrophoresis and the activity was demonstrated using indolyl blue reagent. RESULTS: The BALP isoform was demonstrated in 65% of CCA patients independently of jaundice condition or histological grading of the tumor. The level of serum BALP in non-jaundiced CCA was significantly lower than that of jaundiced CCA, and not correlated with serum bilirubin. No BALP was detected in healthy persons. In the patients with high serum ALP (> 147U/l), BALP can differentiate non-jaundiced CCA patients from other non-jaundiced carcinoma patients with 85% sensitivity, 79% specificity, and positive and negative predictive values of 81% and 83%, respectively. CONCLUSION: The demonstration of serum BALP, in particular in non-jaundiced patients with high serum ALP, may indicate the presence of tumor in the bile duct.

Making sense of liver enzymes, liver function tests, and hepatobiliary disorders at the reference desk.

This paper discusses concepts and terminology of some aspects of the laboratory diagnosis of liver (hepatic) disease and biliary tract disease (hepatobiliary disease) as it relates to medical reference work. Details of anatomic, biochemical, and pathologic processes are not discussed. Knowledge of the specific terminology involved in this area may help to ensure a good approach to developing prudent strategies for database searching of the medical literature and therefore is reviewed. MeSH and EMBASE thesauri terms are discussed and textword synonyms are presented that provide tools for thorough searching techniques. Commonly used medical jargon for this area is also explained. Examples of specific search strategies are illustrated.

Mast cell subpopulations in chronic inflammatory hepatobiliary diseases.

AIM/BACKGROUND: In various hepatobiliary diseases mast cells have been found to be associated with fibrogenesis. However, mast cell subpopulations have not been investigated in the human liver in normal subjects or in disease. Human mast cells are categorized into mast cells positive for tryptase (MC(T)) only and mast cells positive for both tryptase and chymase (MC(TC)). METHODS: In this study we investigated mast cell subpopulations (MC(T) and MC(TC)) by double immunostaining for mast cell tryptase and chymase as well as by a computer-aided quantitative morphometry in 13 normal livers and in 193 liver tissue specimens comprising of primary biliary cirrhosis (n=43), autoimmune hepatitis (n=11), chronic hepatitis B (n=37), chronic hepatitis C (n=41), alcoholic liver disease (n=40) and hepatolithiasis (n=21). RESULTS: The densities of MC(T) and MC(TC) per 1 mm2 stroma were low in normal livers but high in chronic liver diseases, and correlated positively with the degree of fibrosis. The percentages of MC(T) and MC(TC) subpopulations were 25% and 75%, respectively. The percentage was almost the same in normal livers and various hepatobliliary diseases, as well as between less fibrotic cases and more fibrotic cases in liver diseases. CONCLUSIONS: These results suggest that MC(T) and MC(TC) subpopulations in healthy and diseased livers do not change during liver fibrosis of any etiology.

[Cholinesterase in the differential diagnosis of parenchymal and obstructive icterus and in the differentiation between malignant and benign obstruction]. / Cholinesterase in der Differentialdiagnostik des parenchymatischen und obstruktiven Ikterus und bei der Differenzierung maligner und benigner Obstruktion.

Determination of CHE has already been proven as a useful test in the diagnosis of liver diseases. Our investigation included 2 groups of patients: a group suffering from parenchym hepatitis caused by virus infection A and B, and a second group of patients suffering from etiologically different obstructive hepatitis (malign and benign obstruction). Our tests show that there is lower CHE activity in patients with hepatitis B. There is a remarkable difference of CHE activity in benign and malign obstructive hepatitis.

A prospective study of the causes of notably raised aspartate aminotransferase of liver origin.

BACKGROUND AND AIMS: To ascertain the causes of raised aspartate aminotransferase (AST) presumed to be of hepatic origin in two hospitals and the local community served by a centralised biochemistry laboratory. METHODS: From June 1996 to February 1997 all patients with AST greater than 400 U/l were identified by the biochemistry laboratory; the patients' clinical records were studied to determine the diagnosis, the clinical outcome, and whether the raised AST and its significance had been noted. RESULTS: A total of 137 patients with a hepatic cause for the raised AST were found. The cause of the raised AST was hepatic ischaemia/hypoxia in 68, pancreatobiliary disease in 33, primary hepatocellular disease in 23, hepatic malignancy in five, and hepatic haematoma in one. In seven patients the diagnosis was unclear. The overall mortality was high (22%) with the highest mortality in the hepatic ischaemia group (37%). The recording and interpretation of the causes of raised AST was poor with only 48% having the correct diagnosis. In 38% the raised AST was apparently not noticed by the attending clinicians. CONCLUSIONS: The commonest cause of a hepatitis like biochemical picture was hepatic hypoxia (50%) followed by pancreatobiliary disease (24%). Drug induced hepatic necrosis (8.8%) was uncommon and viral hepatitis was rare (3.6%). AST concentrations returned towards normal most rapidly in patients with hepatic hypoxia and calculous biliary obstruction. Hepatitis, viral or otherwise, is an uncommon cause of a typical hepatitic biochemical result in this community.

Distribution of intrahepatic mast cells in various hepatobiliary disorders. An immunohistochemical study.

There is evidence that mast cells are involved in a number of pathophysiological processes. The significance of mast cells in hepatic fibrosis was examined in 28 patients with histologically normal livers, 34 with acute liver diseases, 51 with chronic liver diseases, and 59 with cholestatic biliary diseases, using immunostaining of the mast cell-specific proteinase, tryptase. Mast cells that were positive for tryptase and for chymase were significantly increased in frequency in fibrotic portal tracts and fibrous septa, particularly in cholestatic/biliary diseases. Mast cells were also increased in frequency around the fibrotic septal and intrahepatic large bile ducts and peribiliary glands of biliary diseases. However, they were less common or even rare in the sclerotic bile ducts and in scarred portal or septal fibrosis. More than half of these more numerous mast cells were positive for histamine, and some were also positive for basic fibroblast growth factor. These two substances were detectable by immunoelectron microscopic in the cytoplasmic granules of mast cells. In contrast, mast cell numbers were not significantly increased in acute viral or drug-induced hepatitis, or in zones 2 and 3 of the hepatic acinus with respect to pericellular and perivenular fibrosis in chronic liver diseases. These findings suggest that mast cells increase in number in cholestatic/biliary diseases, and to a lesser degree in chronic liver diseases, and are involved in the active fibrous enlargement of portal tract and fibrous septa formation and also in the fibrosis of the intrahepatic bile ducts as they display fibrosis-promoting factors such as tryptase, fibroblast growth factor and histamine.

[Metabolic disorders in digestive and hepatobiliary pathology in those who worked in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station]. / Narusheniia metabolizma pri digestivnoi i gepatobiliarnoi patologii u likvidatorov posledstvii avarii na ChAES.

A clinical observation over 57 liquidators of the Chernobyl accident aftermath (ChAAL) with associated diseases of the digestive and hepato-biliary system revealed abnormalities in blood enzymic activity, presenting as elevation of, in particular, alanine aminotransferase as well as of asparagine aminotransferase, gamma-glutaminetranspeptidase, alkaline phosphatase, lactate dehydrogenase, and of blood mineral composition at the expense of an increase in certain minerals. Disturbances in underlying process of bodily metabolism promote the development and association of erosive and ulcerous lesions of the stomach and duodenum with chronic noncalculous cholecystitis, persistent hepatitis in ChAAL.

Receiver operating characteristic analysis for biliary complications in liver transplantation.

Receiver operating characteristic (ROC) analysis was used to assess the use of the serum chemical markers, gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), and total bilirubin (BR) as tests for biliary complications in patients who had undergone orthotopic liver transplantation. Our study consisted of 105 consecutive adult transplant patients at the University of Chicago from March 1985 to November 1988. Biliary complications were determined by cholangiogram. Maximum serum values for three postoperative time periods (days 0 to 30, days 31 to 90, and > 90 days) were obtained for each patient. ROC analysis showed that GGT was the best single test during the earliest and latest time periods, whereas BR was best during days 31 through 90. We also assessed the time periods, surgical biliary anastomosis, pretransplant diagnosis, and location of biliary lesions compared with the incidence of biliary pathology for the patients. We found that patients with a pretransplant diagnosis of acute parenchymal liver disease were more likely to have biliary complications, and patients with end-to-end anastomosis with T tube were also more likely to have biliary complications. We further conclude that GGT, BR, and AP are all useful in screening for biliary complications and should be used routinely in liver transplant patients.

Activation energy of serum 5'-nucleotidase as a marker for enzyme heterogeneity.

Using adenosine 5'-monophosphate (Arkesteijn; J. Clin. Chem. Clin. Biochem. 14 (1976) 155) and inosine 5'-monophosphate (Bertrand & Buret; Clin. Chim. Acta 119 (1982) 275) as substrates for the determination of serum 5'-nucleotidase, linear Arrhenius plots were obtained between 25 degrees C and 37 degrees C. With the latter method, in patients with hepatobiliary disease, activation energy is higher than in healthy subjects (67.8 +/- 0.8 kJ.mol-1 vs. 59.2 +/- 1.6 kJ.mol-1, p < 0.001). Neuraminidase treatment resulted in a significant reduction in the activation energy of serum 5'-nucleotidase from patients (63.6 +/- 0.6 kJ.mol-1, p < 0.001). Although the activation energy seen is also influenced by conditions other than sialic acid content, the results obtained are in accordance with the hypothesis that in liver disease serum 5'-nucleotidase becomes more sialylated.

Alkaline phosphatase isoforms in serum after liver allograft surgery.

Orthotopic liver transplantation (OLT) is now the only available treatment for end-stage liver disease; the major postoperative complications of OLT are rejection and infection. Fractionation of alkaline phosphatase (ALP) isoforms in serum by isoelectric focusing can be used to identify patients with complications. Reference ranges for liver-function tests (LFT) and liver ALP isoforms were established for post-OLT patients with stable postoperative courses and compared with those of patients with complications. We found canalicular, hepatocyte, and high-molecular-mass ALP to be statistically higher in nearly all patients with complications as compared with patients who had a stable postoperative course; these tests may identify patients requiring a liver biopsy. When used in conjunction with LFT and other clinical findings, ALP isoforms could aid in the monitoring of complications and treatment and in the adjustment of immunosuppressive therapy in stable OLT cases.

Lipase/amylase ratio: not helpful in the early etiological differentiation of acute pancreatitis.

The value of the lipase/amylase ratio for early etiological differentiation of acute pancreatitis was tested in 103 consecutive patients with acute pancreatitis from an ongoing prospective study. On admission, amylase, but not lipase, was significantly lower in alcoholics than in nonalcoholics in general and especially in patients with biliary pancreatitis. Alcoholics as a group had significantly higher lipase/amylase ratios than non-alcoholics and patients with acute biliary pancreatitis. But although the mean values of the ratio were significant, sensitivity, specificity, positive and negative predictive values of lipase/amylase ratio were insufficient to separate alcoholics from nonalcoholics, patients with alcohol-induced pancreatitis from those with biliary etiology, and patients with biliary pancreatitis from those with pancreatitis of other etiologies in the individual case. Finally, there was no correlation between the ratio and the amount of pancreatic changes as judged from computed tomography. We concluded that the ratio does not allow for early routine clinical differentiation between etiologies of pancreatitis and evaluation of the severity of the disease.

Measles associated hepatobiliary disease: an overview.

In this report the literature on all cases of documented measles with hepatobiliary disease was reviewed to describe the characteristics of measles associated hepatitis. We found 27 patients described. Their age ranged from 9 to 59 years. Male to female ratio excluding military facilities was 1:1. The clinical and laboratory presentation appeared to follow one of two patterns. The first was suggestive of hepatocellular dysfunction characterized by aminotransferase elevation. It was encountered in 24/27 cases, seven of them with atypical measles. This form of liver disease tended to be asymptomatic. It appeared early and resolved in a few days. The second pattern was characterized by cholestasis and jaundice. It was described in three cases. This type of hepatitis became apparent when measles began to recede and persisted for two weeks or longer. The variation in time of appearance of the two types of liver disease may imply distinct pathogenetic mechanisms.

[Bile composition and antibiotic excretion. Observations with T-drainage]. / Gallenzusammensetzung und Antibiotikaausscheidung. Beobachtungen an der T-Drainage.

Patients comparable in disease, therapy and serum bilirubin concentration were either treated with mezlocillin intravenously or not at all. The bile of each patient was collected either from a T-drainage or from a percutaneously placed drainage into the bile ducts. The concentrations of GGT and AP, which were liberated by destroyed liver cells, and of bilirubin and mezlocillin, which were secreted actively, were analysed. Those patients who had normal serum bilirubin concentrations had a significantly higher biliary bilirubin excretion than those with high serum bilirubin level. The maximum excretion was after 4 hours. While the biliary concentration of bilirubin decreased, the concentration of secreted mezlocillin increased. Due to destroyed liver cells those patients with pathologically elevated blood bilirubin levels had a 50-fold lower mezlocillin excretion than those with normal blood values.

Methylene dianiline: acute toxicity and effects on biliary function.

4,4'-Methylene dianiline (4,4'-diaminodiphenylmethane, DAPM), which is used in the polymer industry, causes hepatobiliary damage in exposed humans. Our objectives were to characterize the acute toxicity of DAPM in liver, particularly on secretion of biliary constituents and on biliary epithelial cell gamma-glutamyl transpeptidase (GGT) activity. Biliary cannulas were positioned in Sprague-Dawley male rats under pentobarbital anesthesia. After 1 hr of control bile collection, each rat was given 250 mg DAPM/kg (50 mg/ml) po in 35% ethanol or 35% ethanol only; bile was collected for a further 4 hr. Groups of rats were also examined for liver injury and biliary function at 8 and 24 hr after DAPM. Four hours after DAPM administration, main bile duct cells were severely damaged with minimal damage to peripheral bile ductule cells. Focal periportal hepatocellular necrosis and extensive cytolysis of cortical thymocytes occurred by 24 hr. Serum indicators of liver injury were elevated by 4 hr and continued to rise through 24 hr. By 4 hr, biliary protein concentration was increased 4-fold while concentrations of biliary bile salt, bilirubin, and glutathione were decreased by approximately 80, 50, and 200%, respectively. DAPM also induced a striking effect on biliary glucose with an approximately 20-fold increase. Histochemical staining of main bile duct GGT was absent by 8 hr after DAPM. Bile flow was diminished by 40% at 4 hr; three of five rats had no bile flow by 8 hr and none had any bile flow by 24 hr. These results indicate that DAPM rapidly diminishes bile flow and alters the secretion of biliary constituents and is highly injurious to biliary epithelial cells.

Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980-1990).

The diagnostic efficacy of serum alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities was examined, using the records of 270 dogs initially suspected of having hepatobiliary disease on the basis of history, findings on physical examination, results of baseline screening tests, or any combination of these data. Histologic examination of hepatic tissue was performed in each dog. Sixty-three dogs did not have histologic evidence of hepatobiliary disease and served as the control group. On the basis of diagnosis, dogs were assigned to 1 of 8 groups: dogs with cirrhosis (n = 34), steroid hepatopathy (n = 16), hepatic neoplasia (primary and secondary, n = 36), chronic hepatitis (n = 14), chronic passive congestion (n = 5), hepatic necrosis (n = 17), portosystemic vascular anomaly (n = 35), and cholestasis (extrahepatic bile-duct obstruction and intrahepatic cholestasis, n = 50). Of the 207 dogs with hepatobiliary disease, 29 (14%) had normal ALP and GGT activities, 31 (15%) had normal ALP activity, and 112 (54%) had normal GGT activity. Of the 63 control dogs, 29 (46%) had normal serum ALP and GGT activities, 32 had normal ALP activity (ALP specificity, 51%), and 55 had normal GGT activity (GGT specificity, 87%). The specificity of ALP and GGT in parallel (positive result = result of either test abnormal) was 46%, and in series (positive result = results of both tests abnormal) was 91%. The highest median activities of ALP developed in dogs with cholestasis, steroid hepatopathy, chronic hepatitis, and hepatic necrosis. The highest median activities of GGT developed in dogs with steroid hepatopathy, cholestasis, and hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)