Bilirubin

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Bilirubin

  • direct bilirubin
  • serum bilirubin
  • serum total bilirubin
  • total bilirubin
  • total serum bilirubin

  • Terms modified by Bilirubin

  • bilirubin concentration
  • bilirubin encephalopathy
  • bilirubin level
  • bilirubin production
  • bilirubin toxicity
  • bilirubin value

  • Selected Abstracts


    Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis

    DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2009
    Adelaide Fernandes
    Abstract Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source]


    Preoperative determinants of common bile duct stones during laparoscopic cholecystectomy

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2008
    A. J. Sheen
    Summary Introduction:, The aim of this study is to determine whether there are any clinical or biochemical predictors of common bile duct (CBD) stones in patients undergoing laparoscopic cholecystectomy. Methods:, A prospective database of nearly 1000 laparoscopic cholecystectomies performed under the care of a single surgeon with a standardised technique between 1999 and 2006, was analysed. Clinical presentation, ultrasound and immediate preoperative biochemical results as well as the operative cholangiogram findings were reviewed. Routine cholangiography was attempted in most patients and the primary outcome variable was the detection of bile duct stones. The data was analysed using chi-squared test for categorical variables. The significant variables on univariate analysis were further characterised to identify the independent predictors of bile duct stones using a logistic regression model (significance p < 0.05). Results:, A total of 757 of 988 patients (77%) underwent cholangiography. Male-to-female ratio was 1 : 3 with a median age of 54 years (range: 17,93). Ten per cent of patients had bile duct stones identified on cholangiography. On univariate analysis, jaundice (p = 0.019), cholangitis (p < 0.001), alanine transaminase > 100 (p = 0.024), alkaline phosphatase (ALP) > 350 (p < 0.001) and CBD > 10 mm (p = 0.01) were significant markers for predicting bile duct stones. Bilirubin > 30 (×2 normal) was found not to be significant (p = 0.145). On a logistic regression model, ALP > 350 and/or cholangitis were found to be independent predictive factors of CBD stones (odds ratio 6.1). Conclusions:, If a policy of routine intra-operative cholangiography is not adopted, a history of cholangitis or a raised ALP immediately preoperatively should lead to a high suspicion of CBD stones. [source]


    The effect of total plasma exchange on fulminant hepatic failure

    JOURNAL OF CLINICAL APHERESIS, Issue 2 2006
    M. Akdogan
    Total plasma exchange (TPE) corrects coagulopathy in patients with liver disease and removes hepatotoxins/cytokines. This improvement is transient but can be used as a bridge until an organ is identified for liver transplantation (LTx) or the liver itself regenerates. Our aim was to retrospectively assess the efficacy of TPE in fulminant hepatic failure (FHF) and its impact on liver function tests. Between 1995,2001, 39 patients with FHF who had undergone TPE were reviewed. FHF was defined according to the O'Grady criteria based on the duration of encephalopathy as well as jaundice. TPE was performed using the Cobe Spectra TPE (Gambro®) in Liver Intensive Care Unit, continued on a daily basis, until either adequate clinical response was achieved, the patient expired, or transplantation occurred. INR, PTT, Fibrinogen, ALT, AST, GGT, BUN, Ammonia, and Total Bilirubin were analyzed before and after TPE. Student's t -test and chi-square test and ANOVA were used for statistical analysis. Thirty-nine patients with FHF (31 females, 8 males with mean age of 32.3, range: 7,64) underwent TPE. Coagulopathy, hyperbilirubinemia, hyperammonemia were significantly improved (P < 0.05). Twenty-one patients survived (54%), 12 required LTx, and 18 patients (including one after LTx) expired. TPE was found to be significantly effective for correction of coagulopathy and improvement of liver tests. This intervention can be considered for temporary liver support until recovery or liver transplantation. J Clin Apheresis 2005. © 2005 Wiley-Liss, Inc. [source]


    Serum bilirubin and colorectal cancer risk: a population-based cohort study

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2006
    G. N. IOANNOU
    Summary Background Bilirubin has antioxidant properties and has been postulated to protect against the development of malignancies. Aim To investigate whether baseline serum bilirubin concentration predicts the incidence of colorectal cancer in a nationally representative sample of the US population. Methods Participants of the first National Health and Nutrition Examination Survey were divided into four groups based on quartiles of baseline serum bilirubin concentration in mg/dL: <0.38 (n = 1410), 0.38 to <0.5 (n = 1287), 0.5 to <0.6 (n = 1048) and ,0.6 (n = 1742). The incidence of colorectal cancer during the following 20 years was determined from hospitalization records and death certificates. Results 110 cases of colorectal cancer-related death or hospitalization were identified among 5487 participants during 88 339 person-years of follow-up (12 per 10 000 person-years). There was no association between baseline serum bilirubin concentration and the incidence of colorectal cancer either in unadjusted analyses or after adjusting for age, gender, ethnicity, smoking, body mass index, alcohol consumption and educational attainment. Conclusions Baseline serum bilirubin concentration did not predict the subsequent incidence of colorectal cancer in this population-based cohort study. [source]


    Different methods of creatinine measurement significantly affect MELD scores

    LIVER TRANSPLANTATION, Issue 4 2007
    Evangelos Cholongitas
    Bilirubin (Bil) interferes with creatinine (Cr) measurement. Different laboratory methods are used to overcome this problem. Model for end-stage liver disease (MELD) scoring incorporates Cr and is used to prioritize patients for liver transplantation. Thus, MELD scores may vary with different Cr measurements influencing patients' priority. Our aim was to evaluate 4 different Cr assays (O'Leary modified Jaffe [mJCr], compensated [rate blanked] kinetic Jaffe [cJCr], enzymatic [ECr], and standard kinetic Jaffe [JCr]) in patients with abnormal liver function tests and assess changes in MELD score. A total of 403 consecutive samples from 158 patients' Cr assays were evaluated.. Bland-Altman plots and MELD scores were also evaluated for each assay. Agreement was found to be poor among all Cr assays. Increased variability in Cr occurred with increasing Bil concentrations: Bil <100 ,mol/L ,3-point MELD variation - 3-point difference in 2%; Bil ,400,mol/L ,7-point MELD variation - ,3-point difference in 78%. When MELD was ,25 (mJCr as reference; mean, 30.5 points), MELD variation was greatest: mean, 28 (MELD cJCr), 27.5 (MELD ECr), and 28.4 (MELD JCr) (P < 0.001). In conclusion, there is poor agreement among different assays for Cr. As Bil concentration rises, there is greater variability in each creatinine measurements and thus greater variability in MELD scores that, this affect prioritization for liver transplantation. Liver Transpl, 2006. © 2006 AASLD. [source]


    Bilirubin influence on oxidative lung damage and surfactant surface tension properties

    PEDIATRIC PULMONOLOGY, Issue 3 2004
    Carlo Dani MD
    Abstract To study the hypothesis that hyperbilirubinemia might reduce in vivo oxidative lung damage while also diminishing lung surfactant surface tension properties during acute lung injury, we performed a randomized study in a rabbit model of acute lung injury. Twenty rabbits were randomized to receive bilirubin or saline intravenously. Acute lung injury was induced by lung lavages with saline. Lung tissue oxidation was evaluated by measuring total hydroperoxide (TH), advanced oxidation protein products (AOPP), and protein carbonyls (PC) in bronchial aspirate (BA) samples. Surface surfactant activity was studied in BA samples using a capillary surfactometer. Bilirubin BA concentration increased in bilirubin-treated rabbits, while it remained undetectable in controls. A similar increase in TH, AOPP, and PC bronchial aspirate concentrations was found in both the study and control groups, while surfactant surface activity was lower in the bilirubin than in the control group. We conclude that during hyperbilirubinemia, bilirubin enters the lung tissue, where it can be detected in BA fluid. Bilirubin is not effective as an antioxidant agent and exerts a detrimental effect on lung surfactant surface tension properties. These findings may have relevance to the management of premature neonates suffering from respiratory distress syndrome and hyperbilirubinemia. Pediatr Pulmonol. © 2004 Wiley-Liss, Inc. [source]


    ChemInform Abstract: An Enantiomerically Pure Bilirubin.

    CHEMINFORM, Issue 17 2002
    Absolute Configuration of (, R)-Dimethylmesobilirubin-XIII
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]


    Prediction of hyperbilirubinaemia in the healthy term newborn

    ACTA PAEDIATRICA, Issue 2 2001
    X Carbonell
    The aim is to establish the correlation between transcutaneous bilirubin (TCB) and serum bilirubin (TSB) and its predictive value for significant hyperbilirubinaemia ,290 mcmol/L (17mg/dL). We studied a total of 2004 healthy full-term newborns, weight 3.230g ± 491g; 90% received breast milk. The study was performed in two phases. In the first phase (610 newborns), the following tests were carried out: hematocrit and bilirubin in umbilical cord blood; TCB at 24 h, 48 h and between 60 h and 96 h at the forehead and over the sternum; TSB was measured along with this last test. In the second phase (1394 newborns), the predictive value of TCB and TSB was validated. The incidence of bilirubin >290 mcmol/L was 2.95% and 3.2%. The correlation between TSB and TCB is high (n= 996; r = 0.92; y = 5.916 + 0.804x; p < 0.000). There was a better correlation between TCB and TSB with sternal compared to forehead determination (< 24 h: 0.81 vs 0.77; 24,48 h: 0.887 vs 0.83; and >48 h: 0.94 vs 0.83). The study showed the scant sensitivity of umbilical cord blood bilirubin and good predictive value at 24 h of TSB > 102 mcmol/L (6mg/dL) and at 48 h of TSB > 154 mcmol/L (9mg/dL) and TCB > 13 (equivalent to 154 mcmol/L). Conclusion: There is a good correlation between TCB and TSB. In infants with TSB 102 mcmol/L at 24 h or TSB > 154 mcmol/L or transcutaneous readings > 13 h at 48 h, a TSB test must be performed after 48 h of life. [source]


    Clinical aspects on neonatal cholestasis based on observations at a Swedish tertiary referral centre

    ACTA PAEDIATRICA, Issue 2 2001
    B Fischler
    The aim of the study was to investigate the clinical aspects of neonatal cholestasis. The medical records of 85 cholestatic infants were retrospectively reviewed. A majority of the patients were referred from other parts of the country. The most common diagnoses were extrahepatic biliary atresia (n= 30 patients), ,1 -antitrypsin deficiency (n=11) and progressive familial intrahepatic cholestasis (n= 11). On presentation, the biliary atresia group had higher mean serum values of bilirubin, G-GT and cholesterol than the patients with intrahepatic cholestasis, with no significant differences noticed for any other biochemical parameter. A lack of excretion on hepatobiliary scintigraphy was noticed in all investigated patients with biliary atresia, but also in 9 of 34 patients with intrahepatic neonatal cholestasis. There was no statistical correlation between the age at portoenterostomy and the outcome in patients with biliary atresia. However, both the detection of a partial flow on perioperative cholangiogram and the establishment of a non-icteric phase within 6 mo after the portoenterostomy correlated to a good outcome. Eight of 11 patients with progressive familial intrahepatic cholestasis were treated with a biliary diversion procedure, five of eight experienced a sustained cholestatic remission. Conclusions: Progressive familial intrahepatic cholestasis may be a more common cause of neonatal cholestasis in Sweden than reported elsewhere and that the experience with biliary diversion is positive. While early referral in patients with extrahepatic biliary atresia remains important, a portoenterostomy should be attempted also in patients referred after 3 mo of age. [source]


    Recurrence of kernicterus in term and near-term infants in Denmark

    ACTA PAEDIATRICA, Issue 10 2000
    F Ebbesen
    Classical acute bilirubin encephalopathy (kernicterus) in term and near-term infants had not been seen in Denmark for at least 20 y until 1994. From 1994 to 1998, however, six cases were diagnosed. Aetiology of the hyperbilirubinaemia was known in two infants; spherocytosis and galactosaemia, most likely known in two infants; possible A-O blood type immunization, and unknown in two infants. However, one of these last-mentioned infants had a gestational age of only 36 wk. The maximum plasma total bilirubin concentrations were 531,745 ,mol/L. The increase in the number of cases of kernicterus was considered to have been caused by: (i) a decreased awareness of the pathological signs, (ii) a change in the assessment of the risk of bilirubin encephalopathy, (iii) early discharge of the infants from the maternity ward, (iv) so-called breastfeeding-associated jaundice, (v) demonstration of bilirubin being an antioxidant, and (vi) difficulty in estimating the degree of jaundice in certain groups of immigrants. Accordingly, for prevention: (a) Attempt to change the healthcare workers' understanding of the risk of bilirubin encephalopathy, (b) give further instructions, both orally and in writing, to mothers before discharge from the maternity ward, (c) be more liberal in giving infant formula supplements, (d) conduct home visits by the community nurse at an earlier stage, (e) follow authorized guidelines for phototherapy and exchange transfusion, (f) lower plasma bilirubin concentration limits as an indication for phototherapy and exchange transfusion, (g) screen all term and near-term infants, and (h) measure the skin's yellow colour with a device that corrects for the skin's melanin content. Conclusions: Audit of the six cases presented indicates that measures are necessary in both the primary and secondary healthcare sectors if the risk of kernicterus is to be avoided. Screening may be considered, but in order to identify the problems it would first be reasonable to perform a larger prospective study in which audit is performed on all newborn infants, born at term and near-term, who develop a plasma bilirubin concentration above the exchange transfusion limit. [source]


    Investigation of prolonged neonatal jaundice

    ACTA PAEDIATRICA, Issue 6 2000
    S Hannam
    Jaundice persisting beyond 14 d of age (prolonged jaundice) can be a sign of serious underlying liver disease. Protocols for investigating prolonged jaundice vary in complexity and the yield from screening has not been assessed. In order to address these issues, we carried out a prospective study of term infants referred to our neonatal unit with prolonged jaundice over an 18 mo period. Infants were examined by a paediatrician and had the following investigations: a total and conjugated serum bilirubin, liver function tests, full blood count, packed cell volume, group and Coombs' test, thyroid function tests, glucose-6-phosphate dehydrogenase levels and urine for culture. One-hundred-and-fifty-four infants were referred with prolonged jaundice out of 7139 live births during the study period. Nine infants were referred to other paediatric specialties. One infant had a conjugated hyperbilirubinaemia, giving an incidence of conjugated hyperbilirubinaemia of 0.14 per 1000 live births. Diagnoses included: giant cell hepatitis (n= 1), hepatoblastoma (n= 1), trisomy 9p (n= 1), urinary tract infections (n= 2), glucose-6-phosphate dehydrogenase deficiency (n= 3) and failure to regain birthweight (n= 1). Conclusions: In conclusion, a large number of infants referred to hospital for prolonged jaundice screening had detectable problems. The number of investigations may safely be reduced to: a total and conjugated bilirubin, packed cell volume, glucose-6-phosphate dehydrogenase level (where appropriate), a urine for culture and inspection of a recent stool sample for bile pigmentation. Clinical examination by a paediatrician has a vital role in the screening process. [source]


    Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis

    DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2009
    Adelaide Fernandes
    Abstract Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source]


    Influence of bacitracin on microbial functions in the gastrointestinal tract of horses

    EQUINE VETERINARY JOURNAL, Issue 4 2000
    E. Collinder
    Summary This study investigated the influence of zinc bacitracin on the intestinal flora of horses. The functionally active intestinal flora was examined in 6 horses during treatment with zinc bacitracin. Utilising gas chromatography, spectrophotometry, gel electrophoresis and paper chromatography, samples were analysed on biochemical markers reflecting the action of parts of the intestinal flora. The following 5 flora-related functions were studied in faecal samples and intestinal samples from different sections of the hindgut: conversion of cholesterol to coprostanol and of bilirubin to urobilinogens, degradation of mucin and of ,-aspartylglycine and inactivation of tryptic activity. Conversion to coprostanol, conversion to urobilinogens and degradation of mucin were affected by treatment of zinc bacitracin and conversion to coprostanol was most sensitive. All functions were normalised in a short time, in contrast to man and rats. Differences in environmental exposures are probably the reason for a more rapid normalisation of the intestinal flora functions in horses. [source]


    New concepts in bilirubin encephalopathy

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003
    J. D. Ostrow
    Abstract Revised concepts of bilirubin encephalopathy have been revealed by studies of bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats. Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated bilirubin (Bf), of which the dominant species at physiological pH is the protonated diacid, which can passively diffuse across cell membranes. As the binding affinity of plasma albumin for bilirubin decreases strikingly as albumin concentration increases, previously reported Bf values were underestimated. Newer diagnostic tests can detect reversible neurotoxicity before permanent damage occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at Bf only modestly above aqueous saturation and affects astrocytes and neurons, causing mitochondrial damage, resulting in impaired energy metabolism and apoptosis, plus cell-membrane perturbation, which causes enzyme leakage and hampers transport of neurotransmitters. The concentrations of unbound bilirubin in the cerebro-spinal fluid and CNS cells are probably limited mainly by active export of bilirubin back into plasma, mediated by ABC transporters present in the brain capillary endothelium and choroid plexus epithelium. Intracellular bilirubin levels may be diminished also by oxidation, conjugation and binding to cytosolic proteins. These new concepts may explain the varied susceptibility of neonates to develop encephalopathy at any given plasma bilirubin level and the selective distribution of CNS lesions in bilirubin encephalopathy. They also can suggest better strategies for predicting, preventing and treating this syndrome. [source]


    Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008
    Omer Dizdar
    Abstract Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV(+) patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels. [source]


    Induction of endogenous pathways by antiepileptics and clinical implications

    FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2005
    M. Strolin Benedetti
    Abstract The aim of this study was to review modifications of the endogenous pathways (e.g. enzyme elevations, normal body constituent depletion or higher formation/excretion of endogenous metabolites) which could be ascribed to enzyme induction by antiepileptic drugs (AEDs). Information on older (e.g. phenobarbital, phenytoin and carbamazepine) and newer drugs (where information is available) is discussed together with clinical implications. The enzymes involved in the endogenous pathways and induced by the AEDs will not be limited to the hepatic microsomal enzymes; extrahepatic enzymes and/or enzymes present in other subcellular fractions will also be discussed, if pertinent. The induction of endogenous pathways by AEDs has been taken into account in the past, but much less emphasis has been given compared with the extensive literature on induction by AEDs of the metabolism of concomitantly administered drugs, either of the same or of different classes. Not all of the endogenous pathways examined and induced by AEDs appear to result in serious clinical consequences (e.g. induction of hepatic ALP, increased excretion of d -glucaric acid or of 6, -hydroxycortisol). In some cases, induction of some pathways (e.g. increase of high-density lipoprotein cholesterol or of conjugated bilirubin) might even be a beneficial side-effect, however enzyme induction is considered rather a detrimental aspect for an AED, as induction is generally a broad and a non-specific phenomenon. The new AEDs have generally less induction potential than the older agents. Yet some (felbamate, topiramate, oxcarbazepine and lamotrigine) have the potential for inducing enzymes, whereas others (levetiracetam, gabapentin and vigabatrin) appear to be completely devoid of enzyme inducing characteristics, at least as far as the enzymes investigated are concerned. [source]


    Hereditary spherocytosis in an elderly woman with periodic attacks of jaundice

    GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2005
    Hiroyuki Fukuhara
    Hereditary spherocytosis is a disease with chronic hemolytic anemia found mostly in childhood. We encountered a rare case of sporadic hereditary spherocytosis in a 68-year-old woman who developed periodic jaundice caused by hemolytic crises. Since the hemolytic crises were caused by cholelithiasis-related biliary inflammation, administration of ursodeoxycholic acid was useful for the prevention of the hemolytic crises. In the differential diagnosis of periodic increases in indirect bilirubin, the possibility of hemolytic diseases, including hereditary ones, should be considered, even if the patients are elderly. [source]


    Biliary physiology and disease: Reflections of a physician-scientist,

    HEPATOLOGY, Issue 4 2010
    Gustav Paumgartner
    A review is presented of Gustav Paumgartner's five decades of research and practice in hepatology focusing on biliary physiology and disease. It begins with studies of the excretory function of the liver including hepatic uptake of indocyanine green, bilirubin, and bile acids. The implications of these studies for diagnosis and understanding of liver diseases are pointed out. From there, the path of scientific research leads to investigations of hepatobiliary bile acid transport and the major mechanisms of bile formation. The therapeutic effects of the hydrophilic bile acid, ursodeoxycholic acid, have greatly stimulated these studies. Although ursodeoxycholic acid therapy for dissolution of cholesterol gallstones and some other nonsurgical treatments of gallstones were largely superseded by surgical techniques, ursodeoxycholic acid is currently considered the mainstay of therapy of some chronic cholestatic liver diseases, such as primary biliary cirrhosis. The major mechanisms of action of ursodeoxycholic acid therapy in cholestatic liver diseases are discussed. An attempt is made to illustrate how scientific research can lead to advances in medical practice that help patients. (HEPATOLOGY 2010:51:1095,1106.) [source]


    Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis,

    HEPATOLOGY, Issue 1 2010
    Sanjay Y. Bangarulingam
    Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51%) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH polysomy were 46% and 88%, and for trisomy/tetrasomy they were 25% and 67%, respectively. Survival analysis showed that patients with FISH polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures. Conclusion: In PSC patients, the presence of a dominant stricture plus FISH polysomy has a specificity of 88% for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). (HEPATOLOGY 2009.) [source]


    Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome,

    HEPATOLOGY, Issue 1 2010
    André Nazar
    Terlipressin plus albumin is an effective treatment for type 1 hepatorenal syndrome (HRS), but approximately only half of the patients respond to this therapy. The aim of this study was to assess predictive factors of response to treatment with terlipressin and albumin in patients with type 1 HRS. Thirty-nine patients with cirrhosis and type 1 HRS were treated prospectively with terlipressin and albumin. Demographic, clinical, and laboratory variables obtained before the initiation of treatment as well as changes in arterial pressure during treatment were analyzed for their predictive value. Response to therapy (reduction in serum creatinine <1.5 mg/dL at the end of treatment) was observed in 18 patients (46%) and was associated with an improvement in circulatory function. Independent predictive factors of response to therapy were baseline serum bilirubin and an increase in mean arterial pressure of ,5 mm Hg at day 3 of treatment. The cutoff level of serum bilirubin that best predicted response to treatment was 10 mg/dL (area under the receiver operating characteristic curve, 0.77; P < 0.0001; sensitivity, 89%; specificity, 61%). Response rates in patients with serum bilirubin <10 mg/dL or ,10 mg/dL were 67% and 13%, respectively (P = 0.001). Corresponding values in patients with an increase in mean arterial pressure ,5 mm Hg or <5 mm Hg at day 3 were 73% and 36%, respectively (P = 0.037). Conclusion: Serum bilirubin and an early increase in arterial pressure predict response to treatment with terlipressin and albumin in type 1 HRS. Alternative treatment strategies to terlipressin and albumin should be investigated for patients with type 1 HRS and low likelihood of response to vasoconstrictor therapy. (HEPATOLOGY 2009.) [source]


    Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease,,

    HEPATOLOGY, Issue 4 2007
    Aldo J. Montano-Loza
    Autoimmune hepatitis may fail to respond to corticosteroid therapy, but the frequency and bases for this outcome are uncertain. We aimed to determine the frequency and nature of treatment failure in patients with type 1 autoimmune hepatitis, define features associated with its occurrence, and assess if the model for end-stage liver disease can predict this outcome. Patients failing conventional corticosteroid regimens were compared to patients who responded to similar regimens. Fourteen of 214 patients (7%) failed corticosteroid treatment. Patients who failed therapy were younger (33 ± 3 years versus 48 ± 1 years, P = 0.0008), had higher serum levels of bilirubin at accession (4.1 ± 0.9 mg/dL versus 2.3 ± 0.2 mg/dL, P = 0.02), presented acutely more frequently (43% versus 14%, P = 0.01), and had a higher frequency of HLA (human leukocyte antigen) DRB1*03 (93% versus 53%, P = 0.004) than did patients who achieved remission. An alternative disease (fatty liver disease) emerged in only 1 patient who failed therapy (7%). Scores determined by the model of end-stage liver disease at presentation of patients who failed treatment were higher than those of who achieved remission (16 ± 1 versus 10 ± 0.3 points, P < 0.0001), and score greater than 12 points had greater sensitivity (97%) and specificity (68%) for treatment failure than did HLA DRB1*03 or other features. Conclusion: Onset at an early age, acute presentation, hyperbilirubinemia, and presence of HLA DRB1*03 characterize patients who fail corticosteroid treatment. The model for end-stage liver disease may be a useful instrument for identifying patients prone to this outcome. (HEPATOLOGY 2007.) [source]


    Screening and outcomes in biliary atresia: Summary of a National Institutes of Health workshop,,

    HEPATOLOGY, Issue 2 2007
    Ronald J. Sokol
    Biliary atresia is the most common cause of end-stage liver disease in the infant and is the leading pediatric indication for liver transplantation in the United States. Earlier diagnosis (<30-45 days of life) is associated with improved outcomes following the Kasai portoenterostomy and longer survival with the native liver. However, establishing this diagnosis is problematic because of its rarity, the much more common indirect hyperbilirubinemia that occurs in the newborn period, and the schedule for routine infant health care visits in the United States. The pathogenesis of biliary atresia appears to involve immune-mediated fibro-obliteration of the extrahepatic and intrahepatic biliary tree in most patients and defective morphogenesis of the biliary system in the remainder. The determinants of the outcome of portoenterostomy include the age at surgery, the center's experience, the presence of associated congenital anomalies, and the postoperative occurrence of cholangitis. A number of screening strategies in infants have been studied. The most promising are early measurements of serum conjugated bilirubin and a stool color card given to new parents that alerts them and their primary care provider to acholic stools. This report summarizes a National Institutes of Health workshop held on September 12 and 13, 2006, in Bethesda, MD, that addressed the issues of outcomes, screening, and pathogenesis of biliary atresia. (HEPATOLOGY 2007;46:566,581.) [source]


    Hepatitis B viral load predicts survival of HCC patients undergoing systemic chemotherapy,

    HEPATOLOGY, Issue 6 2007
    Winnie Yeo
    HCC is a common cause of morbidity and mortality. For patients who are not candidates for curative surgery, systemic chemotherapy is one of the standard treatments. In parts of China and the Far East, over 80% of HCC patients have chronic HBV infection. In this study, we aimed to assess the relationship between pre-chemotherapy HBV viral load and the survival of HCC patients. HBV infection status was determined prior to chemotherapy in 188 patients, 170 of whom had evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen [HBsAg]-positive, 10 HBsAg-negative/hepatitis B core antibody,positive). Of these, 125 had pretreatment HBV DNA levels determined via real-time PCR. Virological data were analyzed using conventional clinical variables to identify factors that influenced survival. Multivariate analysis revealed that high total bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 ,M increase; 95% CI 1.015,1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606,30.129), and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076,2.531) affected survival significantly. Exploratory analysis revealed that high levels of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis during chemotherapy. Conclusion: For HCC patients with HBV chronic infection/exposure, a high viral load prior to treatment is an adverse factor for survival and may be associated with a higher incidence of severe hepatitis during chemotherapy. Future strategies to improve the prognosis of HCC patients undergoing chemotherapy should consider supportive therapy that incorporates antiviral therapies to reduce HBV viral load. (HEPATOLOGY 2007;45:1382,1389.) [source]


    Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection,,

    HEPATOLOGY, Issue 2 2006
    Atsushi Ozasa
    The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 ± 16.3 vs. 36.0 ± 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection. (HEPATOLOGY 2006;44:326,334.) [source]


    Serum bilirubin levels and mortality after myeloablative allogeneic hematopoietic cell transplantation,

    HEPATOLOGY, Issue 2 2005
    Ted A. Gooley
    Many patients who undergo hematopoietic cell transplantation experience liver injury. We examined the association of serum bilirubin levels with nonrelapse mortality by day +200, testing the hypothesis that the duration of jaundice up to a given point in time provides more prognostic information than either the maximum bilirubin value or the value at that point in time. We studied 1,419 consecutive patients transplanted from allogeneic donors. Total serum bilirubin values up to day +100, death, or relapse were retrieved,along with nonrelapse mortality by day +200 as an outcome measure,using Cox regression models with each bilirubin measure modeled as a time-dependent covariate. The bilirubin value at a particular point in time provided the best fit to the model for mortality. With bilirubin at a point in time modeled as an 8th-degree polynomial, an increase in bilirubin from 1 to 3 mg/dL is associated with a mortality hazard ratio of 6.42. An increase from 4 to 6 mg/dL yields a hazard ratio of 2.05, and an increase from 10 to 12 mg/dL yields a hazard ratio of 1.17. Among patients who were deeply jaundiced, survival was related to the absence of multiorgan failure and to higher platelet counts. In conclusion, the value of total serum bilirubin at a particular point in time after transplant carries more informative prognostic information than does the maximum or average value up to that point in time. The increase in mortality for a given increase in bilirubin value is larger when the starting value is lower. (HEPATOLOGY 2005,41:345,352.) [source]


    Upper digestive bleeding in cirrhosis.

    HEPATOLOGY, Issue 3 2003
    Post-therapeutic outcome, prognostic indicators
    Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis. The aim of this multicenter, prospective, cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis. A training set of 291 and a test set of 174 bleeding cirrhotic patients were included. Treatment was according to the preferences of each center and the follow-up period was 6 weeks. Predictive rules for 5-day failure (uncontrolled bleeding, rebleeding, or death) and 6-week mortality were developed by the logistic model in the training set and validated in the test set. Initial treatment controlled bleeding in 90% of patients, including vasoactive drugs in 27%, endoscopic therapy in 10%, combined (endoscopic and vasoactive) in 45%, balloon tamponade alone in 1%, and none in 17%. The 5-day failure rate was 13%, 6-week rebleeding was 17%, and mortality was 20%. Corresponding findings for variceal versus nonvariceal bleeding were 15% versus 7% (P = .034), 19% versus 10% (P = .019), and 20% versus 15% (P = .22). Active bleeding on endoscopy, hematocrit levels, aminotransferase levels, Child-Pugh class, and portal vein thrombosis were significant predictors of 5-day failure; alcohol-induced etiology, bilirubin, albumin, encephalopathy, and hepatocarcinoma were predictors of 6-week mortality. Prognostic reassessment including blood transfusions improved the predictive accuracy. All the developed prognostic models were superior to the Child-Pugh score. In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades. Initial treatment stops bleeding in 90% of patients. Accurate predictive rules are provided for early recognition of high-risk patients. [source]


    Histologic and biochemical changes during the evolution of chronic rejection of liver allografts

    HEPATOLOGY, Issue 3 2002
    Desley A. H. Neil
    Criteria for histologic diagnosis of chronic rejection (CR) are based on changes seen late in the disease process that are likely to be irreversible and unresponsive to treatment. Changes occurring during the evolution of CR are less clearly defined. The serial biopsy specimens, failed allografts, and biochemical profiles of 28 patients who underwent retransplantation for CR were examined with the aim of identifying histologic and biochemical features that were present during the early stages of CR. For each case, a point of acute deterioration in liver function tests (LFTs) was identified ("start time" [ST]) that subsequently progressed to graft failure. Biopsy specimens before, at the time of ("start biopsy" [SB]), and after the ST were assessed histologically, and findings were correlated with the biochemical changes. CR resulted from acute rejection (AR) that did not resolve. Centrilobular necroinflammation (CLNI) associated with an elevated aspartate transaminase (AST) level and portal tract features of AR were present at the start. Portal AR features resolved, CLNI persisted, AST level remained elevated, and bilirubin and alkaline phosphatase levels progressively increased throughout the evolution of CR. Portal tracts also showed a loss of small arterial and bile duct branches, with arterial loss occurring early and bile duct loss as a later progressive lesion. Foam cell arteriopathy was rarely seen in needle biopsy specimens. In conclusion, findings from this study may help identify patients at risk of progressing to graft loss from CR at a stage when the disease process is potentially reversible and amenable to treatment. [source]


    Phase I/II study of a fine-powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma

    HEPATOLOGY RESEARCH, Issue 4 2010
    Masamichi Moriguchi
    Aim:, The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine-powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine-powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. Methods:, Fine-powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m2 (level 1) and increased to 65 mg/m2 in 10 mg/m2 increments. Results:, Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m2), the recommended dose was 65 mg/m2. The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. Conclusions:, TACE with a fine-powder formulation of CDDP at a dose of 65 mg/m2 is well tolerated in patients with unresectable HCC. [source]


    The effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 in hepatic fibrosis in bile duct ligated rats

    HEPATOLOGY RESEARCH, Issue 12 2008
    Arezou Rezaei
    Aim:, N-acetylcysteine can inhibit the formation of intracellular reactive oxygen intermediates. Cellular redox state plays a role in regulating the secretion of matrix metalloproteinase-2. We investigated the effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2. Methods:, Bile duct ligated rats were used as a model of hepatic fibrosis. We compared the level of gene expression (using real-time reverse transcription polymerase chain reaction [RT,PCR]), liver function parameters, hepatic reactive oxygen production, lipid peroxidation and glutathione state in experimental groups. Results:, N-acetylcysteine treatment significantly improved liver function parameters including the plasma levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and bilirubin. In addition, significant improvement of glutathione state and reactive oxygen production were observed. Hepatic lipid peroxidation was reversed by N-acetylcysteine treatment. Although N-acetylcysteine treatment did not completely normalize the increased matrix metalloproteinase-2 expression, it significantly decreased its level by 65%. N-acetylcysteine treatment also significantly decreased matrix metalloproteinase-2 activity and normalized tissue inhibitor of matrix metalloproteinase-2 expression. Conclusion:, Collectively, N-acetylcysteine showed inhibition of matrix metalloproteinase-2 expression and activity. In addition, administration of N-acetylcysteine was associated with downregulation of the expression of tissue inhibitor of matrix metalloproteinase-2 and amelioration of oxidative stress in the liver of bile duct ligated rats. [source]


    Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile study

    HEPATOLOGY RESEARCH, Issue 10 2007
    Sheikh Abdullah Tasduq
    Aim:, Biochemical characterization of long-term toxic manifestations of anti-tubercular (anti-TB) drugs , rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) , individually and in two combinations: (i) RIF + INH, and (ii) RIF + INH + PZA in Wistar rats. Methods:, Animals received anti-TB drugs , alone or in combination , once daily p.o. for up to 90 days (doses, in mg/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+-ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule. Results:, Anti-TB drugs-treated animals showed abnormal rises or falls (>1.5,2 fold) in the serum/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15,90 days. The in vivo results were further supported by in vitro results (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. Results indicated that anti-TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant,antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1-mediated bioactivation mechanism. Conclusion:, Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis. [source]