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Jaundice
Kinds of Jaundice Selected AbstractsReview of positive direct antiglobulin tests found on cord blood samplingJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 9-10 2005Dorothy Dinesh Until recently, all babies born in Wellington had umbilical cord blood sampling for direct antiglobulin test (DAT). It is considered to be an important test in identifying babies who are at risk of haemolytic disease of the newborn (HDN). Objective: The aim of this review was to examine the utility of positive DAT results and ascertain: , How many cases required phototherapy? , Were any babies readmitted for phototherapy? , Did the positive DAT influence the detection and treatment of HDN? Methods: The clinical records of all newborn babies found to have positive DATs by Wellington Hospital Blood Bank, over a 6-month period (January 2001,June 2001) were reviewed. Blood group serological results of all babies that received phototherapy during this period were also reviewed. Results: Ninety-four babies had a positive DAT, of which 22 (23%) received phototherapy. The incidence of a positive cord blood DAT was found to be 5.5%. In total, 1724 cord blood samples were analysed by Blood Bank over the first 6 months in 2001. Overall 145 babies received phototherapy, 117 were DAT-negative and six were not tested. Six of the 22 (27%) DAT-positive babies that received phototherapy were alerted by a positive DAT, leading to measurement of serum bilirubin (SBR). Twelve of the 22 (55%) were initially alerted by clinical jaundice, leading to measurement of SBR. Two DAT-positive cases were diagnosed antenatally, both were due to anti-D. Overall 10 babies were readmitted for phototherapy, two had a positive DAT. One baby received an exchange transfusion in addition to phototherapy. Two babies that received phototherapy had SBRs in the exchange transfusion range. Eighty-six per cent of the DAT-positive cases treated with phototherapy were due to anti-A. There were four cases of DAT-negative ABO HDN. Conclusions: The positive predictive value of a positive DAT for HDN is 23%. The sensitivity was estimated to be 86%. Ten babies required readmission for phototherapy, two of these were DAT-positive. Jaundice, rather than the positive DAT, was the first alert in the majority of cases of HDN requiring phototherapy. Recommendations for testing are discussed but remain controversial in practice. Assessment for hyperbilirubinaemia in all infants early in life is fundamental. [source] Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort studyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2008S Maschi Objective, To determine the incidence of early adverse effects associated with antidepressant drug use during pregnancy. Design, Prospective, controlled cohort study. Setting, A Drug and Health Information Centre in Milan, Italy. Population, A total of 200 neonates exposed to antidepressants in utero and 1200 controls. Methods, Women who took antidepressants during pregnancy and delivered liveborn children between 1995 and 2003 were selected. Each case was matched for maternal age and gravidity to six randomly selected controls (not exposed to teratogenic drugs or drugs known to cause neonatal side effects). Odds ratio was estimated for attributable risks. Main outcome measures, Neonatal adverse events and Special Care Unit admission rate, assessed through an interview with the mothers. Results, Of the 200 neonates exposed to antidepressants in utero, 14 had adverse events and 3 required Special Care Unit admission. Jaundice (n = 5), agitation (n = 3) and respiratory distress (n = 2) were the most common symptoms. In the control group, 50 newboms had side effects and no statistically significant differences in the prevalence rate compared to the exposed group were found, even after stratification for drugs and pregnancy period of exposure. Only the prematurity rate was significantly higher in exposed compared to non-exposed newborns (OR = 2.31; 95% CI 1.14,4.63). Conclusions, These results do not support an association between antidepressant exposure and unsafe fetal and neonatal outcomes in newborns. However, a collaborative international multicentre epidemiological monitoring of the use of psychotropic drugs during pregnancy is needed in order to guarantee pregnant women and their children safe and effective treatments, both at brief and long time from exposure. [source] Guidelines for treatment of neonatal jaundice.ACTA PAEDIATRICA, Issue 3 2001Is there a place for evidence-based medicine? Treatment of neonatal jaundice continues to be a controversial issue. Arguments that traditional practice results in over-treatment have led to the adoption of more liberal guidelines in some countries. The importation of liberal guidelines from one country to the next, however, is fraught with danger, because differences in epidemiology, sociology and healthcare delivery systems between countries may not be adequately reflected. The unreflected extension of liberalization to non-target groups of patients can expose the latter to significant risk. It is not clear that the evidence on which guidelines for treatment of neonatal jaundice are based satisfy the requirements for evidence-based medicine. Evidence of adequate quality may be hard to obtain. Conclusions: Introduction of more liberal guidelines for the treatment of neonatal jaundice, if at all contemplated, must be adapted to local circumstances, and any available evidence pertaining to local epidemiology, sociology and healthcare organization has to be carefully weighed and incorporated. The time is ripe for a joint international effort to secure adequate funding for basic and applied research within the mechanisms of bilirubin encephalopathy in the newborn. [source] Recurrence of kernicterus in term and near-term infants in DenmarkACTA PAEDIATRICA, Issue 10 2000F 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] Phototherapy for neonatal jaundice,still in need of fine tuningACTA PAEDIATRICA, Issue 7 2000TWR Hansen No abstract is available for this article. [source] Investigation of prolonged neonatal jaundiceACTA PAEDIATRICA, Issue 6 2000S 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 synaptogenesisDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2009Adelaide 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] Use of a balloon-expandable vascular metal stent for palliation of obstructive jaundice in a post-surgical pediatric patientDIGESTIVE ENDOSCOPY, Issue 3 2010Gabriele Curcio No abstract is available for this article. [source] ENDOSONOGRAPHY-GUIDED GALLBLADDER DRAINAGE FOR ACUTE CHOLECYSTITIS FOLLOWING COVERED METAL STENT DEPLOYMENTDIGESTIVE ENDOSCOPY, Issue 1 2009Osamu Takasawa Endosonography-guided biliary drainage (ESBD) is gaining acceptance as an effective treatment for obstructive jaundice. Only a few reports on the application of this technique to the gallbladder (endosonography-guided gallbladder drainage [ESGBD]) have been published in the literature. In order to relieve acute cholecystitis which developed in a patient with unresectable malignant biliary obstruction after deployment of a covered metal stent (CMS), we applied this technique. ESGBD was carried out by using an electronic curved linear array echoendoscope. After visualization of the gallbladder and determination of the puncture route, a needle knife papillotome was advanced with electrocautery to pierce the gastric and gallbladder walls. Under the guidance of a guidewire inserted through the needle sheath into the gallbladder, a 7.2 Fr, 30 cm-long, single pigtail plastic tube was placed to bridge the gallbladder and the stomach. No complications relevant to the procedure were encountered. ESGBD was quite effective in ameliorating the patient's acute cholecystitis and the drainage tube was removed after 10 days without sequelae. Acute cholecystitis following CMS deployment is considered to be a good indication for ESGBD. [source] INTRADUCTAL ULTRASONOGRAPHY OF THE GALLBLADDER IN APPLICATION OF THE ENDOSCOPIC NASO-GALLBLADDER DRAINAGEDIGESTIVE ENDOSCOPY, Issue 1 2007Daisuke Masuda Background:, Although endoscopic naso-gallbladder drainage (ENGBD) for gallbladder disease is useful, the procedure is difficult and investigations involving many cases are lacking. Furthermore, reports on transpapillary intraductal ultrasonography (IDUS) of the gallbladder using a miniature probe are rare. Methods:, A total of 150 patients (119 suspected of having gallbladder carcinoma, 24 with acute cholecystitis (AC), and seven with Mirizzi's syndrome (MS)) were the subject. (i) ENGBD: We attempted to put ENGBD tube into the GB. (ii) IDUS of the gallbladder: Using the previous ENGBD tube, we attempted to insert the miniature probe into the gallbladder and perform transpapillary IDUS of the gallbladder. In five patients, we attempted three-dimensional intraductal ultrasonography (3D-IDUS). Results:, (i) ENGBD: Overall success rate was 74.7% (112/150); the rate for the patients suspected of having gallbladder carcinoma was 75.6% (90/119), and was 71.0% (22/31) for the AC and MS patients. Inflammation and jaundice improved in 20/22 successful patients with AC and MS. Success rate was higher when cystic duct branching was from the lower and middle parts of the common bile duct than from the upper part, and was higher when branching was upwards than downwards. (ii) IDUS of the gallbladder: Success rate for miniature probe insertion into the gallbladder was 96.4% (54/56). Lesions could be visualized in 50/54 patients (92.6%). Of these, detailed evaluation of the locus could be performed in 41. In five patients attempted 3D-IDUS, the relationship between the lesion and its location was readily grasped. Conclusion:, IDUS of the gallbladder is superior for diagnosing minute images. Improvement on the device will further increase its usefulness. [source] Mirizzi syndrome Type IV: A rare entityDIGESTIVE ENDOSCOPY, Issue 4 2003Everson Luiz De Almeida Artifon Mirizzi's syndrome, characterized by obstructive jaundice due to an extrinsic compression of common hepatic duct by an impacted gallstone in the cystic duct or the neck of the gallbladder, is a rare complication of gallstone disease. The present case describes Mirizzi's syndrome classified as Type IV in a 50-year-old man with obstructive jaundice. Abdominal computed tomography scan demonstrated a dilated intrahepatic biliary tree and a tumoral mass at the porta hepatis, suggesting cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography also suggested cholangiocarcinoma involving the entire circumference of the common hepatic duct in porta hepatis. The diagnosis of Mirizzi's syndrome Type IV was confirmed during cholecystectomy, withdrawal of gallstone and Roux-en-Y hepaticojejunostomy. [source] Lung cancer with metastases to the stomach and duodenum. report of three casesDIGESTIVE ENDOSCOPY, Issue 3 2003Hiroshi Nakamura Over a period of about 1.5 years between September 1999 and April 2000, three cases of lung cancer that metastasized to the stomach and duodenum were encountered. Case 1 was a 74-year-old man with lung cancer at stage IV. During chemotherapy, he passed tarry feces, which led to an endoscopic examination. Subsequently, submucosal tumorous nodules were recognized in the stomach and descending portion of the duodenum, which were diagnosed as metastases. Case 2, a 59-year-old man, underwent radiotherapy for treatment of lung cancer at stage IV. He developed obstructive jaundice 15 months later and, following percutaneous drainage to correct the icteric condition, endoscopic examination was conducted. A 5-cm submucosal tumor was found at the descending portion of the duodenum and a diagnosis of obstructive jaundice caused by a duodenal metastasis was given. Case 3, an 81-year-old male with stage IIIb lung cancer had been receiving oral Tegafur uracil. Because of hypochondriac pain that had lasted for 2 weeks, an endoscopic examination was conducted. A tumorous lesion was discovered in the horizontal part of the duodenum, which proved to be a metastasis. Metastasis of a lung cancer to the digestive system is rare: gastric metastasis is only 4.5% and metastasis to the small intestine, 5.8%. However, our experience suggests that metastases to the digestive system occur more frequently than reports would indicate. Endoscopic screening should be aggressively used, not only for those cases that develop subjective symptoms, but also for the asymptomatic cases to assess accuracy in staging, which may contribute to choosing the most appropriate therapeutic plan. [source] Combined Use of Uncovered Duodenal and Covered Biliary Metallic Stent for Carcinoma of the Papilla of VaterDIGESTIVE ENDOSCOPY, Issue 4 2000Hitoshi Sano We have reported successful implantation of self-expandable metallic stents for palliative treatment in a case of an 87-year-old female patient with carcinoma of the papilla of Vater. She suffered from both duodenal and biliary stenoses, but refused surgical treatment. For the duodenal stenting, a self-expandable knitted nitinol metallic stent, for esophageal use, was inserted endoscopically. For the biliary stenting, a self-expandable metallic stent, partially polyurethane-covered on the proximal part to prevent tumor ingrowth and overgrowth, was inserted via the percutaneous transhepatic biliary drainage route. No major complications occured during these procedures. After the two stents were inserted in an end-to-side fashion, she was able to eat a normal diet adequately and suffered from no abdominal symptoms and jaundice during the follow-up period of 13 months. These stenting procedures might be less invasive and more useful than surgical treatment and provide long patency of biliary stenting and a good quality of life. [source] Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor regionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2006Kiyoshi Kitano Abstract:, Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis. [source] Association of non-alcoholic steatohepatitis (NASH) with chronic neutrophilic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004Chikashi Yoshida Abstract: A 54-yr-old female having chronic neutrophilic leukemia (CNL) associated with severe liver injury is presented. Physical examination on admission showed severe jaundice, hepatosplenomegaly, massive ascites, and pretibial edema. Complete blood count showed a hemoglobin level of 9.1 g/dL, platelet count of 25.8 × 104/,L, and white blood cell count of 36.6 × 103/,L with 89.7% neutrophils. Blood chemistry showed hyperbilirubinemia (21.9 mg/dL) with normal transaminase levels. There was no abnormality in serum cholesterol, triglyceride, or glucose levels. Neutrophil alkaline phosphatase activity was significantly elevated. Bone marrow aspiration showed myeloid hyperplasia with normal karyotype. Rearrangement of the bcr/abl was not detected by either polymerase chain reaction or fluorescence in situ hybridization. Human androgen receptor gene assay (HUMARA) of the bone marrow cells showed clonal proliferation of neutrophils. The patient was diagnosed as having CNL. To evaluate the pathogenesis of the liver injury, a needle biopsy was performed, which showed steatohepatitis with infiltration of neutrophils. As the patient had no history of alcohol abuse, a diagnosis of non-alcoholic steatohepatitis (NASH) was made. Assuming that the infiltration of abnormal neutrophils into the liver contributed to the development of NASH, she was treated with cytoreductive chemotherapy (cytosine arabinoside: 100 mg/d, 1,3 doses/wk). With decreases in white blood cell counts, serum bilirubin levels decreased gradually to 1.5 mg/mL. A postchemotherapy liver biopsy specimen showed marked improvement of the fatty degenerative change. To our knowledge, this is the first report describing the development of NASH in a myeloproliferative disorder. We believe that the infiltration of leukemic cells contributed to the development of NASH in this patient. [source] Naltrexone: report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literatureADDICTION BIOLOGY, Issue 1 2004Colin Brewer Many clinicians appear to be concerned about the potential hepatotoxicity of the opiate antagonist naltrexone (NTX) and this may be one reason why it is not used more widely in treating both heroin and alcohol abusers. Some much-quoted early studies noted abnormalities in liver function tests (LFTs) in very obese patients taking high doses, although there was no evidence of clinically significant liver dysfunction. These concerns may be reinforced by advice in the UK product information sheet to perform LFTs before and during treatment, by high infection rates with hepatitis C virus (HCV) among injecting heroin addicts and by the frequency of abnormal LFTs in alcohol abusers. We describe a heroin abuser in whom clinical and laboratory manifestations of acute hepatitis B and C appeared a few days after the insertion of a subcutaneous naltrexone implant. A decision was made not to remove the implant but the hepatitis resolved completely and uneventfully well within the normal time-scale. A review of the literature indicates that even when given at much higher doses than are needed for treating heroin or alcohol abusers, there is no evidence that NTX causes clinically significant liver disease or exacerbates, even at high doses, serious pre-existing liver disease. During the past decade, NTX has been shown to be safe and effective in the treatment of pruritus associated with severe jaundice caused by severe and sometimes life-threatening cirrhosis and other liver diseases. Its safety, even in these extreme conditions, is particularly reassuring. We suggest that it may be more appropriate and economical to advise patients to report promptly any suspected side effects than to perform regular LFTs, which may be misleading. [source] Study of in vitro glucuronidation of hydroxyquinolines with bovine liver microsomesFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2002Masanobu Kanou Abstract Glucuronidation of drugs by UDP-glucuronosyltransferase (UGT) is a major phase II conjugation reaction. Defects in UGT are associated with Crigler,Najjar syndrome and Gilbert's syndrome with severe hyperbilirubinaemias and jaundice. We analysed the reactivities of some hydroxyquinoline derivatives, which are naturally produced from quinoline by cytochrome P450. The analyses were carried out using a microassay system for UGT activity in bovine liver microsomes in the range 0.5,100 pmol/assay with the highly sensitive radio-image analyser Fuji BAS2500 (Fujifilm, Tokyo, Japan). 3-Hydroxylquinoline is a good substrate for glucuronidation, and the relative Kcat values were 3.1-fold higher than the values for p-nitrophenol. 5,6-Dihydroquinoline-5,6- trans -diol gave a similar Km value to that of 3-hydroxyquinoline, but the Vmax value was approximately 1/15 of that of p-nitrophenol and showed weak reactivity. Quinoline N-oxide gave a low Vmax value and showed marginal activity. The Kcat values of 6-hydroxyquinoline and 5-hydroxyquinoline were 2.1- and 1.2-fold higher than that of p-nitrophenol, respectively. Fluoroquinoline (FQ) derivatives, such as 3FQ, 7,8diFQ and 6,7,8triFQ, did not show any substrate activities. These results suggest that there are therapeutic problems in administration of some quinoline drugs to patients with jaundice. [source] Hereditary spherocytosis in an elderly woman with periodic attacks of jaundiceGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2005Hiroyuki 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] Potential role for Interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection,HEPATOLOGY, Issue 4 2010Jason Grebely Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ,26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). Conclusion: During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (HEPATOLOGY 2010;) [source] Telithromycin-associated hepatotoxicity: Clinical spectrum and causality assessment of 42 cases,HEPATOLOGY, Issue 1 2009Allen D. Brinker Telithromycin is the first of a new class of ketolide antibiotics with increased activity against penicillin-resistant and erythromycin-resistant pneumococci. This agent received approval by the United States Food and Drug Administration (FDA) in 2004 for treatment of upper and lower respiratory infections. Following market introduction, spontaneous reports of telithromycin-associated hepatotoxicity, including frank liver failure, were received. To address these reports, an ad hoc group with expertise in spontaneous adverse events reporting and experience in evaluating drug-induced liver injury was formed, including members of the FDA, other federal agencies, and academia. The primary objective of this group was to adjudicate case reports of hepatic toxicity for causal attribution to telithromycin. After an initial screening of all cases of liver injury associated with telithromycin reported to FDA as of April 2006 by one of the authors, 42 cases were comprehensively reviewed and adjudicated. Five cases included a severe outcome of either death (n = 4) or liver transplantation (n = 1); more than half were considered highly likely or probable in their causal association with telithromycin. Typical clinical features were: short latency (median, 10 days) and abrupt onset of fever, abdominal pain, and jaundice, sometimes with the presence of ascites even in cases that resolved. Concurrence in assignment of causality increased after agreement on definitions of categories and interactive discussions. Conclusion: Telithromycin is a rare cause of drug-induced liver injury that may have a distinctive clinical signature and associated high mortality rate. Consensus for attribution of liver injury to a selected drug exposure by individual experts can be aided by careful definition of terminology and discussion. (HEPATOLOGY 2009;49:250-257.) [source] Serum bilirubin levels and mortality after myeloablative allogeneic hematopoietic cell transplantation,HEPATOLOGY, Issue 2 2005Ted 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] Course and outcome of hepatitis CHEPATOLOGY, Issue 5B 200231 Center Dr., Jay H. Hoofnagle Bldg. 3, Room 9A2 The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy. [source] A missense mutation in FIC1 is associated with greenland familial cholestasisHEPATOLOGY, Issue 6 2000Leo W. J. Klomp Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland. Patients present with jaundice, pruritus, bleeding episodes, and steatorrhea, and die in childhood due to end-stage liver disease. We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC1, the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis. Using single-strand conformation polymorphism analysis and sequencing of the FIC1 exons, a missense mutation, 1660 G,A (D554N), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada. Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and, on transmission electron microscopy, coarsely granular Byler bile, as previously described in patients with progressive familial intrahepatic cholestasis type 1. These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC1 activity for normal bile formation. [source] Refining indications for contemporary surgical treatment of renal cell carcinoma metastatic to the pancreasHPB, Issue 2 2009Aram N. Demirjian Abstract Background:, The pancreas is a rare location for metastatic disease, with only 2,11% of all pancreatic tumours being of non-primary origin. It is also uncommon for renal cell carcinoma (RCC) to metastasize to the pancreas (1,3% of cases) and, when it does, it typically occurs substantially after index nephrectomy. It is not known whether all pancreatic metastases need be resected because today's chemo- and biological therapies are increasingly effective in controlling advanced disease. Methods:, Six patients with a variety of symptoms are discussed. Four patients presented with recurrent gastrointestinal bleeding, ranging from occult to life-threatening in severity. Results:, The four patients with gastrointestinal bleeding had RCC metastases that had eroded into the duodenum and were successfully controlled by palliative pancreaticoduodenectomy or completion pancreatectomy. The other two patients were treated using different chemotherapeutic or biological agents. Conclusions:, Renal cell carcinoma metastases to the pancreas typically occur long after index nephrectomy. Although clinical presentation is variable, palliative resection should be reserved for those who develop complications, such as upper gastrointestinal bleeding, and, in other series, obstructive jaundice. Routine debulking resections do not appear to be indicated because current biological therapies effectively and reliably control disease over long periods. [source] Striving for a better operative outcome: 101 PancreaticoduodenectomiesHPB, Issue 6 2008A.W.C. Kow Abstract Pancreaticoduodenectomy (PD), once carried high morbidity and mortality, is now a routine operation performed for lesions arising from the pancreatico-duodenal complex. This study reviews the outcome of 101 pancreaticoduodenectomies performed after formalization of HepatoPancreatoBiliary (HPB) unit in the Department of Surgery. A prospective database comprising of patients who underwent PD was set up in 1999. Retrospective data for patients operated between 1996 and 1999 was included. One hundred and one cases accrued over 10 years from 1996 to 2006 were analysed using SPSS (Version 12.0). The mean age of our cohort of patients was 61±12 years with male to female ratio of 2:1. The commonest clinical presentations were obstructive jaundice (64%) and abdominal pain (47%). Majority had malignant lesions (86%) with invasive adenocarcinoma of the head of pancreas being the predominant histopathology (41%). Median operative time was 315 (180,945) minutes. Two-third of our patients had pancreaticojejunostomy (PJ) while the rest had pancreaticogastrostomy (PG). There were five patients with pancreatico-enteric anastomotic leak (5%), three of whom (3%) were from PJ anastomosis. Overall, in-hospital and 30-day mortality were both 3%. The median post-operative length of stay (LOS) was 15 days. Using logistic regressions, the post-operative morbidity predicts LOS following operation (p<0.005). The strategy in improving the morbidity and mortality rates of pancreaticoduodenectomies lies in the subspecialization of surgical services with regionalization of such complex surgeries to high volume centers. The key success lies in the dedication of staffs who continues to refine the clinical care pathway and standardize management protocol. [source] Patient preparation before surgery for cholangiocarcinomaHPB, Issue 3 2008E. Oussoultzoglou Abstract Aim. Multiorgan dysfunction is often encountered in jaundiced patients and may compromise the postoperative outcome after liver resection for cholangiocarcinoma (CCA). The aim of the present study was to elucidate evidence-based medicine regarding the benefit of the available preoperative treatments currently used for the preparation of patients before surgery for hilar CCA. Material and methods. An electronic search using the Medline database was performed to identify relevant articles relating to renal dysfunction, bacterial translocation, hemostasis impairment, malnutrition, liver failure, and postoperative outcome in jaundiced patients undergoing liver resection for CCA. Results. There is grade B evidence to expand the extracellular water volume and to administer oral synbiotic supplements. Intravenous vitamin K administration is an effective treatment. Perioperative nutritional support should be administered preferably by the enteral route in severely malnourished patients with compromised liver function undergoing extended liver resection (grade A evidence). There is only grade C evidence to recommend a portal vein embolization in patients with CCA when the future remnant liver volume is <40%. Conclusions. A simplified scheme that might be useful in the management of patients presenting with obstructive jaundice was presented. Despite surgical technique improvements, preparation of patients for surgery will continue to be one of the major determinants for the postoperative prognosis of jaundiced patients. [source] Cholangiocarcinoma: preoperative biliary drainage (Con)HPB, Issue 2 2008A. LAURENT Aim. In patients with malignant hilar obstruction, liver resection is associated with an increased risk of postoperative liver failure attributed to the need for major liver resection in a context of obstructive jaundice. To overcome this issue, most authors recommend preoperative biliary drainage (PBD). However, PBD carries risks of its own, including, primarily, sepsis and, more rarely, tumor seeding, bile peritonitis, and hemobilia. We, unlike most authors, have not used routine PBD before liver resection in jaundiced patients. Material and methods. Our series includes 62 patients who underwent major liver resection for cholangiocarcinoma; 33 of these had elevated bilurubin (60,470 µmol/l) and were operated without PBD. There were 43 extended right hepatectomies and 18 extended left hepatectomies. Results. Hospital deaths occurred in 5 patients (8%) including 3 of 33 jaundiced patients (9%, ns). All deaths occurred after extended right hepatectomy (12%), including 3 patients with a serum bilirubin level above 300 µmol/l and 2 with normal bilirubin. There were no deaths after left-sided resections, whatever the level of bilirubin. Conclusions. PBD can be omitted in the following situations: recent onset jaundice (<2,3 weeks), total bilirubin <200 µmol/l, no previous endoscopic or transhepatic cholangiography, absence of sepsis, future liver remnant >40%. These criteria include most patients requiring left-sided resections and selected patients requiring right-sided resections. In other cases, PBD is required, associated with portal vein embolization in the event of a small future liver remnant. [source] Preoperative biliary drainage before resection for cholangiocarcinoma (Pro)HPB, Issue 2 2008Y. NIMURA Abstract Three types of preoperative biliary drainage (BD): percutaneous transhepatic (PTBD), endoscopic (EBD), and endoscopic nasobiliary (ENBD) can be indicated before resection of cholangiocarcinoma. However, three randomized controlled trials (RCTs) have revealed that preoperative PTBD does not improve perioperative results. Other RCTs have revealed that preoperative EBD for malignant obstructive jaundice has no demonstrable benefit and after EBD for hilar cholangiocarcinoma there are highly developed infectious complications. Most patients with distal cholangiocarcinoma undergo pancreatoduodenectomy (PD) without preoperative BD. However, no RCTs have been performed to clarify the safety of major hepatectomy without preoperative BD for cholestatic patients with hilar cholangiocarcinoma. Furthermore, preoperative intrahepatic segmental cholangitis is a prognostic factor in the outcome of major hepatectomy for biliary cancer. Preoperative BD has another purpose in the preoperative management of patients with hilar cholangiocarcinoma. Selective cholangiography via ENBD and/or PTBD catheters provides precise information about the complicated segmental anatomy of the intrahepatic bile ducts and extent of cancer along the separated segmental bile ducts, which contributes toward designing a type of resective procedure. RCTs in biliary cancer patients undergoing major hepatectomy have revealed that bile replacement during external biliary drainage and perioperative synbiotic treatment can prevent postoperative infectious complications. Although preoperative EBD increases the risk of cholangitis, major hepatectomy combined with preoperative biliary drainage, preferably PTBD and/or ENBD, followed by portal vein embolization has been established as a safer management strategy for perihilar cholangiocarcinoma. [source] Pancreatico-duodenectomy for complicated groove pancreatitisHPB, Issue 3 2007SAKHAWAT H. RAHMAN Objectives. Groove pancreatitis (GP) describes a form of segmental pancreatitis, which affects the pancreatic head at the interface with the duodenum, and is frequently associated with ectopic pancreatic tissue in the duodenal wall. We present a series of symptomatic patients with complicated GP who underwent pancreaticoduodenectomy, and review the diagnostic challenges, imaging modalities, pathological features and clinical outcome of this rare condition. Patients and methods. This was a prospective case base study of clinical, radiological and pathological data collected between the years 2000 and 2005 on patients diagnosed with severe GP , confirmed by histopathological examination following pancreaticoduodenectomy. Results. In total 11 patients were included, presenting with chronic abdominal pain (n= 11), gastric outlet obstruction (n= 5) and jaundice (n= 1). Exocrine dysfunction with associated weight loss (median > 9 kg) was present in 10 patients, and type 2 diabetes in 2 patients. Radiological imaging (CT/MRCP/EUS) provided complementary investigations and correlated well with classic histopathological findings (duodenal wall thickening, mucosal irregularity and Brunner's gland hyperplasia, duodenal wall cysts and pancreatic heterotropia). Following pancreaticoduodenectomy (median follow-up period 52 weeks) all patients experienced significant pain alleviation and weight gain (average 3 kg at 2 months). Conclusion. Pancreaticoduodenectomy is associated with significant improvements in weight gain and alleviates the chronic pain associated with severe GP. [source] Nonoperative imaging techniques in suspected biliary tract obstructionHPB, Issue 6 2006Frances Tse Abstract Evaluation of suspected biliary tract obstruction is a common clinical problem. Clinical data such as history, physical examination, and laboratory tests can accurately identify up to 90% of patients whose jaundice is caused by extrahepatic obstruction. However, complete assessment of extrahepatic obstruction often requires the use of various imaging modalities to confirm the presence, level, and cause of obstruction, and to aid in treatment plan. In the present summary, the literature on competing technologies including endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiopancreatography (PTC), endoscopic ultrasound (EUS), intraductal ultrasonography (IDUS), magnetic resonance cholangiopancreatography (MRCP), helical CT (hCT) and helical CT cholangiography (hCTC) with regards to diagnostic performance characteristics, technical success, safety, and cost-effectiveness is reviewed. Patients with obstructive jaundice secondary to choledocholithiasis or pancreaticobiliary malignancies are the primary focus of this review. Algorithms for the management of suspected obstructive jaundice are put forward based on current evidence. Published data suggest an increasing role for EUS and other noninvasive imaging techniques such as MRCP, and hCT following an initial transabdominal ultrasound in the assessment of patients with suspected biliary obstruction to select candidates for surgery or therapeutic ERCP. The management of patients with a suspected pancreaticobiliary condition ultimately is dependent on local expertise, availability, cost, and the multidisciplinary collaboration between radiologists, surgeons, and gastroenterologists. [source] | |||||||||||||||||||||||||||||||||||||||||||