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Objectives: To characterize the clinical, laboratory, histologic, molecular features, and outcome of gene-confirmed progressive familial intrahepatic cholestasis (PFIC) 1-3 among Arabs and to evaluate for "genotype-phenotype" correlations., Study Design: We retrospectively reviewed charts of 65 children (ATP8B1 defect = 5, ABCB11 = 35, ABCB4 = 25) who presented between 2008 and 2019 with cholestasis. The clinical phenotype of a disease was categorized based on response of cholestasis and itching to ursodeoxycholic acid and ultimate outcome, into mild (complete response), intermediate (partial response, nonprogressive), and severe (progression to end-stage liver disease)., Results: Overall, 27 different mutations were identified (ATP8B1, n = 5; ABCB11, n = 11; ABCB4, n = 11), comprising 10 novel ones. Six patients with heterozygous missense mutations (ATP8B1, n = 2; ABCB11, n = 4) had transient cholestasis. Of the remaining 3 patients with PFIC1, 2 developed severe phenotype (splicing and frameshift mutations). Of the remaining 31 patients with PFIC2, 25 developed severe disease (15 due to frameshift and splicing mutations). Of 25 patients with PFIC3, 10 developed a severe phenotype (1 splicing and 3 frameshift mutations; 6 missense). Patients with PFIC2 had significantly shorter survival time and more rapid disease progression than patients with PFIC3 (P < .001). Patients with frameshift mutations in ABCB11 gene (p.Thr127Hisfs∗6) and ABCB4 gene (p.Phe210Serfs∗5) had significantly shorter survival time than missense mutations (P = .011; P = .0039, respectively)., Conclusions: We identified genotype-phenotype correlations among mutations in ABCB11 and ABCB4 genes, which underscore the prognostic value of early genetic diagnosis. The disease course in patients with PFIC3 could be favorably modified by ursodeoxycholic acid therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date., Approach and Results: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 μmol/L (P = 0.05) tended to be associated with improved NLS., Conclusions: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS., (© The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during pregnancy. ICP has been associated with morbidity but little is known about women's long-term survival. Our aim was to determine whether ICP is associated with mothers' long-term survival., Study Design: The study population comprised 571 women with ICP in at least one pregnancy seen at Tampere University Hospital in Finland between 1969‒1988. The reference group comprised 1333 women: the previous and the following participant in the maternity ward diary. The data were obtained from Statistics Finland in March 2017 containing deaths among the study participants between 1971‒2015. The follow-up time of the cohort was 27-46 years. The Kaplan-Meier method was used., Results: Totally, 39 of the mothers with ICP (6.8%) and 111 of the reference group (8.3%) had died by the end of 2015 (p = 0.267). The mean survival time of ICP women was 77.4 years and of the reference group 79.2 years (p = 0.288). The mean survival time from labour in the ICP group was 45.0 years and in the reference group 44.8 years (p = 0.259)., Conclusions: Based on this study ICP does not seem to be associated with women's survival. There is no need to follow-up ICP mothers' health because of the nonexistent risk of premature death., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder specific to pregnancy and presents with maternal pruritus, raised concentrations of serum bile acids and abnormal liver function tests. ICP is associated with increased rates of spontaneous and iatrogenic preterm labour, fetal hypoxia, meconium-stained amniotic fluid and intrauterine death. Some clinicians treat ICP with ursodeoxycholic acid (UDCA) to improve maternal pruritus and biochemical abnormalities. However, there are currently no data to support the use of UDCA to improve pregnancy outcome as none of the trials performed to date have been powered to address this question., Methods: The PITCHES trial is a triple-masked, placebo-controlled randomised trial, to evaluate UDCA versus placebo in women with ICP between 20 + 0 to 40 + 6 weeks' gestation. The primary objective of the trial is to determine if UDCA treatment of women with ICP between 20 + 0 and 40 + 6 weeks' gestation reduces the primary perinatal outcome: a composite of perinatal death (as defined by in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery (less than 37 weeks' gestation) or neonatal unit admission for at least 4 h (from infant delivery until hospital discharge). The secondary objectives of the trial are (1) to investigate the effect of UDCA on other short-term outcomes for both mother and infant and (2) to assess the impact of UDCA on health care resource use, in terms of the total number of nights for mother and infant, together with level of care., Discussion: Current practice in the UK at the time of trial commencement for the treatment of ICP is inconsistent, with some units routinely prescribing UDCA, others prescribing very little and the remainder offering it variably. Our previous pilot trial of UDCA in women with ICP demonstrated that the trial would be feasible, and the research question remains active and unanswered. Results are highly likely to influence clinical practice, through direct management and impact on national and international guidelines., Trial Registration: ISRCTN registry, ID: ISRCTN91918806 . Prospectively registered on 27 August 2015.

Cholangitis lenta, also known as ductular cholestasis, cholangiolar cholestasis, or subacute nonsuppurative cholangitis, is an uncommon type of cholangitis characterized by ductular reaction with inspissated bile in dilated ductules. The literature on this unique entity has been limited to only a few studies based on a very limited number of cases, which importantly suggest an association with sepsis and/or intra-abdominal infection. The clinical, laboratory, and histologic features of 28 cases of cholangitis lenta are herein investigated. Twenty-five (89.3%) patients were liver transplant recipients. Most notably, the majority of patients showed clinical signs and symptoms of sepsis, and positive microbiology cultures were demonstrated in 24 (85.7%) patients. Significantly, 15 (53.6%) patients died during their hospitalization, ranging from 2 days to 5 months after the initial liver biopsy that showed histologic features of cholangitis lenta. Among the 13 discharged patients, including 2 who received retransplantation, 4 (14.3%) subsequently died of pneumonia, graft dysfunction, or fungal infection within 7 months to 9.3 years. Only 9 (32.1%) patients were alive at the last follow-up, with the follow-up time ranging from 3.8 to 10.4 years. Our data show that the finding of cholangitis lenta on liver biopsy is thus frequently associated with sepsis and with a high mortality rate. Therefore, accurate diagnosis of this condition on liver biopsy is imperative as it is an indication that the patient may have a potentially life threatening condition that requires immediate medical attention and management.

Background/aim: Maternal, fetal, and neonatal outcomes in parturients with intrahepatic cholestasis of pregnancy (ICP) have been retrospectively documented. We aimed to present pregnancy outcomes of parturients with ICP who underwent delivery. The study was conducted during a 1-year period., Materials and Methods: After ethics committee approval, data from 1 January to 31 December 2015 were collected to identify parturients with ICP., Results: Ten out of 37 patients underwent normal spontaneous vaginal delivery (NSVD), and the remaining 27 parturients underwent cesarean section (CS). Five of 27 parturients underwent nonelective cesarean section, while 22 had elective cesarean delivery. As for NSVD deliveries, only one parturient received combined spinal and epidural anesthesia (CSE) for labor. Neuraxial (n = 22 for spinal and n = 1 for CSE) and general anesthesia (n = 4) rates for CSs were 85% and 15%, respectively. Approximately 96% of neuraxial anesthesia choices were spinal anesthesia. Nearly 18.5% of CSs were not elective. Adverse outcomes included 2 preterm births, 2 preterm labors, 2 newborns with hepatitis, and one perinatal fetal death., Conclusion: Parturients with ICP who had normal coagulation parameters despite increased liver enzymes preoperatively underwent cesarean delivery under spinal anesthesia without complication. Although maternal outcomes were generally positive, adverse fetal and neonatal outcomes are more likely to occur, particularly in cases with severe ICP.

Background: Hepatic dysfunction (HD) is a common finding in critically ill patients. The underlying pathophysiological process is one of either cholestasis or hypoxic liver injury (HLI). Using serum bilirubin, our study aimed to determine the incidence of HD in a critically ill trauma population, identify risk factors and analyse the impact on outcomes., Methods: A retrospective observational study was performed on all patients admitted to the Level 1 Trauma Unit ICU at Inkosi Albert Luthuli Central Hospital in Durban, South Africa (IALCH) from 01/01/2012 until 31/12/2012. HD was defined as a total bilirubin greater than 34.2μmol/l (2mg/dL). Additional demographic, physiological, biochemical, and pharmaceutical risk factors for hepatic dysfunction were identified and recorded., Results: Two hundred and twenty five patients were included in the study of whom 48 (21.3%) developed HD. An increased duration of ventilation (median 15days [inter-quartile range 6-19] vs 6days [IQR 3-11] p<0.001), prolonged length of stay (median 19days [IQR 8.5-31] vs 7days [IQR 3-13] p<0.001), and higher mortality rate (31.3% vs. 14.7% p=0.01) were all significantly associated with HD. Shock on admission was twice as common in patients developing HD (p<0.001). The only drugs associated with HD were piperacillin-tazobactam (p<0.001) and enalapril (p=0.04). On multivariable analysis however, HD was not associated with mortality., Conclusion: HD was common in our study population, and was associated with other organ dysfunction, increased mortality and length of stay., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background & Aims: There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease., Methods: In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12)., Results: We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%-89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%-98% of patients without cirrhosis or with compensated cirrhosis, by 85%-88% of patients with moderate hepatic impairment, by 60%-75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation., Conclusion: The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Fibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients., Methods: We matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin., Results: Baseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The sustained viral response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors., Conclusion: Our results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower sustained viral response, patient survival, and graft survival in the FCH recipients., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To determine the safety and feasibility of intraductal radiofrequency ablation (RFA) followed by locoregional tumor treatments in patients with non-resectable malignant biliary obstruction and stent re-occlusion., Methods: Fourteen patients with malignant biliary obstruction and blocked metal stents were studied retrospectively. All had intraductal RFA followed by locoregional tumor treatments and were monitored clinically and radiologically. The practicality, safety, postoperative complications, jaundice remission, stent patency and survival time were analyzed., Results: Combination treatment was successful for all patients. There were no severe complications during RFA or local treatments. All patients had stent patency restored, with a decline in serum bilirubin. Three patients had recurrent jaundice by 195, 237 and 357 days; two patients underwent repeat intraductal RFA; and one required an internal-external biliary drain. The average stent patency time was 234 days (range 187-544 days). With a median follow-up of 384 days (range 187-544 days), six patients were alive, while eight had died. There was no mortality at 30 days. The 3, 6, 12 and 18 month survival rates were 100%, 100%, 64.3% and 42.9%, respectively., Conclusion: Intraductal RFA followed by locoregional tumor treatments for occluded metal stents is safe and practically feasible and potential increase stent patency and survival times.

The BCAP31 gene is located between SLC6A8, associated with X-linked creatine transporter deficiency, and ABCD1, associated with X-linked adrenoleukodystrophy. Recently, loss-of-function mutations in BCAP31 were reported in association with severe developmental delay, deafness and dystonia. We characterized the break points in eight patients with deletions of SLC6A8, BCAP31 and/or ABCD1 and studied the genotype-phenotype correlations. The phenotype in patients with contiguous gene deletions involving BCAP31 overlaps with the phenotype of isolated BCAP31 deficiency. Only deletions involving both BCAP31 and ABCD1 were associated with hepatic cholestasis and death before 1 year, which might be explained by a synergistic effect. Remarkably, a patient with an isolated deletion at the 3'-end of SLC6A8 had a similar severe phenotype as seen in BCAP31 deficiency but without deafness. This might be caused by the disturbance of a regulatory element between SLC6A8 and BCAP31., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the effect of internal-external percutaneous transhepatic biliary drainage (IEPTBD) for patients with malignant obstructive jaundice., Methods: During the period of January 2008 and July 2013, internal-external drainage was performed in 42 patients with malignant obstructive jaundice. During the procedure, if the guide wire could pass through the occlusion and into the duodenum, IEPTBD was performed. External drainage biliary catheter was placed if the occlusion was not crossed. Newly onset of infection, degree of bilirubin decrease and the survival time of patients were selected as parameters to evaluate the effect of IEPTBD., Results: Twenty newly onset of infection were recorded after procedure and new infectious rate was 47.6%. Sixteen patients with infection (3 before, 13 after drainage) were uncontrolled after procedure, 12 of them (3 before, 9 after drainage) died within 1 month. The mean TBIL levels declined from 299.53 umol/L before drainage to 257.62 umol/L after drainage, while uninfected group decline from 274.86 umol/L to 132.34 umol/Lp (P < 0.5). The median survival time for uninfected group was 107 days, and for infection group was 43 days (P < 0.05)., Conclusions: The IEPTBD drainage may increase the chance of biliary infection, reduce bile drainage efficiency and decrease the long-term prognosis, and the external drainage is a better choice for patients with malignant obstructive jaundice need to biliary drainage.

Aims: The aim of the study was to evaluate the significance of total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyltransferase (GGT) for predicting outcome in sepsis-associated cholestasis., Methods: A retrospective cohort review of the hospital records was performed in 181 neonates admitted to the Neonatal Care Unit. A comparison was performed between subjects with low and high liver values based on cut-off values from ROC analysis. We defined poor prognosis to be when a subject had prolonged cholestasis of more than 3.5 months, developed severe sepsis, septic shock or had a fatal outcome., Results: The majority of the subjects were male (56%), preterm (56%) and had early onset sepsis (73%). The poor prognosis group had lower initial values of GGT compared with the good prognosis group (P = 0.003). Serum GGT (cut-off value of 85.5 U/L) and AST (cut-off value of 51 U/L) showed significant correlation with the outcome following multivariate analysis. The odds ratio (OR) of low GGT and high AST were OR 4.3 (95% CI:1.6 to 11.8) and OR 2.9 (95% CI:1.1 to 8), respectively, for poor prognosis. In subjects with normal AST values, those with low GGT value had relative risk of 2.52 (95% CI:1.4 to 3.5) for poorer prognosis compared with those with normal or high GGT., Conclusion: Serum GGT and AST values can be used to predict the prognosis of patients with sepsis-associated cholestasis., (© 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background: Caroli disease (CD) is characterized by dilation of the intrahepatic biliary tree, which may result in malignancy. Treatments include management of symptoms and hepatic resection to decrease disease burden. In patients with CD not amenable to these treatments, orthotopic liver transplantation (OLT) has been used. This study examines if OLT is a reasonable treatment for patients with CD., Materials and Methods: The United Network of Organ Sharing/Organ Procurement and Transplantation Network database between September 30, 1987 and March 31, 2011 was queried. Cases without patient or allograft survival time or without a diagnosis were excluded from analysis. Patients with CD were compared to patients with primary biliary cirrhosis (PBC), secondary biliary cirrhosis (BC), primary sclerosing cholangitis (PSC), and all indications for OLT. Survival analysis was performed by log-rank test and Kaplan-Meier., Results: One hundred forty patients with CD were compared to 4797 patients with PBC, 489 patients with secondary BC, 6033 patients with PSC, and 92,210 patients post-OLT. Patient and allograft survivals of CD patients at 1, 3, 5, and 10 y are, respectively, 88.5%, 83.4%, 80.9%, and 77.8%; and 81.2%, 74.8%, 70.6%, and 67.9%. CD patients have significantly improved patient and allograft survivals after OLT compared to patients with secondary BC (P = 0.003, P = 0.015) and all other patients undergoing OLT (P = 0.003, P = 0.026). There is a trend towards long-term improved patient and allograft survival in transplanted patients with CD compared to patients with PBC and PSC., Conclusions: These results suggest that OLT should be considered an effective treatment modality for patients with CD resulting in excellent long-term outcomes., (Copyright © 2012. Published by Elsevier Inc.)

Background: Alcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear., Methods: We studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model., Results: 43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001)., Conclusions: In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.

Background: Progressive familial intrahepatic cholestasis (PFIC) results in liver cirrhosis. Therefore, some PFIC patients require liver transplantation (LT). Although three types of PFIC have been identified, their etiologies include unknown mechanisms., Patients: A total of 717 recipients who underwent living-donor LT (LDLT) at <20 yr old were enrolled in this study. Among these recipients, 14 PFIC recipients comprising 11 PFIC type 1 (PFIC1) and three PFIC type 2 (PFIC2) were evaluated., Results: Three of 11 PFIC1 recipients died, while all three PFIC2 recipients survived. Eight of 11 PFIC1 recipients showed steatosis after LDLT. Among the eight steatosis-positive PFIC1 recipients, seven showed severe steatosis and seven were complicated with steatohepatitis. Nine of 11 PFIC1 recipients showed fibrosis after LDLT, and eight of the nine fibrosis-positive PFIC1 recipients showed severe fibrosis. In contrast to the PFIC1 recipients, the PFIC2 recipients did not show any steatosis or fibrosis after LDLT., Conclusions: The clinical courses and outcomes of PFIC1 recipients after LDLT are still not sufficient owing to steatosis/fibrosis, unlike the case for PFIC2 recipients. As PFIC1 patients will require LT during the long-term progression of the disease, further strategy improvements are required for PFIC1 patients., (© 2010 John Wiley & Sons A/S.)

Hepatic sarcoidosis is a rare indication for liver transplantation. Using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) database, we evaluated patient and graft survival after orthotopic liver transplantation for sarcoidosis between October 1987 and December 2007. We assessed the potential prognostic value of multiple demographic and clinical variables, and we also compared these patients to a case-matched group of patients with primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC). The 1- and 5-year survival rates for the sarcoidosis group were 78% and 61%, respectively, and these rates were significantly worse than the rates for the PSC/PBC group (P = 0.001). Disease recurrence in the liver is a rare cause of graft loss or patient death. Three deaths occurred in the sarcoidosis group because of recurrent hepatic sarcoidosis, and 1 death was a result of cardiac sarcoidosis. A univariate analysis identified an increasing donor risk index as a significant negative factor for outcomes for the sarcoidosis group [hazard ratio (HR) = 2.06, confidence interval (CI) = 1.04-4.06, P = 0.037], but this finding was not found in a multivariate analysis, in which no independent predictors were found to have a significant impact. A case-matched univariate analysis demonstrated that sarcoidosis and morbid obesity were significant negative factors for outcomes, and in a multivariate analysis, sarcoidosis continued to predict worse outcomes (HR = 2.39, CI = 1.21-4.73, P = 0.012). In conclusion, an analysis of the UNOS/OPTN database indicates that the patient and allograft survival rates for hepatic sarcoidosis are satisfactory, but they are worse in comparison with the rates for other cholestatic liver diseases., (Copyright © 2011 American Association for the Study of Liver Diseases.)

The aim of this study is to evaluate the incidence, etiology, and risk facrors for prolonged severe intrahepatic cholestasis (PSIC) after 129 pediatric living-donor liver transplantations (LDLT). The incidence of PSIC was 25.6% (n = 33). Twenty-eight (84.8%) versus 5 (15.2%) children experienced early versus late PSIC, respectively. Among these 33 children with PSIC, 8 (24.2%) received a donor liver with mild to moderate fatty change, 4 (12.1%) with low graft-body weight ratios, and 4 (12.1%) with ABO incompatibility. The predominant etiologies were acute rejection (n = 15; 45.5%), chronic rejection (n = 6; 18.2%), virus (n = 3; 9.1%), vascular complications (n = 4; 12.1%), and initial graft dysfunction (n = 10; 30.3%). ABO incompatibility (P = .032; odds ratio [OR] 3.25), chronic rejection (P = .012; OR 4.76), and vascular complications (P = .046; OR 1.82) were significant variables associated with PSIC. Donor selection with ABO compatibility as well as early detection and management of chronic rejection and vascular complications may be important to prevet PSIC in LDLT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Whether uni- or bilateral drainage should be performed for malignant hilar biliary obstruction remains a matter of debate. Moreover, endoscopic placement of bilateral metallic stents has been considered difficult and complicated. Although the Y-stent with a central wide-open mesh facilitates bilateral stent placement, it has limitations. This study evaluated the feasibility and efficacy of the Niti-S large cell D-type biliary stent (LCD) with a uniform large cell for both uni- and bilateral drainage of malignant hilar biliary obstruction., Methods: From April 2008 to March 2009, a total of 12 consecutive patients with unresectable malignant hilar biliary obstruction of Bismuth type 2 or greater underwent placement of LCD. Before LCD placement, all the patients underwent endoscopic unilateral biliary drainage using a plastic stent or a nasobiliary drainage tube. If jaundice improved after the procedure, the plastic stent or nasobiliary drainage tube was replaced with the unilateral LCD. If jaundice did not resolve or contralateral cholangitis occurred, bilateral LCD placement was performed., Results: Seven patients had unilateral and five patients had bilateral LCD placement. Technical success was achieved for all 12 patients. An early complication occurred for one patient (8%), and stent occlusion occurred for six patients (50%) because of tumor ingrowth (n=4) or sludge (n=2). These patients were managed by insertion of plastic stents (n=4) or percutaneous transhepatic biliary drainage (n=2). The median stent patency period was 202 days., Conclusions: The newly designed endoscopic metallic stent may be feasible and effective for malignant hilar biliary obstruction, and endoscopic reintervention is relatively simple.

Background: The self-expandable metallic stent (SEMS) has been widely used for unresectable malignant biliary obstruction but eventually becomes occluded by tumor ingrowth/overgrowth and sludge. Therefore, we aimed to determine the therapeutic effectiveness of secondary stents and to find differences according to various combinations of the first and second stents for the management of occluded SEMSs in patients with malignant distal biliary obstruction., Methods: Between 1999 and November 2008, 77 patients with malignant biliary obstruction underwent secondary biliary stent placement as "stent-in-stent" at three university hospitals in Korea (40 covered, 26 uncovered, and 11 plastic stents). The membrane of the covered SEMS was regarded as the barrier against tumor ingrowth. We categorized the patients into three groups based on whether the covered SEMS was either the first or the second stent: membrane-SEMS (18 covered-covered; 9 covered-uncovered; 22 uncovered-covered SEMS), bare-SEMS (17 uncovered-uncovered SEMS), and plastic stent (3 covered-plastic; 8 uncovered-plastic)., Results: The median patency of second stents was 138, 109, and 88 days (covered, uncovered, and plastic stents). The second covered SEMSs had a significantly longer patency than plastic stents (p=0.047). In a multivariate analysis including membrane-SEMS, bare-SEMS, and plastic stent groups, the bare-SEMS had a worse cumulative stent patency (HR=2.04, CI=1.08-3.86) and survival time (HR=2.37, CI=1.25-4.49) than the membrane-SEMS. Patients with ampulla of Vater cancer had better stent patency (HR=0.27, CI=0.08-0.98) and survival (HR=0.17, CI=0.04-0.77) than those with other pancreatobiliary malignancies. In addition, antitumor treatment prolonged survival time (HR=0.50, CI=0.26-0.99)., Conclusions: The placement of additional biliary stents using the "stent-in-stent" method is an effective treatment for an occluded metallic primary stent. In addition, double biliary SEMS placement using at least one covered SEMS (in the primary and/or secondary procedure) might provide longer cumulative stent patency and survival than using uncovered SEMSs in both procedures.

Background: Obstructive jaundice (OJ) is an important clinical consideration associated with a high risk of bacteremia. Hepatocyte nuclear factor-kappa B (NF-kappaB) activation confers an antiapoptotic function. Although the occurrence of hepatocyte apoptosis has been shown in OJ, the activation and role of NF-kappaB over the time course of OJ in conjunction with endotoxemia have not yet been well defined. We hypothesized that NF-kappaB activation may be decreased over the time course of OJ and endotoxemia, which leads to severe liver injury. The aim of the current study was to examine whether NF-kappaB activation can decrease hepatocyte apoptosis and liver injury over the time course of OJ in response to lipopolysaccharide (LPS) administration., Methods: Male C57BL/6 mice were subjected to bile duct ligation and were administered LPS intravenously at 3 days (OJ3) or 14 days (OJ14) after bile duct ligation. NF-kappaB activation; protein expressions of NF-kappaB p65, IkappaB-alpha, Ikappabeta-b, and Pin1; immunohistochemistry of poly adenosine diphosphate (ADP)-ribose polymerase p85 fragment (PARP); and serum alanine transaminase (ALT) levels were examined., Results: Hepatocyte NF-kappaB activation was observed during OJ. After LPS administration, the hepatic NF-kappaB activation defined by electrophoretic mobility shift assay was decreased in the OJ14 group compared with the OJ3 group, which is consistent with a decrease in NF-kappaB p65 protein expression. Changes in phosphorylated Ikappa-B-beta but not phosphorylated IkappaB-alpha mirrored these results. Significant hepatocyte apoptosis defined by PARP immunohistochemistry was observed in the LPS-treated OJ14 relative to the LPS-treated OJ3. Hepatic expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the LPS OJ14 mice were upregulated relative to those in the LPS OJ3. Serum ALT levels increased significantly in the LPS OJ14 relative to other mice. The survival rate was significantly less in the LPS OJ14 relative to other mice., Conclusion: After prolonged OJ, exposure to endotoxemia was associated with a decrease in hepatocyte NF-kappaB activation and an increase in hepatocyte apoptosis and secondary necrosis, thus resulting in liver dysfunction., (Copyright 2010 Mosby, Inc. All rights reserved.)

Introduction: Little is known about the epidemiology, causes and outcomes of neonatal cholestasis in the Asian population beyond Japan and Taiwan., Methods: This was a prospective, observational study on patients with neonatal cholestasis who were referred to the University of Malaya Medical Centre, Malaysia, between November 1996 and May 2004., Results: Biliary atresia (BA) (29 percent) and idiopathic neonatal hepatitis (38 percent) were the two commonest causes of neonatal cholestasis (n is 146) that were referred. Out of the 39 patients (27 percent of the total) who died at the time of review, 35 succumbed to end-stage liver disease. Three of the four patients (three BA, one progressive familial intrahepatic cholestasis [PFIC]) who had a living-related liver transplant (LT) died after the surgery (two BA, one PFIC). Six (four percent) of the remaining 107 survivors had liver cirrhosis. The overall four-year survival rates for patients with native liver and LT as well as those with native liver alone for all cases of neonatal cholestasis were 72 percent and 73 percent, respectively, while the respective survival rates for BA were 38 percent and 36 percent., Conclusion: BA and idiopathic neonatal hepatitis are important causes of neonatal cholestasis in Malaysian infants. In Malaysia, the survival rate of patients with neonatal cholestasis, especially BA, is adversely affected by the lack of a timely LT.

Purpose: Intestinal failure (IF)-associated liver disease (IFALD) complicates the treatment of children with IF receiving parenteral nutrition (PN). We hypothesized that prevention or resolution of IFALD was possible in most children and that this would result in improved outcomes., Methods: We reviewed prospectively gathered data on all children referred to the intestinal rehabilitation and transplantation center at our institution. Total bilirubin level (TB) was used as the marker for IFALD. Patients were grouped based on TB at referral and at subsequent inpatient stays and outpatient visits. Standard treatment consisted of cycling of PN, limiting lipid infusion, enteral stimulation, use of ursodeoxycholic acid, and surgical intervention when necessary. Outcomes such as mortality, dependence on PN, and need for transplantation were assessed. Statistical analyses were performed using Fisher's exact, Mann-Whitney U, and Wilcoxon signed rank tests., Results: Ninety-three patients with intestinal failure and on PN were treated at our center from 2003 to 2009. Median age at referral was 5 months (0.5-264 months). Prematurity was a complicating factor in 63 patients and necrotizing enterocolitis was the most common diagnosis. Eighty-two children had short bowel syndrome, whereas the remaining 11 had extensive motility disorders. 97% of children required significant alteration of their PN administration. At referral, 76 of 93 children had TB 2.0 mg/dL or higher, and 17 had TB below 2.0 mg/dL. TB normalized in 57 of 76 children with elevated TB at referral, and TB remained elevated in 19. Normalization of TB was associated with a mortality of 5.2%, and transplantation was needed in 5.2%. Conversely, when TB remained elevated, mortality was 58% (P = .0002 vs TB normalized), and transplantation occurred in 58% owing to failure of surgical and medical rehabilitation., Conclusions: Most children referred for treatment of IF have IFALD. A dedicated IF rehabilitation program can reverse IFALD in many children, and this is associated with improved outcome., (Copyright 2010 Elsevier Inc. All rights reserved.)

Unlabelled: Arab Gulf countries including Oman have a high rate of consanguineous marriage with an associated increased frequency of a variety of genetic disorders including liver diseases., Aim: To describe the pattern of chronic liver diseases at The Royal Hospital, Muscat during the period January 2005 to January 2007., Methods: A retrospective study of all children with chronic liver diseases seen at the Royal Hospital, which is a tertiary referral centre for gastro-enterology and hepatology for the whole of Oman., Results: Seventy-nine patients with chronic liver disease were identified. The consanguinity rate amongst parents was 78%. The mean (SD) age of patients at the time of final diagnosis was 5 years (4). The two most common liver disorders were progressive familial intrahepatic cholestasis (30%) and fibrocystic disease of liver and kidney (21%). One-third of the patients came from the Sharqiya region. Complications included growth retardation (75%), cirrhosis (26%) and portal hypertension (39%). Three children died and three others received living related liver transplant., Conclusion: About half of the chronic liver disorders in Oman are hereditary in origin. At least three children per year will require liver transplant.

Unlabelled: Bile salt export pump (BSEP; ATP-binding cassette, subfamily B, member 11) mutations in humans result in progressive familial intrahepatic cholestasis type 2, a fatal liver disease with greatly reduced bile flow. However in mice, Bsep knockout leads only to mild cholestasis with substantial bile flow and up-regulated P-glycoprotein genes (multidrug resistance protein 1a [Mdr1a] and Mdr1b). To determine whether P-glycoprotein is responsible for the relatively mild phenotype observed in Bsep knockout mice, we have crossed mouse strains knocked out for Bsep and the two P-glycoprotein genes and generated a triple knockout mouse. We found that a knockout of the three genes leads to a significantly more severe phenotype with impaired bile formation, jaundice, flaccid gallbladder, and increased mortality. The triple knockout mouse is the most severe genetic model of intrahepatic cholestasis yet developed., Conclusion: P-glycoprotein functions as a critical compensatory mechanism, which reduces the severity of cholestasis in Bsep knockout mice.

Background: Intrahepatic bile duct strictures are a serious complication after non-heart-beating (NHB) liver transplantation. Bile salt toxicity has been identified as an important factor in the pathogenesis of bile duct injury and cholangiopathies. The role of bile salt toxicity in the development of biliary strictures after NHB liver transplantation is unclear., Methods: In a porcine model of NHB liver transplantation, we studied the effect of different periods of warm ischemia in the donor on bile composition and subsequent bile duct injury after transplantation. After induction of cardiac arrest in the donor, liver procurement was delayed for 0 min (group A), 15 min (group B), or more or equal to 30 min (group C). Livers were subsequently transplanted after 4 hr of cold preservation. In the recipients, bile flow was measured, and bile samples were collected daily to determine the bile salt-to-phospholipid ratio. Severity of bile duct injury was semiquantified by using a histologic grading scale., Results: Posttransplantation survival was directly related to the duration of warm ischemia in the donor. The bile salt-to-phospholipid ratio in bile produced early after transplantation was significantly higher in group C, compared with group A and B. Histopathologic condition showed the highest degree of bile duct injury in group C., Conclusion: Prolonged warm ischemia in NHB donors is associated with the formation of toxic bile after transplantation, with a high biliary bile salt-to-phospholipid ratio. These data suggest that bile salt toxicity contributes to the pathogenesis of bile duct injury after NHB liver transplantation.

Background: Hodgkin lymphoma (HL)-related vanishing bile duct syndrome (VBDS) and idiopathic cholestasis (IC) are rare conditions that often lead to liver failure and death. The available literature consists primarily of case reports, resulting in little clarity as to the clinical course and ideal treatment for this disease., Material and Methods: We performed a literature search from which we identified all published cases of HL-related VBDS or IC, and created a database of detailed presentation, treatment, and outcome information for all patients. Patient and disease factors were analyzed for an association with overall survival and liver failure-free survival. A case presentation introduces this analysis., Results: Thirty-seven cases of HL-related VBDS/IC were identified. Median follow-up was 7 months; 1-year OS and liver failure-free survival (LFFS) are 43% and 41%, respectively. Sixty-five percent of the patients died while 30% were alive with normal or near-normal stable liver function and no evidence of recurrent HL at last evaluation. Of the 20 patients without residual HL following therapy, 12 (60%) achieved liver failure-free survival. On univariate analysis, factors significantly associated with improved liver failure-free survival were stage I/II HL (p=0.02), a complete response of HL (p=0.0002), and delivery of radiotherapy (pB0.0001). Two patients received chemotherapy without radiation and survived with recovery of liver function., Discussion: HL-related VBDS/IC is potentially reversible and not uniformly fatal, with 30% of presenting patients demonstrating good lymphoma and liver outcomes after definitive therapy for HL. As a complete response of HL provides the only possibility of recovering liver function, patients with this disease should proceed to definitive treatment of HL as soon as feasible.

Recent advances in genetics and in physiopathology of bile composition and excretion have clarified the understanding of progressive familial intrahepatic cholestasis (PFIC). The aim of the present study is to review the experience of our center in terms of diagnosis, management and outcome of 49 pediatric PFIC patients, belonging to the three classical subtypes described. We analyse the clinical, biological, and histological patterns and review the response to the medical and surgical treatment and the global outcome. The only clinical difference between the different subtypes of PFIC patients was the intensity of pruritus. Serum gamma-glutamyltransferase (GGT) and liver histology allowed to differentiate PFIC III from PFIC I and II patients. High levels of biliary bile acids in 2 low-GGT patients was associated with favourable outcome. Response to ursodeoxycholic acid (UDCA) varies from patient to patient and was not associated to a particular subtype of PFIC. In five patients of this cohort, external biliary diversion was performed without improvement. Transplantation is indicated whenever medical treatment fails to restore normal social life, growth and well being of the child and it is associated with excellent survival (> 90%).

Progressive familial intrahepatic cholestasis (PFIC) is a heterogenous group of disorders with various etiologies. Recent molecular and genetic studies have categorized the spectrum of types. Liver transplantation is a curative modality of treatment in this disease. We report our experience with 13 patients with PFIC who underwent living related liver transplantation. The follow-up periods ranged from 12 to 50 months. Two children died at 1 and 2 years posttransplantation, leading to a decrease in survival rate from 100% in the first year to 84.6%.

Background: The aim of this study was to determine whether patency rates differ with respect to the material, design, and surface texture of 3 different plastic stents., Methods: A total of 120 patients (median age 70.5 years; interquartile range 62-78 years) with malignant mid or distal bile duct strictures, seen between March 1996 and May 1999, were prospectively randomized to receive a 10F polyurethane stent, a Teflon Tannenbaum stent, or a hydrophilic hydromer-coated polyurethane stent. The primary study outcome measure was the interval between stent insertion and the first episode of clogging (or the presence of jaundice at death without stent exchange). All 3 types of stent were studied by scanning electron microscopy before insertion., Results: A total of 19 patients were excluded from long-term follow-up. Median duration of stent patency was 76 days overall (interquartile range 29-150 days) and 76 (interquartile range 30-110) days for hydrophilic hydromer-coated polyurethane, 108 (interquartile range 33-186) days for 10F polyurethane, and 58 (interquartile range 21-188) days for Teflon Tannenbaum stents. There were no statistically significant differences among stent types. The hydrophilic hydromer-coated stent had the smoothest surface, as visualized by scanning electron microscopy., Conclusions: No significant differences in the patency of 3 types of stents were detected in this randomized trial. In particular, the hydrophilic hydromer-coated plastic stent did not provide clinical advantages despite its smooth surface.

Background/aims: Hilar bile duct cancer progresses slowly but easily invades the nearby portal vein or hepatic artery. Thus, in some cases, curative resection is impossible, so we need to determine the best non-surgical treatments for this tumor., Methodology: We classified 98 patients with hilar bile duct cancer into 3 categories: a non-surgical group (34 cases), an exploratory laparotomy group (9 cases), and a surgical resection group (55 cases). Survival rates were examined in the light of clinical factors., Results: In the non-surgical group, extensive vessel invasion was the most common reason for unresectability (13 cases), with broad biliary extension the second most common (11 cases). In the exploratory laparotomy group the most common reason for unresectability was severe vessel invasion (6 cases). Cumulative 1- and 2-year survival rates for patients with unresectable tumors without distant metastasis were 26.9% and 7.2%, respectively. One- and 2-year survival rates for patients with unresectable tumors and with total bilirubin of less than 2 mg/dL on discharge were 36.8% and 9.8%, respectively. The 1-year survival rate with placement of an expandable metallic stent was as high as 55.6%; without the stent it was 7.1% (P = 0.005). Radiation therapy gave a better prognosis than did no radiation (P = 0.01)., Conclusions: Portal and arterial invasion were the principal reasons for unresectability. Use of an expandable metallic stent or radiation therapy, and a total bilirubin level of less than 2 mg/dL on discharge, were factors that enhanced survival in unresectable cases, but distant metastasis, dissemination, and poor general condition or liver function were negative factors for survival.

Background: The systematic use of metal stents to treat biliary obstruction is restricted by high cost compared with plastic stents. The aims of this study were to compare cost and efficacy of plastic stents and metal stents in the treatment of patients with malignant common bile duct strictures and to define factors that predict survival of these patients., Methods: One hundred eighteen patients (mean age 75 years) with malignant strictures of the common bile duct were randomized to placement of a plastic stent or metal stent. Comparisons were made with the Mann-Whitney or chi-square test as indicated; survival rates were compared with a Cox proportional hazards model., Results: There was no significant difference in survival between the two groups. Time to first obstruction was longer for patients in the metal stent group (metal stent, median not reached vs. plastic stent, 5 months; p = 0.007). The number of additional days of hospitalization, days of antibiotic therapy, and the numbers of ERCPs and transabdominal US procedures was significantly higher in the plastic stent group. After multivariate analysis, only the presence of liver metastases was independently related to survival (p < 0.0005; OR = 2.25). This variable defined a group with a shorter survival. Median survival of patients with hepatic metastasis at diagnosis was 2.7 months compared with 5.3 months for patients without liver metastasis; in the latter group, the overall cost associated with metal stents was lower than for plastic stents., Conclusions: Metal stent placement is the most effective treatment of inoperable malignant common bile duct stricture. Placement of a metal stent is cost effective in patients without hepatic metastases, whereas a plastic stent should be placed in patients with spread of the tumor to the liver.

Background/aims: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is uncommon. Many drugs have been implicated. Data on its epidemiology are scarce. We performed a population-based prospective study of acute serious liver disease in Catalonia (Spain)., Methods: A collaborating hospital network was set up. All patients with acute serious liver disease and negative viral hepatitis serological markers, without an obvious cause of liver disease, were included., Results: The incidence of acute serious liver disease was 7.4 per 10(6) inhabitants per year (95% CI; 6.0-8.8), which increased with age. The incidence of hepatocellular acute serious liver disease (3.84 per 10(6) per year) was greater than that of cholestatic and mixed patterns. The case-fatality ratio was 11.9% and mortality 0.8 per million person-years. The risk of death was similar among patients with hepatocellular and cholestatic patterns. Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most frequently used drugs., Conclusions: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is rare. Its incidence increases with age. The prognosis of cholestatic acute serious liver disease does not significantly differ from that of the hepatocellular pattern. Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most common drugs likely to be responsible for acute liver disease., (Copyright 2002 European Association for the Study of the Liver)

Goals: To elucidate the natural progression of hepatolithiasis that showed no signs at the time of initial presentation., Study: Over a 17-year period, we observed 122 of 311 patients with hepatolithiasis who reported no symptoms and, thus, who received no treatment at initial presentation. The follow-up period was for up to 15 years (mean, 10.08 years)., Results: Fourteen of 112 patients (11.5%) developed some symptoms attributed to hepatolithiasis. The interval until the onset of symptoms ranged from 9 months to 7.33 years (mean, 3.42 years ). The developing symptoms included abdominal pain, hepatic abscess, cholangitis, and cholangiocarcinoma. Nine of the 14 patients (64.3%) developed stone migration to the extrahepatic bile duct at the onset of clinical symptoms. The incidence of lobar liver atrophy on computed tomography in the patients with symptomatic hepatolithiasis (13 of 14 patients; 92.9%) was significantly higher than that in the patients with asymptomatic hepatolithiasis (14 of 108 patients; 13.0%). The prognosis of the patients with symptomatic hepatolithiasis were as follows: 2 died of cholangiocarcinoma, 1 died of hepatic failure, and 11 survived. Fifteen of asymptomatic patients died, but none of these deaths were attributed to hepatolithiasis., Conclusions: Close observation is an alternative management at initial presentation for patients with asymptomatic hepatolithiasis without extrahepatic stones or lobar liver atrophy.

Background/aims: This study assesses the treatment of biliary obstruction in patients with hilar malignancies by metallic stents., Methodology: Twenty-one consecutive patients with unresectable malignant biliary obstruction at the hepatic hilum (Bismuth type II, III and IV) were treated with percutaneous transhepatic placement of self-expandable metallic endoprostheses. The endoprostheses were successfully inserted in all patients. In 12 patients all segments of the liver were drained and in 9 patients partial segments of the liver were drained., Results: Seventeen patients (81%) showed relief from jaundice and could be freed of external drainage tubes. Ten patients (48%) showed no recurrent symptoms due to stent obstruction until death. Overall survival was 4.86+/-4.15 (mean+/-SD) months, stent patency was 3.76+/-3.64 months and comfort index representing a ratio of well-being was 70.5+/-38.3%. There was no significant difference in survival rate, stent patency or comfort index between the groups with complete and those with partial drainage., Conclusions: Even in patients with complicated hepatic hilar biliary occlusions, internal drainage using metallic stents can relieve jaundice and leave patients free of external tubes with a comfortable quality of life.

Background: Hepatic resection and percutaneous transhepatic cholangioscopic lithotomy (PTCSL) are the two main approaches to the treatment of hepatolithiasis, but comparisons of longterm followup results have not been adequately reported., Study Design: Of 86 patients with hepatolithiasis admitted to our institution between 1980 and 1996, we reviewed 54 patients: 26 who underwent hepatic resection and 28 who underwent PTCSL. Five patients who underwent postoperative cholangioscopic lithotomy were included in the former group. The remainder of the hepatolithiasis patients were not treated by hepatic resection or PTCSL and, therefore, were excluded from this study. Hepatic resections were mainly indicated for left-sided localized intrahepatic calculi, atrophic liver, and possible presence of cholangiocellular carcinoma. PTCSL was performed for right-sided, bilateral or recurrent stones at an average of 6 treatments (range 1 to 20 treatments) for each patient. There were no differences between the two groups in terms of gender or age. The recurrence rate of stones and longterm prognosis were analyzed using the Kaplan-Meier method, and other clinical factors listed below were statistically compared., Results: The rate of complete removal of stones was similarly high in each group (96.2% in the hepatic resection group versus 96.4% in the PTCSL group). The complication (38.5% versus 21.4%) and 5-year survival (85.6% versus 100%) rates were comparable. Remaining bile duct stricture (18.2% versus 60.9%, p < 0.01) and 5-year recurrence rates (5.6% versus 31.5%, p < 0.05) were statistically lower in the hepatic resection group than in the PTCSL group., Conclusions: Hepatic resection, when combined with postoperative cholangioscopic lithotomy, is a preferable treatment for left-sided stones with strictures and bilateral stones.

Background/aims: The authors aimed to study the importance of pre-operative jaundice reduction in the surgical treatment of icteric-type hepatoma (IHCC)., Methodology: A series of 10 patients with IHCC was reviewed. Eight out of the 10 patients underwent biliary drainage. Obstructive jaundice in the other 2 patients resolved spontaneously. Nine patients subsequently underwent transcatheter arterial embolization (TAE), which appeared to have an additional effect in reducing jaundice., Results: Consequently, 9 of the 10 patients achieved sufficient reduction of the jaundice preoperatively. After the evaluation of liver function, 8 patients underwent hepatectomy without any appreciable morbidity or mortality. The median survival time of the resected cases was 18 months., Conclusions: A combination of biliary drainage and subsequent TAE is a recommended pre-operative strategy for the successful surgical treatment of IHCC.

Method: Thirty-five patients with malignant obstructive jaundice were given palliative treatment by percutaneous self-expandable metallic stents. Cholangiocarcinoma was the most frequent cause of biliary obstruction. The stricture was located in the hilum in more of 50% of cases., Results: Adequate biliary drainage was achieved in 97% of cases. Median survival was 182 days. 11% of patients have died within 30 days. Early complications occurred in 31% of patients. 25% of patients have shown recurrent jaundice after an average of 180 days., Conclusion: Percutaneous self-expandable metallic stents are an efficient means treating malignant biliary strictures, particularly of upper biliary obstructions.

We report the clinical and morphological features of an unusual hepatorenal disorder in 2 patients. The main clinical features were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis, leading to renal death in early childhood. Renal histology showed interstitial fibrosis, tubular atrophy and dilatation, glomerular cysts in the cortex and periglomerular fibrosis; liver histology was characterized by portal fibrosis and bile duct abnormalities. Evaluating the 12 patients published in the literature, the long-term prognosis of the liver function appears bad, suggesting the possibility of a combined liver and kidney transplantation.

Sickle cell intrahepatic cholestasis is a rare but potentially fatal complication of sickle cell disease. Its characteristic features include hepatomegaly, extreme total hyperbilirubinemia, coagulopathy, and acute liver failure. Although the pathophysiology is uncertain, most reports in the medical literature indicate that the prognosis is grim. The only effective therapy that has been reported in this setting is exchange transfusion. We describe two hemoglobin SS patients with sickle cell intrahepatic cholestasis. We conclude that exchange transfusion and supportive care aimed at correction of coagulopathy, stabilization of the acute liver disease, and perhaps most important, avoidance of surgical intervention are the keys to a successful outcome.

Between 1987 and 1992 unilateral, segmental bilioenteric bypass-procedures (30 round ligament approach procedures, 4 peripheral bypass-procedures to the segment III bile duct and 3 to the segment V bile duct) were carried out in 37 icteric patients (twenty cholangio-carcinomas, 8 gallbladder-carcinomas, 6 other malignomas, 3 benign strictures). Postoperative complications were seen in 17 (46%) patients. The 30 day mortality rate was 3% (1/37). Relief of symptoms were achieved in 83% of patients. Objectively there was a significant postoperative reduction of serum bilirubin levels from mean 323 mumol/l to 109 mumol/(p < 0.005) and of the alkaline phosphatase from 708 U/l to 336 U/l (p < 0.005) respectively. This was achieved irrespectively of whether the segmental bypass was draining a segment only or the whole liver. Unilateral segmental bilioenteric bypass-procedures achieve an effective palliation in the majority of patients.

Purpose: The endoscopic treatment of malignant hilar obstruction is followed in 70% of the case by infection of undrained biliary sectors. We report the influence of complete biliary drainage on post procedural cholangitis., Method: From January 1990 to January 1993 we treated 120 consecutive patients presenting with a malignant hilar obstruction. There were 61 women and 59 men, mean age 65 +/- 7.5 years. The level of stenosis was type II in 45 patients (37%), type III in 18 patients (13%) and above type III in 57 patients (48%). Complete biliary drainage with multiple biliary access was attempted in all patients. Long term internal drainage was achieved by metallic autoexpansive endoprosthesis., Results: Complete drainage was achieved in all patients with type II or type III biliary stenosis. Drainage was incomplete in all patients with biliary stenosis above type III. Early complications were observed in 35% of the patients. Persistent cholangitis, the most frequent complication (22%) was only observed in patients with above type III biliary stenosis. Mortality at 30 days was 17%. Recurrent biliary obstruction was observed in 22% of the patients after an average of 187 days. Median survival was 95 days., Conclusion: Complete biliary drainage prevents persistent cholangitis in patients with type II or III biliary stenosis without increasing other complications related to biliary drainage.

The results of endoscopic drainage treatment in 69 patients with metastases of the liver have been analyzed for the period from 1982 to 1992. Fifty-five patients had follow-up. Criteria for inclusion were: positive diagnosis of liver metastases, jaundice, and primary origin of tumors distant from the pancreaticobiliary system ("distant" primary). Localisations of metastic obstructions were: hilum of the liver (n = 24), commonbile duct (n = 16), and prepapillary region (n = 15). Treatment was performed by transpapillary applications of one or more (n = 3) pig-tail or Tannenbaum stents. Concentrations of mean serum bilirubin could be reduced from 14.5% to 8.8 mg%, 16 patients reached a normal level (less than 1.0 mg%). The median survival time was 76 days ranging vom 4 to 299 days. The most frequent complication was cholangitis in 29% of the cases with mortality in 6 patients. Patients less than 60 years of age and with obstructions in the mid commonbile duct gained most by this kind of treatment. Results were poor in elderly patients with hilar stenosis. Selected patients with known liver metastases may benefit from endoscopic treatment of jaundice.

The article deals with experience in the treatment of 187 patients (in 1980-1992) with cicatricial stricture of the hepatic ducts in the region of their coalescence (0 stricture). A high cholecystoenteric anastomosis, was formed, on a transhepatic drain in 117 (group I) and a precision anastomosis in 70 patients (group II). Analysis of the results of the operations showed that in group I patients, the early postoperative period was quite severe with the development of specific complications due to use of a replaceable transhepatic drain (hematobilia, leakage of bile into the subdiaphragmatic space, subdiaphragmatic abscess). Ten patients died (8.5%), a recurrent stricture was encountered in 4 patients. In group II patients, the early postoperative period followed a favorable course, there were no fatal outcomes, only one patient had a recurrent stricture. Experience shows that a high precision cholecystoenteric anastomosis can be formed in cicatricial stricture of the hepatic ducts in the region of their coalescence by means of some methodical manipulations. However, it should not be considered an alternative to operations with framed drainage of the bile-draining anastomosis.

Debate continues regarding the optimal management of irresectable malignant proximal biliary obstruction. Controversy exists concerning the ability of unilateral drainage to provide adequate biliary decompression with tumors that have occluded the communication between the right and left hepatic ductal systems. Between October 1986 and October 1989, 18 patients with malignant proximal biliary obstruction were treated by an intrahepatic biliary enteric bypass. Patients were divided into two groups based on the presence or absence of a communication between the right and left biliary systems. In Group I (n = 9), there was free communication; and in Group II (n = 9) there was no communication. There were two perioperative deaths (11%) one due to persistent cholangitis and the other to myocardial insufficiency both with one death in each group. The median survival (excluding perioperative deaths) was 5.6 months. Comparison of pre- and postoperative serum levels of bilirubin and alkaline phosphatase showed a significant decrease in each group, but no difference between the groups in the size of the reduction. Sixteen patients survived at least three months and the palliation was judged as excellent in eight, fair in five, and unchanged in three. These results demonstrate the effectiveness of biliary enteric bypass regardless of communication between the left and right biliary ductal systems.

Prior variceal bleeding may adversely affect the prognosis of orthotopic liver transplantation. We studied this question by evaluating all 175 adult patients undergoing orthotopic liver transplantation at our institution to determine risk factors associated with mortality after transplantation. Seventy patients demonstrated prior variceal bleeding, and of those, 32 had a course of sclerotherapy. Thirteen also had portal systemic shunts. Compared with the 105 transplant patients who had no prior bleeding, patients who bled were more likely to have parenchymal liver disease (74% vs. 50%), equally likely to have cholestatic liver disease (19%), and less likely to have malignancy (6% vs. 19%) or fulminant liver failure (1% vs. 12%). Bleeding patients also were more likely to be Child-Pugh class C (46% vs. 35%). By the common closing date of December 31, 1990, 26 patients (37%) with prior bleeding and 48 patients (46%) without bleeding died after transplantation. From survival curves, patients with prior bleeding had improved survival rates at 1 yr (65% vs. 54%), at 3 yr (60% vs. 47%) and at 5 yr (55% vs. 43%), although the differences were not statistically significant. With a proportional hazards model to adjust for confounding effects, the relative risk of mortality among patients with prior bleeding was 0.60 (95% confidence interval, 0.27 to 1.30). Sclerotherapy or portal systemic shunts did not alter survival. Important adverse risk factors for mortality included older age at transplantation, black race, malignant disease and more advanced Child-Pugh class. This study suggests that prior esophageal variceal bleeding did not adversely affect the mortality of patients undergoing orthotopic liver transplantation.