Primary sclerosing cholangitis (PSC) can result in hepatic decompensation and require liver transplantation (LT). This study investigates the effect of the sex of the donor and recipient as a prognostic risk factor for adverse outcomes after LT in patients with PSC.

UNOS registry was used to select LT patients with PSC from 1987 to 2019. The study cohort was stratified based on the sex of the recipient and further subdivided based on the sex of the donor. The primary endpoints of this study were all-cause mortality and graft failure, which were evaluated using a sequential Cox regression analysis.

This study included 2829 patients; 906 female recipients were transplanted from 441 male donors and 465 female donors. 1923 male recipients were transplanted from 1194 male donors and 729 female donors. Within the mismatch analyses, the male-to-male recipients also had a significantly reduced hazard ratio of graft failure compared to female-to-male transplants [aHR 0.51, 95% confidence interval (CI) 0.33-0.79, P  = 0.003]. No difference in graft failure was observed in the mismatched female recipient subgroup. The mismatched male recipient group also showed a decreased hazard ratio of mortality from graft rejection and respiratory causes. No differences in specific mortality causes were identified in the mismatched female recipient group.

This study demonstrated an increase in the risk of graft failure and mortality secondary to graft failure in male recipients of female donor livers. No differences in mortality or graft failure were identified in female recipients of male livers.

Primary sclerosing cholangitis (PSC) is a rare disease in Asia, and few studies have investigated the disease in this ethnicity, particularly in wait-listed patients for liver transplantation (LT). We aimed to investigate the prognostic factors and outcomes of wait-listed patients with PSC in an Asian transplant center.

Survival was retrospectively analyzed.

Eighteen (10 male and 8 female) wait-listed patients with PSC, with a median age at diagnosis of 44.5 years, were included. Compared with men, women had significantly higher aspartate aminotransferase to platelet ratio index scores (3.28 vs. 1.13; P  = 0.012) and bilirubin levels (7.68 vs. 4.03 mg/dl; P  = 0.043) and more often presented with decompensating events, including ascites [5 (63%) vs. 1 (10%); P  = 0.043] and splenomegaly [8 (100%) vs. 4 (40%); P  = 0.013]. Compared with the non-LT group, the LT group exhibited a superior survival rate for women ( P  = 0.004) but not for men. In the univariable analysis, significant risk factors associated with overall survival included malignancies with a hazard ratio (95% confidence interval) of 5.53 (1.00-30.51) and esophageal varices (EV) [4.18 (1.05-16.61)], whereas female gender [25.00 (1.49-500.00)], LT [0.09 (0.01-0.80)] and EV [39.03 (2.92-521.96)] were indicated in the multivariable analysis.

For Asian wait-listed patients with PSC, EV and female gender were the risk factors related to overall survival, and LT was the protective factor. Our experiences suggested that LT brings more benefits in female patients. Strategies are needed to provide equivalent transplant benefits.

Scheduled endoscopic dilatation of dominant strictures (DS) in primary sclerosing cholangitis (PSC) might improve outcome relative to endoscopic treatment on demand, but evidence is limited. Since randomisation is difficult in clinical practice, we present a large retrospective study comparing scheduled versus on-demand endoscopic retrograde cholangiopancreatography (ERCP) based on patient preferences.

Between 1987 and 2017, all new patients with PSC had been offered scheduled ERCP with dilatation of a DS if diagnosed; the latter was repeated at defined intervals until morphological resolution, independent of clinical symptoms (treatment group). Patients who refused participation were clinically evaluated annually and received endoscopic treatment only on demand (control group). The primary clinical endpoint was transplantation-free survival. Secondary outcomes were overall survival, bacterial cholangitis episodes, hepatic decompensation of liver cirrhosis and endoscopy-related adverse events.

The final study included 286 patients, 133 (46.5%) receiving scheduled ERCP and 153 (53.5%) receiving on-demand ERCP. After a mean follow-up of 9.9 years, the rate of transplantation-free survival was higher in patients receiving scheduled ERCP (51% vs 29.3%; p<0.001), as was transplantation-free survival time (median: 17.9 vs 15.2 years; log-rank: p=0.008). However, the benefit of scheduled ERCP was significant only in patients with the initial (17.1%) or later (45.5%) diagnosis of a DS (17.8 vs 11.1 years; log-rank: p<0.001). IBD (p=0.03), DS (p=0.006), higher Mayo Risk Score (p=0.02) and non-adherence to scheduled endoscopy (p=0.005) were independently associated with transplantation-free survival.

In our large retrospective study, regular ERCP with endoscopic balloon dilatation significantly benefits patients with PSC with DS, diagnosed both at initial presentation and during surveillance, even if asymptomatic. Further studies have to find out how to best identify stricture patients non-invasively.

This study investigated the impact of Model of end-stage liver disease (MELD)-score introduction (MELDi) on waitlist mortality and post-liver transplant (LT) survival in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

LT candidates with PSC or PBC listed between January 1983 and March 2016 were included and followed until December 2016. After MELDi in 2004, PBC patients were listed according to labMELD, PSC patients according to the highest MELD during active cholangitis (chMELD).

In total, 100 PBC and 76 PSC patients were included. Waitlist mortality in PBC was significantly higher than in PSC (16% vs. 5.3%, p = 0.031), whereas PSC patients were significantly more often withdrawn from the waitlist due to improved condition (3.0% vs. 13.2%, p = 0.017). Competing risks analysis identified MELDi (HR = 4.12) and PBC (HR = 2.95) as significant predictors of waitlist mortality. Yet, overall 10 y-patient survival increased after MELDi by 18.8% leading to a 1 y-, 5 y-, and 10 y-patient survival of 98.2%, 70.6% and 70.6% in PBC, and 83.3%, 83.3%, and 80.6% in PSC, respectively.

PSC patients showed significantly lower waitlist mortality irrespective of MELDi, whereas in PBC waitlist mortality further increased after MELDi. Utility of MELD and chMELD did not impair post LT outcome.

Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is an important differential diagnosis in patients presenting with cholestasis and PSC-like cholangiographic changes in endoscopic retrograde cholangiography (ERC). As a relatively newly described entity, SSC-CIP is still underdiagnosed, and the diagnosis is often delayed. The present study aims to improve the early detection of SSC-CIP and the identification of its complications.A total of 2633 records of patients who underwent or were listed for orthotopic liver transplantation at the University Hospital Charité, Berlin, were analyzed retrospectively. The clinical presentation and outcome (mean follow-up 62.7 months) of the 16 identified SSC-CIP cases were reviewed.Cholestasis was the first sign of SSC-CIP. GGT was the predominant enzyme of cholestasis. Hypercholesterolemia occurred in at least 75% of the patients. SSC-CIP provoked a profound weight loss (mean 18 kg) in 94% of our patients. SSC-CIP was diagnosed by ERC in all patients. The 3 different cholangiographic features detected correspond roughly to the following stages: (I) evidence of biliary casts, (II) progressive destruction of intrahepatic bile ducts, and (III) picture of pruned tree. Biliary cast formation is a hallmark of SSC-CIP and was seen in 87% of our cases. In 75% of the patients, the clinical course was complicated by cholangiosepsis, cholangitic liver abscesses, acalculous cholecystitis, or gallbladder perforation. SSC-CIP was associated with worse prognosis; transplant-free survival was ∼40 months (mean).Because of its high rate of serious complications and unfavorable prognosis, it is imperative to diagnose SSC-CIP early and to differentiate SSC-CIP from other types of sclerosing cholangitis. Specific characteristics enable identification of SSC-CIP. Early cooperation with a transplant center and special attention to biliary complications are required after diagnosis of SSC-CIP.

Little data concerning hospital charges and long-term outcomes of LDLT in North American children according to transplant indications have been published. To compare outcomes of patient and graft survival and healthcare charges for LDLT for those with BA vs. other diagnoses (non-BA). A retrospective review of 52 children receiving 53 LDLT (38 BA and 14 non-BA) from 1992 to 2010 at our institution was performed. One-, five-, and 10-yr patient and graft survival data were comparable to national figures reported to UNOS. Average one-yr charges for recipients and donors were $242 849 for BA patients and $183 614 for non-BA (p = 0.074). BA patients were 1.23 ± 1.20 yr of age vs. 4.25 ± 5.02 for non-BA, p = 0.045. Examination of the total population of patients who were alive in 2010 in five chronological groupings showed that the crude five-yr survival rates were 1992-1995: 9/11 (82%); 1995-1997: 6/10 (60%); 1997-1999: 8/10 (80%); 1999-2001: 9/10 (90%); and 2001-2003: 7/7 (100%). Thus, examination of the clinical and financial data together over the entire period of the transplant program suggests that the dramatic improvement in patient survival was accomplished without a dramatic increase in indexed charges. All 53 donors survived, and only 10% had complications requiring hospitalization. LDLT in children results in excellent outcomes for patients and donors. Ways to lower costs and maximize graft outcome should be investigated.

Although there are no specific age-related liver diseases, it is increasingly recognized that the percentage and the actual number of elderly will increase substantially over the next twenty years. Moreover, the developments of new emerging conditions (e.g. non-alcoholic steatohepatitis) and novel therapeutic approaches have provoked increasing enthusiasm among hepatologists. Some liver diseases are particularly frequent in the elderly, e.g. chronic hepatitis C and hepatocellular carcinoma. The clinical course and management of liver disease in the elderly may differ in several aspects from those of younger adults. The problem of whether to offer antiviral treatment to a wide range of patients with chronic hepatitis C has arisen over the last eight to ten years, since the reduction in the risk of hepatocellular carcinoma was analyzed. Selected patients aged 65 and older have a chance of treatment with pegylated interferon plus ribavirin, despite a higher likelihood of side effects. The diagnosis of autoimmune hepatitis should be suspected in a patient over 65 years of age in case of 'acute' presentation with 10-fold increase in transaminases, jaundice and hyper-gammaglobulinemia, to avoid any delay in starting immunosuppressive therapy. The age of an end stage liver disease will increase over the next years, thus we will expects an increasing number of decompensated liver disease and hepatocellular carcinomas.

The prognosis of patients with primary sclerosing cholangitis (PSC) can be accurately determined using the Mayo Clinic Score (MRS), a mathematical model which predicts patient survival. The purpose of our study was to determine the risk of graft loss and/or death among patients who were listed or transplanted because of PSC.

We analyzed the data of 52 patients, who were placed on the transplant list due to PSC between January 2000 and November 2008 and either did or did not undergo liver transplantation (OLT). The primary end point (EP1) of the study was the patient death for any cause. The secondary end point (EP2) was recurrence of PSC or appearance of CCC or death related to the primary liver disease after OLT (PSC recurrence). The observation time was 60 months. According to the calculated MRS, patients were divided into 3 groups: group A (MRS < 0.56); group B (0.56 < or = MRS < 1.56), and group C (MRS > 1.56). The analysis was performed using the LIFETEST and PHREG Procedures of the SAS System.

The risk of EP1 occurrence was 2.0 per 1 point of MRS (P < .0006). The risk of EP2 was 2.1 per 1 point of MRS (P < .001). Groups B and C compared with group A showed risks of death of: 0.79 (P = NS) and 6.59 (P < .08), respectively. The percentage of 5-year patient survival rate were 94%, 94%, and 45% according to groups A, B, and C, respectively.

The risk of death in patients with MRS > 1.56 was 6.59-fold higher than those with MRS < 0.56. MRS > 1.56 significantly decreased 5 year survival among patients with primary sclerosing cholangitis.

The current study presents 1 tertiary endoscopy center's 20-year experience using endoscopic therapy to treat patients with symptomatic primary sclerosing cholangitis (PSC).

Endoscopic therapy for patients with PSC and dominant strictures has been used for more than 20 years, but there is concern that instrumenting a sclerotic biliary tree induces risks that outweigh anticipated benefits.

In this retrospective chart review, 117 patients with PSC were identified using ICD-9 codes. Patients had a mean age of 47 years (range: 15 to 86 y). Mean duration of follow-up was 8 years (range: 2 to 20 y). Of the 117 identified patients, 106 underwent endoscopic retrograde cholangiopancreatography on one or more occasions (for a total of 317 endoscopic retrograde cholangiopancreatographies), and a subset of 84 patients received endoscopic therapy for treatment of dominant strictures and/or deteriorating clinical status. Actual survival for endoscopically treated patients was compared with predicted survival using the Mayo Clinic natural history model for PSC.

Our chart review revealed 23 recognized complications among the 317 procedures performed (7.3%), and no procedure-related deaths. Observed patient survival at years 3 and 4 was significantly higher than that predicted by the Mayo Clinic natural history model for PSC (P=0.021).

Patients with PSC who have a deteriorating clinical course benefited from endoscopic therapy to provide drainage of bile ducts, removal of stones, and/or temporary relief from obstructions, with acceptable procedure-related complications and higher than expected 3-year and 4-year survival.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by progressive inflammation and fibrosis of the bile ducts, resulting in biliary cirrhosis and is associated with a high risk of cholangiocarcinoma. The majority of patients are young, male and have coexisting inflammatory bowel disease. PSC is found with a prevalence of 10/100,000 in Northern European populations. The pathophysiology of PSC is a complex multistep process including immunological mechanisms, immunogenetic susceptibility and disorders of the biliary epithelia. The diagnosis is primarily based on endoscopic cholangiography although magnetic resonance imaging is increasingly used; biochemistry and immunoserology as well as histology play only a minor role. Due to the high risk of developing cholangiocarcinoma and also other tumours of the GI tract, surveillance strategies are essential, however they have yet to be established and evaluated. Biochemical parameters, clinical risk factors, endoscopic procedures and imaging techniques contribute to the early identification of patients at risk. Since medical therapy of PSC with ursodeoxycholic acid does not improve survival, to date, liver transplantation is the only option with a cure potential; if transplantation is accurately timed, transplanted PSC patients have an excellent rate of survival. However if cholangiocarcinoma is detected, a curative treatment is not possible in the majority of cases. The present review critically summarizes the current knowledge on the aetiopathogenesis of PSC and gives an overview of the diagnostic approaches, surveillance strategies and therapeutic options. Primary sclerosing cholangitis is a disease of unknown aetiology and without any further curative treatment options apart from liver transplantation. Therefore it may be regarded as the greatest challenge in hepatology today.

Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5-year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC; however, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG-PET results with histology of explanted livers. Dynamic FDG-PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high-grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver. In conclusion, dynamic FDG-PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG-PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC.

Primary sclerosing cholangitis (PSC) is an important cause of chronic liver disease. We review the management of PSC and report a 20-year follow-up of our initial 10 patients. This is the longest detailed follow-up of a group of PSC patients to date. We discuss the clinical course and results of endoscopic management in these patients and relate these data to management of PSC in general. We compare the actual survival of these patients to predicted survival scores based on the Mayo multicenter survival model. Although our patients presented with cholangitis, which typically reflects advanced stages of liver disease, their survival compares favorably with expected survival in unselected PSC patients. Endoscopic balloon dilation of PSC patients presenting with biliary strictures and cholangitis may have long-term benefit in addition to short-term symptomatic relief.

To determine the efficacy and potential complications of oral naltrexone used in the treatment of pruritus in cholestatic patients and to compare them with other studies.

Thirty-four enrolled cholestatic patients complaining of pruritus were studied. In the initial phase, pruritus scores during day and night were evaluated. Subsequently, patients were given a placebo for one week followed by naltrexone for one week. In each therapeutic course (placebo or naltrexone) day and night pruritus scores were distinguished by a visual analogue scale (VAS) system and recorded in patients' questionnaires.

Both naltrexone and placebo decreased VAS scores significantly. Naltrexone was more effective than placebo in decreasing VAS scores. Both day and night scores of pruritus decreased by half of the value prior to therapy in thirteen patients (38%). Daytime pruritus improved completely in two patients (5.9%), but no improvement in the nighttime values was observed in any patient. Sixteen patients (47%) suffered from naltrexone complications, eleven (32%) of them were related to its withdrawal. Complications were often mild. In the case of withdrawal, the complication was transient (within the first 24-28 h of therapy) and self-limited. We had to cease the drug in two cases (5.9%) because of severe withdrawal symptoms.

Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.

To compare the direct health care cost of living donor liver transplantation (LDLT) with that of cadaver donor liver transplantation (CDLT) in children and identify predictors of cost.

All 16 children who underwent LDLT from January 1997 through January 2002 at Cincinnati Children's Hospital Medical Center comprised the study population. They were matched for age, diagnosis, and nutritional status with 31 children who received CDLT during the same era. A historic cohort analysis was performed.

There was no difference in the 1-year mortality rates between both groups. Costs associated with graft retrieval contributed 15.3% and 31% of the initial transplant cost for LDLT and CDLT, respectively. Mean cost of care in the first year was 60.3% higher for LDLT than CDLT (P=.01). Multivariate analysis identified biliary complications and insurance status as predictors of cost for initial transplantation (R(2)=0.57), whereas biliary complications and pediatric end stage liver disease scores were identified as predictors of cost of care in the first year after transplantation (R(2)=0.77).

The comprehensive cost of LDLT in the first year after transplantation is higher than cadaveric transplantation. This must be balanced against the time spent and care needs of patients on the waiting list.

Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation.

Data from all Nordic PSC patients listed for liver transplantation during 1990-2001 were recorded prospectively. Predictors of hepatobiliary malignancy and patient survival rates have been analysed.

Hepatobiliary malignancy was found in 52/255 (20%) patients accepted to the waiting list. Recent diagnosis of PSC, no ursodeoxycholic acid (UDCA) treatment, clinical suspicion and previous colorectal-cancer were predictors of malignancy. Among 89 patients with a strong suspicion of malignancy prior to acceptance, 35 (39%) had confirmed malignancy. A clinical suspicion had been raised in 35/52 (67%) patients with malignancy. Malignancy was found in 31/223 patients who received a liver allograft. The 1-, 3- and 5-year patient survival rates following transplantation for patients with PSC and cholangiocarcinoma were 65, 35 and 35%, respectively.

Hepatobiliary malignancy is suspected in 1/3 of the PSC patients and found in 1/5. Although cholangiocarcinoma is regarded as a contraindication to liver transplantation (LTX), PSC patients with cholangiocarcinoma had a 35% 5-year survival following transplantation.

Exactly what constitutes a marginal donor remains ill defined. The authors set out to create a scoring system that objectively classifies a donor as marginal or nonmarginal and to define what the maximum acceptable preservation period is for the marginal liver to minimize early graft dysfunction.

The authors performed an analysis on data collected prospectively of 397 cadaveric liver transplants. Both univariate and multivariate analyses were performed on donor, recipient, and perioperative factors with relation to early allograft dysfunction. A score was developed that classified donors into marginal and nonmarginal populations, and the influence of cold ischemia was determined for each group.

Multivariate analysis-determined donor age and steatosis (moderate to severe) were independent predictors of deranged function. This enabled the authors to produce a scoring system to differentiate marginal donors with respect to risk of early allograft dysfunction as follows: Formula=(20.06xsteatosis)+(0.44xdonor age), cutoff 23.1. In the marginal group, the cutoff value of cold ischemia time was 12.6 hr.

The authors developed a scoring system that classified an organ as marginal or nonmarginal depending on the donor age and degree of steatosis. Marginal livers have a strong risk of developing early allograft dysfunction with increasing cold ischemia times and should be transplanted within 12 hr. Cold ischemia time was not found to be an important factor in the development of early allograft dysfunction in nonmarginal donors.

The cause of the pruritus of cholestasis is unknown. It is inferred that pruritus results from the accumulation in plasma of substances that are made in the liver and excreted in bile under physiologic conditions. The idea of neurotransmitters as important mediators in the pruritus of cholestasis has evolved over the past several years. There is evidence to suggest that endogenous opioids contribute to the pruritus of cholestasis and, for the first time, specific treatment for the pruritus has been instituted. The deficiency of studying pruritus with subjective methodology alone has been overcome with the development of objective methodology to study the behavioral manifestation of pruritus, scratching behavior. The use of this tool allows the definition of clear objective end-points, scratching activity, for inclusion in clinical trials.

Primary sclerosing cholangitis (PSC) is the most common indication for liver transplantation in the Nordic countries. Because these patients are difficult to evaluate with regard to timing of liver transplantation, it is important to establish predictors of post-transplant survival.

Data from two groups of patients receiving liver allografts during 1982-2001 were recorded: (a) PSC patients and (b) comparison patients. Outcome following transplantation has been recorded for all patients. Regression analyses have been performed for PSC patients to analyse predictors of patient and graft survival.

A total of 245 PSC and 618 comparison patients received a first liver allograft in the period 1982 until the end of the study. The overall 1-, 3- and 5-year patient survival rates were 82%, 77% and 75%, and 80%, 77% and 74% in the PSC group and comparison group, respectively. Survival following transplantation has increased with time in both the PSC and the comparison group. Recent year of transplantation, no previous hepatobiliary surgery and a lower MELD score were predictors of survival following transplantation for PSC patients. PSC patients had a higher rate of re-transplantations (13% versus 8%, P = 0.01). Predictors of re-transplantation in PSC patients were an episode of early rejection and vascular thrombosis.

In PSC patients, year of transplantation, previous hepatobiliary surgery and MELD score are predictors of survival following transplantation and these patients are more frequently in need of re-transplantation compared to the comparison group.

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation, but evaluation of patients and timing of liver transplantation remain as major problems. Data from PSC and control patients listed for liver transplantation from 1990 through 2000 in the Nordic countries were recorded prospectively. Outcomes from the waiting list and after transplantation have been recorded for both groups. For PSC patients, regression analyses have been performed to analyze predictors of outcome. A total of 255 PSC and 610 control patients were accepted on the liver transplantation waiting list from 1990 to 2000. In the PSC group, 223 patients (87%) received a first liver allograft, and 32 patients (13%) died without transplantation. The corresponding figures for the control group were 89% and 10%. For PSC patients, the 5- and 10-year survival from the time of acceptance was 68% and 58%, respectively. A higher Model for End-Stage Liver Disease score and a shorter duration of PSC predicted death on the waiting list for PSC patients. PSC is a frequent indication for liver transplantation. In our material, serum bilirubin or Model for End-Stage Liver Disease score and PSC duration are predictors of outcome including survival of the waiting list.

To evaluate gastrointestinal permeability in primary biliary cirrhosis (PBC), using a sensitive method to detect epithelial damage, and to correlate it with the Mayo score, histological stage, ascites, spontaneous bacterial peritonitis, endoscopic signs of portal hypertension and Helicobacter pylori infection.

Fifty consecutive patients with PBC and 39 patients with cirrhosis of other aetiologies (non-PBC) were enrolled in the study. Coeliac disease was initially ruled out in all participants. Permeability was assessed using sucrose (gastro-duodenum) and lactulose-mannitol (intestine).

Sucrose excretion was above the limit in both PBC and non-PBC patients. Twenty-two per cent of PBC patients had an increased result for the lactulose-mannitol test compared to 12.8% of non-PBC cirrhotic patients. PBC patients had high sucrose excretion levels irrespective of the presence of any oesophageal varices, which significantly increased the gastroduodenal permeability in non-PBC patients only when associated with hypertensive gastropathy. Sucrose excretion was significantly enhanced by hypertensive gastropathy in non-PBC patients (P < 0.001) but not in PBC patients. No significant correlation was found in either group between gastrointestinal permeability and the other parameters.

Gastrointestinal permeability is increased in PBC. Portal hypertension contributes to altered gastric mucosal permeability in non-PBC cirrhosis, whereas different epithelial dysfunction can be hypothesized in PBC.

To assess the efficacy and safety of naltrexone for the short and long term treatment of pruritus of cholestasis.

Twenty patients with pruritus and cholestasis were included. A baseline pruritus score was obtained over 1 week. Patients were then randomized to receive 50 mg/day of naltrexone or placebo for 2 weeks. Subsequently, a 1-week washout period ensued and patients were crossed over to the other therapy for 2 additional weeks. Pruritus was assessed daily with a visual analogue scale (VAS) from 0 to 10. Patients whose pruritus decreased >50% of basal with naltrexone received naltrexone 50 mg/day for 2 additional months.

Mean basal VAS was similar in both groups. VAS showed greater and more significant changes with naltrexone than with placebo (P<0.0003). In nine out of 20 patients (45%) receiving naltrexone, pruritus decreased >50% compared to basal value, including five whose pruritus disappeared completely. No significant changes were observed in serum biochemistry. Most of the adverse events that occurred during the first 48 h of naltrexone therapy were consistent with opioid withdrawal-like phenomena and spontaneously disappeared 2 days after starting treatment.

Naltrexone can be considered as an alternative option to treat pruritus of cholestasis. In the current study, side effects were transient and did not require specific medication.

To evaluate and compare clinical, pathologic, and helical computed tomographic (CT) findings of primary biliary cirrhosis (PBC).

The authors reviewed the medical records and CT scans of 53 patients who underwent evaluation, treatment, and orthotopic liver transplantation (OLT) at their institution. All patients underwent helical multiphase CT (total, 98 abdominal CT scans; range, one to five scans per patient). Multiple epidemiologic, clinical, and morphologic criteria were evaluated. Advanced disease was defined as hepatic insufficiency leading to OLT within the subsequent 2 years. Clinical and morphologic features were evaluated and compared in the advanced and less advanced cases of PBC.

Common and characteristic findings included the following: 45 (85%) of the 53 patients were women with the onset of disease (diagnosis) in middle age (mean, 50.7 years; range, 26-71 years). The average time from diagnosis to OLT was 6.1 years (range, 1.5-20.0 years). CT findings in advanced PBC often resembled those seen in other forms of cirrhosis, with a small heterogeneously attenuating liver, varices, and splenomegaly. The liver in less advanced disease was usually enlarged or normal in size, with a smooth contour, little atrophy, and lacelike fibrosis and regenerative nodules in nearly one-third of the livers. Patients with less advanced disease frequently had varices (n = 33 [62%]) and ascites (n = 13 [24%]). Lymphadenopathy was seen in 47 (88%) patients. Hepatocellular carcinoma was found in four (8%) patients, two of whom also had chronic hepatitis C. During a follow-up period of 5-72 months (median, 46 months; mean, 42 months) after OLT, only two patients experienced recurrence of PBC.

PBC is an important cause of liver failure, with distinctive clinical and CT findings that may assist diagnosis and allow adequate treatment. CT can demonstrate varices and ascites before frank cirrhosis is evident and can help evaluate the progression of the disease.

[corrected] Hepatobiliary carcinoma (HBC) has been considered to be a late complication of end-stage primary sclerosing cholangitis (PSC). The incidence of HBC is approximately 20% in PSC patients evaluated for liver transplantation. The diagnosis of HBC is difficult, at least at an early stage and the prognosis is poor even after liver transplantation. The aim of the study was to look for signs and risk factors for developing hepatobiliary carcinoma in patients with PSC.

Thirty-six consecutive patients with PSC and HBC (32 with bile duct carcinoma, BDC, and four with hepatocellular carcinoma, HCC) were pair-matched to control patients referred for liver transplantation because of PSC but who did not have HBC. Gender and age at referral were used as matching factors. Clinical and biochemical data were registered.

PSC patients with BDC had a shorter median duration of PSC (1 year) compared with the controls (7 years) and PSC patients with HCC (8 years). There were no statistically significant differences in the liver biochemistry between the patient groups. Varices were more common in patients with PSC and HCC (100%) than in controls (56%) or patients with PSC and HBC (12%) (P < 0.0005).

The relatively short duration of PSC and the absence of varices in patients with BDC suggest that BDC, unlike HCC, is not necessarily a late complication of end-stage PSC, as was previously assumed.

Issues in the selection and timing of liver transplantation for primary sclerosing cholangitis (PSC) remain controversial. Although the Child-Pugh classification (CP) score and Mayo PSC model have similar abilities to estimate pretransplantation survival, a comparison of these 2 scores in predicting survival after liver transplantation has not been conducted. The aim of this study is to compare the Mayo PSC model and CP score in predicting patient survival and related economic outcomes after liver transplantation. Data from 128 patients with PSC, identified from the NIDDK database, were used to calculate patient-specific Mayo PSC and CP scores before transplantation. Levels reflecting a poor outcome were defined a priori. Receiver operating characteristic (ROC) curves and regression methods (Cox proportional hazards and linear regression models) were used to assess the relationship between these 2 scores and 5 post liver transplantation outcome measures. CP score was found to be a significantly (P <.05) better predictor of death 4 months or less after liver transplantation than: (a) length of hospital stay >21 days (or death before discharge) and (b) resource utilization >200,000 units (measured by area under the ROC curve). The Cox model identified statistically significant (P <.05) associations between CP score and each outcome after adjusting for the Mayo PSC risk score. Similar results were not observed for the Mayo PSC model when adjusted for CP score. Among patients with PSC undergoing liver transplantation, CP score was a better overall predictor of both survival and economic resource utilization compared with the Mayo PSC model.

For many patients with malignant disease of the liver, liver transplantation offers the only opportunity for clinical cure or prolonged palliation. As a result of organ scarcity, patients are increasingly selected on the basis of tumour stage and with the predictable likelihood of prolonged survival in mind. Consequently, 3- and 5-year survival rates of 72% and 68% respectively have been described for patients transplanted with hepatocellular carcinoma for tumours measuring less than 5 cm in diameter or up to three in number. Moreover, many centres are developing adjuvant and neo-adjuvant therapeutic protocols to minimize the risks of disease recurrence following transplantation for malignancy. In this chapter, we review the current knowledge in relation to transplantation for hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, cholangiocarcinoma, metastatic neuroendocrine tumours, secondary solid tumours and other rarer malignancies.

The case of a 74-year-old female patient who underwent a right hepatic lobectomy for hepatocellular carcinoma (HCC) which developed in primary biliary cirrhosis (PBC) is reported herein. During a follow-up examination for Parkinson's disease, an elevation of hepatobiliary tract-related enzymes and alpha-fetoprotein was uncovered. Diagnostic imagings showed a hypervascular, solitary, and encapsulated tumor measuring about 7 cm in diameter located mainly in the posterior segment. Positive antimitochondrial and antinuclear antibodies and a preoperative liver biopsy strongly suggested well differentiated HCC developed in PBC (Scheuer's classification stage II). Since the natural prognosis of PBC estimated by the Mayo risk score was fairly good and the liver function indicated sufficient tolerance for major hepatic resection, and preoperative computed tomography (CT) volumetry showed the atrophy of the right hepatic lobe, a right hepatic lobectomy was performed. A pathological examination revealed well encapsulated, moderately differentiated HCC with, in part, well-differentiated HCC in the tumor and stage II PBC in the noncancerous region. CT volumetry performed at postoperative day 14 showed a 146% enlargement of the remnant liver. An early detection of HCC and PBC by strict screening would prevent a limitation of surgical therapy due to a deteriorated liver function.

Primary biliary cirrhosis and primary sclerosing cholangitis are the most common chronic cholestatic liver diseases in adults that lead to biliary cirrhosis and its inherent complications such as portal hypertension and liver failure. Although important advances in the understanding of the pathogenesis of these conditions have been accomplished in the last two decades, much work is needed to uncover the interaction of genetic and immunologic mechanisms involved in their pathogenesis. Ursodeoxycholic acid at dosage of 13 to 15 mg/kg/d is the only agent that can currently be recommended in the treatment of PBC. No medical therapy aimed at disrupting disease progression is available for patients with primary sclerosing cholangitis, although several agents with different properties are currently under evaluation. Liver transplantation is the treatment of choice for patients with primary biliary cirrhosis and primary sclerosing cholangitis with end-stage liver disease.

Liver transplantation expanded rapidly during the first three decades of its application but has undergone slower growth over the past few years because of a limited supply of donor organs. The growing discrepancy between available donor organs and patients listed for transplantation has fuelled recent debate regarding patient selection criteria and listing policies for liver transplantation. Allocation and distribution regulations of the United Network for Organ Sharing have also recently undergone changes to balance the principles of utility (i.e. the overall benefits of liver transplantation to society) and justice (i.e. the needs of the individual patient). The ideal geographical area over which organs can be distributed to balance utility and justice remains uncertain, although there are pressures to widen sharing of donor organs. The sickest patient who has been waiting the longest still receive the next available donor organ, but listing policies for the sickest patients, those with fulminant hepatic failure or acute decompensation of chronic liver disease, were recently revised. A uniform minimal listing criteria that proposes listing patients when their estimated survival with liver disease is less than that expected after liver transplantation was recently proposed and has generally been accepted. Finally, cost-outcome analyses and the reality of managed care with the transfer of financial risk from insurers to providers is beginning to have an influence on patient selection criteria.

Liver transplantation remains the only treatment for patients with end-stage primary sclerosing cholangitis (PSC); however, selection criteria for the procedure and its timing remains uncertain. The aim of this study was to identify pretransplant variables associated with survival after transplantation and to devise a Cox regression model for prediction of post-transplant survival. We studied 118 patients transplanted for PSC at the Queen Elizabeth Hospital, Birmingham, UK, being followed for up to 91/4 years after the procedure. The association between pretransplant data and the post-transplant survival up to 1 year was studied using the logrank test (univariate analyses) and Cox multiple regression analysis. Univariate analyses showed the following variables to be associated with a decreased post-transplant survival: high serum creatinine, high serum bilirubin, biliary tree malignancy, previous upper abdominal surgery, hepatic encephalopathy, ascites, and Crohn's disease, whereas ulcerative colitis was associated with increased post-transplant survival (all P Collapse

There is ample reason to believe that UDCA is the drug of choice in cholestatic liver diseases. It is possible that UDCA has to be administered for prolonged periods to see appreciable reversal in liver damage. Nevertheless, the amelioration of symptoms and improvement in nutrition of patients are equally important. Disabling symptoms such as pruritus are often brought under control, and quality of life improves. Clearly the goal for UDCA therapy is to slow the rate of disease progression, lessen the mortality risk, and improve the quality of life in patients. It is possible that a combination therapy would be more beneficial than UDCA alone. Initial results of administering UDCA with colchicine have shown no improvement in liver histology; however, administration of UDCA together with a strong anti-inflammatory drugs may be helpful to halt immune destruction of liver cells.

In the current era of critical-organ shortage, one of the most controversial questions facing transplantation teams is whether hepatic retransplantation, which has historically been associated with increased resource utilization and diminished survival, should be offered to a patient whose first allograft is failing. Retransplantation effectively denies access to orthotopic liver transplantation (OLT) to another candidate and further depletes an already-limited organ supply. The study group was comprised of 1,356 adults undergoing hepatic retransplantation in the United States between 1990 and 1996 as reported to the United Network for Organ Sharing (UNOS). We analyzed numerous donor and recipient variables and created Cox proportional-hazards models on 900 randomly chosen patients, validating the results on the remaining cohort. Five variables consistently provided significant predictive power and made up the final model: age, bilirubin, creatinine, UNOS status, and cause of graft failure. Although both hepatitis C seropositivity and donor age were significant by univariate and multivariate analyses, neither contributed independently to the estimation of prognosis when added to the final model. The final model was highly predictive of survival (whole model chi2 = 139.63). The risk scores for individual patients were calculated, and patients were assigned into low-, medium-, and high-risk groups (P <.00001). The low degree of uncertainty in the probability estimates as reflected by confidence intervals, even in our high-risk patients, underscores the applicability of our model as an adjunct to clinical judgment. We have developed and validated a model that uses five readily accessible "bedside" variables to accurately predict survival in patients undergoing liver retransplantation.

The possibility of primary sclerosing cholangitis (PSC) recurrence after liver transplantation has been debated. The aim of this study is to examine whether recurrent PSC and chronic rejection (CR) are different expressions of the same disease process.

One hundred consecutive patients receiving 118 grafts for the diagnosis of PSC were reviewed and placed into three groups: group A, recurrent disease, as evidenced by cholangiographic and pathologic findings with radiographic arterial flow to the liver (n=18; 15.7%); group B, those who developed CR (n=15; 13.0%); and group C, all others (n=82; 71.3%). Cholangiograms and histopathologic specimens were examined in a blinded fashion.

Demographic factors were similar, except for age, with a significantly younger age and more episodes of rejection in groups A and B (P<0.03). Group A had a higher incidence of cytomegalovirus hepatitis (P=0.008). Five-year graft survivals for A, B, and C were 64.6%, 33.3%, and 76.1%, respectively (P=0.0001), 5-year patient survivals were 76.2%, 66.7%, and 89.1%, respectively (P=0.0001), and repeat transplantation rates were 27.8%, 46.7%, and 8.5%, respectively (P=0.005). Radiographically, 90% of cholangiograms in patients with recurrent disease showed at least multiple intrahepatic strictures. Histopathologically, patients with recurrent disease and CR shared many features.

We have described a high incidence of recurrent PSC and CR in patients who received transplants for PSC. Histopathologic analysis suggests that CR and recurrent PSC could represent a spectrum of indistinguishable disease. However, the distinct difference in clinical outcome, as evidenced by an increased repeat transplantation rate and lower graft and patient survival in the CR group, clearly suggests that they are two distinct entities that require very different treatment strategies.

Prior studies evaluating the impact of race and payer on cost of liver transplantation did not adjust for clinical factors known to increase cost. We analyzed the impact of race and payer on the cost of liver transplantation after controlling for clinical factors. We analyzed data obtained on patient and graft survival, cost, race, age, sex, payer, and United Network for Organ Sharing (UNOS) status from 153 consecutive liver transplants in 130 patients performed at University of North Carolina Hospitals from September 1991 through December 1996. Race was classified as white or nonwhite, and payer status was classified as commercial or Medicare/Medicaid. Multivariate linear regression was used to compare costs, adjusting for age, sex, race, payer, and UNOS status. For the 130 patients, 1-year patient and graft survival rates were 88% and 82%, respectively. There were no significant differences in patient and graft survival or in the unadjusted average cost of liver transplantation by race or payer. After adjusting for demographic and clinical factors, the cost of transplantation was $28,494 more for Medicare/Medicaid recipients compared with the commercial insurance recipients (P = .02). The Medicare/Medicaid group had higher intensive care unit costs compared with the commercial insurance group ($17,807 and $9,359, respectively; P = .03), and a longer length of stay (41 and 31 days, respectively; P = .04). There was no significant difference in cost between whites and nonwhites adjusting for these factors. Medicare or Medicaid patients had a higher cost of transplantation compared with those with commercial insurance. The cost of liver transplantation was similar for whites and nonwhites.

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC), which usually is widespread in the liver at the time of the diagnosis and which has a median survival of approximately 6 months. Positron emission tomography (PET) is a noninvasive scanning method that allows the assessment of metabolism in vivo by means of positron-emitting radiolabeled tracers. [18F]Fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue that accumulates in various malignant tumors because of their high glucose metabolic rates. The purpose of the study was to develop a PET method to detect small CC tumors in patients with PSC. PET scanning of the liver was performed after intravenous injection of 200 MBq FDG in 9 patients with PSC, 6 patients with PSC + CC, and 5 controls. The scanning was performed at successive time intervals for a total of 90 minutes with simultaneous successive arterial blood sampling for radioactivity concentration determination. In each of the PSC + CC patients, 2 to 7 "hot spots" were seen, with volumes of 1.0 to 45 mL (median, 4.4 mL). There were no hot spots in the two other patient groups. The localization of hot spots was confirmed by single-blind evaluation. Data were analyzed by the Gjedde-Patlak plot, yielding values of the net metabolic clearance of FDG, K [mL min(-1) 100 mL(-1) tissue]. In the CC hot spots, maximum K values were 1.59 to 4.17 (median, 2.34; n = 6); in the reference liver tissues of these patients, K values were 0.40 to 0.69 (median, 0.49); in PSC patients, they were 0.23 to 0.53 (median, 0.36); and in controls, they were 0.20 to 0.34 (median, 0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < .001). We conclude that FDG-PET seems to be able to detect small CC tumors and may be useful in the therapeutic management of PSC.

Poor graft function early after liver transplantation is an important cause of morbidity and mortality. We defined early allograft dysfunction (EAD) using readily available indices of function and identified donor, graft, and pretransplant recipient factors associated with this outcome.

This study examined 710 adult recipients of a first, single-organ liver transplantation for non-fulminant liver disease at three United States centers. EAD was defined by the presence of at least one of the following between 2 and 7 days after liver transplantation: serum bilirubin >10 mg/dl, prothrombin time (PT) > or =17 sec, and hepatic encephalopathy.

EAD incidence was 23%. Median intensive care unit (ICU) and hospital stays were longer for recipients with EAD than those without (4 days vs. 3 days, P = 0.0001; 24 vs. 15 days, P = 0.0001, respectively). Three-year recipient and graft survival were worse in those with EAD than in those without (68% vs. 83%, P = .0001; 61% vs. 79%, P = 0.0001). A logistic regression model combining donor, graft, and recipient factors predicted EAD better than models examining these factors in isolation. Pretransplant recipient elevations in PT and bilirubin, awaiting a graft in hospital or ICU, donor age > or =50 years, donor hospital stay >3 days, preprocurement acidosis, and cold ischemia time > or =15 hr were independently associated with EAD.

Recipients who develop EAD have longer ICU and hospital stays and greater mortality than those without. Donor, graft, and recipient risk factors all contribute to the development of EAD. Results of these analyses identify factors that, if modified, may alter the risk of EAD.

In patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), risk score models that reflect disease severity have been developed and can serve as an objective measurement to assess and evaluate the effect of the severity of liver disease on the outcome of liver transplantation. Thus, using the established Mayo risk scores for PBC and PSC, one not only can estimate survival for the individual patient but can measure disease activity as well. Indeed, several studies have suggested that the optimal timing of liver transplantation with use of the Mayo PBC model may be an important tool to improve survival, decrease morbidity, and decrease overall related costs. Likewise, studies in patients with PSC have yielded similar results. This review explores how prognostic mathematical survival models for PBC and PSC might be applied to individual patients in need of liver transplantation. The following question is addressed: How can the timing of liver transplantation be optimized to increase survival, decrease postoperative morbidity, and ultimately, decrease the overall resource utilization involved in this procedure?

Primary biliary cirrhosis, a chronic liver disease, predominately affects middle-aged women. The diagnosis is established by the presence of disease-specific autoantibodies and compatible liver histology showing focal immune-mediated damage to the intrahepatic bile ducts. Patients now are detected prior to the onset of symptoms typical of cholestasis with abnormal liver function tests, or even prior to the onset of abnormal liver function tests, with positive antimitochondrial antibodies. Earlier diagnosis is changing not only our appreciation of the prevalence of this condition, but also of the natural history. The disease appears to be heterogeneous with some patients having a slow progression and a normal life-expectancy, although other patients have a more aggressive course developing symptoms and end-stage disease that leads to death or liver transplantation.

Primary biliary cirrhosis is a slow, progressive disease. Although many years may elapse before asymptomatic primary biliary cirrhosis patients begin experiencing symptoms of liver disease, their overall survival is significantly lower than the normal population. The Mayo natural history model has been developed to depict patient survival in the absence of effective therapeutic intervention. Although there are a number of caveats in applying this model, it has been validated using external data sets and established as an accepted tool for clinical or research purposes. Furthermore, recent data suggest that the Mayo natural history model continues to provide useful, predictive information in the presence of ursodeoxycholic acid therapy, which has been shown to lower the serum bilirubin to the natural history model for patient survival. In addition to the natural history model for patient survival, mathematical models have been developed to describe histologic progression and development of esophageal varices.

Orthotopic liver transplantation (OLT) is a highly effective but costly therapy for end-stage liver disease. However, there are limited data on the demographic and clinical variables that affect cost. We undertook a preliminary study using multiple regression techniques to analyze factors that influence the cost of OLT.

Patient and demographic data, including laboratory values and charges for all liver transplantations performed between June 1992 and June 1993 were analyzed (n = 111). Linear regression with standard and log-transformed values was performed by using STATA software (Stata Corporation College Station, TX). Independent variables included in the analyses were age, sex, United Network for Organ Sharing (UNOS) status, primary versus retransplantation, liver-kidney transplantation, and laboratory parameters of both liver (aspartate aminotransferase, AST; alkaline phosphatase; bilirubin; albumin; and prothrombin time) and kidney (blood urea nitrogen, BUN; creatinine) function. An F-to-remove strategy was employed with a significance level set at P = .05.

The full model with 12 variables explained 37% of the total variation in charges. When one excludes variables that did not have a significant impact on cost, the remaining significant variables were BUN and UNOS status 1. The final model was Charges (US$) = 3,407 x BUN + 74,474 x status 1 + 102,662. This model accounted for 29% of the total variability with BUN accounting for the vast majority (26%).

Renal function is the most important predictor of cost of OLT (P < .001). UNOS status 1 further increases cost, but other hospitalized patients have similar costs when one controls for other clinical variables. The degree of liver impairment is less important in predicting cost.