Cholangiographic Changes Research Articles

Development of a prognostic MRCP-score (DiStrict) for individuals with large-duct primary sclerosing cholangitis

Magnetic resonance cholangiopancreatography (MRCP) is used for the diagnosis and follow-up of individuals with primary sclerosing cholangitis (PSC). The aim of our study is to develop an MRCP-score based on cholangiographic findings previously associated with outcomes and assess its reproducibility and prognostic value in PSC. The score (DiStrict score) was developed based on the extent and severity of cholangiographic changes of intrahepatic and extrahepatic bile ducts (range 0-8) on 3D-MRCP. In this retrospective, multicentre study, three pairs of radiologists with different levels of expertise from three tertiary centres applied the score independently. MRCP examinations of 220 consecutive individuals with PSC from a prospectively collected PSC-cohort, with median follow-up of 7.4 years, were reviewed. Inter-reader and intrareader agreements were assessed via intraclass correlation coefficient (ICC). After consensus, the prognostic value of the score was assessed using Cox-regression and outcome-free survival rates were assessed via Kaplan-Meier estimates. Harrell's C-statistic was calculated. Forty patients developed outcomes (liver transplantation or liver-related death). Inter-reader agreement between experienced radiologists was good (ICC 0.82; 95% CI 0.74-0.87, and ICC 0.81; 95% CI 0.70-0.87, respectively) and better than the agreement for the pair of experienced/less-experienced radiologists (ICC 0.48; 95% CI 0.05-0.72). Agreement between radiologists from the three centres was good (ICC 0.76; 95% CI 0.57-0.89). Intrareader agreement was good to excellent (ICC 0.85-0.93). Harrell's C was 0.78. Patients with a DiStrict score of 5-8 had 8.2-fold higher risk (hazard ratio 8.2; 95% CI 2.97-22.65) of developing outcomes, and significantly worse survival (p <0.001), compared to those with a DiStrict score of 1-4. The novel DiStrict score is reproducible and strongly associated with outcomes, indicating its prognostic value for individuals with PSC in clinical practice. The diagnosis of primary sclerosing cholangitis (PSC)is based on magnetic resonance cholangiopancreatography (MRCP). However, the role of MRCP in the prognostication of PSC is still unclear. We developed a novel, simple, and reproducible risk-score, based on MRCP findings, that showed a strong association with prognosis in individuals with PSC (DiStrict score). This score can be easily used in clinical practice and thus has the potential to be useful inclinical trials and in patient counselling and management.

Atypical presentation of autoimmune hepatitis\u2013primary sclerosing cholangitis overlap syndrome associated with hypereosinophilia: a case report and review of the\xa0literature

BackgroundAutoimmune hepatitis–primary sclerosing cholangitis overlap syndrome is a form of autoimmune hepatitis with cholestatic features and is characterized by negative anti-mitochondrial antibody and cholangiographic changes on magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography. Peripheral blood hypereosinophilia in conjunction with autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome has not been reported yet. Here we present a case of autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome with hypereosinophilia.Case presentationA 33-year-old Iranian man with the fatigue, jaundice, elevated liver enzymes and alkaline phosphatase, and hypereosinophilia was referred to our hospital. Viral and autoimmune hepatitis were excluded, and secondary workups for hypereosinophilia were all negative. Magnetic resonance cholangiopancreatography showed beaded appearance of intra- and extrahepatic biliary tree, and liver biopsy revealed interface hepatitis. Therefore, the diagnosis of autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome was made, and prednisolone, azathioprine, and ursodeoxycholic acid was initiated. His jaundice and peripheral blood eosinophilia resolved after 2 weeks, and he became completely asymptomatic.ConclusionEosinophils might contribute to the clinical presentation and disease complications.

Fully automated detection of primary sclerosing cholangitis (PSC)-compatible bile duct changes based on 3D magnetic resonance cholangiopancreatography using machine learning.

To develop and evaluate a deep learning algorithm for fully automated detection of primary sclerosing cholangitis (PSC)-compatible cholangiographic changes on three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) images. The datasets of 428 patients (n = 205 with confirmed diagnosis of PSC; n = 223 non-PSC patients) referred for MRI including MRCP were included in this retrospective IRB-approved study. Datasets were randomly assigned to a training (n = 386) and a validation group (n = 42). For each case, 20 uniformly distributed axial MRCP rotations and a subsequent maximum intensity projection (MIP) were calculated, resulting in a training database of 7720 images and a validation database of 840 images. Then, a pre-trained Inception ResNet was implemented which was conclusively fine-tuned (learning rate 10-3). Applying an ensemble strategy (by binning of the 20 axial projections), the mean absolute error (MAE) of the developed deep learning algorithm for detection of PSC-compatible cholangiographic changes was lowered from 21 to 7.1%. Sensitivity, specificity, positive predictive (PPV), and negative predictive value (NPV) for detection of these changes were 95.0%, 90.9%, 90.5%, and 95.2% respectively. The results of this study demonstrate the feasibility of transfer learning in combination with extensive image augmentation to detect PSC-compatible cholangiographic changes on 3D-MRCP images with a high sensitivity and a low MAE. Further validation with more and multicentric data is now desirable, as it is known that neural networks tend to overfit the characteristics of the dataset. • The described machine learning algorithm is able to detect PSC-compatible cholangiographic changes on 3D-MRCP images with high accuracy. • The generation of 2D projections from 3D datasets enabled the implementation of an ensemble strategy to boost inference performance.

Clinical features and MRI progression of small duct primary sclerosing cholangitis (PSC)

PurposeFirst, to evaluate and describe the clinical and MRI progression of patients with small duct primary sclerosing cholangitis (sdPSC), and second, to look for MRI features associated with disease progression to large duct PSC. Method16 patients (7 female, 9 male; median age 27 years) with diagnosis of sdPSC and available MR imaging were included in this retrospective dual-center study. Liver function tests (LFTs) and imaging was reviewed in consensus by two radiologists at baseline and follow-up, and compared by means of non-parametric tests, with p < 0.05 deemed significant. ResultsAt baseline and follow-up patients had a cholestatic liver profile with elevated LFTs. Progressive liver deformity, heterogeneous enhancement and hilar lymphadenopathy were common findings. In 9 patients follow-up MRI was available with a mean interval between imaging of 10.6 years (range 3.6−15.3 years). 5 patients (55.5 %) developed cholangiographic changes diagnostic of large duct PSC. No correlation was observed between MRI findings or LFTs at baseline and the endpoint of developing PSC typical cholangiographic changes at follow-up imaging (p > 0.05). ConclusionsMore than half of sdPSC patients developed cholangiographic changes, supporting that sdPSC may be an early stage of large duct PSC rather than an entity of its own. Larger studies are needed to address the value of MRI for prediction of sdPSC disease progression.

Bile Duct Injury due to Drug Induced Liver Injury.

Drug-induced liver injury (DILI) can present with a variable clinical and pathological phenotype and can be classified using liver enzymes as hepatocellular, cholestatic or a mixed pattern. The cholestatic pattern has been considered amongst the spectrum of direct liver damage at the microscopic level, but recently bile duct injury as a manifestation of DILI has emerged as a distinct entity and this review examines several examples of biliary tract abnormalities due to DILI from a clinical, radiologic and pathologic perspective. Case series and reports have emerged over the last few years of drugs causing cholangiographic changes or direct injury to the intra-and extra-hepatic biliary tree, such as ketamine and several chemotherapy agents. The DILI Network (DILIN) in the United States has published their experience of cases with vanishing bile duct syndrome on histology and sclerosing cholangitis like changes seen on cholangiography. The pathogenesis of these changes is unclear but it appears that this type of injury is more severe and more likely to lead to a chronic injury with increased mortality than other cases of DILI. Bile duct injury due to DILI is an increasingly recognized entity and imaging of the biliary tree in conjunction with liver biopsy should be considered in patients with severe cholestatic DILI.

Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis

Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We aimed to identify novel protein biomarkers of disease severity and prognosis in primary sclerosing cholangitis (PSC). Using a bead-based array targeting 63 proteins, we profiled a derivation panel of Norwegian endoscopic retrograde cholangiography bile samples (55 PSC, 20 disease controls) and a Finnish validation panel (34 PSC, 10 disease controls). Selected identified proteins were measured in serum from two Norwegian PSC cohorts (n=167 [1992-2006] and n=138 [2008-2012]), inflammatory bowel disease (n=96) and healthy controls (n=100). In the bile derivation panel, the levels of 14 proteins were different between PSC patients and controls (p<0.05); all were confirmed in the validation panel. Twenty-four proteins in the bile derivation panel were significantly (p<0.05) different between PSC patients with mild compared to severe cholangiographic changes (modified Amsterdam criteria); this was replicated for 18 proteins in the validation panel. Interleukin (IL)-8, matrix metallopeptidase (MMP)9/lipocalin (LCN)2-complex, S100A8/9, S100A12 and tryptophan hydroxylase (TPH)2 in the bile were associated with both a PSC diagnosis and grade of cholangiographic changes. Stratifying PSC patients according to tertiles of serum IL-8, but not MMP9/LCN2 and S100A12, provided excellent discrimination for transplant-free survival both in the serum derivation and validation cohort. Furthermore, IL-8 was associated with transplant-free survival in multivariable analyses in both serum panels independently of age and disease duration, indicating an independent influence on PSC progression. However, the Enhanced Liver Fibrosis (ELF®) test and Mayo risk score proved to be stronger predictors of transplant-free survival. Based on assaying of biliary proteins, we have identified novel biliary and serum biomarkers as indicators of severity and prognosis in PSC. Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We have identified inflammatory proteins including calprotectin and IL-8 as important indicators of disease severity and prognosis in bile and serum from patients with primary sclerosing cholangitis.

Complicated Portal Cavernoma Cholangiopathy (PCC) in a Patient with Pre-existing TIPS Managed Successfully by Endoscopic Biliary Stenting

PCC is the presence of typical cholangiographic changes in patients with a portal cavernoma due to chronic portal vein thrombosis (PVT), in the absence of other biliary tract diseases. Symptomatic PCC is rare; estimates range between 5-38% of patients with PVT. A 41 year old black woman with a PMH of Hodgkin's lymphoma s/p chemotherapy, isolated factor VII deficiency, complicated cirrhosis s/p TIPS and PVT presented to GI clinic with RUQ pain, dark urine, and acholic stool. Physical examination revealed scleral icterus and RUQ tenderness. The total bilirubin was 3.3 MG/DL, AST 111 U/L, ALT 29 U/L, ALP 603, and INR 1.4. After hospitalization, MRCP and MRI pancreas revealed cavernous portal vein transformation and chronic intrahepatic biliary dilation compatible with PCC. There was narrowing of the biliary system at the confluence secondary to extrinsic compression from cavernous transformation. No CBD dilation or filling defects, pancreatic mass, or PD dilation was noted. ERCP with an occlusion cholangiogram revealed a normal CBD. Unexpected vigorous hemobilia was encountered. Cholangioscopy was limited by fresh blood and clots up to the confluence - a bleeding source could not be identified. Interventional Radiology was consulted. CT angiogram revealed no active bleeding. TIPS was patent. Overnight the patient developed fever, leukocytosis, increasing RUQ abdominal pain, and worsening bilirubin consistent with ascending cholangitis. Antibiotics were initiated. Emergent ERCP was performed. Balloon sweeps of the CBD extracted clots and re-precipitated hemobilia. Cholangiogram revealed turbulence and dilution of contrast at the confluence, suggesting a bleeding source in the vicinity. A fully covered metallic stent was deployed at the confluence. Cholangioscopy was performed through the stent. No active bleeding was noted. The patient did well post procedure with resolution of bleeding, pain, and fever. Treatment of complicated PCC is multi faceted. It involves endoscopic biliary decompression followed by portal decompression (proximal splenorenal shunt or TIPS). Patients who remain symptomatic may undergo biliary drainage surgeries (hepaticojejunostomy or choledochojejunostomy). Hemobilia has been reported rarely after balloon sweeps, attributed to suspected intracholedochal varices and managed successfully by covered metal stents.Figure 1Figure 2Figure 3

Screening primary sclerosing cholangitis and biliary dysplasia with endoscopic retrograde cholangiography and brush cytology: risk factors for biliary neoplasia.

Primary sclerosing cholangitis (PSC) is associated with increased risk of biliary dysplasia and cholangiocarcinoma (CCA). The aim of this study was to evaluate the role of early endoscopic retrograde cholangiography (ERC) with systematic brush cytology to identify risk factors associated with biliary neoplasia. Patients who were referred for their first ERC for suspicion of PSC between January 2006 and October 2011 were included in the study. Brush cytology specimens were scored as benign, suspicious, or malignant. End points were CCA, biliary dysplasia, benign histology, or benign disease course for ≥ 2 years. PSC was diagnosed in 261 patients (125 men, 136 women), most of whom were asymptomatic (n = 211). Cholangiographic changes were mild in 57.1 %. Men presented with advanced disease more often than women. Brush cytology was benign in 243, suspicious in 16, and malignant in 2 patients. Follow-up completed in 249 patients indicated a benign disease course in 232 patients. Seven patients were diagnosed with CCA and eight had biliary dysplasia in the explanted liver. Thus, 15 patients had biliary neoplasia, and suspicious or malignant brush cytology had been detected in 8 of them at initial brushing. Advanced extrahepatic cholangiographic changes with elevated aminotransferases at diagnosis seemed to be associated with increased risk of biliary neoplasia. Even in mostly asymptomatic patients with PSC, 42.9 % had advanced disease and 6.9 % presented with suspicious or malignant brush cytology at first ERC. Advanced extrahepatic ERC changes with elevated aminotransferases at diagnosis might be risk factors for biliary neoplasia.

Secondary Sclerosing Cholangitis in Critically Ill Patients

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.

Ursodeoxycholic acid in primary sclerosing cholangitis: meta‐analysis of randomized controlled trials

The effect of ursodeoxycholic acid (UDCA) treatment on survival and liver histological progression of primary sclerosing cholangitis (PSC) remains uncertain. The aim of the present study was to evaluate the effect and safety of UDCA in PSC. Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science and PubMed (updated to January 2009) and manual bibliographical searches were carried out. A meta-analysis of all randomized controlled trials (RCT) comparing UDCA with placebo or no treatment was carried out. Eight RCT including 465 patients were assessed. UDCA could significantly improve liver biochemistry, but had no effect on pruritus and fatigue. Meta-analysis of the included RCT showed UDCA had no significant effect on the incidence of death, liver transplantation, and death and/or liver transplantation. However, a significant difference for the incidence of histological improvement was found between the two groups (odds ratio [OR], 9.19; 95% CI: 0.98, 86.15; P = 0.05). Meta-analysis also indicated a reduction trend of histological deterioration and an improvement trend of cholangiographic changes. These trends were constant in the sensitivity analyses. The meta-analysis found that UDCA can improve liver biochemistry and there is a trend towards improvement in liver histology and cholangiography, but has no effect on survival free of transplantation.

Immunoglobulin G4 associated cholangitis: Description of an emerging clinical entity based on review of the literature

During the last decade, patients with steroid responsive sclerosing cholangitis have been described in a number of case reports and a few cases series. These patients meet diagnostic criteria for primary sclerosing cholangitis (PSC) but seem to have a better prognosis and are often, but not always, associated with autoimmune pancreatitis (AIP). Unlike biliary strictures in PSC, most PSC-like biliary strictures seen in association with AIP respond well to steroids and some have been shown to resolve after immunosuppressive treatment during prolonged follow-up. In addition, steroid-responsive dominant bile duct lesions, sometimes mimicking infiltrating hilar cholangiocarcinoma, without pancreatic abnormalities have also been reported. Here we review the literature on this emerging clinical entity and suggest that this condition of steroid responsive biliary strictures be named Immunoglobulin G4 (IgG4) Associated Cholangitis (IAC). We performed an electronic database search of MEDLINE for case reports and case series of sclerosing cholangitis with pancreatitis and/or pancreatic mass (1960–July 2006). Articles were limited to English and these case reports and cases series were reviewed and all references on the combination of sclerosing cholangitis and pancreatitis as well as IgG4 positive cholangitis without pancreatic involvement not identified by our original search were obtained. Terminology and Definition

Evaluating the AIH Scoring System

Evaluating the AIH Scoring System

Small-Duct Primary Sclerosing Cholangitis. A Single-Center Seven-Year Experience

Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but without the typical cholangiographic changes are considered to have small-duct PSC. The incidence of small-duct PSC and the natural history still is not known. We performed a retrospective search for patients diagnosed with small-duct PSC between January 1997 and December 2003. The diagnosis of small-duct PSC was based on biochemical features of chronic cholestasis, liver biopsy findings consistent with PSC, and a normal cholangiogram on endoscopic retrograde cholangiography. Six patients fulfilled the diagnostic criteria for small-duct PSC. All patients received medical therapy. After a mean follow-up time of 26.0 +/- 29.8 months (range, 7-84 months), all patients are alive. Repeated liver biopsy was performed in one patient, 58 months after the initial one, and disclosed amelioration of histological findings (reduction in the Ludwig fibrosis score from 4 to 2). During follow-up symptoms disappeared in all patients who were symptomatic at diagnosis; none of those who were asymptomatic at diagnosis developed symptoms. At the time of last follow-up all patients showed significant improvement of their biochemical variables compared to baseline. Administration of aminosalicylates seemed to be of benefit irrespective of the presence of inflammatory bowel disease. No patients underwent liver transplantation or developed cholangiocarcinoma. Even though our study included a low number of patients and the follow-up time was relatively short, we can suggest that small-duct PSC rarely progresses to large-duct PSC and does not seem to be associated with development of cholangiocarcinoma. It thus seems to represent a separate entity with a favorable prognosis.

Overlap syndromes from pediatrics to adulthood

Abstract Overlap syndromes are autoimmune conditions with mixed immunological, clinical and histological features. The most frequent overlaps are between primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH), and between AIH and sclerosing cholangitis (SC). True AIH/PBC overlap syndrome is rare and characterized by elevation of transaminases and immunoglobulin G (IgG), positive anti‐smooth muscle antibodies and a liver biopsy showing interface hepatitis as well as changes typical of PBC. These patients respond to immunosuppressive treatment that must be given promptly, to avoid progression to liver failure. The so‐called ‘autoimmune cholangitis’ defines a small group of patients with cholestatic and histological features of PBC but negative for anti‐mitochondrial antibody (AMA) and positive for PBC‐specific anti‐nuclear antibody (ANA). The positivity for ANA in these patients is a consequence of the AMA negativity, since AMA masks ANA on immunofluorescence. These patients’ clinical course and response to treatment resemble that of classical PBC. AIH/ASC overlap syndrome is characterised by elevated levels of IgG and circulating autoantibodies, including ANA, SMA and atypical perinuclear anti‐neutrophil cytoplasmic antibody, in association with cholangiographic changes typical of SC. This condition affects in particular children and young adults and may represent the early stage of adult primary SC. The parenchymal liver inflammation responds satisfactorily to immunosuppression, while the bile duct damage may progress despite treatment.

Dominant Strictures in Patients with Primary Sclerosing Cholangitis-Revisited

TO THE EDITOR: We read with interest Dr. Kozarek's Editorial about our paper on dominant strictures in primary sclerosing cholangitis (PSC) in the March issue of The American Journal of Gastroenterology (1,2). His interpretation is that from a therapeutic standpoint, our paper misses the point. Unfortunately it seems that Dr. Kozarek does not acknowledge the complicated pathophysiology of PSC. As discussed in the Introduction in our paper, intrahepatic cholangiographic changes have more important prognostic significance than extrahepatic cholangiographic changes in patients with PSC (3,4). Our group has demonstrated that high-grade intrahepatic cholangiographic changes but not extrahepatic changes predicted early jaundice and short survival (4). Similar results were reported from researchers from the Mayo Clinic in a study assessing the prognostic value of cholangiographic findings in patients with PSC (3). Consequently, there is no scientific basis for the assumption that improved plumbing (as Dr. Kozarek calls it) of larger, extrahepatic bile ducts improves prognosis in PSC. Importantly, no randomized studies exist demonstrating the benefits of endoscopic treatment in PSC. Thus, the statement concerning the personal experience of Dr. Kozarek that endotherapy can reduce attacks of recurrent cholangitis and abdominal pain in these patients is not in line with evidence-based medicine. Most experienced hepatologists certainly have experienced patients who have had attacks of fever, cholangitis, and jaundice who yet have spontaneously recovered and normalized bilirubin without any treatment. It is also important to remember that in the three published follow-up studies on small duct PSC, abdominal pain was as common in patients with small duct PSC (with normal cholangiography) as in those with large duct disease (5,6,7). Dr Kozarek's sole support for a long-term therapeutic effect of endotherapy is an uncontrolled nonrandomized study in which observed Mayo risk score was better than predicted (8). We also wonder what kind of data support the statement that endotherapy undertaken early enough may also prevent the loss of one liver lobe or another from progressive obstruction. Finally, Dr. Kozarek, presents a novel explanation for fluctuations in liver chemistries in patients with PSC, being due to black pigment stones. This theory has not to our knowledge been put forward in the literature on the etiopathogenesis of PSC. What scientific evidence exists for this statement?

Portal cavernoma-associated cholangiopathy: A clinical and MR cholangiography coupled with MR portography imaging study

Although biliary symptoms appear to be uncommon in patients with portal cavernoma, almost all of them have endoscopic retrograde cholangiographic abnormalities. The mechanisms underlying the biliary changes are explained poorly. This study in patients with portal cavernoma had 3 aims: (1) to assess the manifestations related to biliary involvement; (2) to evaluate with magnetic resonance (MR) imaging the aspect and frequency of cholangiographic changes; and (3) to clarify the mechanisms underlying biliary involvement. From December 1999 to July 2001, 25 consecutive adults with portal cavernoma without cancer or cirrhosis were studied with MR cholangiography coupled with MR portography. Seven patients presented with clinical manifestations of biliary disease. MR cholangiography findings were stenosis in 21 patients, with upstream dilatation in 16 and displacement in 13. MR cholangiography coupled with MR portography showed in all cases that the biliary abnormalities were secondary to a mass effect directly related to pressure by the cavernoma. In conclusion, in patients with portal cavernoma, clinical manifestations of biliary disease are most frequent; the cholangiographic abnormalities are very common and usually are caused by a mass effect by pressure from the veins composing the cavernoma. MR cholangiography coupled with MR portography is an effective noninvasive examination for simultaneous visualization of bile ducts and their relationship to the cavernoma. (H epatology 2003;37:1302-1308.)

Primary sclerosing cholangitis.

In this article, evidence has been presented that immune mechanisms play a major role in the pathogenesis of PSC. Although considerable progress has been made in our understanding of the pathogenesis and treatment of this disease, many questions remain unanswered. The factors that trigger the disease in a susceptible host are unknown and it is unclear whether an exogenous agent such as retroviral infection is involved or if there is an intrinsic abnormality in the immune system. It is unknown if the pathogenetic mechanisms are the same for patients with PSC alone or patients with PSC and IBD or whether these represent separate clinical entities. Moreover it is unclear if immunosuppressants as high-dose single agents or in combination may halt or slow disease progression. To answer some of these questions, the disease must be identified in patients early in its pathogenesis, perhaps even before the characteristic cholangiographic changes have occurred. Although new noninvasive techniques, such as magnetic resonance cholangiography, may allow screening of patients with UC, early diagnosis is likely to remain difficult. Animal models provide a way of exploring the relationship of PSC and IBD and the early events in pathogenesis. Previous animal models (144, 145) have provided limited insight into PSC because the hepatobiliary damage was more representative of acute rather than the chronic insidious damage of PSC. However studies of colitis in the “knockout” mouse offer the opportunity to explore the relationship between host genetic susceptibility, colitis, and hepatobiliary damage.

Hepatobiliary and Coexisting Pancreatic Duct Abnormalities in Patients with Inflammatory Bowel Disease

Background: We performed a cross-sectional study to evaluate the prevalence of hepatobiliary disease in unselected patients with inflammatory bowel disease (IBD), to estimate the frequency of coexisting cholangiographic and pancreatographic duct abnormalities, and to correlate the findings with clinical, endoscopic, and histologic variables. Methods: We screened 237 IBD patients for increased liver function values. Further, hepatobiliary evaluation consisted of transabdominal ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), and a liver biopsy. In addition, we evaluated the ERCP findings of patients with abnormal pancreatic screening tests (pancreatic enzymes or para-aminobenzoic acid excretion). Results: Laboratory signs of hepatobiliary disease were found in 37 (16%) of our IBD patients. Abnormal liver test results were commoner in patients with Crohn's disease (CD) than in patients with ulcerative colitis (UC) (30.4% versus 11.2%, P > 0.05), and a similar trend was observed in the frequency of primary sclerosing cholangitis (PSC) in the respective groups of IBD patients. When the ERCP findings were combined with liver histology, 26 (11% of the whole study group) patients with PSC were found, with small-duct disease included. In 23 (10% of the whole study group) patients, definite cholangiographic changes consistent with PSC were found. Eleven (48%) of these showed coexisting pancreatic duct abnormalities. The prevalence of coexisting cholangiographic and pancreatographic duct changes in the whole study group was 4.6%. Conclusion: Hepatobiliary disease is at least equally common in patients with UC and CD. Coexisting cholangiographic and pancreatographic duct abnormalities in patients with IBD are relatively frequent and are considered extraintestinal manifestations of IBD.

Antineutrophil cytoplasmic antibody positive autoimmune hepatitis: [formula omitted]. University of Iowa Dept. Internal Medicine and Pathology, Iowa City, IA

Cholangiographic changes of the biliary system in 16 patients with proven hepatic clonorchiasis, diagnosed by positive stool or bile ova isolates, were studied. All patients presented with epigastric pain. Other symptoms included jaundice in 31% (5 of 16) and fever in 12.5% (2 of 16). Praziquantel given at 25 mg/kg for three doses in 1 day were administered. Three consecutive stool tests were performed 3 months after treatment and were negative in 87.5% (14 of 16). ERCP studies were repeated at a mean interval of 31.6 months (range, 8 to 69 months). Measurements of the bile ducts on retrograde cholangiograms before and after treatment were compared using the paired Student’s t test. Filling defects and blunting of the terminal bile ducts seen on the initial cholangiogram, interpreted as the presence of adult worms, disappeared after treatment. However, there was no significant change between pre- and post-treatment measurement of bile duct caliber. Bile duct dilation, irregularities, and ductal proliferation persisted despite eradication of the parasite.

Endoscopic cholangiopancreatography in hepatic clonorchiasis—a follow-up study

Cholangiographic changes of the biliary system in 16 patients with proven hepatic clonorchiasis, diagnosed by positive stool or bile ova isolates, were studied. All patients presented with epigastric pain. Other symptoms included jaundice in 31% (5 of 16) and fever in 12.5% (2 of 16). Praziquantel given at 25 mg/kg for three doses in 1 day were administered. Three consecutive stool tests were performed 3 months after treatment and were negative in 87.5% (14 of 16). ERCP studies were repeated at a mean interval of 31.6 months (range, 8 to 69 months). Measurements of the bile ducts on retrograde cholangiograms before and after treatment were compared using the paired Student's t test. Filling defects and blunting of the terminal bile ducts seen on the initial cholangiogram, interpreted as the presence of adult worms, disappeared after treatment. However, there was no significant change between pre- and post-treatment measurement of bile duct caliber. Bile duct dilation, irregularities, and ductal proliferation persisted despite eradication of the parasite.