Small-duct Primary Sclerosing Cholangitis Research Articles

Primary Sclerosing Cholangitis Limited to Intrahepatic Bile Ducts Has Distinctly Better Prognosis.

There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic). This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC. Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement. Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC. Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.

DOP14 Proctocolectomy is associated with improved transplant-free survival in patients with primary sclerosing cholangitis: results from a pooled collaborative international study

Abstract Background It is hypothesized that the gut-liver axis plays a pivotal role in the aetiology of primary sclerosing cholangitis (PSC). Colectomy before liver transplantation is associated with decreased rates of recurrent PSC.1 We previously observed that proctocolectomy with permanent ileostomy is associated with better transplant-free survival in a population-based Dutch cohort.2 The aim of the present study is to confirm the effect of colectomy on PSC disease course in an international context. Methods We conducted a retrospective analysis on the International PSC Registry (IPSCR), comprising patients from Finland, Norway, Sweden, and the Netherlands. Endpoints were defined as liver transplantation (LT) and PSC-related death (excluding colorectal carcinoma) and were censored in the first year after colectomy to allow for a delayed protective effect. Cox proportional hazards regression was performed, with correction for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, and inflammatory bowel disease (IBD) status (i.e. ulcerative colitis, Crohn’s disease or IBD unspecified). IBD status and colectomy status were included as time-dependent exposure variables, the latter stratified for extent and indication for colectomy. Results A total of 2595 patients were included, of which 1341 from the Netherlands, 560 from Finland, 528 from Norway, and 166 from Sweden. Of all patients 1900(73%) were diagnosed with IBD and 346(15%) had undergone a colectomy; 34(9%) hemi-, 91(26%) subtotal, and 172(50%) proctocolectomy with pouch and 65(19%) with ileostomy. During a total follow-up of 28,282 patient years, 848(33%) patients reached the endpoint LT or PSC-related death. Hazard ratio (HR) of reaching LT or PSC-related death was significantly decreased in patients with proctocolectomy (0.70(0.52-0.93)) compared to patients without colectomy with variation per country (Netherlands 0.82(0.56-1.19), Finland 0.52(0.24-1.13), Norway 0.59(0.31-1.03), Sweden 0.28(0.06-1.24)). This effect was less pronounced in case of a hemi- or subtotal colectomy (HR 0.84(059-1.20)). The effect was most pronounced in the proctocolectomy with permanent ileostomy group (HR 0.55(0.30-0.99)). Of the known risk factors only a concurrent IBD diagnosis had no significant effect on transplant-free survival. Conclusion Our extended data confirm that colectomy is associated with a decreased risk of liver transplantation and PSC-related death. An incremental effect was seen with the extent of the colectomy, with the most pronounced effect in the proctocolectomy group with permanent ileostomy. Our data support the putative role of the gut-liver axis in the disease course of PSC.

Noninvasive prognostic models, imaging, and elastography to predict clinical events in primary sclerosing cholangitis: A review.

Surrogate endpoints are needed to estimate clinical outcomes in primary sclerosing cholangitis (PSC). Serum alkaline phosphatase was among the first markers studied, but there is substantial variability in alkaline phosphatase levels during the natural history of PSC without intervention. The Mayo risk score incorporates noninvasive variables and has served as a surrogate endpoint for survival for more than two decades. Newer models have better test performance than the Mayo risk score, including the primary sclerosing risk estimate tool (PREsTo) model and UK-PSC score that estimate hepatic decompensation and transplant free survival, respectively. The c-statistics for transplant-free survival for the Mayo risk model and the long-term UK-PSC model are 0.68 and 0.85, respectively. The c-statistics for hepatic decompensation for the Mayo risk model and PREsTo model are 0.85 and 0.90, respectively. The Amsterdam-Oxford model included patients with large duct and small duct PSC and patients with PSC-autoimmune hepatitis overlap and had a c-statistic of 0.68 for transplant-free survival. Other noninvasive tests that warrant further validation include magnetic resonance imaging, elastography and the enhanced liver fibrosis score. Prognostic models, noninvasive tests or a combination of these surrogate endpoints may not only serve to be useful in clinical trials of investigational agents, but also serve to inform our patients about their prognosis.

Liver transplant in patients with primary sclerosing cholangitis: A retrospective cohort from Northeastern Brazil.

Primary sclerosing cholangitis (PSC) manifests within a broad ethnic and racial spectrum, reflecting different levels of access to health care. To evaluate the clinical profile, complications and survival rates of patients with PSC undergoing liver transplantation (LTx) at a Brazilian reference center. All patients diagnosed with PSC before or after LTx were included. The medical records were reviewed for demographic and clinical variables, including outcomes and survival. The level of statistical significance was set at P < 0.05. Our cohort represented 1.6% (n = 34) of the 2113 patients receiving liver grafts at our service over the past two decades. Most were male (n = 19; 56%). The average age (40 ± 14 years) was similar for men and women (P = 0.347). The mean follow-up time from diagnosis to LTx was 68 mo. Most patients had the classic form of PSC. Three women had PSC/autoimmune hepatitis overlap syndrome, and one patient had small-duct PSC. Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease. scores were significantly higher in males. Inflammatory bowel research (IBD) was investigated by colonoscopy in 26/34 (76%) and was present in most cases (18/26; 69%). IBD was less common in women than in men (44.4% vs. 55.6%) (P = 0.692). Cholangiocarcinoma (CCA) was diagnosed in 2/34 (5.9%) patients by histopathology of the explant (survival: 3 years 6 mo, and 4 years 11 mo). Two patients had complications requiring a second LTx (one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction). Five patients (14.7%) developed biliary stricture. The overall median post-LTx survival was 66 mo. Most deaths occurred in the first year (infection n = 2, primary liver graft dysfunction n = 3, unknown cause n = 1). The 1-year and 5-year survival rates of this cohort were 82.3% and 70.6%, respectively, matching the mean overall survival rates of LTx patients at our center (87.1% and 69.43%, respectively) (P = 0.83). Survival after 1 and 5 years was similar to that of other LTx indications. The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.

Natural history and prognosis of pediatric PSC with updates on management.

Natural history and prognosis of pediatric PSC with updates on management.

OP10 Proctocolectomy with permanent ileostomy is associated with better transplant-free survival in patients with primary sclerosing cholangitis: a retrospective cohort study

Abstract Background Inflammatory bowel disease (IBD) is the strongest known risk factor for primary sclerosing cholangitis (PSC) and seems associated with a worse prognosis. After liver transplantation, colectomy is associated with decreased rates of recurrent PSC and better graft survival.1 At the same time, the effect of colectomy on the disease course of PSC remains unclear.2 Available evidence depends either on small patient numbers, may be confounded by unobserved risk factors or colectomy was not considered as time-depending covariate. The aim of our study is to estimate the effect of colectomy on the disease course of PSC by taking time dependency and known risk factors into account. Methods We conducted a retrospective cohort study between January 1st 2008 and December 31st 2021 based on the Dutch population-based EpiPSC2 cohort. Transplant-free survival was defined as liver transplantation or PSC-related death (excluding colorectal carcinoma). The effect of colectomy was determined as time depending variable via Cox proportional hazards regression and was corrected for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, time depending IBD status (i.e. no IBD, ulcerative colitis (UC), Crohn’s disease (CD) or IBD Unspecified (IBD-U)), and tertiary centre inclusion. Effect of colectomy was stratified for extent (i.e. hemi-, subtotal, or proctocolectomy with pouch or ileostomy). Indication of colectomy (i.e. active disease, dysplasia and colorectal carcinoma or other) was also considered as predictor variable. Events in the first year after colectomy were censored due to a presumed delayed effect of colectomy on disease course. Results Of the 1341 patients included, 912(68%) were diagnosed with IBD and 187(14%) had undergone a colectomy. During a total follow-up of 14,393 patient years, 370(28%) patients underwent liver transplantation and 318(24%) patients died due to a PSC-related cause. Median transplant-free survival time was 20 years. Hazard ratio (HR) was significantly decreased in patients who had undergone proctocolectomy with ileostomy (HR 0.47(0.24-0.93)) compared to patients without colectomy. This effect was absent in the group with any other type of colectomy (HR 0.90(0.67-1.19)). Indication of colectomy had no apparent effect. Presence of UC, CD or IBD-U was not associated with a worse prognosis compared to absence of IBD (HR 0.99(0.81-1.21), HR 0.85(0.64-1.13), HR 0.75(0.43-1.29)). Conclusion Our data suggest that proctocolectomy with ileostomy confers protection for liver transplantation and PSC-related death. This points towards the putative pathophysiologic role of the colonic microbiota in PSC and may open avenues to a better understanding of the aetiology of PSC.

Reply: Insurance should cover vancomycin for primary sclerosing cholangitis.

Ali and colleagues raise issues of insurance coverage for oral vancomycin (OV) for the treatment of primary sclerosing cholangitis (PSC); however, the purpose of AASLD guidance statements is to help clinicians understand and implement the most recent evidence (https://www.aasld.org/practice-guidelines). The writing group, Practice Guidance Committee, and AASLD Governing Board and supported the final statement that there is insufficient evidence to recommend the use of OV which is consistent with the 2022 European Association for the Study of the Liver guidelines.1 The meta-analysis referred to included only 2 randomized controlled trials of OV.2. The largest study randomized 29 patients to OV or placebo for 12 weeks and reported an improvement in Mayo Risk Score, though total bilirubin did not change. The other randomized controlled trials was not placebo-controlled and included 8 and 9 patients who received low or high doses of OV, respectively, for 12 weeks. Compared with baseline, alkaline phosphatase decreased in both groups, and Mayo Risk Score decreased only in the low-dose group, but without change in total bilirubin. A third study was open-labeled and reported on 30 enrolled subjects and 29 patients treated outside protocol, 25 (42%) of whom had small duct PSC, and several previously treated with OV.3 The methods used to support the claims of imprvements in histology and cholangiograms were not reported. In contrast, a retrospective study of 264 patients found that neither OV nor ursodiol were associated with clinical improvements compared with observation in pediatric patients with PSC.4 Thus, the data supporting the use of OV in PSC is not “robust” and the statements Ali an colleagues made about OV are not supported by current evidence. More concerning is the suggestion that OV might be a substitute for biologics for treating inflammatory bowel disease. Management of PSC-associated inflammatory bowel disease was outside the scope of the Guidance, but multiple society guidelines do not recommend vancomycin for acute severe ulcerative colitis. All stakeholders desire a safe and effective treatment for PSC. Ali and colleagues believe that OV is that treatment, but current evidence does not support this belief.

Primary sclerosing cholangitis-A long night's journey into day.

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Prevalence of inflammatory bowel disease in patients with primary sclerosing cholangitis: A systematic review and meta-analysis.

Previous studies have established an association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC). The disease burden of IBD in PSC patients was not well estimated. The study aimed to quantify the pooled prevalence of IBD in PSC and to investigate whether subtypes of PSC and sex influence the prevalence of IBD. PubMed, Embase, and Web of Science were searched through November 2021 for studies reporting data on IBD among PSC patients. The outcomes were the prevalence of IBD in patients with PSC, as well as the association (odds ratio [OR]) of IBD in PSC according to subtype and sex. Based on the analysis of 25 studies, the prevalence of IBD in patients with PSC was 71.1% (95% CI 68.2-75.1%), most commonly in UC (55.9%, 95% CI 52.5-59.3%). The pooled prevalence of IBD was 76.9% in Australia (95% CI 71.2-82.6%, 1 study), 75.9% (95% CI 69.5-82.3%, 4 studies) in North America, 70.9% (95% CI 65.8-76.0%, 17 studies) in Europe and 67.0% (95% CI 57.9-76.0%, 2 studies) in Asia. Male PSC patients had a higher prevalence of IBD (OR 1.67, 95% CI 1.52-1.83) and UC (OR 2.02, 95% CI 1.56-2.63) and a lower prevalence of CD (OR 0.77, 95% CI 0.67-0.88) than female patients. Large duct PSC patients had a higher prevalence of IBD (OR 2.57, 95% CI 2.03-3.25) and UC (OR 4.51, 95% CI 1.22-16.71) than small duct PSC patients. The study provided the first pooled estimates of the burden of IBD in patients with PSC and could be used as the basis for risk stratification of PSC patients.

P258 Impact of inflammatory bowel diseases on the phenotype and severity of primary sclerosing cholangitis - a systematic review with meta-analysis

Abstract Background Data regarding the impact of co-occurring inflammatory bowel diseases (IBD) on the phenotype and severity of primary sclerosing cholangitis (PSC) are emerging. The purpose of our study was to characterize the phenotype and disease course of PSC in relation to co-occurring IBD. Methods The purpose of our study was to characterize the phenotype and disease course of PSC in relation to co-occurring IBD. The systematic review and meta-analysis were conducted according to Cochrane’s recommendations. PubMed and EMBASE were searched from database inception till January 2020 for studies reporting disease phenotype and severity of PSC in association with co-occurrence of IBD. Meta-analyses were performed using a random-effects model. The quality of the studies was assessed by the Newcastle-Ottawa Scale (NOS). Results The electronic search yielded 12,220 studies which were narrowed down to 132 after screening based on study titles and abstracts. Of these, a full-text review identified 42 eligible studies, including a total of 8,081 and 5,728 patients with PSC and with or without co-occurring IBD, respectively (Figure 1). The mean NOS score was 6.4 ad included 23 (54.8%) and 18 (42.9%) studies of moderate and high methodological quality, respectively. The meta-analysis demonstrated that co-occurrence of IBD was associated with significantly less frequent involvement of the extra-hepatic ducts (risk ratio (RR)=0.50 (95% CI 0.33–0.75), p&amp;lt;0.01, I2=0%) as compared with patients without co-occurring IBD. However, IBD-PSC and PSC without IBD had similar rate of small-duct PSC, histologic stages of PSC, risk of developing cirrhosis, and features of decompensation. Furthermore, in comparison to patients with isolated PSC, co-occurring IBD was associated with an increased overall risk of malignancies (RR=1.53 (95% CI 1.01–2.32), p=0.04, I2=46%), which was ascribed to colorectal cancers (RR=4.77 (95% CI 2.50–9.09), p&amp;lt;0.01, I2=0%) and not cholangiocarcinomas (RR=0.88 (95% CI 0.59–1.31), p=0.54, I2=31%), gallbladder cancers (RR=2.28 (95% CI 0.39–13.21), p=0.36, I2=0%), or hepatocellular carcinomas (RR=4.49 (95% CI 0.57–35.46), p=0.15, I2=0%). Regarding long-term PSC outcomes, having IBD was not associated with the need of liver transplantation (RR=0.84 (95% CI 0.50–1.41), p=0.52, I2=60%) or mortality (RR=0.74 (95% CI 0.37–1.50), p=0.40, I2=37%), but was associated with a longer liver transplantation-free survival (hazard ratio = 0.70 (95% CI 0.60–0.82), p&amp;lt;0.01, I2=5%). Conclusion This systematic review with meta-analysis suggests that IBD is associated with a distinct phenotype and course of PSC, thus emphasizing the importance of a multidisciplinary approach to patients with co-occurring PSC and IBD.

Liver-side of inflammatory bowel diseases: Hepatobiliary and drug-induced disorders

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases (IBD), both in Crohn’s disease and ulcerative colitis (UC), and therefore represent a diagnostic challenge. Immune-mediated conditions include primary sclerosing cholangitis (PSC) as the main form, variant forms of PSC (namely small-duct PSC, PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis) and granulomatous hepatitis. PSC is by far the most common, presenting in up to 8% of IBD patients, more frequently in UC. Several genetic foci have been identified, but environmental factors are preponderant on disease pathogenesis. The course of the two diseases is typically independent. PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies. Risk of cholangiocarcinoma is significantly increased in PSC, as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis. No disease-modifying drugs are approved to date. Thus, PSC management is directed against symptoms and complications and includes medical therapies for pruritus, endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease. Other non-immune-mediated hepatobiliary disorders are gallstone disease, whose incidence is higher in IBD and reported in up to one third of IBD patients, non-alcoholic fatty liver disease, pyogenic liver abscess and portal vein thrombosis. Drug-induced liver injury (DILI) is an important issue in IBD, since most IBD therapies may cause liver toxicity; however, the incidence of serious adverse events is low. Thiopurines and methotrexate are the most associated with DILI, while the risk related to anti-tumor necrosis factor-α and anti-integrins is low. Data on hepatotoxicity of newer drugs approved for IBD, like anti-interleukin 12/23 and tofacitinib, are still scarce, but the evidence from other rheumatic diseases is reassuring. Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD, and adequate screening and vaccination is warranted. On the other hand, hepatitis C reactivation does not seem to be a real risk, and hepatitis C antiviral treatment does not influence IBD natural history. The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis, but it is of paramount importance to make a quick and accurate diagnosis, as it may influence the therapeutic management.

Cytokeratin 7 and Copper Stains Facilitate Diagnosis of Small Duct Primary Sclerosing Cholangitis

Abstract Introduction/Objective Classic primary sclerosing cholangitis (PSC) involves extrahepatic and/or intrahepatic biliary ducts with segmental biliary strictures and dilatations that often allow the diagnosis to be made via cholangiogram. Small duct PSC (sdPSC) is a rare subtype that presents similarly with a cholestatic pattern of injury, yet due to the small size of involved ducts, a cholangiogram is non-diagnostic and diagnosis is dependent on clinical suspicion and liver biopsy. The histopathological features of sdPSC are often subtle and may easily be overlooked. Diagnosis of this entity- though difficult- is important, as early recognition can facilitate the identification of associated disease processes and life-threatening complications. Methods/Case Report We encountered a 33-year-old female presenting with intermittent pruritis, episodes of jaundice, and persistently elevated alkaline phosphatase who was misdiagnosed with only fatty liver at an outside institution. Evaluation with MRCP showed no abnormalities within the biliary tract and a liver biopsy was performed to aid in the diagnosis. The H&amp;E and trichrome findings of atrophic bile ducts and some peribiliary sclerosis were extremely subtle and may have been overlooked without clinical suspicion. Cytokeratin 7 (CK7) highlighted cholangiolar metaplasia in hepatocytes and the bile ductular reaction that occurs in cholestatic disease states. A Rhodamine copper stain showed periportal deposition suggestive of chronic biliary obstruction. Use of CK7 and copper stains supported the presence of chronic biliary injury and suboptimal bile flow, confirming the diagnosis of sdPSC. Results (if a Case Study enter NA) NA Conclusion Diagnosis of sdPSC has historically relied on H&amp;E and trichrome stains. In this case, the findings on H&amp;E and trichrome stains were non-diagnostic, while the use of CK7 and copper stains confirmed the diagnosis of sdPSC. We recommend using CK7 and copper stains to evaluate for sdPSC.

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process

Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases

Background and aimsInflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. MethodsMedical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. ResultsFifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p=0.041; OR: 1.139, 95% CI: 1.006–1.255). Time since the diagnosis of AILD (p=0.003; OR: 1.259, 95% CI: 1.1–1.396), as well as portal hypertension at diagnosis (p=0.014; OR: 18.22, 95% CI: 1.815–182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p=0.012; OR: 7.1, 95% CI: 1.215–42.43). ConclusionBoth groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).

Promyelocytic Leukemia Antigen Expression: a Histological Marker for Primary Biliary Cholangitis Diagnosis?

Background and ObjectivesDistinguishing primary biliary cholangitis (PBC) from other cholestatic diseases at the histological level could be assisted by new methods, such as immunohistochemical staining of specific antigens.MethodsWe evaluated whether the detection of promyelocytic leukemia protein (PML) can serve as a specific and sensitive marker for PBC diagnosis. Liver biopsies from 26 PBC patients, 20 primary sclerosing cholangitis (PSC), 37 viral hepatitis, 11 non-alcoholic steatohepatitis (NASH) and 5 normal patients were investigated after immunostaining with the anti-PML monoclonal PG-M3, IgG1 antibody.ResultsImmunoreactivity in bile ducts was expressed by the PML-score (quotient of positive ducts to the total number of portal tracts multiplied by 2). PML-score was higher in PBC as compared to controls (P < 0.001). Using a cutoff of 0.18, PML-score proved highly sensitive (84.6%) and specific (89.7%) for confirming PBC as compared to only 5% of PSC, 9.1% of NASH and 13.5% of viral hepatitis patients (P < 0.001). Irrespective of the underlying disease, patients with PML-score > 0.18 were older (P = 0.007), more often females (P < 0.001) with higher ALP (P < 0.001), γ-GT (P = 0.001) and IgM (P < 0.001) compared to the patients with PML-score < 0.18.ConclusionsWe postulate that a simple PML immunohistochemical test could be sufficient for histopathological discrimination of PBC in problematic cases of undefined cholestatic disorders, including small-duct PSC and AMA-negative PBC cases.

Focal intrahepatic strictures: A proposal classification based on diagnosis-treatment experience and systemic review.

BACKGROUNDFocal intrahepatic strictures (FIHS) refer to local strictures of the small and medium intrahepatic bile ducts. FIHS are easily misdiagnosed due to their rare incidence, and few studies have focused on the diagnosis and treatment approaches.AIMTo propose a new classification for FIHS in order to guide its diagnosis and treatment.METHODSThe symptoms, biochemistry results, imaging results, endoscopic examination results and initial and final diagnoses of 6 patients with FIHS admitted between January 2010 and December 2019 were retrospectively analyzed.RESULTSThe 6 patients were diagnosed with intratubular growth-type intrahepatic cholangiocarcinoma (IG-ICC), recurrent multiple hepatocellular carcinoma (rmHCC) with bile duct tumor thrombus (BDTT), adenosquamous carcinoma (ASC), hepatolithiasis, small duct primary sclerosing cholangitis (SD-PSC) and autoimmune hepatitis (AIH). The initial and final diagnoses were not consistent in 4 patients. Hepatectomy was performed in patients with IG-ICC, ASC and hepatolithiasis according to the locations of their FIHS. Patients with rmHCC with BDTT received lenvatinib/sintilimab, while patients with SD-PSC and AIH received UDCA. We proposed the following classification system for FIHS: type I: FIHS located within one segment of the liver; type II: FIHS located at the confluence of the bile ducts of one segment or two adjacent segments; type III: FIHS connected to the left or right hepatic duct; and type IV: Multiple FIHS located in both lobes of the liver.CONCLUSIONOur proposed classification system might help to guide the diagnosis and treatment of FIHS. Hepatectomy should be performed not only for malignant FIHS but also for benign strictures with severe secondary damage that cannot be improved by nonsurgical methods.

S2491 Small Duct Primary Sclerosing Cholangitis: An Atypical Presentation

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a chronic progressive disease of the liver and biliary tract causing cholestasis, fibrosis, and strictures in intra and extrahepatic bile ducts. Patients are often asymptomatic, but as the disease progress, complications occur and include: recurrent cholangitis, portal hypertension, cirrhosis of the biliary tract, end-stage liver disease, and hepatobiliary malignancies, namely cholangiocarcinoma. Within the entity of PSC, there are two distinct variants: small duct PSC and large duct PSC. Here we present a case of small duct PSC presenting atypically with chronic portal vein thrombosis and a hilar mass. CASE DESCRIPTION/METHODS: 36- year old Pakistani man presented with right upper quadrant abdominal pain, jaundice, and fever. He reported a history of chronic abdominal pain and recurrent jaundice, as well as chronic portal vein thrombosis (PVT) since childhood. The patient was recently hospitalized in another institute for the same complaint for which he had a Computerized tomography (CT) of the abdomen that revealed marked splenomegaly together with evidence of portal vein occlusion with cavernous transformation as well as Intrahepatic biliary ductal dilation with a transition in the common hepatic duct and a hilar mass. The patient underwent endoscopic retrograde cholangiography (ERC) with biopsies obtained through cholangioscopy that were unremarkable. Liver biopsy showed findings consistent with primary sclerosing cholangitis with acute cholangitis and changes secondary to portal vein thrombosis. DISCUSSION: Primary sclerosing cholangitis is a chronic, incurable disease in which the liver and biliary tract become fibrosed, and strictures form in the intra and extrahepatic biliary ducts causing obstruction, portal hypertension, and eventual liver cirrhosis necessitating a liver transplant. MRC is the most frequently used diagnostic tool due to its high specificity and sensitivity. Although ERC is more sensitive, there are added risks and complications (i.e., pancreatitis and bacterial cholangitis) with this technique. When ERC is performed, findings typically include multifocal short annular strictures, which create a "beaded" pattern. Although most patients are shown to have intra and extrahepatic bile duct involvement, a small subset presents with only intra or extrahepatic bile duct involvement. Only a few small duct PSC cases were reported in the literature, and it rarely presents with an inflammatory mass as well as PVT, as in our case.Figure 1.: Portal fibrosis with mild to focal moderate ductular reaction, accompanied by neutrophils.Figure 2.: A Coronal contrast-enhanced CT image through the abdomen shows intrahepatic beading (red arrow) with intervening sites of alternating strictures, mildly dilated, and normal ducts. There is compensatory hypertrophy of the right lobe and caudate lobe of the liver (green arrows).Figure 3.: A Coronal MRCP Image through the liver shows multiple multifocal diffuse intrahepatic and extrahepatic strictures (red arrows) and severely dilated intrahepatic ducts (blue arrows), with a branching-tree appearance. There is extrahepatic beading with intervening sites of a normal, narrow stricture (long red arrow), and mildly dilated extrahepatic ducts (yellow arrow).

Autoimmune liver diseases

Autoimmune liver diseases comprise aspectrum of progredient idiopathic inflammatory diseases. Typical histological features of autoimmune hepatitis (AIH) include the pattern of chronic hepatitis with predominant plasma cell-rich interface activity, rosetting of hepatocytes, and emperipolesis. Florid bile duct lesions are the key feature of primary biliary cholangitis (PBC); onion-like periductal fibrosis characterizes the primary sclerosing cholangitis (PSC). Variants of AIH, or overlap syndromes, show intersecting histomorphologic findings with PBC or PSC. The diagnosis of the different autoimmune inflammatory liver diseases is based on clinical presentation, a hepatitic or cholestatic pattern of liver enzymes, immuno-serological findings, image analysis in PSC, and liver biopsy as afacultative or obligatory adjunct. Liver biopsy plays amajor role in the diagnosis of AIH, small-duct PSC, AMA-negative PBC, IgG4-related diseases, overlap syndrome, and in the recognition of concurrent liver diseases, especially drug-induced liver diseases. Herewith pathologists can help clinicians find adequate therapy for different autoimmune inflammatory liver diseases.

Eary primary sclerosing cholangitis – a challenging diagnosis

Primary sclerosing cholangitis (PSC) is a rare autoimmune disorder of the biliary system. PSC is fulminant in its course and leads to jaundice and biliary cirrhosis with specific radiological findings of the beading of larger ducts and pruning of smaller ducts. Though cholangiogram is the gold standard for PSC diagnosis, it may be inconclusive in patients with an early disease or small duct PSC or overlap with autoimmune hepatitis. These conditions may require a liver biopsy for confirmation of the underlying pathology. In this case report, we discuss one of these rare instances when a 24-year-old male was admitted with jaundice. During hospitalization, extensive workup, including cholangiograms, remained inconclusive, but based on a high suspicion of PSC, the patient underwent a liver biopsy, which confirmed our diagnoses

Magnetic resonance imaging features of small-duct primary sclerosing cholangitis.

To evaluate the biliary tree and hepatic parenchymal findings on magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) in small-duct primary sclerosing cholangitis (SD-PSC). Thirty-nine patients with biopsy-proven primary sclerosing cholangitis (PSC) without any bile duct abnormality on MRCP (n = 15) or ERCP (n = 24) at the time of diagnosis were identified. Follow-up MRCP was available in 36/39 patients (12/15 Baseline MRCP group and 24 Baseline ERCP group). Two radiologists in consensus assessed the MRI/MRCP findings. The baseline MRI/MRCP of 15 SD-PSC patients was compared with MRI/MRCP of 15 normal healthy potential liver donors (Control group). Comparisons were made between SD-PSC patients and the Control group, and between baseline and follow-up MRI/MRCP findings in the SD-PSC patients. In the 15 Baseline MRCP SD-PSC subjects, the biliary tree was normal with a trend of larger bile ducts compared to the Control group. Periductal enhancement (arterial phase: 70%, 7/10; delayed phase: 90%, 9/10), heterogeneous parenchymal signal on T2-weighted (53%, 8/15) and post contrast-enhanced images (70%, 7/10), and enlarged periportal lymph nodes (73%, 11/15) were frequently present in patients with SD-PSC. Eight (33%) of 24 SD-PSC patients who had normal MRCP at baseline MRCP or initial follow-up MRCP after normal baseline ERCP showed large-duct PSC (LD-PSC) features on follow-up and the 10-year cumulative incidence for progression to LD-PSC rate was 8.5%. SD-PSC patients have a normal biliary tree but frequently have peribiliary enhancement, abnormal parenchymal signal intensity, and periportal lymphadenopathy. One-third shows progression to LD-PSC on follow-up.