Autoimmune Cholangiopathy Research Articles

A Review of IgG4-related Sclerosing Cholangitis (IgG4-SC).

IgG4-related sclerosing cholangitis (IgG4-SC) is a unique, steroid-responsive, fibroinflammatory condition that is more commonly found in older men and is strongly associated with autoimmune pancreatitis (AIP). It may pose a diagnostic challenge at times due to closely mimicking hepatobiliary diseases such as primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and cholangiocarcinoma. IgG4-SC has an excellent prognosis when promptly diagnosed and treated with steroids. Literature search strategy: The authors searched PubMed and Google Scholar, for articles with the search terms "autoimmune cholangiopathy" and "IgG4 cholangiopathy."

MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

Primary sclerosing cholangitis (PSC) is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis, with no curative treatment available, and liver transplantation is inevitable for end-stage patients. Human placental mesenchymal stem cell (hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis, inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease. Here, we prepared hpMSC-derived exosomes (ExoMSC) and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2−/− mice and multicellular organoids established from PSC patients. The results showed that ExoMSC ameliorated liver fibrosis in Mdr2−/− mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis, and the percentage of CD4+IL-17A+T cells was reduced both in ExoMSC-treated Mdr2−/− mice (Mdr2−/−-Exo) in vivo and ExoMSC-treated Th17 differentiation progressed in vitro. Furthermore, ExoMSC improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids. Thus, our data demonstrate the anti-fibrosis effect of ExoMSC in PSC disease by inhibiting Th17 differentiation, and ameliorating the Th17-induced microenvironment, indicating the promising potential therapeutic role of ExoMSC in liver fibrosis of PSC or Th17-related diseases.

Histological diagnosis of primary biliary cholangitis in one patient without cholestasis alterations: a case report that escaped guidelines

Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts for 22.27 cases/100,000 habitants in Europe. To establish the diagnosis of PBC according to the European Association for the Study of the Liver (EASL) guidelines, two criteria must be satisfied among alkaline phosphatase (ALP) alterations, autoantibody positivity, and histologic abnormalities. Early treatment is effective in prolonging survival. Current guidelines do not suggest hepatic biopsy in patients with autoantibody positivity without cholestasis alterations. However, many patients with these characteristics have been diagnosed with PBC disease only histologically, mainly patients with normal ALP and elevated gamma-glutamyl transferase (GGT), whose normalization has been used as a marker for the follow-up. In contrast, this is the case of a patient with autoantibody positivity and both ALP and GGT within the range, diagnosed for PBC by histology. The manuscript wants to propose the re-evaluation of the role of liver biopsy in PBC diagnosis and the need for a serological or histological biomarker in the follow-up of patients without cholestatic alterations.

Clinical performance of AMA-M2, anti-gp210 and anti-sp100 antibody levels in primary biliary cholangitis: When detected by multiplex bead-based flow fluorescent immunoassay.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy, characterized by the presence of some autoantibodies in the serum. This study aimed to evaluate the clinical significance of AMA-M2, anti-gp210 and anti-sp100 antibody levels detected by multiplex bead-based flow fluorescent immunoassay (MBFFI) in PBC. This study cohort included 238 PBC patients, 81 autoimmune hepatitis (AIH) patients, 62 systemic lupus erythematosus (SLE) patients, and 118 healthy controls. Serum AMA-M2, anti-gp210 and anti-sp100 antibody were detected by MBFFI and immunoblotting assay (IBT). The relationship between three antibody levels and cirrhosis, liver function, cholestasis markers and therapeutic effect to ursodesoxycholic acid (UDCA) was evaluated in PBC. MBFFI were presented good coincidence rate (87.39%-95.38%) with IBT. The level of AMA-M2, anti-gp210 and anti-sp100 antibodies in PBC patients were higher than other disease group and healthy controls (p ＜ .01). When compared with the healthy controls group, the AUC of AMA-M2, anti-gp210 and anti-sp100 antibodies were 0.9245, 0.7619, and 0.6789, respectively. In addition, gp210 antibody levels have diagnostic value in patients with liver cirrhosis (AUC: 0.7567). We found that when combine detect these three antibodies, the sensitivity was higher than individually detection. High level of serum anti-gp210 antibody could be related to worse liver function and more severe cholestasis in PBC patients. Moreover, serum antibody levels may decrease or remained flat in patients who responded well to UDCA. The detection of AMA-M2, anti-gp210 and anti-sp100 antibody levels by MBFFI showed good performance in the diagnosis of PBC. Serum anti-gp210 antibody level is related to cirrhosis, poor liver function and severe cholestasis in PBC.

Excellent outcome in patients with primary biliary cholangitis in Northwest Italy followed up for up to 30 years.

Primary biliary cholangitis (PBC) is a rare chronic autoimmune cholangiopathy, characterized by a variable course and response to treatment. We aimed to describe long-term outcomes of PBC patients referred to three academic centres in Northwest Italy. This is an ambispective cohort study of PBC patients (retrospective component: diagnosis before 1 January 2019; prospective component: thereafter), including 302 patients: 101 (33%) followed up in Novara, 86 (28%) in Turin, 115 (38%) in Genoa. Clinical features at diagnosis, biochemical response to therapy and survival were analyzed. Among the 302 patients (88% women, median age 55 years, median follow-up 75 months), alkaline phosphatase (ALP) levels significantly decreased during treatment with ursodeoxycholic acid (UDCA, P < 0.0001) and obeticholic acid (P < 0.0001). At multivariate analysis, ALP at diagnosis was predictive of 1-year biochemical response to UDCA [odds ratio 3.57, 95% confidence interval (CI) 1.4-9, P < 0.001]. Estimated median survival free of liver transplantation and hepatic complications was 30 years (95% CI 19-41). Bilirubin level at diagnosis was the only independent risk factor for the combined outcome of death, transplantation or hepatic decompensation (hazard ratio, 1.65, 95% CI 1.66-2.56, P = 0.02). Patients presenting with total bilirubin at diagnosis ≥0.6 times the upper normal limit (ULN) had a significantly lower 10-year survival compared to those with bilirubin <0.6 times ULN (63% vs. 97%, P < 0.0001). In PBC, both short-term response to UDCA and long-term survival can be predicted by simple conventional biomarkers of disease severity, obtained at diagnosis.

Immunoglobulin G4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis

Immunoglobulin G4-seronegative autoimmune cholangiopathy is a rare cause of biliary strictures. We describe a 27-year-old man presenting with elevated liver enzymes, recurrent cholangitis/bacteremia, biliary strictures, and normal immunoglobulin G4 levels, who was initially diagnosed with primary sclerosing cholangitis, and later listed for transplantation for recurrent bacteremia. Subsequent surveillance imaging demonstrated morphologic changes consistent with biliary strictures and autoimmune pancreatitis. Initiating corticosteroids resulted in liver enzyme normalization and stricture improvement. Diagnosing seronegative autoimmune cholangiopathy remains challenging given similar presentation to primary sclerosing cholangitis. This case highlights importance of a wide differential for biliary strictures, with increased suspicion in those developing pancreatic changes in this setting.

Abstract 136

Introduction: Insulin autoimmune syndrome (Hirata’s disease) is a rare cause of hypoglycemia characterised by recurrent hypoglycemic episodes due to insulin autoantibodies, without any prior exposure to insulin. Method: Retrospective review of patients with hyperinsulinemichypoglycemiawas done. 10 patients (8 females), aged between 7 to 60 years (mean 42.9 years), from year 2005 to 2021 were assessed. Results: Four patients presented with fasting hypoglycemia, while all of them had post-absorptive hypoglycemic episodes. Four (40%) patients had evidence of other autoimmune conditions (three Hashimoto’s thyroiditis &amp; one autoimmune cholangiopathy). Mean insulin was 2782uIU/mL (61-14,332), and mean C-peptide was 12.9 ng/dL (3.6-37.6). Mean anti insulin antibody level was 77.8% (13.6-98.82) in samples evaluated by RIA (till 2015), and 84.7 u/mL by ELISA (2016 onwards). Three (30%) patients had positive history of offending drug usage (clopidpgrel, torsemide and pantoprazole). One of the patients had history of Covid-19 infection three months prior. Treatment with low carbohydrate diet, alpha glucosidase inhibitor &amp;/or prednisolone was effective in all symptomatically. Conclusion: In hyperinsulinemichypoglycemia, when insulin is markedly elevated, but C-peptide is only moderately elevated, insulin autoimmune syndrome should be suspected and insulin in dilution and anti-insulin antibody should be checked. Also, history of other autoimmune conditions, and history of any offending drug usage should be diligently investigated in these patients.

S1935 A Unique Case of Small Duct Primary Sclerosing Cholangitis Leading to Recurrent Cholestatic Hepatitis

Introduction: Small Duct Primary Sclerosing Cholangitis (sdPSC) is the narrowing of intrahepatic bile ducts which often leads to cholestasis and cirrhosis. We present a patient diagnosed with sdPSC which is an uncommon form of PSC. Case Description/Methods: A 42-year-old male patient, with a history of hypertension and gunshot wound with bowel resection presented for abdominal pain associated with recurrent cholangitis. Previous history also included bouts of abdominal pain, jaundice and hyperbilirubinemia that occurred roughly three times a year. A liver biopsy was taken during admission and revealed mild portal inflammation and cholestasis, bridging fibrosis, and intracytoplasmic iron granules. One month later a colonoscopy showed patchy erythema with biopsies demonstrating mild acute proctitis. Given cholestatic pattern, + ANA 1:320, recurrent admissions with sepsis, and recent colonoscopy showing evidence of proctitis (biopsy proven), the patient was diagnosed with sdPSC with overlap of autoimmune cholangiopathy. The sdPSC was treated with a cadaveric liver transplant, and upon explant, the patient’s liver showed chronic obstructive cholangiopathy. His postoperative course was notable for persistently elevated bilirubin of which half was indirect. Upon ERCP, the liver showed a mild anastomotic stricture and tortuous duct which was treated with a stent. However, the stent was removed because of lack of frank stricture. The patient was started on a prednisone taper with tacrolimus. The patient is currently doing well post-transplant on low dose tacrolimus and mycophenolate. Discussion: Clinical presentation of sdPSC often consists of pruritis, jaundice, and acute cholangitis from cholestasis, and fatigue, liver failure and hepatosplenomegaly from liver cirrhosis. Notably, the patient presented with hepatomegaly, and jaundice. With this presentation, PSC, sdPSC, and benign recurrent intrahepatic cholestasis (BRIC) were all possible diagnoses. Unremarkable MRCP imaging highlighted the unlikeliness of PSC, and liver biopsy showed bridging fibrosis which excluded BRIC. Clinical diagnosis of sdPSC is difficult and a high degree of clinical suspicion is needed. The cause for Small Duct Primary Sclerosing Cholangitis is unknown, but there is an association with irritable bowel disease, presence of HLA-B8 and HLA-DR3 and autoimmune disease like hyper IgM.

S1745 IgG4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis

S1745 IgG4-Seronegative Autoimmune Cholangiopathy With Pancreatic and Hepatic Involvement Mimicking as Primary Sclerosing Cholangitis

New insights on the role of human leukocyte antigen complex in primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a rare autoimmune cholangiopathy. Genetic studies have shown that the strongest statistical association with PBC has been mapped in the human leukocyte antigen (HLA) locus, a highly polymorphic area that mostly contribute to the genetic variance of the disease. Furthermore, PBC presents high variability throughout different population groups, which may explain the different geoepidemiology of the disease. A major role in defining HLA genetic contribution has been given by genome-wide association studies (GWAS) studies; more recently, new technologies have been developed to allow a deeper understanding. The study of the altered peptides transcribed by genetic alterations also allowed the development of novel therapeutic strategies in the context of immunotolerance. This review summarizes what is known about the immunogenetics of PBC with a focus on the HLA locus, the different distribution of HLA alleles worldwide, and how HLA modifications are associated with the pathogenesis of PBC. Novel therapeutic strategies are also outlined.

Interplay between Mast Cells and Regulatory T Cells in Immune-Mediated Cholangiopathies.

Immune-mediated cholangiopathies are characterised by the destruction of small and large bile ducts causing bile acid stasis, which leads to subsequent inflammation, fibrosis, and eventual cirrhosis of the liver tissue. A breakdown of peripheral hepatic immune tolerance is a key feature of these diseases. Regulatory T cells (Tregs) are a major anti-inflammatory immune cell subset, and their quantities and functional capacity are impaired in autoimmune liver diseases. Tregs can undergo phenotypic reprogramming towards pro-inflammatory Th1 and Th17 profiles. The inflamed hepatic microenvironment influences and can impede normal Treg suppressive functions. Mast cell (MC) infiltration increases during liver inflammation, and active MCs have been shown to be an important source of pro-inflammatory mediators, thus driving pathogenesis. By influencing the microenvironment, MCs can indirectly manipulate Treg functions and inhibit their suppressive and proliferative activity. In addition, direct cell-to-cell interactions have been identified between MCs and Tregs. It is critical to consider the effects of MCs on the inflammatory milieu of the liver and their influence on Treg functions. This review will focus on the roles and crosstalk of Tregs and MCs during autoimmune cholangiopathy pathogenesis progression.

Advanced Imaging Within the Bile Duct During Endoscopic Retrograde Cholangiopancreatography

Despite innovation in bile duct imaging over the past 2 decades, indeterminate biliary strictures remain a diagnostic challenge. The prototypical case is a patient who presents with a bile duct stricture, usually symptomatic, but no discrete mass is identified on cross-sectional imaging. The differential diagnosis includes cholangiocarcinoma; other malignancies; and fibroinflammatory causes, such as primary sclerosing cholangitis and autoimmune cholangiopathy. How has recent innovation changed the approach to these patients?

Prednisone-Responsive Hypercalcemia in a Patient With IgG4 Disease and Elevated Serum PTHrP Levels

Background: Ninety percent of hypercalcemia cases are related to either primary hyperparathyroidism or malignancy (1). This case presents one of the atypical etiologies of hypercalcemia. Clinical Case: A 53-year-old man with past medical history of nephrectomy was admitted for acute respiratory distress syndrome secondary to SARS-CoV-2. Hospital stay was complicated by septic shock and acute kidney injury requiring hemodialysis. Three months post hospital admission, the patient developed non-parathyroid (PTH) mediated hypercalcemia. Lab work results showed elevated serum calcium of 12.7 mg/dl (8.6–10.6), ionized calcium 6.8 mg/dl (4.2–5.4), albumin 2.6 g/dl (3.4–5.4), serum creatinine of 3.5 mg/dl (0.5–1.5), eGFR of 18.4 ml/min, and a PTH of 4 pg/ml (12–88). Liver profile - total bilirubin of 10.5 mg/dl (0–1.2), direct bilirubin of 5.9 mg/dl (0–0.2), GGTP 2055 U/L (6–60), alkaline phosphatase of 936 u/L (40–125), bone fractionated alkaline phosphatase 216 u/L (0–55), 25-OH Vitamin D of 11 ng/nl (20–80), 1,25 OH vitamin D of <5 pg/ml (19–79), TSH of 3.56 mciu/mL (0.35–4.0), CPK of 20 u/L (21–232) and a normal SPEP and immune-electrophoresisTreatment for hypercalcemia was initiated with calcitonin and oral steroids (prednisone 40mg/day for 4 days, 20mg/day for 1 day, and 10mg/day for 2 days), resulting in normalization of serum calcium. Patient received tube feedings that contained 2192 mcg retinol activity equivalents of vitamin A daily, which is associated with vitamin A intoxication in the presence of renal insufficiency. Vitamin A returned 0.78 mg/L (0.3–1.2). Serum Parathyroid hormone-related peptide (PTHrP) was elevated at 12.4 pmol/L (0.0–2.0). There was no obvious malignancy on various imaging studies. A magnetic resonance cholangiopancreatography (MRCP) showed biliary stricturing suggestive of primary sclerosing cholangitis (PSC), however, liver biopsy was not consistent with PSC. Serum IgG4 level was found to be elevated to 142 mg/dl (range: 1–123) which raised suspicion for autoimmune cholangiopathy. Discussion: Patient presented with non-PTH mediated hypercalcemia with low serum 1,25 OHD levels and elevated serum PTHrP level. Although most cases of elevated PTHrP associated with hypercalcemia are due to solid tumors, increased PTHrP levels have been seen in hypercalcemic patients with hematological malignancies and rare benign causes such as pneumonia (5). Association of elevated hypercalcemia with elevated IgG4 levels and PTHrP levels has not been previously reported. MRCP findings and abnormal morphology detailed in liver biopsy are suggestive of IgG4-related disease (IgG4RD) (3). The responsiveness in hypercalcemia to prednisone also supports this diagnosis. IgG4RD is associated with multi-organ autoimmune involvement. This case report highlights another complication of IgG4RD (i.e. hypercalcemia) associated with elevated PTHrP levels.

Epidemiological and clinical profile of 302 patients with primary biliary cholangitis in Piedmont and Liguria

Introduction and aim: Primary biliary cholangitis (PBC) is a slowly progressive autoimmune cholangiopathy, mainly affecting women. Our aim was to describe clinical and epidemiological profile of PBC patients followed-up in three hub hepatological canters in Piedmont and Liguria.

S2568 DDD: Diagnostic Dilemma in Drug Induced Liver Injury: Adverse Reaction of Abiraterone in Treatment of Metastatic Prostate Cancer

INTRODUCTION: Drug-induced liver injury (DILI) is a benign and reversible form of liver injury that occurs as an adverse reaction to medication use. It is a leading cause of acute liver failure and requires prompt recognition and discontinuation of the offending agent to avoid development of chronic disease. We present a case of severe DILI secondary to Abiraterone use in a patient with prostate cancer. CASE DESCRIPTION/METHODS: A 67 year-old-male without known liver disease was seen for severely elevated liver enzymes, jaundice and abdominal pain. Pertinent history includes stage IV prostate cancer with metastasis to the bone and lymph nodes with initiation of Abiraterone four months prior. He denies excessive alcohol, acetaminophen or herbal supplement use. Initial liver panel results: AST 1668 (peak 2379), ALT 3093 (peak 3330), alk phos 185 (peak 361) and TB 14.3 (peak 29). INR was 1.40 (peak 1.65). While transplant center transfer was considered, given patient's stability and not meeting King's College Criteria for acute liver failure, this decision was deferred and he was placed on NAC for 48 hours. Extensive workup for other causes of elevated liver enzymes were negative including: Wilson’s disease, autoimmune hepatitis, HAV, HBV, HCV, EBV, HSV, CMV, alpha 1 antitrypsin deficiency, portal vasculature thrombosis and acetaminophen toxicity. Core needle biopsies revealed acute hepatitis with confluent and bridging necrosis as well as mild Kupffer cell siderosis with iron accumulation. Serum ferritin level was 28,441 and IgG4 was mildly elevated, which prompted concern for hemophagocytic lymphohistiocytosis(HLH), hemochromatosis and autoimmune cholangiopathy. Patient did not meet criteria for HLH, hemochromatosis types I-IV in the absence of HFE, HFE2, TFR2, HAMP and SLC40A1 gene mutations, nor did MRI or pathology staining reveal IgG4 cholangiopathy. LFTs normalized within four months and ferritin within six months. Abiraterone was not restarted. DISCUSSION: Abiraterone is an antiandrogen that inhibits CYP17. Although the mechanism of hepatic injury is unknown, Abiraterone has been shown to cause elevations in serum aminotransferase levels in up to 13% of patients and ALT elevations above 5x the ULN in 6% of patients, however only few documented cases are known in which patients displayed associated symptoms such as jaundice and no documentation of severe elevations in serum ferritin as seen in our patient. This case also highlights the diagnostic challenge in DILI.Figure 1.: A. Mild to moderate predominantly lymphocytic inflammation. B. Intact bile ducts.Figure 2.: Confluent necrosis with areas of bridging necrosis.Figure 3.: Iron stain with Kupffer cell siderosis.

S1523 Non-Classical Autoimmune Cholangiopathy Associated With Non-Cirrhotic Portal Hypertension

S1523 Non-Classical Autoimmune Cholangiopathy Associated With Non-Cirrhotic Portal Hypertension

1368 Hilar Inflammation Mimicking a Klatskin Tumor

INTRODUCTION: Hilar cholangiocarcinomas or Klatskin tumors (KT) pose significant diagnostic challenges; 15% of resections for KT prove to be non-malignant. Inflammatory, infectious, and other etiologies mimic radiological features of KT. A high index of suspicion is needed to avoid hepatic resection and associated morbidities while aggressively excluding KT. CASE DESCRIPTION/METHODS: A 64-year-old male who presented with jaundice, unintentional 50 lb weight loss, and fatigue was found to have bile duct dilation on ultrasound. A CT confirmed severe right and left hepatic duct dilatation with abrupt cutoff due to a 4 cm infiltrative hilar mass involving the right and left hepatic ducts, and extending into the common hepatic duct. Work-up for causes of jaundice (autoimmune hepatitis, hemochromatosis, alpha-1 antitrypsin deficiency, viral hepatitis, celiac sprue, autoimmune cholangiopathy) via ANA, AMA, F-actin, IgG, IgG4, HFE mutation, TIBC, ferritin, A1AT, tTG, hepatitis serologies was negative. Over 12 weeks, 3 ERCPs failed to confirm KT via biopsies, cytology, and fluorescence in situ hybridization (FISH). A severe proximal common hepatic duct stricture was found on initial ERCP, which was dilated and stented. ERCP with Spyscope showed hepatic bifurcation stricture improvement. This stricture was biopsied and again brushed, dilated and stented. A third ERCP showed further improvement in stricture and otherwise normal intra- and extra-hepatic ducts. Dilation to 8 mm was performed without further stenting. Cytology and FISH were negative for KT. Two CT guided biopsies of the mass were also negative for KT and failed to show biliary ductal thickening or clear evidence of the prior noted hilar mass. Two MRCPs, 7 months apart, showed significant improvement of right and left bile duct confluence stricturing, felt to represent fibrous tissue and scarring. DISCUSSION: Despite improvement in cross sectional imaging, advances in interventional radiologic and endoscopic modalities, differentiation between benign and malignant hilar biliary stenoses remains a major challenge. Up to 20% of hilar resection show chronic fibrosing inflammation without evidence of KT. We aggressively pursued this concern with 3 ERCPs (cytology, FISH, biopsy with Spyscope), and 2 CT guided biopsies. CT and MR showed radiologic improvement of the mass and lack of evidence of KT. Exclusion of autoimmune disease or other etiologies allowed a diagnosis of idiopathic inflammation, thus avoiding surgery.

1273 IgG4 Related Cholangiopathy Masquerading as Cholangiocarcinoma

INTRODUCTION: IgG4 related diseases can involve multiple organs, best described in cases of autoimmune pancreatitis (AIP). IgG4-related cholangiopathy is difficult to distinguish from other forms of biliary ductal disorders including primary biliary cholangitis, primary sclerosing cholangitis (PSC), and cholangiocarcinoma (ChCA). Specifically, IgG4 cholangiopathy and ChCA share many clinical and imaging findings which make it difficult to distinguish these entities. We report a rare case of IgG4 cholangiopathy mimicking a ChCA. CASE DESCRIPTION/METHODS: A 69-year-old male presented with nausea/vomiting, weight loss, painless jaundice, and CT suggestion of a malignant hilar mass. ERCP with cytology and EUS with FNA from the hilar mass were negative for malignancy. Two further ERCPs with Spyscope hepatic duct bifurcation biopsies showed severe stenosis of the right hepatic ducts and diffuse biliary stricturing suggestive of PSC. Brushings for cytology and fluorescence in situ hybridization (FISH) were obtained, balloon dilation and stenting performed. MRCP noted multifocal intrahepatic biliary strictures, suggestive of PSC; a hilar mass, as seen on CT, was not seen. The MR suggested a solid pancreatic uncinate process mass. A repeat EUS showed changes of chronic pancreatitis but no mass. A comprehensive review of the combination of intrahepatic strictures, pancreatic atrophy and uncinate mass suggested a diagnosis of IgG4 disease; an ANA was positive at 1:160 and IgG4 was elevated at 1,250 mg/dL (normal &lt; 123). The patient was started on prednisone and had complete resolution of abnormal liver tests, clinical symptoms, MR biliary ductal dilatation, and MR pancreatic mass within 3 weeks. DISCUSSION: While described in AIP, IgG-4 related diseases can affect multiple organs, including kidneys, liver, salivary gland, orbit, breast, pericardium, aorta, skin, lungs, prostate, meninges, and the pituitary gland. IgG4-related cholangiopathy is a distinct yet rare etiology, characterized by elevated serum IgG4 levels and IgG4-positive plasma cell infiltration with storiform fibrosis/obliterative phlebitis of the bile duct wall. It has been identified in patients with concomitant AIP and is steroid responsive. Early diagnosis of IgG4 cholangiopathy avoids prolonged hospitalizations, unnecessary repeated procedures, and morbidity/mortality due to treatment delay We describe a rare case of IgG4 autoimmune cholangiopathy with delayed diagnosis due to concern for ChCA.

SAT-086 A Rare Case of Cholestatic Liver Disease Causing Markedly Elevated LDL Successfully Managed with Plasmapheresis and Ursodeoxycholic Acid

Background Hypercholesterolemia (HC) in cholestatic liver disease commonly involves a high lipoprotein-X (LpX) and low LDL receptors. No evidence has been found to suggest the association of LpX with an increased risk of cardiovascular disease (CVD). Hence, lipid lowering therapy is unnecessary as HC improves with treatment of cholestasis, but plasmapheresis should be considered in markedly elevated LDL values given the uncertainty of short term complications. Clinical Case A 47-year-old man with HTN, DMT2, nephrotic syndrome secondary to DM glomerulosclerosis and CKD stage 3 was admitted for an NSTEMI and acute heart failure due to non-ischemic cardiomyopathy. On exam he had jaundice and hepatomegaly without xanthelasma or tendon xanthomas. Laboratory evaluation revealed elevated HDL 200 [35-75 mg/dl], LDL 2,182 [0-130 mg/dl] and triglyceride 326 [30-150 mg/dl] although his lipid panel four months ago was normal. He had no family history of HC or premature CAD. Interestingly, two months prior the patient was seen in GI clinic due to jaundice, pruritus, acholia and coluria. Work-up showed cholestasis with total bilirubin 5.2 [0.1-1.2 mg/dl], AST 148 [0-40 U/L], ALT 112 [5-25 U/L], alkaline phosphatase 1,874 [20-120 U/L] and GGT 2,307 [3-60 U/L]. Further evaluation was unrevealing with negative viral hepatitis serologies, antinuclear antibodies, anti-smooth muscle antibody, anti-mitochondrial antibody, ceruloplasmin, α-1antitrypsin. He underwent liver biopsy which demonstrated cholestatic hepatitis with advanced biliary fibrosis, lymphocytic cholangitis and perivenular infiltrate thought secondary to an atypical autoimmune cholangiopathy. Due to concern for hyperviscosity and potential CVD complications, two sessions of plasma exchange were performed with a rapid lowering of LDL to 661 mg/dL. He was given a dose of evolocumab and discharged on ursodeoxycholic acid with improvement in liver function and normalization of lipid panel within three weeks. His HC was presumed mainly from atypical autoimmune cholangiopathy. LpX was unlikely since his Apolipoprotein B was elevated at 239 [RR 52-109 mg/dl]. Once his liver function normalized, he was started on high intensity statin and ezetimibe due to an elevated CVD risk with a low ApoA 30 mg/dL [RR 94-176]. Conclusion This is a rare case of cholestatic liver disease causing markedly elevated LDL, successfully managed with plasma exchange and ursodeoxycholic acid with subsequent resolution of LDL abnormality.

A Case of Primary Biliary Tuberculosis with Subsequent Pulmonary Presentation

Introduction: The term hepatobiliary tuberculosis refers to the rare and localized form of hepatic tuberculosis as a distinct clinical entity, with signs and symptoms related to the hepatobiliary tract. We aimed to report a case of the primary biliary tuberculosis with subsequent pulmonary presentation. Case Presentation: A 28-year-old woman was admitted to our hospital due to recurrent abdominal pain, low-grade fever, and icterus and with a temperature of 38.2°C. According to magnetic resonance cholangiopancreatography (MRCP) with bile duct dilatation, IgG4, and high eosinophil with impression of autoimmune cholangiopathy, corticosteroid was administered. A few weeks later, she was hospitalized again because of fever and leukocytosis and the creation of multiple lymph nodes in the neck and abdomen. Biopsy of cervical lymph node was performed, which was not diagnostic. Smear, culture, and polymerase chain reaction (PCR) to detect tuberculosis were negative. According to eosinophilia and hypointense masses with the possibility of parasitic causes (Fasciola hepatica) triclabendazole was started. The symptoms briefly improved and she had little weight gain, but four months later she was hospitalized with pulmonary symptoms. Culture and sputum smear were positive for acid-fast bacilli. Conclusions: Hepatobiliary tuberculosis has delayed presentations with nonspecific manifestations. In our patient, despite that clinical presentations matched those of hepatobilliary tuberculosis, multiple biopsies from the abdominal and prepheral lymph nodes could not verify it. Therefore, diagnosis was made with delay, and finally, pulmonary presentation and positive smear for acid-fast bacilli confirmed tuberculosis.