Clinical Case Summary

A 48-year-old man was referred to the hospital after an accident at work because of a five-meter fall, associated with multiple trauma requiring amputation of the left upper limb and prolonged hospitalization in an intensive care unit.
During rehabilitation at the outpatient clinic, he had a mild COVID-19 illness, where progressive cholestasis was detected, so he was referred for study in consultation.
Later he was admitted to the gastroenterology department due to jaundice, choluria, and itching that was difficult to manage. Retrospectively, it was found that cholestasis appeared during intensive care hospitalization and has worsened since then. Magnetic resonance cholangiopancreatography (MRCP) was performed showing a 17mm stricture at the common hepatic duct and multiple irregularities of the intrahepatic bile ducts (IHBD). Human immunodeficiency virus serology was negative and serum IgG4 was normal. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a stricture of the common hepatic duct and multiple IHBD strictures (Figure 1 – bile duct strictures on cholangiography); a plastic stent was placed. Cytology of the dominant stenosis was negative for malignancy. Cholangioscopy showed " biliary casts and inflammatory changes of the entire biliary epithelium from the emergence of the cystic duct to the hilum and IHBD, with edema, friability and membranous exudate, more marked in the hilum, aspects not characteristic of primary sclerosing cholangitis. Two stents were placed in the left and right bile ducts". Biopsies revealed “acute xanthogranulomatous cholangitis” (Figure 2 - foamy histiocytes in bile ducts). The diagnosis of critical illness cholangiopathy with an atypical histology was done and the patient was referred for a transplant consultation.
Since then, two episodes of cholangitis happened and ERCP was performed with the extraction of both stents. It was decided at the transplant meeting to start a pre-transplant study.

References

•Martins, P. and Verdelho Machado, M. (2019) ‘Secondary sclerosing cholangitis in critically ill patients: An underdiagnosed entity’, GE - Portuguese Journal of Gastroenterology, 27(2), pp. 103–114. doi:10.1159/000501405.
•Zhang, J.Q. et al. (2022) ‘Xanthogranulomatous cholangitis mimicking cholangiocarcinoma: Case report and review of literature’, International Journal of Surgery Case Reports, 93, p. 106921. doi:10.1016/j.ijscr.2022.106921.

Clinical Case Summary

A 57-year-old woman visited the emergency department due to feeling extremely tired for four weeks. During the examination, she appeared alert but disoriented in space and time. She also had mild jaundice and flapping. The test results showed a total bilirrubin of 12.6mg/dL, direct bilirubin of 5.88mg/dL, ALT 265 IU/L, AST 801 IU/L, alkaline phosphatase 289 IU/L, INR 1.95. An abdominal computed tomography (CT) showed normal liver and no dilation of the bile ducts. The brain CT showed no abnormalities. The diagnosis of acute liver failure was assumed, and the liver transplant team was contacted.
The patient had a medical history of multiple sclerosis and borderline personality disorder. She had been recently hospitalized in a psychiatry unit where an imaging exam identified active lesions of multiple sclerosis. As a result, she underwent treatment with methylprednisolone 1g/day for 5 days and was discharged six weeks before her current visit.
The liver study showed negative results for viral hepatitis; her ceruloplasmin and urinary copper were normal. IgG was increased; ANA had a title of 1/320; ASMA and AMA were negative. A liver Doppler showed patent vessels. A transjugular liver biopsy showed "moderate periportal and severe lobular hepatitis (centrilobular necrosis), with numerous plasma cells, without specific fibrosis - probable autoimmune hepatitis" (Figure 1).
Due to her worsening condition, it was decided to start prednisolone 1mg/kg/day, which showed good clinical and laboratory response. She was discharged with instructions to reduce corticotherapy and to start azathioprine.
There remains a doubt between the diagnosis of autoimmune hepatitis caused by a drug or drug-induced liver injury with autoimmune-like histology. This case is interesting because it is unusual for a corticosteroid to trigger autoimmune pathology. It is also uncommon to prescribe a medication or a similar one that was suspected of causing hepatotoxicity.

Clinical Case Summary

Introduction: PSC is closely associated with IBD and affects up to 3.6% of Crohn's disease patients, while AIH is also more prevalent in IBD patients, in up to 16% of patients.
Case report: We report a female patient who, at the age of 14, presented with right hypochondrial pain and abnormal liver biochemistry (SGOT: 44 U/l, SGPT: 145 U/l, γ-GT: 300 U/l, ALP: 421 U/l, TBL: 1 mg/dL). The patient underwent MRCP (Figure A) which revealed local strictures with prostenotic dilatation in both intrahepatic and extrahepatic bile ducts, suggestive of PSC. One year later the patient presented with severe abdominal pain and bloody diarrhea. Ileocolonoscopy showed terminal ileitis (Figure B) and segmental colitis. Histological evaluation (Figure C) showed disruption of the architecture, focal erosions of the epithelium, mild mucopenia, inflammatory infiltrate in the dermis, sites of cryptitis and focal formation of crypt abscesses with extension of inflammation to the muscularis mucosae, suggestive of Crohn’s Disease. Two years later, in a regular laboratory test, the patient had abnormal liver function tests (SGOT: 211 U/l, SGPT: 603 U/l, γ-GT: 54 U/l, ALP: 105 U/l, TBL: 0.9 mg/dl). Further evaluation with immunoassay revealed ANA (+) 1/80, AMA (-), SMA (+) 1/160, + F-actin, anti-LKM (-), anti-LC (-), anti-LM (-), p ANCA (+) 1/80, so the patient underwent percutaneous liver biopsy with findings of portal spaces with presence of waxy-containing macrophages, thin fibrous septa, parenchyma with centrolobular necrosis with aggregates of inflammatory cells and waxy macrophages, suggestive of Autoimmune Hepatitis. Today, the patient is in clinical remission under treatment with Ursodeoxycholic acid, Ustekinumab and Mycophenolate Mofetil.
Conclusion: The association of IBD with PSC, AIH and variant forms is now known, however the complexity of the diseases presents a challenge for the clinician and the provision of individualized care.

References

1. Ballotin VR, Bigarella LG, Riva F, Onzi G, Balbinot RA, Balbinot SS, Soldera J. Primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome associated with inflammatory bowel disease: A case report and systematic review. World J Clin Cases. 2020 Sep 26;8(18):4075-4093.
2. Saich R, Chapman R. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease. World J Gastroenterol. 2008 Jan 21;14(3):331-7.
3. Rocha HC, Vilela EG. Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases. Gastroenterol Hepatol. 2022 Feb;45(2):83-90. English, Spanish.
4. Malik T, A, Gutierrez A, M, McGuire B, Zarzour J, G, Mukhtar F, Bloomer J: Autoimmune Hepatitis-Primary Sclerosing Cholangitis Overlap Syndrome Complicated by Crohn’s Disease. Digestion 2010;82:24-26.

Clinical Case Summary

This case report describes the clinical history of a 59 years-old female with a delayed diagnosis of primary biliary cholangitis (PBC) and celiac disease (CeD), ultimately requiring orthotopic liver transplantation (OLT). In June 2021 the patient developed weight loss, fatigue, anorexia, diarrhea, and generalized itching. As the patient showed progressive worsening of symptoms, an ultrasound scan was performed in May 2022 revealing hepato-splenomegaly, ascites and cholelithiasis, which required hospitalization. Laboratory tests showed hyperbilirubinemia, elevated liver enzymes with a cholestatic pattern, thrombocytopenia, and anemia; serology was positive for antimitochondrial (AMA) and antinuclear antibodies (ANA) and abdominal MRI confirmed intrahepatic bile duct alterations consistent with PBC. Persistent diarrhea and weight loss despite treatment with ursodeoxycholic acid and cholestyramine, required further evaluation for CeD. High tissue transglutaminase antibody levels and duodenal villous atrophy (3B according to Marsh-Oberhuber Classification) confirmed the diagnosis. A gluten-free diet (GFD) was started with incomplete adherence; the patient’s liver function further deteriorated, leading, in October 2023, to an acute on chronic decompensation with ascites and jaundice (Child-Pugh C13 and MELD 32). She eventually underwent successful OLT via piggyback technique. One year after transplant, the patient showed a significant clinical improvement, resolution of diarrhea and itching associated with better adherence to a GFD, although sarcopenia and nutritional deficiencies persisted. This report underscores the critical need for early diagnosis, screening for other autoimmune diseases, strict dietary adherence, regular follow-up, as well as a multidisciplinary management, in patients with PBC and CeD to prevent severe liver dysfunction and improve outcomes.

Figure 1. Trend of liver function markers (AST, ALT, GGT, ALP), MELD, Child-Pugh since PBC diagnosis

References

1. Kingham JG, Parker DR. The association between primary biliary cirrhosis and coeliac disease: A study of relative prevalences. Gut 1998;42(1)

2. Jena A et al. Liver abnormalities in celiac disease and response to gluten free diet: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2023 Jan;38(1):11-22. doi: 10.1111/jgh.16039.

3. Yang J et al.. Prevalence and effect on prognosis of sarcopenia in patients with primary biliary cholangitis. Front Med (Lausanne). 2024 Feb 29;11:1346165. doi: 10.3389/fmed.2024.1346165

4. Al-Toma et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J. 2019 Jun;7(5):583-613. doi: 10.1177/2050640619844125.

5. European Association for the Study of the Liver, EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017 Jul;67(1):145-172. doi: 10.1016/j.jhep.2017.03.022. Epub 2017 Apr 18. PMID: 28427765.

Clinical Case Summary

Biliary pathology is a frequent motive for consultation in hospitals, and abdominal ultrasound is the first line-imaging test for its study. The genetic syndrome LPAC (Low Phospholipid-Associated Cholelithiasis) leads to the development of intrahepatic lithiasis. In this syndrome, there is a decrease in biliary phospholipids secretion caused by a mutation in the ABCB4 gene, responsible for a dysfunction of the MDR3 transporter. Despite being considered a rare entity, it accounts for 1-5% admissions for biliary pathology, affecting young women more frequently.
Two of three clinical criteria must be met for its diagnosis: symptoms onset before the age of 40, recurrence after cholecystectomy and compatible ultrasound appearance (presence of intrahepatic hyperechogenic spots, "comet tail" images or intrahepatic lithiasis with acoustic shadowing). Identification of the ABCB4 gene mutation is not a diagnostic criterion since it only appears in 50% of patients. Medical treatment with ursodeoxycholic acid is effective and cholecystectomy can be avoided.
We present a 23-year-old male who consulted for epigastric pain associated with vomiting. Laboratory tests showed elevation of amylase greater than three times above the upper limit of normal, which allowed the diagnosis of acute pancreatitis. Liver profile, calcium and triglycerides were within normal limits. The patient had no previous alcoholic intake. Abdominal ultrasound ruled out cholelithiasis but identified multiple intrahepatic hyperechogenic spots and "comet tail" signs. The patient was diagnosed with LPAC syndrome and treatment with ursodeoxycholic acid was initiated. During follow-up he did not present new episodes of biliary symptomatology.
The detection of the typical ultrasound signs of LPAC syndrome is the main tool for its suspicion. This disease is not as uncommon as it may seem, so it is essential to think about it in order to make a correct diagnosis and treatment of these patients.

References

Ultrasound image of intrahepatic lithiasis

Clinical Case Summary

A 48-year-old male previously healthy was referred to our department due to a recent diagnose of inflammatory bowel disease (IBD). A colonoscopy revealed inflammation from the sigmoid colon to the cecum. Histologic samples confirmed a diagnosis of IBD without specific characteristics of either ulcerative colitis or Crohn’s Disease.
Meanwhile at our department, an ongoing study (PROGNOSIS) was recruiting patients with newly diagnosed IBD (1). The patient was enrolled, leading to several examinations not part of standard clinical practice, including magnetic resonance cholangiopancreatography (MRCP). The MRCP was diagnostic for primary sclerosing cholangitis (PSC) despite the absence of symptoms or elevated alkaline phosphatase. Observation of gallbladder polyps were noted as accidental findings on the MRCP and later confirmed by abdominal ultrasound.
It was decided to proceed with an endoscopic ultrasound of the gallbladder, where numerous pedunculated polyps, some up to 10 mm, were found. Given the high risk of gallbladder cancer in patients with PSC, laparoscopic cholecystectomy was performed without complications. Histological examinations of polyps found no signs of dysplasia or malignancies.
PSC is a chronic inflammatory disease of the bile ducts with approximately 75% having concomitant IBD (2). PSC is classified as a premalignant condition due to the increased risk of cholangiocarcinoma, colorectal cancer, and gallbladder cancer with the increased cancer risk being present from the time of diagnosis (3–5). Cancer surveillance with imaging reduces deaths among PSC patients, underscoring the need for lifelong cancer surveillance (5). The patient presented would not have been diagnosed with PSC without the PROGNOSIS study due to normal liver parameters. Previous studies suggest underdiagnosis of PSC in IBD patients (6), emphasizing the need for improved diagnostic markers to identify individuals at high risk of developing PSC to ensure proper cancer surveillance.

References

Illustrations:
MRCP confirming the PSC diagnosis.
Ultrasonic picture from EUL of the gallbladder showing a pendaculated polyp of 10 mm in size.

References:
1. Attauabi, M. et al. Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): The protocol for a Copenhagen IBD Inception Cohort Study. BMJ Open 12, (2022).
2. De Vries, A. B., Janse, M., Blokzijl, H. & Weersma, R. K. Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis. World J Gastroenterol 21, 1956–1971 (2015).
3. Wijnands, A. M. et al. Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis. Gastroenterology 160, 1584–1598 (2021).
4. Sørensen, J. Ø. et al. Inflammatory bowel disease with primary sclerosing cholangitis: A Danish population-based cohort study 1977-2011. Liver International 38, 532–541 (2018).
5. Trivedi, P. J. et al. Effects of Primary Sclerosing Cholangitis on Risks of Cancer and Death in People With Inflammatory Bowel Disease, Based on Sex, Race, and Age. Gastroenterology 159, 915–928 (2020).
6. Lunder, A. K. et al. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterology 151, 660-669.e4 (2016).
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Clinical Case Summary

Introduction: Sarcoidosis is a multi-systemic disorder of unknown etiology that primarily involves the pulmonary system. Nevertheless, a diagnosis can be challenging for clinicians because of the potential for almost any organ to be affected. Hepatic granulomas occur in 50-65% of patients with systemic sarcoidosis, while isolated hepatic sarcoidosis is rare.
Aims & Methods: A 50-year-old Montenegrin female patient was consulted by a gastroenterologist due to multiple focal lesions open etiology in the liver and spleen detected on routine ultrasound examination.
Results: Laboratory results showed normal complete blood count, total bilirubin 11.1 µmol/L, aspartate-aminotransferase 35 U/L, alanine-aminotransferase 25 U/L, gamma-glutamyl transferase 247 U/L, pancreatic amylase 40 U/L, and lipase 23 U/L. Tumor markers were in range: carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, alpha fetoprotein (AFP), CA 72-4, except CA 15-3, which was slightly elevated. Increased activity of serum angiotensin-converting enzyme was shown. Viral and serological tests for hepatotropic viruses and autoimmune liver diseases were negative. Imaging methods performed were: Multi-Slice Computer Tomography (MSCT) of the lungs, abdomen and pelvis, Nuclear Magnetic Resonance of the abdomen with Magnetic Resonance Cholangiopancreatography (MRCP), mammography, upper endoscopy and colonoscopy, but these did not provide an answer to the primary cause of the focal lesion. In the end, a liver biopsy was performed, where non–caseous granulomas were described and a diagnosis of sarcoidosis was established.
Conclusion: The patient had isolated sarcoidosis of the liver and spleen, as no granulomatous abnormalities were identified in other organs. The patient showed a remarkable clinical response to corticosteroid therapy. Isolated hepatic and splenic sarcoidosis should be considered in asymptomatic patients with hepatosplenomegaly and suspected metastatic disease.

References

1. Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J. Sarcoidosis. Nat Rev Dis Primers. 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. Erratum in: Nat Rev Dis Primers. 2019;5(1):49
2. Franzen DP, Brutsche M, Nilsson J, Böni C, Daccord C, Distler O, Elsener D, Funke-Chambour M, Gruner C, Hayward-Könnecke H, Hostettler KE, Kündig T, Ribi C, Seebach JD, Seeger H, Vrugt B, Kolios AGA. Sarcoidosis - a multisystem disease. Swiss Med Wkly. 2022;152:w30049

Disclosure

This abstract was presented at the 11^th Congress of North Macedonian Society of Gastroenterohepatology with international participation held from June 9-11, 2023 in Ohrid, North Macedonia.