Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with underlying inflammatory bowel disease (IBD). This study investigates how PSC predisposes individuals to altered inflammatory immune responses compared with IBD alone. A case-control study was conducted with a cohort of 75 patients, including 16 with PSC (14 with concomitant IBD), 39 with IBD alone, and 20 controls. Serum bile acid profile, proteomic analysis, and immune-related gene expression in the colon tissue were examined. Colonic tissue from PSC patients exhibited up-regulation of immune regulation and inflammatory signaling mRNA markers, including LGR5, IL-8, CCL2, COX2, TWIST1, and SNAIL. Additionally, PSC patients displayed a distinct proinflammatory serum proteomic signature and moderate elevation of some bile acids, such as glycochenodeoxycholic acid (GCDCA). Co-incubation of human-derived monocytes with GCDCA partially replicated the inflammatory profile observed in PSC. These findings suggest that circulating bile acids modulate the peripheral immune system proinflammatory response, contributing to the unique PSC phenotype.

• Keywords
• GCDCA, IBD, PSC, bile acids, immune response,
• MeSH
• Adult MeSH
• Inflammatory Bowel Diseases * immunology   complications   blood   genetics   MeSH
• Colon metabolism   immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Monocytes immunology   metabolism   MeSH
• Proteomics methods   MeSH
• Cholangitis, Sclerosing * immunology   blood   complications   genetics   MeSH
• Case-Control Studies MeSH
• Bile Acids and Salts * blood   immunology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bile Acids and Salts * MeSH

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree, leading to significant liver function impairment over time. There is a strong association with inflammatory bowel diseases (IBD), together representing a distinct and complex medical condition. Patients with PSC-IBD face a heightened risk of various cancers, particularly colorectal carcinoma (CRC) and cholangiocarcinoma (CCA) as the most common types. In this review, we aim to characterize the distinctive features of PSC-IBD-associated carcinomas. Cancer pathogenesis in PSC-IBD is shaped by various factors including dysregulated bile acid metabolism, gut dysbiosis, and unique immune responses. PSC-IBD-associated CRC is often right-sided and warrants vigilant monitoring due to its higher incidence and unique morphological features compared to CRC arising in the terrain of IBD alone. CCA shares substantial genetic similarities with extrahepatic CCA and poses diagnostic challenges since it is frequently detected at advanced stages due to symptom overlap with PSC. Besides, reliable predictive biomarkers for targeted therapy remain largely unexplored. The distinct molecular, genetic, and histopathological profiles of CRC and CCA in PSC-IBD underscore the complexity of these malignancies and highlight the need for continued research to develop precise therapeutic strategies.

• Keywords
• Cholangiocarcinoma, Colorectal carcinoma, Crohn’s disease, Inflammatory bowel disease, Primary sclerosing cholangitis, Ulcerative colitis,
• MeSH
• Cholangiocarcinoma * pathology   etiology   genetics   MeSH
• Inflammatory Bowel Diseases * complications   pathology   MeSH
• Colorectal Neoplasms * pathology   etiology   genetics   MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Bile Duct Neoplasms * pathology   etiology   genetics   MeSH
• Cholangitis, Sclerosing * complications   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

Gastrointestinal tract is the most common locality for well-differentiated neuroendocrine tumors (NET). While their occurrence in patients with ulcerative colitis (UC) is uncommon, it has been well documented. However, the causal relationship between development of NET and chronic intestinal inflammation or dysplasia remains controversial. The presence of NET in the ileal pouch in UC patients has been described only in a few reports to date. In this article, we present a case of such a tumor arising in the pouch in a patient with primary sclerosing cholangitis-associated UC, who underwent a restorative proctocolectomy with ileal pouch anal anastomosis and liver transplantation. The case is supported by a review of a relevant literature. Correspondence address: Ondrej Fabian Clinical and Transplant Pathology Centre Institute for Clinical and Experimental Medicine Videnska 1958/9 Prague, 14021 Czech Republic ondrej.fabian@ikem.cz; ondrejfabian5@gmail.com.

• Keywords
• Ulcerative colitis, carcinoid, neuroendocrine tumor, pouch, ulcerative colitis,
• MeSH
• Humans MeSH
• Ileal Neoplasms pathology   surgery   MeSH
• Neuroendocrine Tumors * pathology   surgery   MeSH
• Colonic Pouches * pathology   MeSH
• Proctocolectomy, Restorative * adverse effects   MeSH
• Cholangitis, Sclerosing * pathology   complications   MeSH
• Colitis, Ulcerative * pathology   complications   surgery   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Review MeSH

BACKGROUND: Periampullary tumours (PAT) may cause obstruction of distal choledochus. The bile stasis is a risk factor for microbial colonisation of bile (bacteriobilia), cholangitis, hepatic insufficiency and coagulopathy. PAT obstruction can be managed surgically or non-operatively - by inserting a biliary drain or stent (BDS). Although BDS allows for adequate bile drainage, liver function restitution and coagulopathy, increased bacteriobilia has been reported and this is associated with an increased incidence of postoperative complications. METHODS: A monocentric, prospective, comparative study including 100 patients operated with PAT. The effects of bacteriobilia and the presence of a drain in the biliary tract on the development of postoperative complications were evaluated. RESULTS: Positive microbial findings in bile were found in 67% of patients. It was 98% in the biliary drain group vs. 36% in non-drained patients (p = 0.0001). In 68% 2 or more different bacterial strains were simultaneously present (p = 0.0001). Patients with a positive microbial finding in bile had more frequent incidence of infectious complications 40.2% (27) vs. 9.1% (3); p = 0.0011. The most frequent infectious complication was wound infection 29.8% (20) vs. 3.03% (1); p = 0.0014. Similarly, a higher incidence of postoperative infectious complications occurred in patients with BDS - 36% (18) vs. 24% (12); p = 0.2752. CONCLUSION: The presence of a drain or stent in the biliary tract significantly increases the microbial colonisation of bile. It is associated with a significant increase in infectious complications, especially infections in the wound.

• Keywords
• Bacteriobilia, Complications, Periampullary tumor,
• MeSH
• Cholangitis * epidemiology   etiology   surgery   MeSH
• Cholestasis * MeSH
• Humans MeSH
• Neoplasms * MeSH
• Postoperative Complications epidemiology   etiology   MeSH
• Prospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Candida and other fungal species play an increasing role in nosocomial infections, including cholangitis and cholangiosepsis. Early diagnosis and prompt treatment are essential in successful patient outcomes. Fluconazole is an antifungal of choice in fluconazole-sensitive Candida infections. Little information is known about the fluconazole biliary excretion. Decreased tissue penetration may be one of the possible causes of treatment failure. Due to favorable pharmacokinetics, therapeutic drug monitoring of this antifungal has not been recommended routinely. In the presented case we report the successful therapeutic drug monitoring-guided fluconazole treatment in a patient with cholangitis and cholangiosepsis caused by fluconazole-sensitive Candida spp.

Lay abstract A successful fluconazole treatment of Candida cholangitis based on therapeutic drug monitoring, is described in our case study. Unlike other azole antimycotic agents, fluconazole is not considered a desirable candidate for therapeutic drug monitoring. However, as shown in our case study, a fixed dosage regimen might not lead to adequate fluconazole exposure in every patient and a personalized dosing regimen might be useful in the achievement of adequate fluconazole exposure and the successful treatment of Candida infection.

• Keywords
• Candida, TDM, bile, cholangitis, concentration, dosing, fluconazole, penetration, personalized, trough,
• MeSH
• Antifungal Agents therapeutic use   MeSH
• Cholangitis * drug therapy   MeSH
• Fluconazole therapeutic use   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Drug Monitoring MeSH
• Sepsis * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antifungal Agents MeSH
• Fluconazole MeSH

IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.

• MeSH
• Diagnosis, Differential MeSH
• Immunoglobulin G MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Bile Duct Neoplasms * diagnosis   MeSH
• Cholangitis, Sclerosing * diagnosis   MeSH
• Rare Diseases MeSH
• Bile Ducts, Intrahepatic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Immunoglobulin G MeSH

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

• MeSH
• Alanine Transaminase blood   MeSH
• Aspartate Aminotransferases blood   MeSH
• Time Factors MeSH
• Child MeSH
• gamma-Glutamyltransferase blood   MeSH
• Glucocorticoids therapeutic use   MeSH
• Inflammatory Bowel Diseases epidemiology   MeSH
• Internationality MeSH
• Drug Resistance MeSH
• Humans MeSH
• Adolescent MeSH
• Hypertension, Portal epidemiology   physiopathology   MeSH
• Graft Survival MeSH
• Disease Progression MeSH
• Recurrence MeSH
• Registries MeSH
• Graft Rejection drug therapy   epidemiology   pathology   MeSH
• Risk Factors MeSH
• Cholangitis, Sclerosing blood   epidemiology   surgery   MeSH
• Liver Transplantation * MeSH
• Age Factors MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Alanine Transaminase MeSH
• Aspartate Aminotransferases MeSH
• gamma-Glutamyltransferase MeSH
• Glucocorticoids MeSH

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease. Differential diagnostics can confuse it with immunoglobulin (Ig) G4-related sclerosing cholangitis (SC), an IgG4-related disease with clearly proven autoimmune origin. Differential diagnosis is made even more challenging because PSC with increased IgG4 levels (PSC-increased IgG4) also occurs. In order to facilitate their differential diagnosis, we reviewed recent literature regarding the etiologies, identifying characteristics, the most useful diagnostics, treatment, and the progression of these partially similar diseases. It is clear that PSC's pathogenesis differs from that of IgG4-related SC. In any differential diagnosis between PSC and PSC-increased IgG4, high IgG1 and low or normal IgG2 levels are characteristic for patients with PSC. Histological examination of the biliary tree wall in patients with IgG4-related SC typically reveals such changes as storiform fibrosis, obliterative phlebitis, and venulitis. These are absent in PSC-increased IgG4, which is characterized by a typical circular thickness in different parts of the biliary ducts. Finally, PSC is associated with inflammatory bowel disease, which is rare in IgG4-related SC, and more frequently is associated with cholangiocarcinomas and colon cancers. As distinct from IgG4-related SC, PSC is not a primary autoimmune disease.

• MeSH
• Autoimmune Diseases * diagnosis   MeSH
• Diagnosis, Differential MeSH
• Immunoglobulin G MeSH
• Humans MeSH
• Cholangitis, Sclerosing * diagnosis   MeSH
• Bile Ducts, Intrahepatic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Immunoglobulin G MeSH

Inflammatory bowel disease (IBD) includes Crohns disease (CD) and ulcerative colitis (UC). Those are chronic gastrointestinal disorders of inflammatory nature and not fully known etiology. As a result of their immune-mediated mechanism and complex impact on the whole organism other organs than gastrointestinal system may be affected in many ways. These extraintestinal manifestations (EIM) and complications may severely deteriorate prognosis of the patient, cause his morbidity and worsen the quality of life. While classical extraintestinal manifestations, such as enteropathic arthropathy, skin or eye involvement or primary sclerosing cholangitis, share common immunopathological mechanism with IBD, whole range of other disorders may result from various anatomical or metabolic abnormalities caused by IBD or its treatment. This review focus on the most common extraintestinal complications, such as anaemia, metabolic bone disease, biliary and urolithiasis, which we meet in our daily clinical practice.

• Keywords
• anaemia, anemia, extraintestinal complications, inflammatory bowel disease, lithiasis, metabolic bone disease,
• MeSH
• Crohn Disease * MeSH
• Inflammatory Bowel Diseases * complications   MeSH
• Skin Diseases * MeSH
• Quality of Life MeSH
• Humans MeSH
• Cholangitis, Sclerosing * MeSH
• Colitis, Ulcerative * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

IgG4-related disease is a recently defined clinical entity that can manifest itself in any organ. The most common gastrointestinal manifestations are diseases of the pancreas (autoimmune pancreatitis type 1) and biliary tree (IgG4-associated cholangitis); involvement of liver parenchyma is uncommon and the affection of tubular organs is very rare. IgG4-related pancreatitis and cholangitis can mimic malignancies in their clinical presentation. Diagnosis is often difficult and requires careful evaluation of the combination of symptoms, serology and imaging findings, while adhering to the established diagnostic criteria. The first line of treatment is the administration of corticoids and the remission is achieved in the vast majority of patients. In case of contraindication, intolerance or failure of corticotherapy, patients should receive B cell depletion therapy (rituximab). Based on the available knowledge, monotherapy with other immunosuppressants is not considered to be sufficiently effective. Some patients may benefit from maintenance treatment to prevent relapse, which is otherwise common in both IgG4-related pancreatitis and cholangitis. Recognized IgG4-related disease has a good prognosis, but some patients develop irreversible fibrotic changes in the affected organ with consequent dysfunction; the possible association of the disease with a higher risk of malignancy has not yet been reliably elucidated.

• Keywords
• IgG4 associated disease, IgG4-related cholangitis, IgG4-related disease, IgG4-related pancreatitis, autoimmune pancreatitis,
• MeSH
• Autoimmune Diseases * diagnosis   MeSH
• Cholangitis * MeSH
• Gastroenterology * MeSH
• Immunoglobulin G4-Related Disease * diagnosis   MeSH
• Humans MeSH
• Pancreatitis * diagnosis   MeSH
• Cholangitis, Sclerosing * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH