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.
- 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
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.
- 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
Gastrointestinální trakt představuje častou lokalitu pro dobře diferencované neuroendokrinní tumory (NET). Jejich výskyt u pacientů s ulcerózní kolitidou (UC) není častý, je však dobře dokumentovaný. Případný kauzální vztah mezi rozvojem NET a chronickým zánětem střevní sliznice či dysplázií epitelu nicméně zůstává nejasný. Výskyt NET v ileálním pouchi u pacientů s UC byl dosud popsán jen v několika kazuistických sděleních. Prezentujeme zde případ takovéhoto nádoru vznikajícího ve sliznici pouche u pacienta s UC asociovanou s primární sklerozující cholangoitidou, který podstoupil transplantaci jater a restorativní kolektomii s následnou ileální pouch-anální anastomózou. Popis případu je doplněn o přehled dostupné literatury.
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
Cholestatická onemocnění jater se vyznačují progresivní povahou a omezenými možnostmi konzervativní léčby. Jedinou efektivní metodou léčby terminálního stadia je transplantace jater, která signifikantně prodlužuje dobu přežití pacientů. Transplantace jater je v současnosti indikována nejen u pacientů s chronickým jaterním selháním nebo hepatobiliární malignitou, ale také u pacientů se sníženou kvalitou života při symptomech z obstrukce žlučovodů. Péče po transplantaci jater je specifická zejména z důvodu přítomnosti imunitně asociovaných onemocnění, např. idiopatických střevních zánětů u pacientů s primární sklerozující cholangitidou. Rekurence základního onemocnění v jaterním štěpu je častou dlouhodobou komplikací, která může negativně ovlivnit přežití štěpu i celkovou délku života. Navzdory riziku rekurence jsou dlouhodobé výsledky transplantace jater pro cholestatické nemoci výborné, přičemž pacienti s těmito diagnózami dosahují delšího přežití ve srovnání s ostatními transplantovanými pacienty.
Cholestatic liver diseases are characterized by their progressive nature and limited conservative treatment options. Liver transplantation is the only effective method of treatment for the terminal stage. Before the era of liver transplantation, patients with cholestatic disease had a significantly reduced life expectancy. Liver transplantation is now indicated not only for patients with chronic liver failure or hepatobiliary malignancy, but also for those with reduced quality of life from cholestatic symptoms. Post-transplant care is particularly specific because of the presence of immune-associated diseases, such as inflammatory bowel disease in patients with primary sclerosing cholangitis. Recurrence of the underlying disease in the liver graft is a common long-term complication that can negatively affect graft survival and overall life expectancy. Despite the risk of recurrence, the long-term outcomes of liver transplantation for cholestatic disease are excellent, achieving longer survival compared to other transplant recipients.
- Keywords
- indikace k transplantaci,
- MeSH
- Cholangitis * complications pathology therapy MeSH
- Inflammatory Bowel Diseases complications therapy MeSH
- Humans MeSH
- Cholangitis, Sclerosing complications pathology therapy MeSH
- Liver Transplantation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
U dětí a adolescentů rozeznáváme tři jaterní poruchy, které jsou asociované s autoimunitní patogenezí: autoimunitní hepatitidu (AIH), autoimunitní sklerotizující cholangoitidu (ASC) a de novo AIH vzniklou po transplantaci jater, která se nově označuje termínem na plazmocyty bohatá rejekce. Jedná se o progresivní onemocnění, které bez léčby vede ve většině případů k jaternímu selhání. Všechny tyto poruchy jsou charakterizovány histologicky zánětlivými změnami a sérologicky přítomností cirkulujících autoprotilátek a hypergamaglobulinemií IgG. Juvenilní AIH se dělí na dva typy podle přítomnosti jednotlivých protilátek: typ 1 a typ 2. Klinické projevy se mohou lišit, od akutních, chronických až po bezpříznakový průběh. Základem léčby je imunosupresivní terapie, kterou je třeba zahájit co nejdříve po stanovení diagnózy.
Autoimmune liver disease in children can be classified as: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC) and de novo AIH after liver transplantation (plasma cell rich rejection). When left untreated, these disorders are progressive in nature and can result in cirrhosis and terminal liver failure. They are characterised by presence of circulating autoantibodies, high levels of IgG class imunoglobulins and inflammatory changes on liver histology. There are two main subtypes of AIH depending on the type of specific autoantibodies detected: type 1 and type 2. AIH has a very wide spectrum of symptoms ranging from being asymptomatic to an acute severe fulminant disease. These liver disorders respond well to theimmunospuresive therapy which must be started as early as possible.
Primární sklerozující cholangitida (PSC) je chronické progresivní onemocnění žlučových cest. Mezi primární sklerozující cholangitidou dospělých a juvenilní formou existuje řada rozdílů. V dětském věku vídáme tuto diagnózu nejčastěji ve spojitosti se zánětlivým střevním onemocněním (IBD). Fenotyp IBD se u pacientů s PSC-IBD liší od těch bez souběžné diagnózy PSC. Obvykle bývá charakterizován mírnějším průběhem a nálezem pankolitidy, rectal sparingu a backwash ileitidy. U těchto pacientů může být častěji přítomná endoskopická aktivita IBD navzdory chybějícím symptomům. Průběh PSC spojené s Crohnovou nemocí je zpravidla méně závažný než u PSC spojené s ulcerózní kolitidou (PSC-UC). Na rozdíl od pacientů s izolovanou formou UC bývají pacienti s PSC-UC častěji léčeni monoterapií aminosalicyláty. Navíc bylo u pacientů s PSC-UC popsáno nižší riziko provedení kolektomie a potřeby kortikosteroidů, thiopurinů nebo biologické terapie než u klasické formy UC. Recentní práce naznačují, že žádná z aktuálně používaných léčebných modalit nedokáže zastavit progresi PSC, přičemž značná část pacientů dospěje do stadia jaterního selhání vyžadujícího transplantaci jater.
Primary sclerosing cholangitis is a chronic progressive disease of the biliary tract. There are many differences between adult primary sclerosing cholangitis and juvenile type. Major part of pediatric PSC patients will develop inflammatory bowel disease (IBD). The phenotype of IBD in patients with PSC-IBD differs from those without associated PSC and is characterized by a milder course and typical findings of pancolitis, rectal sparing and backwash ileitis. Endoscopic activity of the disease is more often present despite the absence of symptoms suggesting subclinical inflammation. The course of PSC associated with Crohn’s disease is usually less severe than that with ulcerative colitis (UC). Compared to patients with an isolated form of UC, patients with PSC-UC are more often treated with amino-salicylates monotherapy. Likewise, these patients have been reported to have a lower risk of undergoing colectomy or requiring steroids, thiopurines, or biologic therapy than patients without associated PSC. Recent data suggest that none of the current treatment modalities can stop the progression of PSC, and significant number of patients will end up with liver failure requiring a liver transplant.
- MeSH
- Child MeSH
- Inflammatory Bowel Diseases complications MeSH
- Humans MeSH
- Cholangitis, Sclerosing * diagnosis etiology complications therapy MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
Gastroenterologie, hepatologie a digestivní endoskopie jsou rychle se rozvíjející obory medicíny s množstvím recentních pokroků v diagnostice a léčbě v rozsahu celého gastrointestinálního traktu. Cílem naší práce je shrnout recentní pokroky na poli významných gastroenterologických situací, jako je akutní pankreatitida, funkční dyspepsie, racionální léčba inhibitory protonové pumpy a idiopatické střevní záněty. Pokrok zaznamenala i hepatologie v přístupu k cholestatickým chorobám, v léčbě alkoholové hepatitidy a nealkoholové choroby jater (NAFLD) a v poznání patofyziologie bilirubinu a žlučových kyselin. Digestivní endoskopie je invazivní částí gastroenterologie a zmíněna jsou klíčová témata jako screening karcino- mu pankreatu, využití umělé inteligence, resekce nízkorizikových neoplázií trávicí trubice, endoskopie tenkého střeva a pankreatobiliárních cest a extraluminální expanze endoskopie v podobě endoskopické submukózní a transmurální disekce, různých typů myotomie a využití lumen apozičních stentů.
Gastroenterology, hepatology and digestive endoscopy are rapidly evolving disciplines with significant advances in the diagnostics and treatment in the entire gastrointestinal tract. The aim of our article was to summarize new perspectives on relevant situations in gastroenterology and hepatology like acute pancreatitis, functional dyspepsia, rational indication of proton pump inhibitors, inflammatory bowel diseases (IBD), cholestatic liver diseases, alcohol induced hepatitis, non-alcoholic fatty live disease (NAFLD) and patophysiology of bilirubin and bile acids. Digestive endoscopy represents an interventional part of gastroenterology and key recent topics are mentioned like pancreatic cancer screening, arteficial intelligence, resection of low-risk neoplastic lesions, enteroscopy techniques, cholangio- and pancreatiscopy and extraluminal expansion of endoscopy techniques by means of endoscopic submucosal and transmural dissection, endoscopic myotomy and lumen apposing stents.
- MeSH
- Hepatitis, Alcoholic diagnosis complications therapy MeSH
- Bilirubin analysis MeSH
- Endoscopy, Digestive System classification trends MeSH
- Gastroenterology * trends MeSH
- Inflammatory Bowel Diseases diagnosis therapy MeSH
- Proton Pump Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Humans MeSH
- Pancreatitis diagnosis therapy MeSH
- Hypertension, Portal diagnosis therapy MeSH
- Cholangitis, Sclerosing diagnosis therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review 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.
BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.
- MeSH
- Bilirubin blood MeSH
- Biopsy MeSH
- Cholangiography MeSH
- Child MeSH
- gamma-Glutamyltransferase blood MeSH
- Humans MeSH
- Adolescent MeSH
- Platelet Count MeSH
- Prognosis MeSH
- Disease Progression MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Serum Albumin analysis MeSH
- Cholangitis, Sclerosing diagnosis mortality pathology surgery MeSH
- Liver Transplantation MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Kyselina ursodeoxycholová jakožto sekundární žlučová kyselina je po řadu desetiletí úspěšně využívána u patologických stavů postihujících žlučové cesty. Kromě disoluce žlučových kamenů se uplatňuje u chronických onemocnění jater či u reaktivní gastritidy navozené refluxem žluči. V následujícím textu je pojednán její terapeutický potenciál na pozadí pleiotropního mechanismu účinku.
Ursodeoxycholic acid, as a secondary bile acid, has been used successfully for many decades in pathological conditions affecting the bile ducts. In addition to the dissolution of gallstones, it is used in chronic liver diseases or in reactive gastritis induced by bile reflux. In the following text, its therapeutic potential against the background of its pleiotropic mechanism of action is discussed.
- MeSH
- Liver Cirrhosis, Biliary drug therapy MeSH
- Cholagogues and Choleretics administration & dosage pharmacology therapeutic use MeSH
- Cystic Fibrosis drug therapy MeSH
- Gastritis drug therapy MeSH
- Gastrointestinal Diseases * drug therapy MeSH
- Ursodeoxycholic Acid * administration & dosage pharmacology therapeutic use MeSH
- Humans MeSH
- Non-alcoholic Fatty Liver Disease drug therapy MeSH
- Cholangitis, Sclerosing drug therapy MeSH
- Check Tag
- Humans MeSH
