The liver and the biliary tree form the main excretory route of manganese (Mn) and copper (Cu). Cholestasis, can lead to the accumulation of these trace elements in the organism, resulting in toxicity to the basal ganglia of the central nervous system. The aim of our study was to reveal the influence of long-term cholestasis on the Mn and Cu levels in the blood of patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We recruited patients with PBC (n = 20) and PSC (n = 32). A control group (n = 40) was also set up. We also examined serum bile acid concentrations and liver enzyme activities. We did not observe any significant differences in any of these parameters between the PBC and PSC groups. The Mn and Cu levels in the PBC and PSC patients differed significantly from the that in the control group (p < 0.0001 and p < .021, respectively). Patients in whom the laboratory cholestasis markers normalized during ursodeoxycholic acid treatment (18/52;35%) presented with significantly lower levels of Mn and Cu (p = .015 and p = .012, respectively). Ten PSC patients showed normal levels of Mn and Cu six months after liver transplantation. Fine tremors, rigidity, dysarthria, and hypomimia were reported in nine (23%), eight (20%), four (10%), and eight (20%) patients, respectively. In addition to monitoring the cholestasis levels, liver function, and Mn and Cu levels during the long-term treatment of PBC and PSC patients, it is important to also regularly monitor the occurrence and development of extrapyramidal symptoms of Parkinson's-like syndromes.

• Keywords
• Manganese, cholestasis, copper, primary biliary cirrhosis, primary sclerosing cholangitis,
• MeSH
• Liver Cirrhosis, Biliary blood   therapy   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Manganese blood   MeSH
• Copper blood   MeSH
• Young Adult MeSH
• Aged MeSH
• Cholangitis, Sclerosing blood   therapy   MeSH
• Case-Control Studies MeSH
• Liver Transplantation MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Manganese MeSH
• Copper 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

Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival.

• Keywords
• bayesian statistics, disease recurrence, liver transplantation, patient and graft survival, primary sclerosing cholangitis,
• MeSH
• Bayes Theorem MeSH
• Humans MeSH
• Recurrence MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Cholangitis, Sclerosing * surgery   MeSH
• Liver Transplantation * adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Cholestasis is defined as hepatocyte and cholangiocyte bile excretion failure or failure of bile transport to the duodenum. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis as chronic progressive cholestatic diseases are the common reasons of chronic cholestasis. Altogether with cholestatic laboratory picture the pruritus, liver osteodystrophy and fatigue are associated symptoms in both diseases. All associated symptoms and complications are needed to be diagnosed and treated early. In case of liver cirrhosis complicatons of accompanied portal hypertension should be treated and liver transplantation must be considered in all those patients. Diagnosis of PBC is based on cholestatic laboratory features, animitochondrial antibody positivity or typical histological patern. Most patients are asymptomatic in time of diagnosis. First line therapy is ursodeoxycholic acid. In case of first line therapy failure, the prognosis is unfavourable. In this case, second line therapy must be considered. In case of PSC the diagnosis is based on MRCP finding mainly, laboratory test and liver biopsy in some cases. Progressive inflamatory and fibrosing impairment affecting intrahepatic and extrahepatict biliary ducts and strong association with inflamatory bowel disease, especially ulcerative colitis is typical for PSC. Endoscopic therapy with dilatation of dominant structure is crucial. The effect of pharmacotherapy is still being discussed and ursodeoxycholic acid could be used. During follow up patients are in the risk of bacterial cholangitis and malignant tumor development (cholangiogenic and colorectal carcinoma mainly). In PSC patients the severe pruritus and reccurent bacterial cholangitis could be an indication for the liver transplantation.

• Keywords
• biliary cholangitis, cholangitis, cholestasis, diagnostics, sclerosing cholangitis, treatment,
• MeSH
• Liver Cirrhosis, Biliary * complications   diagnosis   therapy   MeSH
• Cholestasis * pathology   MeSH
• Ursodeoxycholic Acid MeSH
• Humans MeSH
• Cholangitis, Sclerosing * complications   diagnosis   therapy   MeSH
• Bile Ducts pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Ursodeoxycholic Acid MeSH

Authors report about 3 cases of primary sclerosing cholangitis type I of the total 3,043 patients operated for benign disease of biliary ducts in the course of 10 year's period (1978-1987). Diagnosis was determined not only on the base of clinical symptoms but mainly on the base of ERCP, PTC and histological examination. Two cases of obstructive icterus were treated by hepato-jejuno-anastomosis after Rouxe and one patient by high-hilar anastomosis with jejunum and diahepatal drainage left for 3 months. During the postoperative period patients were treated with hepatoprotectives and corticosteroids.

• MeSH
• Middle Aged MeSH
• Humans MeSH
• Cholangitis, Sclerosing * diagnosis   surgery   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Case Reports MeSH

AIM: To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). METHODS: Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data. RESULTS: Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales. CONCLUSION: PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).

• Keywords
• Dysbiosis, Gut microbiota, Inflammatory bowel disease, Primary sclerosing cholangitis, Ulcerative colitis,
• MeSH
• Bacteria genetics   isolation & purification   MeSH
• Adult MeSH
• Dysbiosis etiology   microbiology   MeSH
• Feces microbiology   MeSH
• Colon microbiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Ribosomal, 16S isolation & purification   MeSH
• Sequence Analysis, RNA MeSH
• Aged MeSH
• Cholangitis, Sclerosing complications   microbiology   MeSH
• Gastrointestinal Microbiome * MeSH
• Intestinal Mucosa microbiology   MeSH
• Colitis, Ulcerative complications   microbiology   MeSH
• Healthy Volunteers MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• RNA, Ribosomal, 16S MeSH

BACKGROUND: Sclerosing cholangitis (SC) is a chronic cholestatic hepatobiliary disease with uncertain long-term prognosis in pediatric patients. This study aimed to evaluate long-term results in children with SC according to the types of SC. METHODS: We retrospectively followed up 25 children with SC over a period of 4-17 years (median 12). The diagnosis of SC was based on biochemical, histological and cholangiographic findings. Patients fulfilling diagnostic criteria for probable or definite autoimmune hepatitis at the time of diagnosis were defined as having autoimmune sclerosing cholangitis (ASC); other patients were included in a group of primary sclerosing cholangitis (PSC). The incidence of the following complications was studied: obstructive cholangitis, portal hypertension, advanced liver disease and death associated with the primary disease. RESULTS: Fourteen (56%) patients had PSC and 11 (44%) had ASC. Patients with ASC were significantly younger at the time of diagnosis (12.3 vs 15.4 years, P=0.032) and had higher IgG levels (22.7 vs 17.2 g/L, P=0.003). The mentioned complications occurred in 4 (16%) patients with SC, exclusively in the PSC group: one patient died from colorectal cancer, one patient underwent liver transplantation and two patients, in whom severe bile duct stenosis was present at diagnosis, were endoscopically treated for acute cholangitis. Furthermore, two other children with ASC and 2 children with PSC had elevated aminotransferase levels. The 10-year overall survival was 95.8% in all patients, 100% in patients without complicated liver disease, and 75.0% in patients with complications. CONCLUSION: In children, ASC is a frequent type of SC, whose prognosis may be better than that in patients with PSC.

• MeSH
• Hepatitis, Autoimmune diagnosis   drug therapy   epidemiology   mortality   MeSH
• Biomarkers blood   MeSH
• Time Factors MeSH
• Child MeSH
• Immunoglobulin G blood   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Incidence MeSH
• Kaplan-Meier Estimate MeSH
• End Stage Liver Disease epidemiology   MeSH
• Humans MeSH
• Adolescent MeSH
• Follow-Up Studies MeSH
• Jaundice, Obstructive epidemiology   MeSH
• Hypertension, Portal epidemiology   MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Proportional Hazards Models MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Cholangitis, Sclerosing diagnosis   drug therapy   epidemiology   mortality   MeSH
• Age Factors MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Biomarkers MeSH
• Immunoglobulin G MeSH
• Immunosuppressive Agents MeSH

BACKGROUND: Immunoglobulin (Ig) G4 associated sclerosing cholangitis is a rare inflammatory disease of the biliary tract. Although it is a very progressive condition, it responds to steroid therapy. IgG4 associated sclerosing cholangitis can mimic pancreatic carcinoma, cholangiocarcinoma, and primary sclerosing cholangitis; therefore, it is very important to obtain a differential diagnosis. IgG4 sclerosing cholangitis is a biliary form of IgG4 related systemic disease, in which afflictions of more organs is afflictions of more organs are common, typically biliary form together with pancreatic one. Nonspecific symptoms are obstructive icterus, fatigue, and weight loss. Atypical imaging of the biliary tree and pancreas can be used to distinguish it from other diseases. Laboratory data show elevation of bilirubin, liver enzymes, IgG4 and total IgG concentrations. Sometimes IgE is also elevated with the eosinophilia, oncomarker CA 19-9 and autoimmune antibody is sometimes detected. CASE: This article presents a case of IgG4 sclerosing cholangitis and its related findings. The patient was intially referred for suspected pancreatic tumour, the presumed diagnosis was later changed to cholangiocarcinoma type 4 with concurrent autoimmune pancreatitis. Atypical imaging in cholangiography made us suspect IgG4 inflammation and the diagnostic process began. CONCLUSION: The diagnosis of this disease uses so called HISORt criteria. It is a very complex process in which the success of steroid therapy as a final step can be conclusive, as it was in our case. It is essential to exclude a malign neoplastic growth. The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 5. 12. 2018 Accepted: 10. 1. 2019.

• Keywords
• IgG4 related systemic disease, IgG4-positive plasma cells, cancer of pancreas, cholangiocarcinoma, cholangiography, immunoglobulin G, prednison, sclerosing cholangitis,
• MeSH
• Diagnosis, Differential MeSH
• Immunoglobulin G metabolism   MeSH
• Humans MeSH
• Pancreatic Neoplasms diagnosis   MeSH
• Bile Duct Neoplasms diagnosis   MeSH
• Prognosis MeSH
• Aged MeSH
• Cholangitis, Sclerosing diagnosis   metabolism   MeSH
• Inflammation diagnosis   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• Immunoglobulin G MeSH

BACKGROUND: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS: Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and bile salt excursions were determined. Serum levels of 7α-hydroxy-4-cholesten-3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19 response. RESULTS: Baseline serum FGF19 levels were comparable between groups, while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge, HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline. PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h, combined with a sustained serum elevation of CDCA and other bile salts. In general, C4 levels declined following FGF19 elevation. In PSC patients with less favorable prognosis, baseline C4 levels were drastically suppressed and did not further decline. CONCLUSION: Following an oral CDCA challenge, PSC patients showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR agonist therapy in PSC could cause prolonged exposure to elevated levels of FGF19, and we propose careful monitoring for detrimental side effects in patient studies.

• Keywords
• Chenodeoxycholic acid, Farnesoid X receptor, Fibroblast growth factor 19, Primary sclerosing cholangitis,
• MeSH
• Administration, Oral MeSH
• Cholestenones blood   MeSH
• Adult MeSH
• Fibroblast Growth Factors blood   metabolism   MeSH
• Liver metabolism   MeSH
• Clinical Protocols MeSH
• Chenodeoxycholic Acid administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Cathartics administration & dosage   MeSH
• Aged MeSH
• Cholangitis, Sclerosing blood   drug therapy   metabolism   MeSH
• Intestinal Mucosa metabolism   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 7 alpha-hydroxy-4-cholesten-3-one MeSH Browser
• Cholestenones MeSH
• FGF19 protein, human MeSH Browser
• Fibroblast Growth Factors MeSH
• Chenodeoxycholic Acid MeSH
• Cathartics MeSH

AIM: To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) before and after transplantation. METHODS: Eight patients with UC and PSC prior to liver transplantation (PSC-UC), 22 patients with UC after liver transplantation for PSC (OLT), 9 patients with active ulcerative colitis without PSC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N) underwent colonoscopy with multiple biopsies. Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53, Bcl-2 and cyclooxygenase-2 (COX-2) markers. Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests. RESULTS: PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT, UCA, UCR and N (P < 0.05). We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53 (P < 0.001). UCA had a higher p53 expression as compared to UCR. OLT had a significantly lower expression of p53 as compared with PSC-UC (P < 0.001). Bcl-2 had a significant higher bcl-2 expression as compared with controls. No difference in COX-2 expression between PSC-UC, UCR and UCA was found. UCA had higher COX-2 expression as compared to UCR. We also found a statistically significant positive correlation between the expression of COX-2 and p53. Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSC-UC (P < 0.001). PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score. CONCLUSION: Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53, suggesting a higher susceptibility of cancer. This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.

• Keywords
• Colorectal carcinoma, Cyclooxygenase-2, Imunohistochemistry, Liver transplantation, Primary sclerosing cholangitis, Ulcerative colitis, bcl2, p53,
• MeSH
• Biopsy MeSH
• Cyclooxygenase 2 analysis   MeSH
• Adult MeSH
• Immunohistochemistry MeSH
• Colonoscopy MeSH
• Colorectal Neoplasms chemistry   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor analysis   MeSH
• Tumor Suppressor Protein p53 analysis   MeSH
• Proto-Oncogene Proteins c-bcl-2 analysis   MeSH
• Aged MeSH
• Cholangitis, Sclerosing etiology   metabolism   surgery   MeSH
• Case-Control Studies MeSH
• Liver Transplantation MeSH
• Colitis, Ulcerative complications   metabolism   surgery   MeSH
• Up-Regulation MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cyclooxygenase 2 MeSH
• Biomarkers, Tumor MeSH
• Tumor Suppressor Protein p53 MeSH
• Proto-Oncogene Proteins c-bcl-2 MeSH
• PTGS2 protein, human MeSH Browser
• TP53 protein, human MeSH Browser