Abstract:Background: Cholangiocarcinoma (CC) is increasing in incidence, but its pathogenesis remains poorly understood. Chronic inflammation of the bile duct and cholestasis are major risk factors, but most cases in the West are sporadic. Genetic polymorphisms in biliary transporter proteins have been implicated in benign biliary disease and, in the case of progressive familial cholestasis, have been associated with childhood onset of CC. In the current study, five biologically plausible candidate genes were investiga… Show more
“…In both cases, no argument supporting the direct relation between ABCB4 mutations and tumorigenesis was found and IHCC may be considered as a consequence of the chronic biliary abnormalities. Genetic polymorphisms in biliary transporters genes have been studied but, to date, no relation has been established between IHCC and ABCB4 mutations [4]. Fig.…”
Section: Complicationsmentioning
confidence: 99%
“…The ‘unchaperoned’ bile acids in the bile of patients with MDR3 deficiency may cause chronic cholangitis. Several other biliary disorders have been associated with ABCB4 /MDR3 mutations: low phospholipid-associated cholelithiasis (LPAC) syndrome, intrahepatic cholestasis of pregnancy (ICP), drug-induced liver injury, transient neonatal cholestasis [TNC], adult biliary fibrosis or cirrhosis [3], and very recently intrahepatic cholangiocarcinoma (IHCC) [4–9]. …”
BackgroundABCB4/MDR3 gene variants are mostly associated with a peculiar form of cholelithiasis in European adults, currently referred to as low phospholipid-associated cholelithiasis (LPAC) syndrome.MethodsLPAC syndrome is a rare genetic disorder, characterised by the following clinical features: biliary symptoms before the age of 40, recurrence of the symptoms after cholecystectomy, and intrahepatic microlithiasis or intrahepatic hyperechogenic foci.ResultsImaging features associated with ABCB4/MDR3 mutations are not specific and correspond to a wide spectrum of biliary abnormalities. The main feature is the presence of intrahepatic lithiasis. Other uncommon presentations have been described, such as uni- or multifocal spindle-shaped dilatations of the intrahepatic bile ducts filled with gallstones, secondary sclerosing cholangitis, biliary cirrhosis, and intrahepatic cholangiocarcinoma.ConclusionThis review focuses on MR features related to ABCB4/MDR3 mutations.Main Messages• LPAC syndrome is characterised by intrahepatic microlithiasis or intrahepatic hyperechogenic foci.• Ultrasound examination is very accurate in detecting intrahepatic stones.• At MR imaging, LPAC syndrome is associated with various presentations.
“…In both cases, no argument supporting the direct relation between ABCB4 mutations and tumorigenesis was found and IHCC may be considered as a consequence of the chronic biliary abnormalities. Genetic polymorphisms in biliary transporters genes have been studied but, to date, no relation has been established between IHCC and ABCB4 mutations [4]. Fig.…”
Section: Complicationsmentioning
confidence: 99%
“…The ‘unchaperoned’ bile acids in the bile of patients with MDR3 deficiency may cause chronic cholangitis. Several other biliary disorders have been associated with ABCB4 /MDR3 mutations: low phospholipid-associated cholelithiasis (LPAC) syndrome, intrahepatic cholestasis of pregnancy (ICP), drug-induced liver injury, transient neonatal cholestasis [TNC], adult biliary fibrosis or cirrhosis [3], and very recently intrahepatic cholangiocarcinoma (IHCC) [4–9]. …”
BackgroundABCB4/MDR3 gene variants are mostly associated with a peculiar form of cholelithiasis in European adults, currently referred to as low phospholipid-associated cholelithiasis (LPAC) syndrome.MethodsLPAC syndrome is a rare genetic disorder, characterised by the following clinical features: biliary symptoms before the age of 40, recurrence of the symptoms after cholecystectomy, and intrahepatic microlithiasis or intrahepatic hyperechogenic foci.ResultsImaging features associated with ABCB4/MDR3 mutations are not specific and correspond to a wide spectrum of biliary abnormalities. The main feature is the presence of intrahepatic lithiasis. Other uncommon presentations have been described, such as uni- or multifocal spindle-shaped dilatations of the intrahepatic bile ducts filled with gallstones, secondary sclerosing cholangitis, biliary cirrhosis, and intrahepatic cholangiocarcinoma.ConclusionThis review focuses on MR features related to ABCB4/MDR3 mutations.Main Messages• LPAC syndrome is characterised by intrahepatic microlithiasis or intrahepatic hyperechogenic foci.• Ultrasound examination is very accurate in detecting intrahepatic stones.• At MR imaging, LPAC syndrome is associated with various presentations.
“…The fact that FXR thus appears to play a role in the protection of the integrity of the intestinal epithelial barrier and its inverse correlation with the level of intestinal inflammation suggest a potential connection between FXR and the molecular pathogenesis of IBD. FXR variants have been previously studied in association with several liver diseases, such as gallstone disease [30], cholangiocarcinoma [31], intrahepatic cholestasis of pregnancy [32], and idiopathic infantile cholestasis [33]. Here, we have investigated five NR1H4 single nucleotide polymorphisms - two common SNPs and three rare variants - which have been previously studied in the context of human disease, in a well-sized IBD vs. non-IBD cohort, and report that two of these genetic variants are associated with IBD.…”
BackgroundPathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), involves interaction between environmental factors and inappropriate immune responses in the intestine of genetically predisposed individuals. Bile acids and their nuclear receptor, FXR, regulate inflammatory responses and barrier function in the intestinal tract.MethodsWe studied the association of five variants (rs3863377, rs7138843, rs56163822, rs35724, rs10860603) of the NR1H4 gene encoding FXR with IBD. 1138 individuals (591 non-IBD, 203 UC, 344 CD) were genotyped for five NR1H4 genetic variants with TaqMan SNP Genotyping Assays.ResultsWe observed that the NR1H4 SNP rs3863377 is significantly less frequent in IBD cases than in non-IBD controls (allele frequencies: P = 0.004; wild-type vs. SNP carrier genotype frequencies: P = 0.008), whereas the variant rs56163822 is less prevalent in non-IBD controls (allele frequencies: P = 0.027; wild-type vs. SNP carrier genotype frequencies: P = 0.035). The global haplotype distribution between IBD and control patients was significantly different (P = 0.003). This also held true for the comparison between non-IBD and UC groups (P = 0.004), but not for the comparison between non-IBD and CD groups (P = 0.079).ConclusionsWe show that genetic variation in FXR is associated with IBD, further emphasizing the link between bile acid signaling and intestinal inflammation.
“…Parasitic infestations (particularly Opisthorchis viverrini, Clonorchis sinensis, and Schistosoma japonicum) result in chronic inflammation and increase the risk of CC. Moreover, diabetes mellitus (DM), smoking, advanced age (65% are 65 years old or older), history of biliary surgery, biliary‐enteric anastomosis, chronic inflammatory diseases, being a chronic carrier of typhoid and having cryptosporidiosis, liver cirrhosis (LC), congenital factors (choledochal cysts, Caroli's disease, and congenital hepatic fibrosis), chemical agents (thorotrast, dioxin, nitrosamines and asbestosis), and long‐term use of certain medications (oral contraceptives and isoniazid) may create a risk . The case we have presented did not have any of the strong risk factors defined for cholangiocellular cancer.…”
Patients with malignancies may develop hypercalcemia due to bone metastases or paraneoplastic reasons. Hepatocellular cancer should be considered in liver masses detected in chronic viral hepatitis B patients with delta agents. However, in our case, we detected cholangiocellular carcinoma in the etiology of hypercalcemia.
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