Situs inversus totalis and secondary biliary cirrhosis: a case report
© Sökmen et al; licensee BioMed Central Ltd. 2011
Received: 7 May 2011
Accepted: 3 August 2011
Published: 3 August 2011
Situs inversus totalis is is a congenital anomaly associated with various visceral abnormalities, but there is no data about the relationship between secondary biliary cirrhosis and that condition. We here present a case of a 58 year-old female with situs inversus totalis who was admitted to our clinic with extrahepatic cholestasis. After excluding all potential causes of biliary cirrhosis, secondary biliary cirrhosis was diagnosed based on the patient's history, imaging techniques, clinical and laboratory findings, besides histolopathological findings. After treatment with tauroursodeoxycholic acid, all biochemical parameters, including total/direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gama glutamyl transferase, returned to normal ranges at the second month of the treatment. We think that this is the first case in literature that may indicate the development of secondary biliary cirrhosis in a patient with situs inversus totalis. In conclusion, situs inversus should be considered as a rare cause of biliary cirrhosis in patients with situs inversus totalis which is presented with extrahepatic cholestasis.
Situs inversus totalis (SIT) is a congenital anomaly characterized by complete transposition of abdominal and thoracic organs. As a birth defect in newborn infants, it has an estimated incidence of 1/15000 to 10000 cases in live births, with a male/female ratio of 3:2. Generally, this rare anomaly is diagnosed incidentally during thoracic and abdominal imaging. The cause of situs inversus (SI) is unknown. More than one genetic mutations including gene mutations which cause ciliopathy and cystic renal diseases were implicated in etiopathogenesis . SIT is associated with various gastrointestinal abnormalities. In the current literature, development of intestinal ischemia due to intestinal malrotation, and also acute appendicitis and liver transplantation due to juvenile biliary atresia were reported [2–4]. However, there is no data for the development of secondary biliary cirrhosis (SBC) due to extrahepatic cholestasis in a patient with SIT. We here presented a case of SIT with SBC who referred to our clinic due to extrahepatic cholestasis.
SI is associated with various gastrointestinal abnormalities such as absence of suprarenal inferior vena cava, polysplenia syndrome, preduodenal portal vein, duodenal atresia or stenosis, tracheoeusophageal fistula (type C), intestinal malrotation, aberrant hepatic arteria, hypoplasia of portal vein, congenital hepatic fibrosis and biliary atresia . In a previous study, it was found that the gallbladder may lie in the midline or be lateralized with the bulk of the hepatic mass .
Although the etiology is not clear, it has been suggested that SIT and ciliopathy are related to each other. However, the mechanism has not been explained entirely. It is suggested that the immobility of nodal cilia inhibits the flow of extra embryonic fluid during embryonic period and this leads to SI development . However, primary ciliary dyskinesia (PCD) is observed only in 25% of SI patients.
Whereas a definition of congenital hepatic fibrosis associated with ciliopathy and SIT is reported in the current literature, there is no data about the concurrence of SIT and SBC. Our case is possibly the first one in literature in terms of such SIT and SBC co-existence. Despite there is no clear evident for the development of SBC in patients with SIT, considering the cases reported in literature, the following hypotheses may be proposed. The cilium is a hair like structure that extends from the cell surface into the extracellular space and it has an axoneme containing microtubules, and the microtubules connected with each other with dynein arms that provide ciliary movement . Electron microscopy of the ciliary microtubules frequently reveals absence or abnormalities of the outer and/or inner dynein arms. Especially the mutations of the gene dynein axonemal heavy chain 11 (DNAH 11) are thought to be associated with ciliopathy and SI . From various studies, it was reported that ciliary dyskinesia has a role in the pathogenesis of nephronophthisis (NPHP) and polycystic renal disease (PCD) and the genes that are associated with renal cystic disease are important for left-right axis determination of the body plan . NPHP may be associated with liver fibrosis; patients develop hepatomegaly and moderate portal fibrosis with mild bile duct proliferation, this pattern differs from that of classical congenital hepatic fibrosis, whereby biliary dysgenesis is prominent. Bile duct involvement in cystic kidney disease may be explained by the ciliary theory, because the epithelial cells lining bile ducts (cholangiocytes) possess primary cilia. It was suggested that especially the mutations of the gene NPHP2/inversin is associated with SI. SI and ciliopathy also cause biliary dysgenenesis, dilatation of biliary tract and portal fibrosis [11, 12].
In our case, chronic rhinosinusitis and frequently recurrent lower respiratory tract infections, abnormal localization of the main biliary tract (on vertebral axis in ERCP) and moderate dilated biliary tracts support the hypothesis of SIT and ciliopathy association.
There is no data about increased incidence of cholelithiasis in SIT patients. Furthermore, in several case reports, it was suggested that pancreatic ductal carcinoma, autoimmune pancreatitis and sclerosing cholangitis may develop [13, 14]. In our patient, there was not any pancreatic pathology. In magnetic resonance cholangiopancreatography (MRCP), ERCP and endoscopic US examinations, there was no finding in favor of cholelithiasis, sclerosing cholangitis or malignity other than moderate choledochal dilatation. Hepatic transaminase enzymes and bilirubin values that were returned to normal ranges with the treatment of a 15 mg/kg/day dose of TUDCA within 2 months supported our diagnosis.
Due to the following reasons, we consider SBC in this case and not primary biliary cirrhosis (PBC): 1) first of all, antimitochondrial antibody was negative in this case; 2) secondly, there was not any symptomatic presentation that seen in PBC such as pruritus, hyperpigmentation, xantalesma; 3) thirdly, in ERCP and MRCP images, choledoc duct was moderately dilated and located on the midline on vertebral axis; 4) finally, it is impossible to differentiate PBC or SBC in such a patient with stage 4 liver fibrosis, but the clinical features and laboratory findings along with histopathological findings supported the SBC. The major causes of SBC are gallstones/choledocholityasis, narrowing of the bile duct following gallbladder surgery, chronic pancreatitis, pericholangitis, idiaptahic sclerosing cholangitis, congenital biliary atresia and cystic fibrosis. In this case, all causes of SBC mentioned above were excluded.
We concluded that this is the first case in literature that may indicate the development of SBC in a patient with SIT.
Written informed consent was obtained from the patient for publication of this Case Report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Hildebrandt F, Zhou W: Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. 2007, 18 (6): 1855-1871. 10.1681/ASN.2006121344.View ArticlePubMedGoogle Scholar
- Wei JM, Liu YN, Qiao JC, Wu WR: Liver transplantation in a patient with situs inversus: a case report. Chin Med J (Engl). 2007, 120 (15): 1376-1377.Google Scholar
- Asensio Llorente M, López Espinosa JA, Ortega López J, Sánchez Sánchez LM, Castilla Valdez MP, Ferrer Blanco C, Margarit Creixell C, Iglesias Berengue J: [First orthotopic liver transplantation in patient with biliary atresia and situsinversus in spain]. Cir Pediatr. 2003, 16 (1): 44-47.PubMedGoogle Scholar
- Cissé M, Touré AO, Konaté I, Dieng M, Ka O, Touré FB, Dia A, Touré CT: Appendicular peritonitis in situs inversus totalis: a case report. J Med Case Reports. 2010, 4: 134-10.1186/1752-1947-4-134.PubMed CentralView ArticleGoogle Scholar
- Lee SE, Kim HY, Jung SE, Lee SC, Park KW, Kim WK: Situs anomalies and gastrointestinal abnormalities. J Pediatr Surg. 2006, 41 (7): 1237-1242. 10.1016/j.jpedsurg.2006.03.045.View ArticlePubMedGoogle Scholar
- Fonkalsrud EW, Tompkins R, Clatworthy HW: Abdominal manifestations of situsinversus in infants and children. Arch Surg. 1966, 92 (5): 791-795.View ArticlePubMedGoogle Scholar
- Nonaka S, Tanaka Y, Okada Y, Takeda S, Harada A, Kanai Y, Kido M, Hirokawa N: Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell. 1998, 95 (6): 829-837. 10.1016/S0092-8674(00)81705-5. Cell 1999, 99(1):117View ArticlePubMedGoogle Scholar
- Cardenas-Rodriguez M, Badano JL: Ciliary biology: understanding the cellularand genetic basis of human ciliopathies. Am J Med Genet C Semin Med Genet. 2009, 151C (4): 263-280. 10.1002/ajmg.c.30227.View ArticlePubMedGoogle Scholar
- Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK, Scamuffa N, Rossier C, Jorissen M, Armengot M, Meeks M, Mitchison HM, Chung EM, Delozier-Blanchet CD, Craigen WJ, Antonarakis SE: Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primaryciliary dyskinesia. Proc Natl Acad Sci USA. 2002, 99 (16): 10282-10286. 10.1073/pnas.152337699.PubMed CentralView ArticlePubMedGoogle Scholar
- Igarashi P, Somlo S: Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2002, 13 (9): 2384-98. 10.1097/01.ASN.0000028643.17901.42.View ArticlePubMedGoogle Scholar
- Delaney V, Mullaney J, Bourke E: Juvenile nephronophthisis, congenital hepatic fibrosis and retinal hypoplasia in twins. Q J Med. 1978, 47 (187): 281-90.PubMedGoogle Scholar
- Otto EA, Schermer B, Obara T, O'Toole JF, Hiller KS, Mueller AM, Ruf RG, Hoefele J, Beekmann F, Landau D, Foreman JW, Goodship JA, Strachan T, Kispert A, Wolf MT, Gagnadoux MF, Nivet H, Antignac C, Walz G, Drummond IA, Benzing T, Hildebrandt F: Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet. 2003, 34 (4): 413-420. 10.1038/ng1217.PubMed CentralView ArticlePubMedGoogle Scholar
- Antonacci N, Casadei R, Ricci C, Pezzilli R, Calculli L, Santini D, Alagna V, Minni F: Sclerosing cholangitis, autoimmune chronic pancreatitis, and situs viscerum inversus totalis. Pancreas. 2009, 38 (3): 345-346. 10.1097/MPA.0b013e3181860b3f.View ArticlePubMedGoogle Scholar
- Quintini C, Buniva P, Farinetti A, Monni S, Tazzioli G, Saviano L, Campana S, Malagnino F, Saviano M: [Adenocarcinoma of pancreas with situs viscerum inversus totalis]. Minerva Chir. 2003, 58 (2): 243-246.PubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.