Intrahepatic cholestasis

Possible increase in serum conjugated bilirubin Obstruction of bile flow commonly due to common bile duct stone or pancreatic carcinoma Failure of bile secretion Extrahepatic cholestasis Intrahepatic cholestasis... 

TABLE 5.13 Examples of Drugs that Induce Intrahepatic Cholestasis or Liver Damage Resembling That Induced by Viral Hepatitis... 

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

Kauppila, A., Korpela, H., Makila, U-M. and Yrjanheikki, E. (1987). Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br. Med. J. 294, 150-152. 

MDR3, a homologue of MDR1, is responsible for the biliary excretion of phospholipids, and a hereditary defect in this gene results in the acquisition of progressive familial intrahepatic cholestasis Type 3 [80-82]. 

S. J., Helgason, C. D., Ackerley, C., Phillips, M. J., Ling, V., Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis, Proc. Natl. Acad. Sci. USA 2001, 98, 2011-2016. 

De Vree JM, Jacquemin E, Sturm E, Cresteil D, Bosma PJ, Aten J et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. 

Jacquemin E, Cresteil D, Manouvrier S, Boute O, Hadchouel M. Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy. Lancet 1999 353(9148) 210-211. 

Dixon PH, Weerasekera N, Linton KJ, Donaldson O, Chambers J, Egginton E et al. Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy evidence for a defect in protein trafficking. Hum Mol Genet 2000 9(8) 1209-1217. 

A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nature Genet 1998 20(3) 233-238. 

Jansen PL, Strautnieks SS, Jacquemin E, Hadchouel M, Sokal EM, Hooiveld GJ et al. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 1999 117(6) 1370— 1379. 

Oral testosterone-replacement regimens can cause hepatotoxicity, ranging from mildly elevated hepatic transaminases to serious liver diseases (e.g., peliosis hepatitis, hepatocellular and intrahepatic cholestasis, and benign or malignant tumors). 

V. Keitel, M. Burdelski, U. Warskulat, T. Kuhlkamp, D. Keppler, D. Haussinger, and R. Kubitz. Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Hepatology. 41 1160-1172 (2005). 

Sakurai, A., Kurata, A., Onishi, Y., Hirano, H. and Ishikawa, T. (2007) Prediction of drug-induced intrahepatic cholestasis ... 

Funk, C. et al. (2001) Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export ofbile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and ihe inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Toxicology, 167 (1), 83-98. 

Intrahepatic cholestasis and hepatitis similar to that seen in chronic active hepatitis can rarely occur fatalities have been reported. Nitrofurantoin can interfere with immature red blood cell enzyme systems found in babies less than 1 month of age and in nursing infants. This leads to cellular damage and anemia. Nitro-... 

Cholestatic. Pertaining to or characterized by suppression or stopping of the flow of bile (cholestasis), having intrahepatic or extra-hepatic causes. 

Back P, Siovall J, Siovall (1974) Monohydroxy bile acids in plasma in intrahepatic cholestasis of pregnancy. Identification by computerized gas chromatography-mass spectrometry. Med Biol 52 31-38... 

Jaundice as a result of oral contraceptive treatment has been repeatedly described. Whereas in the Swedish population figures between 1 100 and 1 4000 were published when the early high-dose formulations were still in use (213), the overall incidence was estimated in 1979 at about 1 10 000 (9), and the current incidence is certainly further reduced. When such hepatic symptoms occur, they usually do so within the first month of medication (214), and jaundice may be accompanied by anorexia, malaise, and pruritus. Very few cases arise after the third month of medication and those reported are regarded by some as unlikely to be due to oral contraceptives. Microscopic examination of the liver shows intrahepatic cholestasis. When medication is stopped, symptoms usually disappear rapidly and the reaction does not seem to leave any sequelae (215). Genetic components seem to be important for the development of the reaction women who have experienced jaundice or severe pruritus in late pregnancy seem to be especially susceptible to jaundice or gallbladder disease when using... 

Wongpaitoon V, Mills PR, Russell RI, Patrick RS. Intrahepatic cholestasis and cutaneous bullae associated with glibenclamide therapy. Postgrad Med J 1981 57(666) 244-6. 

Krivoy N, Zaher A, Yaacov B, Alroy G. Fatal toxic intrahepatic cholestasis secondary to glibenclamide. Diabetes Care 1996 19(4) 385-6. 

During cholestasis, the metabolism of tolbutamide is greatly altered, thus, tolbutamide (100 mg/kg) injected i.v. into rats with experimental cholestasis was eliminated more rapidly than in control animals, this increase was owing to the increase in liver weight and microsomal protein (25). In patients with recurrent intrahepatic cholestasis no differences in tolbutamide metabolism were noted as compared to the control group. In cholestatic hepatitis the plasma half-life of tolbutamide appeared unchanged. The... 

BSEP also known as sister-P-glycoprotein (SPGP) was originally cloned from pig liver (185). BSEP is localized on the canalicular membrane of hepa-tocytes and is responsible for the secretion of bile salts across the canalicular membrane into bile. BSEP appears to be the predominant bile salt efflux system for hepatocytes, and is a critical component in the enterohepatic circulation of bile acids. A number of mutations in the transporter were found to the basis for progressive familial intrahepatic cholestasis type 2 (PFIC2) (186-188). Mutations found in PFIC2 patients include frameshifts, missense mutations, and premature termination codons. Most PFIC2 patients lack immunohistochemically detectable BSEP in their liver. Recently, seven... 

Meier PJ, Kullak-Ublick G. Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance P-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy. Pharmacogenetics 2004 14 91-102. 

Wang L, Soroka CJ, Boyer Jl. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest 2002 110 965-972. 

Dose-independent, drug-induced liver dysfunction (cholestatic jaundice) is not an unusual adverse reaction. Caused by a number of different, commonly used drugs, cholestasis is a hypersensitivity reaction that primarily affects the biliary canaliculi, causing an intrahepatic obstructive jaundice. An alteration in... 

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