| [Aim] Intrahepatic cholestasis (IC) is a rare disease, which is caused by drug, sepsis, pregnancy, total parenteral nutrition, etc. IC sometimes becomes prolonged and progresses to liver failure. The molecular mechanism by which this disease occurs remains unknown. In this study we analyzed hepatic expression of canalicular transporters and sequenced their genes in IC patients. [Materials and Methods] We analyzed canalicular expression of ABCB11, ABCB4 and ABCC2 in liver tissues by immunohistochemistry in 15 IC patients and the results were categorized to -, 1+, 2+ and 3+. As controls, we performed immunohiostochemistry in 37 chronic hepatitis C (CH-C) and 45 PBC patients. We also sequenced ABCB11, ABCB4 and ATP8B1 genes with a next generation sequencer. This study was approved by Ethics Committee. [Results] ABCB11 canalicular expression was 1+: 18%, 2+: 64% and 3+: 18% in IC, which was significantly lower than those in CH-C (1+: 5%, 2+: 32% and 3+: 62%) and PBC (1+:4%, 2+: 36% and 3+: 60%). The expressions of ABCB4 and ABCC2 were similarly impaired. We found 3 possibly damaging variants; ABCB11 c.2077G＞C (A693P), ATP8B1 c.1729A＞G (I577V), and ATP8B1 exon-intron junction variant in 4 patients. [Conclusions] Expression of canalicular transporters was significantly reduced in IC patients. At least 4 patients (27%) had possibly damaging variants in ABCB11 or ATP8B1 genes. Impaired expression of canalicular transporters could be involved in IC occurrence. |
