Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases

Reduced hepatobiliary transporter expression could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resultin g in cholestasis and jaundice. Because little is known about alterations of hepatobiliary transport systems in human cholestatic liver diseases, it wa s the aim of this study to investigate such potential changes. Hepatic mRNA levels in hepatobiliary transport systems for bile salts (NTCP, BSEP), org anic anions (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR 3), and aminophospholipids (FIC1) were determined in 37 human Liver biopsie s and control livers by competitive reverse-transcription polymerase chain reaction (RT-PCR). Transporter tissue distribution was investigated by immu nofluorescence microscopy. In patients with inflammation-induced icteric ch olestasis (mainly cholestatic alcoholic hepatitis), mRNA levels of NTCP, OA TP2, and BSEP were reduced by 41% (P < .001), 49% (P < .005;), and 34% (P < .05) compared with controls, respectively. In addition, NTCP and BSEP immu nostaining was reduced. MRP2 mRNA levels remained unchanged, but canalicula r immunolabeling for MRP2 was also decreased, mRNA expression of MRP3, MDR1 , MDR3, and FIC1 remained unchanged. In contrast to the alterations of tran sporter expression in inflammation-induced icteric cholestasis, transporter expression did not change in anicteric cholestasis caused by primary bilia ry cirrhosis (PBC) stages I and II. In conclusion, reduced expression of he patobiliary transport systems for bile salts and other organic anions may c ontribute to inflammation-induced cholestasis in humans. Reduction of trans porter gene expression can occur at the mRNA level as observed for NTCP, OA TP2, and BSEP. However, reduced MRP2 immunostaining in the presence of cons erved MRP2 mRNA levels suggests an additional role for posttranscriptional/ posttranslational mechanisms.