Focal Nodular Hyperplasia-Like Nodule with Reduced Expression of Organic Anion Transporter 1B3 in Alcoholic Liver Cirrhosis

Abstract

We report a patient with alcoholic liver cirrhosis who had a 15 mm focal nodular hyperplasia (FNH)-like nodule in the liver. This FNH-like nodule was diagnosed as hepatocellular carcinoma (HCC) mainly based on hypervascularity during the hepatic arterial phase, washout pattern during the equilibrium phase and low signal intensity during the hepatobiliary phase in gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI; it was surgically resected. Its histology exhibited hepatocyte hyperplasia, fibrous septa containing unpaired small arteries accompanied by reactive bile ductules, remarkable iron deposits and sinusoidal capillarization, and was compatible with the diagnosis of an FNH-like nodule. When we analyzed the images of the present nodule retrospectively, low signal intensity on in-phase and isosignal intensity on opposed-phase T1-weighted MRI may have reflected iron deposits in the FNH-like nodule. In addition, a low signal intensity on T2-weighted MRI and no detection in diffusion-weighted MRI may help in distinguishing FNH-like nodules from HCC, since these image findings are inconsistent with typical HCC. Immunohistochemical analysis revealed a markedly reduced expression of organic anion transporter (OATP) 1B3 in this nodule, which implied decreased Gd-EOB-DTPA uptake by hepatocytes and accounted for the low signal intensity during the hepatobiliary phase on Gd-EOB-DTPA-enhanced MRI. To the best of our knowledge this is the first report in which an FNH-like nodule was assessed for OATP1B3 expression.

Alcohol Cirrhosis Alters Nuclear Receptor and Drug Transporter Expression in Human Liver

“…Another study reported a patient having lowered SLCO1B3 expression in a hepatocellular carcinoma nodule (Doi et al, 2011), which is consistent with the present data that illustrate decreased SLCO1B3 mRNA expression in alcoholic cirrhosis, too. As other models of liver injury (e.g., acetaminophen, carbon tetrachloride, cholestasis) also increase efflux transporter expression, we acknowledge that the observation was anticipated.…”

“…Rodent models for alcohol-induced liver disease display steatosis and some degree of fibrosis, but no model fully progresses to the human level of cirrhotic liver (Lieber et al, 1965;Tsukamoto et al, 1986). Previous studies with hepatic transporter expression are with small sample size or different liver pathologies like hepatitis C, hepatocellular carcinoma, NASH, or from nondiseased human livers (Nishimura and Naito, 2005;Hilgendorf et al, 2007;Ogasawara et al, 2010;Doi et al, 2011). Hepatitis C virus (HCV) -related cirrhosis increased ABCC4 mRNA and protein expression and ABCC1 mRNA expression in human livers (Ogasawara et al, 2010).…”

Primovist, Eovist: What to expect?

“…4) [58]. A case of FNH-like nodule in liver cirrhosis with lesion hypointensity during the hepatobiliary phase has been recently reported [59]. This lesion also showed arterial hyperintensity and was misdiagnosed as HCC.…”

A LC–MS/MS method to evaluate the hepatic uptake of the liver-specific magnetic resonance imaging contrast agent gadoxetate (Gd-EOB-DTPA) in vitro and in humans

“…Moreover, in vitro uptake studies in oocytes and stably transfected cell lines demonstrated that gadoxetate is a substrate for the human liverspecific uptake carriers OATP1B1 and OATP1B3 [5,6]. There is also convincing clinical evidence that these transporters are critical determinants for the hepatic uptake of gadoxetate [7][8][9].…”