Noninvasive Evaluation of Hepatic Fibrosis in Hepatitis C Virus-Infected Patients Using Ethoxybenzyl-Magnetic Resonance Imaging

Shunsuke Nojiri; Atsunori Kusakabe; Kei Fujiwara; Noboru Shinkai; Kentaro Matsuura; Etsuko Iio; Tomokatsu Miyaki; Takashi Joh

Disclosures

J Gastroenterol Hepatol. 2013;28(6):1032-1039. 

In This Article

Abstract and Introduction

Abstract

Background and Aims: Liver biopsy is the gold standard test to determine the grade of fibrosis, but there are associated problems. Because gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid is secreted partially in hepatocytes and bile, it is possible that ethoxybenzyl-magnetic resonance imaging (EOB-MRI) correlates with liver function and liver fibrosis. The aim of this study was to compare the fibrosis seen in liver biopsy samples to the signal intensity of the hepatobiliary phase measured on EOB-MRI in hepatitis C virus (HCV)-infected patients.

Methods: Two hundred twenty-four (estimation 149, validation 75) HCV-infected patients with histologically proven liver tissue who underwent EOB-MRI were studied. Overall, fibrosis staging was 15/24/19/46/45 for F0/F1/F2/F3/F4, respectively. A 1.5-Tesla magnetic resonance system was used, and the regions of interest of the liver were measured. Four methods were used: (i) relative enhancement: (post-enhanced signal intensity [SI] − pre-enhanced intensity)/pre-enhanced intensity; (ii) liver-to-intervertebral disk ratio (LI): post-enhanced (liver SI/interdisc SI)/pre-enhanced (liver SI/inter disc SI); (iii) liver-to-muscle ratio: post-enhanced (liver SI/muscle SI)/pre-enhanced (liver SI/muscle SI); and (iv) liver-to-spleen ratio: post-enhanced (liver SI/spleen SI)/pre-enhanced (liver SI/spleen SI).

Results: To discriminate F0-1 versus F2-4 or F0-2 versus F3-4 or F0-3 versus F4, LI at 25 min (LI25) had the highest area under receiver operating characteristic (0.88, 0.87, and 0.87, respectively) in these four methods and also in the validation set.

Conclusion: LI at 25 min seems to be a useful method to determine the staging of fibrosis as a non-invasive method in HCV-infected hepatitis or cirrhosis patients.

Introduction

Chronic hepatitis C is the most common cause of cirrhosis in the world. The most appropriate treatment is interferon and ribavirin combination therapy, with efficacy of up to 70%. If this therapy is not effective, patients will progress to cirrhosis 25–30 years after infection.[1] Hepatitis C virus (HCV)-related cirrhosis is associated with an extremely high risk of hepatocellular carcinoma (HCC) development.[2–4] Treatment of HCC at an early stage has a good prognosis,[5–7] but advanced fibrosis increases the risk of carcinogenesis,[3] so it is important to know its fibrotic stage in outpatients. Liver biopsy is the gold standard test to determine the grade of fibrosis, but there are associated problems, such as sample error and severe complications.[8–10] Previously, methods using usual laboratory data have been reported to predict significant fibrosis or cirrhosis in patients, such as Forn's score:[11] platelet count, gamma-glutamyl transpeptidase, total cholesterol, and age; the FibroIndex:[12] platelet count, aspartate aminotransferase (AST), and gamma globulin; the Lok index:[13] platelet, prothrombin time (PT) (international normalized ratio), AST, and alanine aminotransferase (ALT); and the AST-to-platelet ratio index (APRI):[14] AST and platelet count. In recent years, several non-invasive methods have been reported, such as transient elastography (Fibroscan, Echosens, Paris, France),[15] magnetic resonance (MR) elastography,[16] and acoustic radiation force impulse.[17] These methods require special equipment and are expensive, so newly developed techniques that can be used in general hospitals and estimate liver parenchyma are needed. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is an agent that is widely used to detect HCC or metastatic liver tumor.[18] This is a liver-specific agent with 50% uptake in the liver. It partially accumulates in hepatocytes and is excreted into bile, so it is possible that ethoxybenzyl-magnetic resonance imaging (EOB-MRI) correlates with liver function and liver fibrosis. The aim of this study was to compare the fibrosis seen in liver biopsy samples with the signal intensity (SI) of the hepatobiliary phase measured on EOB-MRI and differentiate HCV-infected patients with significant fibrosis (F2–4) from those without significant fibrosis (F0,1) or with extended fibrosis (F3,4) from the others (F0-2), or cirrhosis (F4) from non-cirrhosis followed by determining the best measurement method using EOB-MRI.

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