AJR:189, October 2007 819 AJR 2007; 189:819–823 0361–803X/07/1894–819 © American Roentgen Ray Society Lim et al. MR Spectroscopy of Liver Disease Hepatobiliary Imaging • Original Research 31 P MR Spectroscopy in Assessment of Response to Antiviral Therapy for Hepatitis C Virus–Related Liver Disease Adrian K. P. Lim 1 Nayna Patel 1,2 Gavin Hamilton 1,2 Kailash Mylvahan 1,2 Yu-Ting Kuo 1,3 Robert D. Goldin 4 Simon D. Taylor-Robinson 1,2 Lim AKP, Patel N, Hamilton G, et al. Keywords: hepatitis C, phospholipids, 31 P MR spectroscopy DOI:10.2214/AJR.07.2418 Received September 28, 2006; accepted after revision April 23, 2007. Supported by the British Medical Research Council (grant G99000178) and the United Kingdom Department of Health. A. K. P. Lim was supported by a Kodak Scholarship from the Royal College of Radiologists, UK. 1 Department of Imaging Sciences, Faculty of Medicine, Imperial College London, Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Rd., London W12 0HS, United Kingdom. Address correspondence to A. K. P. Lim (a.lim@ic.ac.uk). 2 Liver Unit, Division of Medicine, Imperial College London, St. Mary’s Hospital, London, United Kingdom. 3 Department of Medical Imaging, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Taiwan. 4 Department of Histopathology, Faculty of Medicine, Imperial College London, St. Mary’s Hospital, London, United Kingdom. OBJECTIVE. An increase in the ratio of phosphomonoester (PME) to phosphodiester (PDE) during 31 P MR spectroscopy of the liver has been observed with increasing severity of hepatitis C–related liver disease. The purpose of this study was to investigate the utility of 31 P MR spectroscopy as a biomarker of response to interferon and ribavirin treatment. SUBJECTS AND METHODS. Forty-seven patients with biopsy-proven hepatitis C un- dergoing viral eradication treatment with interferon and ribavirin underwent hepatic 31 P MR spectroscopy at 1.5 T (voxel size, 70 × 70 × 70 mm; TR, 10,000; number of signals averaged, 48). All underwent baseline imaging before treatment and repeated imaging at 6-month inter- vals after the start of treatment. RESULTS. All patients underwent follow-up imaging 6 months after the start of treatment; 25 patients, 12 months; and 10 patients, 18 months after the start of treatment. According to the Ishak histologic scoring system, nine patients had mild hepatitis; 30 patients, moderate to severe hepatitis; and eight patients, cirrhosis. Thirty-two patients responded to antiviral treat- ment. Among these patients, 25 had a decrease in PME/PDE ratio on follow-up imaging. Among responders the mean baseline PME/PDE ratio decreased from 0.27 ± 0.02 (standard er- ror) to 0.16 ± 0.01 after treatment (paired Student’s t test, p < 0.001). Among the 15 virologic nonresponders, the ratios were similar in six patients; six other patients had an increase on fol- low-up imaging. In the latter nonresponder group, the mean baseline PME/PDE ratio was 0.21 ± 0.03 compared with 0.31 ± 0.08 after treatment (paired Student’s t test, p = 0.24). CONCLUSION. The in vivo hepatic PME/PDE ratio decreased in patients with hepatitis C who responded to antiviral treatment and remained similar or increased in patients without a virologic response. These results suggest that PME and PDE can be used as biomarkers in a noninvasive test of response to treatment. t is estimated that approximately 3% of the global population has chronic infection with the hepatitis C virus (HCV) and that approxi- mately 4 million persons are newly infected each year [1]. There is a great degree of varia- tion in prevalence, ranging from less than 1% in the United Kingdom to more than 20% in Egypt [1]. In 55–85% of persons the infection develops into chronic liver disease, which in many cases remains asymptomatic. In the other cases, the primary symptom is chronic fatigue [2]. In approximately 20% of cases, fibrosis de- velops into cirrhosis, which leads to hepatocel- lular cancer in 5% of cases each year [3]. Liver biopsy is the reference standard for staging and grading chronic liver disease, but this invasive procedure is not without risk. There is a small mortality rate but a high error rate, predominantly owing to undersampling, whereby typically less than 1/50,000 of the liver volume is obtained for histologic evalua- tion [4–7]. As a result of the problems associ- ated with biopsy, a steady drive to find an ef- fective noninvasive method of evaluating liver damage has led to developments both in testing with serologic biomarkers of disease and in imaging. For ethical reasons and because most patients are unwilling to undergo repeated pro- cedures, treatment algorithms in the United Kingdom rarely allow serial liver biopsy. The impetus to find a reliable and repeatable bio- marker of disease activity and response to treatment thus has renewed focus [8]. One particular noninvasive technique for characterizing chronic liver disease is 31 P MR spectroscopy, the results of which were found to be a useful indicator of disease severity in one of our previous studies [9]. In that study we found that the phosphomonoester to phos- I Downloaded from www.ajronline.org by 52.73.204.196 on 05/16/22 from IP address 52.73.204.196. Copyright ARRS. For personal use only; all rights reserved