ISSN: 2373-6372GHOA

Gastroenterology & Hepatology: Open Access
Editorial
Volume 1 Issue 1 - 2014
r-GT, A Promising Marker for HCC Development after SVR in Hepatitis C Patients?
Akiyoshi Kinoshita* and Hirokazu Nishino
Division of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, Japan
Received: April 15, 2014 | Published: April 23, 2014
*Corresponding author: Akiyoshi Kinoshita, Division of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, 4-11-1, Izumihon-cho, Komae-shi, Tokyo, 201-8601, Japan, Tel: 03-3480-1151; Fax: 03-3480-6688; Email: @
Citation: Kinoshita A, Nishino H (2014) r-GT, A Promising Marker for HCC Development after SVR in Hepatitis C Patients? Gastroenterol Hepatol Open Access 1(1): 00001. DOI: 10.15406/ghoa.2014.01.00001
Liver cancer is the sixth most common cancer (749,000 new cases) and the third leading cause of cancer-related deaths (692,000 cases) worldwide and accounts for 7% of all deaths. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and is a major global concern [1].
Approximately 80% of HCC cases are associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections [2]. In North America, Europe and Japan, infection with HCV is the main risk factor for HCC, together with alcohol abuse [2,3]. Infection with HCV increases the risk for HCC, with a 15-20 fold increased incidence compared with HCV-negative subjects in cross-sectional and case-control studies [2].
Current randomized controlled studies and meta-analysis indicate that the risk for HCC development is reduced 57% to 75% in patients with HCV who achieve a sustained virological response (SVR) with antiviral treatment such as interferon [1,2,4]. However, even after the achievement of a SVR with antiviral treatment, some patients still develop HCC. An older age, higher α fetoprotein (AFP) levels, lower platelet counts and a high fibrotic stage before antiviral treatment were reported to be independent risk factors for HCC development in patients after SVR [5]. However, the risk factors for HCC development after SVR in non-cirrhotic patients remain unclear.
Recently, in the Journal of Hepatology (in press), Huang et al. reported their investigation of potential non-invasive markers for HCC development after SVR in hepatitis C patients [6]. First, the authors explored the incidence of HCC development in 642 hepatitis C patients who achieved a SVR after interferon-based therapy. Thirty-three of the 642 (5.1%) patients developed HCC, with cumulative incidence rates 0.5%, 2.7% and 5.8% after one, three and five years of follow-up, respectively. Second, the authors evaluated the predictive factors for HCC development. The Cox regression analysis revealed that the predictive factors for HCC were liver cirrhosis (HR 4.98, P<0.001), age (HR 1.06, P=0.005) and the baseline gamma-glutamyl transferase (r-GT) levels (HR 1.008, P<0.001). Subsequently, the authors performed a subclass analysis. While the cumulative incidence of HCC did not differ significantly between cirrhotic patients with and without high baseline r-GT levels (P=0.53), it was significantly higher in non-cirrhotic patients with higher r-GT levels compared with those with lower r-GT levels (P<0.001). The Cox regression analysis revealed that high baseline r-GT levels remain the strongest factor independently associated with HCC development in non-cirrhotic patients after SVR (HR 6.44, P=0.001), even after the liver fibrotic stage was taken into consideration. The authors concluded that higher r-GT levels are a potential non-invasive marker for HCC development after SVR in non-cirrhotic patients.
r-GT is a heterodimeric glycoprotein that catalyzes the trans-peptidation and hydrolysis of an a-glutamyl group from glutathione and other a-glutamyl compounds [7-9]. It is present predominantly in the liver. Elevated r-GT levels usually indicate the presence of underlying liver disease, such as cholestatic liver disease, alcoholic liver disease, non-alcoholic fatty liver disease and drug-induced liver damage.
In addition to liver disease, the r-GT level has been shown to correlate with the risk of mortality from all causes and the incidence and mortality of cardiovascular disease, diabetes and cancer [10-13]. It is not fully understood why an elevated r-GT level is associated with increased morbidity and mortality under so many diverse conditions. However, an experimental study has demonstrated that active r-GT is present in atherosclerotic plaques and may play a role in the development of reactive oxygen species [10,11]. The relationship between r-GT and oxidative stress may contribute to the increased morbidity and mortality in patients with elevated r-GT levels. With regard to HCC, elevated r-GT levels have previously been demonstrated to be associated with an increased risk for HCC development [14].
The study by Huang et al. is the first to show that elevated r-GT levels are associated with HCC development after the achievement of a SVR in non-cirrhotic patients, irrespective of the liver fibrotic stage. These findings would help clinicians to identify non-cirrhotic patients after SVR who potentially remain at high risk for the development of HCC.

References

  1. European Association for the Study of the Liver, European Organization for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol 56(4): 908-943.
  2. El-Serag HB (2012) Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142(6): 1264-1273.
  3. Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. Lancet 379(9822): 1245-1255.
  4. Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS (2010) A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol 8(3): 280-288.
  5. Chang KC, Hung CH, Lu SN, Wang JH, Lee CM, et al. (2012) A novel predictive score for hepatocellular carcinoma development in patients with chronic hepatitis C after sustained response to pegylated interferon and ribavirin combination therapy. J Antimicrob Chemother 67(11): 2766-2772.
  6. Chung FH, Ming LY, Pei CT, Meng HH, Hua LY, et al. (2014) Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication. J Hepatol doi.org/10.1016/j.jhep.2014.02.022.
  7. Goldberg DM (1980) Structural, functional, and clinical aspects of gamma-glutamyltransferase. CRC Crit Rev Clin Lab Sci 12(1): 1-58.
  8. Guiu B, Deschamps F, Boulin M, Boige V, Malka D, et al. (2012) Serum gamma-glutamyl-transferase independently predicts outcome after transarterial chemoembolization of hepatocellular carcinoma: external validation. Cardiovasc Intervent Radiol 35(5): 1102-1108.
  9. Everhart JE, Wright EC (2013) Association of γ-glutamyl transferase (GGT) activity with treatment and clinical outcomes in chronic hepatitis C (HCV). Hepatology 57(5): 1725-1733.
  10. Ruhl CE, Everhart JE (2009) Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 136(2): 477-485.
  11. Pompella A, Emdin M, Passino C, Paolicchi A (2004) The significance of serum gamma-glutamyltransferase in cardiovascular diseases. Clin Chem Lab Med 42(10): 1085-1091.
  12. Lee DH, Ha MH, Kim JH, Christiani DC, Gross MD, et al. (2003) Gamma-glutamyltransferase and diabetes--a 4 year follow-up study. Diabetologia 46(3): 359-364.
  13. Van Hemelrijck M, Jassem W, Walldius G, Fentiman IS, Hammar N, et al. (2011) Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons - the Swedish AMORIS study. Eur J Cancer 47(13): 2033-2041.
  14. Hu G, Tuomilehto J, Pukkala E, Hakulinen T, Antikainen R, et al. (2008) Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer. Hepatology 48(1): 129-136.
© 2014-2016 MedCrave Group, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use.
Creative Commons License Open Access by MedCrave Group is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://medcraveonline.com
Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version | Opera |Privacy Policy