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Published in: Journal of Gastroenterology 12/2011

01-12-2011 | Original Article—Liver, Pancreas, and Biliary Tract

The determination of GGT is the most reliable predictor of nonresponsiveness to interferon-alpha based therapy in HCV type-1 infection

Authors: Viola Weich, Eva Herrmann, Tje Lin Chung, Christoph Sarrazin, Holger Hinrichsen, Peter Buggisch, Tilman Gerlach, Hartwig Klinker, Ulrich Spengler, Alexandra Bergk, Stefan Zeuzem, Thomas Berg

Published in: Journal of Gastroenterology | Issue 12/2011

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Abstract

Background

The critical analysis of baseline factors has been found to be useful to predict virologic nonresponse (NR), relapse, or sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) who receive antiviral therapy. In the present retrospective study we tried to find out whether gamma-glutamyltranspeptidase (GGT) may be one of the baseline factors which are of special predictive power. We analyzed, in patients with different treatment outcomes, the predictive power of established baseline factors either in combination with GGT or by evaluating the predictive value of GGT independently.

Methods

Individual data from 632 patients chronically infected with HCV type 1 (n = 561) or type 2/3 (n = 71) were analyzed. All patients had received their first course of antiviral therapy and were treated with pegylated interferon α-2a or -2b plus ribavirin.

Results

In patients with HCV type 1, a multivariate multinomial logistic regression analysis identified low GGT (p < 0.0001), high cholesterol (p < 0.0001), age ≤40 years (p < 0.0001), high alanine aminotransferase (p = 0.0006), low viremia (p = 0.0014), and absence of cirrhosis (p = 0.0164) as independent predictors. While these baseline factors heralded improved virologic response, high GGT, in contrast, was significantly associated with NR (p < 0.0001). A strong correlation was found between log10 GGT and a scoring variable S (r = −0.26 for prediction of SVR, p < 0.001; r = 0.11 for prediction of NR, p = 0.016) summarizing predictive information from other baseline factors.

Conclusions

These findings prove the predictive sensitivity of GGT as an independent indicator of nonresponsiveness even at levels that are slightly above the normal range. This new predictive parameter may help to improve individualized therapy in HCV type-1 infection.
Literature
1.
go back to reference Poynard T, Mc Hutchison J, Goodman Z, Ling MH, Albrecht J. Is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALOVIRC Project Group. Hepatology. 2000;31:211–8.PubMedCrossRef Poynard T, Mc Hutchison J, Goodman Z, Ling MH, Albrecht J. Is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALOVIRC Project Group. Hepatology. 2000;31:211–8.PubMedCrossRef
2.
go back to reference D’Souza R, Sabin CA, Foster GR. Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy. Am J Gastroenterol. 2005;100:1509–15.PubMedCrossRef D’Souza R, Sabin CA, Foster GR. Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy. Am J Gastroenterol. 2005;100:1509–15.PubMedCrossRef
3.
go back to reference Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128:636–41.PubMedCrossRef Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128:636–41.PubMedCrossRef
4.
go back to reference Chu CJ, Lee SD, Hung TH, Lin HC, Hwang SJ, Lee FY, et al. Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon α-2b plus ribavirin. Aliment Pharmacol Ther. 2008;29:46–54.PubMedCrossRef Chu CJ, Lee SD, Hung TH, Lin HC, Hwang SJ, Lee FY, et al. Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon α-2b plus ribavirin. Aliment Pharmacol Ther. 2008;29:46–54.PubMedCrossRef
5.
go back to reference Forns X, Ampurdanes S, Llovet JM, Aponte J, Quinto L, Martinez-Bauer E, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36(4):986–92.PubMed Forns X, Ampurdanes S, Llovet JM, Aponte J, Quinto L, Martinez-Bauer E, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36(4):986–92.PubMed
6.
go back to reference Ferrara F, Ventura P, Vegetti A, Guido M, Abbati G, Corradini E, et al. Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C. Am J Gastroenterol. 2009;104:605–16.PubMedCrossRef Ferrara F, Ventura P, Vegetti A, Guido M, Abbati G, Corradini E, et al. Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C. Am J Gastroenterol. 2009;104:605–16.PubMedCrossRef
7.
go back to reference Snoeck E, Wade JR, Duff F, Lamb M, Jorga K. Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin. Br J Clin Pharmacol. 2006;62:699–709.PubMedCrossRef Snoeck E, Wade JR, Duff F, Lamb M, Jorga K. Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin. Br J Clin Pharmacol. 2006;62:699–709.PubMedCrossRef
8.
go back to reference Foster GR, Fried MW, Hadziyannis SJ, Messinger D, Freivogel K, Weiland O. Prediction of sustained virological response in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) and ribavirin. Scand J Gastroenterol. 2007;42:247–55.PubMedCrossRef Foster GR, Fried MW, Hadziyannis SJ, Messinger D, Freivogel K, Weiland O. Prediction of sustained virological response in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) and ribavirin. Scand J Gastroenterol. 2007;42:247–55.PubMedCrossRef
9.
go back to reference Shirakawa H, Matsumoto A, Joshita S, Komatsu M, Tanaka N, Umemura T, et al. Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors. Hepatology. 2008;48:1753–60.PubMedCrossRef Shirakawa H, Matsumoto A, Joshita S, Komatsu M, Tanaka N, Umemura T, et al. Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors. Hepatology. 2008;48:1753–60.PubMedCrossRef
10.
go back to reference Nomura H, Miyagi Y, Tanimoto H, Higashi M, Ishibashi H. Effective prediction of outcome of combination therapy with pegylated interferon alpha 2b plus ribavirin in Japanese patients with genotype-1 chronic hepatitis C using early viral kinetics and new indices. J Gastroenterol. 2009;44:338–45.PubMedCrossRef Nomura H, Miyagi Y, Tanimoto H, Higashi M, Ishibashi H. Effective prediction of outcome of combination therapy with pegylated interferon alpha 2b plus ribavirin in Japanese patients with genotype-1 chronic hepatitis C using early viral kinetics and new indices. J Gastroenterol. 2009;44:338–45.PubMedCrossRef
11.
go back to reference Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, et al. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology. 2003;37:600–9.PubMedCrossRef Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, et al. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology. 2003;37:600–9.PubMedCrossRef
12.
go back to reference Bergmann JF, Vrolijk JM, van der Schaar P, Vroom B, van Hoek B, van der Sluys A, et al. Glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-a-2b in chronic hepatitis C non-responders. Liver Int. 2007;27:1217–25. Bergmann JF, Vrolijk JM, van der Schaar P, Vroom B, van Hoek B, van der Sluys A, et al. Glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-a-2b in chronic hepatitis C non-responders. Liver Int. 2007;27:1217–25.
13.
go back to reference von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, et al. Placebo-controlled trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in chronic hepatitis C virus-1 infection. Hepatology. 2008;48:1404–11.CrossRef von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, et al. Placebo-controlled trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in chronic hepatitis C virus-1 infection. Hepatology. 2008;48:1404–11.CrossRef
14.
go back to reference Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology. 2004;127(6):1724–32.PubMedCrossRef Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology. 2004;127(6):1724–32.PubMedCrossRef
15.
go back to reference Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006;130(4):1086–97.PubMedCrossRef Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006;130(4):1086–97.PubMedCrossRef
16.
go back to reference Berg T, Weich V, Teuber G, Klinker H, Möller B, Rasenack J, et al. Time to HCV RNA negativation in hepatitis C virus (HCV) type 1-infection during PEG-interferon-alpha-2b plus ribavirin therapy. Differences in relation to the assay sensitivity (INDIV-1 study group). Hepatology. 2007;46(4):360A. Berg T, Weich V, Teuber G, Klinker H, Möller B, Rasenack J, et al. Time to HCV RNA negativation in hepatitis C virus (HCV) type 1-infection during PEG-interferon-alpha-2b plus ribavirin therapy. Differences in relation to the assay sensitivity (INDIV-1 study group). Hepatology. 2007;46(4):360A.
17.
go back to reference Berg T, Kronenberger B, Hinrichsen H, Gerlach T, Buggisch P, Herrmann E, et al. Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo- controlled trial. Hepatology. 2003;37:1359–67.PubMedCrossRef Berg T, Kronenberger B, Hinrichsen H, Gerlach T, Buggisch P, Herrmann E, et al. Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo- controlled trial. Hepatology. 2003;37:1359–67.PubMedCrossRef
18.
go back to reference von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, et al. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005;129(2):522–7.CrossRef von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, et al. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005;129(2):522–7.CrossRef
19.
go back to reference Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple non-invasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.PubMedCrossRef Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple non-invasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.PubMedCrossRef
20.
go back to reference Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20.PubMedCrossRef Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20.PubMedCrossRef
21.
go back to reference Hytiroglou P, Thung SN, Gerber MA. Histological classification and quantitation of the severity of chronic hepatitis: keep it simple!. Semin Liver Dis. 1995;15:414–21.PubMedCrossRef Hytiroglou P, Thung SN, Gerber MA. Histological classification and quantitation of the severity of chronic hepatitis: keep it simple!. Semin Liver Dis. 1995;15:414–21.PubMedCrossRef
22.
go back to reference Kronenberger B, Herrmann E, Micol F, von Wagner M, Zeuzem S. Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels. Hepatology. 2003;40:1442–9.CrossRef Kronenberger B, Herrmann E, Micol F, von Wagner M, Zeuzem S. Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels. Hepatology. 2003;40:1442–9.CrossRef
23.
go back to reference Giannini E, Botta F, Fasoli A, Romagnoli P, Mastracci L, Ceppa P, et al. Increased levels of gammaGT suggest the presence of bile duct lesions in patients with chronic hepatitis C: absence of influence of HCV genotype, HCV-RNA serum levels, and HGV infection on this histological damage. Dig Dis Sci. 2001;46:524–9.PubMedCrossRef Giannini E, Botta F, Fasoli A, Romagnoli P, Mastracci L, Ceppa P, et al. Increased levels of gammaGT suggest the presence of bile duct lesions in patients with chronic hepatitis C: absence of influence of HCV genotype, HCV-RNA serum levels, and HGV infection on this histological damage. Dig Dis Sci. 2001;46:524–9.PubMedCrossRef
24.
go back to reference Silva IS, Ferraz ML, Perez RM, Lanzoni VP, Figueiredo VM, Silva AE. Role of γ-glutamyl transferase activity in patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol. 2004;19:314–8.PubMedCrossRef Silva IS, Ferraz ML, Perez RM, Lanzoni VP, Figueiredo VM, Silva AE. Role of γ-glutamyl transferase activity in patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol. 2004;19:314–8.PubMedCrossRef
25.
go back to reference Hwang SJ, Luo JC, Chu CW, Lai CR, Lu CL, Tsay SH, et al. Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. J Gastroenterol Hepatol. 2001;16:190–5.PubMedCrossRef Hwang SJ, Luo JC, Chu CW, Lai CR, Lu CL, Tsay SH, et al. Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. J Gastroenterol Hepatol. 2001;16:190–5.PubMedCrossRef
26.
go back to reference Taliani G, Badolato MC, Nigro G, Biasin M, Boddi V, Pasquazzi C, et al. Serum concentration of γ-GT is a surrogate marker of hepatic TNF-α mRNA expression in chronic hepatitis C. Clin Immunol. 2002;105:279–85.PubMedCrossRef Taliani G, Badolato MC, Nigro G, Biasin M, Boddi V, Pasquazzi C, et al. Serum concentration of γ-GT is a surrogate marker of hepatic TNF-α mRNA expression in chronic hepatitis C. Clin Immunol. 2002;105:279–85.PubMedCrossRef
27.
go back to reference Lonardo A, Lombardini S, Scaglioni F, Carulli L, Ricchi M, Ganazzi D, et al. Hepatic steatosis and insulin resistance: does etiology make a difference. J Hepatol. 2006;44:190–6.PubMedCrossRef Lonardo A, Lombardini S, Scaglioni F, Carulli L, Ricchi M, Ganazzi D, et al. Hepatic steatosis and insulin resistance: does etiology make a difference. J Hepatol. 2006;44:190–6.PubMedCrossRef
28.
go back to reference Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.
29.
go back to reference Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, et al. Common variation of IL 28 affects gamma-GTP-levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol. 2010;53:439–43.PubMedCrossRef Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, et al. Common variation of IL 28 affects gamma-GTP-levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol. 2010;53:439–43.PubMedCrossRef
30.
go back to reference Shiffmann ML, Berg T, Poordad FF, Bronowicki JP, Muir AJ, Gordon SC, et al. A study of telaprevir combined with peginterferon-alfa-2a and ribavirin in subjects with well-documented non-response or relapse after previous peginterferon-alfa-2a and ribavirin treatment: interim analysis. Hepatology. 2008;48(Suppl. S):1135–6. Shiffmann ML, Berg T, Poordad FF, Bronowicki JP, Muir AJ, Gordon SC, et al. A study of telaprevir combined with peginterferon-alfa-2a and ribavirin in subjects with well-documented non-response or relapse after previous peginterferon-alfa-2a and ribavirin treatment: interim analysis. Hepatology. 2008;48(Suppl. S):1135–6.
31.
go back to reference Soriano V, Peters MG, Zeuzem S. New therapies for hepatitis C virus infection. Clin Infect Dis. 2009;48:313–20.PubMedCrossRef Soriano V, Peters MG, Zeuzem S. New therapies for hepatitis C virus infection. Clin Infect Dis. 2009;48:313–20.PubMedCrossRef
Metadata
Title
The determination of GGT is the most reliable predictor of nonresponsiveness to interferon-alpha based therapy in HCV type-1 infection
Authors
Viola Weich
Eva Herrmann
Tje Lin Chung
Christoph Sarrazin
Holger Hinrichsen
Peter Buggisch
Tilman Gerlach
Hartwig Klinker
Ulrich Spengler
Alexandra Bergk
Stefan Zeuzem
Thomas Berg
Publication date
01-12-2011
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 12/2011
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-011-0458-y

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