Effect of Antiviral Therapy on Serum Activity of Angiotensin Converting Enzyme in Patients with Chronic Hepatitis C

Azra Husic-Selimovic, Amela Sofic, Jasminko Huskic, Deniz Bulja, Azra Husic-Selimovic, Amela Sofic, Jasminko Huskic, Deniz Bulja

Abstract

Introduction: Renin-angiotenzin system (RAS) is frequently activated in patients with chronic liver disease. Angiotenzin - II (AT-II), produced by angiotenzin converting enzyme (ACE), has many physiological effects, including an important role in liver fibrogenesis. Combined antiviral therapy with PEG-IFN and ribavirin besides its antiviral effect also leads to a reduction in liver parenchyma fibrosis.

Aim of the study: Determining the value of ACE in serum of patients with chronic hepatitis C before and after combined antiviral therapy, as well as the value of ACE activities in sera of the control group.

Materials and methods: We studied 50 patients treated at Gastroenterohepatology Department, in the time-period of four years. Value of ACE in serum was determined by Olympus AU 400 device, with application of kit "Infinity TN ACE Liquid Stable Reagent". HCV RNA levels in sera were measured by real time PCR. HCV RNA test was performed with modular analysis of AMPLICOR and COBAS AMPLICOR HCV MONITOR test v2.0, which has proved infection and was used for quantification of the viruses and monitoring of the patients' response to therapy. Liver histology was evaluated in accordance with the level of necroinflammation activity and stage of fibrosis.

Results: Serum activities of ACE in chronic hepatitis C patients is statistically higher than the values in the control group (p=0.02). Antiviral therapy in chronic hepatitis C patients statistically decreases serum activities of ACE (p= 0.02) and indirectly affects fibrogenesis of the liver parenchyma. Correlation between ACE and ALT activity after the therapy was proved (0.3934).

Conclusion: Our findings suggest that the activity of ACE in serum is a good indirect parameter of the liver damage, and could be used as an indirect prognostic factor of the level of liver parenchyma damage. Serum activity of ACE can be used as a parameter for non-invasive assessment of intensity of liver damage.

Keywords: Angiotensin-converting enzyme; antiviral response; chronic hepatitis C; interferon.

Conflict of interest statement

• Conflict of interest: There is no conflict of interest of any of listed authors.

Figures

Figure 1
Figure 1
Line diagram of ACE values in patients measured before (ACE1) and after therapy (ACE2).
Figure 2
Figure 2
Line diagram of logarithms at base 10 for PCR values measured before (logPCR1) and after therapy (logPCR2). Negative findings have been replaced by zeroes. Correlations in a set of treated patients
Figure 3
Figure 3
Concentration of ACE in serum of patients with chronic hepatitis C, before therapy, after therapy and in control group. Mean values (X+SEM) of ACE concentration in control group of respondents, group of patients before and after therapy are presented. Control-respondents without liver disease manifestations (N=30). CHC before Th-patients with chronic hepatitis C before therapy (N=50). CHC after Th- patients with chronic hepatitis C after therapy (N=50) measured before (logPCR1) and after therapy (logPCR2). Negative findings have been replaced by zeroes. Correlations in a set of treated patients

References

    1. Schuppan D, Krebs A, Bauer M, Hahn EG. Hepatitis C and and liver fibrosis. Cell Death Differ. 2003;10(Suppl.1):S59–S67.
    1. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, et al. Angiotensin II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology. 2001;34(4):745–9.
    1. Kardum D, Huskic J, Fabijanic D, Banic M, Buljevac M, Kujundžic M, et al. Activity of serum angiotensin-converting enzyme as a tumor marker of hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 1999;11(11):1209–13.
    1. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y. Angiotensin- II type 1 receptor interaction is a mayor regulator for liver fibrosis development in rats. Hepatology. 2001;34:745–50.
    1. Yoshiji H, Yoshiji J, Ikenaka Y, Noguchi R, Tsujinone H, Nakatani T. Inhibition of renin angiotensin system attenuates liver enzyme altered preneoplastic lesions and fibrosis development in rats. J Hepatology. 2002;37:22–30.
    1. Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatits C. Lancet. 2003;362:2095–2100.
    1. Sethi A, Shiffman ML. Approach to the managment of patients with chronic hepatitis C who failed to achieve sustained virological response. Infect Dis Clin North Am. 2006;20:115–35.
    1. Inagaki Y, Nemoto T, Kushida M, Sheng Y, Higashi K, Ikeda K, Kawada N, Shirasaki F, Takehara K, Sugiyama K. Interferon alpha down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice. Hepatology. 2003;23:348–56.
    1. Arthur MJ. Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology. 2004;122:1515–28.
    1. Hammel P. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med. 2001;344:418–23.
    1. Dixon JB, Bhathal PS, Huges NR, Obrien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology. 2004;39:1647–54.
    1. Ramadori G, Saile B. Portal tract fibrogenesis in the liver. Lab invest. 2004;84:153–9.
    1. Poynard T. Natural history of HCV infection. Bailliers Best Pract Res Clin Gastroenterology. 2000;14:211–28.
    1. Kanno K, Tazuma S, Chayama K. AT 1 A-defficient mice show less severe progression of liver fibrosis induced by CCI. Biochem Biophys Res Commun. 2003;308:177–83.
    1. Terui Y, Saito T, Watanabe H, Togashi H, Kawata S, Kamada Y. Effect of angiotensin receptor antagonist on liver fibrosis in early stages of chronic hepatitis C. Hepatology. 2002;36:1022.
    1. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T. Angiotensin-II type 1 receptor interaction in a majoe regulator for liver fibrosis development in rats. Hepatology. 2001;34:745–50.
    1. Rimola A, Londono MC, Guevara G, Bruguera M, Navasa M, Forns X, Garcia-Retortillo M, Garcia-Valdecasas JC, Rodes J. Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantataion. Transplantation. 2004 Sep 15;78(5):686–91.
    1. Suzuki K, Aoki K, Ohnami S, Yoshida K, Kazui T, Kato N. Adenovirus-mediated gene transfer of interferon alpha improves dimethylnitrosamine-induced liver cirrhosis in rat model. Gene Ther. 2003;10:765–73.
    1. Leung NW. Menagment of viral hepatitis C. J Gastroeneterology and Hepatology. 2002;17(Suppl):S146–54.
    1. Maher J. Interactions between hepatic stellate cells and the imune system. Semin. Liver Dis. 2001;21:417–26.
    1. Inagaki Y, Nemoto T, Kushida M, Sheng Y, Higashi K, Ikeda K. Interferon alfa down-regulates collagen gene transcription and supresses experimental hepatic fibrosis in mice. Hepatology. 2003;38:890–9.
    1. Holmquist L, Mattern F, Schiele B, Alahuhta P, Beigl M, Gellersen H. Smart-its friends: A technique for users to easily establish connections between smart artefacts. In Proc. of UBICOMP. 2001 Atlanta, GA, US.
    1. Pinzani M, Rombouts K, Colagrande S. Fibrosis in chronic liver diseases: diagnosis and management. Journal of Hepatology. 2005;42:S22–S36.
    1. Albanis E, Friedman S. Hepatic fibrosis. Pathogenesis and principles of therapy. Clin Liver Disease. 2001;5:315–34.
    1. Massard J, Ratziu V, Thabut D, Moussali J, Lebray P, Benhamou Y. Natural history and predicors of disease severity in chronic hepatitis C. J Hepatology. 2006;44:19–24.
    1. Powell EE, Edwards-Smith CJ, Hay JL, Clouston AD, Crawford DH, Shorthouse C, Purdie DM, Jonsson JR. Host genitic factors influence disease progression in chronic hepatitis C. Hepatology. 2000;31(4):828–33.
    1. Bataller R, Schwabe R, Robert F, Choi Y, Yang L, Paik YH, et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest. 2003;112(9):1383–94.
    1. Guillaud O, Gurram KC, Puglia M, Lilly L, Adeyi O, Renner EL, Selzner N. Angiotensin blockade does not affect fibrosis progression in recurrent hepatitis C after liver transplantation. Transplant Proc. 2013 Jul-Aug;45(6):2331–6.
    1. Yoshiji H, Kuriyama S, Fukui H. Blockade of renin-angiotensin system in antifibrotic therapy. J Gastroenterol Hepatol. 2007 Jun;(22 Suppl 1):S93–5.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere