期刊论文详细信息
BMC Gastroenterology
Study of the effect of antiviral therapy on homocysteinemia in hepatitis C virus- infected patients
Muhammad Naeem3  Ali Raza Kazmi1  Salman Akbar Malik2  Saleem Qureshi1  Sofia Hussain3  Mubin Mustafa2 
[1] Khan Research Laboratories (KRL) Hospital, Islamabad, Pakistan;Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan;Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan
关键词: Homocysteine;    Ribavirin;    Interferon;    Infection;    Hepatitis C virus;   
Others  :  1088682
DOI  :  10.1186/1471-230X-12-117
 received in 2012-04-25, accepted in 2012-08-22,  发布年份 2012
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【 摘 要 】

Background

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease (CLD). About 80% of those exposed to the virus develop a chronic infection. Hyperhomocysteinemia, which is an independent risk factor for atherosclerotic vascular disease and thromboembolism

    ,
may develop in HCV-infected patients although altered alanine amino transferase (ALT) enzyme levels are generally associated with damage to liver cells. The gold standard therapy for chronic hepatitis C patients is pegylated interferon combined with an anti-viral drug (ribavirin). The current study aimed to investigate the effect of antiviral therapy on plasma homocysteine (Hcy) levels in HCV patients in addition to other parameters.

Methods

532 HCV-infected patients and 70 healthy controls were recruited for the study. All patients were subjected to laboratory investigations including HCV-RNA levels, complete blood cell counts, serum levels of homocysteine, ALT, alkaline phosphatase (ALP), lipid profile and liver ultrasonographic examination. The outcome of treatment with pegylated interferon α plus ribavirin treatment and sustained virologic response (SVR) was determined 6–9 months post-therapy.

Results

Hyperhomocysteinemia was found in 91.35% of HCV-infected patients. The difference in plasma Hcy concentrations reached statistical significance between the patient and control groups. ALT, cholesterol and triglycerides (TGs) levels were found higher than normal in the patients group. After receiving a combined therapy for 24 weeks, 43.66% patients showed an SVR (responders); 30.98% patients were non-responders while 25.35% patients initially responded to therapy but again retrieved positive status of HCV infection six months post-therapy (relapse-cirrhotic patients). The mean levels of plasma Hcy, ALT and ALP were significantly reduced in responders within 10 weeks of therapy when compared with non-responders and relapse-cirrhotic patients.

Conclusion

Elevated homocysteine levels in serum due to HCV infection can be reduced to normal range with the standard interferon α plus ribavirin treatment. This study highlights the significance of the measurement of serum homocysteine levels in the diagnosis and monitoring of HCV infection treatment in addition to other laboratory parameters.

【 授权许可】

   
2012 Mustafa et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]National Institutes of Health Consensus Development Conference Panel statement: Management of hepatitis C. Hepatology 1997, 26:2S-10S.
  • [2]Wilkins T, Malcolm JK, Raina D, Schade RR: Hepatitis C: diagnosis and treatment. Am Fam Physician 2010, 81:1351-1357.
  • [3]Burke MD: Liver function: test selection and interpretation of results. Clin Lab Med 2002, 22:377-390.
  • [4]Taha K, El-Shayeb A, Shafeh R, Deghady A, Eldin SZ: Clinical significance of plasma homocysteine concentration in chronic hepatitis C patients with liver cirrhosis. Bull Alex Fac Med 2009, 45:755-760.
  • [5]Roblin X, Pofelski J, Zarski JP: Steatosis, chronic hepatitis virus C infection and homocysteine. Gastroenterol Clin Biol 2007, 31:415-720.
  • [6]García-Tevijano ER, Berasain C, Rodríguez JA, Corrales FJ, Arias R, Martín-Duce A, Caballería J, Mato JM, Avila MA: Hyperhomocysteinemia in Liver Cirrhosis: Mechanisms and Role in Vascular and Hepatic Fibrosis. Hypertension 2001, 38:1217-1221.
  • [7]Finkelstein JD: Methionine metabolism in liver diseases. Am J Clin Nutr 2003, 77:1094-1095.
  • [8]Avila MA, Berasain C, Torres L: Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma. J Hepatol 2000, 33:907-914.
  • [9]Blackmund M, Meyer K, Von Zielonka M: Treatment of hepatitis C infection in injection drug users. Hepatol 2001, 34:188-193.
  • [10]Davis GL, Rodrigue JR: Treatment of chronic hepatitis C in active drug users. New Engl J Med 2001, 345:215-217.
  • [11]Bosy-Westphal A, Ruschmeyer M, Czech N, Oehler G, Hinrichsen H, Plauth M, Lotterer E, Fleig W, Muller MJ: Determinants of hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation. Am J Clin Nutr 2003, 77:1269-1277.
  • [12]Waheed Y, Shafi T, Safi SZ, Qadri I: Hepatitis C virus in Pakistan: A systematic review of prevalence, genotypes and risk factors. World J Gastroenterol 2009, 15:5647-5653.
  • [13]Halifeoglu I, Gur B, Aydin S: Plasma trace elements, vitamin B12, folate and homocysteine levels in cirrhotic patients compared to controls. Biochem 2004, 69:693-696.
  • [14]Gulsen M, Yesilova Z, Bagci S, Uygun A, Ozcan A, Ercin CN, Erdil A, Sanisoglu SY, Cakir E, Ates Y, Erbil MK, Karaeren N, Dagalp K: Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non-alcoholic fatty liver disease. Hepatol 2005, 20:1448-1455.
  • [15]Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel H, Dietrich M, Trautwein C, Manns MP: Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001, 345:1452-1457.
  • [16]Werstuck GH, Lentz SR, Dayal S: Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J Clin Invest 2001, 107:1263-1267.
  • [17]Baron S, Tyring SK, Fleischmann WR, Coppenhaver DH, Niesel DW, Klimpel GR, et al.: The interferons: mechanisms of action and clinical applications. JAMA 1991, 266:1375-1383.
  • [18]Capra F, Casaril M, Gabrielli GB, Tognella P, Rizzi A, Dolci L, Colombardi R: α-Interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers. J Hepatol 1993, 18:112-118.
  • [19]Manabe N, Chevallier M, Chossegros P, Causse X, Guerret S, Trepo C, Grimaud JA: Interferon-α2b therapy reduces liver fibrosis in chronic non-A, non-B hepatitis: a quantitative histological evaluation. Hepatol 1993, 18:1344-1349.
  • [20]Hiramatsu N, Hayashi N, Kasahara A, Hagiwara H, Takehara T, Haruna Y, Naito M, Fusamoto H, Kamada T: Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha. J Hepatol 1995, 22:135-142.
  • [21]Yamada G, Takatani M, Kishi F, Takahashi M, Doi T, Tsuji T, Shin S, Tanno M, Urdea MS, Kolberg JA: Efficacy of interferon alfa therapy in chronic hepatitis C patients depends primarily on hepatitis C virus RNA level. Hepatol 1995, 22:1351-1354.
  • [22]Kumada T, Nakano S, Takeda I, Sugiyama K, Osada T, Kiriyama S, Toyoda H, Sasa T, Shibata M, Marishiba T, Nakano I, Fukuda Y, Tameda Y, Nakashima M: Long-term administration of natural interferon-α in patients with chronic hepatitis C: Relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus. J Gastroenterol Hepatol 1996, 11:159-165.
  • [23]Manns MP, McHutchison JG, Gordon SC: Peginterferon alfa-2b in combination with ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: results of a randomized trial. Lancet 2001, 358:958-965.
  • [24]Weiss N, Heydrick S, Zhang YY: Cellular redox state and endothelial dysfunction in mildly hyperhomocysteinemic cystathionine beta-synthase-deficient mice. Asterioscler Thromb Vasc Biol 2002, 22:34-41.
  • [25]Delgado-Reyes CV, Wallig MA, Garrow TA: Immuno-histochemical detection of betaine-homocysteine S-methyl-transferase in human, pig, and rat liver and kidney. Arch Biochem Biophys 2001, 393:184-186.
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