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Vitamins in the treatment of chronic viral hepatitis

  • Sirio Fiorino (a1) (a2), Fabio Conti (a2), Annagiulia Gramenzi (a2), Elisabetta Loggi (a2), Carmela Cursaro (a2), Roberto Di Donato (a2), Lorenzo Micco (a2), Stefano Gitto (a2), Andrea Cuppini (a1), Mauro Bernardi (a2) and Pietro Andreone (a2)...


Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related chronic infections represent a major health problem worldwide. Although the efficacy of HBV and HCV treatment has improved, several important problems remain. Current recommended antiviral treatments are associated with considerable expense, adverse effects and poor efficacy in some patients. Thus, several alternative approaches have been attempted. To review the clinical experiences investigating the use of lipid- and water-soluble vitamins in the treatment of HBV- and HCV-related chronic infections, PubMed, the Cochrane Library, MEDLINE and EMBASE were searched for clinical studies on the use of vitamins in the treatment of HBV- and HCV-related hepatitis, alone or in combination with other antiviral options. Different randomised clinical trials and small case series have evaluated the potential virological and/or biochemical effects of several vitamins. The heterogeneous study designs and populations, the small number of patients enrolled, the weakness of endpoints and the different treatment schedules and follow-up periods make the results largely inconclusive. Only well-designed randomised controlled trials with well-selected endpoints will ascertain whether vitamins have any role in chronic viral hepatitis. Until such time, the use of vitamins cannot be recommended as a therapy for patients with chronic hepatitis B or C.

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Corresponding author

*Corresponding author: Professor P. Andreone, fax +39 051 345806, email


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1 Kane, M (1995) Global programme for control of hepatitis B infection. Vaccine 13, S47S49.
2 Lee, WM (1997) Hepatitis B virus infection. N Engl J Med 337, 17331745.
3 Di Bisceglie, AM (1998) Hepatitis C. Lancet 351, 351355.
4 European Association for the study of the liver (2009) EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 50, 227242.
5 Delaney, WE 4th & Borroto-Esoda, K (2008) Therapy of chronic hepatitis B: trends and developments. Curr Opin Pharmacol 8, 532540.
6 Manns, MP, McHutchison, JG, Gordon, SC, et al. (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358, 958965.
7 Fried, MW, Shiffman, ML, Reddy, KR, et al. (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347, 975982.
8 Hadziyannis, SJ, Sette, H Jr, Morgan, TR, et al. (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140, 346355.
9 Soriano, V, Peters, MG & Zeuzem, S (2009) New therapies for hepatitis C virus infection. Clin Infect Dis 48, 313320.
10 Vento, S, Cainelli, F & Temesgen, Z (2008) Perspectives in therapy for hepatitis C. Expert Opin Investig Drugs 17, 16351639.
11 Guidotti, LG & Chisari, FV (2006) Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol 1, 2361.
12 Bertoletti, A & Ferrari, C (2003) Kinetics of the immune response during HBV and HCV infection. Hepatology 38, 413.
13 Bertoletti, A & Gehring, AJ (2006) The immune response during hepatitis B virus infection. J Gen Virol 87, 14391449.
14 Rehermann, B (2007) Chronic infections with hepatotropic viruses: mechanisms of impairment of cellular immune responses. Semin Liver Dis 27, 152160.
15 Medina, J & Moreno-Otero, R (2005) Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 65, 24452461.
16 Waris, G, Huh, KW & Siddiqui, A (2001) Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kB via oxidative stress. Mol Cell Biol 22, 77217730.
17 Wang, HC, Huang, W, Lai, MD, et al. (2006) Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer Sci 97, 683688.
18 Wang, HC, Chang, WT, Chang, WW, et al. (2005) Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes. Hepatology 41, 761770.
19 Wang, JH, Yun, C, Kim, S, et al. (2003) Reactive oxygen species modulates the intracellular level of HBx viral oncoprotein. Biochem Biophys Res Commun 310, 3239.
20 Ghosh, AK, Steele, R, Meyer, K, et al. (1999) Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth. J Gen Virol 80, 11791183.
21 Waris, G, Tardif, KD & Siddiqui, A (2002) Endoplasmic reticulum (ER) stress: hepatitis C virus induces an ER-nucleus signal transduction pathway and activates NF-kappaB and STAT-3. Biochem Pharmacol 64, 14251430.
22 Gong, G, Waris, G, Tanveer, R, et al. (2001) Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappaB. Proc Natl Acad Sci USA 98, 95999604.
23 Korenaga, M, Okuda, M, Otani, K, et al. (2005) Mitochondrial dysfunction in hepatitis C. J Clin Gastroenterol 39, S162S166.
24 Piccoli, C, Scrima, R, Quarato, G, et al. (2007) Hepatitis C protein expression causes calcium-mediated mitochondrial bioenergetic dysfunction and nitro-oxidative stress. Hepatology 4, 5865.
25 Farinati, F, Cardin, R, Bortolami, M, et al. (2007) Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma. J Viral Hepat 14, 821829.
26 Fialkow, L, Wang, Y & Downey, GP (2007) Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med 42, 153164.
27 Okuda, M, Li, K, Beard, MR, et al. (2002) Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122, 366375.
28 Moriya, K, Nakagawa, K, Santa, T, et al. (2001) Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res 61, 43654370.
29 Majano, PL, García-Monzón, C, López-Cabrera, M, et al. (1998) Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation. J Clin Invest 101, 13431352.
30 Majano, P, Lara-Pezzi, E, López-Cabrera, M, et al. (2001) Hepatitis B virus X protein transactivates inducible nitric oxide synthase gene promoter through the proximal nuclear factor kappaB-binding site: evidence that cytoplasmic location of X protein is essential for gene transactivation. Hepatology 34, 12181224.
31 Sprengers, D & Janssen, HL (2005) Immunomodulatory therapy for chronic hepatitis B virus infection. Fundam Clin Pharmacol 19, 1726.
32 Rocchi, E, Casalgrandi, G, Ronzoni, A, et al. (2001) Antioxidant liposoluble vitamins and carotenoids in chronic hepatitis. Eur J Intern Med 12, 116121.
33 Maggini, S, Wintergerst, ES, Beveridge, S, et al. (2007) Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br J Nutr 98, S29S35.
34 Lin, CC & Yin, MC (2009) Vitamins B depletion, lower iron status and decreased antioxidative defense in patients with chronic hepatitis C treated by pegylated interferon alfa and ribavirin. Clin Nutr 28, 3438.
35 Souza dos Santos, RM, de Bem, AF, Colpo, E, et al. (2008) Plasmatic vitamin C in nontreated hepatitis C patients is negatively associated with aspartate aminotransferase. Liver Int 28, 5460.
36 Petta, S, Cammà, C, Scazzone, C, et al. (2010) Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology 51, 11581167.
37 Arteh, J, Narra, S & Nair, S (2009) Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci 55, 26242628.
38 George, J, Ganesh, HK, Acharya, S, et al. (2009) Bone mineral density and disorders of mineral metabolism in chronic liver disease. World J Gastroenterol 15, 35163522.
39 Fisher, L & Fisher, A (2007) Vitamin D and parathyroid hormone in outpatients with noncholestatic chronic liver disease. Clin Gastroenterol Hepatol 5, 513520.
40 Grønbaek, K, Sonne, J, Ring-Larsen, H, et al. (2005) Viral load is a negative predictor of antioxidant levels in hepatitis C patients. Scand J Infect Dis 37, 686689.
41 Van Thiel, DH, Friedlander, L, Fagiuoli, S, et al. (1994) Response to interferon alpha therapy is influenced by the iron content of the liver. J Hepatol 20, 410415.
42 Bonomi, F & Pagani, S (1991) Uptake of iron by apoferritin from a ferric dihydrolipoate complex. Eur J Biochem 199, 181186.
43 Lai, CL, Lok, AS, Lin, HJ, et al. (1987) Placebo-controlled trial of recombinant alpha 2-interferon in Chinese HBsAg-carrier children. Lancet ii, 877880.
44 Lai, CL, Lin, HJ, Lau, JN, et al. (1991) Effect of recombinant alpha 2 interferon with or without prednisone in Chinese HBsAg carrier children. Q J Med 78, 155163.
45 Wallace, AE & Weeks, WB (2001) Thiamine treatment of chronic hepatitis B infection. Am J Gastroenterol 96, 864868.
46 Meydani, M (1995) Vitamin E. Lancet 345, 170175.
47 Sies, H & Murphy, ME (1991) Role of tocopherols in the protection of biological systems against oxidative damage. J Photochem Photobiol B 8, 211218.
48 Halliwell, B & Gutteridge, JM (1984) Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy. Lancet 1, 13961397.
49 Andreone, P, Fiorino, S, Cursaro, C, et al. (2001) Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial. Antiviral Res 49, 7581.
50 Dikici, B, Dagli, A, Ucmak, H, et al. (2007) Efficacy of vitamin E in children with immunotolerant-phase chronic hepatitis B infection. Pediatr Int 49, 603607.
51 Gerner, P, Posselt, HG, Krahl, A, et al. (2008) Vitamin E treatment for children with chronic hepatitis B: a randomized placebo controlled trial. World J Gastroenterol 14, 72087213.
52 Morbitzer, M & Herget, T (2005) Expression of gastrointestinal glutathione peroxidase is inversely correlated to the presence of hepatitis C virus subgenomic RNA in human liver cells. J Biol Chem 280, 88318841.
53 Kelner, MJ, Bagnell, RD, Montoya, MA, et al. (2000) Structural organization of the human gastrointestinal glutathione peroxidase (GPX2) promoter and 30-nontranscribed region: transcriptional response to exogenous redox agents. Gene 248, 109116.
54 Hamamoto, S, Fukuda, R, Ishimura, N, et al. (2003) 9-cis Retinoic acid enhances the antiviral effect of interferon on hepatitis C virus replication through increased expression of type I interferon receptor. J Lab Clin Med 141, 5866.
55 Böcher, WO, Wallasch, C, Höhler, T, et al. (2008) All-trans retinoic acid for treatment of chronic hepatitis C. Liver Int 28, 347354.
56 von Herbay, A, Stahl, W, Niederau, C, et al. (1997) Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: a randomised, double blind, placebo-controlled study. Free Radic Res 27, 599605.
57 Look, MP, Gerard, A, Rao, GS, et al. (1999) Interferon/antioxidant combination therapy for chronic hepatitis C – a controlled pilot trial. Antiviral Res 1143, 113122.
58 Idéo, G, Bellobuono, A, Tempini, S, et al. (1999) Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study. Eur J Gastroenterol Hepatol 11, 12031207.
59 Houglum, K, Venkataramani, A, Lyche, K, et al. (1997) A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 113, 10691073.
60 Groenbaek, K, Friis, H, Hansen, M, et al. (2006) The effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status: a randomized trial among chronic hepatitis C virus-infected patients. Eur J Gastroenterol Hepatol 18, 985989.
61 Falasca, K, Ucciferri, C, Mancino, P, et al. (2008) Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection. J Med Virol 80, 19001906.
62 Harrison's, (2004) Principles of Internal Medicine, 16th ed., pp. 403410. New York: McGraw-Hill.
63 Goodman, & Gilman's, (2001) The Pharmacological Basis of Therapeutics, 10th ed., chapters 63 and 64, pp. 16651699. New York: McGraw-Hill.
64 Ghany, MG, Strader, DB, Thomas, DL, et al. (2009) Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 49, 13351374.


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Vitamins in the treatment of chronic viral hepatitis

  • Sirio Fiorino (a1) (a2), Fabio Conti (a2), Annagiulia Gramenzi (a2), Elisabetta Loggi (a2), Carmela Cursaro (a2), Roberto Di Donato (a2), Lorenzo Micco (a2), Stefano Gitto (a2), Andrea Cuppini (a1), Mauro Bernardi (a2) and Pietro Andreone (a2)...


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