Oxidative-inflammatory damage in cirrhosis: effect of vitamin E and a fermented papaya preparation

J Gastroenterol Hepatol. 2007 May;22(5):697-703. doi: 10.1111/j.1440-1746.2007.04937.x.


Background and aim: Oxidative DNA damage occurs as an early event in hepatitis C virus (HCV) infection and is an indication of the potential for carcinogenesis. The aim of this study was to test a novel antioxidant/immunomodulator in patients with HCV-related cirrhosis.

Methods: The study group consisted of 50 patients with HCV-related cirrhosis with transaminase values less than twofold increased (alanine aminotransferase [ALT] < 80 IU/L). Patients underwent a standardized food-vitamin composition assessment and were assessed for dietary intake, nutritional status and iron level. Patients were randomly allocated into two groups and then given either alpha-tocopherol 900 IU/day or 9 g/day of a fermented papaya preparation (FPP, Immun-Age, Osato Research Institute, Gifu, Japan) at bedtime for 6 months. Ten healthy subjects served as controls. Patients were checked monthly for: routine tests, redox status (reduced glutathione, glutathione peroxidase, oxidized glutathione, malondialdehyde), plasma alpha-tocopherol, 8-hydroxy-deoxy-guanidine (8-OHdG) level in circulating leukocyte DNA and serum levels of cytokines.

Results: Patients with cirrhosis showed a significant imbalance of redox status (low antioxidants/high oxidative stress markers) (P < 0.005 vs controls). Neither treatment regimen affected transaminases as a whole. However, vitamin E supplementation almost normalized ALT only in the limited vitamin-E-deficient subgroup. A significant improvement of redox status was obtained by both regimens. However, only FPP significantly decreased 8-OHdG and the improvement of cytokine balance with FPP was significantly better than with vitamin E treatment (P < 0.05).

Conclusions: Although the present data seem to suggest a potential supportive role of antioxidants/immunomodulators as FPP in HCV patients, more studies are needed to substantiate their effect on the natural history of the disease.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • Alanine Transaminase / blood
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Carica*
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Female
  • Fermentation
  • Fruit
  • Glutathione / blood
  • Glutathione Peroxidase
  • Hepatitis C / blood
  • Hepatitis C / complications*
  • Hepatitis C / enzymology
  • Hepatitis C / genetics
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Plant Preparations / pharmacology
  • Plant Preparations / therapeutic use*
  • Receptors, Tumor Necrosis Factor, Type II / blood
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood
  • alpha-Tocopherol / pharmacology
  • alpha-Tocopherol / therapeutic use*


  • Antioxidants
  • Immunologic Factors
  • Plant Preparations
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • 8-Hydroxy-2'-Deoxyguanosine
  • Glutathione Peroxidase
  • Alanine Transaminase
  • Deoxyguanosine
  • Glutathione
  • alpha-Tocopherol