Sirs, We have read with interest the meta-analysis by Bjelakovic et al.1 where they conclude that no evidence exists to support or refute antioxidant supplements in patients with liver disease. These findings most probably constitute a frustrating reality as, in clinical practice, liver disease patients are frequently supplemented with antioxidants. Based on experimental studies and isolated clinical data, attenuation of oxidative and nitrosative stress could be beneficial in liver injury, ultimately improving inflammation and fibrosis progression.2 As examples, it has been recently shown that oxidative stress and insulin resistance contribute to steatosis, accelerating the progression of fibrosis in chronic hepatitis C patients infected by non-3 genotype;3 moreover, administration of the glutathione precursor S-adenosyl-methionine to patients with alcoholic liver cirrhosis showed beneficial effects,4 possibly acting as a methyl donor compound contributing to restoration of mitochondrial glutathione content and attenuating the hepatic production of nitric oxide through the modulation of nitric oxide synthase-2.5
Nitric oxide has deleterious effects in the presence of reactive oxygen species, as peroxynitrites are formed contributing to the pathophysiology of viral and autoimmune liver diseases.6, 7N-acetyl-cysteine modulates the expression of iNOS in human hepatocytes stimulated with pro-inflammatory cytokines; this effect occurs through the blockade of the activation of the iNOS promoter and is associated with modulation of NF-κB activity, a central transcription factor for induction of iNOS expression.8
Incomplete evidence suggesting that antioxidants could be effective in the attenuation of oxidative and nitrosative stress in liver injury exists.1 Surprisingly, substantial information is lacking on antioxidant therapy in a very prevalent disease as non-alcoholic steatohepatitis (NASH), although N-acetyl-cysteine appears to improve histological steatosis and fibrosis in patients with NASH9 and melatonin is able to diminish oxidative stress in a rat model of bile-duct obstruction.10 It could be worth testing these drugs in multicentre randomized clinical trials,1 including patients with diverse liver diseases, and importantly, identifying biomarkers for the evaluation of oxidative stress degree and the efficacy and safety of antioxidant therapies.