Relations between oxidative stress, hepatocyte growth factor, and liver disease in hemodialysis patients

Background: Hepatocyte growth factor (HGF) and copper/zinc superoxide dismutase (Cu/Zn SOD) protect against tissue injury, including that due to oxidative stress (SOX). We studied whether they could be associated with each other, SOX markers, prevalence of viral hepatitis, and cardiovascular disease (CVD) and their laboratory surrogates in maintenance hemodialysis (HD) patients. Methods: In 24 patients, pre-dialysis serum HGF, plasma Cu/Zn SOD, total lipid peroxides, and serum auto-antibodies against oxidized LDL were measured by ELISAs. Viral hepatitis B and C markers were determined by third generation microparticle ELISAs, and CVD was identified on a clinical basis. Results: In HD patients, circulating HGF, Cu/Zn SOD, and the other SOX markers were higher than in healthy controls, and HGF directly correlated with Cu/Zn SOD levels (P = 0.0006). Both HGF (P = 0.021) and Cu/Zn SOD (P = 0.017) were positively associated with prevalence of viral hepatitis and serum alanine aminotransferase activity (P = 0.021 and P = 0.040, respectively). Presence of CVD directly correlated with HGF (P = 0.001) but not with Cu/Zn SOD levels (P = 0.087). Circulating HGF positively related to serum C-reactive protein (P = 0.043). In patients without viral hepatitis and CVD, both HGF and Cu/Zn SOD were lower than in those with, and higher than in healthy controls. CVD (P = 0.003) and viral hepatitis (P = 0.024) were independent predictors of increased HGF, while positive viral hepatitis marker predicted increased Cu/Zn SOD levels (P = 0.019) in HD patients. There were no associations between HGF and the SOX markers in controls. Conclusions: In maintenance HD patients, circulating Cu/Zn SOD and HGF levels are increased, likely as a part of the reparatory reaction against liver damage. Viral hepatitis status and liver function should be considered in further studies of Cu/Zn SOD in these subjects.