Predictive Power of Biomarkers of Oxidative Stress and Inflammation in Patients with Hepatitis C Virus-Associated Hepatocellular Carcinoma

Maki, Akira; Kono, Hiroshi; Gupta, Mayetri; Asakawa, Masami; Suzuki, Tetsuya; Matsuda, Masanori; Fujii, Hideki; Rusyn, Ivan

doi:10.1245/s10434-006-9049-1

Cited by 116 publications

(88 citation statements)

References 30 publications

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“…Previous studies have suggested that oxidative stress induced by increased ROS and/or impairment of antioxidant mechanism is one of the reasons for hepatocellular damage in chronic infections [38][39][40][41][42] and might be associated with the development of HCC [9]. It has also been suggested that oxidative stress biomarkers could potentially be used as a useful clinical diagnostic tool to predict the duration of survival in patients with HCVassociated HCC [43]. Since patients with greater intrahepatic oxidative stress are associated with increase risk of HCC, the present study looked at the potential role of antioxidant defense system enzymes as a useful clinical diagnostic tool in predicting the duration of disease in patients with chronic hepatitis-associated HCC.…”

Section: Discussionmentioning

confidence: 99%

Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections

et al. 2011

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The present study evaluated the plausible role of circulating biomarkers in immune pathogenesis of chronic hepatitis considered a priority in clinical hepatology. Total viral load of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) patients was quantified and correlation studies were performed with circulating levels of Th1/Th2 cytokines; C reactive protein and circulating nucleosomes; glutathione reductase (GR) and superoxide dismutase. To our knowledge, the study is first among its kind that validates strong positive correlation of viral load with IL-4, IL-6, GR in HBV and IL-6, IL-10, GR in HCV infections. Although, multi-centric studies including large cohorts are required for translating our findings to clinical practice, however, role of these biomarkers with potential diagnostic or prognostic significance might be helpful in clinical assessment of high-risk individuals, thereby, designing interventional strategies, towards development of personalized medicare. The results of our study also offer valuable insights of immune signaling mediators engaged in development of hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections

et al. 2011

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“…Especially in the group of patients with hepatic 8-OHdG counts exceeding 75 positive cells per 10 5 mm 2 , the HCC incidence during the first 3 years was extremely high (38.8%) ( Figure 3A), indicating that these patients constitute a very high-risk subgroup for developing HCC and should necessarily be carefully monitored by several modalities. Recently, Maki et al (2007) evaluated the expression levels of 8-OHdG of non-cancerous hepatic tissues in HCV-infected patients who developed HCC and received curative tumour resection. The postoperative cumulative HCC-free survival was significantly shorter in patients with the highest percentage of 8-OHdG-positive hepatocytes, indicating that the hepatic 8-OHdG levels are also useful for prediction of HCC recurrence in patients with chronic HCV infection who developed HCC.…”

Section: Discussionmentioning

confidence: 99%

Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C

et al. 2008

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Although the oxidative stress frequently occurs in patients with chronic hepatitis C, its role in future hepatocellular carcinoma (HCC) development is unknown. Hepatic 8-hydroxydeoxyguanosine (8-OHdG) was quantified using liver biopsy samples from 118 naïve patients who underwent liver biopsy from 1995 to 2001. The predictability of 8-OHdG for future HCC development and its relations to epidemiologic, biochemical and histological baseline characteristics were evaluated. During the follow-up period (mean was 6.7±3.3 years), HCC was identified in 36 patients (30.5%). Univariate analysis revealed that 16 variables, including 8-OHdG counts (65.2 ± 20.2 vs 40.0 ± 23.5 cells per 10 5 mm 2 , Po0.0001), were significantly different between patients with and without HCC. Cox proportional hazard analysis showed that the hepatic 8-OHdG (P ¼ 0.0058) and fibrosis (P ¼ 0.0181) were independent predicting factors of HCC. Remarkably, 8-OHdG levels were positively correlated with body and hepatic iron storage markers (vs ferritin, Po0.0001 vs hepatic iron score, Po0.0001). This study showed that oxidative DNA damage is associated with increased risk for HCC and hepatic 8-OHdG levels are useful as markers to identify the extreme high-risk subgroup. The strong correlation between hepatic DNA damage and iron overload suggests that the iron content may be a strong mediator of oxidative stress and iron reduction may reduce HCC incidence in patients with chronic hepatitis C.

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“…4-HNE was reported to be a good biomarker for predicting disease-free survival in patients with HCC and CH-C; however, a weaker association with disease outcome when compared to 8-OHdG was noted (36). maki et al reported high expression of 4-hnE in livers with ch-c and hcc compared to controls (36), while in another study, 4-hnE protein adducts were detected in only a few hepatocytes in livers with CH-C (37). The expression level of 4-hnE protein adducts in livers with ch-B was found to be lower than that in livers with CH-C (38).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that high expression of 8-OHdG in livers with CH-C predicted the development of primary hcc (33,34) and also postoperative recurrence (35,36), suggesting the association of 8-OHdG and carcinogenesis in livers with CH-C. However, the expression levels of 8-OHdG in the livers of Group N were low, suggesting that abundant expression of 8-OHdG is not essential for developing HCC.…”

Section: Discussionmentioning

confidence: 99%

Characteristic expression pattern of oxidative stress in livers with cryptogenic hepatocellular carcinoma

et al. 2010

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Abstract. the mechanism responsible for the development of hepatocellular carcinoma (hcc) in the setting of oxidative stress has yet to be clearly defined. We studied the role of oxidative stress in hepatocarcinogenesis in subjects without underlying chronic viral hepatitis. The subjects were 24 patients negative for serum hepatitis B surface antigen and hepatitis c antibody tests, who underwent hepatic resection for HCC (Group N). Subjects were excluded if diagnosed with liver disease predisposing to HCC. immunohistochemical staining for oxidative stress-related markers was performed on non-cancerous liver regions. resected liver tissues adjacent to hcc from 24 patients with chronic hepatitis B (Group B) and 21 patients with chronic hepatitis C (Group C) were also examined. The percentage of 8-hydroxydeoxyguanosine-positive hepatocytes in Group N was significantly lower than that in Group B and that in the combined population of Groups B and C. The percentage of the area positive for 4-hydroxynonenal in Group n was significantly higher than that in Groups B or C. Meanwhile, the percentage of the area positive for manganese superoxide dismutase in Group n was not different from that in Groups B and C. In conclusion, the mechanism of hepatocarcinogenesis through oxidative stress for patients without known liver disease predisposing to hcc may differ from that for patients with chronic viral hepatitis.

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Predictive Power of Biomarkers of Oxidative Stress and Inflammation in Patients with Hepatitis C Virus-Associated Hepatocellular Carcinoma

Cited by 116 publications

References 30 publications

Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections

Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections

Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C

Characteristic expression pattern of oxidative stress in livers with cryptogenic hepatocellular carcinoma

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