Association between high serum alanine aminotransferase levels and more rapid development and higher rate of incidence of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis

Tarao, Kazuo; Rino, Yasushi; Ohkawa, Shinichi; Shimizu, Akio; Tamai, Setsuo; Miyakawa, Kaoru; Aoki, Hiroharu; Imada, Toshio; Shindo, Kazutoshi; Okamoto, Naoyuki; Totsuka, S

doi:10.1002/(sici)1097-0142(19990815)86:4<589::aid-cncr7>3.0.co;2-k

Cited by 146 publications

(104 citation statements)

References 24 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current finding that plasma ADAMTS13 activity or antigen level significantly correlated with serum AST and ALT levels may explain this. Of note, it was previously shown that the higher serum ALT is associated with the higher rate of incidence of HCC development (31) and HCC recurrence after the surgical treatment (32) in HCV-related cirrhosis, suggesting that more hepatocellular damage increases a risk for HCC development in the liver of the same stage of fibrosis. Because plasma ADAMTS13 activity or antigen level reflect hepatocellular damage and subsequent wound healing as well as liver fibrosis stage, plasma ADAMTS13 activity, or antigen level may act distinctly from liver stiffness value in the risk analysis of HCC development.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Hepatocellular Carcinoma Development by Plasma ADAMTS13 in Chronic Hepatitis B and C

Ikeda

Tateishi

Enooku

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background: Chronic liver injury evokes a wound healing response, promoting fibrosis and finally hepatocellular carcinoma (HCC), in which hepatic stellate cells play an important role. Although a blood marker of hepatic stellate cells is not known, those cells importantly contribute to the regulation of plasma a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity, a defect of which causes thrombotic thrombocytopenic purpura.Methods: Plasma ADAMTS13 was evaluated in chronic hepatitis B or C patients with or without HCC.Results: Plasma ADAMTS13 activity significantly correlated with serum aspartate aminotransferase and alanine aminotransferase, liver stiffness value, and aspartate aminotransferase-to-platelet ratio index, irrespective of the presence of HCC, suggesting that it may reflect hepatocellular damage and subsequent wound healing and fibrosis as a result of hepatic stellate cell action. During the three-year follow-up period for patients without HCC, it developed in 10 among 81 patients. Plasma ADAMTS13 activity was significantly higher in patients with HCC development than in those without and was a significant risk for HCC development by univariate and multivariate analyses. Furthermore, during the one-year follow-up period for patients with HCC treated with radiofrequency ablation, HCC recurred in 55 among 107 patients. Plasma ADAMTS13 activity or antigen level was significantly higher in patients with HCC recurrence than in those without and was retained as a significant risk for HCC recurrence by multivariate analysis.Conclusions: Higher plasma ADAMTS13 activity and antigen level was a risk of HCC development in chronic liver disease.Impact: Plasma ADAMTS13 as a potential marker of hepatic stellate cells may be useful in the prediction of hepatocarcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(10); 2204-11. Ó2011 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Prediction of Hepatocellular Carcinoma Development by Plasma ADAMTS13 in Chronic Hepatitis B and C

Ikeda

Tateishi

Enooku

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…The 5-year cumulative HCC incidence in cirrhosis is between 10% and 30% in HBV and HCV infection, depending on the geographic region, approximately 20% in hereditary hemochromatosis and 8% in alcoholic cirrhosis (Fattovich et al, 2004). Predictors of HCC in cirrhosis include the severity of liver disease determined by the ChildPugh score (Bolondi et al, 2001), the disease activity, reflected by serum transaminase activities (Benvegnu et al, 1994;Tarao et al, 1999), and some histological criteria, such as the presence of large cell changes (LCC) (Borzio et al, 1995;Ganne-Carrié et al, 1996), macronodules (Borzio et al, 2003) and markers for hyperregeneration (Donato et al, 2001;Trerè et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

Seitz

Stickel

2006

Biological Chemistry

282

178

View full text Add to dashboard Cite

Hepatocellular cancer is the fifth most frequent cancer in men and the eighth in women worldwide. Established risk factors are chronic hepatitis B and C infection, chronic heavy alcohol consumption, obesity and type 2 diabetes, tobacco use, use of oral contraceptives, and aflatoxin-contaminated food. Almost 90% of all hepatocellular carcinomas develop in cirrhotic livers. In Western countries, attributable risks are highest for cirrhosis due to chronic alcohol abuse and viral hepatitis B and C infection. Among those with alcoholic cirrhosis, the annual incidence of hepatocellular cancer is 1-2%. An important mechanism implicated in alcohol-related hepatocarcinogenesis is oxidative stress from alcohol metabolism, inflammation, and increased iron storage. Ethanolinduced cytochrome P-450 2E1 produces various reactive oxygen species, leading to the formation of lipid peroxides such as 4-hydroxy-nonenal. Furthermore, alcohol impairs the antioxidant defense system, resulting in mitochondrial damage and apoptosis. Chronic alcohol exposure elicits hepatocyte hyperregeneration due to the activation of survival factors and interference with retinoid metabolism. Direct DNA damage results from acetaldehyde, which can bind to DNA, inhibit DNA repair systems, and lead to the formation of carcinogenic exocyclic DNA etheno adducts. Finally, chronic alcohol abuse interferes with methyl group transfer and may thereby alter gene expression.

show abstract

“…Some authors have been found that recurrence was mainly associated with adverse tumor factors such as tumor size, vascular invasion, and microsatellite [10][11][12][13][14]17,18] . Others demonstrated a liver function status [26][27][28][29][30][31][32]38] . Poon et al showed that tumor factors were linked to early recurrence, whereas the nontumorous liver status was linked to late recurrence [19] .…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of hepatitis B surface antigen (HbsAg) and antibody to HCV in HCC patients were reported to be 63.2% and 11.2% respectively in China [25] , and coexisting cirrhosis occurred in 88.8% (888/1000 patients) for patients with small HCC [14] . The liver damage in patients with HCC after resection is also a risk factor for recurrence and prognosis [26][27][28][29][30][31][32] . Hence, a new stage accounting for both liver function and tumor extension is necessary to predict HCC prognosis.…”

Section: Introductionmentioning

confidence: 99%

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

Zhao¹,

Ma²,

Zhou³

et al. 2002

WJG

View full text Add to dashboard Cite

The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP). CLIP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not published. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection. METHODS:A retrospective survey was carried out in 174 patients undergoing resection of HCC from January 1986 to June 1998. Six patients who died in the hospital after operation and 11 patients with the recurrence of the disease were excluded at 1 month after hepatectomy. By the end of June 2001, 4 patients were lost and 153 patients with curative resection have been followed up for at least three years. Among 153 patients, 115 developed intrahepatic recurrence and 10 developed extrahepatic recurrence, whereas the other 28 remained free of recurrence. Recurrences were classified into early (3 year) recurrence. The CLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portal thrombosis (0-1). By contrast, portal vein thrombosis was defined as the presence of tumor emboli within vascular channel analyzed by microscopic examination in this study. Risk factors for recurrence and prognostic factors for survival in each group were analyzed by the chi-square test, the Kaplan-Meier estimation and the COX proportional hazards model respectively. RESULTS:The 1-,3-,5-,7-,and10-year disease-free survival rates after curative resection of HCC were 57.2%,28.3%, 23.5%,18.8% and 17.8%,respectively. Median survival time was 28,16,10,4, and 5mo for CLIP score 0,1,2,3, and 4 to 5, respectively. Early and late recurrence developed in 109 patients and 16 patients respectively. By the chi-square test, tumor size, microsatellite, venous invasion, tumor type (uninodular, multinodular, massive), tumor extension (50% of liver parenchyma replaced by tumor), TNM stage, CLIP score, and resection margin were the risk factors for early recurrence, whereas CLIP score and ChildPugh stage were significant risk factors for late recurrence. In univariate survival analysis, Child-Pugh stages, resection margin, tumor size, microsatellite, venous invasion, tumor type, tumor extension, TNM stages, and CLIP score were associated with prognosis. The multivariate analysis by COX proportional hazards model showed that the independent predictive factors of survival were resection margins and TNM stages.CONCLUSION: CLIP score has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis in the patients with HCC after resection.

show abstract

Association between high serum alanine aminotransferase levels and more rapid development and higher rate of incidence of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis

Cited by 146 publications

References 24 publications

Prediction of Hepatocellular Carcinoma Development by Plasma ADAMTS13 in Chronic Hepatitis B and C

Prediction of Hepatocellular Carcinoma Development by Plasma ADAMTS13 in Chronic Hepatitis B and C

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

Contact Info

Product

Resources

About