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Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B.

ABSTRACT: Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8(+) T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8(+) T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8(+) T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.

SUBMITTER: Sitia G

PROVIDER: S-EPMC3420192 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B.

Sitia Giovanni G Aiolfi Roberto R Di Lucia Pietro P Mainetti Marta M Fiocchi Amleto A Mingozzi Francesca F Esposito Antonio A Ruggeri Zaverio M ZM Chisari Francis V FV Iannacone Matteo M Guidotti Luca G LG

Proceedings of the National Academy of Sciences of the United States of America 20120702 32

Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8(+) T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may pr ...[more]

PMID: 22753481

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Project description:Hepatocellular carcinoma (HCC) is the main cause of mortality in patients with chronic viral hepatitis (CVH). We determined the impact of surveillance and treatments on long-term outcomes in patients with CVH who developed HCC. Between 1984 and 2014, 333 patients with HCC and with hepatitis B or hepatitis C virus infection were evaluated. An adjusted lead time bias interval was added to patients with HCC who presented with HCC (no surveillance), and their survival was compared to patients whose HCC was detected by surveillance. After HCC treatments, survival rates within and beyond 3 years of follow-up were compared. In 175 (53%) patients, HCC was detected through surveillance using alpha-fetoprotein and abdominal ultrasound examinations. Compared to 158 (47%) patients with HCC who had no surveillance, more patients with HCC detected by surveillance received surgical and locoregional treatments (P < 0.0001 to P < 0.001), and their 1-, 3-, and 5-year overall and disease-free survival rates were significantly higher (P < 0.001 for both). During the first 3 years of follow-up, patients with HCC receiving liver transplantation had similar survival rates as those with liver resection or radiofrequency ablation (RFA); however, due to HCC recurrence, survival in resection and RFA patients became significantly less when followed beyond 3 years (P = 0.001 to P = 0.04). Factors associated with mortality included tumors beyond University of California at San Francisco criteria (hazard ratio [HR] 2.02; P < 0.0001), Child-Pugh class B and C (HR, 1.58-2.26; P = 0.043 to P = 0.015, respectively), alpha-fetoprotein per log ng/mL increase (HR, 1.30; P < 0.0001), previous antiviral therapy in hepatitis B virus patients (HR, 0.62; P = 0.032), and treatments other than liver transplantation (HR, 2.38-6.45; P < 0.0001 to P < 0.003). Conclusion. Patients with HCC detected by surveillance had prolonged survival. Due to HCC recurrence, survival rates after liver resection and RFA were lower when followed beyond 3 years after treatments. (Hepatology Communications 2017;1:595-608).

Dataset Information

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B.

Publications

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B.

Similar Datasets

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