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Ribavirin induced hemolysis:A novel mechanism of action against chronic hepatitis C virus infection

World Journal of Gastroenterology 2014年第43期20卷 16184-16190页

作者： kaartik soota Benedict Maliakkal Department of Internal Medicine Unity Health SystemRochesterNY 14626United States Department of Gastroenterology and Hepatology University of Rochester Medical CenterRochesterNY 14642United States

Hepatitis C virus (HCV) is not usually cleared by our immune system, leading to the development of chronic hepatitis C infection. Chronic HCV induces the production of various cytokines, predominantly by Kupffer cells (KCs), and creates a pro-inflammatory state in the liver. The chronic dysregulated production of interferon (IFN) and other cytokines by KCs also promotes innate immune tolerance. Ribavirin (RBV) monotherapy has been shown to decrease inflammation in liver of patients with chronic hepatitis C. Sustained virological response (SVR) is significantly higher when IFN is combined with RBV in chronic HCV (cHCV) infection. However, the mechanism of their synergy remains unclear. Previous theories have attempted to explain the anti-HCV effect based on direct action of RBV alone on the virus or on the immune system; however, these theories have serious shortcomings. We propose that hemolysis, which universally occurs with RBV therapy and which is considered a limiting side effect, is precisely the mechanism by which the anti-HCV effect is exerted. Passive hemolysis results in anti-inflammatory/antiviral actions within the liver that disrupt the innate immune tolerance, leading to the synergy of RBV with IFN-α. Ribavirin-induced hemolysis floods the hepatocytes and KCs with heme, which is metabolized and detoxified by heme oxygenase-1 (HMOX1) to carbon monoxide (CO), biliverdin and free iron (which induces ferritin). These metabolites of heme possess anti-inflammatory and antioxidant properties. Thus, HMOX1 plays an extremely important anti-oxidant, anti-inflammatory and cytoprotective role, particularly in KCs and hepatocytes. HMOX1 has been noted to have anti-viral effects in hepatitis C infected cell lines. Additionally, it has been shown to enhance the response to IFN-α by restoring interferon-stimulated genes (ISGs). This mechanism can be clinically corroborated by the following observations that have been found in patients undergoing RBV/IFN

关键词： Chronic hepatitis C Therapy Ribavirin Hemolysis Heme oxygenase-1

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Utility of endoscopic ultrasound and endoscopy in diagnosis and management of hepatocellular carcinoma and its complications: What does endoscopic ultrasonography offer above and beyond conventional cross-sectional imaging?

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World Journal of Gastrointestinal Endoscopy 2018年第2期10卷 56-68页

作者： Mohit Girotra kaartik soota Amaninder S Dhaliwal Rtika R Abraham Mauricio Garcia-Saenz-de-Sicilia Benjamin Tharian Division of Gastroenterology University of Miami Miller School of Medicine Division of Gastroenterology and Hepatology University of Iowa School of Medicine Division of Gastroenterology and Hepatology University of Nebraska School of Medicine Department of Medicine University of Miami Miller School of Medicine Division of Gastroenterology and Hepatology University of Arkansas for Medical Sciences Division of Gastroenterology University of Arkansas for Medical Sciences

Hepatocellular carcinoma constitutes over 90% of the primary liver tumors, the rest being cholangiocarcinoma. It has an insidious presentation, which is responsible for the delayed presentation. Hence, the management strategy relies on screening to diagnose it an early stage for curative resection and/or treatment with local ablative techniques or chemotherapy. However, even with different screening programs, more than 60% of tumors are still detected at an advanced stage, leading to an unchanged mortality rate, thereby implying a room for improvement in the screening and diagnostic process. In the last few years, there has been evolution of utility of endoscopy, specifically endoscopic ultrasonography along with Fine needle aspiration, for this purpose, which we comprehensively review in this article.

关键词： Hepatocellular carcinoma Liver Cancer Fine needle aspiration Endoscopy Endoscopic ultrasound Endoscopic ultrasonography Staging Management Treatment

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