Abstract
Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.
Highlights
Hepatocellular carcinoma (HCC) is a cause of systemic disorders and fatal human disease [1].Several agents are strongly associated with the development of hepatocellular carcinoma (HCC) including chemicals such as aflatoxin B1 and alcohol as well as viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) [2,3,4]
Moderate centrilobular necrosis was detected in the liver of the non-transgenic mice (NTG) and TG-K (Figure 1)
Oxidative stress is increased in both patients with alcoholic liver disease and individuals infected with Hepatitis C virus (HCV)
Summary
Several agents are strongly associated with the development of HCC including chemicals such as aflatoxin B1 and alcohol as well as viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) [2,3,4]. HCV is the major etiologic agent of chronic hepatitis, a disease that is closely linked to the development of HCC in many countries [2,5]. Most cases of HCV infection start without clinical symptom before progressing to persistent viremia, chronic hepatitis, hepatic cirrhosis and HCC [2]. Generation of HCV core transgenic mice has demonstrated the major role of core protein in HCC progression. These mice present chronic steatosis and develop HCC [6]. HCV core protein has been shown to induce apoptosis in mice [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
