Treatment for Viral Hepatitis as Secondary Prevention for Hepatocellular Carcinoma

Abstract

Chronic infections with either hepatitis B or C virus (HBV or HCV) are among the most common risk factors for developing hepatocellular carcinoma (HCC). The hepatocarcinogenic potential of these viruses is mediated through a wide range of mechanisms, including the induction of chronic inflammation and oxidative stress and the deregulation of cellular pathways by viral proteins. Over the last decade, effective anti-viral agents have made sustained viral suppression or cure a feasible treatment objective for most chronic HBV/HCV patients. Given the tumorigenic potential of HBV/HCV, it is no surprise that obtaining sustained viral suppression or eradication proves to be effective in preventing HCC. This review summarizes the mechanisms by which HCV and HBV exert their hepatocarcinogenic activity and describes in detail the efficacy of anti-HBV and anti-HCV therapies in terms of HCC prevention. Although these treatments significantly reduce the risk for HCC in patients with chronic viral hepatitis, this risk is not eliminated. Therefore, we evaluate potential strategies to improve these outcomes further and address some of the remaining controversies.

Hepatocellular organellar abnormalities following elimination of hepatitis C virus

“…Virulence factors such as inflammation, cirrhosis, dysregulation of cancer‐related pathways, ER stress, oxidative stress, and epigenetic changes have been reported as causes of carcinogenesis by HCV 31,32 . We evaluated EM findings characteristic of HCC cases after achieving SVR to analyse the cause of carcinogenesis that continues after the elimination of HCV.…”

“…Virulence factors such as inflammation, cirrhosis, dysregulation of cancer-related pathways, ER stress, oxidative stress, and epigenetic changes have been reported as causes of carcinogenesis by HCV. 31,32 We evaluated EM findings characteristic of HCC cases after achieving SVR to analyse the cause of carcinogenesis that continues after the elimination of HCV. This study found a significant difference in the level of ER abnormalities in the liver of patients with HCC after >1 year compared to patients with HCC after <1 year (Figure 4).…”

Pegylated interferon‐α‐2b combined with tenofovir disoproxil fumarate, granulocyte‐macrophage colony‐stimulating factor, and hepatitis B vaccine treatment for naïve HBeAg‐positive chronic hepatitis B patients: A prospective, multicenter, randomized controlled study

“…Guidelines for antiviral therapy for CHB have been established; HBsAg loss or seroconversion is an ideal endpoint of treatment, 3,4,18 and is termed a functional cure of CHB. In patients with CHB who achieve a functional cure, the development of liver cirrhosis and HCC is prevented or delayed 19,20 . IFN has been used to treat CHB for decades; it has modest antiviral and immunomodulatory actions and may accelerate the degradation of closed circular covalent DNA, decreasing its transcription, or both 21 .…”

“…In patients with CHB who achieve a functional cure, the development of liver cirrhosis and HCC is prevented or delayed. 19,20 IFN has been used to treat CHB for decades; it has modest antiviral and immunomodulatory actions and may accelerate the degradation of closed circular covalent DNA, decreasing its transcription, or both. 21 As of date, IFN remains the main drug for the functional cure of hepatitis B. IFN can achieve a higher functional cure rate in treating e-antigen-negative CHB or HBsAg in inactive HBsAg carriers.…”

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation

“…This campaign in China has reduced the prevalence of new HBV infections by 90%. It will prevent approximately 2.8 to 3.5 million HBV-related deaths in the future[ 95 ]. Mother-to-child transmission (MTCT) is the main route of HBV transmission and its prevention is very important to eliminate HBV.…”