Mechanism of Hepatitis B Virus Persistence in Hepatocytes and Its Carcinogenic Potential

Abstract

Liver disease associated with persistent infection with hepatitis B virus (HBV) continues to be a major health problem of global impact. Despite the existence of an effective vaccine, at least 240 million people are chronically infected worldwide, and are at risk of developing liver cirrhosis and hepatocellular carcinoma. Although chronic HBV infection is considered the main risk factor for liver cancer development, the molecular mechanisms determining persistence of infection and long-term pathogenesis are not fully elucidated but appear to be multifactorial. Current therapeutic regimens based on the use of polymerase inhibitors can efficiently suppress viral replication but are unable to eradicate the infection. This is due both to the persistence of the HBV genome, which forms a stable minichromosome, the covalently closed circular DNA (cccDNA), in the nucleus of infected hepatocytes, as well as to the inability of the immune system to efficiently counteract chronic HBV infection. In this regard, the unique replication strategies adopted by HBV and viral protein production also appear to contribute to infection persistence by limiting the effectiveness of innate responses. The availability of improved experimental systems and molecular techniques have started to provide new information about the complex network of interactions that HBV establishes within the hepatocyte and that may contribute to disease progression and tumor development. Thus, this review will mostly focus on events involving the hepatocyte: the only target cell where HBV infection and replication take place.

A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats

“…Similarly, the character of DCH-associated HCC shared features with hepatopathies caused by HBV and/or woodchuck hepatitis virus, including regions of vacuolar change and individual hepatocellular necrosis, although individual histologic features of HCC did not distinguish DCH-positive from DCH negative cases. Greater hepatocyte proliferation observed in DCH-associated areas of HCC compared with virus negative regions is worthy of note since hepatocyte proliferation driven by the host immune response contributes to hepatocyte transformation in HBV-associated HCC [11]. The consistency of this finding should now be tested in a larger number of DCH-associated HCCs.…”

TPX2 silencing exerts anti‑tumor effects on hepatocellular carcinoma by regulating the PI3K/AKT signaling pathway

“…Liver cancer is the fourth most common malignant tumor in the world and the third leading cause of cancer-associated death (1). China has a high incidence of chronic hepatitis B, and persistent infection and replication of hepatitis B virus causes liver fibrosis and cirrhosis or possibly liver cancer as the diseases progresses (2). A recent analysis reported that 45.69% of liver cancer deaths were due to HBV infection, so the incidence and mortality of hepatocellular carcinoma (HCC) is high as a result (3).…”

HBV T1719G mutation reduced HBV replication through mutant Enh II and HBx protein in vitro

“…More than 600 000 people die from HBV infection each year . At present, although the nucleotide analogues (NAs) drugs and interferon have been widely used in the treatment of HBV infection, HBV‐related diseases have not been effectively controlled . Therefore, exploring the molecular mechanism of viral replication and pathogenesis is urgently needed, and more attention should be paid to the study of HBV virological features, such as replication, life cycle and mutation.…”