Consequences Of Hepatitis B Virus Infection Research Articles

Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes.

Phosphorylation is a major post-translation modification (PTM) of proteins which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either promote or counteract viral replication. Among more than 500 kinases constituting the human kinome only few have been described as important for the hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core (HBc) protein. In addition, little is known on the consequences of HBV infection on the activity of cellular kinases. The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape early after infection. For this, primary human hepatocytes (PHHs) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phosphoproteomic analysis was conducted 2- and 7-days post-infection. The results indicated that while, as expected, HBV infection only minimally modified the cell proteome, significant changes were observed in the phosphorylation state of several host proteins at both time points. Gene enrichment and ontology analyses of up- and down-phosphorylated proteins revealed common and distinct signatures induced by infection. In particular, HBV infection resulted in up-phosphorylation of proteins involved in DNA damage signaling and repair, RNA metabolism, in particular splicing, and cytoplasmic cell-signaling. Down-phosphorylated proteins were mostly involved in cell signaling and communication. Validation studies carried out on selected up-phosphorylated proteins, revealed that HBV infection induced a DNA damage response characterized by the appearance of 53BP1 foci, the inactivation of which by siRNA increased cccDNA levels. In addition, among up-phosphorylated RNA binding proteins (RBPs), SRRM2, a major scaffold of nuclear speckles behaved as an antiviral factor. In accordance with these findings, kinase prediction analysis indicated that HBV infection upregulates the activity of major kinases involved in DNA repair. These results strongly suggest that HBV infection triggers an intrinsic anti-viral response involving DNA repair factors and RBPs that contribute to reduce HBV replication in cell culture models.

Debunking the myth: low knowledge levels of HBV infection among Asian American college students

Objective:To examine the hepatitis B virus (HBV)-related knowledge among Asian American college students and to determine whether there are significant differences in the level of HBV knowledge among Asian American subgroups.Methods:A cross-sectional survey was self-administered to assess a sample of 258 Asian American students’ knowledge about HBV at the campus of the research site.Results:Knowledge regarding transmission and consequences of HBV infection was poor. Of a possible knowledge score of 14, the median number of correct answers was eight. There were no significant differences between the subgroups of Asian American college students in total knowledge of HBV infection.Conclusion:The findings of this study point to the fact that the lack of knowledge and awareness is not limited to community settings only but also includes higher education environment. This finding brings to the forefront the importance of HBV education for Asian American college students.

Hepatitis B virus and renal transplantation

Hepatitis B virus (HBV) infection remains an important cause of liver disease in the renal transplant (RT) population, potentially diminishing survival. Consequences of HBV infection after RT include progression to decompensated cirrhosis and an increased risk of hepatocellular carcinoma. Although precautions initially recommended by the Centers for Diseases Control and Prevention 30 years ago have substantially reduced HBV transmission within hemodialysis units, acute HBV outbreaks continue to be reported in patients with chronic kidney disease on maintenance hemodialysis. In addition, immigration from areas of high HBV prevalence implies that HBV-infected organs with chronic kidney disease will continue to enter the RT pool. Fortunately, the advent of oral therapy for HBV infection now reduces the risk of HBV progression post-RT.

Endemic hepatitis B virus infection and chronic liver disease mortality in the Republic of Palau, 1990–2002

In the Republic of Palau, a Pacific island nation, approximately 20% of the population is chronically infected with hepatitis B virus (HBV) and is at risk of developing chronic liver disease (CLD), including cirrhosis and hepatocellular carcinoma (HCC). To examine the consequences of HBV infection, we sought to quantify HBV-related CLD mortality in this population. The cause of death was abstracted from death certificates of all persons who died in Palau during 1990-2002. CLD deaths were categorised as cirrhosis or HCC. HBV serological status was determined by review of a hospital database. The cause of death was determined for 1,366 (85%) of 1,608 deaths. CLD was the fifth most common cause of death, accounting for 102 (7%) deaths with a known cause. Of deaths due to CLD, 55 (54%) were from cirrhosis and 47 (46%) were from HCC. Sixty-five percent of CLD decedents and 19% of non-CLD decedents were chronically infected with HBV (P<0.01). The attributable fraction of HBV-related CLD was 54% (58% for cirrhosis and 53% for HCC). CLD mortality rates were approximately twice the worldwide CLD rate. HBV-related CLD is a common cause of death in the Republic of Palau, highlighting the importance of routine infant hepatitis B vaccination, especially in countries with high endemicity.

Association between the accumulation of hepatitis B virus core gene deletion mutants and progression of liver disease in long-term renal transplant patients

Hepatitis B virus (HBV) infection remains an important cause of liver disease in the renal transplant (RT) population, potentially diminishing survival. Consequences of HBV infection after RT include progression to decompensated cirrhosis and an increased risk of hepatocellular carcinoma. Although precautions initially recommended by the Centers for Diseases Control and Prevention 30 years ago have substantially reduced HBV transmission within hemodialysis units, acute HBV outbreaks continue to be reported in patients with chronic kidney disease on maintenance hemodialysis. In addition, immigration from areas of high HBV prevalence implies that HBV-infected organs with chronic kidney disease will continue to enter the RT pool. Fortunately, the advent of oral therapy for HBV infection now reduces the risk of HBV progression post-RT.

Strategy for vaccination against hepatitis B in areas with high endemicity: focus on Korea.

Hepatitis B vaccination strategies may vary from country to country depending on hepatitis B virus (HBV) endemicity, predominant modes of infection, age of infection, and health care resources. In areas with high endemicity like Korea, transmission of virus from carrier mothers to infants during the perinatal period, and from other horizontal sources to infants and children, account for most cases of HBV infection. The consequences of HBV infection at an early age are serious, as more than 70% remain chronic carriers of the virus. These chronic carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing other serious diseases, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Theoretically, therefore, routine infant immunisation supplemented with prenatal screening of pregnant women for HBsAg or HBeAg and mass immunisation of children is the appropriate strategy for control of hepatitis B in these countries. To prevent primary liver cancer associated with HBV infection, however, immunisation of adults at high risk would also be prudent. Mandatory vaccination of all neonates is recommended in highly endemic areas, together with hepatitis B immune globulin in babies born to HBsAg carrier mothers.