Hepatitis type B viral infection is a common and serious disease that is caused by the hepatitis B virus (HBV). HBV is a DNA virus with partial double strands and belongs to the Hepadnaviridae family. One-third of the world’s population is believed to have been infected by HBV of which 6% have chronic HBV infection. Depending on the rate of infection and carrier rate, the world is divided into low, medium and high endemicity regions (Franco et al. 75). The HBV resides in the bodily fluids of an infected individual and is transmitted via the same (Aspinall et al. 532).
The disease has multiple stages and has highly complex dynamics, which depends on the age of the host, sex of the host, route of infection and the patient’s immune response (Kim, Revill and Ahn 1169). Treatment of HBV infection includes vaccines and antiviral drugs. However, due to the ability of the viral genome to rapidly mutate and become resistant to current pharmaceutical drugs, it has been difficult to contain and eradicate the disease (Michel et al. 1286).
Epidemiology
Literature suggests that HBV is highly prevalent in western sub-Saharan Africa with 12% prevalence in children and adolescents. The prevalence of HBV in developed countries such as Canada and the US is very low and has shown a decline in recent years. The prevalence in these countries is 2.1% among children and only 1% among adults. In recent years, developing countries such as India and southeast Asian countries are showing a steady decline in prevalence, especially among children (Ott et al. 2217).
According to the World Health Organization (WHO), 2000 million people worldwide have had HBV infection and about 350 million of them are affected by chronic HBV infection. Chronic infections tend to damage the liver considerably and account for 65 million deaths, globally (Aspinall et al. 531). HBV complications such as cirrhosis of the liver and liver cancer (hepatocellular carcinoma) caused due to chronic hepatitis B (CHB) infection are responsible for more than 1 million deaths, annually (Franco et al. 75).
Causative agent: HBV
An HBV virion is 42 nm in size, containing 3 to 3.3 kb of partial double stranded DNA that makes up a 27 nm nucleocapsid. This nucleocapside is enclosed in an envelope of lipoprotein and contains the surface antigen, HBsAg. The virion also contains a DNA-dependent polymerase that acts as a reverse transcriptase (Cento et al. 144; Liang S14). HBV has ten genotypes, from A to J, and numerous subgenotypes that have unique geographic and ethnographic distributions (Franco et al. 74; Cento et al. 144). HBV type A is predominantly found in North America, Western Europe and, Southern and Eastern Africa. HBV type B and type C are prevalent in Asia. HBV type D is found all over the world. HBV type E is found in Western Africa. HBV type F and H are found in Latin America. HBV type G is prevalent in Europe and North America. HBV type I and J are found in Vietnam and Japan, respectively; however, these two subtypes have not yet been understood properly and require more study (Kim et al. 1173).
Transmission and pathogenesis
Transmission of HBV occurs via puncture to the skin (parenteral route), from mother to her child and through sexual contact. Most of the infected individuals are asymptomatic in the earlier stages. About 30% of the patients would develop hepatitis and jaundice while about 0.5% would experience fulminant liver failure (Aspinall et al. 532). The pathogenesis passes through 5 phases. The first phase is the immune tolerant phase where the body exhibits immunity against the infection even when there is active viral replication within the host body. This latent phase corresponds to the asymptomatic phase, where the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are normal and liver histology shows no or very minimal signs of fibrosis and inflammation. If the serum were to be tested at this point, the tests would reveal detectable levels of HBe antigen and HBs antigen. The immunity lasts only against the HBc antigen and not the other two antigens (Kim et al. 1178; Aspinall et al. 533). The second phase is the immune reactive (clearance) phase or HBeAg-positive CHB phase, where the immune system tries to combat and clear out the HBsAg, HBcAg and the HBeAg. The liver histology shows chronic inflammation with elevated ALT. Once the HBeAg is reduced in number, the patient is said to be in the low replicative phase or inactive phase, which is the third phase. Individuals who have had a prior HBV infection would skip the first phase and move to the second phase very quickly (Kim et al. 1178; Aspinall et al. 533). During the third phase, the HBV DNA is so low that it is virtually undetectable and HBeAg is negative. Depending on the damage during the second phase, the liver may or may not exhibit inflammation. From this third phase, about 4-20% will revert to the second phase many years after the infection while about 10-30% will go into the fourth phase, namely, the reactivation phase (Kim et al. 1178; Aspinall et al. 533). During the reactivation phase, the viral replication restarts and the individual shows signs of liver damage and elevated ALT levels. The fifth phase is the immune control phase, where the person’s immune system continually clears the HBsAg and tries to keep the body in an inactive phase (Kim et al. 1178; Aspinall et al. 533).
Alteration of host immunity during HBV infection
During the initial phase of HBV infection, the natural killer (NK) cells secrete interferon (IFN)-γ and there is a surge in the interleukin (IL)-10 levels. After this initial phase, adaptive immunity is triggered about 6 weeks later when the CD4 T-cell and CD8 T cells proliferate and help in combating the viral load. The newly formed HBV-specific T-cell destroy virus infected hepatocytes by the secretion of IFN-γ and tumor necrosis factor (TNF)-α. The infection is controlled and clearance of HBV antigens is achieved by humoral responses (Michel et al. 1287).
Clinical presentation and diagnosis
Symptoms of acute HBV infection can range from nausea and fatigue to jaundice. The incubation period is usually 2 to 3 months but can range anywhere between 1 to 6 months, depending on the viral load. This is followed by a preicteric phase, which is characterized by symptoms such as body aches, loss of appetite, fever and fatigue. The ALT level is elevated during this period. This phase usually lasts for about a week. The icteric phase, which follows the preicteric phase is characterized by jaundice and lasts about a couple of weeks. The convalescence phase follows the icteric phase, which is characterized by clearing up of jaundice and HBV antigens (Liang S18). According to the Centers for disease control and prevention (CDC), HBV is diagnosed by testing for HBsAg for those individuals who present elevated ALT or AST levels. If the individual tests positive for HBsAg, then test for HBeAg and HBV DNA load are tested to categorize the patient as low, medium or high-risk patient. If the individual is an organ or tissue donor, then a test for HBV DNA is performed. In case the patient is an organ recipient and is receiving immunosuppressive therapy, a test for Anti-HBc IgG is performed (Liang S16; Aspinall et al. 535).
Treatment of HBV infection
It is not possible to rid the host body of all HBV DNA since the patient’s liver cells (hepatocytes) will contain the viral DNA within its nucleus. Treatment is administered when the patient is in the second or fourth phase of the infection while no treatment is advised when the patient is in the first phase of the infection. Current treatment regimen for HBV are lamivudine, tenofovir, entecavir, telbivudine, adefovir, conventional interferon (IFN) and pegylated IFNα therapies. IFN therapy boosts the host’s immune response while the pharmaceutical drugs stop the viral replication (Aspinall et al. 537). IFN therapy provides the advantage of the non - emergence of resistance from the virus. For children, treatment is advised as soon as HBV infection is confirmed. Approved for use in children are the drugs lamivudine and adefovir along with IFN therapy. For pregnant women, IFN therapy is contraindicated (Aspinall et al. 537; Franco et al. 76).
Prevention of HBV infection
Since HBV infection has life-long implications and that chronic carriers become reservoirs for HBV infection, it is best to prevent contraction of the infection. One of the first steps would be to prevent new infections in newborns. Screening all pregnant women must be made compulsory to prevent spread of infection to the fetus. The best way to prevent infection after birth is through neonatal immunization. Three dosages of anti-HBs vaccines would provide 100% immunity to children and 95% of the adults. In case of suspected rapid infection, an accelerated dosage scheme could help break the infection (Franco et al. 76). Since the commencement of immunization for HBV more than 20 years ago, the prevalence of HBV infection in children and young adults has reduced remarkably. In the US, the incidence of HBV infection reduced more than 80% per year in adults and more than 98% per year in children (Aspinall et al. 538). Future approaches to therapy include nasal immunization, DNA vaccines, new preventive HBV vaccines and HBV gene therapy (Michel et al. 1289).
Conclusion
Even though mass immunization has helped in decreasing the incidence rate, the reservoir of the virus among chronically infected individuals will be threat to completely eradicate the disease. To reduce the global burden of the disease, it is, therefore, essential to implement proper prevention policies, especially in high endemicity regions. Unfortunately, many of the developing countries that cannot afford preventive screening technologies fall under the high endemicity region, making it even harder to overcome this challenge. This, along with the fact that the natural course of HBV is strongly associated with socioeconomic status makes the implementation of health and prevention policy a lingering question mark.
Works Cited
Aspinall, E. J., et al. "Hepatitis B prevention, diagnosis, treatment and care: a review." Occupational medicine 61.8 (2011): 531-540.
Cento, Valeria, et al. "Overlapping structure of hepatitis B virus (HBV) genome and immune selection pressure are critical forces modulating HBV evolution." Journal of General Virology 94.1 (2013): 143-149.
Franco, Elisabetta, et al. "Hepatitis B: Epidemiology and prevention in developing countries." World J Hepatol 4.3 (2012): 74-80.
Kim, B. K., P. A. Revill, and S. H. Ahn. "HBV genotypes: relevance to natural history, pathogenesis and treatment of chronic hepatitis B." Antiviral therapy 16.8 (2011): 1169-1186.
Liang, T. Jake. "Hepatitis B: the virus and disease." Hepatology 49 (2009): S13-S21.
Michel, Marie-Louise, Qiang Deng, and Maryline Mancini-Bourgine. "Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: perspectives and challenges." Journal of hepatology 54.6 (2011): 1286-1296.
Ott, J. J., et al. "Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity." Vaccine 30.12 (2012): 2212-2219.
