The Pathophysiology of Hepatitis B - Term Paper Example

? 24 November The Pathophysiology of Hepatitis B Hepatitis B, an infectious disease caused bythe Hepatitis B virus (HBV, a DNA virus), was formerly called serum hepatitis, inoculation hepatitis and post-transfusion hepatitis. Infection with HBV may result in acute, fulminant or chronic hepatitis, sometimes even resulting in a chronic asymptomatic carrier state, apart from hepatocellular carcinoma and liver cirrhosis (Davis 179). The disease is transmitted when an individual comes in contact with infected blood or objects. It may also be transferred from an infected mother to her infant either during or after birth (Harrison, Dusheiko and Zuckerman 211). Transmission may also occur by accidental inoculation from infected needles and hospital equipment, intravenous drug abuse, body piercing, tattooing, and mouth-mouth kissing (Harrison, Dusheiko and Zuckerman 210). The risk of Hepatitis B is particularly high in individuals with multiple sex partners, and in homosexuals. The HBV virus occurs in morphologically different forms in the serum of infected individuals. HBV infection has an incubation period of about 75 days. Systemic symptoms of the disease include fatigue, fever, dyspepsia, arthralgia, malaise, and rash, while local symptoms include hepatomegaly, jaundice, dark urine, and pale stools (Davis 179; Harrison, Dusheiko and Zuckerman 210). Anatomical/physiological/biochemical changes that lead to the disease Hepatitis B results from cellular injury to the liver, subsequently affecting its metabolic functions. However, the HBV is not cytopathic by itself. The pathogenesis of Hepatitis B occurs as a result of the interactions between the host’s immune system and the virus. The host immune system targets HBV in liver cells (hepatocytes), inadvertently causing damage to the liver. HBV derived proteins (nucleocapsid antigens – HBcAg and HBeAg) present on the surface of infected hepatocytes are recognized and targeted by activated CD4+ and CD8+ lymphocytes, resulting in an immunologic reaction that leads to hepatocellular damage (Pyrsopoulos & Reddy; Harrison, Dusheiko and Zuckerman 221). The immune response against hepatitis B is T-cell mediated. These immune responses against infected hepatocytes result in liver cirrhosis or hepatocellular carcinomas. Damage to hepatocytes also manifests as spotty acidophilic necrosis and lymphohistiocytic lobular inflammation in the liver (UPMC). Anatomical/physiological/biochemical changes the disease causes Hepatitis B disease pathology is mainly a result of impaired liver function due to hepatocellular damage. The anatomical and physiological changes that result from HBV infection are arthralgia, cholecystitis, cholangitis, bradycardia, irritability, lethargy, jaundice, fever, erythema, nausea, spider angiomas, splenomegaly and bile duct obstruction in some cases (Turkington and Ashby, 148; Davis 181). Patients experience extreme fatigue and malaise, and discharge dark urine and pale stools. In addition, there is significant weight loss. Chronic hepatitis may result in liver cancers (hepatocellular carcinomas). The incidence of hepatocellular carcinoma is highest in individuals with HBV infected cirrhotic liver (Harrison, Dusheiko and Zuckerman 234). These cancers develop due to integration of viral DNA in host genome, apart from a variety of other factors. Biochemical changes as a result of HBV infection include elevated aspartate aminotransferase (AST) levels due to liver damage. Jaundice, a common symptom in HBV infections, results from impaired bilirubin metabolism in the liver. Bilirubin is a yellow pigment that results from the breakdown of hemoglobin. Hemoglobin breakdown mainly occurs in the hepatocytes, where the resulting bilirubin is converted into a water-soluble compound and excreted through bile into the gut. Impairment of the hepatocytes due to HBV infection prevents the liver from carrying out this function effectively. Inability to excrete bilirubin results in its redistribution throughout the body causing a yellow discoloration of the sclera and skin. The serum levels of AST, ALT (alanine transaminase) and bilirubin fluctuate throughout the course of the disease and may intermittently revert back to normal levels (Fagan & Harrison 36). In addition, impaired bile production and amino acid metabolism in the liver result in abnormal stool and urine. Treatments available and their mechanism of action Most patients infected with HBV revive from the infection without any specific treatment (Davis 183). However, patients with chronic hepatitis are treated with antiviral agents and immunotherapy. Antiviral agents include nucleoside analogues such as Lamivudine and Adefovir Dipivoxil. Lamivudine is a cytidine analogue and inhibits the synthesis of viral DNA by interfering with the incorporation of cytidine residues. The drug is converted to mono-, di-, and tri-phosphates after ingestion and prevents viral DNA synthesis through chain termination. Adefovir Dipivoxil is an analogue of adenosine monophosphate. The drug is activated by nucleoside kinases in the cells to yield adefovir diphosphate that interferes with the function of HBV DNA polymerase. The drug competitively inhibits dATP, resulting in chain termination and inhibition of viral DNA synthesis. Both these antiviral agents stall the growth and spread of the virus. Treatment of HBV infections is also done using INF-? therapy. INF-? is a naturally occurring interferon that carries out antiviral activity by inhibiting immunomodulation and cellular proliferation by the virus (Harrison, Dusheiko and Zuckerman 228). HuIFN-a-n1 (Wellferon), rIFN-a2a, (Roferon-A) and rIFN-a2b (Intron A) are some of the INF-? interferons available for the treatment of chronic hepatitis B (Harrison, Dusheiko and Zuckerman 228). Interleukin-12 is also used as a biological response modifier for the treatment of hepatitis B. It functions by modulating the host immune responses helping in the clearance of the virus. Prognosis of the disease While some patients recuperate at a fast rate after an acute HBV infection, others show a very slow improvement with a prolonged disease course that extends over several months. Fulminate hepatitis results when patients experience rapid disease progression at the acute stage, developing widespread and severe liver damage that may be fatal. Chronic hepatitis that continues for elongated periods increases the risk of liver cirrhosis, liver failure and even death (Davis 179). Patients with liver cirrhosis are highly likely to develop hepatocellular carcinoma upon subsequent infection with HBV, at a 73-month mean follow-up (Pyrsopoulos and Reddy). Moreover, the probability of developing hepatocellular carcinoma after being diagnosed with cirrhosis is about 6%. There is also a possibility of co-infection of HBV with HDV (Hepatitis D virus). Older age, firmness of the liver and thrombocytopenia predispose hepatitis B patients to a high risk of carcinonegenesis (Pyrsopoulos and Reddy). A prognostic index constructed for calculating the probability of survival after HBV infection has six variables that include albumin level, age, splenomegaly, hepatitis B e antigen (HBeAg), bilirubin level, and platelet count (Pyrsopoulos and Reddy). The disease prognosis can be done by calculating the prognostic index based on the status of these six variables. Conclusion HBV infection is complex and affects a large population worldwide. The discovery of the Australia antigen (HBsAg) in 1965 by Blumberg et al. (1965) set the stage for rapid progress in understanding and counteracting the disease (qtd in Harrison, Dusheiko and Zuckerman 210). Liver function tests help in estimating the extent of damage caused to the liver during HBV infection. Diagnosis is done by detecting viral specific antigens in the serum. Both active and passive immunization options exist for disease prophylaxis. However, it is always best to practice caution over the parenteral, sexual and other routes of transmission of the disease for effective disease prevention and prophylaxis. Works cited Davis, G. L. A Practical Guide to Clinical Virology. Ed. Haaheim, L. R., J. R. Pattison and R. J. Whitley. West Sussex: John Wiley and Sons, 2002. Fagan, Elizabeth Ann and Tim Harrison. Viral Hepatitis. New York: BIOS Scientific Publishers Ltd., 2005. Harrison, Tim, Geo?rey M. Dusheiko and Arie J. Zuckerman. Principles and Practice of Clinical Virology. Ed. Zuckerman, Arie, Jangu E. Banatvala, John R. Pattison et al. West Sussex: John Wiley and Sons, 2004. Pyrsopoulos, Nikolaos and K Rajender Reddy. “Hepatitis B.” Emedicine.medscape.com (2011). 24 Nov. 2011 < http://emedicine.medscape.com/article/177632-overview#a0104 > Turkington, Carol and Bonnie Ashby. The encyclopedia of infectious diseases. New York: Infobase Publishing, 2007. UPMC. “Acute and Chronic Viral Hepatitis, Type B.” Tpis1.upmc.com. 24 Nov. 2011 < http://tpis1.upmc.com:81/tpis/liver/ILACHepB.html > Read More