Hepatitis Viruses

The liver is the largest organ inside the body. It helps the body digest food, store energy, and remove poisons. Hepatitis is an inflammation of the liver. Viruses cause most cases of hepatitis. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. In 2013, about 1.5 million people died from viral hepatitis, most commonly due to hepatitis B and C. East Asia, in particular Mongolia, is the region most affected.

The most common causes of viral hepatitis are the five unrelated hepatotropic viruses hepatitis A, B, C, D, and E. Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein-Barr virus, and yellow fever. There also have been scores of recorded cases of viral hepatitis caused by herpes simplex virus.

Hepatitis A virus (HAV)

The HAV is a symmetrical RNA virus comprising of a 7500-bp long genome which encodes 3 polyproteins (P1, P2, P3) in a single open reading frame (ORF). Viral proteases cleave those 3 polyproteins into 4 capsid protein (P1region) and 7 non-structural protein (P2 and P3).

The virus spreads by the fecal–oral route, and infections often occur in conditions of poor sanitation and overcrowding. Hepatitis A is an infectious disease of the liver caused by Hepatovirus A (HAV). Many cases have few or no symptoms, especially in the young. It can be transmitted by the parenteral route, but very rarely by blood and blood products. About 40% of all acute viral hepatitis is caused by HAV.

Hepatitis A can be prevented by vaccination, good hygiene, and sanitation. No specific treatment for hepatitis A is known. Recovery from symptoms following infection may take several weeks or months. The risk of death from acute liver failure following HAV infection increases with age and when the person has underlying chronic liver disease.

Hepatitis B virus (HBV)

The HBV has 3200 bp long dsDNA with four ORFs: S (Virus envelop surface protein, divided into pre S1, pre S2 and S regions), C (Core region; gives rise to viral capsid), P (large polymerase protein; gets divided into three domains) and X (a large protein involved in different functions).

Identified methods of HBV transmission include contact with blood, blood transfusion (now rare), unsanitary tattoos, sex (through sexual intercourse or contact with bodily fluids), or mother-to-child by breast feeding; there is minimal evidence of transplacental crossing. The detection of hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host. The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection.

Hepatitis B virus is the cause of hepatitis B, a hepadnavirus that can cause both acute and chronic hepatitis. Chronic hepatitis develops in the 15% of adults who are unable to eliminate the virus after an initial infection. Acute hepatitis B infection does not usually require treatment and most adults clear the infection spontaneously. Early antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy.

Hepatitis C virus (HCV)

The HCV has 9600 bp long positive sense ssRNA with a single ORFand encodes structural proteins (core, E1, E2) and non-structural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B).

Hepatitis C virus is predominantly a blood-borne virus, with very low risk of sexual or vertical transmission. Because of this mode of spread the key groups at risk are intravenous drug users (IDUs), recipients of blood products and sometimes patients on haemodialysis.

The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma, abbreviated HCC) and lymphomas in humans. Those with chronic hepatitis C are advised to avoid alcohol and medications toxic to the liver. Use of acetaminophen is generally considered safe at reduced doses. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended in those with advanced liver disease due to an increased risk of bleeding. The purpose of HCV treatment is to eleminate the infection, reduce the transmission to other people and decrease the risk of HCC development.

Hepatitis D virus (HDV)

The HDV is a small, spherical virus with a 36 nm diameter. It has an outer coat containing three kinds of HBV envelope protein – large, medium, and small hepatitis B surface antigens – and host lipids surrounding an inner nucleocapsid. The nucleocapsid contains single-stranded, circular RNA of 1679 nucleotides and about 200 molecules of hepatitis D antigen (HDAg) for each genome.

The routes of transmission of hepatitis D are similar to those for hepatitis B. Infection is largely restricted to persons at high risk of hepatitis B infection, particularly injecting drug users and persons receiving clotting factor concentrates.

Hepatitis delta virus (HDV) is the cause of hepatitis D. Current established treatments for chronic hepatitis D include conventional or pegylated interferon alpha therapy. Latest evidence suggests that pegylated interferon alpha is effective in reducing the viral load and the effect of the disease during the time the drug is given, but the benefit generally stops if the drug is discontinued. The efficiency of this treatment does not usually exceed ~20%, and late relapse after therapy has been reported.

Hepatitis E virus (HEV)

The HEV has approximately 7200bp positive sense ssRNA and three open reading frame (ORF): ORF1 (nonstructura l proteins), ORF2 (capsid protein) and ORF3 (multifunctional proteins).

HEV is the second most common hepatitis virus transmitted by the fecal–oral route. It is a common cause of waterborne epidemics and endemic to developing countries.

Therapies

All the Hepatitis viruses cause acute hepatitis but type B and C turn the disease to chronic hepatitis. Chronic viral hepatitis operates in a very mild and nonspecific way, thus the diagnosis often gets delayed. This chronic viral hepatitis turns to fatal diseases like liver damage and failure, cirrhosis of liver, liver cancer and thus treatment at proper time is important for chronic viral hepatitis. Infection by hepatitis virus can be avoided by applying vaccines. Vaccines are available for hepatitis types A, B and E but those are not capable of doing cross-protection. So, immunization with one specific hepatitis vaccine can’t assure the full protection from viral hepatitis.