Introduction
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The word hepatitis is derived from the Greek word “Hepar” meaning liver and the suffix, “itis” meaning inflammation. Worldwide, the most common cause of liver inflammation or hepatitis is viral hepatitis.
Viral hepatitis is inflammation of the liver due to a viral infection or caused by a virus. It may be present in acute or chronic forms. When it lasts for less than six months, it is acute but when it persists for longer than six months, it is chronic. The condition can be self-limiting (heal on its own) or can progress to more severe medical condition.
Several different viruses cause viral hepatitis but the most common cause of viral hepatitis is the hepatitis A, B, C, D and E viruses. Other viruses that can cause liver inflammation include herpes simplex, cytomegalo virus, and yellow fever.
Types of hepatitis viruses
Scientist have identified five unique hepatitis viruses that cause viral hepatitis infection identified by the letters A, B, C, D, and E. While all cause liver disease, they vary in different ways.
Hepatitis A virus (HAV): This is a picornavirus that causes an acute infectious disease of the liver known as hepatitis A. It is present in the faeces of infected persons and is most often transmitted through consumption of contaminated water or food (Matheny, 2012). Many cases have little or no symptoms especially in the young with most people making a full recovery and remaining immune from further HAV infections.
Hepatitis B virus (HBV): It belongs to the hepadna family of double stranded DNA viruses. It causes an infectious illness of the liver known as hepatitis B. The virus can live for a long period of time away from the body. It is a resilient virus can exist on almost any surface for about one month. Sodium hypochloride 0.5% (1:10 household bleach) destroys the HBV antigenicity within three minutes but the virus is stable at minus 20oC for about 20 years (Brook, 2004).
Hepatitis C virus (HCV): This is a flavivirus that belongs to the genus hepacivirus. It affects primarily the liver causing an infectious disease known as hepatitis C. The infection is often asymptomatic but chronic infection can lead to scaring of the liver (Ryan, 2004).it is the major reason for liver transplantation.
Hepatitis D virus (HDV) This is a circular RNA that is more similar to a plant, a viroid, than a complete virus. It is classified as hepatitis delta virus and it causes the hepatitis D viral infection. It is considered a sub-viral satellite because it can propagate only in the presence of the hepatitis B virus. It cannot produce infective virions without the help of a co-infecting helper virus,this helper virus is hepatitis B virus that supplies the HBsAg surface protein.
Hepatitis E virus (HEV): This is an RNA virus similar to a calicivirus that causes the hepatitis E viral infection. it is mostly transmitted through consumption of contaminated water or food.
All of these viruses cause acute or short term viral hepatitis. The hepatitis B, C, and D viruses can also cause chronic hepatitis in which the infection is prolonged. Sometimes lifelong chronic hepatitis can lead to cirrhosis, liver failure, and liver cancer.
Structure and morphology
Hepatitis A virus is a picornavirus. It is non-enveloped and icosahedral in shape and contains a single stranded RNA packaged on a protein shell. There is only one serotype of virus while multiple genotypes exist. It also has a poor internal ribosome entry site. In the region that codes for the HAV capsid, there are highly conserved clusters of rare codon(a sequence of 3 adjacent nucleotides) that restrict antigenic variability. It is among the smallest and structurally simplest of the RNA viruses. It has a diameter of 27-32 nm and is composed entirely of viral protein and RNA.
Hepatitis B virus abbreviated HBV is a species of the genus orthohepadnavirus which is a part of the hepadnaviridae family of viruses. It is a 42nm partially double stranded DNA virus composed of a 27 nm nucleocapsid core (hepatitis b core antigen) made up of protein surrounded by an outer lipid envelope or lipo protein coat containing the surface antigen HBsAg. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity similar to retroviruses. The outer envelope contains embedded proteins which are involved in viral binding and entry into susceptible cells. It is divided into four major serotype and eight genotypes. (kramvis, 2005)
Hepatitis C virus is a small enveloped single stranded virus with a diameter of about 60 nm. (Carreno, 2008)
The HCV particle consist of a core of genetic material (RNA) surrounded by an icosahedral protective shell of protein and further encased in a lipid (fatty) envelope of cellular origin. Two viral envelope glycoproteins E1 and E2 are embedded in the lipid envelope. Eleven HCV genotypes with several distinct subtypes have been identified throughout the world.
Hepatitis D virus is a small spherical virus with 36 nm in diameter; it has an outer coat containing three HBV envelope proteins (called large medium and small hepatitis B surface antigens) and host lipids surrounding an inner nucleocapsid. The nucleocapsid contains single stranded, circular RNA genome and about 200 molecules of hepatitis D antigen (HDAg) for each genome.
Hepatitis E virus is a non enveloped spherical single stranded RNA virus. Several different strains have been isolated, partially characterized and molecularly cloned (a group of identical cells derived from a single cell). The virion is non-enveloped and has a diameter of 27-37 nm and is composed entirely of virion protein and RNA.
Clinical signs and symptoms
Symptoms of viral hepatitis include, jaundice which causes a yellowing of the skin and eyes, fatigue, abdominal pain, loss of appetite, nausea, vomiting and diarrhoea. Early symptoms of hepatitis A infection can be mistaken for influenza but some especially children exhibit no symptoms at all. Symptoms typically appear 2 to 6 weeks after the initial infection with an average of 28 days. The symptoms usually last less than 2 although some people can be ill for as long as 6 months (Connor, 2005). Hepatitis B begins with general ill health, loss of appetite, dark urine and nausea, the illness last for a few weeks with a chronic inflammation of the liver which lead to cirrhosis over a period of several years.
Symptoms of hepatitis C are generally mild including a decreased appetite and weight loss (Wilkins, 2010) and rarely does acute liver failure result. Most cases are not associated with jaundice. Symptoms of hepatitis B and D are similar, hepatitis D can also cause symptoms of hepatitis B to worsen or appear in those who have been infected but have not yet developed symptoms. The incubation period of hepatitis B varies from 3-8 weeks. Viral RNA becomes detectable in the blood during incubation period and failure to clear the infection at the acute stage can lead to the chronic stage causing liver fibrosis and cirrhosis.
Transmission
Hepatitis A and E is transmitted primarily through food or water contaminated by faeces from an infected person and it often occur in condition of poor sanitarian and overcrowding. It is rarely spread through contact with infected blood. Hepatitis B is transmitted through contact with infected blood and blood fluids, sexual intercourse with an infected person and from mother to child during childbirth. Hepatitis C is also spread primarily through contact with infected blood such as in blood transfusion and unsafe medical procedures. Hepatitis D is spread through contact with infected blood and only occurs when hepatitis B is present. It can also be contacted at the same time with hepatitis B virus.
Pathogenesis
Hepatitis A enters the body by ingestion and intestinal infection; the virus then spread to the liver, a target organ, large number of virus particles are detectable in faeces during the incubation period, beginning as early as 10-14 days after exposure and continuing in general, until peak elevation of serum amino transferase. Virus is also detected in faeces early in the acute phase of illness but relatively infrequently after the onset of clinical jaundice (Matheny, 2012).
Hepatitis B virus gain entry into the liver cell by binding to a receptor on the surface of the cell and enters it by endocytosis. The virus membrane then fuses with the host cell’s membrane releasing the DNA and core proteins into the cytoplasm. The DNA is then transferred to the cell nucleus by the host proteins. (Brook, 2004)
Hepatitis C virus enter the cell and is uncoated in the cytoplasm to enter the cell, it recognise and bond with CD81 surface receptors present in the surface of hepatocytes and lymphocytes. After entering the host, it invades, infects and replicates within the blood stream as it proceed to the liver. The liver is the principal site of HCV replication and it infects approximately 10% of hepatic cells. Hepatitis D gains entry into liver cells via the NTCP(sodium taurocholate co-transporting polypeptide) bile transporter. It recognises its receptor through the N-terminal domain of the large hepatitis B surface antigen HBsAg (Engelke, 2006). After entering the hepatocyte, the virus is uncoated and the nucleocapsid translocated to the nucleus due to a signal in HDAg.
Hepatitis E virus enters the host through the oral route and begins replicating in the intestinal tract, the portal veins transport the virus to the liver where it replicates in the cytoplasm of hepatocytes and induces histologic changes.
Diagnosis
Diagnosis of viral hepatitis is based on symptoms and physical findings as well as blood tests for liver enzymes, viral genetic materials (DNA & RNA) and viral antibodies. These tests include liver function tests, polymerase chain reaction (PCR), Elisa tests and rapid test strips. Others are electron microscopy, complement fixation and liver-Biopsy.
Liver Function Test: These are test for liver enzymes such as aspartate amino transferase (AST) and alanine amino transferase (ALT). These enzymes are normally contained within the liver cells. If the liver is injured, the liver cells spill the enzymes into the blood increasing the enzyme level in the blood and signalling that the liver is damaged. ALT levels are greater than AST levels in hepatitis infection. It has a normal range of 7-56 units per litre of serum while that of AST is 5-40 u/l
Polymerase Chain Reaction (PCR): These are tests carried out to detect the presence of viral DNA/RNA in the serum. Their presence indicates active viral replication and a high state of infectivity. It is a technique used to amplify a single copy of a piece of DNA across several orders of magnitude generating thousands of copies of a particular DNA sequence.
Elisa Test: The use of enzyme linked immuno absorbent assay (Elisa) provides an economical, rapid and highly sensitive method for the detection of antibodies which can be detected within weeks of infection. It is based on antigen-antibody interaction and subsequent enzymatic action on a substrate yielding a soluble coloured product.
Immunochromatographic Rapid Test Strip for Hepatitis B and C: The rapid test strip for HCV contains hepatitis C antigen used to detect for HCV present in serum while that of HBV contains antibody to Hepatitis B surface antigen (anti HBsAg) used to detect for HBSAg in sample.
Procedure
- Unseal the pouch and remove the test strip
- Immerse the strip into the plasma for 15 seconds ensuring that it does not exceed the maximum level on the test strip.
- Place the strip on a flat or non-absorbent surface and allow to react
- Read and record results.
Treatment
Hepatitis A and E usually resolves on their own over several weeks, there is no specific treatment for them, patients are advised to rest, avoid fatty foods and alcohol, eat a well balanced diet, and stay hydrated. But the use of ribavirin over a three month period has been associated with viral clearance in about two-thirds of chronic cases for hepatitis E.
Drugs approved for the treatment of chronic hepatitis B include alpha interferon and peginterferon, which slow the replication of the virus and antiviral drugs like, lamivudine, adefovir dipiroxil, entecavir and telbivudine. Other drugs are also been evaluated. In rare cases, hepatitis C infection can clear without treatment. Those with chronic HCV are advised to avoid alcohol and to be vaccinated for hepatitis A and B (Wilkins, 2010). Chronic hepatitis C is treated with peginterferon together with the antiviral drug ribavirin. If acute hepatitis C does not resolve on its own within 2-3 months, drug treatment is recommended. Overall, 50-80% of people treated are cured. Those who develop cirrhosis or liver cancer may require a liver transplant. Chronic hepatitis D is usually treated with pegylated interferon which reduce the severity of the infection and the effect of the disease during the time the drug is given, but the benefit generally stops when the drug is discontinued indicating that it does not cure the disease.
Prevention
Hepatitis A can be prevented by vaccination, good hygiene, and sanitation. The vaccine provide active immunity against a future infection, and protect against HAV for longer than 25 years .for hepatitis E, improving sanitation is the most important measure of prevention, this consists of proper treatment and disposal of human waste, improved personal hygiene and sanitary food preparation.
The hepatitis B vaccine offers the best protection from hepatitis B virus. All infant and unvaccinated children, adolescents, and at risk adult should be vaccinated. Reducing exposure to the virus can help prevent it and this include avoiding the sharing of drug needles and personal items such as razors, tooth brushes, and nail clippers with an infected person. This also goes for hepatitis C for which there is no vaccine available. The vaccine for hepatitis B protects against hepatitis D virus because of the latter’s dependence on the presence of hepatitis B virus for it to replicate. The screening of blood donors and adhering to universal precautions within health care facilities is also very important.
Conclusion
The hepatitis A,B,C,D and E are of general concern because of the burden of illness and death they cause which include in the case of hepatitis B, C and D chronic acute hepatitis and cirrhosis. Vaccines offer protection from hepatitis A and B but no vaccine is available for hepatitis C, D, and E. Hepatitis A and E usually resolve on their own while hepatitis B, C, and D can be chronic and serious. While drugs are available to treat chronic hepatitis, reducing exposure to the viruses, offers the best protection.
References
Brook, C. Hepatitis virus. In Butel, J.S.; Muse, S. [eds] (2004). Medical Microbiology, Boston: McGraw Hill Company Inc. (23rd ed.) pp 466-476
Carreno, V.; Bartolome, J.; Castillo, J. (2008). “Occult hepatitis B virus and hepatitis C virus infections” Reviews in Medical Virology 18(3): 139-157
Connor, B. A. (2005). Hepatitis “A vaccine in the last minute traveller” Am. J. Med 118 (suppl WA): 585-625.
Engelke, M.; Mills, K.; Seitz, S. (2006). “Characterization of a hepatitis B and hepatitis A virus receptor binding site” Hepatology (Baltimore md) 43(4): 750-760
Kramvis, A.; Kew, M.; Francois, G. (2005). “Hepatitis B virus genotypes” Vaccine 23(19): 2409-2423
Matheny, S.C.; Kingery, J.E. (2012). “Hepatitis A”, Am. Fam physician 86(11): 1027-1034.
Ryan, K. J.; Ray, C. G. [eds] (2004). Sherris Medical Microbiology (4th ed). Boston: McGraw Hill. pp 541-544
Wilkins, T.; Malcolm, J. K.; Raina, P. (2010). “ Hepatitis C: diagnosis and treatment. American Family Physician 81(11): 139-157.
