Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected worldwide, and 350 million suffering from chronic HBV infection. The 10th leading cause of death worldwide, HBV infections result in 500 000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year. In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood. Here are the prevalence of hepatitis B virus infection accoding to WHO:
- i) Hepatitis B is endemic in China and other parts of Asia. Most people in the region become infected with HBV during childhood. In these regions, 8% to 10% of the adult populations are chronically infected. Liver cancer caused by HBV is among the first three causes of death from cancer in men, and a major cause of cancer in women.
- ii) High rates of chronic infections are also found in the Amazon and the southern parts of eastern and central Europe.
- iii) In the Middle East and Indian sub-continent, an estimated 2% to 5% of the general population is chronically infected.
- iv) Less than 1% of the population in western Europe and North American is chronically infected.
The virus does not directly kill hepatocytes. The host's immune response to viral antigens is thought to be the cause of the liver injury in HBV infection. The cellular immune response, rather than the humoral immune response, seems to be primarily involved in disease pathogenesis. Induction of antigen-specific T-lymphocyte response is thought to occur when host T lymphocytes are presented with viral epitopes by antigen-presenting cells in lymphoid organs. These antigen-specific T cells mature and expand and then migrate to the liver. In acute HBV infection, CD4+ T (helper T) lymphocytes are stimulated by the MHC-2, which then stimulates the CD8+ (cytotoxic T) lymphocytes, together with the interferon-gamma and tumour necrosis factor-alfa to clear the viral DNA from hepatocytes.These cause down-regulation of viral replication, and trigger direct lysis of infected hepatocytes. In contrast, the clearance mechanism in people with chronic HBV infection are mainly by the non-antigen specific(or natural immune response) ways rather than specific one.
Four different stages have been identified in the viral life cycle of hepatitis B.
- The first stage is immune tolerance. The duration of this stage for healthy adults is approximately 2-4 weeks and represents the incubation period. For newborns, the duration of this period is often decades. Active viral replication is known to continue despite little or no elevation in the aminotransferase levels and no symptoms of illness.
- In the second stage, an inflammatory reaction with a cytopathic effect occurs. HBeAg can be identified in the sera, and a decline of the levels of hepatitis B virus (HBV) DNA is seen. The duration of this stage for patients with acute infection is approximately 3-4 weeks (symptomatic period). For patients with chronic infection, 10 years or more may elapse before cirrhosis develops.
- In the third stage, the host can target the infected hepatocytes and the hepatitis B virus (HBV). Viral replication no longer occurs, and HBeAb can be detected. The HBV DNA levels are lower or undetectable, and aminotransferase levels are within the reference range. In this stage, an integration of the viral genome into the host's hepatocyte genome takes place. HBsAg still is present.
- In the fourth stage, the virus cannot be detected and antibodies to various viral antigens have been produced. Different factors have been postulated to influence the evolution of these stages, including age, sex, immunosuppression, and coinfection with other viruses.
- • Immunocompetent adult (70%) are asymptomatic and self-limiting, with clearance of virus from the blood and liver, and lasting immunity to re-infection.
- • Immunoincompetent (due to immature liver) 95% of those infected become asymptomatic chronic HBV carriers
- • Patients who develop chronic HBV have a 10% to 30% risk of developing cirrhosis, particularly older patients with high levels of HBV DNA, or patients with hepatitis C, hepatitis D, or HIV co-infection.
In summary, during HBV infection, the host immune response causes both hepatocellular damage and viral clearance. Although the innate immune response does not play a significant role in these processes, the adaptive immune response, particularly virus-specific cytotoxic T lymphocytes, contributes to most of the liver injury associated with HBV infection. Most of the infected person will be asymptomatic or resolved by themselves, yet, some may progress into chronic carrier or superinfection with other disease.
- - Flu-like symptoms
- - Fever
- - Headache
- - Nausea
- - Muscle aches
- - Weakness
- - Jaundice
- - Abdominal pain
- - Dark-coloured urine
May progress to chronic hepatitis, liver cirrhosis, liver cancer and liver failure
There is no specific treatment for acute hepatitis B. Care is aimed at maintaining comfort and adequate nutritional balance, including replacement of fluids that are lost from vomiting and diarrhoea. 4 medications that are currently approved by the Food and Drug Administration (FDA) for treatment of chronic hepatitis B infection.
1. Alfa Interferon
• Interferon is an antiviral agent with antiproliferative and immunomodulatory agent.
• It is given through subcutaneous injection daily or three times per week, for 12-16 weeks or longer.
• Good prognostic factors for response to IFN-a treatment are high levels of aminotransferases, a low viral load, and infection with the wild type.
• Side Effects:
- i. Depression. This is more commonly seen in patients with a prior history of depression.
- ii. Muscle aches, fatigue, and low grade fevers.
- iii. Occasionally, patients may develop low white blood cell count, headaches, irritability, and thyroid dysfunction.
- iv. Underlying autoimmune disorders can be unmasked.
2. Lamivudine
• Inhibits hepatitis B viral DNA synthesis. It acts as a Thymidine analogue that blocks viral replication by competitive inhibition of viral reverse transcriptase.
• It should be taken orally, once daily.
• Lamivudine appears to be effective for patients who do not have a treatment response to Alpha Interferon.
• It is approved for use in adults and children and is usually tolerated well.
• It may cause a rise in the liver enzyme Alanine Aminotransferase, ALT.
• It should be taken orally, once daily.
• Lamivudine appears to be effective for patients who do not have a treatment response to Alpha Interferon.
• It is approved for use in adults and children and is usually tolerated well.
• It may cause a rise in the liver enzyme Alanine Aminotransferase, ALT.
3. Adefovir dipivoxil
• Inhibits DNA polymerase activity and reverse transcriptase by competing with the natural substrate deoxyadenosine triphosphate (dATP) and by causing DNA chain termination after its incorporation into viral DNA.
• The efficacy of adefovir dipivoxil has been tested in HBeAg-positive, HBeAg-negative, and lamivudine-resistant patients with encouraging results.
• It is taken orally on a daily basis and is typically well tolerated. The optimal duration of therapy is not yet clear.
• It can be associated with kidney dysfunction, particularly if used in high doses.
4. Entecavir
• It is the latest drug approved by the FDA for treatment of chronic hepatitis B.
• It is a Guanosine nucleoside analogue with activity against HBV polymerase. It competes with natural substrate deoxyguanosine triphosphate (dGTP) to inhibit HBV polymerase activity (ie, reverse transcriptase).
• It is less effective for lamivudine-refractory HBV infection
• This drug is taken orally, once daily and the optimal duration of therapy is not yet established.
• Side effects include headache, fatigue, dizziness, nausea, and transient elevation in liver enzymes.
Acute
90%-recover within 6 months and develop immunity to the virus
Chronic
1%-fulminant hepatitis
9%-HBsAg persists >6months
- Recover completely
- Asymptomatic carrier state
- Chronic persistent hepatitis->extrahepatic disease eg polyarteritis nodosa
- Chronic active hepatitis- eg cirrhosis,hepatocarcinoma
-co-infected with hepatitis D
In addition to the hepatitis B vaccine, other ways to protect yourself from HBV infection include:
- If you are sexually active, practice safe sex. Correct use of latex condoms can help prevent transmission of HBV, but even when used correctly, condoms are not 100% effective at preventing transmission. Men who have sex with men should be vaccinated against both hepatitis A and hepatitis B.
- If you inject drugs, don't share needles or other equipment.
- Don't share anything (including grooming products) that might have blood on it, such as a razor, toothbrush, fingernail clippers, etc.
- Think about the health risks if you are planning to get a tattoo or body piercing. You can become infected if the artist or person piercing you does not sterilize needles and equipment, use disposable gloves, or wash hands properly.
- Health care workers should follow standard precautions and handle needles and sharps safely.
- If you are pregnant or think you might be pregnant, tell your health care practitioner if you have any of the risk factors for HBV infection.
