"The deadly disease called hepatitis B" by Ashoke K. Roy

Hepatitis B is a liver disease caused by HBV infection. HBV can cause short-term (acute) illness that may lead to flu-like symptoms (loss of appetite, diarrhoea and vomiting, fever) and jaundice (yellow skin or eyes), and long-term (chronic) illness that may lead to liver damage (cirrhosis), liver cancer and death. Individuals with chronic infection may become carriers capable of spreading the disease to others.

World-wide, the disease is a major health problem: more than 2 billion people have been infected with HBV, about 400 million are estimated to be HBV carriers, and HBV-associated liver cancer and cirrhosis account for over 1 million deaths each year. About 75 per cent of the long-term carriers live in Asia Pacific.

Global Situation: It is estimated that at least 1 million people worldwide die prematurely each year as a result of Hepatitis B infection and there are more than 350 million long-term carrier of the disease.

* High endemicity - Hepatitis B is highly endemic in developing regions with high population densities such as South East Asia, parts of China, sub-Saharan Africa and the Amazon Basin. In these areas, 70–95 per cent of the population show serological evidence of previous or current HBV infection. Most infections occur during infancy or childhood. Carrier rates are therefore also high, at 8–20 per cent of the population.

* Intermediate endemicity - In parts of Eastern and Southern Europe, the Middle East, Japan, North Africa, Central and Latin America. 20–55 per cent of the population have HBV markers of infection and 2–7 per cent are carriers. There is a high proportion of infection in children, but infection in adults is also quite common.

* Low endemicity - The endemicity of HBV is low in North America, Northern and Western Europe and Australia. In these regions, HBV infects 4–6 per cent of the population. The disease most commonly affects adolescents and young adults. 0.5–2 per cent of the population are chronic carriers.The patterns of HBV prevalence and the incidence of hepatitis B are constantly shifting. For example, in the 1980s in the US, the number of hepatitis B infections in homosexuals showed a significant decrease, yet the number of infections in heterosexuals increased significantly.Changes in living standards, behavior and vaccination policies can all influence disease patterns.

Population groups at high-risk: In low endemicity countries, the prevalence of hepatitis B in some population groups may be markedly higher than average. For example, in the US 70–85 per cent of immigrants from high endemicity areas have HBV markers indicating past infection, and about 13 per cent are carriers.

Other groups with a high prevalence of hepatitis B include the institutionalized mentally retarded and the staff caring for them, homosexual males, intravenous drug abusers, household contacts of carriers, patients who require regular blood transfusions or hemodialysis, prisoners and prison staff, health care workers, people with sexually transmitted diseases, prostitutes and the sexually promiscuous. All of these are at increased risk as their activities may bring them into contact with infected body fluids.

Morbidity and mortality: HBV is one of the most significant viruses in terms of world-wide morbidity and mortality. In fact, the data shown here may be grossly underestimating the problem.

The virus has infected over 2000 million people and there are over 350 million chronic carriers. The pool of carriers is increasing by 2–3 per cent a year. These carriers make up an enormous reservoir from which hepatitis B can spread to susceptible individuals.

HBV is responsible for 1 million deaths a year, the majority of fatalities being due to cirrhosis and primary hepatocellular carcinoma (PHC), a form of liver cancer. Epidemiological data indicate that there is a consistent and specific causal association between infection with HBV and hepatocellular carcinoma.

Hepatocellular carcinoma is the most common form of primary liver cancer, and one of the ten most common cancers in the world. Up to 80 per cent of the world’s primary liver cancer cases are attributed to HBV. HBV is second in importance only to tobacco among the known human carcinogens. After introduction of vaccine in America in 1981 the incidence of Hepatitis B started to fall down from 1985.

In Bangladesh: Not very well studied. Several studies found huge number of patients and carriers. It is estimated that 7-9 per cent of our population may be suffering from the disease or carrying the virus. This is a great cause of concern.

HBV and the chronic carrier state: Every year millions of people are newly infected by the hepatitis B virus. About two-thirds of infected adults will show clinical symptoms which can vary in seriousness from mild to severe. In a small but significant number of cases, the infection is fatal.

Some people who are infected are unable to mount an effective immune response to eliminate the virus. They become long-term HBV carriers.

The risk of becoming a chronic carrier depends on age. Up to 80–90 per cent of newborns and infants infected with HBV may become long-term chronic hepatitis B patients. 5–10 per cent of infections in adults will also lead to a chronic carrier state. The milder the primary infection, the greater the risk of becoming a chronic carrier. Most chronic HBV carriers do not suffer from any clinical symptoms and seem perfectly healthy. However, their livers are being progressively damaged and, eventually, severe chronic liver disease may result.

Chronic carriers are also able to infect others and therefore represent a constant public health risk. It is estimated that there are over 350 million carriers of HBV world-wide - that is about 5 per cent of the world’s population!

How it spreads: HBV is spread through contact with the blood or other body fluids of an infected person, for example, by sexual contact, from mother to child during birth, by intravenous drug use with infected needles or by needle-stick injuries in certain occupations, even sharing toothbrushes or razors. In travelers from developed countries it is the second most frequent vaccine preventable disease.

Prevention of hepatitis B : Vaccination is the most effective way of preventing hepatitis B disease. Vaccination against hepatitis B is recommended for inclusion in childhood immunization programs worldwide and for groups at risk of HBV infection (e.g. healthcare workers and travelers to countries with a high prevalence of hepatitis B). More than 100 countries world wide have implemented this program already. Hepatitis B vaccines are the first which have been shown to prevent cancer (liver cancer).

Vaccination: Vaccination is the most effective and convenient way of preventing hepatitis B disease and the chronic carrier state or liver cancer that can result from it.

From that point of view Hepatitis B vaccine is the first anti-cancer vaccine.

Protection from acute and chronic infection, as well as clinical illness, is virtually complete among persons who develop a protective antibody response (anti-HBs>=10 mIU/ml) following vaccination. It is generally accepted that the threshold anti-HBs titer for protection is 10 mIU/ml. However, some health authorities (e.g. in the UK) have set the limit more conservatively at 100 mIU/ml.

The magnitude of the antibody response induced by the primary vaccination series is predictive of the persistence of detectable antibodies. Current follow-up studies indicate that protection from clinically significant HBV infection and chronic carriage remains intact for at least 15 years in immunocompetent individuals, and that immune memory continues to provide protection even when anti-HBs levels have become undetectable.

Widespread use of hepatitis B vaccine has been shown to dramatically reduce hepatitis B virus infection and the development of liver cancer from chronic hepatitis B infection. Consequently, the Centres for Disease Control and Prevention (CDC) and the World Health Organization (WHO) regard hepatitis B vaccine as the first anti-cancer vaccine since it prevents this serious consequence of hepatitis B infection. The WHO states that hepatitis B vaccine is the first and currently the only vaccine against a major human cancer.

The two main types of hepatitis B vaccine currently available are-

* plasma-derived vaccines

* genetically-engineered vaccines

Plasma-derived vaccines: Preparation of a plasma-derived vaccine.

During an HBV infection, large quantities of the surface antigen HBsAg are synthesized in the liver and released into the blood stream. This phenomenon is exploited in the production of plasma derived vaccines, when HBsAg particles are isolated from the blood of chronic carriers, purified and incorporated into a vaccine.

Plasma derived vaccines were the first vaccines to be used against hepatitis B. They have since been widely used and have been found to be safe and effective. However, with a production cycle of 1 year, supplies of these plasma-derived vaccines were limited, and there were widespread, but unjustified, fears that the vaccines could be contaminated with other blood-borne diseases such as HIV. Also the complex production procedures and lengthy testing mean that plasma-derived vaccines were expensive. 

Genetically engineered vaccines: Preparation of a genetically-engineered vaccine.

The discovery of the gene expressing HBsAg in the 1970s together with developments in molecular biology have made it possible to produce genetically-engineered vaccines against hepatitis B. Today large quantities of HBsAg can be generated by inserting the gene expressing HBsAg into a suitable vehicle such as yeast. As the vehicle multiplies, the implanted DNA induces the production of HBsAg. The surface antigen is then extracted and purified and incorporated into a vaccine.

These genetically-engineered vaccines provide effective protection against hepatitis B. They also have a number of advantages compared to plasma-derived vaccines:

* They can be produced more quickly.

* They can be manufactured in larger quantities. 

* They are produced from cells which contain only part of the genetic code of the hepatitis B virus, so they are free from infectious virus particles. 

* Their production does not rely on the availability of carrier plasma, with its associated risk of contaminants.

Treatment: Till last year the treatment option for Hepatitis B was very limited. Only Interferon was the drug that was very expensive, toxic and the treatment success was less than 20 per cent. Now an oral medicine is available that developed in the laboratory of GlaxoSmithKline. It available at an affordable price and well tolerated. Still prevention is better and preferable. Emphasis should be given on Vaccination. Prevention is better than cure. Vaccination is preferred and easy means of preventing the deadly disease.