A tiny virus, that loves to live inside the liver, occasionally causes disease and is almost impossible to get rid of. That sums up the story of hepatitis B. Of the 2 billion people who have evidence of infection worldwide, 250 million are now chronic carriers; hepatitis B virus (HBV) remains a formidable opponent despite major strides made in the fields of prevention and treatment. A relatively difficult medical topic, this article is written to help understand the natural history of Hepatitis B infection, methods of prevention and the principles of treatment.
Being a lot easier to spread than the HIV or Hepatitis C virus, HBV is a major cause of liver disease. It is confirmed by the detection of HBsAg (Hepatitis B surface antigen) in the blood. Although a large number of infected people lead healthy lives, there are several others who are not so lucky - HBV causes liver cirrhosis and liver cancer in a substantial number of patients.
The hepatitis B virus can enter the body through a blood transfusion, needle-stick injury, an open wound or unprotected sexual contact. This is called horizontal transmission, which occurs between adults. The virus can stay alive for seven days outside the body, which means that a sharp object contaminated with a patient’s blood can infect another person through an injury occurring anytime within a week. Hollow needles carry greater risk of infection due to the amount of blood and viral particles trapped inside the cavity of the needle, as opposed to a solid needle commonly used for sewing or suturing.
Many people inherit the infection from their mothers – the virus passes from mother to baby as blood flows through the placenta. This is called vertical transmission, and accounts for the majority of hepatitis B carriers in the world. In a few cases, however, the mode of contracting the infection remains unknown.
Once this virus enters the blood stream, it finds its way to its favorite spot in the body: the liver cell. HBV has the unique capability to break itself into parts and become a part of our cell, literally blending in. Its cccDNA stays hidden inside the nucleus of the liver cell even after the rest of the body has recovered from an acute infection. This makes it almost impossible to fully eradicate the virus. If such a person is subjected to immunosuppressive treatment in the future, these hidden virus particles are capable of launching a full-scale attack.
Once settled in, the virus might decide to live in peace with the body for a long time, or attract the attention of the body’s immune system. In fact, the attempts by our immune cells to destroy the virus cause more damage to tissue than the virus itself can bring about - a process that can even be called collateral damage. Outcomes like acute hepatitis, chronic hepatitis, cirrhosis and liver cancer are downstream effects of this infection.
Antigens (Ag) are proteins located in the body of the virus, while antibodies (Ab) are specialized counter-attack molecules manufactured by our immune system against these antigens. Antibodies that are made instantly for short-term use are of the IgM type, while the IgG type (which takes longer to manufacture) is for the long term.
In simple terms, the hepatitis B virus has three antigens associated with it: the HBs Ag, HBe Ag and HBc Ag (fig. 1). The HBs Ag is short for ‘surface’ antigen: it is seen on the outer shell of the virus. Just beneath the shell is a tiny bomb-shaped antigen called Hbe Ag, it is seen early in the blood as soon as the virus starts multiplying in the body. The HBcAg is short for ‘core’, which is located deepest inside the virus.
In acute hepatitis B, as the virus attacks the body, the immune system first manufactures anti HBc IgM antibody (against the ‘core’ antigen), followed by anti HBe Antibody (against the ‘e’ antigen) and anti HBs IgG antibody (against the surface antigen) after a few weeks of preparation. As these antibodies attack the virus and subdue it, the rate of virus multiplication falls and recovery occurs.
The natural history of HBV infection is variable. Typically, it starts with a process called acute hepatitis, three months after the virus gains entry into the body. Many people have no symptoms, but those who do may experience fever, body pains and nausea. After a few days, the person’s skin and eyes turn yellow: this is called jaundice and is due to the accumulation of bilirubin, a yellow pigment formed by the natural breakdown of haemoglobin. Among other things, the healthy liver cleanses the blood of bilirubin, expelling it through bile. As the ailing liver is not able to get rid of bilirubin quickly enough, some of it spills back into the bloodstream, and levels rise. The normal blood level of bilirubin is under 1.2 mg/dl. When levels rise over 3.5 mg/dl, skin turns yellow.
It is noteworthy that jaundice can have several causes of varying seriousness, and HBV infection is only one of them. Jaundice can occur when red blood cells break down more than usual (hemolysis), when the liver is unable to absorb all of the bilirubin from blood (Gilbert syndrome, a harmless condition), in liver cell dysfunction from assorted illnesses, and also if the drainage pipe of the liver (the bile duct) is blocked.
In acute HBV infection, as the days go by, jaundice lightens and the liver recovers its normal function. In a few weeks, as shown above, the body’s immune system would have mounted an effective counterattack against the intruder. In fact, over 95 percent of adults who contract an acute hepatitis B viral infection are able to get rid of it on their own – without treatment. This is the reason why medications are not used in acute hepatitis B, with rare exceptions.
In the remaining 5 percent who are unable to get rid of the virus, HBV continues to live inside the liver cells for a very long time. This is called inactive carrier state, during which the person will not have any health problems in most cases. They do not require treatment, as their viral DNA levels are very low or undetectable, and have normal liver enzymes.
Among those who become carriers, a few will develop chronic hepatitis -- an ongoing inflammation of the liver. When this process continues unchecked, it can lead on to liver cirrhosis and liver cancer in a significant number of cases.
It should be noted that unlike infection occurring in adulthood, those babies who get the infection from their mothers are not able to get rid of the HBV virus in the majority of cases. Most of them go on to become inactive carriers, among whom a few will progress to chronic liver disease. In fact, most of the HBV infection in the world exists as inactive carriers.
Not everyone with chronic hepatitis B infection requires treatment. Those with low viral loads and no ongoing liver inflammation can be safely left alone. However, these people need to stay under regular watch every few months, to make sure that the virus does not suddenly shift gears resulting in a flare-up of the illness.
Those who have chronic inflammation of the liver along with high viral load require treatment, the aim being to bring down the number of virus particles in the body. Treatment is available in the form of tablets (antivirals) as well as injections (interferon). Among the available tablets, Entecavir and Tenofovir are preferred due to lower chance of the virus becoming resistant to treatment.
As it is almost impossible to get rid of the virus completely, the aim of HBV treatment is to prevent complications such as liver cirrhosis and liver cancer. We have reliable scientific evidence from research trials such as the REVEAL study from Taiwan that those with the lowest viral counts are least likely to develop these complications. The duration of treatment required to achieve this can be quite long, even indefinite. Treatment endpoints such as sustained disappearance of HBsAg and HBe Ag are achieved only infrequently; doctors commonly use disappearance of HBV DNA in blood and normalization of liver enzymes as acceptable criteria of treatment success.
For those using tablets, it can take several years of treatment to achieve durable response, with only about 25 percent patients succeeding in the first year. Interferon injections are for a finite duration – typically 48 weeks. Whether to treat, what to treat with and how long to treat – are decisions to be made after consulting an experienced physician. Scientific progress in this area is rapid, and treatment guidelines periodically get updated as new research findings are appraised.
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As treatment is rather prolonged, cumbersome and expensive, it is important to emphasize prevention of hepatitis B. Three doses of vaccine given at 0, 1 and 6 months offer a high degree of protection against this infection. It is now part of the universal vaccination schedule for children. Within two months after the third dose, if the antibody titre is over 10 IU/L, then it confers 100 percent immunity. For babies being born to mothers harboring HBV, an additional injection of HBIG (Hepatitis B immunogobulin) is also required at birth to reduce the chance of vertical transmission.
Living with someone who has hepatitis B is not anything to be afraid of, but does require a few simple precautions. HBV does not spread by casual contact like handshakes or sharing of the toilet or kitchen utensils. Sharing of sharp objects like razors is to be avoided. The household contacts should first be checked for HBV and then vaccinated if they do not already have the infection. As the virus can spread through contact of the patient’s body fluids with an open wound, universal precautions are to be followed. If there is a blood spill, household bleach diluted 1:10 with water will help neutralize the virus.
Although liver cirrhosis and liver cancer are more talked about in this context, anxiety is one of the major under-recognized complications of getting diagnosed with hepatitis B. Much of this anxiety is unwarranted, as the risk of liver complications is largely restricted to those few patients who have active liver inflammation from hepatitis B, in comparison with the vast majority of people who are true inactive carriers with much lower risk. Anxiety is fuelled by difficulty among doctors as well as patients in understanding this complex disease, failure to estimate actual risk of complications, uncertainty of treatment duration along with financial burden, and non-uniformity of treatment practices. In a country where the family’s financial resources are often limited, therapeutic decisions will need to be customized better so that the expense is justifiable in the long term.
In summary, the task is to first correctly identify those few people who are at greater risk for liver cirrhosis and liver cancer from among those with Hepatitis B virus infection, and then attempt to reduce their viral load through medical treatment.
The complexity of treatment decisions for hepatitis B is likely to remain high until a medical breakthrough happens like in the case of hepatitis C, which can now be completely cured with tablets given over a short duration of time.
(The author is a Senior Consultant Gastroenterologist and the Deputy Medical Director, Sunrise Group of Hospitals, Kochi. His column, Everyday Health, will appear every alternate week)