An Indian medicine for hepatitis B

Nearly 20 per cent of the people in Southeast Asia are carriers of hepatitis B, one of the deadliest diseases of modern times.

In India, 4-4.75 per cent carry the virus. Only less than 2 per cent of Americans are carriers, but the incidence rate is much higher among Asians living in the US.

"Many studies have shown that in Asian and African populations, hepatitis virus has much more chances to cause chronic carrier problems rather than in the White population. It could be the genetic susceptibility of the population that is causing the problem," says Dr S P Thyagarajan, head of the Department of Microbiology at the Madras University's Dr A L Mudaliar Institute of Post-graduate Medical Sciences.

Another alarming fact about the hepatitis B virus is that it is more infectious than HIV, scoring 33 per cent on an 'infectivity' rate scale against HIV's 0.3.

With nearly 42 million carrying the hepatitis B virus, India is bracketed in the 'intermediate zone' [between 2-7 per cent of the population].

Of the five hepatitis viruses -- A, B, C, D and E -- the first and the last are waterborne and, therefore, spread less easily.

Hepatitis B, C, and D are very dangerous and, like HIV, can be passed on through blood transfusion, needles, body fluids and sexual intercourse.

These three viruses not only produce acute jaundice, but slowly lead to diseases like liver sclerosis and liver cancer.

Treatment of hepatitis B carriers is expensive. An injection of Interferon costs Rs 6,000 and the patients have to take these every week for at least a year. Another option is Lamuvidine tablet and a single one costs Rs 30. The treatment may go beyond five years. The efficacy is between 30-40 per cent and the treatment is reported to have many side effects.

It is against this background that the scientific discovery of Dr Thyagarajan becomes important. The ayurvedic physicians of Kerala have been using an extract from a plant locally termed Keezharnelli for centuries to treat jaundice. But like all traditional Indian medicines, it has never been scientifically tested. It was the medicinal qualities [empirically found effective, but still anecdotal in terms of Western science] of Keezharnelli and the alarming spread of hepatitis B that attracted the attention of Dr Thyagarajan and he began doing his PhD on the plant in 1979.

When rediff.com met Dr Thyagarajan in 1999, he had successfully extracted the active substances of the plant and had applied for a patent for Keezharnelli, or phyllanthus amarus in the name of the University of Madras.

He was also developing the drug clinically. It was through years of hard work and a series of clinical and scientific tests that he proved that the extracts could cure hepatitis B.

Three therapeutically active substances of phyllanthus amarus show activity against the hepatitis virus, improve the body's immune system and protect the liver.

Dr Thyagarajan extracts all these three substances separately and converts them into tablets.

"This is a major breakthrough because this is one plant that has been scientifically evaluated in our country and is accepted the world over. In India, there is a wealth of information available in the traditional ayurveda and siddha branches of medicine. But the problem is we have not bothered to study them scientifically," Dr Thyagarajan says.

It was not an easy journey for Dr Thyagarajan. He got acceptance and support only after international scientists, particularly Dr Baruch Blumberg, who won the Nobel Prize for discovering the hepatitis B virus, accepted his findings. Dr Blumberg, along with Irving Millman, also invented the hepatitis B vaccine.

Dr Thyagarajan did a lot of collaborative work with Dr Blumberg in testing the extracts in animals for acute and chronic toxicological studies.

That was long ago.

The ayurvedic formulation from Keezharnelli was awarded a patent in the US [June 2002], South Africa [September 2002] and North Korea [October 2002]. The process to acquire a patent for the formulation is on in ten other countries, including the UK and Japan.

"Usually there is a criticism in the Western countries that there is lack of standardisation in the case of traditional medicine in general and in the case of herbal drugs in particular. That is mainly because a lot of herbs are included in a medicine, and the herbs are collected from different parts, and you cannot generally guarantee uniformity. They may not have the same efficacy during all times of the year. In fact, this is already indexed in ayurvedic literature. We have addressed that part of the criticism. So there will not be any batch-to-batch variation in our plant-based drug. That is the basis of our patent," Dr Thyagarajan explains.

Once the tablet was tested, Rallys India Pharmaceuticals [which has merged with Sreya Life Sciences, Mumbai] expressed a desire to sign a memorandum of understanding with the University of Madras.

The formulation in the tablet form was named Virohep [the compound is called Hepavirin] and launched on December 23, 2000. The tablet is now available in India and many other countries.

If the treatment under allopathic regimen is expensive and long, it is necessary to treat patients suffering from jaundice for only two weeks with Virohep, says Dr Thyagarajan. In the case of carriers of hepatitis B, the treatment continues for 3-6 months. One tablet costs only Rs 6.

Dr Raghuram of the Vijaya Hospital, Chennai, has been treating his patients with the drug.

"I was also a collaborator in the research. So you can say we have been using it for the last 20 years. The only difference is that it has been experimentally proven now. Virohep is the same as Keezharnelli. The most important aspect about Virohep is that it does no harm to the individual, while the allopathic medicine has a lot of harmful effects, and it can be used in chronic cases. Also, the allopathic medicines are very costly. We have found that in 40 per cent of individuals who are carriers of hepatitis B virus, the virus has been eradicated from the system. I am quite satisfied with Virohep," says Dr Raghuram.

Dr Eric Walker, who is now the Consultant Physician of Scottish Centre for Infections, Glasgow, UK, first noted the use of phyllanthus amarus as a herbal remedy for jaundice when he was working in primary care at the Christian Medical College, Vellore in the 1970s. Then he met Dr Thyagarajan, 'and became very much interested in his scientific work'.

Later, in the 1980s, as a part of a multi-centre trial with Dr Thyagarajan, he started prescribing the medicine to his patients.

"I am convinced of its properties in protecting the liver from infection and encouraging the body to eliminate the virus from liver cells," says Dr Walker.

He adds, "Our trials in Scotland have been small but confirm the work done in Chennai that around 60 per cent of hepatitis B carriers will eliminate E-Antigen to their obvious benefit in preventing eventual complications and removing infectivity. We have encouraging preliminary evidence that it may also give some benefit to hepatitis C carriers."

Prakashchand Jain came to know that he was a carrier of the hepatitis B virus when he went to donate blood. His physician, Dr Shanmugha Sundaram, immediately directed him to Dr Jayanthi, the gastroenterologist who in turn asked him to meet to Dr Thyagarajan. During that period, Dr Thyagarajan was in the process of developing the extract of Keezharnelli.

"At the University of Madras lab, I was tested positive. He had not made any tablet then. I was given a powder. After taking the medicine for quite sometime, I was tested negative. If I am well today, I have to thank only that professor," he says.

Paandi, another patient who was treated with the powdered extract of Keezharnelli was also cured.

They now plan to market the drug in the US and Asian and African countries. A multi-centric trial is essential for international regulations like the FDA clearance.