Indigenous drug for Hepatitis-B
R. Prasad

A GREAT medical breakthrough has been achieved by discovering a drug for treating the virulent Hepatitis-B infection. The discovery by Mr. A. L. Thyagarajan, head of the Department of Microbiology at the Dr. A. L. Mudaliar Post Graduate Institute of Basic Medical Sciences of the University of Madras, comes after nearly twenty years of research. With this the 400 million suffering from Hepatitis-B around the world, with 42 million in India alone, have a chance to get cured of the infection. Hepatitis-B kills more people in the world than AIDS does in one year. The discovery can therefore be hailed as one of the greatest Indian contributions to the medical world in the 20th century.

The drug has been developed based on a locally available kizhanelli (Phyllanthus amarus) plant. Kizhanelli has been traditionally known to cure jaundice (Hepatitis-A and Hepatitis- E). The discovery has been able to point out the efficacy of Phyllanthus amarus to cure Hepatitis-B provided the type of soil to be used, preparation of the soil for cultivation, biotyping (the biological tests to find out the various active properties of the plant to treat Hepatitis-B and liver damage) and finally chemotyping (to check the corresponding chemical constituents responsible for this biological properties) are taken care of.

The idea to use kizhanelli to treat Hepatitis-B was first tried out by Mr. Thyagarajan in 1972. It was found to reduce the bilirubin level in from 38 ml to 12 ml per CC in two weeks of treatment and completely clear it in four weeks time. Bilirubin is released by dead liver cells infected by Hepatitis-B and is used as a direct measure to evaluate the state of liver infection.

Studies revealed presence of five species of Phyllanthus (Kizhanelli) in India. And it was only in 1989-90 that the anti- viral property of Phyllanthus amarus was discovered. Strangely, Phyllanthus amarus, found only in South India, showed the required activity. Even in South India, the anti-viral property of the plant depends on the soil condition, preparation of the soil, and the season when the plant is collected. ``The patent is based on these vital properties which gives the plant the required anti-viral properties,'' says Mr. Thyagarajan.

Jaundice transmitted through contaminated water, otherwise known as Hepatitis-A and Hepatitis-E, is mostly prevalent in India and most other developing countries. Hepatitis-B on the other hand is transmitted through infected blood and blood products, infected needles, sexual contact and vertical transmission (mother to new born baby). But the drugs presently available in the market never cure Hepatitis-B completely. When left untreated, Hepatitis-B can cause cirrhosis of the liver and even liver cancer. The Interferon alfa drug available in the market can only achieve 33 per cent suppression of viral multiplication (loss of Hepatitis-B e antigen) after six months of treatment. Lamivudine on the other hand has higher virus suppression but the virus shoots back to pre-treatment level once the treatment is stopped. Besides, these treatments cost more than Rs. 1 lakh and have side effects too.

Field trials have shown the efficacy of the drug developed by Mr. Thyagarajan to completely clear the virus in the case of acute Hepatitis-B within eight weeks of treatment. All clinical symptoms are cleared within four weeks of treatment. In the case of chronic patients, the drug has been able to achieve 60 per cent viral clearance. This high viral clearance nearly stops the progress of the disease thus keeping the end stage diseases like cancer and cirrhosis at bay.

The drug according to Mr. Thyagarajan, can be given to babies affected by vertical transmission in the absence of vaccination. ``It is ideal to start treatment before the baby is five years old,'' says Mr. Thyagarajan. This is because the DNA of the virus has an affinity to combine with the DNA of the host liver cell leading to an ``integrated state'' of the virus with the liver cell. Once this happens removal of the virus from the liver cell becomes difficult. It is this integrated state of the virus which determines the efficacy of the drug.

In the case of acute Hepatitis-B patients, the host liver cell reacts with the virus thus preventing an integration of the virus. The efficacy of the drug is thus very high. However, in the case of chronic Hepatitis-B patients, integration of the virus is possible over a period of time thus affecting the potency of the drug. This makes an early treatment imperative. In spite of the drug's ability to cure, prevention through vaccination remains paramount.

The Phyllanthus amarus plant for drug preparation can be grown only in the tropical climate as open farm cultivation and in certain soil conditions. But the standard protocol developed by Mr. Thyagarajan to prepare the soil for cultivation, special type of seeds required for cultivation and various tests to check if the soil has been prepared to specifications, and biological and chemical fingerprinting techniques will ensure that soil requirements do not pose a limitation for production.

This becomes all the more important as the demand for the drug will be high considering the rate of increase of Hepatitis-B infection around the world. In India alone, the rate of infection had increased from 3 per cent in 1992 to 4.7 per cent in 1998.

The discovery and sale of the patent to Rallis India and Phytopharma of the U.K., comes at a time when the western world is closely looking at Indian traditional medicines. And patenting drugs by the developed countries based on traditional medicinal properties known to Indians is now becoming more a norm than an exception. Against this backdrop, the patenting of Phyllanthus amarus based drug should be hailed.

Yet, the importance of a drug to treat Hepatitis-B notwithstanding, the saga of Indian scientific institutions finding little industrial support for R&D work continues. Says Mr. Thyagarajan, ``Indian pharmaceutical companies did not understand the value of this drug preparation and they did not pay much importance. Initially they did not attach much significance so we did not succeed in having a collaborative work. Else, we could have developed this drug long back.'' The highlight is of course the paltry Rs. 10 lakh paid by Rallis India and $40,000 by Phytopharma for the technology transfer and the 7.5 per cent royalty from sales proceeds. Price for Indian research!