INTERFERON ALPHA
The hepatitis B virus has infected 350 million people around the world and amongst them one milllion will die of liver failure or liver cancer every year. All this is because there is still not a very effective form of treatment, especially in managing the extremely large number of carriers.A disease of such a magnitude has been driving scientists around the world in search of a better therapy. They did succeed in developing a vaccine to protect uninfected individals, however it is not of any use to people who already harbour the virus. Although an ideal treatment is not yet available, nevertheless, there is a drug of moderate efficacy called Interferon alpha, which occupies an important position.
The name Interferon was coined by the scientists who discovered a substance in the body that interfered with the multiplication of viruses. These are proteins produced whenever any virus successfully invaded the body. In response, the white blood cells make a specific protein called Interferon alpha which does not allow the virus to multiply in adjacent healthy cells, although the infected cells are destined to die. It is this property that makes Interferon useful in the treatment of chronic hepatitis B infection. However, after the preliminary necessary tests in laboratory animals, many clinical trails have to be carried out in patients before it can be approved for general use.
Mazella et al. (1999) tested the drug by giving one group of patients a dose of 5 million units per square meter of body surface, three times weekly for 6 months, and another group was not given the drug. The results showed the treated patients had a faster, more complete and sustained clearing of “viral markers” than the control group. The viral markers are parts of the virus which indicates it is still active inside the body. Another indicator is ALT, a biochemical index which reflects the degree of liver injury when it goes above normal levels.
Since Interferon alone does not produce ideal results, researchers tested the effects of combining it with other synthetic drugs which also has the ability to stop viral replication. Schalm et al. (1999) administered to one group of patients Lamivudine 100 milligram daily for 8 weeks, then added Interferon 10 million units three times weekly for 10 weeks, another group recieved only Interferon for 16 weeks, whereas a third group only Lamivudine for 52 weeks. The results showed that HBeAg, an important viral marker, disappeared in 29% of patients who received two drugs, and only 19% and 18% in the second and the third groups respectively.
Patients treated with liver transplantation for advanced disease have the problem of being reinfected with a hepatitis B virus which is resistant to drugs like Lamivudine and Famciclovir (Seehofer et al. 2000). However, they found that the addition of Interferon to Lamivudine greatly diminished the rate of viral reproduction. 75% of the patients showed disappearence of HBV-DNA, another viral marker; also ALT in all the patients returned to normal level. It is known that chronic active hepatitis B infection always lead to liver cirrhosis, a condition of shrinkage and hardening of the liver, which in turn will terminate in liver failure or cancer. An anonymous international group (1998, Lancet) had analyzed the clinical data of 913 patients and reported that Interferon reduced the rate of progression of chronic hepatitis to liver cancer by two-fold.
There are two weaknesses in Interferon alpha therapy; one being that of low efficacy and the other is the abundance of side effects. The first may be due to insufficient concentrations of the drug inside liver cells and the second becuase the protein has biological effects on many different types of cells. Aurisicchio et al. (2000) carried out an experiment in mice to see if it is possible to restrict production of Interferon in liver cells by using the technique called gene therapy. They used a virus which specifically attacked liver cells and made it carry the gene for Interferon alpha. In addition, this gene was placed under the control of a special piece of regulatory DNA called the Transthyretin promoter which is activated only in liver cells. Injecting this altered virus made sure that Interferon will be generated only in the liver. Infecting the mice afterwards with mouse hepatitis virus, they found a very high concentration of Interferon inside liver cells which also did not show any sign of liver damage. The mice not protected this way showed extensive liver disease. Furthermore, only a very low level of drug was detected in the blood which might considerably lessen the side effects.
Analysis of the available data from animal experiments and clinical trials seems to predict the possibility of an effective cure for chronic hepatitis B infection. The hope lies in gene therapy which will enable the precise delivery of the right gene to the right cells producing the maximum therapeitic effect.
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