common route: HCV is primarily transmitted through infected blood products

Nine out of 125 isn?t a large number. But virologist Priya Abraham says it is enough to warrant an intensive survey for a particularly nasty version of a hepatitis virus that may have established its roots in India. Medical scientists have detected the virus in nine out of 125 patients with jaundice and other symptoms of severe liver disease at the Christian Medical College (CMC) in Vellore over the past several months.

Routine diagnostic tests revealed that the 125 patients were infected with the hepatitis C virus (HCV), a virus commonly transmitted through infected blood products or sexual contact. But further examination of the genetic structures of the viruses isolated from each of the patients showed that nine of them were HCV genotype 4, a subgroup known to be resistant to anti-viral treatment.

?We may have a new strain of HCV to worry about,? says Dr Abraham, professor at the department of clinical virology at the CMC. The study was part of an ongoing effort to find out which genotypes, or subgroups, of HCV are circulating in India. Virologists have classified HCV from various parts of the world into six genotypes on the basis of differences in their genomes. The exact genotype of the virus can determine the severity of the disease as well as the response of the virus to treatment.

Genotype 4 had until now been primarily found in Egypt and other pockets of the Mediterranean region. Although doctors have previously isolated genotype 4 of HCV from patients, in most cases the patients who were found infected with the virus had either travelled to the Mediterranean region or were suspected to have had sexual contact with those who had travelled there and become infected.

Doctors have long been concerned about HCV because it is one of the hepatitis viruses that can cause irreversible damage to the liver. Although it is primarily transmitted through infected blood products, the virus can also move from one person to another via sexual contact. In many patients, the exact route of entry of HCV remains unknown. In developing countries, researchers suspect there may be unconventional routes of transmission, such as unhygienic dental extractions or even through barber shops where blades are reused on many customers.

Public health experts estimate that the number of people infected with HCV in India could range anywhere from one million to six million. In a report published in the Indian Journal of Medical Research, Abraham and her colleague Sukanya Raghuraman at the CMC have cautioned that given such a large pool of HCV carriers as well as the unrecogni-sed routes of transmission, HCV may be ?poi-sed to become a silent epidemic in the coming years, posing a major health problem.?

The virus can cause chronic infection in up to 70 per cent of infected people and a large proportion of these can get chronic liver disease. Until now, most studies have indicated that the majority of HCV isolated from patients in India belonged to HCV genotype 3, which responds well to treatment. Interferon and ribavarin are two drugs approved for the treatment of chronic HCV infection. Studies indicate that a large number of patients infected with HCV genotype 3 may be able to get rid of the virus through several months of therapy that combines interferon and ribavarin.

However, HCV replicates through an error-prone process that can facilitate the generation of subtle genetic differences in subsequent generations of viruses as they reproduce. Some of these genetic variants of HCV may be resistant to therapy. Over the past five years, several foreign studies have indicated that genotype 4 of HCV is resistant to interferon as well as combination interferon and ribavarin therapy.

Now, the new study by Abraham and her colleagues at the CMC showing that nine out of 125 HCV patients had genotype 4 will be published in the December issue of the Journal of Clinical Virology. Given the small size of their sample of patients with genotype 4, it is still too early to say how much impact genotype 4 will have on the HCV situation in India.

?We?ll need to wait and watch and see if more cases turn up,? says Abraham. What the CMC doctors found surprising was that none of the nine patients reported any history of travel to Egypt or other Mediterranean regions known to be associated with HCV genotype 4. The absence of travel history indicates that each of them had picked up the infection in India from someone else who had been infected previously.

?This suggests that a genotype resistant to therapy has established its roots in India and is likely to be spreading locally,? says Abraham. Gastroenterologists caution that if HCV genotype 4 were to spread within India, doctors may need to rethink treatment strategies. A standard therapy involves giving patients a combination of interferon and ribavarin for a period of six months. But because genotype 4 is resistant to treatment, patients infected with this strain may need therapy for up to 12 months ? and this surely means higher treatment costs.