Year : 2004 | Volume
: 1 | Issue : 1 | Page : 7--9
Shivaram Prasad Singh1, Yogesh Kumar Chawla2,
1 Department of Gastroenterology, S.C.B. Medical College, Cuttack, India
2 Postgraduate Institute of Medical Education and Research, Chandigarh, India
Shivaram Prasad Singh
Department of Gastroenterology, S.C.B. Medical College, Cuttack
|How to cite this article:|
Singh SP, Chawla YK. Editorial.Hep B Annual 2004;1:7-9
|How to cite this URL:|
Singh SP, Chawla YK. Editorial. Hep B Annual [serial online] 2004 [cited 2020 Sep 25 ];1:7-9
Available from: http://www.hepatitisbannual.org/text.asp?2004/1/1/7/27915
Hepatitis B infection affects almost 43 million people in India. Hepatitis B virus is considered to be much more infectious than hepatitis C virus and AIDS virus. This book has chapters written on various aspects of Hepatitis B by experts, which would benefit both the student and scientists who read this book.
While the epidemiology of hepatitis B has changed in most of the developed countries, in India the incidence of acute hepatitis B does not seem to have decreased much, in spite of mandatory screening in blood banks for HBsAg, HB vaccination camps that have been conducted all over the country and increasing public awareness.
The virology and the replication cycle of the HBV virus is more well defined now. The HBV replication begins with the attachment of the virion to the hepatocyte mediated by the PreS1 surface glycoprotein and an unidentified receptor. Inside the hepatocyte, the HBV genome is converted to a covalently closed circular DNA molecule (ccc DNA), which acts as a template for producing both mRNA for viral proteins as well as pregenomic RNA. Nucleoside analogue antiviral agents act largely on reverse transcriptase or DNA polymerase and have little effect on cccDNA, which explains the rapid reappearance of HBV DNA after cessation of antiviral therapy.
The DNA polymerase and reverse transcriptase activities of HBV are effective and rapid, but lack proof reading activity and are thus prone to errors. Variations in HBV sequences have been detected in almost all regions of the HBV genome, and hence HBV circulates as quasispecies. Seven genotypes (A-G) of HBV have been identified. In India genotypes D and A are common. It is difficult at present to conclude whether any differences in clinical outcome and response to treatment occur with different genotypes.
HBV DNA estimations are valuable in the management of viral infections but their use is limited due to lack of standardization and variability in sensitivity. There appears to be a level of HBV DNA below which the disease is inactive and non-progressive and this level arbitrarily ranges between 10 4 and 10 6 genome copies/ml. Values below 10 5 genome copies/ml are consistent with a patient having inactive HBsAg carrier state. This level also correlates arbitrarily with seroconversion of HBeAg from levels of 10 7-10 10 millions copies/ml to less than 10 5 genome copies/ml, which are not detected by hybridization techniques. Not all patients who seroconvert have low levels of HBV DNA. Patients who are HBeAg negative - chronic hepatitis B but have high HBV DNA levels constitute a group in the spectrum of HBV disease, which responds poorly to antiviral therapy.
The degree of liver injury and amount of fibrosis is now assessed semi quantitatively using the histologic activity index (HAI). Trials with antivirals are considered successful, if there is more than 2-point improvement in HAI score. Immunostaining for HBV antigens in liver biopsy specimens has shown a strong expression of HBsAg and HBeAg in uninjured hepatocytes, which suggests that the necroinflammatory injury in hepatitis B is immunologically mediated. Interferon alfa therapy for HBeAg positive chronic hepatitis B shows an HBeAg seroconversion rate of 33% and a loss of HBsAg in 7.8%. 95-100% of responders remain HBeAg negative even during 5-10 years follow up. HBeAg negative chronic hepatitis B patients on the other hand show a 40-60% response with therapy, with 50% relapse when therapy is stopped. A durable response to a 12 month course of interferon has been reported in only 15-25% of cases. Interferon treated patients on long term follow up have shown improved survival and a decrease in HCC incidence.
Lamivudine achieves HBeAg seroconversion in 17-33% of cases after 1 year of therapy, which is similar to interferon response. It is still unresolved as to how long lamivudine needs to be given and the durability of its response. Yet another problem with lamivudine is the development of resistance by causing YMDD mutation, which causes a rise in transaminases and HBV DNA titres.
A combination of lamivudine and interferon has also been tried, but the results have not been very encouraging.
Preliminary trials with adefovir, another nucleoside analogue have shown good results in HBeAg positive and HBeAg negative chronic hepatitis and patients with lamivudine resistance as well. Patients with compensated cirrhosis due to Hepatitis B virus should be treated and so also should HBsAg positive patients with extrahepatic manifestations. Patients with decompensated cirrhosis should only be treated with oral antivirals which are safer than interferon in this group of patients and have been shown to improve the severity of liver disease in them, who then become less urgent or unnecessary for a liver transplant.
The greatest need for the future in the field of Hepatitis B is the development of a safe and more effective regimen of therapy. It would also be important to develop reliable and standard assays for qualitative assessment of HBV DNA, and easy identification of the genotypes, so that the differences in their management could be identified. Better therapeutic drugs for managing of hepatitis B patients in problem populations like patients with renal failure, organ transplantation, HIV coinfection and hepatic decompensation are also urgently needed.