Year : 2004 | Volume
: 1 | Issue : 1 | Page : 17--24
Epidemiology of hepatitis B virus infection in India
Department of Gastroenterology, Institute of Post Graduate Medical Education & Research, Kolkata 700020, West Bengal, India
Department of Gastroenterology, Institute of Post Graduate Medical Education & Research, Kolkata 700020, West Bengal
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Chowdhury A. Epidemiology of hepatitis B virus infection in India.Hep B Annual 2004;1:17-24
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Chowdhury A. Epidemiology of hepatitis B virus infection in India. Hep B Annual [serial online] 2004 [cited 2020 Apr 2 ];1:17-24
Available from: http://www.hepatitisbannual.org/text.asp?2004/1/1/17/27917
Hepatitis B virus infection (HBV) is a global public heath problem. Nearly two billion people in the world have been acutely infected by HBV and there are nearly 350 million people chronically infected with HBV.,, At least 15-25% of chronically HBV infected people will die due to liver disease caused by HBV and this constitutes nearly one million people each year. It is the most common cause of chronic liver disease, including cirrhosis of the liver and hepatocellular carcinoma worldwide. An effective vaccine is available for over two decades and has brought about remarkable changes in the global epidemiology of HBV infection.
However, the significance and the magnitude of the problem vary from country to country. The developed countries of Northern Europe and America have considerably controlled the infection by means of effective vaccination and improved sanitation, particularly measures taken for transfusion safety. HBV infection is present in less than 1% of the population of these countries and contributes to only 5-10% chronic liver diseases in these countries. This contrasts with the situation in the developing countries of Asia and Africa, particularly those of Far East and South Africa. In these countries, HBV infection occurs in 5-10% of the general population and is responsible for more than 50% of chronic liver diseases, constituting a public health priority. Importantly, in many countries of this region, particularly China and Taiwan, an effective immunization programme is changing the epidemiological situation very fast with decrease in the prevalence, incidence as well as impact of HBV infection. The situation in India is somewhere in between, with nearly 3-4% of the population infected by the virus, and chronic hepatitis B constituting more than 50% of the chronic hepatitis cases in the country. This, in the context of a large population and absence of a national immunization programme would spell off a projected increasing burden of infection and liver disease due to HBV in this country in the years to come. In this perspective, the HBV epidemiology in India becomes relevant not only nationally, but also internationally, because of the possibility that India may soon have the largest HBV infection pool in the world.
Apart from this change in the magnitude of infection, a qualitative change has also occurred in the understanding of HBV infection in general. With the advent of molecular tools in the study of HBV infection, genetic variants of HBV have been described that have differences in genetic structure, influencing the outcome of infection as well as therapy of HBV infection. Molecular epidemiology, in addition to the traditional sero epidemiological studies have improved understanding of the significance of the problem, particularly in terms of development of disease and formulating management strategies.
In contrast to many other viral infections, chronic HBV infection passes through different phases, each of which is in dynamic equilibrium with the other, determined by a closely integrated interaction between the virus and the host immune system [Table 1].
Hepatitis B virus Infection (HBV infection) - Natural History
In the natural history of HBV infection, the most important event is HBeAg seroconversion characterized by loss of HBeAg and development of antibody to HBeAg (Anti Hbe). This generally occurs years after replicative phase and indicates transition to a low/non replicative phase with potential for resolution of infection and improvement of necro-inflammation in the liver. Age of acquisition of the virus, immune competence of the host and the strength of immune response to the viral antigens are some of the determinants of timing and efficiency of seroconversion. The prognosis of chronic HBV infection is dependent upon the amount of inflammation, necrosis and fibrosis in the liver at this point of seroconversion. If significant liver damage is already present at this point, then the prognosis after seroconversion, spontaneous or treatment related is unlikely to be good, despite suppression of viral replication. On the other hand, if the seroconversion had occurred early and is maintained, then the long-term prognosis is excellent. It has been shown that the probability of development of hepatocellular carcinoma is many fold higher in persons who are HBeAg positive, than who are only HBsAg positive and HBeAg negative. In a subset of persons, this relationship between seroconversion and suppression of viral replication does not hold true. In them, despite anti-HBe positivity, active viral replication persists due to emergence of mutants in the pre core and basal core promoter regions of HBV. This state, characterized by continuing viral replication despite anti HBe positivity has been termed as HBe Ag negative hepatitis. ,, It has been increasingly recognized that HBeAg negative hepatitis is progressively increasing in prevalence globally. In India also, the majority of HBV infected persons are HBeAg negative, although the exact frequency and prevalence of HBeAg negative Hepatitis has not been estimated. The outcome of HBeAg negative hepatitis is different from that of the HBeAg positive phenotype. Fluctuating disease activity with periodic ALT flares accompany viral replication that progresses indolently to chronic liver disease. Response to anti viral therapy in HBeAg negative hepatitis is also different from the HBeAg positive disease., It would therefore be important to delineate the molecular character, viral load and response to therapy in HBeAg negative hepatitis in India.
SEROEPIDEMIOLOGY OF HBV INFECTION IN INDIA
A large number of studies on the epidemiology of HBV infection have been carried out in this country over the last two decades. There are several levels of variability amongst these studies. These include the sample size, the methodology for assay of HBV serological markers, the age group covered, general population sample versus blood donor and risk population samples, ethnicity and geography of the study population. All these factors have also been shown to influence the prevalence of HBV infection globally. Thus, while in the pre 1990 studies, HBsAg was assayed by the relatively insensitive RPHA method, in recent studies this has largely been replaced by ELISA. Studies based on blood donors have mostly included urban middle class young males, because of the trend in blood donation in this country. The relatively few general population based studies have included mostly selective population, mostly young school going children. Despite these limitations, these studies have provided significant information on the prevalence and other epidemiological characteristics of the hepatitis B infection in India.
Based on these data, between 3-4% of the Indian population are HBV infected (HBsAg positive). There is wide variation in the prevalence in different regions of the country, and the highest prevalence has been reported amongst the aborigines of Andaman as well as from Arunachal Pradesh. In a population based study involving the rural population in Birbhum district in West Bengal, a population of 7653 of all ages and both sexes ware studied. All were asymptomatic. The prevalence of HBsAg was 2.97% and there was a peak of prevalence after the second decade of life. Most (90%) of these HBV infected subjects were HBeAg negative; majority (80%) had normal ALT in India. The prevalence of HBeAg among asymptomatic HBsAg positive persons varies from 9-20%.,,
An important determinant of the epidemiology of HBV is the age of acquisition of the virus. It has been estimated that HBV infection is largely acquired by horizontal transmission in childhood and adolescence. Perinatal transmission plays a less important role.
Amongst the mode of transmission of the virus, a very important mode would be the unsafe injection practice prevailing in the vast rural areas of the country. It needs to be mentioned that the rural poor are still dependent upon the untrained paramedics for their treatment needs. Unfortunately, the sterilization of syringes, needles and minor surgical instruments are often improperly done in rural areas. This might be an important mode of dissemination of the virus in the community as had been demonstrated for Hepatitis C virus.
Molecular Epidemiology Of HBV infection in India
An important facet of global HBV epidemiology is the emergence and increasing significance of HBeAg negative infections as well as the distribution and significance of HBV mutants, particularly those in the pre core (PC) and basal core promoter (BCP) regions of the HBV genome. The prevalence of this e negative chronic hepatitis B and its molecular basis varies geographically. Thus, in the Mediterranean countries, nearly 90% of the HBeAg negative infections are associated with the precore mutants, while this is 50% in the Far East and 25% in the USA.
Very little information on the prevalence and molecular character of HBeAg negative hepatitis has emerged from India. In North India, the prevalence of precore mutants has been reported to be 15% amongst chronic liver disease patients. In West Bengal, amongst asymptomatic HBV infected, HBeAg negative, Anti HBeAg positive subjects, the prevalence of precore mutants was 9% and that of the basal core promoter mutants (BCP) was 4%. Rest (87%) of the HBeAg negative infections in the community, mostly inactive biochemically were associated with the wild type virus in this study.
Based on the nucleotide sequence homology and divergence amongst HBV isolates globally, seven genotypes of HBV are described (A to G). The distribution of HBV genotypes varies geographically. HBV genotypes have been correlated with disease progression (genotype C progresses to chronic hepatitis faster than B, and D faster than A), timing of e antigen seroconversion (genotype B earlier than genotype C), and poorer response to antiviral therapy (Genotype C). Moreover, HBV genotypes have also been correlated with human population migration in Japan.
In India, genotype D had been the predominant genotype both in North and Eastern India. However genotype C too had been described from West Bengal.,
IMPLICATIONS FOR PREVENTIVE PLANNING
India is on the doorsteps of adopting an HBV prevention programme. Based on the global experience, it is likely that an effective childhood immunization programme will reduce the burden of infection in this country. However, based on the knowledge of the predominant mode of HBV transmission through unsterile injection practice, health education and awareness about safe injection usage should form an integral component of such a programme. A shotgun approach through indiscriminate and unplanned immunization of the entire population alone is unlikely to be helpful. The evolving molecular epidemiological information will also improve the understanding of the disease and pave the way for a rational approach to the different phases of infection relevant for this country.
|1||Lee WM. Hepatitis B virus infection. N Engl J Med 1997;337: 1733-45.|
|2||Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000 - Summary of a workshop. Gastroenterology 2001;120:1828-53.|
|3||Lavanchy D. Public health measures in the control of viral hepatitis: A world health organization perspective for the next millennium. J Gastroenterol Hepatol 2002;17-S4:s452-s459.|
|4||Lok AS. Natural history and control of perinatally acquired hepatitis B virus infection. Dig Dis 1992;10:46-52.|
|5||Hadziyannis SJ, Vassilopoulos D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology 2001;34:617-24.|
|6||Hadziyannis SJ, Bramou T, Alexopoulou A, Makris A. Immunopathogenesis and natural course of anti-HBe positive chronic hepatitis with replicating B virus. In: Hollinger FB, Lemon SM, Margolis HS, Eds. Viral Hepatitis and Liver Disease. Baltimore: Williams and Wilkins,1991:673-6.|
|7||Hunt CM, McGill JM, Allen MI, Condreay LD. Clinical relevance of hepatitis B viral mutations. Hepatology 2000; 31:1037-44.|
|8||Miyakawa Y, Okamoto H, Mayumi M. The molecular basis of hepatitis B e antigen (HBeAg)-negative infections. J Viral Hepat 1997;4:1-8|
|9||Funk ML, Rosenberg DM, Lok ASF. World wide epidemiology of HBeAg negative chronic hepatitis B and associated precore and core promoter variants. J Viral Hepat 2002;9:52-61.|
|10||Chowdhury A, Santra A, Pal S, Chakravarty R, et al. Community based epidemiological study of Hepatitis B virus infection (HBV). Indian Journal Gastroenterol. 2001:20(Suppl 2) A2.|
|11||Tandon BN, Acharya SK, Tandon A. Epidemiology of hepatitis B virus infection in India. Gut 1996;389(Suppl 2) S56-S59.|
|12||Aggarwal R, Ghoshal UC, Naik S R. Assessment of cost-effectiveness of universal hepatitis B immunization in a low income country with intermediate endemicity using a Markov model. J Hepatol 2003;38:215-22.|
|13||Chu CJ, Hussain M, Lok ASF. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology . 2002; 122:1756-62.|
|14||Chowdhury A, Santra A, Chaudhuri S, Dhali G K, Chaudhuri S, Maity SG, Naik TN et al. Hepatitis C virus infection in the general population: A community -based study in West Bengal, India. Hepatology 2003;37:802-9.|
|15||Guptan RC, Thakur V, Sarin SK, Banerjee K, Khandekar P. Frequency and clinical profile of precore and surface hepatitis B mutants in Asian-Indian patients with chronic liver disease. Am J Gastroenterol . 1996;91:1312-7.|
|16||Thakur V, Guptan RC, Kazim SN, Malhotra V, Sarin SK. Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent. J Gastroenterol Hepatol 2002;17:113-5.|