VOLUME 19, NUMBER
Communicable Diseases 203
hepatitis in India
S. K. ACHARYA, KAUSHAL MADAN, S. DATTAGUPTA, S. K. PANDA
Viral hepatitis, caused by hepatitis viruses A through E,
is a major public health problem in India.1 Since
1955, several epidemics of hepatitis have been reported.2–8 Although
hepatitis A virus (HAV)9 and
hepatitis E virus (HEV), both enterically transmitted, are
highly endemic in India, HEV
has been responsible for most of these epidemics.2–8,10–17 In
India, HEV infection is responsible for 30%–70%
of cases of acute sporadic hepatitis and is the major cause
of acute liver failure (ALF).18–21 Among
children, HAV is the predominant cause of acute hepatitis,9,22–25 and
dual infection with HAV and HEV have been more frequently
reported among children with ALF.26
In India, hepatitis B virus (HBV) infection is of intermediate
endemicity, with nearly 4% of the population being chronic
HBV carriers, i.e. about 40 million people.27 Most
of them are asymptomatic (high endemicity >8%, intermediate 2%–8%,
low <2%).27–30 The
frequency of hepatitis C virus (HCV) infection, as evaluated
by anti-HCV antibody positivity,
has been reported to be 1%–2% among voluntary blood
donors31–34 and 0.87%
in the community;35 these figures
are similar to those from developed countries such as Japan
and the USA. HBV and HCV are parenterally transmitted and
cause both acute as well as chronic disease. About 15%–30%
of acute hepatitis in India is due to HBV.21,37 However,
HCV is an infrequent cause of acute icteric hepatitis,31 but
causes most of post-transfusion hepatitis.39,40 HBV
is the major cause of chronic hepatitis, cirrhosis and primary
liver cell cancer in India.27,31,41,42 About
50% of chronic liver disease (CLD) is due to HBV and 20%
is due to HCV infection.27,31 Hepatitis
D virus (HDV) infection is found in fewer than 10% of patients
with acute or chronic HBV infection.43
Based on data from Indian hospitals, annually about 250 000
people die of viral hepatitis or its sequelae. This article
reviews the epidemiological, clinical, biochemical, histological
and treatment data related to viral hepatitis in India published
in the English literature. However, this effort is limited
by the lack of a hepatitis registry, and of good community-based
epidemiological and seroepidemiological studies.
HEPATITIS E VIRUS (HEV)
HEV infection is the most frequent cause of acute sporadic
and epidemic hepatitis in India.2–8,10–17,44 HEV
has a positive-stranded, 7.5 kb, RNA genome with 3 open reading
frames (ORFs).44,45 It is transmitted
predominantly through faecal contamination of waterand food.2–8,46 During
the past 5 decades, several epidemics of HEV infection have
been documented in India.2–8 HEV
is also the major cause of ALF in India.19–21,47,48 It
has recently been shown to be a common cause of acute superinfection
damage among patients with chronic liver disease due to various
causes.49,51 Thus, HEV is a
major public health problem in India and its importance may
not have been fully realized
yet by public health professionals, clinicians and basic
The first and the most well-studied epidemic of HEV affected
29 300 people in Delhi between December 1955 and January
1956.1 Most of the information
on the epidemiological aspects of HEV has been derived from
this epidemic. Several well-studied
epidemics reported subsequently (Table I)2–8,10,12 have
had similar epidemiological features. In these epidemics,
faecal contamination of the source of drinking water was
documented. The contamination of drinking water was due to
backflow of sewage during floods,6,7 leaking
sewers located close to corroded drinking water pipes2 and
contamination of shallow well water during the rainy season.3–5
Unlike other faeco-orally transmitted viral infections (HAV,
rotaviruses and polioviruses), person-to-person transmission
of HEV is much less frequent.52–54 During
HEV epidemics, secondary attack rates among household contacts
individuals are 0.7%–2%.16,44,52,53,55 During
sporadic HEV infection also, person-to-person transmission
is infrequent.53 A
few reports have raised the possibility of parenteral transmission.53–61 A
parenteral inoculum of sera pooled from patients with acute
HEV infection was able to transmit the infection to Rhesus
monkeys.15,16 Medical personnel
looking after a patient with acute hepatitis E acquired the
disease.59 In a recent study,
Khuroo et al. documented that serological evidence of HEV
infection was more frequent among those receiving blood transfusions
compared with non-transfused controls.56 They
also found that recipients of HEV-infected donor blood developed
of HEV infection.56 Mathur et
al. detected the presence of IgM anti-HEV among 244 of 2070
children (12%) attending medical
facilities for minor ailments.61 These
data suggest that subclinical infection with HEV in endemic
regions is frequent
and transfusion from infected donors may cause HEV infection.
However, the sequence homology of HEV isolates from such
donors and recipients with HEV infection has yet to be reported.
In another study, Khuroo et al. reported the presence of
HEV RNA in 5 of 8 infants born to HEV-infected mothers, indicating
vertical transmission of HEV.62
The incubation period of HEV infection has been estimated
to be 2–9 weeks (mean 6 weeks) (Table I).2–8 During
epidemics of HEV infection, clinical hepatitis is more frequent
among adults than among children below 15 years
of age, and among men than among women.2–8 However,
icteric sporadic hepatitis has been
TABLE I. Major epidemics of hepatitis E virus (HEV) infection in India
Incubation period (days)
Attack rate (%)
Overall n (%)
Pregnant women (%)
* serology negative for hepatitis
B and A viruses † presumed aetiology, serological studies
not done ‡ positive serology for HEV
5 of 48 (10.5%) pregnant women died compared with 60 of 29 252 (0.2%)
of men and non-pregnant women (p<0.001)
|| Of 275 affected persons, 8 were pregnant women of whom 6 (75%) died,
compared with 4 of 267 (1.4%) men and non-pregnant women
Mortality among non-pregnant women was 13.4% and among men was 8.4%
** Of 48 deaths, 13 (27%) occurred in pregnant women
documented among children.53,61 During
HEV epidemics, anicteric hepatitis is more frequent than icteric
In India, HEV infection has also been associated with severe
liver disease. During epidemics, pregnant women in their second
and third trimesters get infected more frequently (12%–20%)
than men and non-pregnant women (2%–4%).2–8,16,17,20 The
frequency of ALF is higher (10%–22%) among pregnant
women with HEV infection than among men and non-pregnant women
the mortality rate is significantly higher among pregnant women
who develop hepatitis during epidemics
(10%–39%) than in the general population affected with
hepatitis (0.06%–12%; Table I).2–8,16,17,51 In
the sporadic setting, evidence of HEV infection has been detected
in 30%–45% of patients with ALF.20 Among
children, combined HEV and HAV infection is frequently associated
with ALF.26 In
patients with compensated chronic liver disease, superinfection
with HEV has been reported to cause decompensation.49–51 However,
patients with HEV infection do not develop any chronic sequelae.63
The structural region of the HEV genome (ORF2 and ORF3) has been
cloned and its encoded polyproteins have been expressed.64,65 Commercial
enzyme immune assays (EIAs) are now available to detect IgG and
IgM antibodies against ORF2- and ORF3-encoded peptides.
Most commercial EIAs use both these peptides. In non-endemic
regions, the presence of either IgM or IgG antibodies in a patient’s
serum is considered evidence of acute HEV infection.64 However,
in India, where subclinical HEV infection is common, the diagnostic
accuracy of these EIA systems has not been evaluated fully.53,54,65,66 IgG
anti-HEV has been reported to persist for many years and is detected
in 10%–40% of the general population in India.50,51,53,57,61,67 However,
the frequency of IgM antibody in the general population has been
reported to be 10%–15%.50,51,61,65 We
evaluated the diagnostic accuracy of an in-house kit incorporating
coded from ORF1, ORF2 and ORF3 and found that it has a sensitivity
of 97% in comparison with 69% for a commercial EIA.68 The
most definitive evidence of HEV infection is the detection of
RNA in the serum.53,54,65,69 However,
for seroepidemiological studies, IgG anti-HEV should be used
and for the diagnosis of
acute HEV infection, IgM anti-HEV should be used. These tests
are less expensive, easily performed and widely available.53,69
During the 1955–56 epidemic in Delhi, 78 needle liver biopsy
specimens from patients with acute hepatitis E were studied.70 The
prominent feature observed in 45 of these was the presence of
canalicular and intracanalicular cholestasis with formation
of pseudoglandular structures resembling embryonal bile ducts.70 In
addition, mononuclear infiltration was prominent in the portal
tracts and hepatic lobules, along with ballooned hepatocytes.
Similar histological features have been described subsequently.71
Tam et al. in 1991 sequenced the entire HEV genome and described
its genomic organization.45 Even
after 15 years, little is understood about its mechanisms of
replication and transcription, primarily
because of the non-availability of a reliable in vivo propagation
system. Several authors have reported propagation of HEV in cell
culture systems but their work needs independent confirmation.72–75 HEV
can infect several commonly available macaques and these infected
animals have served as the source material for HEV for
several years.15,76,77 The
development of an infectious cDNA clone for HEV by Panda et al. provides
a useful tool for the study of mechanisms involved in viral replication
during HEVinfection.78 The recent
development of HEV replicons that express reporter genes should
also help in this direction.
The current understanding of the replication strategy of HEV
is based on similarities with other positive-strand RNA viruses.
Apart from the detection of negative-strand RNA in infected rhesus
macaque liver and presence of subgenomic RNA in experimentally
infected cynomolgus macaque and cell culture systems,45,79,80 only
one study provides evidence of HEV replication. However, several
issues in HEV replication remain unresolved;54 these
include the mechanism of ORF1 polyprotein processing, functions
of viral replicase and protease included in the ORF1 protein,
regulatory factors controlling HEV gene expression,
cis-acting elements involved
in viral gene expression and replication, and the translation
mechanics of ORF2 and ORF3 proteins.
Arankalle et al. undertook HEV genotyping of 17 Indian HEV isolates
from epidemic and sporadic cases occurring between 1971 and 1991.81 By
sequencing the RNA polymerase (RdRp) region, they divided HEV
isolates into 3 genotypes (>15% heterogeneity). Genotype
1 was further subdivided into 1A, 1B, 1C and 1D. The majority
of Indian isolates belonged to genotype 1A. In Indian cities
that had 2 outbreaks 10 years apart, there was a shift in the
subgenotype from 1B (Ahmedabad, 1976) to 1A (Ahmedabad, 1984)
and from 1A (Kolkata, 1981) to 1D (Kolkata, 1991).81 Aggarwal et al.82 sequenced short
ORF1 and ORF2 subgenomic regions from isolates obtained during
3 different outbreaks. They found that
sequences within an outbreak were 99.3%–100% identical
in both ORF1 and ORF2 regions. However, HEV isolates from different
outbreaks had genomic sequence homology of 97.1%–99.2%
and 96.4%–100% in the ORF1 and ORF2 regions, respectively.82
Despite considerable genomic variability, all the HEV genotypes
belong to one serotype.83
In rural India, defaecation in the open is common. This is the
major cause of well water contamination, especially during the
rainy season. Better sanitation, provision of clean drinking
water, proper sewage disposal and public education are the mainstays
for prevention of HEV infection. However, since these are difficult
to achieve in developing countries with limited resources, the
development of a vaccine may be a useful preventive strategy.
Recent studies have evaluated recombinant HEV
ORF2 proteins as candidate vaccines.84 An
ORF2-derived 62 kD recombinant protein
prepared from the Burmese HEV strain and expressed in baculovirus
has shown protection against biochemical or histological hepatitis
in monkeys upon challenge with a large dose of a heterologous
HEV strain.84 However, the protection
was short-lived. DNA vaccine administered through the gene gun
has also been found to be immunogenic in animals.85
HEPATITIS A VIRUS (HAV)
HAV is an RNA virus which is transmitted through contaminated
water and food. HAV infection is highly endemic in most developing
countries including India.9,21 However,
unlike HEV infection, HAV infection is associated with the development
immunity.9 Further, HAV infection
is frequently mild and asymptomatic in childhood. In developing
countries, HAV infection is common
during childhood, is often subclinical, and confers immunity
to a large proportion of the population.9 Therefore,
HAV hepatitis usually occurs in children, and infection in adults
infrequent.9 However, in the paediatric
population dual infection with both the enteric hepatitis viruses
(HAV and HEV) is not
infrequent and may cause ALF.26 Parenteral
and vertical transmission of HAV is unusual. In contrast, in
the developed world, lack
of exposure to HAV during childhood results in a large non-immune
adult population. In adults, HAV infection has been reported
to cause more severe liver disease such as cholestatic and relapsing
hepatitis, which has a prolonged course.86,87 However,
mortality due to HAV is extremely low (0.05%–0.1%).88,89 HAV
superinfection in patients with pre-existing chronic liver disease
has been reported to cause liver failure and death, particularly
in the West. Therefore, routine HAV vaccination is recommended
in the West for patients with chronic liver disease.90
A few recent hospital-based studies suggest that the prevalence
of anti-HAV antibodies among Indian adults has declined to <70%,23–25 possibly
due to improved sanitation and urbanization (Table II). This
decline was more marked among the higher socioeconomic group.25 However,
these latter studies were not community-based and included select
populations. In community-based studies among unselected
schoolchildren, anti-HAV antibodies were detected in nearly 80%
of children by the age of 5 years and in nearly all children
by the age of 16 years (Fig. 1, Table III).9,91 Similarly,
anti-HAV antibody was detected in around 97% of
TABLE II. Hepatitis A virus antibody (anti-HAV) prevalence
rates among children
Anti-HAV positivity n (%)
|Age <5 years
||Age >5 years
|Dhawan et al.25
|Mall et al.23
|Acharya et al.9
TABLE III. Age-wise prevalence
of hepatitis A virus antibody (anti-HAV) in schoolchildren
in New Delhi9
|Age group (years)
||Anti-HAV positivity (%)
Fig 1. Age-stratified
prevalence of anti-HAV antibody among Indian schoolchildren
aged 4 to 18 years.9,91
Indian patients with
chronic liver disease.9,92 A
large study found no increase in the number of cases of acute
A (Fig. 2) or ALF
due to hepatitis A over a decade (Fig. 3).9
Fig 2. Number of patients
with acute hepatitis A (HAV) among those with acute viral hepatitis
Fig 3. Number of patients
with acute hepatitis A (HAV) among those with acute liver failure
(ALF) at a tertiary care hospital in India.9,91
The preventive strategies for HAV infection are similar to
those for HEV infection. However, unlike HEV, an effective
live, attenuated HAV vaccine93 is
commercially available in India and is being marketed aggressively.
it provides seroconversion rates of >90% and nearly 100%
after one and two doses (4–6 weeks apart), respectively.93,94
The extremely high prevalence of anti-HAV
antibody in the general population in India implies that
a mass immunization
against HAV would not be cost-effective. As the anti-HAV
test is cheaper than the HAV vaccine, it may be cost-effective
to do this test before administering the HAV
HEPATITIS B VIRUS (HBV)
Chronic HBV infection, a major global public health problem,
can lead to the development of liver cirrhosis and liver
cancer. Despite the presence of a substantial HBV disease
has not yet embarked on a national programme for the control
of this infection.
In India, the frequency of HBV infection has been studied
in 4 distinct population groups: (i) blood donors and pregnant
(ii) general population, (iii) subjects at high risk of acquiring
HBV infection, and (iv) patients with various liver diseases.
Blood donors. Table IV shows the HBsAg positivity rates among
Indian blood donors. The studies done in the 1970s used less
sensitive techniques such as gel diffusion, immuno-electrophoresis
or counter-immunoelectrophoresis, whereas those in 1990s
used more sensitive techniques such as EIAs or reverse passive
assays (RPHA). Despite the variation in tests used, hepatitis
B surface antigen (HBsAg) prevalence
TABLE IV. Prevalence of hepatitis B surface antigen (HBsAg)
positivity among the normal population
|Hillis et al. (1970)95
et al. (1973)96
Pal et al. (1973)97
Sama et al. (1973)98
Shanmugham et al. (1973)99
Dutta et al. (1972)100
Singhvi et al. (1990)101
Elavia et al. (1991)102
Irshad et al. (1994)103
Nijhawan et al. (1997)104
Choudhury et al. (2005)36
TABLE V. Hepatitis B surface
(HBsAg) and e (HBeAg) antigen prevalence among pregnant women
||HBsAg positivity (%)
Among HBsAg-positive patients
|HBeAg positivity (%)
||Anti-HBe positivity (%)
|Tandon et al. (1986)30
Nayak et al. (1987)105
Sehgal et al. (1992)106
Gill et al. (1995)107
Prakash et al. (1998)108
na not available
rates were 1%–4.2% in these studies. The HBsAg positivity
rates among pregnant women have also been similar (Table V).30,105–108 Whether
or not these rates are representative of those in the general
population continues to be debated. Further, all these
studies were point prevalence studies and did not meet the defining
criterion for HBsAg carrier—HBsAg positivity lasting for
at least 6 months.109 In a recent
report a correction was applied to the available HBsAg positivity
rates for false positivity
and false negativity of HBsAg tests and it was calculated that
the true HBsAg positivity rate may lie between 1% and 2%.110 However,
based on studies in blood donors and the general population,
we still believe that the prevalence rate for HBsAg lies between
2% and 4%. Moreover, 70% of the Indian population lives in rural
areas and one large study that systematically sampled a rural
population reported the HBsAg prevalence rate to be 2.97%.36
General population. Community data on HBsAg and antibody
to hepatitis B surface antigen (anti-HBs) positivity in the Indian population
are scarce. In 2 such recent studies that included about 7653
and 730 healthy individuals, the HBsAg positivity rate was reported
to be 2.9% and 2.1%, respectively, and that of antibody to hepatitis
B core antigen (anti-HBc) was reported to be 19.5% and 16.5%,
most studies among blood donors, pregnant women and the general
indicate an HBsAg carrier frequency
of 2%–4% and anti-HBs positivity of around 18%–20%.
Indian studies on age-stratified HBsAg positivity rates indicate
that a carrier rate of 2%–3% is reached by the age of 5
years112 and does not increase further
with age. However, the anti-HBs positivity rates continue to
increase with age (Fig.
4).29 This indicates that the HBV
carrier state is acquired mainly in early childhood and that
control strategies against chronic
HBV infection should focus on children.
High risk populations. The high risk groups reported from India
include (i) individuals with repeated parenteral exposure such
as multitransfused patients with thalassaemia/haemophilia, patients
undergoing haemodialysis and professional sex workers, (ii) professional
blood donors, (iii) healthcare workers with occupational exposure,
(iv) household contacts of individuals with chronic HBV infection,
and (v) individuals living in specific hyperendemic geographical
In patients with thalassaemia and haemophilia, HBsAg and anti-HBs
positivity rates of 6%–60% and 29%–70%, respectively,
have been reported (Table VI).113–122 HBsAg
positivity among professional blood donors has been reported
to be 15%–20%.123,124 However,
among healthcare workers, HBsAg positivity has been reported
to be 1.7%–40%.125,126 Recently,
2 studies have shown that within India hyperendemic regions for
may exist—HBsAg positivity of 23.3% among the tribal population
in the Andaman and Nicobar Islands,127 and
5.2% among the Lambada
TABLE VI. Prevalence (%) of serological markers of hepatitis
B and C (HCV) virus in multitransfused populations
Bhattacharya et al
Amarapurkar et al.
Choudhry et al.
of 44% was observed in the donor blood HBsAg hepatitis B surface
antigen anti-HBs antibody to hepatitis B surface antigen anti-HBc
antibody to hepatitis B core antigen tribe
of Andhra Pradesh.128 Further
studies to identify the route of transmission and risk factors
for acquisition of
HBV infection in these areas may help in developing appropriate
Household contacts, particularly spouses and children of
persons with chronic HBV infection, are known to be at an
increased risk of acquiring HBV infection.129,130 Therefore,
such household contacts need to be screened for HBV infection
and preventive steps taken if they are not already infected.
A substantial proportion of patients with various acute and
chronic liver diseases have HBV infection—12.5%–21%
of those with acute hepatitis22,95–97,100 (Table
VII), 40% with subacute hepatic failure,131 11%–27% with
acute liver failure,20 35%–60% with cirrhosis of the
60%–80% with primary liver cell
HBV carriers may also have superinfection with another virus
such as HEV leading to severe liver disease.50,51
As mentioned previously, the HBV carrier pool in India reaches
a plateau by the age of 5 years.29,112 The
predominant route of transmission among children is horizontal
during the preschool
and early school years.112 A
well-designed study by Nayak et al.105 which included
8575 pregnant women found 3.7% of them to be HBsAg positive.
Of these, only 7.8% were HBeAg
positive; a frequency much lower than that in Southeast Asian
countries but similar to that in sub-Saharan Africa where
horizontal HBV transmission occurs. The HBV infection rate
was 19% among children of HBsAg-positive mothers compared
with 3% among those of HBsAg-negative mothers. Among children
born to HBsAg-positive mothers, the rate of HBV infection
was 87.5% among the offspring of hepatitis B e antigen (HBeAg)-positive
mothers and <10% among children of HBeAg-negative mothers.
Fig 4. Age-stratified
prevalence of hepatitis B surface antigen (HBsAg) and antibody
to hepatitis B surface antigen (anti-HBs) in India.29,112
TABLE VII. Prevalence of hepatitis B virus infection among
patients with acute viral hepatitis
|Hillis et al. (1970)95
|Sama et al. (1973)96
|Dutta et al. (1972)100
|Pal et al. (1973)97
|Chadha et al. (2003) 22
data suggest that in the general population about 75% of carriers
acquire the infection by horizontal spread during early childhood
and the remaining acquire it by vertical (mother-to-child)
transmission.28 A multicentric
a WHO collaborative study29 evaluating
age-stratified HBsAg prevalence rates as
well as studies assessing HBV infection rates among household
contacts129,130 indicate that
horizontal spread of infection may be the predominant route
of transmission responsible for
the HBV carrier state.
The introduction of mandatory screening of blood donors for HBsAg
in India during the 1990s has resulted in a marked decrease in
post-transfusion HBV infection.38–40 However,
despite donor screening for HBsAg, about 25% of post-transfusion
is still due to HBV.39,134 A
recent report indicated that about 25% of voluntary blood donors
were HBsAg negative but anti-HBc
positive were HBV DNA positive.135 It
may be possible to prevent post-transfusion hepatitis B using
anti-HBc screening of blood
donors. However, due to the shortage of donated blood in India,
discarding anti-HBc positive blood may be difficult. To develop
a rational policy in this regard, one would need more data on
the frequency of post-transfusion HBV infection following HBsAg
donor screening, the proportion likely to be prevented
by discarding anti-HBc positive blood, and the effect on the
availability of blood.
Another possible route of transmission of HBV infection is the
use of non-disposable glass syringes in rural India.136,137 Data
on the importance of other routes of HBV transmission in India
such as tattooing, visits to barbers, body piercing practices
and homosexual behaviour are scarce.
Immune pressure leads to selection of various mutant HBV strains
in asymptomatic HBV carriers as well as persons with HBV-associated
liver disease. Core promoter (CP) and precore (PC) mutants of
HBV are unable to produce HBeAg and have been described predominantly
among patients with HBeAg-negative, chronic hepatitis B (CH-B).
Though data on HBV mutants in India are limited, these may account
for 15%–20% of patients
The classical HBsAg
mutation (G145A) has been identified among patients with CH-B
in one report.138 However,
HBV DNA-positive (occult HBV infection) patients with CLD have
also been reported. In a recent study, about 10% of patients
with HBsAg-negative CLD had HBV DNA in their sera.140 These
patients were also anti-HBc positive. Further, 25% of HBsAg-negative,
anti-HBc positive donors had HBV DNA in their sera.135 The
frequency of HBV transmission, disease occurrence, chronicity
and the natural
course of such HBV mutants
(HBsAg negative) are not yet known.
HBV genotypes A and D appear to be the most predominant among
Indian patients with HBV-induced acute and chronic liver diseases.141–143 Further,
the prevalence in India of genotype A (Aa) has been found to
be different from that in Europe (Ae).142 HBsAg
carriers with the Aa genotype are less likely to be HBeAg positive
(31% v. 49%, p=0.033) and have significantly lower HBV
DNA levels regardless of the HBeAg status (3.46 v. 6.09 log copies/ml;
than Ae infected individuals. The relevance of these genotypes
to disease manifestations, natural course, transmission efficiency
and response to therapy needs further evaluation.
Treatment: Indian scenario
Currently, it is difficult to treat patients with cirrhosis of
the liver due to HBV infection. Treatment is directed predominantly
at patients with CH-B. In these patients, suppression of HBV
replication as evidenced by HBeAg seroconversion to presence
of antibody to hepatitis B e entigen (anti-HBe), loss or reduction
of HBV DNA to levels <105 copies/ml, and normalization of
alanine aminotransferase (ALT) are associated with a survival
benefit and prevention of serious complications such as cirrhosis
and primary liver cancer.144,145 Whereas
HBeAg-positive CH-B is more amenable to therapy, HBeAg-negative
CH-B (CP/PC HBV mutants)
is difficult to treat.144–146 Similarly,
CH-B patients with associated chronic renal failure, liver or
or HCV or HIV infection are difficult to treat,144,145 with
response rates of only 10%–15%, compared with 30%–50% in other
Interferon-a 2b, interferon-a 2a, pegylated interferons and nucleoside
analogues such as lamivudine, adefovir, entecavir and tenofovir
have been used to treat HBV infection.145,147–150 The
results of these therapies have been reported predominantly from
and Southeast Asian countries. Unfortunately, therapeutic data
from the Indian subcontinent are scarce.
Two published trials from India, using low dose interferon-a
2b (3 million units thrice weekly for 6 months) have reported
sustained virological response (SVR) in more than 60% of treated
patients.151,152 However, the results
of interferon therapy have been unsatisfactory among HBeAg-negative
patients; despite achieving
an optimal decrease in HBV DNA load, these patients relapse frequently
(80%) after the drug is stopped.152
Using a Markov transitional probability mathematical model, Aggarwal
et al. showed that the cost incurred to gain 1 year
of life using interferon treatment was Rs 432 000. The cost for
life-year gained was Rs 275 000. These estimates were 20.5 and
13.1 times greater than the per capita GNP of the Indian population.
They, therefore, recommended that interferon treatment should
not be supported from public funds.153
Lamivudine, a nucleoside analogue, has been reported to be either
as effective or more effective than interferon for the treatment
of HBeAg-positive CH-B.145,147 However,
long term use of this drug is associated with the emergence of
HBV mutants (YMDD mutants).145,147 Unfortunately,
no head-to-head comparison of lamivudine and interferon therapy
in patients with
CH-B has been done. Studies on the efficacy of lamivudine therapy
among Indian patients are also scarce. At our institution, a
recent prospective study showed that 3-year therapy with lamivudine
had a significantly better response (54%) than 4–6 months
of interferon treatment among HBeAg-positive patients, whereas
both the drugs had similar efficacy among HBeAg-negative patients
(<20% response).154 Phyllanthus
amarus, a plant product, has been shown to suppress HBV replication.155 However,
except for one Indian study,156 other
failed to establish a definite therapeutic role for this product
Studies on treatment with pegylated interferon and adefovir among
Indian patients are limited.159,160
China and Southeast Asia, transmission of HBV infection associated
with the development of chronic HBV infection is predominantly
vertical; in the West it occurs in adults due to intravenous
drug abuse. In India it is due to horizontal transmission in
childhood. The HBV genotypes in China and Southeast Asia are
predominantly B and C, which are more frequently associated with
liver cancer and progressive liver disease,161,162 whereas
in India and the West the prevalent genotypes are A and D.141–143 Further,
recent studies have shown that the subtype of genotype A prevalent
in India (Aa) has a lower HBV replication rate and
lower HBV DNA load than that of the genotype A prevalent in the
West.142 These differences may explain
the better response rates observed in a few available Indian
studies. Thus, it seems that
HBV infection in India has characteristics that are distinct
from the infection seen in Southeast Asia, China and western
Epidemiology and prevention strategies in India
HBV vaccination is a cost-effective method of preventing mortality
due to such diseases.163,164 According
to the Yaounde Declaration of WHO, to which India is a signatory,
by 2000165 all countries
in the world would adopt universal HBV vaccination. Universal
HBV vaccination has already been documented to decrease the carrier
frequency and disease burden in Taiwan.166
From the epidemiological data, it is evident that HBV causes
a considerable disease burden in India with substantial loss
of human life. Therefore, India requires an appropriate preventive
strategy to target identified population groups. However, there
are several gaps in the available epidemiological data that need
to be addressed before a comprehensive policy can be devised
for control of HBV infection in India.
The population prevalence of HBsAg positivity is about 4% as
estimated from data derived predominantly from select populations
such as blood donors and pregnant women. Some skeptics argue
that this rate is likely to be about 1%–2%. Large, community-based
prevalence studies are needed to resolve this issue. However,
despite conflicting views on HBV carrier frequency, it is clear
that immunization against HBV remains the most cost-effective
strategy for India.28,163,164 In
India, HBV is believed to have a predominantly horizontal transmission,
based on a large study
in which the HBeAg positivity rate among HBsAg-positive pregnant
women was reported to be <10%.105 However,
some small studies have reported higher HBeAg positivity rates
of up to 48%.106 In
a multicentric cross-sectional study from India,112 the
carrier rates were similar among children aged <1, 1–5 and >5
years. Another multicentric study29 also
suggested that horizontal transmission may not have a major role
to play. There is a clear
need for large studies on age-specific HBV seroprevalence rates
in India. Despite the lack of such data, it is clear that childhood
infection is the major cause of the HBV carrier state (Fig. 5)
and universal childhood HBV immunization will be the most effective
HBV control strategy in India. However, if vertical transmission
is dominant, then it may be important to administer the first
dose of HBV vaccine at birth.
Inclusion of the HBV vaccine in the universal immunization schedule
is likely to be the most cost-effective strategy to decrease
HBV carrier frequency and disease burden in India. Aggarwal et al. have reported that universal immunization would be more
cost-effective than selective immunization.163 While
adopting universal immunization, efforts will be needed to ensure
coverage rate. In countries where HBV vaccination has successfully
decreased the carrier frequency and disease burden, at least
80% of the target population has been vaccinated.166 ‘Catch
up’ immunization of adolescents is unlikely to be cost-effective.
More data on this are needed from India before any recommendation
can be made.
Fig 5. Percentage of people
who would develop hepatitis B carrier state as a function of
the age at which they acquire
Quality control of donor screening in India is another area where
more efforts are needed. In a study from New Delhi, 6% of HBsAg-negative
units of blood from various blood banks in Delhi were found to
be HBsAg positive on re-testing using a sensitive micro-ELISA
Awareness campaigns on the routes of community-acquired infection
and on steps to prevent household and nosocomial spread of HBV
infection need to be launched. All household contacts and medical/paramedical
staff should be vaccinated against HBV. High risk groups need
to be identified, screened for HBsAg and vaccinated against HBV.
While adopting universal immunization, for a successful HBV control
programme it is necessary to evaluate the durability of protection,
appearance of vaccine escape mutants and compliance of the population.
Unless 80% of the target population is vaccinated, the impact
on horizontal transmission may be obtunded (in countries where
HBV vaccination has decreased the carrier frequency and disease
burden, at least 80% of the target population has been vaccinated).166
The dynamics of post-needlestick HBV transmission are not available
from India. Therefore, post-needlestick injuries should be dealt
with as anywhere else, i.e. with passive and active immunization
combining hepatitis B immunoglobulin and HBV vaccine.167
HEPATITIS C VIRUS (HCV)
HCV has a single-stranded, positive-sense, RNA genome, approximately
9600 nucleotides in length.168 Its
genome has an
untranslated region (UTR)
at each end with one ORF located in between, which encodes
for a nearly 3000 amino acid long polyprotein.169 The
binds with the host cell ribosome to begin the process of translation,
whereas the 3'-UTR is necessary for viral replication.
The two UTRs represent the most conserved regions of the viral
genome.169 HCV RNA replication
occurs in the cytoplasm, during which a mixed population of
RNA sequences (quasispecies) are
produced. Over time, natural selection occurs under the influence
of host immune pressure, leading to gradual drift of the HCV
genome and evolution of HCV genotypes, which can vary by up
to 35% in their nucleotide sequences. Till now, 11 genotypes
and 70 subgenotypes have been described; of these, genotypes
1–6 are the major ones. Genotypes 1 and
4 are associated with resistance to therapy,161 whereas
genotypes 2, 3, 5 and 6 are more amenable to treatment.170,171 The
genotypes 1 and 4 are prevalent in Japan and the USA; genotype
3 is more
common in India.172–178
HCV causes both acute and chronic liver disease, including
liver cancer.179 Unlike
HBV infection, which becomes chronic in <5%
of infected immunocompetent adults, up to 80% of adults with
HCV infection develop chronic viraemia.179 However,
only a quarter of chronically infected patients develop chronic
quarter of whom progress to cirrhosis.179 Among
those who develop cirrhosis, 1%–4% progress to liver cancer
annually (Fig. 6).179 The
rate of progression of HCV-related liver disease is slow and
it takes 25–30 years for clinically important
liver disease to develop.179 However,
progression may be faster in immuno-compromised persons, alcoholics
and obese people.179
HCV infection is usually diagnosed by detecting hepatitis C
virus antibody (anti-HCV) (ELISA/RIBA) and/or HCV RNA (RT-PCR)
in the serum.180 Data are available
on the prevalence of HCV infection in India among blood donors,
the general community,
high risk groups such as multitransfused patients with thalassaemia
and healthcare workers. Reports are also available on the disease
burden due to HCV infection.
Using third-generation ELISA, the prevalence of anti-HCV antibody
among voluntary or replacement blood donors has been reported
from India in 5 large studies that included 57 671 blood donors31,32,181–183 and
has ranged from 0.7% to 1.8% (Table VIII). Overall, 902 donors
(1.5%) were found to be anti-HCV positive.
Among similar populations
in the USA and Japan, the prevalence rate is about the same.184 However,
the frequency of HCV viraemia (detectable HCV RNA) in the Indian
population has not been reported. In contrast
to developed countries where HCV is the aetiological agent
in 30%–50% of CLD, in India, of patients attending a
large tertiary care hospital, HCV infection was the cause of
CLD in only 14%.31 Long term follow up studies on these anti-HCV
positive persons are not available.
The anti-HCV prevalence rate in blood donors
may not be representative of the situation in the general population.
Two studies have
evaluated the community prevalence of HCV in India. Chadha et
1054 healthy volunteers in 4 villages of Bohr Taluka in Pune
and found only
1 person to be positive for anti-HCV
as well as HCV RNA. In another study, Chowdhury et al.35 used
a systematic sampling procedure to select 3579 individuals from
among 10 737 inhabitants of 9 villages in the Birbhum district
of West Bengal; of these, 2973 individuals (83%) could be screened
for anti-HCV antibody using a sensitive third-generation commercial
ELISA. The frequency of anti-HCV in this population was 0.87%
(26 of 2973); 81% (21 of 26) of those who were anti-HCV positive
were viraemic (HCV RNA positive). Further, only 0.3% of children
(2 of 646) below 10 years of age were anti-HCV positive, and
the positivity rate increased with age (Table IX), indicating
that HCV infection in India is a disease of adults. These data
suggest that about 10 million Indians are anti-HCV positive and
5 million of them may be viraemic. Of these,
nearly 25%, i.e. over 1 million, may develop CLD within 2 decades
and 1%–4% of them may develop liver cancer. Treatment of
such a large number of persons with CLD would need a massive
High risk groups
Since HCV is transmitted parenterally, people who have received
multiple transfusions of blood and blood products such as those
with thalassaemia and haemophilia, patients with renal failure
undergoing haemodialysis, patients who have had a renal transplant
and healthcare workers are at an increased risk of contracting
HCV infection.184 The point prevalence
of HBV and HCV markers
Arankalle et al.
Panigrahi et al.
*RIBA-III test used. All
others used ELISA-III
TABLE IX. Age distribution of hepatitis C virus antibody (anti-HCV)
positivity in India35
individuals (Table VI) has been reported to be very high (11%–62%).
However, these studies were conducted before 2002 when mandatory
screening of blood donors for anti-HCV was introduced in India.
Thus, the current rates may be lower. For instance, among patients
undergoing haemodialysis, the anti-HCV rates (initially 24%–28%)
have come down to about 4%186 with
the use of dedicated haemodialysis units for HCV-infected patients
and screening of blood donors.
The point prevalence of anti-HCV among healthcare
workers in India is similar to the general population (0%–1.5%).182,187–189 However,
one report from Rajasthan showed an anti-HCV positivity rate
of 5.4% among dentists.189 Larger
studies are needed among healthcare workers of various categories,
as they may be transmitting
HCV infection to their patients. A report from Kolkata has estimated
the frequency of seroconversion to anti-HCV following a needlestick
injury to be 9% (6 of 68).190 In
India, anti-HCV prevalence data have not been reported among
intravenous drug abusers, sex workers and homosexuals.
HCV infection is transmitted predominantly by the parenteral
route. Sexual and vertical transmission is infrequent except
when HIV co-infection is present.184 In
India, HCV infection is acquired most often through transfusion
of blood or blood
infection is another major route.35
In a report from northern India, about half
the patients with chronic hepatitis C (CH-C) had received blood
study from Vellore in southern India reported that 61% of 90
patients with chronic HCV infection had acquired the infection
following blood transfusion.177 In
another report, 7% of patients who had undergone coronary artery
bypass surgery and transfusion
developed post-transfusion hepatitis; 80% of them had evidence
of HCV infection.39 In a community
study, 81% of anti-HCV positive individuals reported having received
injections using unsterile
glass syringes and none had received a transfusion.35 The
presence of HCV infection was associated with the use of glass
with a crude odds ratio of 3.8, but not with age, sex, educational
status, socioeconomic status, shaving by community barber, transfusion,
tattooing or dental therapy.35
A study from Pune did not detect anti-HCV in any of 430 pregnant
women or children <5 years of age (n=86).182 In
a recent survey of 5–17-year-old schoolchildren (n=1900) in Delhi, none
was positive for anti-HCV.9 These
figures suggest that sexual and vertical transmission of HCV
is negligible in India. Recently,
a study from Punjab reported an anti-HCV positivity rate of 16%
among household contacts of index cases.191 However,
in this study only 50% of household contacts had been evaluated.
there is a need for further studies on this subject.
TABLE X. Genotypic distribution of HCV in India
Valliammai et al.
5' UTR, NS5
Panigrahi et al.
Amarapurkar et al.
Raghuraman et al. (2003)177
Type-specific primers, PCR
Chowdhury et al. (2003)35
Type-specific primers, PCR
* 11 patients could not
be genotyped UTR untranslated region NS5 non-structural region
5 PCR polymerase chain reaction
In India, several traditional body-piercing practices are prevalent
in rural and tribal populations. However, data on the prevalence
of anti-HCV in these select populations are lacking.
Certain viral characteristics have been associated with the
progression and severity of HCV-related liver disease and therapeutic
response. Genotype 1 HCV infection is resistant to treatment
and is associated with progressive disease.192 A
viral load >3.5
million copies/ml has been associated with a poor therapeutic
response;192 however, a relationship
with disease severity has not been established.192
Several published reports from India describe the relative
frequency of various HCV genotypes (Table X),35,172–177 in
the northern172,173,176 and southern175,177 parts.
In these studies, genotype 3 was found in 54%–90% of HCV-infected
patients; overall, 60% of patients had genotype 3, 25% had
genotype 1, 8% had genotype 2 and 2% had genotype 4 infection.
HCV genotype 1 infection was more frequent in southern India
than in the rest of the country.
Data on viral load estimation in Indian patients with HCV infection
are scarce. In a study from southern India (n=73), the mean
HCV viral load using the commercial Amplicor assay was 106 copies/ml
(range 1.2×105–2.5×107 copies/ml);177 the
viral load was higher in patients with genotype 1 infection
(1.2×106 copies/ml) than
in those with genotype 3 (5.4×105 copies/ml;
In contrast, in a study from northern India (n=65)173 based
on competitive reverse-transcriptase PCR, the mean (SD) viral
load was much higher, being 24.1 (12.5)×108 copies/ml
(range 0.5×106–25×108 copies/ml).
Also, 54% of the patients had a viral load >5×106 copies
per ml. Despite the high viral load in these patients, SVR
and ribavirin treatment was achieved in 75% of cases. None
of the Indian studies evaluated the relationship between viral
load, genotype and disease characteristics.
Of patients with CLD, HCV is the aetiological agent in 14%–26%31,132,133,193,194 and
14%–20% of patients with hepatocellular cancer in
Among 247 patients with sporadic acute viral hepatitis, 9%
had HCV viraemia.31 Similarly,
HCV RNA could be detected in 7 (14%) of 50 patients with ALF;195 5
of these 7 patients had associated HBV and 2 had associated
acute HEV infection. HCV
is rare in ALF in other parts of the world except in Japan
HCV infection has been documented in about 40% of patients.196
Extrahepatic manifestations of HCV such as cryoglobulinaemia,
membranoproliferative glomerulonephritis, porphyria cutanea
tarda, sicca syndrome, lichen planus, etc. have been reported
infrequently from India. Agarwal et al. failed to detect cryo-
TABLEXI. Prevalence rates (%) of hepatitis D virus antibody
among patients with liver disease, healthcare workers (HCW)
and patients with chronic renal failure (CRF) in India
Amarapurkar et al
Arankalle et al.
hepatitis B virus nr not reported CLD chronic liver disease
HCC hepatocellular cancer
globulinaemia among 37 patients with CH-C and HCV infection
among 53 patients of membranoproliferative glomerulonephritis.197
We believe that the magnitude of HCV infection among patients
with CLD is likely to rise during the coming years. Screening
for anti-HCV in blood banks in India has recently been introduced
and all those individuals who have been exposed before this
time will develop the disease in the next 15–30 years
and we can expect an epidemic of CH-C and its complications
over the next 2 decades.
Combination therapy with pegylated interferon a 2b (1.5 mg/kg/week)
or a 2a (180 mg/week) with ribavirin (10.6 mg/kg/day) is recommended
for patients with CH-C and compensated cirrhosis of the liver
(Child A).192 The recommended
duration of this treatment is 12 months for genotype 1 infection,
and 6 months for genotype
2 or 3 infection. In the West, with this therapy, SVR rates
of 40% and 80% have been reported among patients with HCV genotype
1, and HCV genotypes 2 and 3, respectively.192
Hazari et al.173 have
recently reported an SVR of >90% in
India with a combination of interferon a 2b (3 million units/day)
and ribavirin (10.6 mg/kg/day), and of 64% with a combination
of interferon a 2b (3 million units three times a
week) and ribavirin (10.6 mg/kg/day). Another study from India
an SVR of 57% with the latter regimen.174 Due
to the high frequency of genotypes 2 and 3 in India, a 6-month
course of daily interferon and ribavirin in adequate doses
would achieve an excellent SVR. In a recently completed multicentric
study conducted by the Indian Council of Medical Research (unpublished),
using interferon a 2b (3 million units/day for 6 months) combined
with either ribavirin (SVR 70%) or glycyrrhizin (SVR 56%) satisfactory
results were obtained. Daily interferon with ribavirin for
6 months is cheaper by about Rs 150 000 than pegylated interferon
and ribavirin for the same duration.173
HEPATITIS D VIRUS (HDV)
HDV is a small RNA virus, 36 nm in diameter, which shares several
properties with defective plant RNA viruses, including viroids
and satellite RNAs.198 The HDV
genome encodes for a protein, the hepatitis D antigen (HDAg),
which together with the viral
RNA requires encapsidation with the HBsAg.199 Therefore,
HBV infection is mandatory for the existence of a replicative
HDV infection is common in Italy and Eastern Europe, South America,
the Amazon basin and in the Mediterranean region; about 15 million
persons are infected with HDV globally.200 The
infection is transmitted among HBV-infected persons by the parenteral
route.201 HDV co-infection
(simultaneous infection of HBV and HDV) and HDV superinfection
(HDV infection superimposed on pre-existing chronic HBV infection)
are both associated with progressive and severe liver disease.200,201 During
HDV infection, IgM anti-HDV, IgG anti-HDV and HDV RNA can be
detected in serum, and HDAg can be detected in the liver
tissue.202 HDV co-infection and
superinfection are diagnosed based on the presence and absence,
respectively, of IgM anti-HBc
in the presence of one of the HDV markers.200,202
Table XI shows that HDV superinfection and co-infection are rather
infrequent in India. Initial studies from Chandigarh, 203 Delhi,204–206,
Mumbai207 and Kashmir210 reported
a high prevalence of anti-HDV among patients with acute and chronic
hepatitis, fulminant hepatitis
and subacute liver failure. Recent studies207,209 have
shown lower prevalence rates in healthy donors and in patients
severe liver disease.
Khuroo et al.210 reported
in 1988 an epidemic of HDV from southern Kashmir, in which 35 of the 51 icteric
patients were HBV carriers.
Of the 24 HBV carriers who were tested for anti-HDV, 22 tested
positive. The authors could not provide any explanation for the
mode of spread of HDV in this epidemic.
Thus, both HDV superinfection and co-infection do occur in India
though at a relatively low rate, and may be the cause of severe
liver disease in a subset of patients.
OTHER RARE HEPATITIS VIRUSES
Hepatitis G virus (HGV), Sen virus and TT virus (TTV) are candidate
hepatitis viruses. Although these agents are transmitted through
blood transfusion, there is little evidence to associate these
with liver disease.
In India, Kar et al. showed HGV RNA in 4% of 50 healthy controls
and 47% of 46 healthy commercial blood donors.211 Panigrahi
et al.212 reported
HGV viraemia in 39.7% of multi-transfused thalassaemic
children; sequence analysis of 11 of their HGV isolates showed
81.3%–94.5% homology to isolates from the rest of the world.
Kapoor et al.213 could
detect HGV RNA in 5/35 (14.3%) patients with acute viral hepatitis
and in 4/15 (26.6%) patients with
ALF; however, its relation to disease was doubtful, because HGV
RNA persisted even 6 months after full clinical and biochemical
VIRAL HEPATITIS AND HEPATOCELLULAR CANCER
Globally, hepatocellular cancer (HCC) is the fourth most common
cause of cancer-associated deaths.214 About
80% of these liver cancers as well as mortality related to the
disease occurs in
Asia and Africa.214 Five-year survival
among patients with symptomatic HCC is less than 5%.215 About 60%–80% of HCC throughout
the world are associated with chronic HBV or HCV infections and
a similar proportion have underlying cirrhosis.215
Information on HCC in India is scarce and comes from three
main sources:216 (i) autopsy data, (ii) cancer registry
data, and (iii) published
reports. Autopsy studies have reported the preva-lence
of HCC to be 0.2%–1.6%,216 being higher in southern India
(1%–2%) than in other parts of India (<0.2%).216 However,
in contrast to autopsy studies, cancer registry data revealed
similar prevalence of HCC throughout the country, which
is lower than that for China, Southeast Asia and Japan but higher
than that for the USA, UK and Europe.216 Based
on the population registry data, the mean incidence of HCC per
100 000 population
was reported to be 2.77 and 1.28 for men and women, respectively.216 The
incidence among the immigrant populations in Singapore and Australia,
as documented in cancer registries in these countries,
also indicate that Indians are less prone to develop HCC than
Chinese or Malays (Table XII).
However, there is a dearth of cohort studies among Indian patients
who are at a high risk to develop HCC, such as those with HBV-
and HCV-induced cirrhosis. In an ongoing study (unpublished),
9 of 194 cirrhotics during a 3-year follow up period developed
HCC—an annual incidence of 1.63 among these cirrhotics.217
Globally, HBV and HCV are the major aetiological agents associated
with HCC.215 In India, 36%–74% of HCC were associated with
HBV and about 30% with HCV infection.216 In
a recent large series of 215 patients with HCC from India,218 55%
TABLEXII. Age-standardized incidence of hepatocellular cancer
per 100 000 population216
patients had HBV infection,
9% had HCV infection and 6% were alcoholics. More than one
aetiological factor was present in 10% of patients, whereas
in 26% no underlying cause was found. Only 69 (32%) of these
215 patients could be provided curative (surgery, radiofrequency
ablation or percutaneous acetic acid injection) or palliative
(transarterial chemoembolization or radioisotope embolization)
therapy. The remaining patients had advanced disease with portal
vein thrombosis or extrahepatic spread.
Therefore, the incidence of HCC in India seems
to be lower than that in other Asian and African countries. The
reason for this
remains unclear but may be related either to host factors (genetic
predisposition) or to viral factors (HBV genotype, viral load,
etc.). In India, genotypes A and D of HBV and genotypes 2 and
3 of HCV are prevalent. These prevalent genotypes presumably
are less virulent than the genotypes B and C of HBV or genotypes
1 and 4 of HCV, which are more prevalent in countries with a
higher incidence of HCC such as Japan, Taiwan and China. Control
of HBV and HCV infections should lead to a reduced incidence
Viral hepatitis is a major public health problem in India, which
is hyperendemic for HAV and HEV. Seroprevalence studies reveal
that 90%–100% of the population acquires anti-HAV antibody
and becomes immune by adolescence. Many epidemics of HEV have
been reported from India. HAV related liver disease is uncommon
in India and occurs mainly in children. HEV is also the major
cause of sporadic adult acute viral hepatitis and ALF. Pregnant
women and patients with CLD constitute the high risk groups to
contract HEV infection, and HEV-induced mortality among them
is substantial, which underlines the need for preventive measures
for such groups. Children with HAV and HEV coinfection are prone
to develop ALF.
India has intermediate HBV endemicity, with a carrier frequency
of 2%–4%. HBV is the major cause of CLD and HCC. Chronic
HBV infection in India is acquired in childhood, presumably before
5 years of age, through horizontal transmission. Vertical transmission
of HBV in India is considered to be infrequent. Inclusion of
HBV vaccination in the expanded programme of immunization is
essential to reduce the HBV carrier frequency and disease burden.
HBV genotypes A and D are prevalent in India, which are similar
to the HBV genotypes in the West. HCV infection in India has
a population prevalence of around 1%, and occurs predominantly
through transfusion and the use of unsterile glass syringes.
HCV genotypes 3 and 2 are prevalent in 60%–80% of the population
and they respond well to a combination of interferon and ribavirin.
About 10%–15% of CLD and HCC are associated with HCV infection
in India. HCV infection is also a major cause of post-transfusion
hepatitis. HDV infection is infrequent in India and is present
about 5%–10% of patients with HBV-related liver disease.
HCC appears to be less common in India than would be expected
from the prevalence rates of HBV and HCV.
The high disease burden of viral hepatitis and related CLD in
India, calls for the setting up of a hepatitis registry and formulation
of government-supported prevention and control strategies.
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India Institute of Medical Sciences, Ansari Nagar, New
Delhi 110029, India
S. K. ACHARYA, KAUSHAL MADAN Department of Gastroenterology
S. DATTAGUPTA, S. K. PANDA Department of Pathology
Correspondence to S. K. ACHARYA; firstname.lastname@example.org