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REVIEW ARTICLE

INCIDENTALLY DETECTED ASYMPTOMATIC

HBSAG POSITIVE SUBJECTS

Vinod Kumar Dixit, Sushant Kumar Jena

Department of Gastroenterology, Institute of Medical Sciences,
Banaras Hindu University, Varanasi - 221 005, India

Correspondence: V. K. Dixit, Department of Gastroenterology, Institute of

Medical Sciences, Banaras Hindu University, Varanasi - 221 005, India.
E-mail: drvkdixit@gmail.com
DOI: 10.4103/0972-9747.58808

ABSTRACT
Hepatitis B virus [HBV] affects almost five per cent of the
total population worldwide and majority of the affected population
are detected incidentally without any symptoms. This mammoth
pool of Hepatitis B virus infected population needs to be properly
assessed and followed up to minimize morbidity and mortality in
them. This article reviews literature related to this subset of HBV
patients and attempts to provide a rational guideline to approach
and manage them.
Keywords: Chronic hepatitis B, Hepatitis B virus, incidentally
detected asymptomatic HBsAg positive subjects, HBeAg, HBsAg,
IDAHS

INTRODUCTION
Hepatitis B virus (HBV) is a small DNA containing virus
that may cause persistent infection of the liver. Approximately 400
million people comprising five per cent of the total population are
affected worldwide with chronic hepatitis B virus infection, with
India having about 45 million of them. Chronic HBV infection is
a dynamic process with a wide spectrum of afflictions - on one
extreme is the incidentally detected asymptomatic HBsAg positive

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subject (IDAHS) with no clinical evidence of liver disease, the other

extreme being end stage cirrhosis and hepatocellular carcinoma
(HCC). For many decades these IDAHS were considered to have a
benign non progressive infection and referred to as inactive HBsAg
carrier. The prognosis of the inactive HBsAg carrier is considered
primarily benign in the West, where majority of HBV infection is
acquired during adulthood. However, it is remarkably different in
follow-up studies from Asian countries where most chronic HBV
infection is acquired during infancy or childhood.
INCIDENTALLY DETECTED ASYMPTOMATIC HBSAG POSITIVE
SUBJECTS (IDAHS)
Definition and classification
By definition these subjects have no present / past symptoms
or signs of liver disease and have HBsAg positivity on two occasions
more than six months apart.
Typically, this subgroup seeks medical attention because
HBsAg is detected either during a routine checkup, blood donation,
family screening of contacts of patients with HBV related CLD or a
routine test showing abnormal ALT or AST. A large proportion of
IDAHS acquire the infection through perinatal exposure or horizontal
transmission. Although on presentation they are asymptomatic and
look healthy, a large proportion of IDAHS show biochemical and
histological abnormality and carry the risk of progression to cirrhosis
and HCC. According to ALT levels and serum HBeAg status they
are classified into two groups.
1. HBeAg positive group either with normal or raised ALT
2. HBeAg negative group (anti-HBe positive) either with normal or
raised ALT
If any among either group is found to have increased ALT
greater than 40 IU/L and/or histological activity index (HAI) greater
than three (with other causes of liver disease excluded), the person
should be categorized as chronic HBV infection with significant liver
disease and considered for further assessment and therapy. In fact
among inactive HBsAg carriers, 20-30% may under go reactivation
and develop progressive liver disease.1
Mode of transmission
HBV is transmitted by contact with blood or body fluids

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of an infected person. Worldwide, most infections occur from

infected mother to child, child-to-child contact in household
settings, unprotected sexual activity, blood transfusion, and reuse
of unsterilized needles and syringes. In many developing countries,
almost all children born from infected mothers become infected
with the virus. About 90% of infants infected at birth or during their
first year of life, and 30-50% of children infected between one and
four years of age develop a chronic infection. This risk of chronic
infection declines to ~five per cent for older children and adults.
HBV infection from blood transfusion has been almost completely
eradicated by routine screening and the use of voluntary blood
donors.
Clinical features in IDAHS
Most IDAHS are asymptomatic. The most frequent complaint
made by them is fatigue and malaise. Weight loss may occur if the
subjects have a mass lesion in liver. Hepatomegaly and vary rarely
splenomegaly may be found if the patient have inactive cirrhosis.
Laboratory profile in IDAHS
The results of liver function tests with regard to serum bilirubin,
albumin, and globulin are mostly normal in IDAHS, except a raised
trans aminses in a small proportion of the subjects.
Following demonstration of HBsAg for more than six months,
determination of ALT and HBeAg testing should be done in all
these patients. In HBeAg negative individuals, baseline HBV DNA
should be tested to determine the replicative status of the virus.
Liver biopsy is normally not recommended except in subjects with
age more than 40 years having ALT values close to upper limit
of normal (one to two times). These tests have to be done in
conjunction with clinical assessment including history and physical
examination, and an ultrasound examination and endoscopy.
These asymptomatic patients should be followed up closely
as there is a constant interplay of host and viral factors that may
swing the status of liver towards either side. These patients should
be evaluated and managed appropriately whenever there is a rise
in trans aminase to control the disease at an early stage.
HBe antigen negative group (HBeAg positive)
From several studies in the West, HBeAg positivity has been
found in 10% of IDAHS, and 20-30% of them showed chronic

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active hepatitis. In a large series of 317 asymptomatic HBsAg

subjects in Canada,2 65% showed raised ALT greater than 40 IU/L
and HBeAg positivity was seen in six per cent of cases. This was
similar to another study from Italy by De Franchis et al3 showing
70% with raised ALT and HBeAg positivity in four per cent of
asymptomatic HBsAg carrier with 50% having CAH (HAI greater
than three) on liver biopsy. The above studies support the earlier
study by Dragosics et al4 in which HBeAg positivity was found in
7.5% of cases, and among HBeAg positive subjects 26% had
histologically CAH (HAI greater than three). A study in India by
Chandra et al5 found HBeAg positivity in 45% of cases, and 76%
among them had raised ALT and nearly 70% of HBeAg positive
subjects had abnormal liver histopathology with HAI greater than
three. This study also revealed that even at normal ALT levels,
27% of HBeAg positive subjects had HAI greater than three.
HBe antigen negative group (Anti-HBe positive):
The prevalence of anti HBe in IDAHS from various studies
range from 53-96%: Villeneuve et al.2 (94%), Dragosis et al.4(93.5%),
Chandra et al5 (83%); Dixit et al6 (79%). Hepatic damage which
correlates with ALT level, HBV DNA level, and necro inflammatory
status of liver is present in 2-20% of anti HBe group. In anti HBe
positive group, raised ALT is found in 10-20% of cases (12% - De
Franchis et al3, 14% - Villeneuve et al2, 1994, 10% by Chang7) which
differs from the Asian experience where it is 57% by Chandra et al5,
and 69% by Chan et al.8 HBV DNA was positive in 20% of subjects
in the study by De Franchis et al.3 which is different from the Asian
experience where it was found positive in 57% by Sarin et al.5
and in 46% by Chan et al8. Among DNA positive cases, 50-70%
showed HAI greater than three. Although HBV DNA levels correlate
with necroinflammatory activity, it is less accurate than raised ALT.
Another study9 reported that 45% of anti-HBe hepatitis cases
with raised ALT and necroinflammatory changes in liver histology
had HBV DNA level less than 105 copies/ml casting doubt on
the cut-off value. Hence, along with HBV DNA level, ALT level
too should be taken into account to differentiate active from truly
inactive liver disease.
Risk of progression to cirrhosis
The prognosis of asymptomatic HBsAg carrier state is
usually benign; during long term follow-up only a few subjects

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develop cirrhosis. The progression to severe liver diseases depends

upon genotype (genotype C higher risk of cirrhosis), DNA level,
the stage of fibrosis and severity of necro inflammation. The
progression to cirrhosis is increased with concurrent infection
with HCV, HBV, HIV and alcohol use. A higher rate of cirrhosis
occurs in HBeAg negative patients with raised ALT than HBeAg
positive patients, because of the longer duration of infection in HBeAg
negative subjects.
Risk of hepatocellular carcinoma (HCC)
There is a very low incidence of HCC among IDAHS. Risk
factor for HCC among HBV carriers include male sex, family
history of HCC, older age, cirrhosis, co infection with HCV and
alcohol use.
No treatment is available or recommended for inactive non
replicative chronic HBV infection. That means, in subjects who
have normal or less than twice ALT levels, absent or minimal
necroinflammatory activity antiviral therapy is currently not
recommended.
RECOMMENDATIONS
1. No treatment is required for most patients.
2. Reassurance should be given to patients.
3. Family members should be screened with HBsAg; if negative
they should be vaccinated.
4. Protected intercourse should be practiced until partner has
developed protective antibodies. Eventual offspring needs
active and passive vaccination.
5. Avoid alcohol.
6. Patients should be made aware of possibility of reactivation or
super infection by other viruses and advised to consult their
physician if there is jaundice, malaise or increased fatigue.
7. They should regularly be followed up at every 6-12 months
intervals with trans aminases as fluctuations in ALT and HBV
DNA levels are common during the course of chronic HBV
infection.
8. If person is more than 50 years of age or there is positive
family history of HCC, AFP estimation and USG should be
performed every 6-12 months.
9. They should not be denied employment or hospital treatment.

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Universal precautions should be taken while treating such

patients in the hospital
10. They should not be allowed to donate blood, organ or semen
11. Close monitoring is required and prophylactic lamivudine therapy
should be given if undergoing chemotherapy or receiving
immunosuppressive medications
12. For pregnant women, vaccinate the newborn at birth with acute
and passive immunization within 12 hours of birth.
CONCLUSIONS
HBsAg testing should be mandatory in all routine medical
check ups to know the prevalence and appropriate measure to
reduce the carrier load in the community. Contacts of HBV related
CLD patients should be screened for HBsAg and those who will
be negative should be vaccinated. HBeAg testing should be done
in all pregnant women who are HBsAg positive to know replicative
status and apply measures to prevent vertical transmission. Safe
sex and use of sterilized needles and blood product, strict measures
for HBsAg detection at blood bank before blood donation are the
need of the hour. As IDAHS subjects are more prone to develop
alcohol related liver damage it is wise to recommend that such
patients abstain from alcohol.
A significant proportion of incidentally detected asymptomatic
positive subjects (IDAHS) have biochemical and histological
evidence of liver disease in the absence of symptoms. In IDAHS
HBeAg status is neither a reliable indicator of CAH/cirrhosis nor of
prognosis and in fact HBeAg negative subjects possess a higher
risk because of older age and prolonged period of infection. As
chronic HBV infection is a dynamic process with fluctuating levels
of serum ALT and DNA levels especially in HBe antigen negative
subjects, periodic examination of ALT and DNA by PCR assay is
required to correctly assess the prognosis.
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Source of Support: Nil, Conflict of Interest: None declared.

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