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Year : 2004  |  Volume : 1  |  Issue : 1  |  Page : 210-216
Approach to the management of an incidentally detected HBsAg carrier

Professor of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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How to cite this article:
Chawla YK. Approach to the management of an incidentally detected HBsAg carrier. Hep B Annual 2004;1:210-6

How to cite this URL:
Chawla YK. Approach to the management of an incidentally detected HBsAg carrier. Hep B Annual [serial online] 2004 [cited 2024 Feb 21];1:210-6. Available from: https://www.hepatitisbannual.org/text.asp?2004/1/1/210/27926

India has an estimated 45 million persons affected with hepatitis B infection. This pool is likely to increase because of increasing awareness of HBsAg, widespread use of HBsAg screening in blood donor population and executive health check up programs. Most of these turn out to be asymptomatic HBsAg carriers. These groups of patients were previously labeled as Hepatitis B carriers and used to be clubbed with patients of active liver disease, who had either chronic hepatitis or active cirrhosis. It is now known that the natural history of these groups of patients is different.

The natural history of HBV infection is basically a dynamic process with replicative and non-replicative phases based on virus host interactions. The first phase is the immunotolerant phase seen usually with perinatal infection, where the patient has no symptoms, normal or slightly increased serum aminotransferase (ALT) levels, and minimal histological activities, which implies a lack of or a very weak immune response against the infected hepatocytes. In this phase, the patient shows positivity of HBsAg and HBeAg, and high levels of HBV DNA in the serum.

After a variable duration, for unknown reasons the tolerogenic effect is lost and patients enter the second immunoactive phase , associated with a decrease in HBV DNA concentration, increased ALT levels and increased histologic activity, reflecting immune mediated lysis of infected hepatocytes. This phase has a variable duration from months to years.

The third phase is of non-replication , which occurs after seroconversion from HBeAg positivity to antibody to HBeAg. This phase is preceded by a marked reduction of serum HBV DNA to levels that are not detectable by hybridization techniques followed by normalization of ALT levels and resolution of liver necroinflammation. In many patients HBV DNA remains detectable by sensitive techniques like PCR

This phase is called an inactive carrier state . Inactive HBsAg carriers form the largest group of chronic HBV infected patients. This phase may last for a lifetime. During this stage, HBV DNA may still be detectable by PCR in serum and more often the liver. In rare cases of immunosuppresion, as with cancer chemotherapy or after organ transplantation, HBV can be reactivated with reappearance of HBeAg and high levels of HBV DNA.

Inactive HBsAg carrier state is diagnosed by the demonstration of HBsAg for more than 6 months, no signs and symptoms of liver disease, absence of HBeAg and presence of anti-HBe, undetectable or low levels of HBV DNA with PCR based assays (HBV DNA < 10000 copies/ml), repeated normal ALT levels and minimal or no necroinflammation, slight fibrosis or even normal histology on biopsy (HAI < 4). Inactive cirrhosis may be present in patients who had active liver disease during the replicative phase of infection.

Two studies from India have described the profile in patients with asymptomatic chronic HBV infection. In the first study of the 157 incidentally detected asymptomatic HBsAg subjects, only 45% were HBeAg positive, 71% patients with raised transaminases had an HAI of > 3 on liver biopsy as compared to only 36% of patients with normal transaminases. Inactive carriers who were HBeAg positive and had normal transaminases were more likely to have a significant histological lesion than those who were anti-HBe positive.[1]

Another study from Mumbai showed that 48 (83%) of the 58 asymptomatic chronic carriers were HBeAg negative and 44 of them had normal transaminases. Of the 10 patients who were HBeAg positive, 50% had raised transaminases. Those with normal transaminases had normal histology. On a follow up of 12 months, all patients with normal transaminases continued to have normal liver functions tests.[2]

Thus three categories of patients with inactive HBsAg carrier state may be seen

(i) HBeAg positive and anti-HBe negative, (ii) HBeAg negative and anti HBe positive and (iii) HBeAg and anti-HBe negative. Majority of our Indian patients belong to the second group.[3]

Koertz et al's study on liver biopsies in patients with normal transaminases (compiled data from different studies) revealed that only 2% of these patients showed advanced liver disease in the form of cirrhosis or chronic hepatitis. The commonest finding in patients with normal histology is the presence of ground glass hepatocytes with minimal portal tract inflammation. These patients have an excellent prognosis and a very low risk of development of cirrhosis of the liver and HCC.[4],[5]

They can have a normal histology in 7.5 - 32%, mild inflammation in 50%, significant liver histology in 18-25% which includes chronic persistent hepatitis in 14-19%, chronic active hepatitis in 3-6%, cirrhosis in 1.6% and HCC in 0-0.2%. This remains unchanged in 73.2%, improves in 5.4% and worsens in 21.4% on long-term follow up.[4],[6]

The prognosis of the inactive HBsAg carrier state is usually benign and long term follow up of upto 18 years of these carriers has shown that the vast majority show sustained biochemical remission and very low risk of cirrhosis or hepatocellular carcinoma. However, rarely, even non cirrhotic patients may develop liver cancer during the inactive HBsAg carrier state.

Approximately 20-30% of persons in the inactive HBsAg carrier state may undergo spontaneous reactivation of hepatitis B during follow up. Multiple episodes of reactivation or sustained reactivation can cause progressive hepatic damage and even hepatic decompensation, and may some times mimic acute viral hepatitis. Acute flares of hepatitis should be differentiated from superinfection with other hepatotrophic viruses. Almost 20-30% of these acute exacerbations may be caused by superinfection with HCV, HEV or HAV, all of which may increase the risk of fulminant hepatic failure.[7],[8],[9]

Some carriers eventually become HBsAg -ve and develop anti-HBs. The incidence of delayed HBsAg clearance has been estimated to be 1-2% in the West where HBV infection is usually acquired in adulthood, but a lower rate from 0.05-0.8% per year is prevalant in endemic areas where HBV infection is mostly acquired perinatally or in early childhood. Clearance of HBsAg has been reported to be higher in women than in men and in older than in younger carriers. Prognosis is improved by loss of HBsAg as liver disease is usually inactive and nonprogressive, but HBsAg clearance does not completely prevent occurrence of decompensation or HCC in patients who have already developed cirrhosis.[10]

Differentiation from chronic HBeAg negative hepatitis B, requires serial testing of ALT and HBV DNA for 1 year before designating a carrier state. In subjects with inactive carrier state, testing, for HBV DNA and liver biopsy are not recommended.

Recommendations for management of an inactive HBsAg carrier[11]

  1. No treatment is required
  2. Reassurance should be given to patients
  3. Family members should be screened with HBsAg and anti-HBs; if negative they should be vaccinated and success of vaccination should be tested by anti-HBs assay
  4. Protected intercourse should be practised 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 superinfection 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 transaminases, 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. Universal precautions should be taken while treating such patients in the hospital
  10. In the case of health care workers, they should be allowed to do routine designated duties and there is no need for changing the duty. They must follow universal precautions.
  11. They should not be allowed to donate blood, organ or semen
  12. Close monitoring is required and prophylactic lamivudine therapy should be given if undergoing chemotherapy or receiving immunosuppressive medications
  13. For pregnant women vaccinate the newborn at birth with acute and passive immunization within 12 hours of birth.

Finally the workup of an inactive HBsAg carrier should include:

Demonstration of HBsAg for more than 6 months with determination of ALT, HBeAg testing should be done in all these patients irrespective of ALT status. Anti-HBe should be done if HBeAg is negative. In an anti-HBe positive individual, baseline HBV DNA should be tested to determine the replicative status of the virus. A liver biopsy is normally not recommended except as a protocol if HBeAg persists for more than 6 months or in an anti-HBe positive individual with a high viral load or if the transaminases are minimally elevated. 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 thus 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 however be treated whenever there is a rise in transaminases in order to control the disease at an early stage.

In a large epidemiological study performed in Taiwan by Beasley et al, the relative risk of HCC development was 100 times higher in HBsAg positive persons as compared to HBsAg negative individuals. However, there was still a five times increased risk for anti-HBc or anti-HBs positive individuals as compared to individuals who are negative for all HBV markers. In these patients, the malignant transformation was probably initiated during the active phase of hepatitis B by either increased cell turnover and oxidative DNA damage associated with liver inflammation or HBV DNA integration into or rearrangements in critical region of the cellular genome. In addition, ongoing low level HBV replication and inflammation may be responsible for malignant transformation in some of these patients.

  References Top

1.Chandra R, Kapoor D, Agrawal SR, et al. Profile of asymptomatic chronic HBV infection in India. End of carrier saga. Ind J Gastroenterol 2001;20:(suppl 2):A6.  Back to cited text no. 1    
2.Verma GR, Sharma J, Bapat MR, et al. Natural history of asymptomatic chronic HBsAg carriers. Indian J Gastroenterol 2001;20(suppl 2):A81.  Back to cited text no. 2    
3.De Franchis R, Meucci G, Vecchi M, et al. The natural history of asymptomatic hepatitis B surface antigen carriers. Ann intern Med 1993;118:191-4.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Villeneuve JP, Desrochers M, Infante-Rivard C, et al. A long term follow up study of asymptomatic hepatitis B surface antigen carriers in Montreal Gastroenterology 1994;106:1000-5.  Back to cited text no. 4  [PUBMED]  
5.Dragosics B, Ferenci P, Hitchman E, et al. Long term follow up study of asymptomatic HBsAg positive voluntary blood donors in Austria. A clinical and histological evaluation of 242 cases. Hepatology 1987;7:302-6.   Back to cited text no. 5  [PUBMED]  
6.Bortolotti F, Jara P, Civellaro C, et al. Outcome of chronic hepatitis B in caucasian children during a 20 year observation period. J Hepatol 1998;29:189-90.  Back to cited text no. 6    
7.Hsu YS, Chien RN, Yeh CT, et al. Long term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology 2002;35:1522-7.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Perrillo RP. Acute flares in chronic hepatitis B. The natural and unnatural history of an immunologically moderated liver disease. Gastroenterology 2001;120:1000-22.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Huo T-I, Wu JC, Lee PC, et al. Seroclearance of HBsAg in chronic carriers not necessarily implies a good prognosis. Hepatology 1998;28:231-6.  Back to cited text no. 9    
10.Thyagarajan SP, Jayaram S, Mohanratti B. Prevalence of HBV in the general population of India. SK Sarin, Singhal AK, Eds Hepatitis B in India. Problems and Prevention. CBS publisher and distributors. New Delhi 1996;pp5-16.  Back to cited text no. 10    
11.Beasley RP. Hepatitis B virus: the major etiology of hepatocellular carcinoma. Cancer 1988;61:1942-56.  Back to cited text no. 11  [PUBMED]  

Correspondence Address:
Yogesh Kumar Chawla
Professor of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

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