HBEAG NEGATIVE CHRONIC HEPATITIS B VIRUS INFECTION

MAMUN-AL-MAHTAB

Department of Hepatology, Bangabandhu Sheikh Mujib Medical University,

Dhaka, BANGLADESH

Over 350 million people worldwide are infected with hepatitis B virus (HBV) and globally around 1 million die due to consequences of this infection annually. There is high prevalence of HBeAg-negative chronic hepatitis B in the Asia-Pacific region in particular. In Bangladesh, 48.7% chronic hepatitis B (CHB) patients positive for HBeAg, while the rest 51.3% test negative.

HBeAg negative CHB represents mutant variety of HBV resulting from mutation in precore or core promoter region of the viral genome giving rise to HBeAg-negative CHB. Besides, HBeAg seroconversion does not necessarily mean complete cessation of viral replication. It is very important to distinguish chronic inactive HBsAg carriers from HBeAg-negative CHB, as the later group has the potential of developing marked viral reactivation and has less chance of response to antiviral medications. The only way to distinguish between these two entities in a clinical setup is performing a liver biopsy.

The goal of treatment of any CHB patient is to prevent the development of cirrhosis, hepatic failure and hepatocellular carcinoma (HCC). In HBeAg-negative CHB, response to treatment is said to have been obtained when one becomes negative for HBV DNA by PCR along with normalization of ALT and seroconversion to anti-HBe. The problem, however, is that many HBeAg-negative CHB patients test positive for anti-HBe at baseline and have persistently normal or near normal ALT. Moreover, there is high incidence of relapse in this group of patients, even after HBV DNA becomes undetectable by PCR with treatment, the reason why initiating as well as determining the endpoint of treatment in this group remains extremely difficult. The American Association for the Study of the Liver (AASLD) advocates treatment of HBeAg-negative CHB patients till HBsAg becomes undetectable. This is an approach that is perhaps not too appropriate in the Asian setting. The reason for saying so is multifold, including lack of trained specialists, poor socio-economic condition, lack of patient awareness, poor follow-up, high cost of drugs, etc. Besides this, all oral antivirals currently approved for CHB treatment are also associated with variable risk of inducing viral resistance on long-term use. This risk is highest with lamivudine (LAM) and minimal with entecavir (ETV) and tenofovir (TNV). This means that there will be high risk of introducing mutant HBV strains.

Emergence of HBV mutant can lead to negotiation of initial treatment. Patients are also at increased risk of developing hepatitis flares and decompensation. Such mutation is initially characterized by viral breakthrough, where there is a >10 log rise in HBV DNA. Viral breakthrough precedes biochemical breakthrough by months. In the later, there is rise in serum ALT. Such patients also develop cross-resistance to other antivirals, like patients resistant to LAM will have cross-resistance to telbivudine (LdT) and vice versa.

Pegylated IFN for 48 weeks yields better results, and the viral suppression is also better if LAM is added to pegylated IFN, however, the sustained virologic response does not improve with this combination.

Patients with HBeAg-negative CHB must, therefore, be managed judiciously and in certain situations kept under close follow-up instead of rushing to treatment. However, this does not mean advocating adoption of a too conservative approach, allowing many to proceed to irreversible and progressive liver disease.

Date: 2014-12-28; view: 1035