VI Rological Features of Inactive Carrier State of Chronic Hepatitis B Virus Infection

  • Chu, Chia-Ming (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


The natural history of chronic HBV infection consisted of three chronological phases: (1) Immune tolerance phase: HBeAg positive with normal ALT; (2) Immune clearance phase: HBeAg positive with raised ALT; and (3) Inactive carriers: anti-HBe positive with normal ALT. The third phase may remain stably inactive in a lifetime. On the other hand, HBV also can reactivate either by reversion back to the previous HBeAg-positive phase or, much more frequently, by progression to HBeAg-negative chronic hepatitis. Among these phases, the inactive carrier state may be a retrospective-prospective diagnosis as inactive carriers show some propensity to reactivation. A viral load threshold of 104 copies/mL has been used to discriminate active HBV infection from its inactive form. However, two recent studies from Taiwan and Indian have revealed a substantially high serum HBV DNA levels in inactive carriers with persistently normal ALT levels for at least 1 or 2 years, with viral load >105 copies/ml in 37.2% and 35.3%, respectively. According to the long-term observations of a large series of anti-HBe-positive HBsAg carriers with normal ALT levels from Taiwan, reactivation of hepatitis B most often occurred during the first 5–10 years of follow-up and became extremely rare thereafter. However, in most previous studies the so-called inactive carriers had persistently normal ALT levels for a relatively short period of only 1–2 years; therefore, future reactivation can be anticipated in some of these carriers. Clearly, viral load status of the inactive carrier state needs to be further defined. Since reactivation of hepatitis B in inactive carriers became extremely rare 10 years after entry, inactive carriers with persistently normal ALT levels over 10 years can be considered as “real” inactive carriers. Serum HBV DNA levels in such carriers may represent the viral load status of inactive carrier state. In this investigation, we first studied viral load in inactive carriers with persistently normal ALT levels for more than 10 years. Our preliminary observation showed around 30% to 40% of inactive carriers with persistently normal ALT levels over 10 years indeed had viral load ≥104 copies/ml. Furthermore, to identify factors that correlate with inactive carrier state among anti-HBe-positive carriers with viral load ≥104 copies/ml, the clinical and virological features (viral load, genotype and mutants) of inactive carriers with viral load≥104 copies/ml were compared with age-matched patients with HBeAg-negative chronic hepatitis. These data might provide therapeutic implication for management anti-HBe-positive carriers with viral load >104 copies/mL and normal ALT levels. The prognosis of inactive carriers with persistent normal ALT levels is excellent, but in rare occasions HCC may develop albeit at extremely low incidence with the estimated annual rate of approximately 0.02 to 0.2% per year. Because of its extremely rare occurrence, the risk factors of HCC in inactive carriers with normal ALT levels remained unclear. To identify clinical and virological factors predictive of HCC in inactive carriers without cirrhosis, we first compared the clinical and virological features between cirrhotics with HCC and non-cirrhotics with HCC, and then between inactive carriers and non-cirrhotic HCC.

Project IDs

Project ID:PC10001-1145
External Project ID:NSC99-2314-B182-029-MY3
Effective start/end date01/08/1131/07/12


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