The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(-) hepatitis B infection: association with liver disease progression. A prospective cohort study.

Background/aims: To evaluate the fluctuating course of serum HBV-DNA levels during the natural history of chronic HBV infection in the general population of North-Eastern Greece, in association with liver disease progression.

Methods: Two hundred and sixty-three adults with chronic HBV, median 34 years of age, were randomly selected and prospectively followed-up for a maximum period of 12 years. Viral markers, liver biochemistry and physical examination were performed every 6 months, and liver biopsy/abdominal ultrasound every 2-4 years.

Results: At entry, 195/263 (76%) were HBeAg (-)/anti-HBe (+) inactive carriers: (a) almost all 195 individuals with undetectable or HBV-DNA levels <2000IU/ml had no liver disease at entry and at follow-up period by imaging or liver histology evaluation (b) only 4/195 (2%) showed HBV reactivation with HBV-DNA >2000IU/ml. At entry, 48/263 (18%) patients were chronic HBeAg(-); (a) 1/3 patients had intermittently HBV-DNA <2000IU/ml for at least one occasion and were misclassified as inactive carriers (b) 22/48 (46%) had moderate/severe histology at entry and 5/48 (10%) showed liver disease progression during follow-up. Logistic regression analysis was used to derive OR (95%CI) for factors associated with liver disease progression.

Conclusions: Close monitoring of serum HBV-DNA levels is useful in the management of chronic HBeAg(-) patients, as associated with liver disease progression.