Research ArticleProfiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: Implications for antiviral therapy
Introduction
Chronic hepatitis B (CHB) is a significant health burden worldwide with an estimated 400 million persons affected globally. Of these, 15–40% will develop cirrhosis and its complications, including hepatocellular carcinoma (HCC) [1]. Hepatitis B virus (HBV) plays a pivotal role in hepatocarcinogenesis, and the incidence of HCC is the highest in areas such as Asia and Africa where CHB is endemic. Previous studies have shown that factors such as age, male gender, presence of a core promoter mutation, and hepatitis B e-antigen (HBeAg) positivity have been associated with an increased risk of HCC development [2], [3], [4].
More recently, the level of serum HBV DNA has been shown to be an important risk factor for cirrhosis and HCC [5], [6], [7], [8]. In a study of 2763 CHB subjects from Taiwan, followed up for a median of 11 years, those with HBV DNA >105 copies/ml had a significantly higher mortality from HCC compared to those with lower levels (relative risk 11.2 vs 1.7, p <0.001) and chronic liver disease (relative risk 15.2 vs 1.5, p <0.001) [7]. Another study from Taiwan, of 3653 CHB subjects followed up for a median of 11.4 years, showed that HBV DNA level of ⩾104 copies/ml was a strong independent predictor of HCC even after adjusting for age, sex, smoking, alcohol intake, HBeAg status, ALT level, and the presence of cirrhosis at study entry [6].
In spite of the recognition of the importance of HBV DNA measurement, population studies on HBV DNA levels according to age, sex, HBeAg-status, and the natural history of CHB infection are essentially lacking. These population studies are needed because they have important bearings on the healthcare system, especially in regions where CHB is endemic. Although the cost of antiviral therapy can be high, this has to be balanced with the cost of managing HCC and decompensated cirrhosis, complications that may be successfully prevented by instituting treatment earlier.
In many countries where HBV infection is endemic, the virological profile in patients with elevated ALT is not known. Conversely, the proportion of patients with CHB who have normal ALT, but with very high viral load is also unclear. The aim of the current study is to determine the virological profile in Chinese subjects with CHB, and to determine the implications of these findings with current treatment guidelines.
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Materials and methods
Patients with CHB were regularly followed up at the Liver and Hepatitis Clinics at Queen Mary Hospital, University Department of Medicine, Hong Kong. All patients were HBsAg positive for at least 6 months. At each visit, liver biochemistry, alpha-fetoprotein, and hepatitis B serology including hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg) were performed, and the serum was stored at −70 °C. For the current study, patients seen between April 2005 and September 2009 were
Results
A total of 1400 Chinese patients with CHB were included in the current study, with a median age of 45 years (range, 17–75) and with a male predominance (62%). The demographic and laboratory data of the overall population are summarized in Table 1. A total of 301 (22%) patients were positive for HBeAg, with a significantly higher rate of HBeAg-positivity observed in males compared to females (24% vs 18%, respectively, p = 0.013). The median ALT was 43 U/L (range, 7–512), with 360 (26%) of the study
Discussion
In the present study, the virological profile of 1400 Asian CHB patients was determined. We believe the findings were fairly representative of our local CHB population as our two clinics accept referrals and provide follow-up for both asymptomatic and symptomatic CHB patients irrespective of their HBeAg status, HBV DNA, and ALT levels. A large proportion of the patients being followed up for long-term monitoring had normal ALT levels. The median ALT level in the present study population was 43
Conflict of interest
The authors have declared that they received funding from the drug companies involved in order to carry out their research in this manuscript.
Acknowledgements
This study has been generously supported by an unrestricted grant from Bristol-Myer-Squibb.
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