Elsevier

Journal of Hepatology

Volume 54, Issue 2, February 2011, Pages 195-200
Journal of Hepatology

Research Article
Profiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: Implications for antiviral therapy

https://doi.org/10.1016/j.jhep.2010.06.031Get rights and content

Background & Aims

We determined the virological profile in Chinese chronic hepatitis B (CHB) subjects and its implications regarding current treatment guidelines.

Methods

A total of 1400 treatment-naïve CHB patients had their HBV DNA levels determined using the Cobas Taqman assay. Patient demographics, HBeAg status, and liver biochemistry were also recorded.

Results

The subjects were predominantly male (62%), had a median age of 45 years, and 301 (22%) were HBeAg-positive. In subjects aged ⩽25, 26–35, 36–45, 46–55, and >55 years, there was a decreasing trend of HBV DNA levels of 9.9, 9.3, 8.2, 7.4, and 7.3 log copies/ml, respectively (p <0.001), in HBeAg-positive subjects, while the pattern was reversed with HBV DNA levels of 3.7, 4.4, 4.7, 4.9, and 5.2 log copies/ml, respectively, in HBeAg-negative subjects (p <0.001). In HBeAg-negative subjects, the proportion of patients with elevated ALT compared to those with normal ALT was significantly higher in older age groups (p <0.001). In our study population, by applying the AASLD, EASL, and APASL guidelines, 64%, 99%, and 64% would be eligible for antiviral therapy, respectively, in HBeAg-positive patients (with elevated ALT), and 38%, 72%, and 43%, respectively, in HBeAg-negative patients (with elevated ALT). Up to 54% of patients over the age of 40 years would be recommended for liver biopsy to determine further eligibility for treatment.

Conclusions

For HBeAg-negative CHB, more patients had elevated ALT and a higher viral load with increasing age. Close monitoring is recommended in this group so that treatment may be considered. By applying the current treatment guidelines, a wide discrepancy can be observed in the proportion of patients eligible for treatment in the absence of histological data.

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.

Section snippets

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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