EASL 2009: Does HBV Viral Load Level Predict Development of Liver Fibrosis?


Two studies presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last month in Copenhagen looked at the association between HBV DNA level and development of fibrosis, with findings suggesting that the role of HBV viral load differs for hepatitis B "e" antigen (HBeAg) negative and HBeAg positive individuals.

Over years or decades, chronic hepatitis B virus (HBV) infection can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC). Studies have shown that sustained HBV clearance reduces the risk of disease progression, but it is unclear whether HBV DNA levels in patients with persistent viremia is associated with disease severity. This is an important consideration, because viral load could potentially be used to guide decisions about when to start treatment, which is only required if liver disease is progressing.

HBV Viral Load

In the first study, C. Croagh and colleagues from Australia evaluated the prevalence of significant fibrosis or cirrhosis and examined the relationship between serum HBV DNA and alanine aminotransferase (ALT) levels, and liver inflammation and fibrosis scores in chronic hepatitis B patients.

The investigators reviewed the St Vincent's Hospital HBV database to identify patients with chronic hepatitis B who had undergone liver biopsy. Baseline demographic, biochemical, serological, and virological variables were correlated with biopsy results. Complete data on baseline serum markers and liver biopsy were available for 394 patients.

Liver fibrosis was scored according to the Metavir system (fibrosis stages F0 through F4; histological activity stages A0 through A3). Significant fibrosis was defined as F2-F4 and significant inflammation as A2-A3.


"The prevalence of significant fibrosis is highest in HBeAg negative patients with viral load of > 25,000, but is not insignificant in HBeAg negative patients with lower levels of viremia," the investigators concluded.

"Increasing HBV DNA levels correlate with increasing prevalence of significant fibrosis and inflammation in HBeAg negative disease, however in HBeAg positive disease the correlation is inverse," they added.

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia.

Age and ALT

In the second study, researchers from Hong Kong aimed to determine which clinical factors might help predict advanced fibrosis in HBeAg positive chronic hepatitis B patients.

The investigators prospectively studied 453 treatment-naive HBeAg positive patients referred for liver stiffness measurement by transient elastography (FibroScan), a non-invasive method of estimating fibrosis. Individuals with other causes of liver diseases besides hepatitis B were excluded.

Based on the researchers' previous histological (biopsy) validation, insignificant fibrosis was defined as liver stiffness 6.0 kPa (kiloPascals), while advanced fibrosis was defined as liver stiffness > 9.0 kPa when ALT was normal. When ALT was elevated (up to 5 x the upper limit of normal [ULN]), the corresponding thresholds were 7.5 kPa and > 12.0 kPa, respectively.


Based on these findings, the researchers concluded, "Risk of advanced liver fibrosis increased in HBeAg positive patients aged over 35 years with ALT > 0.5x ULN," but did not correlate with higher HBV viral load.

Chinese University of Hong Kong, Hong Kong, Hong Kong S.A.R.



C Croagh, S Bell, Y Kong, and others. Prevalence of Significant Fibrosis and Correlations between Histological Inflammation and Fibrosis Scores and Serum Hepatitis B (HBV) DNA Levels in Chronic Hepatitis B. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.

HL Chan, GL Wong, PC Choi, and others. Clinical Factors Predicting Advanced Liver Fibrosis in Hepatitis B e Antigen Positive Chronic Hepatitis B. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.