Does
HBV Viral Load Level Predict Development of Liver Fibrosis? By
Liz Highleyman  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.
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. 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. Results
The prevalence of stage F2-F4 liver fibrosis was 58% in HBeAg negative patients
with HBV DNA > 25,000 IU/ml, compared with 36% for HBeAg negative patients
with HBV viral load below this level (P = 0.005).
The fibrosis prevalence in HBeAg negative patients with high viral load was also
higher than that of HBeAg positive individuals, at 40% (P = 0.002).
In a logistic regression analysis, a significant interaction was observed between
HBV DNA and HBeAg status with regard to F2-F4 fibrosis (P < 0.001).
The odds ratio for risk of F2-F4 fibrosis with a 1 log IU/ml increase in HBV DNA
was 1.42 (about 40% higher) for HBeAg negative patients, but only 0.71 (slightly
lower) for HBeAg positive individuals.
A similar interaction was found between HBV DNA level and HBeAg status with regard
to stage A2-A3 liver inflammation (P < 0.013).
The odds ratio for risk of A2-A3 inflammation with a 1 log IU/ml HBV DNA increase
was 1.17 (roughly equal) for HBeAg negative patients and 0.59 (almost half) for
HBeAg positive patients.
Increasing baseline ALT level was associated with greater prevalence of significant
fibrosis and inflammation in both HBeAg positive and HBeAg negative patients.
"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. Results
Among 74 patients with available liver biopsy results, the selected liver stiffness
thresholds had 90% sensitivity to exclude and 95% specificity to confirm stage
F3-F4 fibrosis.
Based on liver stiffness, 48% of patients had insignificant fibrosis and 30% had
advanced fibrosis.
In a multivariate analysis, age and ALT were independently associated with liver
stiffness.
However, male sex, obesity, and higher HBV DNA level were not independent predictors
of greater liver stiffness.
The risk of advanced fibrosis began to increase when ALT was higher than 0.5 x
ULN (odds ratio 5.0; P< 0.001).
Among the 47 patients aged 35 or older with ALT ? 0.5 x ULN, 83% had liver stiffness
measurements suggesting insignificant fibrosis, while 2% (1 patient) had advanced
fibrosis.
Among the 217 participants younger than 35 with ALT > 0.5 x ULN, 28% had liver
stiffness suggestive of insignificant fibrosis and 37% had advanced fibrosis.
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. 5/29/09 References 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.
EASL
2009 MAIN PAGE
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