Hepatitis B Persistence after HBsAg Clearance Is Associated with Increased Risk
of Hepatocellular Carcinoma
Clearance
of serum hepatitis B surface antigen (HBsAg) is one measure of recovery from hepatitis
B virus (HBV) infection, either spontaneous or due to treatment.
But low levels of HBV may persist in patients with HBsAg clearance, which may
lead to detrimental long-term outcomes.
HBsAg
clearance and HCC risk
In
the October 2008 issue of Gastroenterology, M.F. Yuen and colleagues from
Hong Kong described a study of virological, histological, and clinical outcomes
in chronic hepatitis B patients with HBsAg seroclearance. In particular, the researchers
looked at age at the time of HBsAg clearance and other factors associated with
the development of liver fibrosis and progression
to hepatocellular carcinoma (HCC).
The
study included 298 chronic hepatitis B patients followed for a median of 108 months.
Liver stiffness was assessed in 229, histology by liver biopsy in 26, serum HBV
DNA levels over time in 265, intrahepatic HBV DNA with covalently closed circular
DNA (cccDNA) levels in 29, and messenger RNA (mRNA) expression in 11.
Results
•
The median age at the time of HBsAg seroclearance was 49.6 years.
•
7 patients overall (2.4%) developed HCC.
•
Cumulative risk for the development of HCC was higher in patients with HBsAg seroclearance
at age 50 years or older compared with < 50 years (P = 0.004).
•
29.5% of patients with seroclearance at age > 50 and 7.9% of those with
seroclearance at age < 50 had significant fibrosis according to liver stiffness
measurement (P = 0.001).
•
Intrahepatic total HBV DNA was detected in all patients (100%).
•
79.3% had detectable cccDNA.
•
All patients had undetectable surface and precore/pregenomic HBV RNA transcripts.
•
1 patient (9.1%) showed X mRNA expression.
•
Serum HBV DNA was detectable in:
•
13.4% of patients within 1 year after HBsAg seroclearance;
•
6.1% within 5-10 years after seroclearance;
•
3.7% > 10 years after seroclearance.
•
82.1% of patients had persistently normal alanine aminotransferase (ALT) levels.
"HBV
persisted at low replicative and transcriptional levels after HBsAg seroclearance,"
the study authors concluded. "HBsAg seroclearance at age < 50 years was
associated with a lower risk for the development of HCC."
More
sensitive HBsAg testing
In
a related study published in the July 2008 Journal of Hepatology, H. Togashi
and colleagues from Japan investigated what could be revealed by extending the
sensitivity of HBsAg detection below the present limit.
They examined
the sensitivity of an investigational immunoassay compared with real-time PCR
detection of HBV DNA using serially diluted sera from HBV carriers. Low HBsAg
was measured in 210 presumed healthy volunteers and 368 patients with non-HBV
chronic liver disease who were HBsAg negative using a standard enzyme immunoassay
method.
Results
•
The more sensitive immunoassay was able to detect HBsAg at a concentration of
0.025 ng/mL.
•
Low-level HBsAg was detectable in:
•
6 of 210 healthy volunteers (2.86%);
•
5 of 65 patients with non-HBV/non-HCV cirrhosis
(7.69%);
•
6 of 62 patients with non-HBV/non-HCV hepatocellular carcinoma (9.68%; P = 0.04
vs healthy volunteers);
•
12 of 134 chronic hepatitis C patients (8.96%; P < 0.02 vs healthy volunteers);
•
11 of 107 HCC patients with chronic hepatitis C (10.28%; P < 0.008 vs healthy
volunteers).
•
Although HBV DNA was not positive in any healthy volunteers, 9 patients with non-HBV
chronic liver disease had detectable HBV DNA by real-time PCR analysis.
Based
on these findings, the investigators concluded, "Increasing the sensitivity
of HBsAg detection to below the present limit has revealed that infection with
HBV, including occult HBV, is far more endemic than suspected previously."
10/21/08 References MF
Yuen, DK Wong, J Fung, and others. HBsAg Seroclearance in Chronic Hepatitis B
in Asian Patients: Replicative Level and Risk of Hepatocellular Carcinoma. Gastroenterology
135(4): 1192-1199. October 2008. (Abstract).
H Togashi, C
Hashimoto, J Yokozawa, and others. What can be revealed by extending the sensitivity
of HBsAg detection to below the present limit? Journal of Hepatology 49(1):
17-24. July 2008. (Abstract). |
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