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HBsAg Seroclearance: The More and
Earlier, the Better
Dear Sir:
We read with great interest the article entitled “HBsAg
Seroclearance in Chronic Hepatitis B in Asian Patients:
Replicative Level and Risk of Hepatocellular Carcinoma”
by Yuen et al in the October 2008 issue of GASTROENTEROLOGY.
1 Although effective vaccines have been available
for 2 decades,2 chronic hepatitis B virus (HBV) infection
remains a leading cause of end-stage liver disease
and hepatocellular carcinoma (HCC) worldwide. In clinical
practice, seroclearance of hepatitis B surface antigen
(HBsAg) has been recognized as an important endpoint
in both natural history of HBV infection and treatment
of chronic hepatitis B.3,4 However, because of the rarity of
spontaneous or treatment-induced HBsAg seroclearance,
the incidence and long-term outcomes of HBV carriers
experiencing this event remain disputed.5,6 Yuen et al
analyzed 298 patients who achieved HBsAg seroclearance
between 1980 and 2006. Among them, the risks of
significant hepatic fibrosis and HCC were significantly
lower in patients with HBsAg seroconversion at ages
50 years than at 50.1 Their findings suggested that
earlier HBsAg seroconversion with sustained suppression
of HBV DNA and remission of liver damage can
bring out a better prognosis over time. Although these
data are important to practicing gastroenterologists
and hepatologists, some of their results deserve further
discussion.
In a long-term follow-up cohort in Taiwan, a total 245
patients achieving spontaneous HBsAg seroclearance
were identified.7 The annual HBsAg seroclearance was
estimated to be 1.15% on the basis of 21,267 person-years
follow-up (1965 anti-HBe–positive HBsAg carriers with
10.8 5.4 years of follow-up). In the current study, the
number of patients achieving HBsAg seroclearance was
even greater than that in the Taiwanese study. Unfortunately,
the number of HBV carriers and total person-years
of the entire cohort were not offered. If the authors
would provide relevant data, we could understand more
about the annual incidence of spontaneous HBsAg seroclearance
in Asian HBV carriers.
Two possible flaws were also noted in this study. First,
the surveillance for HCC was to perform ultrasound of
the liver in patients with elevated -fetoprotein levels.
This measure is misleading and obviously violates the
recommendations of current guidelines of HCC management,
3 and may lead to a later diagnosis of HCC in their
patients. Second, intrahepatic HBV-related mRNAs were
analyzed and none but X-mRNA was identified in 1 of
the 11 HBsAg seroconverters. This observation is contradictory
to our understanding of HBV lifecycle. It is
known that all 4 HBV-related mRNAs overlapped at the
open reading frame of X gene8; therefore, only X-mRNA
could be found by using region-specific primers seems
unusual. One possibility is that the visible band on the
gel might not be X-mRNA alone, but the summation of
all m-RNAs. Further studies are needed to clarify this
interesting observation.
In summary, existing lines of evidence indicate that
spontaneous or treatment-induced HBsAg seroclearance,
albeit rare, does occur in chronic hepatitis B patients. The
better prognosis of earlier HBsAg seroclearance is likely
caused by less HBV replication as well as less liver damage.
To provoke more and earlier HBsAg seroclearance in
HBV carriers, a better understanding of the mechanisms
involved in HBsAg seroclearance is required. |
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楼主: 放牛哥哥
发表于 2010-3-1 10:36
