HCC may appears on HBV patients whose AntiHBs -, HBsAg -, but AntiHBc +. But with HBV DNA + Those cases be called occult HBV.

1. Occult Hepatitis B Infection
a potential risk factor
in
the development of HCC
• Bui Dac Chi,MD
• Medic Center

3. The presence of individuals with OBI has
been appreciated since the late 1970s, but
only extensively studied since 2000, and
the current consensus definition was
adopted at an international expert meeting
in Taormina, Italy, in 2008

4. • More than 30 years ago(1978), it was shown that
patients who received HBsAg-negative, anti–hepatitis B
core antibody (HBcAb)–positive blood were still at risk of
developing post-transfusional hepatitis B . In addition,
patients who were HBsAg negative, hepatitis B surface
antibody (HBsAb) positive, undergoing cancer
chemotherapy, developed reactivation of HBsAg
associated with severe, life-threatening hepatitis . With
the development of PCR technology ,it was clearly
shown that not only patients with only hepatitis B
antibodies in their serum, but also patients with chronic
liver disease and with no serological markers of
HBVinfection, could still be shown to have HBV DNA
present in their serum or liver . Thus the concept of
“occult” HBV infection emerged.

5. • ‘‘the presence of HBV DNA in the liver (with
detectable or undetectable HBV DNA in the
serum) of individuals testing hepatitis B surface
antigen (HBsAg) negative by currently available
assays.’’ In addition, OBI can be serologically
classified as seropositive OBI (e.g., hepatitis B
virus core protein [anti-HBc] and/or hepatitis B
virus surface protein [anti-HBs positive]) or
seronegative OBI (anti-HBc and anti-HBs
negative)

7. • Reliable OBI diagnosis can at present be
performed only in highly specialized
laboratories. The development in the near
future of valid and commercially available
assays (i.e., real time PCR on DNA
extracts from liver tissue fine-needle
aspiration) allowing the detection of OBI in
all cases

9. • OBI is a phenomenon essentially
attributed to the long-lasting presence of
HBV cccDNA into the hepatocytes and to
a strong inhibition of HBV replication and
protein synthesis.

12. Schematic representation of
the various conditions
leading to different OBI
serological profiles

13. OBI is related to replication-competent viruses that
are strongly suppressed in their activities
(replicative and transcriptional) by the host’s
defense mechanisms. Very importantly, this
suppression (a) does not have an absolute
effect and residual, low-levels of replication and
transcription may persist over time, and (b) may
be reversible in particular circumstances leading
to viral reactivation and development of a typical
HBsAg-positive (namely, “overt”) infection

15. • A significantly higher prevalence of OHB was
observed in patients with HCC in the presence
or absence of HCV infection when compared
with control populations without HCC.
Correspondingly, among adequately designed
prospective studies, the cumulative probability of
developing HCC was significantly greater among
patients with OHB than among HBV DNA-
negative patients in the presence or absence of
HCV infection.

17. • Despite more than a decade of research
pertaining to the association of OHB and HCC,
knowledge of the role of occult HBV in the
development of HCC is still very limited and
often confounded by current therapy and testing
methodology. Thus, there remain many
unanswered questions regarding its
pathogenesis and clinical significance. Both
epidemiological studies and molecular studies
have provided more insight into occult HBV, but
the potential role of OHB in HCC requires further
investigation.

19. OBI may maintain most of the pro-
oncogenic properties of the overt HBV
infection, including the capacity to
integrate into the host’s genome, to
produce proteins with transforming
properties (even if at low levels) and a
mild but persisting necroinflammation

20. OHB should be considered a potential risk
factor in the development of HCC
whenever it is encountered .

21. HBV may not be recognized in a certain
number of patients if the diagnosis is
solely based on detecting HBsAg.
Although controlling HBsAg levels can
slow down disease progression and
prevent HCC,there is still a sgnificant risk
of cancer development in OBI patients
whose HBsAg markers are negative.