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. 2021 Jan 25;5:240. Originally published 2020 Oct 14. [Version 2] doi: 10.12688/wellcomeopenres.16157.2

Table 2. Summary of factors in the case of an adult presenting with an acute biochemical hepatitis favouring either AHB or CHB-AR.

Evidence in support of AHB Evidence in support of CHB-AR
Patient history      •    Recent travel to Malaysia as a possible
risk factor for HBV acquisition (prevalence
estimated to be up to 9% 47).
     •    No household members are HBsAg
positive, and no (known) history of HBV
infection in parents or siblings.
     •    No precipitating factors identified for
CHB-AR
     •    Patient’s own description of previous similar events, possibly
representing previous episodes of CHB-AR.
     •    Origin in Pakistan where HBV prevalence is estimated to be
up to 4% 48, 49, with a history of infection in extended family
members.
Routine clinical
laboratory data
     •    Relatively high peak bilirubin level 20
(227 mol/L at highest).
     •    Some studies indicate an anti-HBc-IgM S/CO >10 is indicative
of AHB 17. In this case, the S/CO level of 7.43 does not meet
this threshold, suggesting CHB-AR may be more likely.
     •    High HBV DNA level at diagnosis (5.5 log10 IU/ml). Studies
have indicated this level of HBV DNA fits more with
CHB-AR 7, 16, 50.
     •    Relatively low rise in ALT (486 IU/ml at peak).
     •    Patient remains HBsAg-positive six months after initial
presentation. Since >90% of adults clear AHB infection,
remaining HBsAg-positive is more in keeping with
pre-existing CHB.
Deep sequencing
data
     •    No polymorphisms associated with
CHB-AR identified at consensus level
     •    Viral sub-genotype is D1, known to circulate in Pakistan 51,
suggesting infection early in life, and supported by 6/7 of
the other sequences from Pakistan being D1.
     •    Presence of several minority variant mutations associated
with CHB-AR and lack of mutations described to be
associated with AHB.
     •    Relative lack of nucleotide diversity in the HBV genome could be a feature of AHB due to a small number of
HBV variants establishing new infection. Could also represent high viral load CHB where there is reduced
immune selection and unregulated replication of conserved viral populations.
     •    The pattern of deletions seen here has not been reported as typical of association with either AHB or CHB-AR.

AHB – acute hepatitis b virus infection; CHB-AR – acute reactivation of chronic hepatitis b virus infection; S/CO – sample to cut off ratio.