To the Editor‐in‐Chief

We would like to applaud Chen and colleagues for their recent study of hepatitis B screening data in US travelers attending travel clinics in the Boston area.1 This article elegantly described how pretravel encounters represent unique opportunities to screen travelers for the most common cause of chronic liver disease worldwide,2 to identify and educate those infected with the hepatitis B virus (HBV), and to promote vaccination for those found to be susceptible.

In their analysis, 48 of 496 travelers with available test results (10%) had antibody to the hepatitis B core antigen (anti‐HBc) as the only positive HBV serum marker. The authors describe this test profile as indicative of “possible HBV exposure” without elaborating further. However, we would like to emphasize that travel health providers taking care of foreign‐born travelers from HBsAg high‐prevalence areas that are at times also highly prevalent for infection with the human immunodeficiency virus (HIV) and hepatitis C virus (HCV)2,3 need to recognize this serological pattern, and understand its clinical implications.

Isolated anti‐HBc, only rarely reported (<1%) in HBsAg low‐prevalence areas, has been frequently observed (10%–20%) in HBV‐endemic countries or in immigrant groups from such countries,4–6 as well as in individuals coinfected with HIV or HCV.7 While a false‐positive test result has been suggested as a likely explanation for this serological pattern in individuals from HBsAg low‐prevalence regions, the “window phase” of acute HBV infection, resolved HBV infection with low or undetectable levels of anti‐HBs, or occult chronic HBV infection with low or undetectable HBsAg or mutant HBsAg (that prevents its detection) need to be considered as diagnostic possibilities in immigrants from HBsAg high‐prevalence areas.8

The frequency of occult chronic HBV infection mostly characterized by low‐level viremia and no or minimal signs of liver inflammation has been quite variable (0%–40%) depending on the population studied, and its potential for chronic liver disease has been questioned.8,9 Yet, significant viral reactivation has been observed in the setting of immunosuppression such as chemotherapy, solid organ/bone marrow transplantation, HIV infection, or antitumor necrosis factor therapy.9,10

So, what are the practical implications for travelers with isolated anti‐HBcAg? Identifying this serological status may in fact offer another opportunity for additional diagnostic work‐up that the traveler may benefit from in the short as well as long term. Repeat testing for anti‐HBc, HBsAg, anti‐HBe, and anti‐HBs may help rule out a false‐positive result, and vaccination might be in order.8,9 The presence of IgM anti‐HBc or anti‐HBe would indicate recent HBV infection or prior exposure to HBV, respectively, and further follow‐up to assess serum alanine aminotransferase activity and changes of serological markers may be necessary. Finally, in individuals with persistent isolated anti‐HBc, serum HBV DNA to exclude chronic HBV infection and screening for HCV and HIV may also merit consideration.8,9

References

1
Chen
LH
Barnett
ED
Wilson
ME
, et al.
Hepatitis B screening in US travelers seen at the Boston area travel medicine network
.
J Travel Med
 
2013
;
20
:
29
36
.
2
Kourtis
AP
Bulterys
M
Hu
DJ
Jamieson
DJ
.
HIV‐HBV coinfection—a global challenge
.
N Engl J Med
 
2012
;
366
:
1749
1752
.
3
Madhava
V
Burgess
C
Drucker
E
.
Epidemiology of chronic hepatitis C virus infection in sub‐Saharan Africa
.
Lancet Infect Dis
 
2002
;
2
:
293
302
.
4
Lok
AS
Lai
CL
Wu
PC
.
Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs
.
Hepatology
 
1988
;
8
:
766
.
5
Gibney
KB
Torresi
J
Lemoh
C
Biggs
BA
.
Isolated core antibody hepatitis B in sub‐Saharan African immigrants
.
J Med Virol
 
2008
;
80
:
1565
1569
.
6
Majori
S
Baldo
V
Tommasi
I
, et al.
Hepatitis A, B, and C infection in a community of sub‐Saharan immigrants living in Verona (Italy)
.
J Travel Med
 
2008
;
15
:
323
327
.
7
Witt
MD
Lewis
RJ
Rieg
G
, et al.
Predictors of the isolated hepatitis B core antibody pattern in HIV‐infected and ‐uninfected men in the multicenter AIDS cohort study
.
Clin Infect Dis
 
2012
;
56
:
606
612
.
8
Grob
P
Jilg
W
Bornhak
H
, et al.
Serologic pattern “anti‐HBc alone”: report on a workshop
.
J Med Virol
 
2000
;
62
:
450
455
.
9
Knöll
A
Hartmann
A
Hamoshi
H
Weislmaier
K
Jilg
W
.
Serological pattern “anti‐HBc alone”: characterization of 52 individuals and clinical significance
.
World J Gastroenterol
 
2006
;
12
:
1255
1260
.
10
Lee
YH
Bae
SC
Song
GG
.
Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti‐tumor necrosis factor therapy
.
Clin Exp Rheumatol
 
2013
;
31
:
118
121
.