Scandinavian Journal of Gastroenterology.

2012; 47: 692–701

ORIGINAL ARTICLE

Population-based comparative epidemiological survey of hepatitis B, D,

and C among Inuit migrated to Denmark and in high endemic
Greenland

KARSTEN FLEISCHER REX1,2, HENRIK B KRARUP3, PETER LAURBERG4 &

STIG ANDERSEN1,2
1
Department of Internal Medicine, Queen Ingrid’s Hospital, Nuuk, Greenland, 2Aalborg University Hospital, Arctic
Health Research Centre, Denmark, 3Department of Clinical Biochemistry, Aalborg University Hospital, Denmark, and
4
Department of Endocrinology, Aalborg University Hospital, Denmark

Abstract
Objective. Infection with hepatitis B virus (HBV) is endemic among Arctic populations where it may have a benign course.
However, the relation of HBV to migration to low endemic areas is unknown, as it is for hepatitis D and C, and details on the
influence of delta virus at a population level are lacking. Material and methods. Population-based investigation of
Greenlanders living in Denmark (n = 136) and in Greenland (n = 441). We tested for HBsAg, anti-HBs, anti-HBc, HBeAg,
anti-HBe, HBV-DNA, HBV genotypes, anti-HDV, HDV-RNA, anti-HCV, HCV-Elisa test, HCV-RNA, aspartate amino-
transferase, gamma-glutamyl transferase, bilirubin, and albumin, and performed a physical examination. Results. Partici-
pation rate was 52/95% in Denmark/Greenland. Half of participants in Denmark had lived more than half of their lives in
Denmark, and 54.5% had been exposed to HBV. This was similar to 53% among Greenlanders living in West Greenland
(p = 0.76). HBsAg was positive in 4.4% of Greenlanders in Denmark (n = 6), who all were anti-HBe positive and had low viral
load. Serological signs of HBV infection associated with having both parents born in Greenland (p = 0.007) and with IV drug
use (p = 0.03). We found serological signs of HDV exposure among participants in Denmark/Greenland in 0.7/1.1% (n = 1/5)
and HCV exposure in 1.5/0.0% (n = 2/0). Liver biochemistry was elevated in Greenlanders exposed to HDV. Conclusions.
Hepatitis B, D, and C occurrences among Greenlanders in Denmark mirrored that of Greenland. Importantly, previously
undetected exposure to delta virus associated with elevated liver biochemistry, and the introduction of delta virus is a liability to
Greenlanders and to Greenland.

Key Words: arctic Greenland, Denmark, Greenland Inuit, health, hepatitis B virus infection, hepatitis C virus infection,
hepatitis D virus infection, migration, viral load

Introduction of hepatitis B surface antigen (HBsAg) and develop-

Hepatitis B virus (HBV) is one of the most common
viral infections and more than one-third of the world’s
population has serological markers of present or pre-
vious HBV infection [1]. More than 400 million per-
sons are chronically infected and at risk of developing
cirrhosis or hepatocellular carcinoma [2].
Most adult persons infected with HBV recover
from the acute infection, as manifested by clearance
ment of antibody to hepatitis B surface antigen (anti-
HBs) [3]. Perinatal transmission of infection carries a
90% risk of chronic HBV infection while transmission
later in childhood carries a 30% risk [4].
Frequency and distribution patterns of hepatitis
vary widely according to geographical locality [4,5].
One of the highest rates of HBV infection is found
among the indigenous populations of the Arctic [4].
Early reports of a high occurrence of hepatitis among

Correspondence: Karsten Fleischer Rex, MD, Department of Internal Medicine, Queen Ingrids Hospital, Box 3333, 3900 Nuuk, Greenland. Tel: +299344000.
E-mail: karsten_rex@hotmail.com

(Received 27 August 2011; revised 12 October 2011; accepted 17 October 2011)

ISSN 0036-5521 print/ISSN 1502-7708 online  2012 Informa Healthcare
DOI: 10.3109/00365521.2011.634026

Greenland Inuit [6] were confirmed with the devel-
opment of methods to measure HBsAg [7]. We
recently detailed these observations and documented
HBV exposure in 55% and 88% and chronic HBV
infection in 3% and 29% of 50- through 69-year-olds
in West and in East Greenland respectively using
advanced methods [8]. Still, data on HDV and
HCV exposure need to be reported.
Greenland was under the Danish crown from the
eighteenth century and gained self-government in
2009. Citizens of Greenland have Danish citizenship
and Denmark hosts a group of Greenland Inuit [9].
Migration may be related to disease [10], but even
though there are a number of reports on hepatitis
among Inuit in the Arctic [4,11], studies of hepatitis
in migrated Inuit are lacking. Also studies of HDV
and HCV in Inuit are scarce and lacking in Inuit who
have migrated.
This led us to investigate hepatitis B, D, and C virus
infection among Greenland Inuit living in Denmark
and to add analysis of HDV and HCV to our previous
investigation of HBV among Inuit in Greenland [8] in
order to compare the frequency of serological markers
of infection between Inuit in Greenland and in
Denmark for estimation of the association with migra-
tion. Furthermore, we estimated the influence on
measures such as body-build and liver biochemistry.
Methods
Denmark hosts a population of Greenlanders that
counts more than 5000 individuals born in Greenland
[9]. Among these, we included individuals who had at
least one parent born in Greenland, were 40 through
69 years of age, and lived in Aalborg or Århus County
in Denmark. The regional ethics committee for
Viborg County and Nordjylland County approved
the study in Denmark (VN 20060038). The Com-
mission for Scientific Research in Greenland
approved the study in Greenland (505–99). All sub-
jects gave informed written consent in Danish or
Greenlandic by participant choice.
Participants in Denmark
Name and address of persons born in Greenland and
living in the study areas were obtained from the
National Civil Registration System in which every
person living in Denmark, the Faroe Islands, and
Greenland is recorded.
A letter of invitation was sent to all 312 subjects
identified (Figure 1). Each of the 220 responders was
contacted by telephone for a short telephonic
Hepatitis B, D, C in Inuit and migration 693
interview. We excluded 54 because they did not
have parents born in Greenland, had died, moved
out of the study area, or were unable to give informed
consent for medical reasons. We were unable to
determine the eligibility of the 92 subjects who did
not respond. One hundred and sixty-six were subse-
quently invited to participate. Thirty refrained from
attending (Figure 1).
Participants in Greenland
The methods used in the survey in Greenland have
been reported in detail previously [8]. In brief, we
invited a random sample of 25% of men and women
aged 50 through 69 years in Nuuk in West Greenland
and all men and women in that age range in Tasiilaq,
Tiniteqilaaq, Sermiligaaq, Kuummiut, and Kulusuk
in East Greenland. The participation rate was 95%.
In the present analysis, we included also seven
persons born in Greenland with only one parent
born in Greenland. The investigational procedures
were similar in Greenland and Denmark.
Investigational procedures
We used an interview-based questionnaire in Danish
or Greenlandic as appropriate for the subject. Physical
Selected
312
Not eligible
54
258
No contact
92
166
Nonattenders
30
136
Investigated
Figure 1. Flowchart for identification and inclusion of Greenlan-
ders in Denmark.
694 K. F. Rex et al.
examination included height without shoes, weight in
indoor clothing, and detection of scleral signs of
icterus, spider naevi, and recording of any major
disabilities. KR and SA did this in Denmark and
SA and PL in Greenland.
Information on gender and age was obtained from
the National Civil Registration System. Information
on parents’ birthplace, number of individuals per
room during childhood, education, smoking habits,
alcohol intake, age at first intercourse, number of
sexual partners, IV drug use, and dietary habits
were obtained by using questionnaires. Questions
were asked as written in the questionnaires. Alcohol
intake above two units per day for women and three
for men defined an excess intake. Classification of
dietary habits was based on a food frequency ques-
tionnaire as described in detail elsewhere [12].
A venous blood sample was drawn using minimal
tourniquet, separated and stored at -20 C. Blood
samples were blinded using an 8-digit code and
analyzed in random order. Blood sampling was omit-
ted in four participants in Denmark by participant
choice.
Region of origin was defined as follows: participants
born and raised on the west coast of Greenland north
of the capital Nuuk were classified as “North,” born
and raised in the capital Nuuk were classified as
“West,” born and raised south of capital were classi-
fied as “South,” and born and raised on the east coast
of Greenland were classified as “East.”
Serology
Testing for HBsAg, anti-HBs, HBeAg, anti-HBe,
anti-HBc (total), and anti-HCV was performed using
HBsAg (V2), confirmatory HBsAg, AUSAB, HBe
2.0, anti-HBe 2.0, CORE, anti-HCV 3.0 (Abbott
Axsym System, Abbott Diagnostics a/s, Germany).
Additional testing for anti-HCV was done using
Ortho HCV 3.0 Elisa Test (Ortho-Clinical Diagnos-
tics, Inc., USA) and INNO-LIA HCV Score (Inno-
genetics GmbH, Germany). Testing for anti-delta
antibodies was done using Murex anti-delta (total)
(Murex Biotech Limited, UK).
Virology
HBV-DNA, HBV genotypes, and HCV-RNA were
analyzed with in-house real-time PCR methods using
oligonucleotides as previously published [8].
Nucleic acid. Total DNA was isolated from 200-ml
plasma using QIAamp Virus BioRobot 9604 kit
according to the manufacturer’s instructions (Qiagen
GmbH, Hilden, Germany) and eluted with 125-ml
H2O. Detection and quantification of viral nucleotide
sequences were performed by real-time PCR using
molecular beacons on an Mx3005P Real-Time PCR
System (Stratagene, La Jolla, CA, USA).
Quantification of HBV. Primers were selected from the
pre-core region, amplifying a product of 189 base
pairs (bp) (pos. 1779–1967). Conversion factor
3.7 particles to 1 IU, based on WHO 1st International
Standard for HBV DNA Nucleic Acid-based Tech-
niques (NAT), NIBSC code 97/746. All samples were
analyzed in two independent extractions and runs.
Samples with discordant results were retested in
duplicate [8].
HBV genotyping. Genotype-specific primer pairs and a
common beacon probe were selected from the pre-
S region of the genome, amplifying a PCR product of
approximately 250 bp [8,13].
Quantification of HDV. HDV-1 and HDV-2, located in
the highly conserved area of the HDV genome, ampli-
fied as a product of 175 bp in RT-PCR. A synthetic
RNA internal standard was constructed from a
144 base DNA nucleotide, containing sequences cor-
responding to primers, internal standard probe, and a
T7 promoter at the 5’ terminus. The nucleotide was
amplified with a T7 primer (GTAATACGACTCAC-
TATAGGGG) and HDV-2, precipitated with EtOH,
dissolved in H2O, and transcribed with T7 RNA
polymerase (Roche). After treatment with DNase
1 (Invitrogen), the RNA internal standard was diluted
in H2O containing 20: g/ml tRNA (Pharmacia). An
external standard was prepared by RT-PCR of RNA
isolated from an HDV-positive sample. A 10-fold dilu-
tion series of the purified product was used as external
standards.
Reverse transcription. To 30 l of sample RNA were
added 10 l RT-mix containing 200 mmol/l Tris-
HCl (pH 8.3), 300 mmol/l KCl, 12 mmol/l MgCl2,
5 mmol/l dithiothreitol, 1.25 mmol/l of dATP, dGTP,
dCTP, and dUTP, 0.1 g random hexamer (pd(N)6,
Pharmacia), 2.5 U ribonuclease inhibitor (Invitro-
gen), 2 U reverse transcriptase (Superscript III, Invi-
trogen), and 103 copies of RNA internal standard.
Reverse transcription was carried out for 30 min at
37 C, followed by 5 min at 95 C, and cooled to room
temperature. Ten liters of sample cDNA or external
standard was added to 20 l reaction mix containing
50 mmol/l Tris-HCl (pH 8.8), 75 mmol/l KCl,
10 mmol/l MgCl2, 0.15% Tween 20, 250 mol/
l each of dATP, dGTP, dCTP, and dUTP (Roche),
0.25 U Taq DNA polymerase (BioTaq), 1 mol/l of

HDV-1 and HDV-2, 0.05 mol/l internal-standard
beacon, and 0.25 mol/HDV-beacon. PCR was per-
formed by 45 cycles of denaturation (95 C, 10 s),
annealing/detection (60 C, 30 s), and extension
(72 C, 30 s).
Quantification of HCV. HCV-RNA was measured
by an in-house RT-PCR method as previously
described [8].
Biochemistry
Aspartate aminotransferase (AST), gamma glutamyl-
transferase (GGT), bilirubin (bili), and albumin (alb)
were measured on a Vitros Chemistry System
950 (Ortho-Clinical Diagnostics, Inc., Raritan, NJ,
USA). AST but not alanine aminotransferase and
international normalized ratio were measured as
serum was frozen for transport to the laboratory in
Denmark. AST was considered the more relevant
aminotransferase for evaluation of liver cirrhosis.
Statistics
Results are described by frequencies or by median
values with 25 and 75 percentiles as appropriate. Chi-
squared test was used for comparison of proportions
and Mann–Whitney U-test for comparison of median
values.
Serologically determined exposure to HBV was
entered as dependent variable in multivariate logistic
regression while explanatory factors entered were
gender, age, number of parents born in Greenland,
alcohol use, history of IV drug use, age at first inter-
course, and living less than 10 years in Greenland.
Liver biochemistry was entered as dependent var-
iable in multivariate linear regression after logarithmic
transformation with gender, age, alcohol, BMI, intake
of Greenlandic diet, and exposure to HBV entered as
explanatory variables.
Data were processed and analyzed using Corel
Quattro Pro X3 (Corel Corporation, Ottawa,
Ontario, Canada) and the Statistical Package for
the Social Sciences version 13.0 (SPSS Inc., Chicago,
Ill., USA). A two-sided p value of less than 0.05 was
considered significant.
Results
Participation rate in Denmark was 52.2%. The
136 Inuit in Denmark comprised 33 men and
103 women of which 81% had both parents born in
Greenland (Table I) and 46% had lived more than
Hepatitis B, D, C in Inuit and migration 695
half of their life in Denmark. Excess alcohol intake
was reported by 17% while 75% reported some alco-
hol intake, 66% were smokers, and 2.2% IV drug
users. More than one sexual partner within the pre-
vious year was reported by 5.1%. History of hepatitis
(7.5%) and hepatitis vaccination (10.7%) did not
associated with HBV status (p = 0.69 and
p = 0.86). We found one (0.7%) with spider naevi
and eight (5.9%) with yellow sclera without associa-
tion with HBV infection (p = 0.33 and p = 0.60).
The 434 participants in Greenland with both par-
ents born in Greenland have been described in detail
previously [8]. Here we included also 7 with only one
parent born in Greenland thus counting 288 Inuit in
East Greenland and 153 in Nuuk in West Greenland.
Hepatitis B, D, and C in Greenland
Serological signs of hepatitis B exposure are shown
in Table II. None had signs of liver disease on the
physical examination.
Testing for delta virus was done on all samples with
positive HBsAg, anti-HBs, or anti-HBc (n = 342).
Anti-delta was positive in five (Table II). Testing for
HDV-RNA found four with immeasurable HDV-
RNA and one could not be amplified (Table III).
All samples were tested for HCV antibodies and
35 (8.1%) were anti-HCV positive. Further testing
with Ortho HCV 3.0 Elisa Test found 2 of the
35 positive, while none of the 35 was positive using
INNO-LIA HCV Score as confirmatory test (Table
II). HCV-RNA was immeasurable in all 35 samples.
Hepatitis B, D, and C in Denmark
Serological markers of hepatitis B, D, and C exposure
are shown in Table II. One participant had been
exposed to both hepatitis B and D virus and one
had been exposed to both hepatitis B and C virus.
The latter had lived in Denmark for 47 of 50 years and
had a history of IV drug use.
Present HBV infection was found in five women
and one man (Table IV). All were anti-HBe positive
and viral load was low, 200 copies/ml being the high-
est. Detection of precore mutation and genotype was
not possible in any of these subjects. None were anti-
HDV or anti-HCV positive. Two reported excess
alcohol intake, of which one had a history of IV
drug use and had elevated GGT (Table IV).
Hepatitis and demography
Having parents both born in Greenland associated with
a higher probability of HBV infection (p = 0.01) as did
IV drug use (0.028) (Table I). Age, gender, smoking
696 K. F. Rex et al.

Table I. Occurrence of HBV infection among Greenlanders who have migrated to Denmark.
All Hepatitis B virus infectiona
Present Previous Never pb
n % n % n % n %
c
Overall 136 100 6 4.5 66 50.0 60 45.5
Anti-HCVd Positive 2 1.6 0 0.0 1 50.0 1 50.0
Negative 126 98.4 5 4.0 63 50.0 58 46.0
Anti-HDVe Positive 1 1.4 0 0.0 1 100 na
Negative 69 98.6 6 8.7 63 91.3 na
Gender Men 33 24.3 1 3.1 13 40.6 18 56.3 0.36
Women 103 75.7 5 5.0 53 53.0 42 42.0
Age 40–49 37 27.2 1 2.8 18 50.0 17 47.2 0.41
50–59 73 53.7 2 2.9 37 52.9 31 44.3
60–69 26 19.3 3 11.5 11 42.3 12 46.2
Smokerf Never 16 11.9 1 6.7 4 26.7 10 66.7 0.22
Past 30 22.4 0 0.0 14 50.0 14 50.0
Present 88 65.7 5 5.7 47 54.0 35 40.2
Alcoholg,h Never 8 6.0 0 0.0 6 85.7 1 14.3 0.088
Past 25 18.8 3 13.0 10 43.5 10 43.5
Present 100 75.2 3 3.0 48 48.5 48 48.5
Excessg 23 17.4 2 9.1 10 45.5 10 45.5 0.55
Parents born in Greenlandi Both 110 81.5 5 4.6 60 55.6 43 39.8 0.010
One 25 18.5 0 0.0 6 26.1 17 73.9
Region of origini North 67 49.6 2 3.0 35 53.0 29 44.0 0.14
West 18 13.3 0 0.0 9 50.0 9 50.0
South 45 33.3 4 9.5 17 40.5 21 50.0
East 5 3.7 0 0.0 5 100 0 0.0
Years in Denmarkf 0–9 33 24.6 0 0.0 19 59.4 13 40.6 0.064
10–29 46 34.3 4 9.1 25 56.8 15 34.1
30+ 55 41.0 2 3.7 21 38.9 31 57.4
IV drug usef Yes 3 2.2 1 33.3 2 66.7 0 0.0 0.028
No 131 97.8 5 3.9 64 49.6 60 46.5
Number of persons per room at the age of 5h <1 24 18.0 2 9.1 6 27.3 14 63.6 0.40
2 69 51.9 2 2.9 36 52.9 30 44.1
3 20 15.0 1 5.0 11 55.0 8 40.0
4+ 20 15.0 1 5.3 11 57.9 7 36.8

Abbreviation: na = not applicable.

a
Present: HBsAg positive; Previous: HBsAg negative and anti-HBS and/or anti-HBc positive; Never: HBsAg, anti-HBS, and anti-
HBc negative. Analysis not possible in four who chose not to have blood sampled.
b
Chi-squared test for difference between HBV groups.
c
Blood sampling omitted in four by participant choice.
d
Data missing in eight.
e
Tested in 70 exposed to HBV.
f
Data missing in two.
g
More than 14/21 units per week for women/men at any period in life. Present drinkers include those with excess intake.
h
Data missing in three.
i
Data missing in one.

habit, alcohol intake, age at first intercourse, number of
sexual partners, education, and crowding during child-
hood did not associate with HBV infection (Table I).
Exposure to HBV was more likely with both than
with only one parent born in Greenland (OR 4.1, 95%
CI, 1.5–11.7, p = 0.007) after adjusting for gender, age,
and IV drug use in multivariate logistic regression.
Hepatitis and health
Infection with HBV did not influence height, weight,
or BMI among Greenlanders in Denmark (Table V)
or in Greenland [8]. Also liver biochemistry did not
differ with HBV infection in the crude comparisons
(Table V) or after adjusting for age, gender, BMI,
Greenlandic diet, and alcohol use in multivariate
linear regression models.
Details on the six Greenlanders who harbored delta
virus are given in Table III. Three had never lived
outside Greenland, two had lived 1 and 8 years in
small towns in Denmark, and one lived in Denmark
since 18 years. The latter had lived 35 years in West
Greenland north of Nuuk. All had elevated GGT and
one had elevated AST.
 Hepatitis B, D, C in Inuit and migration 697

Table II. Hepatitis B, D, and C virus exposure among Greenlanders who have migrated to Denmark or live in Greenland.
Hepatitis virus exposure in Greenland Inuit living in
Denmark West Greenland East Greenland
n % n % n % pa pb

Hepatitis Bc < 0.001 ns

Present 6 4.5 4 2.6 83 28.9
Previous 66 50.0 78 51.7 169 58.9
Hepatitis Dd ns ns
Present 0 0.0 0 0.0 0 0.0
Previous 1 0.7 1 0.7 4 1.4
Hepatitis Ce ns ns
Present 0 0 0 0.0 0 0.0
Previous 2 1.5 0 0.0 0 0.0
a
Chi-squared test for comparing occurrence in Denmark and Greenland; ns: not significant.
b
Chi-squared test for comparing occurrence in Denmark and West Greenland; ns: not significant.
c
Present: HBsAg positive; Previous: HBsAg negative and anti-HBS and/or anti-HBc positive.
d
Present: Anti-delta antibody and HDV-RNA positive. Previous: Anti-delta positive but HDV-RNA negative.
e
Present: Anti-HCV antibody and HCV-RNA positive. Previous: Anti-HCV positive but HCV-RNA negative.

Hepatitis and migration
The pattern of HBV infection among Greenlanders
living in Denmark is depicted in Figure 2 by region of
origin. This portrayed the pattern found in Greenland
(East Greenland, p = 0.18; West Greenland, p = 0.76).
Also Greenlanders living in Greenland and in Den-
mark had similar frequencies of HBsAg (East/West
Greenland origin, p = 0.15/0.48), anti-HBs (p = 0.31/
0.57), and anti-HBc (p = 0.68/0.87).
Discussion
Hepatitis virus infection frequencies vary depending
on geography. HBV is endemic in the Arctic [11,14]
but varies between Inuit populations. Thus, 1.7% to
3.2% were reported HBsAg positive in Russia, 5%
among Canadian Arctic residents with 20 times
higher HBV exposures compared with Canadian
South, and 6.4% were HBsAg positive in Alaska
natives. In Greenland, 7.0% were reported HBsAg
positive in two towns on the west coast [15], 3% in the
capital [8], and 29% in East Greenland [8] consistent
with early findings [7,16]. The wide range of HBV
infections in Arctic populations from below 2% to
almost 30% should be considered among Inuit who
migrate to other regions. This has gained some atten-
tion among refugees in other populations [17] but
poses equal challenges to health-care providers to
Inuit migrants.
Migration associates with a number of health
aspects. Migration from Greenland to Denmark
itself may influence cardiovascular risk factors, that
is, blood pressure and obesity [10], and cancer
[18,19]. The frequency of some cancers increase
with migration while it remains unaltered for others
[18,19]. This suggests that both environmental and
genetic factors may influence the change in frequen-
cies of disease with migration. These studies were,
however, based on cancer registries that have inher-
ited limitations. Diagnostic threshold and capacities
differ between Greenland and Denmark, and this may
influence the detection of disease as well as the
migration as some move to Denmark for diagnostic
workup and treatments not available in Greenland.
These limitations may be overcome by population-
based surveys such as the present.
This is the first population-based comparative
epidemiological investigations of hepatitis virus infec-
tions in Arctic populations, and we report frequencies of
serological markers of hepatitis B, D, and C virus infec-
tion among Greenlanders living in Greenland and
migrated to Denmark. The data on HBV among the
former were included here for comparison though they
have been reported previously [8]. Analysis of HDV and
HCV were added here and methods used were identical.
None of the participants received antiviral therapy.
We found similar occurrences of HBV infection
among Greenlanders in Greenland and in Denmark.
This was further confirmed in direct comparisons of
the frequencies of HBsAg, anti-HBs, and anti-HBc.
The lower HBsAg frequency in West Greenland
compared with previous findings (7%) by Langer
[15] and (19%) by Børresen [20] may likely be due
to differences in recruitment of participants.
Langer et al. enrolled participants from the hospital,
factories, shops, restaurants, and via the local radio
with the risk of introducing selection bias, and
Børresen et al. investigated 115 of 133 living in one
settlement. Still, large variations were seen with 27%
 698

Table III. Descriptions of the six Greenlanders in Greenland and Denmark who had serological signs of HDV exposure.
Parents born Region of Country of Years in Excess
Age Gender in Greenland origin residence Denmark alcohol HBsAg Anti-HBs Anti-HBc HBV-DNAa Anti-HBe Anti-HDV HDV-RNA Anti-HCV ASTb GGTc Albd Bilie

53 Man Both East Greenland 0 No - + + - + - - 30 282 39 3

54 Man Both East Greenland 0 No + 0 + + - - 45 76 45 4
K. F. Rex et al.

57 Woman Both East Greenland 0 No - + + - + - - 35 297 44 3

59 Man Both East Greenland 1 No - + + - + - - 34 292 45 4
58 Man Both West Greenland 8 No - + + - + - - 108 230 41 12
53 Woman Both West Denmark 18 No - + - - + - - 30 78 49 4
a
iU/ml.
b
Laboratory reference range 10–50 U/l.
c
Laboratory reference range 12–75 U/l.
d
Laboratory reference range 40–51 g/l.
e
Laboratory reference range 4–21 mM/l.

Table IV. Descriptions of the six Greenlanders migrated to Denmark who had present HBV infection. All had too low viral load to allow for genotype determination.
Parents born Region of Years in Excess I.V.
Age Gender in Greenland origin Denmark alcohol drugs HBsAg HBV-DNAa HBeAg Anti-HBe Anti-HDV Anti-HCV ASTb GGTc Albd Bilie

46 Man na North 24 No No + 200 - + - - 21 35 41 na

51 Woman Both South 20 No No + 0 - + - - 20 28 43 4
52 Woman Both South 39 Yes Yes + 0 - + - - 47 121 46 10
62 Woman Both South 11 No No + 0 - + - - 41 52 47 4
65 Woman Both North 16 No No + 60 - + - - 21 23 40 na
69 Woman Both South 37 Yes No + 80 - + - - 25 53 43 na

na Uncertain birthplace of one parent.

a
iU/ml.
b
Laboratory reference range 10–50 U/l.
c
Laboratory reference range 12–75 U/l.
d
Laboratory reference range 40–51 g/l.
e
Laboratory reference range 4–21 mM/l.
 Hepatitis B, D, C in Inuit and migration 699

0.51
0.57
0.52
0.13
0.90
0.17

0.57
0.38
0.59
0.90
in one settlement on the west coast [20] and 29%

pb
in Ammassalik district in East Greenland [8] as
discussed [8]. The lack of indicators of liver
disease among the participants conforms to the

30.2
29.7
percentile

183
163
88
77

27
67

51
notion of a benign course of hepatitis B among adult

6
25, 75

167,
153,
73,
55,
24.9,
22.8,

10,
26,
3,
43,
Greenland Inuit irrespective of migration. However,
the risk of introduction of delta virus is a liability to
Never

Greenlanders.
Arctic HDV infection has been reported in 4 of
Median

245 HBsAg-positive sera from Yukon and Northwest

26.6
23.7
172
157
83
61

22
35

46
5
Territories in western Canada [21] while none of
186 native Indian and Inuit and nonnative in
Newfoundland and Labrador [22] and none of

Present: HBsAg positive; Previous: HBsAg negative and anti-HBS and/or anti-HBc positive; never: HBsAg, anti-HBS, and anti-HBc negative.
53 HBsAg-positive Alaskan natives had evidence of
Hepatitis B virus infectiona

29.3
28.4
percentile

175
160

HDV infection [23]. We found 6 anti-HDV positive

89
69

29
92

51
6
25, 75

in 342 HBV exposed Greenlanders in Greenland and

166,
152,
68,
51,

10,
27,
23.7,

3,
43,
21.0,
Table V. Body-build and liver biochemistry by hepatitis B virus infection status among Greenlanders who have migrated to Denmark.

1 in 136 in Denmark. This is lower than the previous

Previous

findings of 10% and 7% in HBsAg positive in two

towns in West Greenland [15,24]. Langer et al.
reported 14 anti-HDV positive out of 35 HBsAg-
Median

27.5
23.2
171
156
81
58

22
36

45

positive individuals among 501 participants, of which

4

210 had been exposed to HBV [15]. Børresen et al.

Abbreviations: BMI = body mass index; AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase.

found HDV antibodies in 21 of 31 HBsAg positive

among 115 dwellers of one settlement that differed
22.8, 34.9

from a neighboring settlement of similar size that

percentile

151, 166

57, 82

21, 42
27, 70

41, 46
4, 10
NA

hosted none with HDV among 4 HBsAg positive

Difference between HBV exposed and non-exposed. Mann–Whitney U-test for comparing medians.
25, 75

na

na

[20]. Such large variation may introduce uncertainty

Present

in the investigations of the occurrence of HDV in

Greenland, where the population of a mere 56,000 is
scattered and live in isolated cluster habitats along the
Median

20.8
26.0

coast. Our investigation in Denmark included Green-

173
155
63
71

23
43

43
4

landers from all over Greenland and did not suggest

high rates of HDV in general. Our single participant
in Denmark with evidence of former HDV infection
had average height and weight, and reported icterus
29.8
28.7
percentile

177
163
89
74

28
71

51

when aged 22 years, and was at that time living in

6
25, 75

166,
153,
71,
53,
24.2,
21.8,

10,
27,
3,
43,

the region of West Greenland studied previously

[15,20,24]. Still, the high rates of HBV exposure
All

confirmed in Greenlanders in both Greenland and

Denmark call for attention as all our Greenland
Median

participants with evidence of HDV infection had

171.4
156.0

27.2
23.7
83
60

22
36

46
4

elevated liver biochemistry even though HDV-RNA

could not be detected.
Our HCV screening result of 8% positive is in
contrast to the confirmatory tests. At least half of
Women

Women

Women

persons truly exposed to HCV would have chronic

Men

Men

Men

infection and be HCV-RNA positive. We found

none. Immeasurable HCV-RNA could be explained
na Data not applicable.

by dual infection with both HCV and HBV as one of

the infections usually becomes dominant. However,
Liver biochemistry

Bilirubin (mmol/l)

our HCV screening positive results were not

Albumin (g/l)
BMI (kg/m2)
Height (cm)

attached to HBsAg-positive persons. We believe

Weight (kg)
Body-build

GGT (U/l)
AST (U/l)

that the screening results relate to test problems

and not HCV infection. Thus, our finding of around
1% of Greenlanders in Denmark with anti-HCV is
b
a
700 K. F. Rex et al.

100%
North (n = 67)
80%
HBV infection

60%

40%

20%

0%
Never Previous Present

100%
Capital (n = 18)
80%
HBV infection

60%
East (n = 5)
40%
100%
20%
80%

HBV infection
0%
60%
Never Previous Present
40%
100%
20%
South (n = 45)
80%
HBV infection

0%
60% Present Previous Never

40%

20%

0%
Never Previous Present

Figure 2. Map with the occurrence of markers of hepatitis B virus (HBV) infection among Greenlanders who have migrated to Denmark
depicted by region of origin.

in keeping with the single report of 0.8% anti-
HCV positive in the selected population in two
towns in West Greenland [15] and similar to reports
of low frequency of HCV in the remaining Arctic
[4,11].
We identified 312 potential participants in Den-
mark. Some could be excluded because they were not
of Greenlandic descent or had moved. We were
unable to determine the eligibility of 92 subjects
who did not respond. Some may have chosen not
to respond because they were of non-Greenlandic
descent. Also migrated Greenlanders change address
within Denmark relatively frequently and some delay
in the recording thereof is common and may explain
some of the nonresponders. Finally, some Greenland
Inuit in Denmark have no permanent address. The
latter may contribute an underestimation of the
frequency of hepatitis but counted for only a few
individuals.
In conclusion, migration is a complex process, but
similar frequencies of hepatitis B, D, and C found in
Denmark and Greenland suggest that hepatitis does
not motivate migration. The HDV outbreak in a
settlement in West Greenland caused alert, and it
may be inferred from this population-based study that
HDV infection can turn into a problem among Inuit
from other regions in Greenland. The group with
chronic HBV infection is confirmed to be of consid-
erable size and poses a risk to the society of Greenland
and should be kept in mind among individuals who
have migrated from high endemic areas.
Acknowledgements
Supported by grants from Greenland Homerule; the
Aalborg City Christmas Lottery; the Obel Family
Foundation; the Northern Jutland Research Founda-
tion; the Danish Hospital Foundation for Medical

Research region of Copenhagen, the Faroe Islands,
and Greenland.
Declaration of interest: The authors report no
conflicts of interest. The authors alone are responsible
for the content and writing of the paper.
References
[1] Alter MJ. Epidemiology and prevention of hepatitis B. Semin
Liver Dis 2003;23:39–46.
[2] Lavanchy D. Hepatitis B virus epidemiology, disease burden,
treatment, and current and emerging prevention and control
measures. J Viral Hepat 2004;11:97–107.
[3] McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and
clinical outcomes of 1536 alaska natives chronically infected
with hepatitis B virus. Ann Intern Med 2001;135:759–68.
[4] McMahon BJ. Viral hepatitis in the Arctic. Int J Circumpolar
Health 2004;635(2 Suppl):41–8.
[5] Hadler SC, Margolis HS. Epidemiology of hepatitis B virus
infection. In Ellis R, editor. Hepatitis B Vaccines in Clinical
Practice. New York: Dekker M, Inc; 1993. pp 141–57.
[6] Berthelsen A. Hepatitis epidemica. Grønlands medicinsk sta-
tistik og nosografi. Meddelelser Om Grønland 1943;177:137–9.
[7] Skinhøj P, McNair A, Andersen ST. Hepatitis and hepatitis
B-antigen in Greenland. Am J Epidemiol 1974;99:50–7.
[8] Krarup HB, Andersen S, Madsen PH, Okkels H,
Hvingel BH, Laurberg P. Benign course of long-standing
hepatitis B virus infection among Greenland Inuit? Scand J
Gastroenterol 2008;43:334–43.
[9] Greenlanders living in Denmark. Report by The North
Atlantic Group in the Danish Parlament; 2007.
[10] Bjerregaard P, Jørgensen ME, Lumholt P, Mosgaard L,
Borch-Johnsen K. Higher bloodpressure among Inuit
migrants in Denmark than among the Inuit in Greenland.
J Epidemiol Community Health 2002;56:279–84.
[11] Tulisov A, McMahon BJ, Koch A, Minuk G, Chulanov V,
Bruce MG. Viral Hepatitis in the Arctic. A Review from a
Circumpolar Workshop on Viral Hepatitis, ICCH13. Alaska
Med 2007;49(2 Suppl):193–203.
[12] Andersen S, Hvingel B, Kleinschmidt K, Jørgensen T,
Lauerberg P. Changes in iodine excretion in 50–69-y-
old denizens of an Arctic society in transition and
iodine excretion as a biomarker of the frequency of
Hepatitis B, D, C in Inuit and migration 701
consumption of traditional Inuit foods. Am J Clin Nutr
2005;81:656–63.
[13] Naito H, Hayashi S, Abe K. Rapid and specific genotype
system for hepatitis B virus corresponding to six major
genotypes by PCR using type-specific primers. J Clin
Microbiol 2001;39:362–4.
[14] Gish RG, Gadano AC. Chronic hepatitis B: current epide-
miology in the Americas and implications for management.
J Viral Hepat 2006;13:787–98.
[15] Langer BC, Frosner GG, Brunn AV. Epidemiological study
of viral hepatitis A, B, C, D and E among Inuits in West
Greenland. J Viral Hepat 1997;4:339–49.
[16] Skinhoj P. Hepatitis and hepatitis B-antigen in Greenland II:
Occurrence and interrelation of hepatitis B associated
surface, core, and "e" antigen-antibody systems in a highly
endemic area. Am J Epidemiol 1977;105:99–106.
[17] Lifson AR, Thai D, O’Fallon A, Mills WA, Hang K. Prev-
alence of tuberculosis, hepatitis B virus, and intestinal par-
asitic infections among refugees to Minnesota. Public Health
Rep 2002;117:69–77.
[18] Prener A, Nielsen NH, Hansen JP, Jensen OM. Cancer
pattern among Greenlandic Inuit migrants in Denmark,
1968–1982. Br J Cancer 1987;56:679–84.
[19] Boysen T, Friborg J, Andersen A, Poulsen GN, Wohlfahrt J,
Melbye M. The Inuit cancer pattern-the influence of
migration. Int J Cancer 2008;122:2568–72.
[20] Børresen ML, Olsen OR, Ladefoged K, McMahon BJ,
Hjuler T, Panum I, et al. Hepatitis D outbreak among
children in a hepatitis B hyper-endemic settlement in
Greenland. J Viral Hepat 2010;17:162–70.
[21] Cheng HH, Wang DQ, Minuk GY, Anand CM, Stowe TC,
Buchan KA. The prevalence of antibody to delta virus in
western Canada. Clin Invest Med 1986;9:156–9.
[22] Ratnam S, Head CB, Butler RW. Lack of evidence of
hepatitis D (delta) infection in Newfoundland and Labrador.
Can Med Assoc J 1986;134:905–7.
[23] Harpaz R, McMahon BJ, Margolis HS, Shapiro CN,
Havron D, Carpenter G, et al. Elimination of new
chronic hepatitis B virus infections: results of the
Alaska immunization program. J Infect Dis 2000;181:
413–18.
[24] Olsen OR, Skinhøj P, Krogsgaard K, Baek L. Hepatitis B
- an endemic sexually transmitted infection in a local
community in Greenland.Ugeskr Laeger. 1989;151:
1668–70.
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