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RESEARCH ARTICLE
The high burden of comorbidities in
Aboriginal and Torres Strait Islander
Australians living with chronic hepatitis B in
Far North Queensland, Australia, and the
implications for patient management
Jordan Riddell
1
, Allison Hempenstall
2
, Yoko Nakata
2
, Sandra Gregson
2
, Richard Hayes
2
,
Simon Smith
1
, Marlow Coates
2
, Lizzie Charlie
2
, Christine Perrett
2
, Victoria Newie
2
,
Tomi Newie
2
, Sharna Radlof
1
, Josh HansonID
1,3
*
1Department of Medicine, Cairns Hospital, Cairns, Queensland, Australia, 2Torres and Cape Hospital and
Health Service, Queensland, Australia, 3Kirby Institute, University of New South Wales, Sydney, Australia
*jhanson@kirby.unsw.edu.au
Abstract
Background
Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B virus (HBV)
infection have a significant burden of hepatocellular carcinoma (HCC). The prevalence of
comorbidities that increase the risk of HCC in this population is incompletely defined.
Methods
This cross-sectional study was performed in remote tropical Queensland, Australia in Janu-
ary 2021. All individuals living with chronic HBV in the region were identified; the prevalence
of relevant comorbidities was determined by reviewing medical records.
Results
All 236 individuals in the cohort identified as Aboriginal and Torres Strait Islander Austra-
lians; their median (interquartile range (IQR)) age was 48 (40–62) years; 120/236 (50.9%)
were female. Of the 194/236 (82.2%) engaged in HBV care, 61 (31.4%) met criteria for HBV
therapy and 38 (62.2%) were receiving it. However, 142/236 (60.2%) were obese, 73/236
(30.9%) were current smokers and 57/236 (24.2%) were drinking alcohol hazardously; 70/
236 (29.7%) had 2 of these additional risk factors for HCC, only 43/236 (18.2%) had none.
Among the 19 patients with confirmed cirrhosis, 9 (47%) were obese, 8 (42%) were cur-
rently—or had a history of—drinking alcohol hazardously and 5 (26.3%) were current smok-
ers. Patients also had a median (IQR) of 3 (2–4) cardiovascular risk factors (cigarette
smoking, hypertension, impaired glucose tolerance, dyslipidaemia, renal impairment/pro-
teinuria). Only 9/236 (3.8%) did not have one of these 5 comorbidities.
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OPEN ACCESS
Citation: Riddell J, Hempenstall A, Nakata Y,
Gregson S, Hayes R, Smith S, et al. (2023) The
high burden of comorbidities in Aboriginal and
Torres Strait Islander Australians living with
chronic hepatitis B in Far North Queensland,
Australia, and the implications for patient
management. PLoS ONE 18(4): e0284151. https://
doi.org/10.1371/journal.pone.0284151
Editor: Mohamed El-Kassas, Helwan University,
EGYPT
Received: April 8, 2022
Accepted: March 26, 2023
Published: April 6, 2023
Peer Review History: PLOS recognizes the
benefits of transparency in the peer review
process; therefore, we enable the publication of
all of the content of peer review and author
responses alongside final, published articles. The
editorial history of this article is available here:
https://doi.org/10.1371/journal.pone.0284151
Copyright: ©2023 Riddell et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: Data cannot be
shared publicly because of the ethical protections
Conclusions
Aboriginal and Torres Strait Islander Australians living with chronic HBV in this region of
remote Australia have a high engagement with HBV care and the majority of individuals eli-
gible for antiviral therapy are receiving it. However, a significant comorbidity burden
increases their risk of cirrhosis, HCC, and premature death. It is essential to integrate
chronic HBV care with management of these comorbidities—rather than focusing on HBV
alone—to achieve optimal health outcomes.
Introduction
Australia’s burden of chronic hepatitis B (CHB) is disproportionately borne by its first people,
Aboriginal and Torres Strait Islander Australians (hereafter respectfully referred to, collec-
tively, as Indigenous Australians). The national prevalence of CHB in Indigenous Australians
is estimated to be 2.0%, compared to a prevalence of 0.9% in the general population [1]. This
contributes to a 4–6 times higher incidence of hepatocellular carcinoma (HCC) in Indigenous
Australians, with CHB present in 25.3% of Indigenous Australians diagnosed with HCC com-
pared to 9.9% of non-Indigenous Australians with this cancer [2,3].
The optimal approach to reducing HCC-related mortality among Indigenous Australians
living with CHB remains incompletely defined. The prescription of antiviral therapy, when
indicated, is clearly essential—and highly cost-effective—although HCC can still develop on
therapy [4,5]. To identify HCC earlier in those both on—and off—antiviral therapy, it is rec-
ommended that all Indigenous Australians 50 years of age receive 6-monthly ultrasound sur-
veillance for HCC, with or without alpha-fetoprotein (AFP) [6,7]. However, it is challenging
to provide this HCC surveillance for Indigenous Australians living in remote Australia, indeed,
the cost-effectiveness of the strategy has yet to be established [8–11]. Access to imaging is usu-
ally limited in these locations and there are many other health conditions—particularly macro-
vascular disease, diabetes mellitus, chronic lung disease and chronic kidney disease—that
compete for finite resources [9,12].
These other health conditions, strongly linked to socioeconomic disadvantage, have their
own attributable morbidity and mortality [12–14]. Furthermore, they also make a significant
contribution to the poor outcomes seen in Indigenous Australians diagnosed with HCC.
Indeed, in a large Australian study of patients diagnosed with HCC, a higher comorbidity bur-
den and remote residential address were the strongest predictors of HCC-related mortality;
Indigenous status was not, in fact, independently prognostic [2].
The current prevalence of CHB in some communities in the Torres Strait Islands (TSI) and
Northern Peninsula Area (NPA) in remote tropical Australia is similar to that seen in some
Southeast Asian countries [15,16]. Other comorbidities that increase cirrhosis and HCC risk
are also common; most importantly obesity and hazardous alcohol consumption [17–19].
There is also a significant burden of other chronic diseases—particularly macrovascular dis-
ease and complications of the metabolic syndrome—that have an even greater heath impact
[13,20]. This study was performed to determine the burden of these comorbidities in an effort
to inform the delivery of optimal—and holistic—chronic disease care to the people living with
CHB in the region.
Methods
This cross sectional study was performed in January 2021 in the TSI and NPA region of
remote, Far North Queensland (FNQ), Australia (Fig 1). The area covers approximately 48,000
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of the Queensland Public Health Act of 2005.
However, data are available from the Far North
Queensland Human Research Ethics Committee
(contact via email FNQ_HREC@health.qld.gov.au)
for researchers who meet the criteria for access to
confidential data.
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.
km
2
and has an estimated resident population of approximately 11000, over 90% of whom
identify as an Indigenous Australian [21]. The population is spread across 18 island communi-
ties on the Torres Strait and 5 communities in the NPA (Australian Bureau of Statistics Local
Government Areas 36950, 36960 and 35780). People living with CHB that were resident in the
region were eligible for inclusion in the study.
Hepatitis B is a notifiable disease in Queensland with all notifications reported to the
Queensland Notifiable Conditions System (NOCS) database. This database provides a data
extract for a local database (the FNQ HBV database) that allows local clinicians to identify—
and expedite the care of—people living with CHB in the region. The FNQ HBV database was
used to identify individuals eligible for this study. CHB was defined as 2 documented posi-
tive hepatitis B surface antigen (HBsAg) serology results 6 months apart. Further demo-
graphic, clinical, laboratory and radiology data were collected using electronic medical records
and laboratory and radiology databases.
All individuals receiving care in Queensland’s public health system, are asked whether they
identify as an Aboriginal Australian, a Torres Strait Islander Australian, both or neither; this
Fig 1. The study region of the Torres Strait Islands and Northern Peninsula Area in remote Far North Queensland, Australia. The map was constructed
using mapping software (MapInfo version 15.02, Connecticut, USA) using data provided by the State of Queensland (QSpatial). Queensland Place Names—
State of Queensland (Department of Natural Resources, Mines and Energy) 2019, available under Creative Commons Attribution 4.0 International licence
https://creativecommons.org/licenses/by/4.0/. ‘Coastline and state border–Queensland—State of Queensland (Department of Natural Resources, Mines and
Energy) 2019, available under Creative Commons Attribution 4.0 International licence https://creativecommons.org/licenses/by/4.0/.
https://doi.org/10.1371/journal.pone.0284151.g001
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was recorded. Patients were defined as being engaged in care if they were receiving anti-HBV
therapy (tenofovir disoproxil fumarate (TDF) or entecavir, both are provided to local patients
free-of-charge by the public health system) or had a quantitative HBV viral load requested in
the 2020 calendar year. Patients were said to have cirrhosis if their most recent AST to Platelet
Ratio Index (APRI) score was >2 [22], if they had a transient elastography score of >11.7kPa
[23], if they had a diagnosis of cirrhosis on imaging that had been reported by a specialist radi-
ologist, or if a diagnosis of cirrhosis was documented in the medical record. While some
patients were able to have elastography performed, the machine in use was not able to deter-
mine a controlled attenuation parameter (CAP) score; accordingly fatty liver was said to be
present if it was described in the report of a specialist radiologist.
Patients were staged using the Australasian Society for HIV, Viral Hepatitis and Sexual
Health Medicine (ASHM) guidelines into immune tolerance, immune clearance, immune
control or immune escape phases [24]. Patients who had two negative HBsAg tests 6 months
apart were said to have cleared the virus. Those without serology or an HBV viral load in 2020
were classified as “unable to be staged”. Patients were deemed to be eligible for treatment if
they were in the immune clearance or immune escape stage with evidence of active hepatitis (a
serum alanine aminotransferase (ALT) >45 IU/L) or had cirrhosis [25]. If patients were
deemed eligible for treatment but were not on therapy, the medical record was reviewed to
determine the reason.
The participants’ medical records were examined for significant comorbidities. A history of
any co-existing liver disease was documented. Obesity was defined as a body mass index
(BMI) >30 kg/m
2
(using the most recent recorded height and weight). The World Health
Organization definition of metabolic syndrome was used to define the features of this syn-
drome, although in the absence of a recorded waist measurement in almost all the patients, if a
patient had a BMI of 30 mg/kg
2
and two or more of impaired glucose tolerance, hyperten-
sion or dyslipidaemia, they were said to satisfy a modified definition of metabolic syndrome
[26]. Impaired glucose tolerance was defined as a glycosylated haemoglobin (HbA1c) 5.7%
at any time [27]. Hypertension was said to be present if a blood pressure of >140/90 was
recorded on two occasions or the patient was receiving anti-hypertensive therapy [28]. Dyslipi-
daemia was said to be present if a patient had a reduced high-density lipoprotein (0.9 mmol/
L in males, 1.0 mmol/L in females) or a serum triglyceride level 1.695 mmol/L at any time
[29]. The presence of renal impairment (estimated glomerular filtration rate (eGFR) <60 ml/
minute/1.73m
2
) and proteinuria (urinary albumin: creatinine excretion ratio 2.5 g/mol in
males or 3.5 g/mol in females in the absence of concurrent illness) was also sought [30].
Participants’ electronic medical records—which are updated at each clinic review—were
reviewed to determine if they were a current, past, or never smoker. They were also reviewed
to determine if there was current—or a history of—hazardous alcohol use (regular consump-
tion of >10 units of alcohol per week or regular binges of greater than 4 units per day) [31].
Cigarette smoking, impaired glucose tolerance, hypertension, dyslipidaemia, and renal
impairment/proteinuria were said to be modifiable cardiac risk factors [32]. A BMI of 30 kg/
m
2
, current smoking or current hazardous alcohol use were defined as additional risk factors
for HCC [19].
The participants’ medications were reviewed. The use of daily aspirin or statin therapy was
determined for each patient. The number of regular medications (including ingested, inhaled
but not implanted medications) was also recorded. Polypharmacy was defined as the prescrip-
tion of 5 medications [33].
Data were de-identified, entered into an electronic database (Microsoft Excel) and analysed
using statistical software (Stata version 14.2). Groups were analysed using the Kruskal-Wallis,
chi-squared and Fisher’s exact test, where appropriate. The study was approved by the Far
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North Queensland Human Research Ethics Committee (QCH106-1082). As the data were de-
identified, the committee waived the requirement for informed consent.
Results
Of the 276 individuals identified as potential study participants, 13 (4.7%) had cleared their
HBV, 6 (2.2%) had died and 21 (7.6%) had moved from the area, leaving 236 individuals satis-
fying inclusion criteria for the study; this represented a current local community CHB preva-
lence of 2.2%. All 236 identified as Indigenous Australians: 217 (92.0%) identified as a Torres
Strait Islander, 18 (7.6%) identified as both Torres Strait Islander and Aboriginal and 1 (0.4%)
identified as an Aboriginal Australian; 120/236 (50.9%) were female. The median (interquartile
range (IQR)) age of the cohort was 48 (40–62) years; 24/236 (10.2%) were born after 1985, the
year when vaccination against HBV began in the region.
Engagement in care and eligibility for treatment
Of the 194/236 (82.2%) engaged in HBV care, 61 (31.4%) met criteria for HBV therapy, 38
(62.2%) of whom were receiving it (19 were receiving TDF and 19 were receiving entecavir).
Among the remaining 23, 10 (43.5%) were engaged in case receiving appropriate care (they
had been referred for specialist review or were receiving close monitoring while therapy was
being discussed). There were 13/61 (21.3%) who were engaged in care and eligible for therapy,
but in whom there was no documented plan for therapy; in these patients the opportunity for
consideration of treatment appeared to have been missed (Fig 2).
Ultrasound surveillance
Overall, 128/236 (54.2%) of the patients received a liver ultrasound during the previous 12
months. This included 84/119 (70.6%) of those meeting criteria for HCC screening and 78/104
(75%) of those engaged in care and meeting criteria for HCC screening.
Fig 2. A flow chart demonstrating the proportion of patients living with chronic hepatitis B in the study region
who were engaged in care and who were receiving antiviral therapy (stratified by clinical phenotype).
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Cirrhosis and HCC
There were 19/236 (8.1%) who met criteria for a diagnosis of cirrhosis; 9/116 (7.8%) males and
10/120 (8.3%) females. Patients with cirrhosis were older than those without cirrhosis (median
(IQR): 61 (52–65) compared with 47 (39–60), p = 0.001). Of the 19 patients with cirrhosis, 18
(94.7%) were engaged in care and 12 (66.7%) were on therapy (Fig 2). The single case with an
active, confirmed HCC was a 48-year-old, male, overweight former smoker with a history of
hazardous alcohol consumption and cirrhosis, who was on anti-HBV therapy. He was diag-
nosed with multifocal HCC when he presented with ascites; a surveillance ultrasound 8
months prior had not revealed a focal lesion. His AFP at diagnosis (2.7 μg/L) was normal. His
case was discussed in a multi-disciplinary team meeting with a transplant centre and as he had
decompensated disease, no locoregional or systemic options were available to treat the HCC
and a palliative approach was recommended.
Other liver disease, hazardous alcohol use and cigarette smoking
Among the 217 non-cirrhotic patients, 115 (53.0%) had another liver disease documented, this
was fatty liver disease in 112 (97.4%). Two patients had hypoechoic lesions on ultrasound con-
sistent with a haemangioma, the other had a focal area of echogenicity consistent with a hae-
mangioma or fatty change. Current hazardous alcohol use was documented in 57/236 (24.2%),
past hazardous use in 28/236 (11.9%). Current tobacco smoking was documented in 73/236
(30.9%), while previous tobacco smoking was recorded in 78/236 (32.6%).
Obesity and its complications
There were 219/236 (92.8%) who had a height and weight that permitted calculation of a BMI;
their median (IQR) BMI was 32.7 (28.7–36.9) kg/m
2
. There were 198/219 (90.4%) with a BMI
>25 kg/m
2
, 143/219 (65.3%) with a BMI >30 kg/m
2
, and 82/219 (37.4%) with a BMI >35 kg/
m
2
.
There were 170/236 (72.0%) who had laboratory evidence of impaired glucose tolerance,
106/236 (44.9%) with hypertension, and 190/236 (80.5%) with dyslipidaemia. Of the 219
patients with a recorded BMI, 115 (52.5%) satisfied the modified criteria for the presence of
the metabolic syndrome.
Cardiovascular risk factors
All but 9 (3.8%) patients had at least one modifiable cardiovascular risk factor; 195/236
(82.6%) had 2 cardiovascular risk factors (Fig 3). There were 5/236 (2.1%) individuals with a
recorded eGFR <30 mL/min/1.73m
2
and 31/236 (13.1%) with an eGFR <60 mL/min/1.73m
2
.
There were 94/236 (39.8%) with documented proteinuria.
Medication burden
Patients were taking a median (IQR) of 2 (0–5) medications; 74 (31.4%) were taking 5 medi-
cations. There were 76/236 (32.2%) prescribed a statin and 47/236 (19.9%) prescribed regular
aspirin.
Additional risk factors for HCC
In the entire cohort, there were only 43/236 (18.2%) who were not obese, currently smoking or
currently drinking alcohol hazardously, while 70/236 (29.7%) had 2 or more of these risk fac-
tors for HCC (Fig 4). Among the 19 patients with cirrhosis, only 9/19 (47.4%) were not obese,
currently smoking or currently drinking hazardously. Among these 19 patients with cirrhosis,
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9 (47.3%) had a BMI>30 kg/m
2
, 2 (11.1%) were currently drinking alcohol hazardously, while
6 (31.6%) had a history of past hazardous alcohol consumption. Meanwhile, 5/19 (26.3%) were
current smokers and 5/19 (26.3%) were past smokers.
Discussion
Over 80% of individuals living with CHB in this remote region of Australia were engaged in
care, one of the highest rates of engagement in Australia, and well above Australia’s National
Strategy target for engagement of 50% by 2022 [1]. Meanwhile, over 60% of those eligible for
therapy were currently receiving antiviral therapy, with almost half of the remaining individu-
als eligible for therapy having either been referred for specialist review or having elected, in
shared decision making with their primary care provider, to defer therapy. However, despite
the encouraging rates of engagement and antiviral treatment, over 80% of the individuals in
the cohort were obese or were currently smoking tobacco or drinking alcohol in a hazardous
manner. If unaddressed, these comorbidities would not only increase the risk of cirrhosis and
HCC [34–36], but they would also be expected to have a significant impact on general health
outcomes [37–39]. These data emphasise the importance of a more holistic approach to CHB
care in the region.
Current Australian guidelines for the management of HBV have a strong emphasis on viro-
logical markers of disease, co-infection with other blood borne viruses, indications for antiviral
therapy and screening for hepatic complications, particularly HCC [7,40]. This virological
emphasis is understandable as it is currently estimated that 27% of people living in Australia
with CHB are undiagnosed, that only 22.6% of are engaged in care, and that only about half of
the 20% who are estimated to require treatment are currently receiving it [1]. However there is
far less emphasis on identifying and aggressively addressing co-morbidities that can have a sig-
nificant impact on liver health and associated risk of HCC development [6,41,42].
Fig 3. A histogram showing the number of modifiable risk factors for cardiovascular diseasein each of the
patients in the cohort.
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This is important given the significant impact that these comorbidities—specifically obesity,
the metabolic syndrome and smoking and hazardous alcohol use—have on the incidence of
cirrhosis and HCC [2,43–47]. In FNQ, obesity, smoking and hazardous alcohol have an even
greater significance given the crucial role that they play in the 5 most common causes of death
in the local Indigenous Australians population: coronary heart disease, diabetes mellitus, lung
cancer, cerebrovascular disease and chronic obstructive pulmonary disease [48]. There is sig-
nificant potential overlap between the lifestyle interventions recommended to prevent the
development of these conditions, their optimal medical management and the care for people
living with CHB [19,49–53]. An integrated approach which manages CHB and these comor-
bidities concurrently—rather than the siloed approach that is seen too frequently—would be
expected to translate into both better liver and general health outcomes [54,55]. Although a
single individual was diagnosed with HCC in the region in the 2020 calendar year, 25 individu-
als required aeromedical evacuation from the region for an acute coronary syndrome during
the same time period [56].
Other studies to examine CHB-related HCC in Indigenous Australians have provided very
limited data about the relative contribution of comorbidities to the development of HCC [16,
57]. A large, multi-jurisdictional study that compared the characteristics and outcomes of
HCC in Indigenous and non-Indigenous Australians, identified that comorbidity—quantified
using the Charlson Comorbidity Index—was the strongest risk factor for death in the cohort.
Indeed, in multivariate analysis of this cohort, Indigenous status was not an independent
Fig 4. Venn diagram demonstrating the number of people living with chronic hepatitis B in the region who were
also obese, currently smoking or currently drinking hazardously.
a
19 individuals were obese, current smokers and
were currently drinking alcohol in a hazardous manner.
b
23 individuals were obese and current smokers.
c
13
individuals were current smokers and were currently drinking alcohol in a hazardous manner.
d
12 individuals were
obese and were currently drinking alcohol in a hazardous manner.
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predictor of survival [2]. However, comorbidity in this study was determined retrospectively
using International Classification of Diseases (ICD) coding of hospital separations, during a
period when understanding of fatty liver disease was evolving. The authors acknowledged that
it was therefore unlikely to capture precisely the relative contributions of these comorbidities
to outcomes [58]. This present cross-sectional study—which uses primary care data—is likely
to provide a more accurate assessment of the prevalence of these comorbidities in the commu-
nity, and therefore the potential role that they play in the development of liver disease.
After appropriate antiviral prescription and optimal management of comorbidities, the
incremental value of HCC surveillance in reducing HCC-related mortality in this region is
uncertain. Australian national guidelines recommend biannual screening with ultrasound and
consideration of AFP testing in people living with CHB who are at increased risk of HCC; this
includes all patients with cirrhosis and Indigenous Australians who are older than 50 years [7].
The recommendation for screening in Indigenous Australians is based on a series of 22
HBsAg-positive cases of HCC in the Northern Territory between 2000 and 2011 and an addi-
tional 16 cases that were HBcAb-positive, however, the comorbidities of the cases in this series
were not presented, which is important as the authors’ model suggested that 60% of HCC in
Indigenous Australians was due to HBV [57]. Furthermore, the generalisability of the North-
ern Territory findings to the care of Indigenous Australians living in other parts of remote
Australia has not been defined, particularly the contribution of the HBV genotype to clinical
outcomes [59]. Northern Territory Investigators have produced an impressive body of work
describing the ubiquity and clinical implications of the C4 viral genotype in that jurisdiction
[57,60,61], however, different HBV genotypes are prevalent outside the Northern Territory,
which may have less oncogenic potential [59,62]. Indeed, is notable that there has not been a
single case of HBV-related HCC reported to the Queensland state cancer registry since 2000 in
an Aboriginal individual from FNQ, despite a community HBV prevalence of >2% in some
Aboriginal communities in the region. Instead, all HBV-related HCC in Australian born resi-
dents of FNQ in this period have occurred in Torres Strait Islander Australians [16].
There are other challenges with delivering HCC surveillance to this population. In meta-
analyses, the sensitivity of ultrasound for HCC detection ranges from 60–84%, although this
falls to 47% for early stage disease [63,64]. The sensitivity of ultrasound falls even further to
21% in obese (BMI 30 kg/m
2
) patients [65]. Transport of ultrasound equipment around the
48,000 km
2
region is also challenging and the costs associated with confirmation or exclusion
of ultrasound findings are significant as the the nearest computed tomography or magnetic
resonance imaging is almost 800km away and accessible only by air. Meanwhile AFP testing
offers no additional benefit to ultrasound [66].
However, although over 70% of the cohort that were eligible for HCC surveillance received
an ultrasound in the prior 12 months, it was notable that despite the high burden of risk factors
for HCC, there was only a single confirmed case of HCC in the cohort. Whilst incomplete
screening raises the possibility of underdiagnosis, screening rates (during a period impacted
significantly by the global COVID-19 pandemic) were not worse than those reported in Aus-
tralian metropolitan settings [67].
Indeed, other cancers—many which require more invasive diagnostic testing than is
required for HCC diagnosis—are diagnosed more frequently in the region. The incidence of
HCC between 2010 and 2018 was 8/100,000/year making it the region’s 9
th
commonest cancer
(S1 Table) [68]. It is notable that reducing rates of smoking, obesity and hazardous alcohol
consumption would not only tend to reduce the incidence of HCC but would also be expected
to have also have a salutary effect on 7 of the 8 more common cancers (lung, breast, colorectal,
uterine, cervical, oesophageal and stomach cancer). The financial and logistic investment in
attempting to provide biannual ultrasound surveillance may be better directed to
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implementing the cancer screening programmes that are unequivocally cost-effective in Aus-
tralia such as cervix or bowel cancer screening, where specimens—in even remote locations—
can be self-collected [69–71]. Alternatively, public health resources could be redeployed in
augmenting existing public health strategies that address the underlying carcinogens (such as
programmes to assist with smoking cessation, moderating alcohol consumption and reducing
weight).
Of course, the difficulties of delivering comprehensive, culturally appropriate, longitudinal
chronic disease care and executing public health strategies in a region of almost 50000km
2
in
remote Australia cannot be ignored [72]. Local CHB management is made more challenging
by limited local laboratory and radiology support; there is no local elastography and specialist
services are based—with the computed tomography—almost 800km away. The management
of other chronic diseases faces similar challenges. Travel between the communities in the
region is by ferry or more commonly plane, which is expensive and, in the wet season in this
tropical region, sometimes impossible. There is significant staff turnover which results in loss
of knowledge and interrupts the delivery of programmatic care. It is therefore notable, that
despite these challenges, engagement in CHB care is one of the highest in Australia and the
proportion of patients on antiviral therapy, who meet criteria for treatment, is also far higher
than is seen in most well-resourced metropolitan centres [1].
This study has several limitations. It is almost certain that some HbsAg-positive individuals
living in the region have not been captured in this cohort, however as hepatitis B is a notifiable
disease in the state of Queensland, and this register was used to identify patients, it is unlikely
that a large number have been missed. Indeed, the prevalence of chronic hepatitis B in the
cohort (2.2%) is actually higher than the current estimated national prevalence in Indigenous
Australians (2.0%) [1], and any missing patients are unlikely to significantly change the con-
clusions of the study. Almost 20% of the cohort were not engaged in CHB care, precluding
determination of their disease stage and requirement for therapy. Only a few of the patients
had received transient elastography, and almost half of the cohort did not receive an ultra-
sound during the study period, potentially leading to an underestimation of the current bur-
den of cirrhosis, however only 13/234 patients in whom an APRI score could be determined
had a score >1.0, suggesting that this is unlikely to be a major issue [22]. Incomplete surveil-
lance—and poor sensitivity of ultrasound testing in obese patients—may have led to an under-
diagnosis of HCC in the cohort, however the single case of HCC is similar to the 19 cases of
HCC in HbsAg-positive Indigenous Australians in the region between 1999 and 2016 [16] and
it is notable that some cancers—including gastric and oesophageal cancer—that require more
invasive testing for diagnosis actually have a higher incidence in the region, suggesting that
underdiagnosis is unlikely to be a major issue. The study did not include a formal health eco-
nomic analysis of the local cost-efficacy of the HCC surveillance strategies recommended in
national guidelines nor community consultation about the perceived value of this care; both
could be examined in future studies. Future research could also examine how best to practi-
cally integrate the management of CHB with the care of patients with complex comorbidity
living in remote socioeconomically disadvantaged communities in the region.
Conclusions
This study is one of the first to systematically examine the burden of comorbidities in Indige-
nous Australians living with CHB and their potential impact on the incidence of HCC. Indeed,
with the success of HBV vaccination rollout in Australia, these comorbidities are likely to
assume more importance in the future [34,73]. It emphasises that, even in a region where the
engagement in CHB care is amongst the highest reported in Australia, optimal liver outcomes
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Comorbidity in Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B
PLOS ONE | https://doi.org/10.1371/journal.pone.0284151 April 6, 2023 10 / 15
will not be possible without simultaneously addressing these comorbidities. Optimising the
management of comorbidities in Indigenous Australians living in the region with CHB would
not only be expected to improve their liver health but also reduce the burden of other chronic
diseases that have, potentially, an even greater effect on their long-term health outcomes.
Supporting information
S1 Table. The annual incidence of the 9 most common cancers in the study region, the
availability of screening programmes and whether tobacco smoking, alcohol use and obe-
sity are risk factors for the disease [68].
(DOCX)
Acknowledgments
The authors would like to acknowledge all the health workers who were involved in the care of
the patients. The authors would also like to acknowledge the Queensland Cancer Control
Analysis Team (QCCAT) who provided data about the incidence of different cancers and the
Statistical Services Branch of Queensland Health who provided data about the most common
causes of death in the region. The authors would also like to thank Mr Peter Horne for his
assistance with the preparation of Fig 1.
Author Contributions
Conceptualization: Josh Hanson.
Data curation: Jordan Riddell, Allison Hempenstall, Yoko Nakata, Sandra Gregson, Richard
Hayes, Sharna Radlof.
Formal analysis: Josh Hanson.
Investigation: Jordan Riddell, Allison Hempenstall, Sharna Radlof, Josh Hanson.
Methodology: Josh Hanson.
Project administration: Allison Hempenstall, Lizzie Charlie, Christine Perrett, Victoria
Newie, Tomi Newie, Sharna Radlof, Josh Hanson.
Supervision: Simon Smith, Josh Hanson.
Validation: Allison Hempenstall, Josh Hanson.
Writing – original draft: Jordan Riddell, Josh Hanson.
Writing – review & editing: Allison Hempenstall, Yoko Nakata, Sandra Gregson, Richard
Hayes, Simon Smith, Marlow Coates, Lizzie Charlie, Christine Perrett, Victoria Newie,
Tomi Newie, Sharna Radlof, Josh Hanson.
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