DISEASE-SPECIFIC CANCER CONTROL
CANCER CONTROL 2015 99
collaboration between Imperial College, London; MRC Unit,
The Gambia in Fajara, The Gambia; IARC, Lyon France; Le
Dantec University Hospital, Dakar and University of Thiès,
Sénégal; and Jos University Teaching Hospital, Jos, Nigeria.
The overall aim of the project is to reduce the incidence of
HBV-related HCC in West Africa. Specific aims of the project
include:
‰ Investigating the natural history and epidemiology of
HBV-related liver disease and HCC in West Africa,
including overall burden of disease;
‰ Demonstrating the feasibility of mass screening for HBV
infection and subsequent enrolment in an antiviral
treatment programme;
‰ Establishing whether treatment of HBV with nucleoside
analogues is a cost-effective method to reduce the
burden of HBV-related liver disease and liver cancer in
West Africa;
‰ Developing novel biomarkers to predict and diagnose
HBV-related liver fibrosis and HCC has also been a key
research goal for the project.
Ultimately, data provided by the study will be used to
develop screening and treatment guidelines for both HBV
and HCC for the African context, which will then inform
WHO HBV guideline development for resource-poor
settings.
PROLIFICA study design
The PROLIFICA study consists of two platforms: West
African Treatment Cohort for HBV (WATCH) and
hepatocellular carcinoma case-control study (HC4). The
WATCH study has been conducted in two parts.
The first part is a population-based study, with 13,500
people screened for HBV infection using a point-of-care test
in Senegal and The Gambia. Subjects were invited for
screening from community, workplace, health service and
voluntary blood donor sites. In The Gambia, most
participants were recruited from community screening
through stratified selection from urban and rural areas
representative of western Gambia and also voluntary blood
donors; whereas in Senegal screening has been
predominantly through health facilities and workplaces. All
HBsAg positive participants and a proportion of HBsAg
negative control subjects are then invited to participate in a
full liver assessment. This includes clinical evaluation by a
trained hepatologist, ultrasound, transient elastography
(FibroScan™, Echosens, France), liver biopsy where required
and blood tests. HBsAg negative controls provide a single
blood and urine sample and HBsAg positive participants
provide blood and urine samples at regular intervals, when
they also attend for liver disease assessment and follow-up.
The second study is a non-randomised, open label study of
tenofovir therapy for HBsAg positive patients who fulfilled
EASL 2012 treatment guidelines for nucleoside analogue
therapy (1). These include HBsAg positive patients with 1)
advanced liver fibrosis or cirrhosis (Metavir F3 or greater
fibrosis stage on biopsy or equivalent on Fibroscan) and any
detectable HBV viral load; or 2) HBV DNA level >
2000IU/mL, ALT >40IU/mL and moderate fibrosis (as
evidenced on elastography or liver biopsy) and/or significant
inflammation on liver biopsy; or 3) HBV DNA level
>20,000IU/mL and ALT >80IU/mL; or 4) viral load
>20,000IU/mL and a family history of hepatocellular
carcinoma, or age over 30 years and any ALT level.
In parallel, HBsAg positive patients who did not fulfil EASL
criteria for nucleoside analogue therapy were followed up
over time and offered six-monthly HCC screening by
ultrasound as per EASL guidelines (1, 8). Once on therapy,
participants undergo close monitoring for side effects from
tenofovir therapy and to assess virological and clinical
response to therapy. Study participants are then followed
for five years and the effect of treatment on HBV disease
outcome will be compared to historical control data of
matched patients available for each country. The outcome of
those who did not fulfil EASL treatment criteria will also be
assessed, to gauge whether current international guidelines
for HBV therapy are appropriate for the African setting.
The HC4 study was designed to develop a research
platform for discovering and validating biological markers of
HCC in Nigeria, The Gambia and Senegal. HCC cases as well
as controls have been recruited in tertiary hospitals in these
countries.
Achievements of the PROLIFICA research platform
so far
Screening and recruitment is now complete in The Gambia
and almost complete in Senegal. In The Gambia, 5,980
inhabitants in randomly selected communities have been
screened for HBsAg and clinical information and samples
have been collected. To date, the PROLIFICA study has
provided important insights into HBV-related HCC in West
Africa, including identification of novel metabonomic
biomarkers which may prove useful for HCC diagnosis in
resource-poor settings (22, 23), validation of simple,
inexpensive tests more appropriate for Africa to guide HBV
therapy (24, 25) and epidemiological insights into risks for
more severe HBV-related liver disease (26-28). These are
now outlined in more detail.