Page 0097

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.

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