improving risk stratification and early detection of...
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Improving risk stratification and early detection
of Hepatocellular Carcinoma in Africa
Cairo Sep 2019
Ashraf Omar M,D
Prof Hepatology and Endemic Medicine
Cairo University
Head of the Egyptian Society Of Liver
Cancer (ESLC)
Head of MENA NCCN Committee for HCC
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• Disclosure
Nothing to disclose
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• HCC is a major health problem in Africa
• It is a major cause of premature death in Africa (chronic HBV)
• Risk factors are well known and avoidable in most cases.
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HCC In Africa
• Fourth most common cancer in both genders.
• Burden :64,779 new cases , 63,562 d. ..incidence matches mortality rate : 0.9
• Prevalence of about 56,736 cases in 2018.
• In men, it is the second most common cancer and the second cause of death due to cancer.
• Socioeconomic : Rural>>Urban
Ferlay J et al , global Cancer Observatory 2018Lancet 2016;388
MORTALITY
INCIDENCE
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Ferlay J et al , global Cancer Observatory 2018
Incidence and Mortality
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• Depending on the region, liver cancer is thought to result from the exposure to many risk factors.
• Risk factors vary from one place to another, depending on habits, lifestyle, food consumed and surrounding infections.
• Prevention of liver cancer requires knowledge of these risk factors and ways to avoid them
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Risk factors in Africa
Major risk
• 78% due to viral hepatitis (WHO)
• HBV …..50-80% (G)C
• HCV …..10- 25%
• Aflatoxin B1 (sub/ Saharan Africa)
• Dietary iron overload (sub/ Saharan Africa)
Minor risk
• Alcohol
• Obesity /NAFLD/DM
Bahri O et al, World J Hepatol,2011Kew MC,2013
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Africa Liver Cancer Consortium
• HBV is the main cause .
• Over 50 – 60% in SSA are HBsAg+
• Another 20 -50 % have previous chronic B or occult HBV infection
• 43% of HBV –related HCC developed in adults younger than 40 y (32.5-37.5ys
• HCV is important cause in north Africa (Egypt)
• HCV –related cases occurred later after 50 ys with a peak between 57.5-62.5 ys
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Africa Liver Cancer Consortium
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Africa Liver Cancer Consortium
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Surveillance of HCC
*Slightly lower (£30,000) or significantly higher levels (up to $150,000) have been proposed to account for inflation, specific national healthcare resources and other factorsEASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019
• High rate of HCC in certain risk groups makes surveillance a cost-effective route to reducing mortality
Recommendations
• Implementation of screening programmes to identify at-risk candidate populations should be improved
• Such programmes are a public health goal, aiming to decrease HCC-related and overall liver-related deaths
Low Strong
Patients at high risk of developing HCC should be entered into surveillanceprogrammes. Government health policy and research agencies should address these needs
Moderate Strong
Level of evidence Grade of recommendation
Influenced by a number of factors• Incidence of HCC in target populations
• Availability of efficient diagnostic tests at acceptable costs
• Availability and effectiveness of treatments
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Surveillance in patients at high risk of HCC
*Patients at low HCC risk left untreated for HBV and without regular 6-month surveillance must be reassessed at latest on a yearly basis to verify progression of HCC risk. †PAGE-B score is based on decade of age (16–29 = 0, 30–39 = 2, 40–49 = 4, 50–59 = 6, 60–69 = 8, ≥70=10), gender (M = 6, F = 0) and platelet count (≥200,000/µl = 0, 100,000–199,999µl = 1, <100,000 = 2): a total sum of ≤9 is considered at low risk of HCC (almost 0% HCC at 5 years) a score of 10–17 at intermediate risk (3% incidence HCC at 5 years) and ≥18 is at high risk (17% HCC at 5 years) EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019
• Surveillance is recommended in specific target populations
• Interval should be dictated by rate of tumour growth and tumourincidence in target population
• 6-month interval is reasonable and cost-effective
Recommendations
• Cirrhotic patients, Child–Pugh stage A and B Low Strong
• Cirrhotic patients, Child–Pugh stage C awaiting LT Low Strong
• Non-cirrhotic HBV patients at intermediate or high risk of HCC* (according to PAGE-B† classes for Caucasian subjects, respectively 10−17 and ≥18 score points)
Low Weak
• Non-cirrhotic F3 patients, based on an individual risk assessment Low Weak
Level of evidence Grade of recommendation
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Surveillance between East and West
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Prevention
*Level of evidence high, grade of recommendation strongEASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019
• Primary prevention of HCC can be achieved with universalvaccination against HBV
• Progression to cirrhosis and HCC can be prevented by:
• Antiviral treatment in patients with chronic hepatitis B and C*
• Adoption of healthy lifestyle measures
Recommendations
Vaccination against hepatitis B reduces the risk of HCC and isrecommended for all newborns and high-risk groups
High Strong
Governmental health agencies should implement policies that:• Prevent HBV/HCV transmission• Counteract chronic alcohol abuse• Promote lifestyles that prevent obesity and metabolic syndrome
Moderate Strong
In patients with chronic hepatitis, use antiviral therapies to: • Maintain HBV suppression in chronic hepatitis B• Maintain SVR in chronic hepatitis C
High Strong
Level of evidence Grade of recommendation
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Prevention of HBV and HCV Avoid Aflatoxin B1 Avoid dietary Iron overl
HCC preventive interventions
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HCC Surveillance programmes
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Prevention Strategies in AfricaSustainable Development Goals
WHO strategies for non communicable disease and viral hepatitis
Primary prevention :
Elimination of viral hepatitis as a major health problem threat by 2030
o Mass treatment of HCV
o HBV immunization
o safe injection
o avoid parental treatment
Decrease aflatoxin exposure
Reducing Alcohol and tobacco
Control DM and obesity
Community and patient education programs
o risk factors for hepatitis
o Aflatoxin and associated liver disease
o health lifestyle options
Who : Global sector strategy on viral hepatitis 2016-2021Who : global action plan for the prevention and control of noncommunicable diseases 2013- 2020
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HCV
• Prevention of HCV
• Egypt role model in mass treatment
• Impact of HCV treatment
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Access to HCV Therapy
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POLARIS OBSERVATORY
o Polaris Observatory, an initiative of the non-profit CDA Foundation, provides epidemiological data, modeling tools, training and decision analytics to support eliminating Hepatitis B and C globally by 2030.
o Offers the most up-to-date estimates for the hepatitis C virus (HCV), hepatitis B virus (HBV) disease burden and economic impact, and offers strategies for elimination of each virus, along with financing options.
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Impact of HCV Treatment
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Endorsement of Success
.
110000055%485000
24%
35000018%
450002%
250001%
2,005,000patients
governmentalsupport
HIO
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Total number of treated patients
in Egypt
110000055%
48500024%
35000018%
450002%
250001%
2,005,000patients
governmental support
HIO
private
*Police & Army forces
Presidential initiative
Before mass screening initiative in 1st Oct 2018
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Impact of HCV treatment
Waked I, et al. Arab J Gastroenterol 2014;15:45–52
2013
2020
a) Increase efficacy only
b) Increase efficacy and treatment
Treated (annual) 65,000 65,000 325,000
Treatment rate 1.1% 1.1% 7.1%
Average SVR 48% 90% (2014) 90%
Newly diagnosed (annual) 125,000 125,000 340,500
Common treatment age 15–59 15–59 15–74
Treated stages ≥ F2 ≥ F2 ≥ F0
6.000.000
4.045.000
280.000
0
1.000.000
2.000.000
3.000.000
4.000.000
5.000.000
6.000.000
7.000.000
Total infected
-95%
630.000
507.000
76.000
0
200.000
400.000
600.000
800.000
Compensated cirrhosis
-88%
16.000 16.000
2.400
0
10.000
20.000
HCC
-85%
138.000
110.000
17.000
0
50.000
100.000
150.000
Decompensated cirrhosis
-87%
2013
201320132013
2030a 2030b
2030a 2030b2030a 2030b2030a 2030b
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HBV
• HBV vaccination
• Perinatal transmission prevention
• Antiviral treatment for HBV
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HBV Vaccination
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HBV Perinatal infection Transmission Prevention
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Impact of HBV Treatment
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HBV TreatmentPolaris Observatory
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Prevention of HBV –related liver Fibrosis and cancer in Africa : The PROLIFICA study
• PROLIFICA
• PRevention Of LIver Fibrosis and Cancer in Africa
• Established in 2011 in three West African countries: Senegal, the Gambia and Nigeria
• This is an on-going five-year translational research project funded by the European Union Framework 7 (www.prolifica.eu; EU-FP7 #265994) .
• Aim of the project is to reduce the incidence of HBV- related HCC in West Africa :
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The PROLIFICA study
PROLIFICA study design
• 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:
➢a population-based study, with 13,500 people screened for HBV infection using a point-of-care test in Senegal and The Gambia.
➢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
➢The HC4 study was designed to develop a research platform for discovering and validating biological markers of HCC in Nigeria, The Gambia and Senegal.
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The PROLIFICA study
.
The data provided by PROLIFICA will be crucial for the development of local &
WHO guidelines
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AflatoxinDistribution of HCC RELATED AFB1
Liu Y, enviro Health Perspect ,2010
• Accounts 40% of HCC
• Causes mutation of p53 gene
• Aflatoxin B1 and HBV have synergstic effect (RR 54.1 ) with dual exposure
• Decrease AFB1 below detectable limits will decrease HCC incidence in general population by 15 -19% and in HbsAg population by 10-29%.
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Aflatoxin Prevention Strategy
Iqbal et al, food safety and security.2018Nieru RW,2014
adequate irrigation & use of fungicides
Sun-drying on cloth not groundRemoving mouldy cropsImprove storage facilities
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HCC in Africa….what we need??? • HCC is a preventable disease ..Primary Prevention Strategy remains the most important with a
Public health approach on risky behaviours. Immunization of HBV at birth is critical
but remains poorly implemented in Africa.
• HCC could be curable ……….Establish a simple program for early detection will improve OS.
• Implement “Screen & treat” for HBV & HCV at low coast
• Develope adaptable resource –sensitive HCC Guidelines for Africa
• Develop centers of excellence in African countries (Improve diagnostic and curative methods.)
management
training
Clinical trials/ regestries
• Effective fight against aflatoxin and alcohol consumption..