epidemiologia, fatores de risco “around the world”.€¦ · intermediate stage (b)...
TRANSCRIPT
Epidemiologia, fatores de risco “around the world”. • JOSE EYMARD MEDEIROS FILHO
• Professor Associado
• Universidade Federal da Paraíba
Em conformidade com a RDC 96 de 17/12/2008, declaro que:
Nos últimos 12 meses, participei como palestrante em simpósios
e/ou recebi apoio para congressos de
BMS
TAKEDA
Gilead
Abbvie
Janssen
DECLARAÇÃO DE CONFLITO DE INTERESSE
Cancer Fígado: Sexta causa mais comum de cancer no mundo
• Liver cancer is the third most common cause of cancer-related death1
• HCC is the most common primary liver malignancy in adults2
198.783
204.449
274.289
300.571
356.557
462.117
493.243
626.162
679.023
933.937
1.023.152
1.151.298
1.352.232
0 200.000 400.000 600.000 800.000 1.000.000 1.200.000 1.400.000 1.600.000
Corpus Uteri
Ovary
Oral Cavity
Non-Hodgkin's Lymphoma
Bladder
Esophagus
Cervix Uteri
Liver
Prostate
Stomach
Colon/Rectal
Breast
Lung
1. Parkin DM, et al. CA Cancer J Clin. 2005;55:74-108. 2. Pons-Renedo F, et al. Med Gen Med. 2003;5:11.
The global burden of HCC.
Globocan, 2012
Hepatocellular carcinoma is the second leading
cause of death among cancer patients worldwide
-60% -45% -30% -15% 0% 15% 30% 45% 60%
Liver & bile duct
Melanoma
Jemal et al. CA-Cancer J Clin 2009
Liver cancer US Mortality (1990-2005)
-60
%
-45
%
-30
%
-15
%
0% 15% 30% 45% 60%
Hodgkin lymphoma
Prostate
Colon & Rectum
Lung
Brain
Myeloma
Kidney
Pancreas
Human hepatocarcinogenesis
Cornellà et al., 2011
Risk Factors for HCC Worldwide by Geographic Region (2000)
*Excluding Japan.
Llovet JM, et al. Lancet. 2003;362:1907-1917.
Other
Alcohol
Hepatitis B
Hepatitis C Asia/Africa* Europe/North America Japan All
50%-70%
70%
70%
20%
10%-20%
≤10%
0 20 40 60 80
Cases (%)
10%-20%
10%-20%
Risk Factors for HCC in US Patients
Di Bisceglie AM, et al. Am J Gastroenterol. 2003;98:2060-2063. El-Serag HB. Gastroenterology.
2004;127:S27-S34. Bosch FX, et al. Gastroenterology. 2004;127:S5-S16.
Known Risk Factor in the US: Viral Hepatitis (N = 691)
5
15
33
47
0
20
40
60
80
100
HBV + HCV HBV HCV Neither
Pre
sen
ce o
f R
isk F
acto
r
Am
on
g H
CC
Pa
tie
nts
(%
)
N %
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 1990
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC.
Obesity Trends* Among U.S. Adults BRFSS, 2010
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Mortality from HCC in the United States
Data downloaded from CDC
Increasing association of non-alcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma in the united states: Data from surveillance, epidemiology and end results (SEER)-medicare
registries (2004-2009)
• Represented 28% of U.S. population: cohort included 5,748 cases of HCC and 17,244 non-HCC matched controls (3:1)
Younossi Z, et al. EASL 2015, Vienna. #O041
8
14
4
26
48
HBV
Alcoholic liver disease
Autoimmune hepatitis /biliary cirrhosis
NAFLD
HCV
Cause of chronic liver disease in HCC (N=5,748)
BA: 16.1% (2 Centers)
RJ: 29.1% (2 Centers)
PR: 2.2% (1 Center)
RS: 11.8 %(1 Center)
n = 110
MG: 6.5% (1 Center)
SP: 34.3 % (3 Centers)
HCC ASSOCIATED WITH NASH IN BRAZIL: A CRESCENT PROBLEM
COTRIM HP, OLIVEIRA CP, CARRILHO FJ & Brazilian Society of Hepatology Members. 2013
n = 110
HCC ASSOCIATED WITH NASH IN BRAZIL: A CRESCENT PROBLEM
COTRIM HP, OLIVEIRA CP, CARRILHO FJ & Brazilian Society of Hepatology Members. 2013
73,1 54,8 52,7
39,8 52,7
0 10 20 30 40 50 60 70 80
Risk Factors %
GIDEON
23
Latin America
Europe & Canada / Middle East / Africa
Asia / Pacific
Japan
US:
645 enrolled
553 valid for efficacy
563 valid for safety
US Patients by
Physician Specialty, n=563
Med/Onc, 299
Surgery; 23 IR; 7
Hep/GI; 228
Missing, 6
90 US centers participated;
most centers enrolled
1-5 patients
Over-representation of risk factors for NASH in subjects with cryptogenic cirrhosis (CC) and
hepatocellular cancer
Obesity Dyslipidemia T2DM0
25
50CC
HCV
ETOH
Risk factors for NAFLD
%
Bugianesi et al, Gastro, 2002; 123:134-140
N=23 cases of CC + HCC
HCC in Cirrhotic patients in Vitória - ES, Brazil.
Patients features
GONÇALVES PL. Doctoral Thesis, 2013. Federal University of Espirito Santo.
Etiology
No. of HCC = 274
(%)
Male : Female
Age
Mean + SD
Alcohol 47 (17.1) 46 : 1 61.0 + 10.3
HBV 64 (23.4) 15 : 1 53.3 + 16.0
HBV + alcohol 39 (14.2) 39 : 0 54.1 + 11.4
HCV 37 (15.5) 3.7 : 1 59.1 + 9.8
HCV + alcohol 25 (9.1) 25 : 0 54.6 + 8.5
NAFLD 7 (2.6) 0.4 : 1 56.5 + 20.2
Criptogenic 53 (19.3) 1.7 : 1 65.0 + 11.6
NASH is driving increase in HCC requiring liver transplantation
Wong et al, Hepatology, 2014
AFLATOXIN
• Aflatoxin B1 is the most potent naturally
occurring chemical liver carcinogen
• Group1 human carcinogen (IARC)
• HCC vs aflatoxin vs HBV
✴risk of liver cancer: 30x greater in
HBV + aflatoxin vs aflatoxin alone
Liu Y & Wu F. Environmental Health Perspectives 2010; doi: 10.1289/ehp.0901388, //ehponline.org.
Estimated HCC Incidence ( /100,000/yr )
attributable to Aflatoxin by WHO region
WHO region HBV prevalence HCC due to aflatoxin - HBsAg neg
HCC due to aflatoxin - HBsAg pos
Africa 3 - 20% 0.1 - 1.8 3 - 54
North America 0.3 - 2% 0.003 - 0.01 0.08 - 0.3
Latin America 0.3 - 3% 0.2 - 0.5 6 - 15
Eastern Mediterranean
0.4 - 10% 0.1 - 0.8 3 - 24
South-East Asia 2 - 8% 0.3 - 1 9 - 30
Western Pacific Region
1 - 16% 0.15 - 0.5 4.5 - 15
Europe 0.5 - 7% 0 - 0.04 0 - 1.2
Liu Y & Wu F. Environmental Health Perspectives 2010; doi: 10.1289/ehp.0901388, //ehponline.org.
Portal pressure/
bilirubin
HCC
RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACE Resection Symptomatic
treatment (20%)
Survival < 3 months Curative treatments (30%)
5-year survival 40–70%
Palliative treatments (50%)
Median survival 11–20 months
Associated diseases
Yes No
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Bruix J, Sherman M. Hepatology. 2010. Available from:
http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20
Practice%20Guidelines/HCCUpdate2010.pdf. Last accessed November 2010.
Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.
Barcelona Clinic Liver Cancer (BCLC) staging
system and treatment strategy
PST = performance status test;
RFA = radiofrequency ablation;
TACE = transarterial chemoembolization.
32
15%33%
65%82%
17%
29%
27%
14%
68%
38%
8%4%
0%
25%
50%
75%
100%
1987 a 93 1994 a 98 1999 a 2003 2004 a 2008
> 5 cm
3,1 - 5 cm
< 3 cm
ULTRASOUND PROCEDURES AND
RESULTS OF THE SURVEILLANCE PROGRAM
Fonte: Sistema de Gestão e Informação Hospitalar - SIGH
ULTRASOUND
0
500
1.000
1.500
2.000
2.500
3.000
3.500
4.000
4.500
5.000
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
HCC in Brazil Screening Program in 1,375 cirrhotic patients
São Paulo Clínicas Liver Cancer Group
Single nodule = 73.6%
Multiple nodules = 26.4%
0
20
40
60
< 20 mm
> 20 and <
30 mm
> 30 and <
50 mm
> 50 mm
%
45.3%
30.2%
17.0%
7.5%
Number and Size of nodules n = 72 HCC
PARANAGUÁ-VEZOZZO D et al. Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort. Ann Hepatol 13(4):386-93, 2014.
HCC in Brazil Screening Program in 1,375 cirrhotic patients
São Paulo Clínicas Liver Cancer Group
0
20
40
60
80
100
YES NO
%
87.5%
12.5%
Included in Milan Criteria n = 72 HCC
PARANAGUÁ-VEZOZZO D et al. Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort. Ann Hepatol 13(4):386-93, 2014.
Conclusões
• Mortalidade elevada, incidência crescente
• Mudança do perfil etiológico, impacto futuro do DAA sobre o CHC – VHC
• CHC – NASH – Uma nova doença?
• Rastreio e detecção precoce vs. Tratamento radical