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