Hepatocellular Carcinoma

Transcription

1 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Flair José Carrilho MD, PhD, Professor São Paulo Clínicas Liver Cancer Group Division of Clinical Gastroenterology and Hepatology Hospital das Clínicas University of São Paulo School of Medicine São Paulo, Brazil

2 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Incidence Etiological Risk Factors o HCV, HBV, Alcohol o Aflatoxin o NAFLD Emergent etiologies Prevention

3 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations The incidence of HCC is increasing in Worldwide; it is amongst the leading causes of cancer death globally (evidence high). EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

4 World Cancer Prevalence Estimates number of cases (1-year - top 10 cancer) in 2012 Both Sexes Males Females Liver Position 10 Liver Position 6

5 World Cancer Incidence Estimates age-standardized rates in 2012 Both Sexes Males Females Liver Position 7 Liver Position 5 Liver Position 9

6 World Cancer Mortality Estimates age-standardized rates in 2012 Males Females Liver Position 2 Liver Position 6

7 Hepatocellular Carcinoma Estimated Incidence in Latin America

8 Liver Cancer incidence according to region and sex. The age-standardized rates / 100,000 inhabitants Latin America < / 100,000 Torre L et al. CA Cancer J Clin 2015; 65:

9 Number of Notified Deaths¹ Finally, the magnitude of patients shows consistency when compared to death notification system (SIM) Number of notified deaths by year (DataSUS - SIM) HCC Only Bayer - HCC Early Diagnosis ¹Considering all HCC ICDs (C22 group of ICDs)

10 Surveillance Program for HCC in Cirrhotic patients in São Paulo, Brazil. Higher Annual Incidence of HCC 2.9% Diagnosis of HCC 12.4% 14.3% in 5 yrs 8.6% 5.2% 1.7% 0% With Ultrasound 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.

11 HCC new cases last 6 months number 103 new cases

12 No history of underlying disease¹ t ~ 35 mths t ~ 17 mths 1,4% t ~ 23 mths Over 60% of patients undergo palliative care due late diagnosis Illness centered patient flow HCC new cases in MAT06/15 Patient flow until HCC diagnosis (MAT06/15) Diagnosis staging (MAT06/15) HCV/HBV t ~ 41 mths 6,4% 9,8% Initial t ~ 18 mths 12,3% Intermediate 88,4% 0,3% HCC² n = (100%) 7,9% Advanced Cirrhosis t ~ 14 mths 3,5% 62,2% Palliative care Cirrhosis preceding HCV/HBV HCV/HBV preceding cirrhosis No Cirrhosis nor HBV/HCV precedents Cirrhosis or HBV/HCV precedents 7,8% Not enough information for classification Bayer - HCC Early Diagnosis ¹Patients without assessed ICDs (Cirrhosis, HBV, HCV and HCC) ² ~85% of patients haven t been diagnosed with underlying diseases prior nor after HCC ³ For patients without death notification: <6 months history and at least 1 year no show

13 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Incidence Etiological Risk Factors o HCV, HBV, Alcohol o Aflatoxin o NAFLD Emergent etiologies Prevention

14 Etiological Risk Factors Regional variations of HCC categorized by age-adjusted Mortality rates / 100,000 persons The Global Burden Llovet JM et al. Nature Reviews Dis Primers 2016; 2:1-23.

15 HCC in Latin America Fassio E et al. Etiology of HCC in Latin America: a prospective, multicenter, international study. Ann Hepatol 9(1):63-8, 2010.

16 South America Survey of HCC, 2016 No. of patients = 1,336 Participants Countries 16% 2% 19% 5% 18% Argentina Brazil Colombia Ecuador Peru Uruguay 40% DEBES JD, CARRILHO FJ et al. Liver Int 2018; 38: CHAN AJ, CARRILHO FJ et al. Clin Gastroenterol Hepatol 2017; 15:

17 South America Survey of HCC, 2016 No. of patients = 1,336 - Predominance of HCV Risk Factors HCV - 48% Alcohol - 22% HBV - 14% NAFLD - 9% OTHERS - 8% DEBES JD, CARRILHO FJ et al. Liver Int 2018; 38: CHAN AJ, CARRILHO FJ et al. Clin Gastroenterol Hepatol 2017; 15:

18 Etiology of HCC National Survey of HCC in Brazil, 2009 CARRILHO FJ & Members of Brazilian Society of Hepatology. Clinics 65: , KIKUCHI L et al. Antiviral Therapy 18:445-9, 2013.

19 HCC in Cirrhotic patients in Vitória - ES, Brazil. Patients features Etiology No. of HCC / no. of cirrhosis (%) Alcohol 49 / 602 (8.1) HBV 88 / 313 (28.1) HBV isolated 51 / 199 (25.6) HBV + alcohol 37 / 114 (32.4) HCV 56 / 352 (15.9) HCV isolated 30 / 221 (13.5) HCV + alcohol 26 / 131 (19.8) Criptogenic 30 / 149 (20.1) Others 9 / 92 (9.7) GONÇALVES PL. Doctoral Thesis, Federal University of Espirito Santo.

20 HCC in Cirrhotic patients in Vitória - ES, Brazil. Patients features Etiology No. of HCC = 274 (%) Male : Female Age (Mean + SD) Alcohol 47 (17.1) 46 : HBV 64 (23.4) 15 : HBV + alcohol 39 (14.2) 39 : HCV 37 (15.5) 3.7 : HCV + alcohol 25 (9.1) 25 : NAFLD 7 (2.6) 0.4 : Criptogenic 53 (19.3) 1.7 : GONÇALVES PL. Doctoral Thesis, Federal University of Espirito Santo.

21 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: /ehp , //ehponline.org.

22 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% North America 0.3-2% Latin America 0.3-3% Eastern Mediterranean % South-East Asia 2-8% Western Pacific Region 1-16% Europe 0.5-7% Liu Y & Wu F. Environmental Health Perspectives 2010; doi: /ehp , //ehponline.org.

23 Estimated Global Burden of HCC cases attributable to Aflatoxin Exposure in HBsAg (+) and HBsAg (-) population WHO region Population (millions) HCC cases due to aflatoxin - HBsAg neg HCC cases due to aflatoxin - HBsAg pos Africa 755 2,150-2,940 9,230-50,600 North America Latin America , ,060 Eastern Mediterranean , ,200 South-East Asia ~1,734 1,740-17,300 1,460-27,600 Western Pacific Region ~1,740 2,710-6,510 6,310-21,200 Europe Total World 6,280 7,700-40,000 17, ,000 Total annual HCC cases attributable to Aflatoxin Worldwide = 25, ,000 Liu Y & Wu F. Environmental Health Perspectives 2010; doi: /ehp , //ehponline.org.

24 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Incidence Etiological Risk Factors o HCV, HBV, Alcohol o Aflatoxin o NAFLD Emergent etiologies Prevention

25 Worldwide Obesity Prevalence, ages >18 years, Estimate Brazil [Female ( %) > Male ( %)]

26 Worldwide Overweight Prevalence, ages >18 years, Estimate Brazil [Male ( %) = Female)]

27 Worldwide Systolic Blood Pressure Mean, ages >18 years, Aged Standardized Estimate Brazil [Male (>130 mmhg) > Female ( mmhg) ]

28 Worldwide Raised Fasting Blood Glucose Prevalence Mean, ages >18 years, Aged Standardized Estimate Brazil [Male ( %) = Female]

29 Worldwide Physical Inactivity Prevalence (%), Aged Standardized Estimate Brazil [Adolescents ( %) > Adults ( %)]

30 Worldwide Insufficient Physical Activity Prevalence (%), Aged Standardized Estimate Brazil [Adolescents Females ( %) > Males ( %)]

31 Worldwide Life Expectancy at Birth Both Sexes, 2015 Brazil = Healthy Life Expectancy years; Life Expectancy years

32 World Cancer Mortality Noncommunicable Diseases Brazil = 41-50%; per 100,000 population

33 Risco Relativo de Morte por Câncer na Presença de Sobrepeso e Obesidade El-Serag HB & Rudolph KL. Gastroenterology 2007; 132:

34 Risco Relativo de Morte por Câncer na Presença de Sobrepeso e Obesidade El-Serag HB & Rudolph KL. Gastroenterology 2007; 132:

35 Obesidade e Risco de Carcinoma Hepatocelular Rosmorduc O & Fartoux L. Clin Res Hepatol Gastroenterol 2012; 36:202-8.

36 Diabetes Increases the Risk of Chronic Non-alcoholic Liver Disease and HCC CNLD HCC El Serag et al. Gastroenterology 2004; 126:460-8.

37 Association of Obesity and HCC Early adulthood HASSAN et al. Gastroenterology 2015; 49:

38 Association of Obesity / HCV-HBV and HCC Early adulthood HASSAN et al. Gastroenterology 2015; 49:

39 Association of Obesity / Diabetes and HCC Early adulthood HASSAN et al. Gastroenterology 2015; 49:

40 Association of Obesity / Alcohol and HCC Early adulthood HASSAN et al. Gastroenterology 2015; 49:

41 Epidemiologia Estudo brasileiro multicêntrico (16 centros): 1280 pacientes Idade média: 49,6 ± 13,5 anos (53,3% homens e 85% assintomáticos) Dislipidemia: 66,8% dos casos Obesidade: 44,7%, Sobrepeso: 44,4% Diabetes: 22,7% 30% 25% 27% 20% Síndrome metabólica: 41,3% dos casos 437 casos com biópsia hepática: 42% 58% 15% 15,4% Esteatose isolada: 42% Esteatohepatite: 58% e 27% destes com fibrose 10% Cirrose:15,4% Carcinoma hepatocelular: 0,7% NASH Esteatose 5% 0,7% 0% Fibrose Cirrose HCC Cotrim HP, Parise ER, Oliveira CP, et al. Ann Hepatol. 2011; 10:33-7.

42 Carcinoma Hepatocelular na América Latina Etiologia Fassio E, Diaz S, Santa C, et al. Ann Hepatol 2010; 9:63-9.

43 DHGNA e Carcinoma Hepatocelular Brazilian Journal of Medical and Biological Research (2009) 42: Hepatology 2010;51(5):

44 Baffy G, Brunt EM, Caldwell SH. J Hepatol 2012; 56:

45 Transplante de Fígado Registros Brasileiros ( ) TxF no Brasil TxF no Estado São Paulo 215 TxF no Hospital das Clínicas FMUSP Criptogênica (6,51%) NASH(2,8%) CHC(24,18%) VHC/VHB 38,6% Indicação por NASH HC-FMUSP Outras(33,9%) 0,5% ,5x 2,8% 2014

46 American Journal of Clinical Oncology, 2014

47 Clinics, Accepted for publication No. of patients = 110 % Gender Male Female Elevated aminotransferases Metabolic syndrome Obesity Diabetes Hypertension Dyslipidemia Conclusions 1. This survey suggests that NASH is a relevant risk factor of HCC in Brazil associated or not with cirrhosis. 2. HCC was observed in elevated number of patients without cirrhosis. 3. A surveillance protocol to investigate HCC in NAFLD in Brazilian patients should be discussed.

48 Carcinoma Hepatocellular in Argentina NASH as an Emergent Etiology NAFLD-HCC had a 6-fold increased during the period from PIÑERO F et al. World J Hepatol 2018; 10:41-50.

49 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Incidence Etiological Risk Factors o HCV, HBV, Alcohol o Aflatoxin o NAFLD Emergent etiologies Prevention

50 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations Vaccination agains hepatitis B reduces the risk of HCC and is recommended for all newborns and high-risk groups (evidence high; recommendation strong). EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

51 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations Government health agencies should implemente policies to prevent HCV / HBV transmission, counteract chronic alcohol abuse, and encourage life styles that prevent obesity and metabolic syndrome (evidence moderate; recommendation strong). EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

52 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations In general, chronic liver disease should be treated to avoid progression of liver disease (evidence high; recommendation strong). EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

53 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations In patients with chronic hepatitis, antiviral therapies leading to maintained HBV suppression in chronic hepatitis B and sustained viral response in hepatitis C are recommended, since they have been shown to prevent progression to cirrhosis and HCC development (evidence high; recommendation strong). EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

54 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations Once cirrhosis is established, antiviral therapy is beneficial in preventig cirrhosis progression and decompensation. Furthermore, successful antiviral therapy reduces but not eliminate the risk of HCC development (evidence moderate). Antiviral therapies should follow the EASL guidelines for management of chronic hepatitis B and C infection. EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

55 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations Patients with HCV-associated cirrhosis and HCC treated with curative intent, maintain a high rate of HCC recurrence even after subsequent DAA therapy resulting in sustained viral response. It is presently unclear whether this represents the inherent risk of HCC development in advanced cirrhosis, or if DAA therapy increases recurrence rates. Thus, further research is encouraged. Currently, close surveillance is advised in these patients. The benefit of viral cure must be weighed against a potentially higher recurrence risk (evidence low; recommendation strong). EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

56 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations Coffee consumption has been shown to decrease the risk of HCC in patients with chronic liver disease. In these patients, coffee consumption should be encouraged (evidence moderate; recommendation strong). EASL Clinical Practice Guidelines Management of HCC. J Hepatol, 2018.

57 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Recommendations BRAVI F et al. Clin Gastroent Hepatol, 2013; 11:

58 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention RRs of HCC for Coffee consumption vs No consumption BRAVI F et al. Clin Gastroent Hepatol, 2013; 11:

59 Hepatocellular Carcinoma Epidemiology, Risk Factors and Prevention Bioactive Compounds in Coffee Caffeine Compound Composition Proposed hepatoprotective mechanism Purine alkaloid antagonizes A1 and A2A subtypes of the adenosine receptor Modidfies TGF-beta pathway to decrease liver fibrosis Hepatic detoxification via activation of uridine 5 -diphospho-glucuronosyltransferase Cafestol and kahweol Chlorogenic acids Fat-soluble diterpenes typically are removed from coffee by paper filters Esters are formed between quinic and trans-cinnamic acids, an important group of dietary phenois Activ ates the cis-acting antioxidantresponsive element sequence Antioxidant activity in vitro, metabolized in colon Exact mechanism unknown Ng V & SAAB S - Editorial. Clin Gastroent Hepatol, 2013; 11:

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61 Hepatocellular Carcinoma Prevention Coffee ALEKSANDROVA K et al. Am J Clin Nutr, 2015; 102:

62 Hepatologia Prof. Dr. Flair J. Carrilho Dra. Aline L. Chagas Dra. Regiane S.S. M. Alencar Dra. Cláudia Tani Dra. Lisa Rodrigues Profa. Dra Suzane Ono Nita Profa. Dra Cláudia Oliveira Ultra-sonografia Profa Dra. Denise C. Paranaguá Vezozzo Patologia Prof. Dr. Venâncio A. F. Alves Biologia Prof. Dr. Evandro Sobroza de Mello Dr. José Thadeu Stefano Cinira Camargo Cirurgia do Fígado e Transplante Hepático Prof. Dr. Luiz Carneiro D Albuquerque Prof. Dr. Paulo Herman Radiologia Prof. Dr. Manoel Rocha Dr. Roberto Blasbalg Radiologia Intervencionista Prof. Dr. Francisco Carnevale Prof. Dr Airton Mota Prof. Dr. Marcos Menezes Oncologia Prof. Dr. Jorge Sabbaga Dr. Tulio Piffer

63 Thank you for your attention!