Presentazione a cura del Dottor Claudio Puoti - "HOT TOPICS IN GASTROENTEROLOGIA - I TUMORI DELL'APPARATO DIGERENTE: cosa è cambiato e cosa bisogna sapere" - Roma 10/11/2018

1. Liver UnitLiver Unit
INI Research Institute and Clinics, Grottaferrata, Rome,INI Research Institute and Clinics, Grottaferrata, Rome,

2. HCC : the main cause of death in patients with cirrhosisHCC : the main cause of death in patients with cirrhosis
Cohort effectCohort effect
Early diagnosisEarly diagnosis
Better tx of complicationsBetter tx of complications
New antiviral agentsNew antiviral agents

3. HCC incidence in the worldHCC incidence in the world
3-4/100.00 120/100.000
HBVHBVHCVHCV

4. Incidence of primary liver cancer in Europe
EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019
Incidence rates per 100,000

7. Epidemiology of HCCEpidemiology of HCC
in Italyin Italy
HCV positive 49%HCV positive 49%
Alcohol 21%Alcohol 21%
HBV positive 13%HBV positive 13%
Virus + alcohol 12%Virus + alcohol 12%
HCV/HBV neg 16%HCV/HBV neg 16%
Mean age : 60 yearsMean age : 60 years
(HBV 59,(HBV 59, HCV 66HCV 66))
M/F: 3.3:1M/F: 3.3:1
(HBV 10:1, HCV 2.8:1)
HCC on cirrhosis: 93%HCC on cirrhosis: 93%
mean incidence : 2-4% / yearmean incidence : 2-4% / year
HBV: 1-2%HBV: 1-2%
HCV: 2-8%HCV: 2-8%
Single nodule: 70%Single nodule: 70%
M 13.4 x 100,000 inhabitantsM 13.4 x 100,000 inhabitants
F 4.4 x 100.000 inhabitantsF 4.4 x 100.000 inhabitants

8. Prevention
*Level of evidence high, grade of recommendation strong
EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019
• Primary prevention of HCC can be achieved with universal
vaccination 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 is
recommended 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
11
22
33

9. HCC preventive interventions
Fujiwara N, et al. J Hepatol 2018;68:526–49
EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019

10. Impact of coffee on HCC development
EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019
• Numerous epidemiological studies have addressed the prevention
of HCC in patients with chronic liver disease
– Trials analyzing the effect of coffee consumption have shown a
consistently positive effect with regard to lowering HCC incidence
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
Moderate Strong
Level of evidence Grade of recommendation

11. HCC prevention is based on two pillarsHCC prevention is based on two pillars
• removal of the causeremoval of the cause
• surveillancesurveillance

12. HBV CLDHBV CLD
HCV CLDHCV CLD
Alcoholic Liver DiseaseAlcoholic Liver Disease
Steatosis, NASH, diabetesSteatosis, NASH, diabetes
HemochromatosisHemochromatosis
PBC, PSCPBC, PSC
Wilson diseaseWilson disease
……
When the cause of CLD
has been removed,
the risk of HCC is fully abolished,
significantly decreased
or it remains unmodified ?

13. Cumulative incidence of HCC inCumulative incidence of HCC in
pts with CHB according topts with CHB according to
geographical area and clinicalgeographical area and clinical
status.status.
17%17%
3%3%
1%1%
10%10%
1%1%
0.1%0.1%

16. Once infected, always infectedOnce infected, always infected

19. 18 LAM
28 LAM + ADV
71 ETV

20. 5 yr5 yr 7 yr7 yr 10 yr10 yr
NAs 2.7% 3.3% 3.3%
No NAs 11.3% 26% 40%

21. Probability of HCC in cirrhotic ptsProbability of HCC in cirrhotic pts
(ETV vs controls)(ETV vs controls)
Probability of HCCProbability of HCC
(viral suppression vs no suppression)(viral suppression vs no suppression)

22. J. J. Y. Sung, Aliment Pharmacol Ther , 2008
Treatment of HBV infectionTreatment of HBV infection
reduces risk of HCCreduces risk of HCC

24. Conclusions I :Conclusions I :
does antiviral treatment decreasedoes antiviral treatment decrease
the risk of HCC in HBV cirrhosis ?the risk of HCC in HBV cirrhosis ?
1.1. The natural history of chronic hepatitis B might beThe natural history of chronic hepatitis B might be
dramatically improved by antiviral treatment.dramatically improved by antiviral treatment.
2.2. Prevention of HCC is not achieved in the absence of stablePrevention of HCC is not achieved in the absence of stable
viral suppressionviral suppression
3.3. Patients with stable viral suppression show lower ratesPatients with stable viral suppression show lower rates
of hepatic decompensation as well as liver-related mortalityof hepatic decompensation as well as liver-related mortality
and HCC incidence.and HCC incidence.
4.4. Maintained HBV DNA suppression does not fully abrogateMaintained HBV DNA suppression does not fully abrogate
abrogate the risk of HCC in patients with pre-existing cirrhosisabrogate the risk of HCC in patients with pre-existing cirrhosis

25. - previr- previr - asvir- asvir - buvir- buvir
Might the incidence of HCCMight the incidence of HCC
in HCV cirrhosisin HCV cirrhosis
be decreased in the futurebe decreased in the future
by the newby the new
direct antiviral agents ?direct antiviral agents ?

26. DAAs II generation now available in Italy
SofosbuvirSofosbuvir ((SovaldiSovaldi Gilead)Gilead) Nov, 2014Nov, 2014
SimeprevirSimeprevir ((OlysioOlysio Janssen Cilag)Janssen Cilag) Feb, 2015Feb, 2015
DaclatasvirDaclatasvir ((Daklinza BMSDaklinza BMS)) Apr, 2015Apr, 2015
Sofosbuvir/ledipasvirSofosbuvir/ledipasvir ((HarvonHarvoni Gilead)i Gilead) May, 2015May, 2015
Ombitasvir/paritaprevir/ritonavirOmbitasvir/paritaprevir/ritonavir ((ViekiraxViekirax AbbVieAbbVie)) May, 2015May, 2015
DasabuvirDasabuvir ((ExvieraExviera AbbVieAbbVie)) May, 2015May, 2015
Grazoprevir/elbasvirGrazoprevir/elbasvir ((ZepatierZepatier BMS)BMS) Jan, 2017Jan, 2017
Sofosbuvir/velpatasvirSofosbuvir/velpatasvir ((EpclusaEpclusa Gilead)Gilead) Apr, 2017Apr, 2017
Glecaprevir/ PibrentasvirGlecaprevir/ Pibrentasvir ((MaviretMaviret AbbVie)AbbVie) Sett, 2017Sett, 2017

27. HCCHCC ComplicationsComplications

28. Singal AK, et al. Clin Gastroenterol Hepatol 2010Singal AK, et al. Clin Gastroenterol Hepatol 2010
HCC occurrence in patients with HCV-relatedHCC occurrence in patients with HCV-related
cirrhosis according tocirrhosis according to SVRSVR

38. CONCLUSIONSCONCLUSIONS
1.1. HCC is the main cause of death in pts with cirrhosisHCC is the main cause of death in pts with cirrhosis
2.2. Incidence of HCC is increasing in Europe and worldwideIncidence of HCC is increasing in Europe and worldwide
3.3. Vaccination against HBV and control of HCV spread mightVaccination against HBV and control of HCV spread might
decrease HCC incidencedecrease HCC incidence
4. Stable suppression of HBV replication and SVR in pts with HCV might4. Stable suppression of HBV replication and SVR in pts with HCV might
dramatically decrease the incidence of HCC in cirrhotic pts, althoughdramatically decrease the incidence of HCC in cirrhotic pts, although
treatment does not completely eliminate the risk of HCC.treatment does not completely eliminate the risk of HCC.
5. In Western countries, causes others than viral (NASH, diabetes) might in5. In Western countries, causes others than viral (NASH, diabetes) might in
the next future increase the incidence of HCC in the general population.the next future increase the incidence of HCC in the general population.
6. Elimination of the cause of cirrhosis not only improves the natural history6. Elimination of the cause of cirrhosis not only improves the natural history
of the disease, but also decrease the risk of HCCof the disease, but also decrease the risk of HCC

39. спасибо за ваше вниманиеспасибо за ваше внимание
(Grazie per la cortese attenzione)(Grazie per la cortese attenzione)