Malattie trasmissibili e vaccini
Dr.ssa Elena Raffetti
Unità di Igiene, Epidemiologia e Sanità Pubblica
Università degli Studi di Brescia
Epidemics and Pandemics have shaped
our history…
Aldighieri, PAHO, 2012
1st Millenium
Middle Ages
20th Century
William Stewart, Surgeon General in a message to Congress, 1969
… it is time to close the book on
infectious diseases. The war
against pestilence is over…
Infectious diseases pages 764
Percentage of global years of life lost from 1990 to 2010
Lozano R et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095-128.
COHOLERA H1N1
SARS
TUBERCULOSIS HIV
New pathogens
Old pathogens
Chronic infections
Acute infections
2000 : West Nile
2003 : SARS
2004 : H5N1
2009 : H1N1
2011 : MERS-CoV
2013 : H7N9
2014 : polymielitis alarm
2014 : Ebola
… what next?...
Only in the new millennium
Fattori favorenti l’emergenza di nuove
infezioni
• Crescita popolazione, urbanizzazione
• Aumentata produzione animale
• Alterazioni habitat vettori / animali
• Mobilità umana, vettori, germi, reservoir animale
• Modificazioni dell’ecosistema (deforestazione, clima, etc.)
• Comportamento umano
• Pressione farmacologica (uomo e animale)
• Adattamento microbico
• Bioterrorismo ?
Crescita popolazione e Urbanizzazione
World Urbanization Prospects 2014 - ESA - the United Nations
Mobilità umana
Vaccination campaigns
New treatments
War
against pestilence
Infectious Disease
Modelling
Epidemiological Survelliance
New Vaccines
Monitoring resistence of antimicrobial
drugs
Outbreaks control
Scientific Research
Cost effectivness evaluations
Revisione sistematica e metanalisi
dell’incidenza e dei fattori di rischio per
epatocarcinoma in soggetti con infezione
cronica da virus dell’epatite B
Dr.ssa Elena Raffetti
Unità di Igiene, Epidemiologia e Sanità Pubblica
Università degli Studi di Brescia
• The benefit of anti-viral therapy of hepatitis B virus (HBV) infection in
reducing the risk of hepatocellular carcinoma (HCC) is still debated due to
uncertain data on HCC risk in untreated controls.
• Several studies on HCC incidence in untreated HBV infected subjects have
provided contrasting results due to differences in study design, geographical
area and host, viral and environmental factors.
• Previous reviews and meta-analyses did not evaluate HCC risk in untreated
HBV infected subjects according to the above mentioned factors properly
and/or exhaustively.
Background
to estimate in untreated subjects with chronic HBV infection:
• HCC incidence rate according to macro-area of origin and clinical status, i.e.
asymptomatic carriers, inactive carriers, chronic hepatitis or cirrhosis
• the association of gender, age, HBV genotypes, tobacco, alcohol, diabetes
and obesity with the risk of developing HCC.
Objectives
We selected studies according to the following criteria:
a) cohort studies and randomized clinical trials with an untreated control
group of HBV-infected chronic patients aged 18 years or older
b) less than 5% of subjects treated for HBV infection
c) data suitable for computing incidence rates
Inclusion criteria
Exclusion criteria a) hepatitis C virus (HCV) infection
b) hepatitis delta
c) HIV co-infection
d) non-compensated cirrhosis (Child Pugh B and C)
• The HCC incidence rate (IR) was estimated for each study.
• When the data were not reported, an estimation of the rate was done using the
number of events and duration of follow -up or cumulative incidence.
• Summary measures were calculated on the basis of random effects models.
Statistical analysis
Records screened (n=1961)
Full-text articles assessed for
eligibility
(n=239)
MEDLINE (n=1140)
EMBASE (n=1210)
The Cochrane Library (n=47)
Records identified
through other sources (n=18)
HCC incidence
(n=65)
HCC risk factors (n=18)
Studies included (n=67)
Inactive carriers
0.03 (0.00-0.10)
0.06 (0.02-0.10)
0.05 (0.03-0.08)
Asymptomatic carriers
0.07 (0.05-0.09)
0.19 (0.07-0.31)
0.42 (0.21-0.63)
0.31 (0.22-0.41)
Chronic hepatitis
0.12 (0.00-0.27)
0.49 (0.32-0.66) 0.42 (0.27-0.56)
Chirrosis
2.03 (1.30-2.77)
3.37 (2.48-4.26)
2.97 (2.35-3.59)
Five-year cumulative HCC incidence
0.3
2.4
15.5
9.7
0.6
0.1
Meta-regression analyses for HCC incidence
Full model without age Full model
Variables Coef.* 95% CI P value Coef.* 95% CI P value
Macro-area
Europe Ref. Ref.
North America-Oceania 0.06 -0.17, 0.28 NS -0.01 -0.24, 0.21 NS
East Asia 0.17 0.03, 0.30 0.018 0.05 -0.08, 0.19 NS
Clinical Disease Status
Inactive carrier Ref. Ref.
Asymptomatic carrier 0.19 0.03, 0.35 0.019 0.20 0.00, 0.39 0.049
Chronic hepatitis 0.25 0.04, 0.45 0.018 0.36 0.15, 0.58 0.001
Compensated cirrhosis 2.10 1.17, 3.02 <0.001 2.04 1.06, 3.03 <0.001
Mean age (years) 0.12 0.00, 0.25 0.057
Mean male percent 0.02 -0.02, 0.07 NS 0.02 -0.03, 0.07 NS
Risk factor First author
Europe East Asia North America and Oceania
Overall
RR (95% CI) RR (95% CI) RR (95% CI)
Age (years) 20-39 Beasley 1 40-49 0.8 (0.5-1.6) 50-59 5.2 (2.4-13.3) 60-69 6.2 (2.5-17.7)
Chen 0.9 (0.8-1.1) 30-34 Fang 1 35-39 2.7 (1.2-6-3) 40-44 1.8 (0.7-4.5) 45-49 3.9 (1.6-9.5) 50-54 5.4 (2.2-12.9)
≥40 vs <40 Hsu* 1.7 (0.1-15.0)
>45 vs ≤45 Kobayashi* 2.2 (1.3-3.9)
≥57 vs <57 Kusakabe 1.4 (0.4-5.3) Loomba 1.1 (1.1-1.1)
≥40 vs <40 Park* 5.5 (2.0-15.4)
28-39 Tseng 1 40-49 1.7 (1.2-2.5) 50-59 3.0 (2.1-4.5)
≥60 6.9 (4.5-10.6) ≥65 vs <65 Wang 3.8 (1.5-9.1)
Yu 1.1 (1-1.2)
Pooled RR (≥40-45 vs <40-45 years)
2.8 (1.5-5.3) I2 =20.9%
Relative risks (RRs) of HCC incidence
Risk factor First author
Europe East Asia North America and Oceania
Overall
RR (95% CI) RR (95% CI) RR (95% CI)
Gender (male vs female)
Chiaramonte 2.3 (0.3-105.2) Fang 2.7 (1.5-4.7) Hsu 1.6 (0.2-72.1) Kusakabe 2.4 (0.4-15.0) Loomba 2.4 (1.6-3.4) Park 6.1 (0.8-46.1) Tong 3.9 (1.2-20.1) Tseng 2.7 (1.9-3.8) Wang 3.8 (1.1-12.8)
Pooled RR 2.6 (2.1-3.3) I2 =0%
2.7 (2.1-3.3) I2 =0%
Relative risks (RRs) of HCC incidence
Relative risks (RRs) of HCC incidence
Risk factor First author
Europe East Asia North America and Oceania
Overall
RR (95% CI) RR (95% CI) RR (95% CI) Alcohol drinking (yes vs no)
≥30 g/d vs <30 g/d Bedogni 3.6 (1.3-26.5) Borresen 1.1 (0.8-1.5)
≥60 g/d vs <60 g/d Ikeda 8.4 (2.7-25.9) Loomba 1.5 (1.1-2.0) Wang 1.1 (0.3-3.9) Yu 1.7 (0.5-5.3)
Pooled RR (≥60 g/d vs <60 g/d)
2.1(1-4.6) I2 =65.7%
Tobacco smoking (yes vs no)
Kusakabe 2.8 (0.6-12.8) Loomba 1.1 (0.8-1.7) Wang 1.9 (0.8-4.8) Yu 1.3 (0.4-4.1)
Pooled RR 1.2 (0.9-1.7) I2 =0%
HBV genotypes C vs B Kusakabe 0.7 (0.1-4.4) C vs B Lim 1.9 (0.5-6.9)
C vs B or B+C Lee 2.5 (1.8-3.6) A vs B Tong 0.4 (0.0-2.1) C vs B Tong 1.3 (0.5-3.5) C vs B Tseng 3.1 (2.2-4.3)
Pooled RR (C vs B )
2.7 (2.0-3.7) I2 =28.3%
1.5 (0.7-3.2) I2 =0%
2.5 (1.9-3.4) I2 =20.9%
• This systematic review and meta-analysis provides estimates of HCC
incidence rates in untreated subjects with HBV infection, according to
geographical area. These estimates can be valuable to assess the impact of
antiviral therapy on the risk of HCC occurrence in subjects with HBV
infection.
• The role of various risk factors for HCC development in HBV infection is still
undefined, apart from gender, due to the lack of studies investigating these
aspects properly and the high heterogeneity among studies.
Conclusions
The authors declare no conflict of interest