Malattie trasmissibili e vaccini

Dr.ssa Elena Raffetti

Unità di Igiene, Epidemiologia e Sanità Pubblica

Università degli Studi di Brescia

e.raffetti@unibs.it

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

e.raffetti@unibs.it

• 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