strength points:

_All procedures applied were in accordance with:

• 1- international guidelines,
• 2-the standards of human experimentation of the local Ethics
Committees
• 3-Helsinki Declaration of 1975-1983.
_Compliance with Italian laws
_each patient gave his/her informed consent to participate.
Study population
• We analysed :_ 12,262 patients with chronic liver disease
_95 Italian liver units in 2001 or 2014
• Criteria of enrolment:_ age over 18 years
_altered with chronic liver disease or
_ presence of etiologic markers or
_symptoms consistent with chronic liver disease
• Reference category: patient unexposed to factors HCV infection , HBV
infection and alcool abus
TEST AND PROCEDURE
• 1_For each patient, a precoded questionnaire containing
demographic, epidemiological and clinical data was filled out.
• We dichotomized alcohol intake as <3 units/day vs >3 units/day in
men, and <2 units/day vs 2 >units/day in women.
• Criteria of enrolment :1- age over 18 years
2-altered either hepatic biochemistry
3-presence of etiologic markers of liver
damage or symptoms consistent with chronic liver disease.
Disease Detection of presence by
HBV Presence of serum HBsAg
HCV Detection of HCV

Autoimmune chronic hepatitis & primary biliary cirrhosis According the standardized criteria
Hereditary hemochromatosis Abnormal ferritin serum & transferrin saturation serum
values ,genetic markers . Liver histology

wilson’s disease Prsence of a metabolic syndrome

Non alcoholic fatty liver disease Abnormal serum alanine aminotransferase(ALT),

histological/ultrasound pattern of heaptic steatosis , in
absence of other known causes of chronic liver disease

Chronic hepatitis Diagnosed based on liver histology , persistence of abnormal

ALT in the absence of clinical,biomedical &ultrasound

Liver cirrhosis Liver biopsy(LB), presence of characteristic clinical

,biomedical & ultrasound

Hepatocellular carcinoma(HCC) Alpha-1-fetoprotein serums level, histological &imaging

finding
Statistical analysis
• Crude O.R. were adjusted for the confounding effect of age and B.M.I.
by multiple logistic regression analysis.
• Additive interaction, means that the observed joint effect of two or
more factors on the disease incidence (in this case cirrhosis), exceeds
the sum of the effect of exposure to each single factor minus 1.
• Multiplicative interaction means that the observed joint effect of
factors on the disease incidence exceeds the product of the effect of
exposure to each single factor.
• patients enrolled in the 2001 and 2014 surveys and unexposed to
these three factors were taken as the reference category for all
calculations.