Ratziu hépatites nane vhg ttv du 2012
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Transcript of Ratziu hépatites nane vhg ttv du 2012
Hepatites Non A-E
Virus G et TTV …et autres considérations métaboliques
Vlad Ratziu, DU Hépatites Virales 2012Hôpital Pitié Salpêtrière,
Paris, France
Evidence for Additional Hepatitis Agents
Prospective transfusion-associated hepatitis studies : 12%
Acute cases of overt hepatitis : 20%
Fulminant hepatitis : 25%
Chronic liver disease : 20-30%
Hepatitis-associated aplastic anemia : most of them
HGV Epidemiology and Diagnosis
● HGV transmission: parenteral +++; vertical● Risk groups: polytransfused, hemophiliacs,
hemodialysis, patients infected with HIV, HCV, HBV
● Diagnosis: ● ongoing infection : HGVRNA without anti-E2● exposure with viral clearance : anti-E2 Ab
HGV Epidemiology and Diagnosis
● HGV prevalence : blood donors 1.5-2.5% chronic NA-NE hepatitis 10-13% cryptogenic cirrhosis 20% HCV infection 18-20% HBV infection 8-10%
Prevalence of Serum HGVRNA in Acute Hepatitis of Viral Origin
● non A-E 9 ● HBV 32* ● HAV 25● HCV 20
%
* : p<0.05 vs HAV and HCV
Alter M, NEJM 1997
HGV : is it an Hepatotropic Virus ?
● low level of hepatic HGVRNA compared to HCVRNA
● no interaction of hepatic HCVRNA and HGVRNA levels when patients with monoinfection are compared with those infected with both viruses
Pessoa, Hepatology 1998
HGV has no Pathogenic Role on the Course of Acute Hepatitis
● No apparent effect on the clinical course of acute disease among the patients with hepatitis A, B or C
● No effect on the frequency or severity with which chronic hepatitis C develops
● Long-standing HGV viremia but no chronic hepatitis
HGV and Transfusion associated Hepatitis (TAH)
HGV can be transmitted by transfusion +++
Protracted viremia possible (years) but 90% are mild
Prevalence of HGV is not higher in non-A-C transfusion associated hepatitis than in HCV, minor ALT elevation or transfused patients with no hepatitis
HGV milder forms than HCV; HCV-HGV not more severe than HCV
A CAUSAL RELATION BETWEEN HGV AND TAH IS NOT ESTABLISHED
Alter H, NEJM 1997
HGV in End-Stage Liver Disease and Liver Transplantation
HGV infection frequently present in end-stage liver disease (13% in HCV, 22-64% in cryptogenic cirrhosis)
HGV frequently present and/or acquired after liver transplantation
HGV does not influence the clinical outcome after liver transplantation.
Fried, Hepatology 1997Pessoa, Hepatology 1998
No Histopathologic Impact of HGV on Chronic Hepatitis C
● Patients: ● Chronic HCV alone in 85 pts● Chronic HCV-HGV in 17 pts
● No difference in the necroinflammatory grade, fibrosis stage, proportion of cirrhosis, steatosis or bile duct lesions
HGV INFECTION DOES NOT MODIFY THE COURSE OF CHRONIC HCV INFECTION
CONTRIBUTION TO LIVER DISEASE LESS THAN OTHER HEPATOTROPIC VIRUSES
Bralet, Gastroenterology 1997
Establishing Causality for New Viruses
● Pathogen present in most cases of the disease● Pathogen found preferentially in the target
organ● Should not be significantly detectable in
subjects without the disease● Copy number should decrease or become
undetectable with resolution of the disease● Copy number should correlate with disease
severity Alter, Postgraduate Course, AASLD 2000
Etiologie de la Cirrhose (n=78) Etude Dionysos (Hepatology 1994)
HCV28 %
HBV 9 %
HBV+ALCOOL 3 %
HEMOCHROMATOSE
1 %
ALCOOL26 %
CBP1 %
HCV+ALCOOL 3%
CRYPTOGENIC24 %
Factors Associated with ALT Levels
● SEX● BMI
● Cholesterol● Triglycerides● Glycemia● Oral contraceptives● Smoking● Age● Physical exercise● Medications
Piton, Hepatology 1998Prati, Ann Intern Med 2002
What is a Normal ALT Value ?
“Normal” ALT ranges from ● 26 UI/l (females, 95th percentile) to ● 66 UI/l (males BMI > 26 kg/m²)
New definitions of normal ALT (no overweight, lipid, carbohydrate alterations) :● 30 UI/l for men● 19 UI/l for women Piton, Hepatology 1998
Prati, Ann Intern Med 2002
Clinical Implications of the Different Thresholds for Normal ALT
Blood donors ● male donors : 4 - 20%● female donors : 1.5 - 16%
HCV infection ● males : 13 - 22 %● females : 20 - 45 %
Piton, Hepatology 1998
abnormal ALT
Chronic Liver Disease - Beyond the Viruses ...
● Etiologies :➪ Overweight, Diabetes +++➪ Covert Alcohol➪ Drugs➪ Seronegative autoimmune liver diseases➪ Vascular liver diseases➪ Celiac disease➪ Occult HBV
Impact of Overweight on Chronic L iver Disease
< 25 32 0.3 (0.32-0.33)
25-27 25 1.16 (1.15-1.17)
> 27 45 1.83 (1.81-1.85)
BMI (kg/m2) % Relative Risk (CI 95%)
Dionysos Study, n = 1211 (6917 total)
(Bellentani Hepatology 1994)
Proportion of Patients With Cryptogenic Cirrhosis according to BMI - UNOS Database
0
5
10
15
20
25
30
35
40
> 40 BMI35 - 4030 - 3525 - 30< 25
HCV Alcohol CryptogenicN =19271
%
(Nair, Hepatology 2002)
0
5
10
15
20
25
30
35
40
Obésité et C irrhose Cryptogénétique
Cirrhose X NASH Cirrhose C CBP
N
Age
Obésité (% )
Femmes (% )
Diabète (% )
70 50 39 33
63(+/- 11) 49(+/-14) 60(+/-7) 54(+/-10)
70 56 36 100
47 64 3 15
53 42 25 15
Caldwell, Hepatology 1999
Normal : 10 %
Steatosis alone : 48 %
Steatohepatitis : 42 %
L iver Histology in Overweight Patients
n = 858 ; 9 studies, 1978 - 2002
Prevalence of NASH/NAFLD
First (or second) cause of chronic liver disease in Western Countries
Prevalence among patients with abnormal LFTs of undetermined etiology (n=673, 5 studies)
steatosis alone : 30%
steatohepatitis : 26%
Hepatic Fibrosis in NASH
None or mild 65
Severe (cirrhosis excepted) 20
Cirrhosis 15
%
n= 572, 9 studies 1980 - 2001
Risk Factors for Severe Fibrosis in NASH
Age > 45-50 yrs
Diabetes
ALT>2N
BMI > 27 kg/m²
HTA
HyperTG
AST/ALT > 1Ratziu, Gastroenterology 2000Ratziu, Gastroenterology 2000
Angulo, Hepatology 1999Angulo, Hepatology 1999
Dixon, Gastroenterology 2001Dixon, Gastroenterology 2001