NATURAL HISTORY OF HEPATITIS B

Transcription

1 NATURAL HISTORY OF HEPATITIS B AND DIAGNOSTIC: STATE OF THE ART O. BAHRI LABORATORY OF MEDICAL BIOLOGY AZIZA OTHMANA HOSPITAL TUNIS, TUNISIA The 2 nd Congress of The Federation of Arab Societies of Clinical Microbiology and Infectious Diseases Tunisia, May 2012

2 HEPATITIS B = GLOBAL HEALTH PROBLEM One of the most common chronic viral infections HBV contact 2 billion HBV chronically infected million Death Ranked cause of cancer Ranked cause of death by cancer 1 million annually 5 th worldwide 3 th worldwide Mutimer D et al, Medicine 2011

3 HEPATITIS B = GLOBAL HEALTH PROBLEM High endemicity: - Asia - Africa - Parts of southern, eastern Europe El Gouhari H et al, Cleveland Clin. J. Med 2008

4 NATURAL HISTORY OF HBV INFECTION HBV infection = a dynamic process VIRAL REPLICATION HOST IMMUNE RESPONSE - Course of viral infection - Severity of liver damage

5 NATURAL HISTORY OF HBV INFECTION Immune response against HBV infection Ganem D, NEJM 2004

6 NATURAL HISTORY OF HEPATITIS B Acute HBV infection Immune response is adequate CD8+ Immune response is enhanced CD8+ HBV clearance Moderate liver damage Resolved form HBV clearance Massive liver damage Fulminant form Lok AS and McMahon BJ. Hepatology 2007;45:507-39

7 NATURAL HISTORY OF HEPATITIS B Acute HBV infection - Fulminant form is characterised by: - Presence of IgM against HBcAg - Absence of HBV DNA Ganem D, NEJM 2004

8 NATURAL HISTORY OF HEPATITIS B Acute HBV infection Chronic infection - Inefficient Immune response -cccdna in hepatocytes Progressive chronic hepatitis Inactive carrier state 2% - 6%/year Cirrhosis 2.5% - 5%/year Death HCC Lok AS and McMahon BJ. Hepatology 2007;45:507-39

9 ROLE OF AGE OF CONTAMINATION IN THE EVOLUTION OF HEPATITIS B Acute HBV infection Perinatal Early childhood Adult 20-50% 10% 95% Resolved infection Chronic infection Resolved infection Chronic infection El Gouhari H et al, Cleveland Clin. J. Med 2008

10 NATURAL HISTORY OF CHRONIC HEPATITIS B

11 IMMUNOTOLERANT PHASE > 10 8 cp/ml

12 IMMUNOCLEARANCE PHASE > 10 5 cp/ml

13 INACTIVE CARRIER STATE < 10 4 cp/ml

14 REACTIVATION PHASE > 10 4 cp/ml

15 SEROLOGICAL AND VIROLOGICAL PROFILES FOR STATES OF INFECTION

16 QUANTIFICATION OF HBV DNA HBV Digene Hybrid-Capture II Ultra-sensitive HBV Digene Hybrid-Capture II Versant HBV DNA 3.0 Assay Amplicor HBV Monitor Cobas Amplicor HBV Monitor Cobas Taqman HBV Real-Art HBV PCR Assay

17 QUANTIFICATION OF HBV DNA Objectives: - Determine the state of chronic infection - Survey evolution of chronic hepatitis B - Explore viral reactivation - Indicate and monitor treatment - Detect an emergence of resistant mutants to treatment

18 NEW DIAGNOSTIC TOOLS cccdna Quantification infected of cccdna liver cell in burden biopsy

19 NEW DIAGNOSTIC TOOLS QUANTIFICATION OF HBSAG A useful new tool for monitoring and optimization of hepatitis B treatments - Levels of serum HBsAg and intrahepatic cccdna are closely correlated - HBsAg quantification = indirect reflect of the number of infected hepatocytes. - The decline of HBsAg levels in serum = A predictive marker for sustained virological response, and clearance of HBsAg.

20 NATURAL HISTORY OF HEPATITIS B Acute HBV infection Chronic infection Progressive chronic hepatitis Inactive carrier state 2% - 6%/year Cirrhosis 2.5% - 5%/year Death HCC Lok AS and McMahon BJ. Hepatology 2007;45:507-39

21 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS 1- Host factors 2- Host-viral interaction 3- Viral factors Xu H; Current Hepatitis Rec 2011

22 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS HOST FACTORS Strentgh of association Male ++ Age> 40y ++ Genetic susceptibility? (under evaluation) (polymorphism of IL10, IL18 ) Family history of HCC + Regular alcohol consumption +/- Xu H; Current Hepatitis Rec 2011

23 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS HOST-VIRAL INTERACTIONS Risk Factors Strength of association Cirrhosis ++ ALT levels + ALT levels = poor predictor for progression to severe forms especially the reactivation phase (fluctuation of ALT) Xu H; Current Hepatitis Rec 2011

24 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS VIRAL FACTORS Risk Factors Strength of association High HBV DNA levels ++ Genotype C + Mutations Precore mutation - Core Promoter mutation ++ Pre-S + HBx + Xu H; Current Hepatitis Rec 2011

25 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS HBV DNA LEVELS REVEAL HBV study: Population-based prospective cohort in Taiwan (3582 HBV carriers) Cirrhosis HCC Kao J; Hepatol intern 2007

26 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS VIRAL GENOTYPES Risk for HCC D > A C > B Hadzyanis S; J. Hepatology 2011

27 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS Pre-S deletion VIRAL MUTATIONS Nt 1766/1768 Nt 1653/1753 Kao J; Hepatol intern 2007

28 RISK FACTORS FOR SEVERE EVOLUTION OF CHRONIC HEPATITIS OTHER RISK FACTORS Kao J; Hepatol intern 2007

29 RISK FACTORS AND PREDICTIVE SCORES Some authors proposed predictive scores To monitor treatment and to survey HCC

30 RISK FACTORS AND PREDICTIVE SCORES Yuen MF et al Yang et al Wong et al Studied population Parameters used 820 untreatedpatients with CHB 3600 HBV infected patients 1000 HBV infected patients Age Gender HBV DNA level Core/BCP mutations Cirrhosis Sex Age Family history of HCC Alcohol HBeAg HBV DNA level HBV genotype Age Albumin Bilirubin HBV DNA level Cirrhosis Predictive scores must be evaluated before introduction in routine

31 CONCLUSION Characteristics of chronic hepatitis B Complexity High variabiliy Implication of several risk factors Cohort studies in differents parts of the world are needed to best: Understanding of the evolution for HBV infection Monitoring of chronic infection