Hépatites virales Pr. M. Messast.

Présentation au sujet: "Hépatites virales Pr. M. Messast."— Transcription de la présentation:

1 Hépatites virales Pr. M. Messast

2 Introduction Problème de santé mondial HVB HVC
2,000,000 infections porteurs chroniques 620,000 décès par an 1ère cause des carcinome hépatocellulaire HVC Hépatite chronique (B, C, D) Cirrhose Carcinome hépatocellulaire

3 Hépatite virale B Huit génotypes : A à H I. Epidémiologie
1) Agent : VHB Hepadnaviridae, ADN (intranucléaire) Particule de Dane Capside : Ag HBc, Ag HBe Enveloppe : Ag HBs Huit génotypes : A à H Algérie : D

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5 2) Réservoir : Homme 3) Transmission Parentérale : sang et dérivés, injections Sexuelle et salivaire Mère-enfant 4) Modalités Zones basse, moyenne et haute endémie

6 Répartition géographique deVHB
[SLIDE 41, SLIDE 42] Global Patterns of Chronic HBV Infection, Geographic Distribution of Chronic HBV infection* Approximately 45% of the global population live in areas with a high prevalence of chronic HBV infection (> 8% of the population is HBsAg‑positive); 43% in areas with a moderate prevalence (2%‑7% of the population is HBsAg‑positive); and 12% in areas with a low prevalence (< 2% of the population is HBsAg‑positive). In high prevalence areas, the lifetime risk of HBV infection is >60%, and most infections are acquired at birth or during early childhood when the risk of developing chronic infection is greatest. In these areas, because most infections in children are asymptomatic, very little acute disease related to HBV occurs, but rates of chronic liver disease and liver cancer in adults are very high. In moderate prevalence areas, the lifetime risk of being infected is 20%‑60% and infections occur in all age groups. Acute disease related to HBV is common in these areas because many infections occur in adolescents and adults; however, the high rates of chronic infection are maintained mostly by infections occurring in infants and children. In low prevalence areas, the lifetime risk of infection is <20%. Most HBV infections in these areas occur in adults in relatively well defined risk groups. *(Note: The map of HBsAg prevalence generalizes available data and patterns may vary within countries.) Prévalence Ag HBs ³8% - Haute 2-7% - Moyenne <2% - Basse

7 II. Pathogénie Virus peu cytopathogène Réaction immune de l’hôte
Très forte hépatite fulminante Forte : hépatite aiguë Faible et adéquate : hépatite asymptomatique Faible et inadéquate : chronicité Nulle : portage chronique

8 III. Clinique 1) incubation : 4 à 28 semaines
Polymorphisme clinique 1) incubation : 4 à 28 semaines 2) Forme asymptomatique : 90% 3) Forme aiguë Phase pré-ictérique : syndrome pseudogrippal Fièvre, Asthénie, nausées, arthralgies Phase ictérique Ictère cutanéomuqueux

9 IV. Biologie 1) Atteinte hépatique 2) Sérologie
Cytolyse hépatique : ALAT, ASAT > 5 N Cholestase : phosphatases alcalines Insuffisance hépatocellulaire (TP) < 50% : sévère < 30% : grave 2) Sérologie Ag HBs, Ag HBe Ac anti-HBs, anti-HBe, anti-HBc ADN viral

10 Hépatite virale B aiguë
Semaines après exposition Symptomes HBeAg anti-HBe Ac anti-HBc totaux IgM anti-HBc anti-HBs HBsAg 4 8 12 16 20 24 28 32 36 52 100 Titre [SLIDE 34] Acute Hepatitis B Virus Infection with Recovery: Typical Serologic Course Serologic markers of HBV infection vary depending on whether the infection is acute or chronic. The first serologic marker to appear following acute infection is HBsAg, which can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks (mode, 30‑60 days) after exposure to HBV. In persons who recover, HBsAg is no longer detectable in serum after an average period of about 3 months. HBeAg is generally detectable in patients with acute infection; the presence of HBeAg in serum correlates with higher titers of HBV and greater infectivity. A diagnosis of acute HBV infection can be made on the basis of the detection of IgM class antibody to hepatitis B core antigen (IgM anti‑HBc) in serum; IgM anti‑HBc is generally detectable at the time of clinical onset and declines to subdetectable levels within 6 months. IgG anti‑HBc persists indefinitely as a marker of past infection. Anti‑HBs becomes detectable during convalescence after the disappearance of HBsAg in patients who do not progress to chronic infection. The presence of anti‑HBs following acute infection generally indicates recovery and immunity from reinfection.

11 V. Evolution 1) Favorable : 90% 2) hépatite fulminante :< 1% TP < 30% Encéphalopathie : trouble de la conscience, astérixis, syndrome hémorragique et hypoglycémie Décès : 80% Guérison sans séquelles

12 3) hépatites chroniques
a) Portage chronique Ag HBs : transaminases normales, Ac Anti-HBe, pas d’ADN viral b) Hépatite chronique : persistance de l’Ag HBs, élévation des transaminases pendant plus de 6 mois, ADN viral positif Hépatite chronique persistante Hépatite chronique active 4) cirrhose post-hépatitique 5) cancer primitif du foie

13 Hépatite virale B chronique
IgM anti-HBc anti-HBc totaux HBsAg Aiguë (6 mois) HBeAg Chronique (années) anti-HBe 4 8 12 16 20 24 28 32 36 52 Semaines après contamination Titre [SLIDE 35] Progression to Chronic Hepatitis B Virus Infection: Typical Serologic Course In patients with chronic HBV infection, both HBsAg and IgG anti‑HBc remain persistently detectable, generally for life. HBeAg is variably present in these patients. The presence of HBsAg for 6 months or more is generally indicative of chronic infection. In addition, a negative test for IgM anti‑HBc together with a positive test for HBsAg in a single serum specimen usually indicates that an individual has chronic HBV infection.

14 4 Phases de l’Infection chronique VHB
Ag HBe Ac Anti-HBe HBV DNA activité des ALAT ALT, alanine aminotransferase; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus. This slide reviews the different phases of HBV infection. Of course, not all HBV carriers will move through these 4 phases uniformly. The first phase of infection is the immune-tolerance phase where the level of HBV DNA is very high because it is the phase when the virus replicates very rapidly and significantly, although the alanine aminotransferase (ALT) is quite normal. Typically, these patients will not complain of any symptoms and will have normal liver function tests. This can be followed by an immune-clearance phase. In this phase of the infection, the virus and the host immune system are at odds, resulting in the ALT fluctuating up and down or remaining high, and the HBV DNA can also fluctuate, but at a fairly high level. This can be followed by an inactive carrier state in which both HBV DNA levels and ALT levels come down to near-normal levels. If a liver biopsy were performed, in this phase, the liver could either be normal or there may be minimal inflammation and fibrosis. These individuals can then experience HBV reactivation, when the HBV DNA and ALT levels again rise, and the patient can be quite symptomatic. The ideal times for treatment or intervention with antiviral drugs are during the phases of high HBV DNA and ALT levels when active inflammation is occurring. Phases Tolérance Immune Clearance Immune Portage inactif Reactivation Foie inflammation et fibrose minimes Inflammation chronique active Hepatite modérée et fibrose minime Inflammation Active Temps idéal de traitement

15 Formes aiguës communes Formes fulminantes Formes chroniques
VI. Traitement 1) curatif Formes aiguës communes Pas de traitement Formes fulminantes Traitement symptomatique Formes chroniques Interféron alpha, pégylé Entécavir, Ténofovir…

16 2) préventif Vaccination (0, 1, 6 mois) Sérothérapie
Obligatoire à la naissance Obligatoire Personnel soignant Sérothérapie Nouveau-né (mère Ag HBs + Accident d’exposition au sang

17 Hépatite virale C I. Epidémiologie 1) Agent : VHC 2) Réservoir : Homme
Flaviviridae, ARN 6 génotype : 1 à 6 (Algérie G1) 2) Réservoir : Homme 3) Transmission : comme VHB 4) Modalités Algérie 3,5% population

18 II. Clinique 1) Incubation : 4 à 12 semaines 2 ) Peu symptomatique Anictérique : 90% III. Biologie 1) Transaminases : N fluctuations 2) Sérologie Ac anti-HVC Amplification génique (PCR) Etat du foie Fibroscan, fibrotest

19 2) Hépatite chronique : 85%
IV. Evolution 1) guérison : 15% 2) Hépatite chronique : 85% 20% cirrhose en ans 3-5 % CHC par an

20 Hépatite virale C guérie
HCV RNA Symptomes +/- Évolution après contamination Titre Anti-HCV ALT Normale 1 2 3 4 5 6 années Mois [SLIDE 52] Acute HCV Infections with Recovery: Typical Serologic Course The incubation period for acute hepatitis C has been reported to average 6 – 7 weeks, but may range 2 – 26 weeks. Children and adults with acute hepatitis C are typically either asymptomatic or exhibit mild clinical illness. In adults with acute HCV infection, studies have shown up to 40% had some symptomatic illness and 15 –30% had jaundice. The course of acute hepatitis C is variable, although its most characteristic feature is fluctuating alanine aminotransferase (ALT) patterns. Normalization of ALT may occur and suggest full recovery although symptomless ALT elevations can follow, indicating chronic infection. Fulminant hepatic failure following acute hepatitis C is rare.

21 Hépatite virale C chronique
Symptomes +/- Temps après exposition Titres Anti-HCV ALT Normale 1 2 3 4 5 6 Années Mois HCV RNA [SLIDE 53] Progression to Chronic HCV Infection: Typical Serologic Course Persistent HCV infection develops after the onset of acute hepatitis C in most persons (>85%). Chronic hepatitis C develops in 60 – 70% of HCV-infected persons, and 10 – 20% of these individuals may develop cirrhosis over the course of 20 – 30 years. Chronic hepatitis C progresses at a slow rate without symptoms in the majority of patients during the first two decades subsequent to infection. Usually chronic hepatitis C is not diagnosed until symptoms, such as fatigue appear with advanced liver disease.

22 V. Traitement 1) Curatif 2) Prophylaxie Moyens
Sofosbuvir :1 cp/j (cp 400 mg) + Daclatasvir : 1 cp /j (cp 60 mg) Sofosdac : 1cp/j Hépatite virale chronique C 12 semaines 95% de guérison Surveillance Transaminases PCR sérique 2) Prophylaxie Dépistage chez les donneurs de sang Désinfection du matériel

23 Hépatite Delta 1) Epidémiologie 2) Clinique 3) Diagnostic : sérologie
Agent : VHD, virus défectif à ARN Transmission parentérale 2) Clinique Co-infection VHB/VHD : hépatite fulminante Surinfection : 80% hépatite chronique 3) Diagnostic : sérologie

24 Conclusion HVB : Prévenir mais pas guérir
HVC : Guérir mais pas prévenir