Hepatitis B and C Dr George S. Potamitis F.E.B.G.H Gastroenterologist Hepatologist-Internal Medicine
Viral Hepatitis A Fecal - Oral Rarely fatal Not chronic B Parenteral Sexual Vertical Usually self-limiting C Parenteral Some sexual Vertical Usually Chronic D Requires HBsAg Coinfection Superinfection E Fecal - Oral Not Chronic G Poorly characterized Likely parenteral
HEPATITIS Β
The improvement of the socioeconomic conditions, the change in high risk behavior, and the vaccination programs resulted in changes in the epidemiology of HBV infection worldwide.
Hepatitis B infection has a wide range of seroprevalance in the Mediterranean Countries There is obvious decrease of acute B cases, a decrease of HbsAg seropositivity, especially in small ages and movement of the contamination to persons older than 20 years of age.
Cyprus is a country of low endemicity. HB s carriers ~ 2% C sexual contact- intrafamiliar exposure
Most or all of the cases of CHB in Cyprus HBeAg negative chronic Hepatitis B
Areas of high endemicity Mammari 5 8 % Anayia
Thalasseamic group HBsAg (+) ~ 10%
Άτομα υψηλού κινδύνου 1. Σεξουαλικοί σύντροφοι και συγκάτοικοι ασθενών με χρόνια ηπατίτιδα Β που δεν έχουν ανοσία. 2. Άτομα με πολλαπλούς ερωτικούς συντρόφους. 3. Χρήστες ναρκωτικών ουσιών. 4. Άτομα που εκτίθενται λόγω επαγγέλματος σε βιολογικά υγρά: γιατροί, νοσηλευτικό προσωπικό, οδοντιάτροι, παρασκευαστές εργαστηρίων, αστυνομικοί, πυροσβέστες και εργαζόμενοι σε γραφεία κηδειών. 5. Πολυμεταγγιζόμενοι με αίμα ή παράγωγα του. 6. Άτομα που μεταγγίσθηκαν πριν το 1980. 7. Τρόφιμοι και προσωπικό φυλακών. 8. Ασθενείς που υποβάλονται σε αιμοκάθαρση. 9. Μεταμοσχευμένοι. 10. Άτομα που ταξιδεύουν σε χώρες με υψηλή συχνότητα ηπατίτιδας Β.
In 1992 the WHO recommended that all countries include Hepatitis B in their routine infant immunization programs.
In Cyprus immunization strategy includes 1. prevention of perinatal infection through routine screening of all pregnant women and appropriate postexposure immunoprophylaxis of infants born to HbsAg (+) women. 2. Routine vaccination of infants 3. Routine vaccination of children and adolescents who have not previously vaccinated. 4. Vaccination of adults at increased risk of infection.
Acute Hepatitis B Icteric phase Dark urine Later pale stools Yellowish coloration of: - mucous membranes - conjuctiva - scleva - skin
Διάγνωση: HBeAg antihbeιgg/igm HBeAg antihbeag HBVDNA Τρανσαμινάσες Χολερυθρίνη Χρόνος Προθρομβίνης
Chronic carrier state of Hepatitis B Definition: Hepatitis B surface antigen delectable in the blood >6months Infuencing factors: Severity of acute disease Age at infection Immunological status
Genotype *B C
Progression of Hepatitis B infection Resolution Resolution Silent Cirrhosis Short tern Long tern Cirrhosis Liver Death Infection Hepatitis Cancer Long tern Cirrhosis Death Carrier 30-50 year
Antiviral treatment 1990 IFN a2b IFN a2a
Consensus EASL for treatment of HBeAg (-) CHB Conventional INF Treatment Pegylated IFN (genea) ΝΑ Duration of treatment: IFN 6 months LAM?
More epidemiological studies to see whether the prevalence is decreasing (rate of HBV markers) and the rate of chronic HBV carriers.
HEPATITIS C
The mortality due to HCV infection, terminal liver failure and HCC will continue to increase.
Prevalence of Hep. C in Cyprus <0.5% Parenteral exposure was the main risk factor for the transmission of HCV infection.
Συνήθεις τρόποι μετάδοσης Μετάγγιση Επαμβάσεις Χρήση μολυσμένων βελονών
Hepatitis C Clinical Spectrum Alcohol Genotype, Age, other factors
Διάγνωση Ηπατίτιδας C antihcv HCVPCR
Gene type 1a (1b) 2, 3
Special groups Thalasseamic patients: 8-10%
Acute infection of Hep. C New cases? Non responders Reccurrent cases
Extraintestinal manifestation Aplastic anaemia (Cyprus Med. Journal, 93.1991) Optic Neuritis (FALK Symposium 115, 1999, Basel)
Educational programs for GPs-Family Doctors
Interpretation of HCV assays Anti HCV HCVRNA Interpretation Positive Positive Acute or chronic depending on the clinical context Positive Negative Resolution of HCV Acute of Negative Positive Early acute HCV infection chronic HCV in setting of immunosuppressed state False positive HCVRNA test Negative Negative Absence of HCV injection
Patients with HCV infection Goals of Antiviral Therapy Viral clearance Delay decompensation Prevent HCC Prevent HCV Recurrence after liver transplantation
100 50 0 27.4 Συν. Ασθενών Γονότυπος 1 24 weeks 48 weeks Therapy management of patients with normal transaminases The indication for treatment of hepatitis C is not connected with the level of transaminase but with the potential evolution of the virus Presence of symptoms (extrahepatic) Histological lesions Risk of virus transmission from the patient 80 70 60 50 40 30 20 24 weeks 48 weeks καμιά θεραπεία 10 0 Συν. Ασθενών Γονότυπος 1 Γονότυπος 2/3
Advances in Therapy 100% Sustained Virologic Response Peg-IFN + ribavirin 50% No treatment IFN IFN (12mos) (6mos) IFN + ribavirin Peg-IFN mono 1990 2000 2004
Therapy of Chronic Hepatitis C HCV Γονότυπος 1 PEG IFN + Ribavirin Peg IFN a-2b, 1,5 mgr/kg/w Peg IFN a-2a 180 mgr/w RIVA 1000-1200mg 12 weeks PCR Neg Continue PCR POS >2 log drop Continue PCR POS <2 log drop Stop 24 weeks PCR Neg PCR POS Continue Stop 48 weeks Stop Stop
Contraindication for treatment of CHC Advance liver Cirrhosis Depression Pregnancy History of suicide attacks Contraindication for RBV Hemolytic disease Heart problem Renal failure Cr>2mg/dl
55%-60% of treatment naïve patients fail to achieve SRV, with inteferon + ribavirin Only 11% of nonresponders achieve SRV when retreated with peginterferon + ribavirin New therapeutic strategies must be explored
Direct-acting antiviral (DAA) agents NS3/4A protease inhibitors Telaprevir Boceprevir
Το HCV γονιδίωμα και οι πιθανοί φαρμακευτικοί στόχοι. To γονιδώμα του HCVRNA χρησιμεύει ως μήτρα και ως ιικός RNA αγγελιοφόρος για την παραγωγή του ιού. Μεταφράζεται σε μία πολυπρωτείνη η οποία διασπάται από τις πρωτεάσες. Όλα τα HCV ένζυμα (ΝS2-3 + NS4 πρωτεάσες, η NS3 ελικάση και η NS%B RdRp), είναι απαραίτητες για τον πολλαπλασιασμό του HCV και αποτελούν δυνητικούς στόχους των φαρμάκων.
SVR (%) SVR with BOCEPREVIR or TELAPREVIR + PR compare with previous compination treatment 100 80 Relapsers 69-83 > Naive Partial > Responders > 63-75 Null Responders 60 40-59 40 29-40 20 0 Poordad F, et al. N Engl J Med. 2011;364:1195-1206. Jacobson IM, et al. N Engl J Med. 2011;364: 2405-2416. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. Zeuzem S, et al. N Engl J Med. 2011;364: 2417-2428. Bronowicki JP, et al. EASL 2012. Abstract 11.
Experience with triple therapy PegIFN+RIBAVIRIN+Telaprevir in 7 treatment experienced patients infected with HCV genotype 1.
In Cyprus we have what is necessary for good practice in order to treat patients with Hepatitis B and C
High standard Molecular Biology Labs (PCR) Experience Histopathologists High standard Imaging Centers
One referral Center for Fibroscan High sensitivity and specificity in F3 and F4 in order to avoid biopsy.
But we need more recent epidemiological studies and educational programs.