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- 1. Training workshop on Clinical Management of Viral Hepatitis
- 2. Learning objectives At the end of this sessions, learners should understand the following • Natural history of acute and chronic hepatitis B virus infection • Various phases in natural history of chronic HBV infection • Identify the phase of hepatitis B infection in individual patients
- 3. National Guidelines - India
- 4. Consequences of hepatitis B virus infection Hepatitis B virus infection Acute infection (short duration: <6 mo) Chronic infection (duration >6 mo) Asymptomatic Acute viral hepatitis Acute liver failure Chronic hepatitis B Cirrhosis: compensated Cirrhosis: decompensated
- 5. Outcome of HBV infection: Acute vs chronic Outcome depends largely on age the time of infection Younger the age at infection: Greater the risk of chronic infection Lower the risk of symptomatic during initial phase
- 6. Acute vs chronic hepatitis B From public health viewpoint: •We are worried primarily about chronic hepatitis B, because – It causes long-term morbidity and early death – It is a reservoir for transmission of HBV •Acute hepatitis B is not a public health concern – Causes a short lasted illness, with loss of mandays of work – But no long-term morbidity and very little excess mortality – Unlikely to be responsible for transmission of HBV So HBV infection acquired during childhood is the primary concern and focus from public health viewpoint
- 7. Acute hepatitis and acute liver failure
- 8. Acute hepatitis (true for all hepatitis viruses) • Incubation period HBV: 6 weeks to 6 months (different for different viruses) • Three phases of illness – Prodrome Malaise, fatigue, low-grade fever nausea, vomiting, aversion to food mild itching, joint/muscle pain lasting a few days – Icteric phase Dark urine, yellow eyes, light stool color, prodromal symptoms improve lasts a few days to weeks (usually <6 wk) – Convalescence Gradual recovery is nearly the rule
- 9. Acute liver failure (due to any virus) • Features similar to those of acute hepatitis to begin with • But more severe liver damage and leads to serious clinical state • Altered behaviour and consciousness (encephalopathy) • Bleeding tendency • Small liver • Brain edema • High risk of death
- 10. Acute HBV infection vs acute liver failure Acute viral hepatitis (AVH-B) Acute liver failure (ALF-B) Prodromal symptoms Present Sudden jaundice Present SGPT/SGOT Markedly elevated IgM anti-HBc Positive Encephalopathy Absent Present Coagulation Near normal Markedly deranged Liver size Slightly large Small
- 12. Natural history of hepatitis B: Another view Host’s immunity Hepatitis virus A duel between the virus and the host’s immune response Depends on who has the upper hand
- 13. Natural history of chronic hepatitis B Chronic hepatitis B Immune- tolerant phase Immune-active phase Immune-control phase Reactivation phase Immune clearance (cure) Discussed further in the next talk
- 14. Natural history of chronic HBV infection Discussed further in the next talk
- 15. Natural history of chronic HBV Time since infection Immune control by host HBV virus load ALT/AST 3 4 2 1 Relative amount 1: Immune tolerant 2: Immune active 3: Immune control 4: Reactivation (only in some)
- 16. Serological markers in chronic HBV Phase of chronic HBV Immune tolerant Immune- reactive Immune clearance Reactivation ALT/SGPT HBV DNA HBeAg Anti-HBe Anti-HBV immune control Need for treatment
- 17. Serological markers in chronic HBV Phase of chronic HBV Immune tolerant Immune- reactive Immune clearance Reactivation ALT/SGPT HBV DNA HBeAg Anti-HBe Anti-HBV immune control Weak Strong Strongest Weak Need for treatment
- 18. Serological markers in chronic HBV Phase of chronic HBV Immune tolerant Immune- reactive Immune clearance Reactivation ALT/SGPT Low HBV DNA High HBeAg + Anti-HBe - Anti-HBV immune control Weak Strong Strongest Weak Need for treatment No
- 19. Serological markers in chronic HBV Phase of chronic HBV Immune tolerant Immune- reactive Immune clearance Reactivation ALT/SGPT Low High HBV DNA High Moderate HBeAg + +/- Anti-HBe - -/+ Anti-HBV immune control Weak Strong Strongest Weak Need for treatment No Yes
- 20. Serological markers in chronic HBV Phase of chronic HBV Immune tolerant Immune- reactive Immune clearance Reactivation ALT/SGPT Low High Moderate HBV DNA High Moderate Low HBeAg + +/- -/+ Anti-HBe - -/+ +/- Anti-HBV immune control Weak Strong Strongest Weak Need for treatment No Yes No
- 21. Serological markers in chronic HBV Immune phase of chronic HBV Immune tolerant Immune- reactive Immune clearance Reactivation ALT/SGPT Low High Moderate Low/mod HBV DNA High Moderate Low Low/mod HBeAg + +/- -/+ -/+ Anti-HBe - -/+ +/- +/- Anti-HBV immune control Weak Strong Strongest Weak Need for treatment No Yes No Yes
- 22. Natural history of chronic hepatitis Prolonged chronic HBV infection Hepatocellular carcinoma Liver cirrhosis
- 23. Cirrhosis An advanced stage of liver disease characterized by extensive hepatic fibrosis alteration of liver architecture disrupted hepatic circulation liver nodularity
- 24. Compensated versus decompensated cirrhosis • A person with cirrhosis initially continues to function normally because of a large reserve capacity in liver function • At some stage, this ‘compensation’ fails and cirrhosis starts to affect body function and threatens survival: ‘decompensation’ • Decompensated cirrhosis is characterized by features of portal hypertension plus features of liver failure
- 25. Natural history of chronic hepatitis Complications (decompensation) • Variceal bleeding • Ascites • Encephalopathy Prolonged chronic HBV infection Liver cirrhosis Hepatocellular carcinoma
- 26. Decompensated cirrhosis Decompensation: presence of one of the following features a)Ascites b)Hepatic encephalopathy c)Total bilirubin >2.5 x ULN* + prolonged prothrombin time (>3 second increase or INR** >1.5) d)Variceal bleed * Upper limit of normal ** International normalized ratio
- 27. Summary • HBV infection in infants or small children (<5 y) has a high risk of progression to chronic infection • HBV infection in older children or adults results in acute hepatitis with spontaneous clearance in 90-95% • Chronic HBV infection passes through several stages, with progression to cirrhosis and/or liver cancer in a proportion • Patients with cirrhosis can develop decompensation and liver- related death • Liver cancer can occur even without cirrhosis • Among persons with chronic HBV infection, only those with elevated ALT and high HBV DNA need drug treatment