1. Viral Hepatitis Jade Woolley jlw1g10@soton.ac.uk

2. Definition Hepatitis: inflammation of the liver involving hepatocyte necrosis and inflammatory cell infiltration Acute Usually viral Self limiting Chronic Sustained inflammation for > 6 months Risk factor for cirrhosis and hepatocellular carcinoma

3. Acute Liver Damage Tumour infiltration Vascular obstruction (Budd-Chiari malformation) Biliary obstruction Autoimmune hepatitis Toxins Alcohol Viral hepatitis

4. Normal Liver Function

5. Impaired Liver Function Liver FunctionMechanismClinical effect PhysicalHepatocyte damageIncreased AST/ALT Distension of liver capsuleRUQ pain and nausea Detoxification & excretion Reduced biliary excretionJaundice Reduced detoxificationEncephalopathy Synthetic function Reduced protein productionHypoalbuminaemia – oedema, ascites Coagulopathy Reduced gluconeogenesisHypoglycaemia (Main symptoms in viral hepatitis) In most viral infections, symptoms come in waves within a 3-6 week period

6. Measures of liver biochemistry Bilirubin – ↑ with Haemolysis, Gilbert’s syndrome, biliary tract obstruction Aminotransferases – AST and ALT – ALT more specific for the liver – Produced by hepatocytes – Leaks into circulation with liver cell damage (eg hepatitis) Alkaline phosphatase – Produced in biliary epithelium – Levels rise with cholestasis Gamma GT – Hepatic enzyme transiently induced by alcohol

7. Measures of liver biochemistry Bilirubin – ↑ with Haemolysis, Gilbert’s syndrome, biliary tract obstruction Aminotransferases – AST and ALT – ALT more specific for the liver – Produced by hepatocytes – Leaks into circulation with liver cell damage (eg hepatitis) Alkaline phosphatase – Produced in biliary epithelium – Levels rise with cholestasis Gamma GT – Hepatic enzyme transiently induced by alcohol ALT > Alk Phos = hepatocellular pattern – hepatitis, cirrhosis Alk Phos > ALT = cholestatic pattern – biliary obstruction Prothrombin time: marker of synthetic liver function Used to assess disease severity

8. Viral Hepatitis Viruses that specifically infect the liver: – Hepatitis A, E, B, C and D Systemic viruses that affect the liver: – Epstein-Barr virus – Cytomegalovirus, herpes virus, yellow fever, varicella

9. Hepatitis A Acute and self-limiting – Can be asymptomatic Common, especially in developing countries Spread by faecal-oral route 2-6 week incubation period RNA virus Can be vaccinated against – Hep A vaccine lasts for 10 years Does not develop into chronic disease

10. Hep A: think electives!

11. Hepatitis E The same as Hep A – Water-borne virus spread by faecal-oral route, RNA virus, self-limiting, does not progress to chronic disease BUT: – More serious – usually more acute and more symptomatic – Very nasty in pregnant women – 25% mortality – No vaccine Hep E: think pregnant woman on elective

12. Hepatitis B Blood-borne virus – Parenteral spread – sexual, IV, vertical Common in developing countries ≈6 month incubation period DNA virus – T-cell mediated apoptosis of infected cells Can be vaccinated against Can progress to chronic infection – 10% develop chronic Hep B, where viral load is seen persisting after 6 months

13. Hep B: think dodgy tattoo on elective

14. Hepatitis D Can only occur with Hep B infection Co-existent infection – 90% -↓Hep B severity by reducing replication rate ‘Superinfection’ – 10% - worse prognosis

15. Hepatitis C Similar to Hep B – Blood-borne, progresses to chronic disease BUT: – No vaccine – Not really spread sexually – mainly blood and IDU 80% of haemophiliacs in the UK have Hep C – RNA virus Long dormancy period – decades 80% of pts develop chronic disease – Worldwide leading cause of liver disease

16. Hep C: think dodgy tattoo on elective forty years ago

17. Chronic Hepatitis Infection Hep B and especially Hep C Chronic hepatitis progresses to cirrhosis Cirrhosis progresses to hepatocellular carcinoma ‘Ground-glass’ hepatocytes of chronic Hep B

18. Cirrhosis and HCC Cirrhosis: 1.Hepatocyte necrosis 2.Fibrosis 3.Nodular regeneration of hepatocytes HCC: Red flags – anorexia and weight loss w/ cirrhosis Diagnostic imaging Prognosis 6-20 months

19. Treatment Acute infections are self-limiting Chronic infection: Interferons – IFN α – Given subcutaneously for 1 year – Inhibits viral replication, increases immune response to virus Antivirals – tenofovir, lamivudine – Given orally – Reverse transcriptase inhibitors

20. Summary Hep AHep EHep BHep C VirusRNADNARNA TypeWater-borneBlood-borne TransmissionFaecal-oral route Parenteral (needles, vertical, sexual) Chronic disease? NoYes Vaccine?YesNoYesNo Others Severe in pregnancy High risk of HCC Co-infection with Hep D Long dormant period