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Viral Hepatitis. Jade Woolley jlw1g10@soton.ac.uk. Definition. Hepatitis : inflammation of the liver involving hepatocyte necrosis and inflammatory cell infiltration. Acute Usually viral Self limiting. Chronic Sustained inflammation for > 6 months
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Viral Hepatitis Jade Woolley jlw1g10@soton.ac.uk
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
Acute Liver Damage Viral hepatitis Toxins Alcohol Autoimmune hepatitis Tumour infiltration Vascular obstruction (Budd-Chiari malformation) Biliary obstruction
Impaired Liver Function (Main symptoms in viral hepatitis) In most viral infections, symptoms come in waveswithin a 3-6 week period
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 (eghepatitis) • Alkaline phosphatase • Produced in biliary epithelium • Levels rise with cholestasis • Gamma GT • Hepatic enzyme transiently induced by alcohol
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 (eghepatitis) • Alkaline phosphatase • Produced in biliary epithelium • Levels rise with cholestasis • Gamma GT • Hepatic enzyme transiently induced by alcohol ALT > AlkPhos = hepatocellular pattern – hepatitis, cirrhosis Prothrombin time: marker of synthetic liver function Used to assess disease severity AlkPhos > ALT = cholestatic pattern – biliary obstruction
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
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 vaccinatedagainst • Hep A vaccine lasts for 10 years • Does notdevelop into chronic disease
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 pregnantwomen– 25% mortality • No vaccine Hep E: think pregnant woman on elective
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 vaccinatedagainst • Can progress to chronic infection • 10% develop chronic Hep B, where viral load is seen persisting after 6 months
Hepatitis D • Can only occur with Hep B infection • Co-existent infection – 90% -↓Hep B severity by reducing replication rate • ‘Superinfection’ – 10% - worse prognosis
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 dormancyperiod – decades • 80% of pts develop chronic disease • Worldwide leading cause of liver disease
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
Cirrhosis and HCC Cirrhosis: Hepatocyte necrosis Fibrosis Nodular regeneration of hepatocytes • HCC: • Red flags – anorexia and weight loss w/ cirrhosis • Diagnostic imaging • Prognosis 6-20 months
Treatment Acute infections are self-limiting Chronic infection: • Interferons– IFNα • Given subcutaneously for 1 year • Inhibits viral replication, increases immune response to virus • Antivirals– tenofovir, lamivudine • Given orally • Reverse transcriptase inhibitors