Liver and diseases I 2024.PDF

Liver and diseases I Overview Jaundice Hepatitis Learning outcomes To show basic knowledge on major primary liver diseases To understand the causes of jaundice To describe pathological features of clinically important hepatitis Liver and diseases I Overview Jaundice Hepatitis Overview I The main fun...

Liver and diseases I Overview Jaundice Hepatitis Learning outcomes To show basic knowledge on major primary liver diseases To understand the causes of jaundice To describe pathological features of clinically important hepatitis Liver and diseases I Overview Jaundice Hepatitis Overview I The main function of the liver − Synthesis & metabolism of carbohydrate, lipids, protein & drugs − Metabolism & excretion of bilirubin and bile acids Dual supply of blood vessels Vulnerable to a wide variety of insults (metabolic, toxic, microbial, circulatory & neoplastic) Overview II Major primary liver diseases: − − − − Viral hepatitis Alcohol liver disease Nonalcoholic fatty liver disease, Hepatocellular carcinoma Major causes of liver disease: − In the West: alcohol and hepatitis C virus − Elsewhere: hepatitis B virus, but the incidence is decreasing (vaccination) Bilirubin metabolism Blood systemic circulation Albumin Liver and diseases I Overview Jaundice Hepatitis Jaundice (icterus) Yellow sclerae and skin; serum bilirubin > 50µmole/L Haemolytic jaundice (pre-hepatic) Congenital hyperbilirubinaemias (non-haemolytic) Cholestatic jaundice Haemolytic jaundice (pre-hepatic) ↑ breakdown of RBC Investigations: – Haemolysis – serum unconjugated bilirubin – Normal alkaline phosphatase (ALP) & transferase Congenital hyperbilirubinaemias: Most common - Gilbert’s syndrome: UDP-glucuronyl transferase activity → → conjugation of bilirubin with glucuronic acid unconjugated bilirubin↑; other tests normal Cholestatic jaundice: Intrahepatic cholestasis: - Abnormal bile excretion - Bile channel obstruction Extrahepatic cholestasis: - Bile flow obstruction: distal to the bile canaliculi In hepatocyte damage, unconjugated bilirubin also↑ Investigation: Serum liver biochemistry; jaundice (conjugated bilirubin). - Early in hepatitis:   ALT&AST,  ALP - Extrahepatic obstruction:   ALP,  ALT&AST - Ultrasound: dilated bile ducts (extrahepatic cholestasis) & the level of obstruction - Serum hepatitis markers: acute hep A or hep B; antibodies to hepatitis C - Other tests: Cholestasis → ↓Vitamin K → ↑ prothrombin time ↓ liver synthetic function → ↑ prothrombin time + ↓albumin Autoimmune liver disease → Serum antibodies Liver and diseases I Overview Jaundice Hepatitis Hepatitis Pathology: Liver cell necrosis & inflammatory infiltration Normal Acute hepatitis Hepatitis Presentation: Enlarged & tender liver(+/-); Jaundice(+/-), etc Investigation: Serum transferase(↑), etc Types: acute & chronic Acute hepatitis: Causes: Viruses: hepatitis viruses (most common), etc. Non-viral infection: toxoplasma gondii, etc. Alcohol Drugs: anti-TB (isoniazid), etc. Others: pregnancy, etc Clinical feature: Usually (viral) self-limiting, return to normal structure & function Occasionally progression to massive liver necrosis, even death; Investigation: ↑ serum ALT (best indicator of acute hepatic injury), Prothrombin time and bilirubin (reflect disease severity) Conjugated & unconjugated Chronic hepatitis: - A sustained inflammatory disease Causes: Due to any cause - Viral - Chemical - Autoimmune Clinical feature: Lasting for more than 6 months Hepatitis A Acute viral hepatitis Virus: HAV Spread: faecal-oral Mechanism of liver damage: Cytopathic & Immunity-mediated (by T-cells) Hepatitis A Clinical features: Relatively short incubation period, nonspecific symptoms: flu-like Signs - jaundice: +/- hepatomegaly (moderate) - spleen palpable (10% cases) Lab test: serum transferase  Acute, self-limiting; no chronic stage; (fulminant hepatitis, rare) Hepatitis A Management: − No specific treatment Prophylaxis: Immunisation − Active: inactivated strain − Passive: immunoglobulin Hepatitis B Epidemiology: Worldwide, prevalent in parts of Africa, Middle & Far East Virus: HBV, DNA virus HBV Protein Core - Protein of core particle Pre-core - Pre-core/core cleaves to HBeAg Surface – Envelope protein; HBsAg; basis of current vaccine Hepatitis B Spread: - Parenteral - Close personal contact - Vertical Mechanism of liver damage: Immunity-mediated (by T-cells) Hepatitis B Clinical features: − Long incubation period − Chronic carriers: HBsAg >6mo.; HBeAg or viral DNA - highly infectious, risk of chronic hepatitis & cirrhosis − Chronic hepatitis: 3-5% acute hep B, serum liver biochemistry abnormal; liver biopsy/histology: mild inflammatory changes to cirrhosis Hepatitis B Treatment: Antiviral agents with indications: e.g. serum HBsAg, HBV DNA Prophylaxis: Avoid high-risk factors Immunization: active (vaccine) & passive Hepatitis C Virus: HCV; non-A, non-B Spread: Blood or blood products Other routes (eg., vertical, but rare) Mechanism of liver damage: Immunity-mediated (by T-cells) Hepatitis C Special clinical features: − Short incubation − 60-90% becoming carriers − High risk of developing: chronic, active hepatitis cirrhosis hepatocellular carcinoma Hepatitis C Diagnosis: − by exclusion Management: − Interferon used in acute cases to prevent chronic disease − Needle-stick injuries must be followed and treated early Prophylaxis: − HCV is a RNA virus; a rapid change in envelope proteins, hence vaccine difficult Which of the following statement is true about haemolytic jaundice? a) An increase in serum ALT b) An increase in serum unconjugated bilirubin c) A decrease in serum unconjugated bilirubin d) An increase in serum conjugated bilirubin e) A decrease in serum conjugated bilirubin The spread of infection for Hepatitis A is mainly by: a) Blood b) Vertical transmission c) Personal contact d) Faecal-oral route e) All of the above