Please enable JavaScript.

Coggle requires JavaScript to display documents.

LIVER DISEASE - Coggle Diagram

- - - - ratio >5 = hepatocellular liver injury
      - ratio <2 = cholestatic
      - 2<ratio<5 = mixed
    - - DILI very common
    - - AST/ALT/ALP/GGT
  - - - renal failure, acidosis, hypoglycaemia
  - - - but small proportion converted by CYP2E1 to reactive intermediate metabolite NAPQI
        
        NAPQI normally detoxified by glutathione
        
        when glutathione runs out, NAPQI causes liver injury with free radicals
        
        NAPQI levels (?)
    - - does not measure individual susceptibility
      - depends on accurate history
      - late stages may be undetectable
    - - not tissue/drug specific, not sensitive, slow to rise/fall, not predictive of severity
    - - very specific to liver and paracetamol DILI
  - - - dose-dependent, common, low toxicity/mortality, treated by adjusting dose
    - - dose-independent, rare, high toxicity/mortality, treated by stopping drug
        
        idiosyncratic liver toxicity
        
        reactive metabolite binds to native protein
        
        taken up by Kupffer cells
        
        presented by MHC class II to Th cells
        
        PK or PD or immune polymorphism, DDI, alcohol, gender, age, disease
        
        methotrexate-induced hepatic fibrosis
        
        psoriasis, chronic ingestion of alcohol, liver disease, etc.
- - - - decreased activation of PDK3 and then AKT
        
        failed deactivation of FoxO1
        
        FoxO1 translocates to nucleus and upregulates ABCG5/8 (specific for cholesterol)
        
        increased cholesterol secretion
        
        reduced bile acid synthesis
        
        impaired cholesterol solubility
        
        1 more item...
        
        ABCB11 is specific for bile acids
- - - - bilirubin does not undergo glucuronidation by glucuronyl transferase
        
        elevated unconjugated bilirubin
  - - - bilirubin cannot be secreted into canaliculi
        
        back-up of conjugated bilirubin in liver and blood
        
        elevated conjugated bilirubin
- - - - 2x risk of developing HCC, further increased if HCV positive
    - - protect against HCC
      - sulfonylureas and insulin injections do not protect against HCC (increase risk)
  - - - hepatocyte apoptosis/proliferation
        
        activation of hepatic stellate cells by TGF-ß, PDGF, etc.
        
        produce collagen and ECM
        
        fibrosis
        
        decreased blood flow through liver
        
        Liver failure
        
        6 more items...
        
        nodular appearance
  - - - severe splanchnic vasodilation
        
        RAAS activation
        
        excessive salt/water retention
        
        fails to compensate
        
        further vasoconstriction
        
        failure of renal perfusion
        
        1 more item...
        
        octreotide/terlipressin
      - oesophageal/gastric varices
        
        severe bleeding
        
        resuscitation with packed cells (Hb) and clotting factors
        
        portal hypertensive gastropathy
        
        more chronic bleeding and anaemia
        
        primary prevention: ß-blockers and variceal ligation
        
        secondary prevention: endoscopic banding, ß-blockers, TIPS, surgical shunt, liver transplant
    - - stop nephrotoxic drugs (diuretics, NSAIDs)
- - - - can be asymptomatic
      - jaundice, fatigue, abdominal pain (RUQ), loss of appetite, N/V, diarrhoea, low grade fever, headache
      - very high transaminases (AST/ALT) >1000 U/L
        
        DDx: viral hepatitis, DILI/toxic liver injury, ischaemic hepatitis, autoimmune hepatitis, acute biliary obstruction (transiently)
        
        alcoholic hepatitis only has moderately elevated AST/ALT (<500 U/L)
      - bilirubin very elevated
      - GGT and AlkPhos mildly/not elevated
      - all RNA viruses except HBV (DNA)
      - Hep A and E resolve with no chronic sequelae (except HEV in immunosuppressed)
        
        Hep B, C, D have chronic consequence of HCC
        
        HAV
        
        RNA virus (Picornaviridae)
        
        single serotype globally (vaccine preventable)
        
        faecal-oral spread
        
        contaminated food/water or close contact
        
        can also be transmitted via blood (rare)
        
        age of onset early childhood (high prevalence countries) or adulthood (low prevalence)
        
        travellers
        
        clinical criteria
        
        discrete onset of symptoms
        
        jaundice (common in adults)
        
        rare complications: acute liver failure, cholestatic hepatitis (pruritus), relapsing hepatitis
        
        laboratory criteria (serology)
        
        anti-HAV IgM positive
        
        incubation period 15-50 days
        
        vaccine or immunoglobulin
        
        1 more item...
        
        jaundice or elevated aminotransferases (AST/ALT)
        
        HEV
        
        most common cause of acute hepatitis globally (1/3 infected)
        
        genotypes 1/2 - endemic and waterborne
        
        genotype 3 - sporadic, zoonotic, contaminated pork products
        
        contaminated drinking water (minimal person-person)
        
        travel to endemic areas
        
        incubation period 15-60 days
        
        illness severity increased with age or pregnancy
        
        acute liver failure
        
        5 more items...
        
        neurological complications: Guillain-Barre syndrome, Bell's palsy, neuralgic amyotrophy, acute transverse myelitis, acute meningoencephalitis
        
        1 more item...
        
        avoid unpurified water/uncooked products
      - Hep A, B, D have vaccine
      - Serology
  - - - HCV
        
        6 genotypes (1b and 3a most common in Australia)
        
        targets for DAAs are NS3, NS4A, NS5A, NS5B on genome
        
        parenteral exposure e.g. IVDU, tattoos, etc.
        
        mother to child (minor)
        
        serology (anti-HCV), RIBA, PCR, viral load, genotyping assays
        
        acute
        
        incubation period 6-7 weeks average
        
        symptoms uncommon (mild jaundice)
        
        rarely results in ALF
        
        EIA for anti-HCV
        
        cannot diagnose on serology/RNA testing alone - need to know prior tests were negative
        
        anti-HCV positive for life after infection
        
        serum HCV RNA within 1-3 weeks
        
        chronic (60-90%)
        
        older, male, MHC genes, no clinical presentation with acute, no favourable IL-28B polymorphism
        
        most have asymptomatic persistent infection
        
        20-30% develop end stage liver disease (cirrhosis, portal HT, HCC, liver failure)
        
        exclusion of cirrhosis
        
        4 more items...
        
        male, older, obese, T2DM, alcohol
        
        anti-HCV, HCV PCR and viral load, LFTs
        
        direct acting antivirals (DAAs)
        
        pangenotypic (new)
        
        reduces cirrhosis/liver failure/HCC and eradicates HCV in 95%
      - HBV
        
        HBsAg in envelope circulates, HBcAg doesn't but HBcAb does
        
        perinatal/vertical (most common), early childhood/horizontal, parenteral, sexual
        
        liver biopsy
        
        HBsAg causes granular eosinophilic staining (ground glass hepatocytes)
        
        serology: HbsAg, anti-HBs, IgM anti-HBc
        
        HbsAg persists lifelong if chronic, HBeAg (core) persists but not lifelong
        
        all negative = no infection but susceptible
        
        only HbsAg negative = resolved HBV infection but not cured (low levels in liver reactivate in immunosuppression)
        
        only anti-HBs positive = vaccinated
        
        IgM anti-HBc - done if suspecting acute, not helpful in chronic
        
        1 more item...
        
        vaccine
        
        acute: incubation period 60-90 days
        
        chronic
        
        inactive and active carriers at risk of HCC
        
        immune tolerance: high levels of HBV DNA, HBeAg +ve, HBsAg +ve, ALT normal, asymptomatic
        
        immune clearance/active chronic hepatitis: HBV DNA and HBeAg fall, anti-HBe, ALT elevated
        
        immune control: HBV DNA undetectable, ALT normal, anti-HBe +ve and HBeAg -ve, elevated risk of HCC
        
        1 more item...
      - HDV
        
        requires HBV for synthesis of envelope protein made of HBsAg
        
        must have concurrent or past HBV infection
        
        percutaneous (IVDU), transmucosal (sex)
        
        coinfection with acute HBV
        
        causes acute, severe disease
        
        1 more item...
        
        superinfection on top of chronic HBV
        
        usually develop chronic HDV
        
        2 more items...
- - - - nuclei of hepatocytes displaced by large fat globule in cytoplasm
      - inflammation
        
        inflammatory infiltrates (neutrophils and lymphocytes)
        
        liver biopsy (gold standard)
        
        not performed if asymptomatic with normal LFTs
        
        NAFLD fibrosis score or transient elastography (non-invasive)
        
        fibrosis
        
        starts pericellularly (around central vein and portal tracts)