Acute Liver Disease

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Author:
jcu1
ID:
214620
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Acute Liver Disease
Updated:
2013-04-22 21:23:29
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GI Exam
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Mohammed
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  1. indicators that LD is predominantly cholestatic
    • inc in alkaline phosphatase vs aminotransferases
    • inc in GGT (not specific)
  2. indicators that LD is predominantly hepatocellular injury
    • inc in aminotransferases vs. alkaline phosphatase
    • inc in PT/INR
  3. indications that LD is chronic
    • dec albumin
    • AST:ALT ratio either >1 or <1
  4. what does an AST:ALT ratio > 1 mean?
    cirrosis in non-alcoholic liver disease
  5. what does an AST:ALT ratio < 1 mean?
    chronic viral hepatitis or non cirrhosis
  6. indications that LD is acute
    • normal alb
    • AST:ALT ratio > 2 and inc in GGT
  7. What is indicated by AST:ALT ratio > 2 and an inc in GGT?
    ALD: alcoholic hepatitis OR alcohol abuse
  8. 2 types of liver disease
    • cholestatic
    • hepatocellular injury
  9. examples of cholestatic liver disease
    • primary biliary cirrhosis
    • rimary sclerosing cholangitis
    • autoimmune cholestatic liver disease
    • gallstone disease
    • drug-induced cholestatis
  10. examples of hepatocell injury
    • acute and chronic alcoholic hepatitis
    • viral hep
    • drug-induced liver disease
    • autoimmune chronic hepatitis
  11. how is severe ALD determined (symptoms)
    • jaundice
    • encephalopathy
    • PT doesn't improve even with administration of alb
  12. if the alkaline phosphatase is significantly increased in relation to the aminotransferases, what does this indicate?
    predominantly cholestatic liver disease
  13. if the GGT is increased, what does this indicate?
    predominantly cholestatic liver disease
  14. if the aminotransfereases are significanly increased compared to alkaline phosphatase, what does this indicate?
    predominantly hepatocellular injury
  15. low albumin indicates what?
    chronic liver disease
  16. definition of acute liver failure
    • INR ≥1.5
    • mental status change
    • no preexisting cirrhosis
    • <26 wk duration of illness
  17. HE indication
    positive (i.e. asterixis) AND and inc ammonia levels
  18. HE grades (0-4)
    • grade 0: - asterixis; minimal hepatic encephalopathy
    • grade 1: +/- asterixis
    • grade 2: + asterixis
    • grade 3: - asterixis; +Babinski
    • grade 4: coma
  19. clinical complications of acute liver disease
    • HE --> cerebral edema, seizures, ICH
    • acute renal failure
    • GI bleeding
  20. Treatment for ALD
    • supportive care (fluid resuscitation/pressor)
    • treat and remove precipitating factors
  21. precipitating factors of ALD
    • avoid sedation/hyponotcs, esp in grade 1 and 2 HE
    • infections (esp before a transplant)
    • treat hypoglycemia with dextrose (10%)
    • phosphate, Mg, K supplement (if needed)
  22. treating intracranial hypertension
    • maintain <20-25 mmHg
    • severe: hypertonic saline or mannitol (0.5-1g/kg) bolus
  23. treat HE
    • lactulose (first line)
    • rifaximin
    • neomycin
  24. treat seizures
    • phenytoin
    • low dose benzo
  25. between cholestatic injury and hepatocellular injury, which has a better prognosis
    cholestatic injury
  26. is chronic liver disease a higher risk factor for drug-induced liver disease?
    many enzymes preserved in advanced liver disease
  27. drugs associated with cholestatic injury
    • estrogen
    • erythromycin
    • amox/clav
    • bactrim
    • clopidogrel
  28. drugs associated with hepatocellular injury
    • labetalol
    • rifampin
    • APAP
    • valproic acid
  29. drugs associated with mixed hepatocellular and cholestatic injury
    • NSAIDs
    • sulfonamides
    • macrolides
  30. indication of drug induced predominantly cholestatic liver disease
    • inc alkaline phophatase vs. aminotransferases
    • inc in alkaline phosphatase over 2 times the upper limit
    • inc conjugated bilirubin and GGT
  31. indication of drug induced predominantly hepatocellular injury liver disease
    • inc aminotransferase (500-800 x UNL) vs. alkaline phosphatase
    • inc in ALT > 2 times ULN or
    • ALT:alkaline phophatase ratio >5
  32. drugs that can increase the risk of apap related liver toxicity
    • isoniazid
    • phenobarbital
    • warfarin
  33. therapeutic concentraton of apap
    10-20 mcg/ml
  34. toxic doses of apap
    • acute single dose: adult (7.5 g); children (150) mg/kg
    • chronic daily dose: adult (4 g); children (150-175 mg/kg)
  35. initial treatment of acute alap overdose
    • activated charcoal 1g/kg (max 50 g) x 1 dose
    • can give with 70% sorbitol (adult: 30mg; children: 1-2ml/kg, max 30ml)
  36. monitoring for charcoal
    bowel sounds
  37. when do you draw apap levels after an acute single ingestion?
    • 4 hrs and 24 hrs
    • immediately if ingestion was >4 hrs before presentation
  38. used to assess possibility of hepatic toxicity with acute apap overdose ≤ 24 hrs of ingestions
    modified rumack-matthew nomogram
  39. treating late presentation of apap overdose (>24)
    NAC
  40. treating overdose with ER apap
    get apap concentration 4 hrs after ingestion and then every 2 hrs afterwards
  41. NAC MOA
    • glutathione precursor: repletes glutathione
    • sulfur donor: inc sulfation
    • detoxifies NAPQI and prevents cellular injury
  42. Oral NAC dosing and AEs
    • LD: 140 mg/kg
    • MD : 70 mg/kg q4h for 17 doses (72 hrs total)

    AEs: N/V, bad odor
  43. IV NAC dosing and AEs
    • 1st dose: 150 mg/kg in 200 mL over 60 min
    • 2nd dose: 50 mg/kg in 500 mL over 4 hrs
    • 3rd dose: 100 mg/kg in 1000 mL over 16 hrs

    duration 21 hrs

    AEs: anaphylaxis, fluid overload
  44. lab values for severe alcoholic hepatitis
    • AST: 2-6 x UNL
    • AST:ALT ratio: >2 in pts without cirrhosis; >3 in alcoholic liver disease
    • inc GGT
  45. treating severe alcoholic hepatitis
    prednisolone 40 mg qd x 28 days, then dc or 2 week taper

    if in early renal failure or steroid contraindicated: pentoxifylline 400 mg TID x 4 wks
  46. risk factors for fatal liver injury due to apap
    • max doses - 4 g/day x ≥5 consecutive days
    • max doses in fasting state
    • > 2 g/day while drinking alcohol
    • other apap-contaiing drugs
    • drugs like isoniazid, phenobarb, warfarin
    • serious liver disease
  47. alcoholic steatosis pathogenesis
    • initial stage
    • potentially reversible
    • hepatocyte fat accumulation
    • liver enlarges
  48. alcoholic steatosis clinical presentation
    • asymptomatic
    • enlarged liver (smooth)
  49. alcohol steatohepatitis or hepatitis pathogenesis
    • "fatty liver" + diffuse liver inflammatory + liver necrosis
    • mallory bodies
  50. alcohol steatohepatitis or hepatitis clinical presentation
    • variable
    • right upper quad pain, tender hepatomegaly
    • fever, fatigue, jaundice
    • hepatic bruit
  51. alcoholic cirrhosis pathogenesis
    • extensive fibrosis
    • liver shrinks
  52. alcoholic cirrhosis clinical presentation
    • compensated, so asymptomatic
    • variable symptoms (similar to alcohol hepatitis to cirrhosis)
    • small liver
  53. prognostic factors for severe alcoholic hepatitis
    • Maddrey Discriminant Function (MDF) ≥32
    • Model for End-Stage Liver Disease (MELD) ≥18
    • presence of HE
  54. how to calculate MDF
    4.6 (pt's PT - control PT) + total bilirubin (mg/dl)

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