361.4 ð ç« æ«éèš Summary
361.4.1 ð äžå¥è©±çžœçµ
Acute liver failure (ALF) = severe acute liver injury + encephalopathy (hallmark) + coagulopathy INR ⥠1.5 + no preexisting cirrhosis + duration < 26 weeks; classification by jaundice â HE interval â hyperacute < 7 days (often acetaminophen, cerebral edema common, paradoxically best spontaneous recovery), acute 7-21 days, subacute 21-26 weeks (worst prognosis); etiology US/UK â acetaminophen top (~ 50%) + idiosyncratic DILI (amox-clav, isoniazid, anticonvulsants, herbals) + viral (HAV, HBV, HEV in pregnancy 3rd trimester 20% mortality, HSV in immunocompromised/pregnancy) + autoimmune + Wilson + Budd-Chiari + ischemic + pregnancy (HELLP, AFLP) + Amanita mushroom + idiopathic ~ 15%; clinical features â HE grades I-IV (West Haven), cerebral edema (major cause of death, particularly hyperacute), coagulopathy with INR â but bleeding less common than INR suggests (rebalanced), hypoglycemia, multi-organ failure (renal, CV, pulmonary, sepsis), lactic acidosis; workup â acetaminophen level + viral serologies (HAV IgM, HBsAg + anti-HBc IgM, HEV IgM, HSV PCR) + autoimmune markers (ANA, anti-SMA, IgG) + ceruloplasmin + KF rings + pregnancy test + Doppler US (Budd-Chiari) + lactate + ABG + glucose + phosphate (low = regeneration good prognostic); Kingâs College Criteria for transplant â acetaminophen: pH < 7.30 OR all of INR > 6.5 + Cr > 3.4 + grade III/IV HE; non-acetaminophen: INR > 6.5 OR any 3 of (age < 10 or > 40, non-A non-B/drug/halothane, jaundice â HE > 7 days, INR > 3.5, bilirubin > 17.6); MELD ⥠30 also useful; management â ICU + airway protection grade III-IV HE + cerebral edema management (head 30°, mannitol 0.5-1 g/kg, hypertonic saline 3%, target Na 145-150, ICP < 20, CPP > 60) + NAC for acetaminophen AND early non-acetaminophen ALF (Lee 2009 ALF Study Group, improves transplant-free survival HE I-II) + glucose monitoring + minimize FFP (interferes with INR) + sepsis surveillance + CRRT + nutrition (no protein restriction) + plasma exchange (Larsen 2016) emerging + transplant evaluation Status 1A; outcomes â with transplant 1-yr 80-85%, 5-yr 70%; without transplant varies by etiology â acetaminophen ~ 65% spontaneous recovery, HAV ~ 60%, HBV ~ 25%, idiosyncratic DILI ~ 25%, Wilson < 10%, idiopathic ~ 25%ã
361.4.2 ð æ²»ç粟èŠ
- NAC for acetaminophen ALFïŒIV â 150 mg/kg over 1 hr â 50 mg/kg over 4 hr â 100 mg/kg over 16 hr; effective even if late presentation; continue until INR < 1.5 + clinical improvement
- NAC for non-acetaminophen early ALF (HE I-II, Lee 2009)ïŒIV à 72 hours
- cerebral edema managementïŒhead of bed 30° + mannitol 0.5-1 g/kg IV bolus + 3% hypertonic saline target Na 145-150 + hyperventilation acutely; minimize stimulation + treat fever; target ICP < 20, CPP > 60
- HBV ALFïŒentecavir or tenofovir immediately
- HSV hepatitisïŒacyclovir IV 10-15 mg/kg q8h â empiric if suspected
- Wilson ALFïŒpenicillamine limited role; plasmapheresis + liver transplant mainstay
- Amanita mushroomïŒsilibinin + NAC + penicillin G (silibinin blocks toxin uptake)
- coagulopathyïŒavoid routine FFP correction (interferes with INR monitoring + volume overload); treat active bleeding or pre-procedure only; vitamin K cofactor
- plasma exchange (high-volume)ïŒLarsen 2016 â improves transplant-free survival
- liver transplantationïŒStatus 1A allocation; Kingâs College Criteria identifies candidates; MELD ⥠30 alternative; 1-yr 80-85%
361.4.3 ð¯ ç§é«åž«çèåæé
- ALF definition (memorize): encephalopathy + INR ⥠1.5 + no preexisting cirrhosis + < 26 weeks â three pillars + temporal definition
- Classification by jaundice â HE interval: hyperacute < 7 days (acetaminophen typical, cerebral edema major issue, paradoxically best spontaneous recovery) vs acute 7-21 days vs subacute 21-26 weeks (worst, less cerebral edema, more ascites)
- Etiology US/UK: acetaminophen top (~ 50%) â check level + history; viral HBV/HAV/HEV worldwide; HEV in 3rd trimester pregnancy 20% mortality; HSV in immunocompromised/pregnancy â empiric acyclovir
- Kingâs College Criteria â acetaminophen: pH < 7.30 (irrespective of HE) OR all of INR > 6.5 + Cr > 3.4 + grade III/IV HE
- Kingâs College Criteria â non-acetaminophen: INR > 6.5 OR any 3 of (age < 10/> 40, non-A non-B/drug, jaundiceâHE > 7d, INR > 3.5, bili > 17.6)
- NAC for ALL ALF: acetaminophen + non-acetaminophen ALF in early HE (I-II, Lee 2009 ALF Study Group) â improves transplant-free survival
- Cerebral edema = major cause of death in hyperacute ALF: head 30° + mannitol 0.5-1 g/kg + 3% hypertonic saline Na 145-150 + minimize stimulation + treat fever; target ICP < 20, CPP > 60
- Wilson ALF clues: ALP : bilirubin < 4 + AST : ALT > 2.2 + Coombs-negative hemolytic anemia + low alkaline phosphatase paradoxical; almost always needs transplant
- Coagulopathy paradox: INR markedly elevated but bleeding less common (rebalanced â factor VIII preserved + â anticoagulants); avoid routine FFP (interferes with INR monitoring)
- Transplant for ALF Status 1A: highest priority in US allocation; Kingâs College Criteria identify candidates; MELD ⥠30 also indicator; 1-yr 80-85%, 5-yr 70%; plasma exchange (Larsen 2016) emerging bridge therapy
PART 10 = neurological approach + headache + pain + syncope + dizziness + seizures + coma + delirium + stroke + dementia + Parkinson + movement disorders + ALS + MS + neuromuscular + CNS infections + neuro-oncologyã
æ¬éšåæ¶µèåŸ approach to neurologic patient (history + exam + neuroimaging + EEG + LP/CSF) å° headache (migraine CGRP era + cluster TAC + tension + secondary), syncope + dizziness/vertigo, weakness/paralysis + movement disorders (tremor, dystonia, chorea, tics) + sleep disorders, seizures/epilepsy + status epilepticus (ESETT 2019 fosphenytoin/valproate/levetiracetam comparable), coma + brain death + delirium, stroke (ischemic + hemorrhagic + DAWN/DEFUSE-3 extended window thrombectomy + tenecteplase ATTEST/AcT 2022) + cerebrovascular, dementia (Alzheimer: lecanemab Leqembi FDA Jan 2023, donanemab Kisunla FDA July 2024; FTD, LBD, vascular), Parkinson disease + parkinsonism (ON-OFF + DBS + new advanced therapies), ALS (tofersen SOD1 FDA 2023, AMX0035 withdrawn) + motor neuron diseases, multiple sclerosis (ofatumumab + ocrelizumab + ublituximab + cladribine + new oral S1P agents) + NMOSD (eculizumab, satralizumab, inebilizumab) + MOGAD, neuromuscular (myasthenia gravis efgartigimod + ravulizumab + rozanolixizumab + zilucoplan 2023, muscular dystrophies), neuroimmunology (autoimmune encephalitis), CNS infections (meningitis + encephalitis + brain abscess + neurocysticercosis), brain tumors (glioma, meningioma, primary CNS lymphoma)ã