Acute Liver Injury and Failure¶
Hannah Lomzenski, and Lauren Chan
Background¶
-
Acute liver injury (ALI): elevated liver enzymes + INR ≥1.5 but NO encephalopathy
-
Acute liver failure (ALF): elevated liver enzymes + encephalopathy/AMS in the absence of pre-existing liver disease*
- *Chronic autoimmune hepatitis, HBV, Wilson disease, and Budd-Chiari syndrome can have ALF if they develop new AMS, despite the presence of a pre-existing liver disease
-
Alcohol-associated hepatitis (AH) is not ALF (see above)
Etiology¶
-
R-factor (if history, exam, and diagnostic data are inconclusive i.e. R-factor is not a replacement to clinical judgement) = (ALT/uln ALT) / (ALP/uln ALP); See chart below
- R > 5 = hepatocellular injury; R<2 = cholestatic injury; R 2-5 = mixed injury
-
Isolated hyperbilirubinemia: Differentiate direct versus indirect
- Direct: Refer to cholestatic pattern
- Indirect: Gilbert vs hemolysis
-
Drugs Associated with liver injury
-
Hepatocellular pattern: acarbose, Acetaminophen, Allopurinol, Amiodarone, Baclofen, Bupropion, Fluoxetine, HAART (Nevirapine), Kava kava, Isoniazid, Ketoconazole, Lisinopril, Losartan, Methotrexate, NSAIDs, Omeprazole, Oxacillin/Nafcillin, Paroxetine, Pyrazinamide, Propylthiouracil, Rifampin, Risperidone, Sertraline, Statins, Tetracycline, Trazodone, Valproic Acid
-
Mixed pattern: Amitriptyline, Azathioprine, Captopril, Carbamazepine, Clindamycin, Cyproheptadine, Enalapril, Flutemide, Nitrofurantoin, Phenobarbital, Phenytoin, Sulfonamides, Trazodone, Verapamil
-
Cholestatic pattern: Amoxicillin-clavulanic acid, Anabolic steroids, Chlorpromazine, Clopidogrel, Oral contraceptives, Erythromycins, Estrogens, Irbesartan, Mirtazapine, Phenothiazines, Terbinafine, Tricyclics
-
Hepatocellular Injury: R factor > 5 (Primary elevation of AST/ALT) | ||
---|---|---|
Acetaminophen intoxication$ | Acetaminophen lvl Aspirin lvl |
|
Acute Viral Hepatitis | Hep A$, B*$, C*, D, E EBV, CMV, HSV, VZV |
Viral serologies (see below), hx of tattoos, IVDU, piercings, blood transfusion prior to 1990s, intranasal cocaine use and mass vaccinations (in 3rd world countries) |
Autoimmune hepatitis\* | Autoantibodies and high serum globulins | Anti-smooth muscle (f-actin), ANA, ANCA, anti-liver kidney microsome (anti-LKM-1), anti-soluble liver antigen/liver-pancreas IgG |
Budd-Chiari Syndrome\* | Hepatic vein obstruction | Ultrasound of abdomen w/ doppler, CT w/ contrast |
DILI – Drug Induced Liver Injury\*$ | Many drugs | See above \*Query NIH Liver Tox database: https://www.livertox.nih.gov |
HELLP Syndrome, Acute Fatty Liver of Pregnancy | Pregnancy | Requires urgent delivery regardless of gestational age |
Ischemic Liver Injury (Shock Liver)$ | Shock (can be of any variety) | AST and ALT can be in the thousands, high LDH, history of hypotension |
Toxins | Ethanol, cocaine, mushroom (Amanita phalloides) | UDS, ethanol level, PEth lvl |
Wilson’s Disease\* | Copper overload | Ceruloplasmin level (screening), 24h urine copper (confirmation), quantitative copper on liver biopsy |
\*May present with chronic liver injury as well; $May present with AST/ALT >100 |
Cholestatic Injury: R Factor \< 2 (Primarily elevated Alkaline phosphatase) | ||
---|---|---|
Acute biliary obstruction | Gallstones | Abdominal ultrasound, MRCP, ERCP |
DILI – Drug-induced liver injury*$ | Many drugs, consult livertox website | Common: Augmentin, Bactrim, amiodarone, Imuran |
Malignancy* | Pancreas, cholangiocarcinoma | CT abdomen, ERCP |
Primary Biliary Cirrhosis* | Autoimmune | Anti-mitochondrial antibody |
Primary Sclerosing Cholangitis* | Autoimmune, associated with IBD | MRCP, ERCP |
Critical illness or COVID cholangiopathy | Hypotension, COVID | MRCP with biliary stenosis, appropriate history |
*May present with chronic liver injury as well; $May present with AST/ALT >100 |
Evaluation¶
- Consult hepatology early! (to assist with workup AND for transplant evaluation)
-
Labs:
- CBC w/diff, CMP, Dbili, Mg, Phos, T&S, BCx, UCx, PT/INR, aPTT, fibrinogen
- Amylase, lipase
- Beta-hCG for females of reproductive age
- ABG with arterial lactate, ammonia (arterial >124 predicts mortality and CNS complications e.g. need for intubation, seizures, cerebral edema, <75 very unlikely to develop ICH)
- Viral etiologies: Virtal hepatitis serologies (HAV panel, HBV panel, HCV IgG ± PCR quant, HDV if known HBV (with low or undetectable HBV load as Misc Reference Test, Hepatitis E PCR ent as miscellaneous if pregnant or travel to southeast Asia), HIV p24 Ag and HIV Ab, EBV Qt, CMV Qt, HSV ½ Qt, VZV IgM/IgG
- Toxins: UDS, ethanol level ± Peth, acetaminophen level (drawn > 4 hours after last known ingestion), Salicylate level
- Autoimmune / genetic: ANA, ASMA, IgG, AMA (if predominantly elevated ALP), ceruloplasmin
-
Imaging:
- RUQ abdominal ultrasound with doppler (important to assess vasculature!)
- Consider CT with contrast in patients with normal renal function and high suspicion of Budd-Chiari syndrome or malignancy with negative ultrasound (better for assessing the hepatic veins) and helps with transplant evaluation
- Consider TTE to rule out cardiac dysfunction; helpful for transplant consideration
Criteria for Transplantation:¶
- King’s College criteria:
helps identify patients needing transplant referral/consideration
- ALF due to acetaminophen:
- Arterial pH \<7.3 after resuscitation and >24 hr since ingestion, OR
- Arterial Lactate >3 after adequate fluid resuscitation, OR
- Grade III-IV HE, SCr >3.4, and INR >6.5 all within 24h period
- ALF due to acetaminophen:
- ALF not due to acetaminophen: INR > 6.5 OR 3 of the 5 following
criteria:
- Indeterminate etiology, drug-induced hepatitis
- Age \<10 or >40
- Interval of jaundice to encephalopathy >7 days
- Bilirubin > 17.5 mg/dl (300 micromol/L)
- INR >3.5
Management¶
- Any pt with concern for ALF should be cared for in MICU (even if mild change in mental status)
- Pts with ALF die acutely from hypoglycemia, cerebral edema, and infection
- ABC’s:
- Intubate for GCS \<8, Grade 3 or 4 HE
- IVF resuscitation with isotonic crystalloid (most pts are volume deplete; avoid hypotonic fluids due to risk of cerebral edema)
- Vasopressive agents for persistent hypotension (norepinephrine preferred)
- Monitoring:
- Q1-2h neuro checks, Q1-2h glucose checks
- Closely monitor CMP, INR q6-8 hrs
- Treatment of Primary Injury
- IV N-acetylcysteine - improves transplant-free survival even in
patients WITHOUT acetaminophen induced acute liver failure
- Initial loading dose = 150mg/kg over 1 hour, then 50mg/kg/hr for 4 hours, then 100mg/kg/hr for 16 hours
- Patients with early stage hepatic encephalopathy (grade I/II) have increased transplant free survival, while those with grade III/IV do not
- See below for etiology-specific treatment; hepatology consult for LT eval
- Early toxicology consultation if suspected ingestion/overdose
- For acute management contact Poison Control 800-222-1222
- IV N-acetylcysteine - improves transplant-free survival even in
patients WITHOUT acetaminophen induced acute liver failure
- Treatment of Secondary Complications
- Infection: abx only if progressing HE, signs of infection, or development of SIRS; ppx abx do not reduce mortality
- Cerebral edema/increased ICP: elevated HOB to 30 degrees, quiet and dimly lit room, minimize IVF, goal Na 145-155, hyperventilation if concern for impending herniation. Consider 3% saline (500mL) and/or mannitol (1g/kg, 20%) for pt at highest risk (serum ammonia >150, grade III/IV HE, ARF, vasopressor support
- Seizures: phenytoin (no evidence to support seizure ppx)
- Renal Failure: early CRRT if persistent Metabolic Acidosis, Volume Overload, Hyperammonemia, falling UOP
- Coagulopathy: IV Vit K; products for invasive procedures or active bleeding only
- Additional Supportive Care
- PPI for bleeding ppx
- Enteral nutrition within 2-3 days; avoid TPN if possible; avoid NG feeds if progressive HE; NG should only be placed w/ intubation as gagging increases ICP
- Prefer propofol for sedation for better neuro exams and may reduce cerebral blood flow
Specific Management by Etiology:¶
- Acetaminophen
- Early toxicology consultation if suspected ingestion/overdose
- For acute management contact Poison Control 800-222-1222
- Activated charcoal within 4 hours of ingestion, most effective within 1 hour
- IV N-acetylcysteine per protocol, look up Rumack-Matthew Nomogram and consult with toxicology
- In Epic: search “N-acetylcysteine” and select order set “Acetaminophen overdose”
-
AFLP/HELLP – delivery
-
Amanita phalloides – IV fluid resuscitation, PO charcoal, IV penicillin, IV acetylcysteine
-
Autoimmune – IV steroids following approval by hepatology (and typically post biopsy). Azathioprine generally deferred until cholestasis resolved (Mycophenolate can be used instead)
-
Budd-Chiari – anticoagulation, IR-guided endovascular therapy, transplant (must rule out underlying malignancy and evaluate for thrombotic disorders)
-
HAV/HEV – supportive care, consider ribavirin for ALF due to HEV
-
HBV – nucleos(t)ide analogue; orthotopic liver transplant
-
HSV – acyclovir