Acute Liver Injury

Poorly defined, but generally accepted as an acute elevation in AST, ALT, and/or INR without observed hepatic encephalopathy. This is different from Acute Liver Failure, which is defined as an INR > 1.5 with observed hepatic encephalopathy in the setting of a previously normal liver.

R-Ratio Calculation ₍₁₎: (ALT / UNL ALT) / (Alk Phos / UNL Alk Phos)

• Cholestatic Pattern: R-Ratio < 2
• Mixed Pattern: R-Ratio 2-5
• Hepatocellular Pattern: R-Ratio > 5

This calculation attempts to differentiate whether the main pathology is occurring in the bile ducts (“cholestatic”) or in the hepatic parenchyma (“hepatocellular”).

Differential Diagnosis

AST and ALT > 1,000

• Ischemic
  • Secondary to hypotension/shock
  • Diagnosis: Clinical picture and ruling out of the etiologies below
  • Management: Treat hypotension as well as underlying etiology of shock (see Shock)
• Hepatic Infarction
  • Secondary to arterial thrombosis/embolism, most commonly after liver transplant
  • Diagnosis: RUQ Ultrasound with Doppler followed by CT imaging
  • Management: Identify potential sources of emboli (atrial fibrillation, infective endocarditis, etc.) or hypercoagulability (see Coagulation).
  • Re-transplantation is gold standard of treatment, but other options include arterial reconstruction, surgical thrombectomy, and radiologically guided thrombolysis ₍₂₎
• Portal Vein Thrombosis
  • Diagnosis: RUQ Ultrasound with Doppler
  • Management: Anticoagulation with either enoxaparin or warfarin for patients with acute thromboses. DOACs still under investigation. Benefit of anticoagulation less clear in chronic thromboses or in those who are asymptomatic and without a cancer diagnosis ₍₃₎
• Budd-Chiari Syndrome
  • Hepatic Vein Obstruction, usually from VTE
  • Diagnosis: RUQ Ultrasound with Doppler
  • Management: Anticoagulation with enoxaparin or warfarin (DOACs may be considered), thrombolysis can be considered, and percutaneous angioplasty may be considered if thrombolysis is contraindicated or if it is unsuccessful ₍₄₎
• Autoimmune Hepatitis
  • Diagnosis: ANA, anti-smooth muscle Ab, elevated IgG, and biopsy
  • Management: Prednisolone or prednisone with azathioprine. Steroids can be tapered after AST, ALT, and IgG normalize and patient can be maintained on azathioprine (or Mycophenolate if TPMT deficient) ₍₅₎
• Drug-induced (Acetaminophen, TB medications, antibiotics, etc.)
  • Diagnosis: Acetaminophen level, history
  • Management: Discontinue offending medication. NAC for Acetaminophen overdose if deemed appropriate per nomogram.
• Viral Hepatitis
  • Diagnosis: Viral serologies (For further, including management, see Viral Hepatitis)
• Acute Choledocholithiasis
  • Diagnosis: RUQ U/S, CT A/P with contrast, MRCP
  • Management: ERCP with stone retrieval +/- stent placement

AST and ALT <1,000

• Any of the above may also cause milder elevations
• Acute Alcohol use
  • Diagnosis: Clinical, EtOH levels
  • Management: Supportive, monitor for withdrawal symptoms
• NAFLD/NASH
  • Diagnosis: Optimally a biopsy, but realistically usually on the basis of ruling out other liver disease and looking at the clinical picture
  • Management: Weight loss and exercise
• Hemochromatosis
  • Diagnosis: Ferritin > 200 μg/L, % Iron Saturation > 45%: Obtain genotype testing C282Y HFE mutation ₍₆₎
  • Management: Phlebotomy
• Wilson’s Disease
  • Diagnosis: Ceruloplasmin < 20 mg/dL, 24-hour urinary copper excretion of >100 mcg, slit-lamp examination for Kayser-Fleischer rings, biopsy, and genetic testing ₍₇₎
  • Management: Chelating agents (pencillamine), biopsy if necessary
• α-1-Antitrypsin Deficiency
  • Diagnosis: Low α-1-antitrypsin level
  • Management: Transplant if necessary, but also can supplement with exogenous α-1-antitrypsin ₍₈₎
• Congestive Hepatopathy (secondary to heart failure)
  • Diagnosis: Clinical
  • Management: Fluid removal usually with diuresis
• Infections (EBV, CMV, HSV, VZV)
  • Diagnosis: Serology
  • Management: Treatment of underlying infection
• Obstructions (Biliary stricture, choledochal cyst, liver fluke, malignancy, stones, PSC, PBC)
  • Diagnosis: RUQ U/S, CT A/P with contrast, MRCP
  • Management: ERCP with stone removal, stent placement, etc.

Initial Workup

• RUQ Ultrasound, with Doppler exam of blood vessels if occlusion suspected
• Hepatitis A Virus IgM, Hepatitis B surface antigen, Hepatitis B surface antigen antibody, Hepatitis B core antigen antibody
• ANA, anti-smooth muscle antibody

References:

1. R Factor for Liver Injury. MDCalc. (n.d.). https://www.mdcalc.com/r-factor-liver-injury#evidence.&nbsp;
2. Mourad, M. M., Liossis, C., Gunson, B. K., Mergental, H., Isaac, J., Muiesan, P., Mirza, D. F., Perera, M. T. P. R., & Bramhall, S. R. (2014, May 26). Etiology and management of hepatic artery thrombosis after adult liver transplantation. AASLD. Retrieved November 17, 2021, from https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/lt.23874.&nbsp;
3. Wu, M., Schuster, M., & Tadros, M. (2019, June 28). Update on management of portal vein thrombosis and the role of novel anticoagulants. Journal of clinical and translational hepatology. Retrieved November 19, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609842/.&nbsp;
4. Hernandez-Gea, V., De Gottardi, A., Leebeek, F., Rautou, P.-E., Salem, R., & Garcia-Pagan, J. C. (n.d.). Current knowledge in pathophysiology and management of Budd-Chiari syndrome and non-cirrhotic non-tumoral splanchnic vein thrombosis. Journal of Hepatology. Retrieved November 19, 2021, from https://www.journal-of-hepatology.eu/article/S0168-8278(19)30130-8/fulltext#secst115.&nbsp;
5. Mack, C. L., Adams, D., Assis, D. N., Kerkar, N., Manns, M. P., Mayo, M. J., Vierling, J. M., Alsawas, M., Murad, M. H., & Czaja, A. J. (2020, May 12). Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the study of liver diseases. AASLD. Retrieved November 19, 2021, from https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.31065.&nbsp;
6. Tavill, A. S., & Adams, P. C. (2006, August). A diagnostic approach to hemochromatosis. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. Retrieved November 19, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659937/.&nbsp;
7. Ferenci, P. (n.d.). Diagnosis of wilson disease. Handbook of clinical neurology. Retrieved November 19, 2021, from https://pubmed.ncbi.nlm.nih.gov/28433100/.&nbsp;
8. Treatment – alpha-1 foundation. Alpha. (2021, January 15). Retrieved November 19, 2021, from https://www.alpha1.org/newly-diagnosed/living-with-alpha-1/treatment/.&nbsp;