Module 23 · GI, liver & haematology

Liver failure

NewPhase 2

Liver failure in the ICU: acute liver failure with King's College criteria, acute-on-chronic liver failure (EASL-CLIF and APASL), hepatic encephalopathy, ascites/SBP/hepatorenal syndrome, and coagulopathy of liver disease, with transplant referral throughout.

5 topics

Drugs in this module

Doses written for this module's context. The same drug may read differently in another module.

N-acetylcysteine

Glutathione precursor / antidote

Indications
Paracetamol hepatotoxicity; early-grade (I-II HE) non-paracetamol ALF
Adult dose
Non-paracetamol ALF (Lee 2009): 150 mg/kg/h for 1 h, then 12.5 mg/kg/h for 4 h, then 6.25 mg/kg/h for 67 h (72 h total). Paracetamol: 21-h regimen 150 mg/kg over 1 h, 50 mg/kg over 4 h, 100 mg/kg over 16 h; continue 6.25 mg/kg/h if ALF.
Preparation (India)
200 mg/mL (Indian vials 1 g/5 mL and 2 g/10 mL); dilute in 5% dextrose.
Cautions
Anaphylactoid reactions (flushing, bronchospasm) mostly during loading; slow or pause, give antihistamine. Fluid load in small patients.

Vitamin K1 (phytomenadione)

Vitamin

Indications
Possible vitamin K deficiency (cholestasis, malnutrition, antibiotics)
Adult dose
10 mg IV slowly once (repeat daily for 3 days if response).
Cautions
Slow IV (anaphylactoid reactions).

Prednisolone

Corticosteroid

Indications
Severe alcoholic hepatitis (Maddrey DF ≥ 32 or MELD > 20) without contraindication
Adult dose
40 mg orally once daily for 28 days; stop at day 7 if Lille score ≥ 0.45.
Cautions
Exclude/treat infection, GI bleed, AKI first; risk of infection.

Tenofovir disoproxil fumarate / entecavir

Nucleos(t)ide analogue

Indications
HBV-related ALF or ACLF (HBV reactivation/flare)
Adult dose
Tenofovir DF 300 mg orally once daily (or entecavir 0.5 mg daily); adjust for renal function.
Renal / hepatic
Dose-adjust for CrCl < 50 mL/min.

Lactulose

Non-absorbable disaccharide

Indications
Hepatic encephalopathy treatment and secondary prophylaxis
Adult dose
25-30 mL (oral/NG) every 1-2 h until a bowel motion, then titrate to 2-3 soft stools/day (usually 15-30 mL two to three times daily). Enema 300 mL in 700 mL water if NG not possible.
Preparation (India)
10 g/15 mL syrup (Indian 3.35 g/5 mL).
Cautions
Over-use causes dehydration, hypernatraemia, hypokalaemia and can worsen HE/AKI.

Rifaximin

Non-absorbable antibiotic

Indications
Add-on for recurrent HE
Adult dose
550 mg orally twice daily (or 400 mg three times daily).
Preparation (India)
400 mg and 550 mg tablets available in India.

Polyethylene glycol 3350-electrolyte

Osmotic laxative

Indications
Overt HE (alternative to lactulose)
Adult dose
4 L over 4 h orally or by NG (single dose) (HELP trial).
Cautions
Aspiration risk in encephalopathic patients; give via NG with airway protection if needed.

Human albumin 20%

Colloid

Indications
SBP, large-volume paracentesis, HRS-AKI
Adult dose
SBP: 1.5 g/kg day 1 and 1 g/kg day 3 (max ~100 g/day). LVP > 5 L: 6-8 g per litre removed. HRS-AKI: 1 g/kg (max 100 g) day 1-2, then 20-40 g/day with terlipressin.
Preparation (India)
20% 100 mL = 20 g.
Cautions
Pulmonary oedema, especially with terlipressin; monitor lungs/POCUS.

Ceftriaxone

Third-generation cephalosporin

Indications
Community-acquired SBP; GI bleed prophylaxis in cirrhosis
Adult dose
SBP: 2 g IV once daily for 5-7 days (or cefotaxime 2 g q8h). Use piperacillin-tazobactam or carbapenem for nosocomial SBP or high-MDR settings.

Cryoprecipitate

Blood product

Indications
Bleeding with fibrinogen < 100-120 mg/dL in liver disease
Adult dose
1 unit per 10 kg (about 8-10 units adult) or per viscoelastic test.

Module references (15)

  1. 1

    European Association for the Study of the Liver. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017;66:1047-81.

  2. 2

    Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the AASLD. Hepatology 2021;74:1014-48.

  3. 3

    de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol 2022;76:959-74.

  4. 4

    O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989;97:439-45.

  5. 5

    Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 2009;137:856-64.

  6. 6

    Larsen FS, Schmidt LE, Bernsmeier C, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol 2016;64:69-78.

  7. 7

    European Association for the Study of the Liver. EASL Clinical Practice Guidelines on acute-on-chronic liver failure. J Hepatol 2023;79:461-91.

  8. 8

    Sarin SK, Choudhury A, Sharma MK, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019;13:353-90.

  9. 9

    European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol 2022;77:807-24.

  10. 10

    Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350-electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med 2014;174:1727-33.

  11. 11

    European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018;69:406-60.

  12. 12

    Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-9.

  13. 13

    European Association for the Study of the Liver. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol 2022;76:1151-84.

  14. 14

    European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of alcohol-related liver disease. J Hepatol 2018;69:154-81.

  15. 15

    Louvet A, Naveau S, Abdelnour M, et al. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology 2007;45:1348-54.