Acute liver failure medical therapy

Jump to navigation Jump to search

Acute liver failure Microchapters


Patient Information


Historical Perspective




Differentiating Acute Liver Failure from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

X Ray



Other Imaging Findings

Other Diagnostic Studies


Medical Therapy


Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Acute liver failure medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Acute liver failure medical therapy

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical

US National Guidelines Clearinghouse

NICE Guidance

FDA on Acute liver failure medical therapy

CDC on Acute liver failure medical therapy

Acute liver failure medical therapy in the news

Blogs on Acute liver failure medical therapy

Directions to Hospitals Treating Acute liver failure

Risk calculators and risk factors for Acute liver failure medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2] Husnain Shaukat, M.D [3]


The management of acute liver failure involves resuscitation of the patient with adequate nutrition and optimization of fluid balance, monitoring and treating the complications and providing nutritional support. The patient should be treated in an appropriate setting preferably a center with liver transplantation facility. Infections and sepsis are common occurrences of fulminant liver failure. The high standards of infection control should be practiced to minimize the nosocomial sepsis. The diagnosis of hepatic injury in hyperacute cases can be a challenge as jaundice can be minimal during that period and confusion or agitation may be the dominant findings. In acute liver failure, the sedative medications should be used with caution as they may mask the worsening encephalopathy and the hepatic clearance may be decreased which can aggravate the sedative effect. However, the short-acting benzodiazepines in low dose can be used during agitation. In acute liver failure patients, opioids are avoided as they decrease the seizure threshold. H2 receptor blockers and proton pump inhibitors are indicated to prevent and treat stress gastropathy. In stage 3 and 4 encephalopathy, intubation and mechanical ventilation are indicated. Acetylcysteine is used for acetaminophen poisoning for up to 72 hours after ingestion. It can dramatically improve the outcome if administered within eight hours of acetaminophen ingestion. The patients with acute liver failure may not have a clear history of acetaminophen intake. Therefore, the threshold for administering acetylcysteine should be low and can also be administered in an acute liver failure of unknown etiology. Every effort should be made to seek out the specific cause of acute liver failure since specific treatments are available for some causes of acute liver failure. However, inappropriately prolonged investigations may make surgery impossible because of progression of sepsis and multiorgan failure.

Medical Therapy

  • The management of acute liver failure involves taking care of the patient in an appropriate setting, preferably a center with liver transplantation facility, monitoring and treating the complications and providing nutritional support.[1][2][3][4][5][6]

General measures

Management of complications


  • The goal of management is to limit the severity of encephalopathy and reduce the risk of cerebral edema.
  • Grade I can be managed on the floors with adequate skilled nursing staff in a calm atmosphere, as it helps in reducing agitation.
  • Grade II encephalopathy has must be managed in ICU setting.
  • For grades III/IV encephalopathy, intubation, and mechanical ventilation are required for management.
  • Monitoring and management of hemodynamic and renal parameters as well as glucose, electrolytes and acid-base status is also important.

Increased Intracranial Pressure


  • The use of antimicrobials as a prophylaxis may reduce infections in a few patients with acute liver failure, but has no survival benefit.[7]
  • If prophylaxis is not started, there should be ongoing surveillance for the development of infections.
  • The antibiotics are administered preemptively in patients with organ failure, encephalopathy or coagulopathy and in whom illness progression is considered likely. The high standards of infection control should be practiced to minimize the nosocomial sepsis.

Coagulopathy and Bleeding Complications

  • Coagulopathy constitutes a part of the definition of acute liver failure.
  • If there is no evidence of bleeding and INR is not in the normal range, treating the INR with fluids such as plasma may lead to volume overload and may cause transfusion-related lung injury.
  • Vitamin K should be administered routinely (5- 10 mg SC) as there is a decreased synthesis of clotting factors from the liver tissue.
  • In high-risk procedures or clinically significant bleeding, clotting factor deficiencies should be treated.
  • Bleeding mainly occurs from the capillaries, and is usually from mucosal surfaces of the stomach and lung.
  • The mucosal surfaces of the gastrointestinal tract are the most common source of bleeding. So, the patient should receive stress ulcer prophylaxis with proton pump inhibitors or H2 blocking agents.

Hemodynamic and Metabolic Disturbances

Renal and pulmonary complications

Treatment for the Specific Underlying Cause

Acetaminophen Poisoning

Mushroom Poisoning

  • In mushroom poisoning, the early administration of activated charcoal is recommended as it is associated with improved survival.
  • Aditional therapy include Penicillin G - 300,000 to 1 million units/kg/day

Drug Induced Hepatoxicity

Viral Hepatitis

  • Supportive care
  • Viral hepatitis A (and E) related acute liver failure must be treated with supportive care as no virus specific treatment has proven to be effective.
  • Nucleoside analogs should be considered for hepatitis B associated acute liver failure and for prevention of post transplant recurrence.

Herpes Simplex Hepatitis

Wilson's Disease

Autoimmune Hepatitis

HELLP Syndrome

  • Hepatic rupture or hemorrhage are fatal complications of HELLP syndrome requiring immediate resuscitation and intervention.
  • Early diagnosis of the complications, and delivery of the baby helps in improving the outcome.
  • Transplantation my be considered if there is postpartum deterioration.

Shock Liver

  • Treatment of underlying cause of ischemia in shock liver is very important, and determines the prognosis of the condition.
  • Transplantation is seldom indicated.

Budd-Chiari Syndrome

Etiology Diagnostic Indicators Management Recommendations
Acetaminophen toxicity
  • Activated charcoal:
    1g/kg PO within 1 hour after drug ingestion (may be beneficial even when administered within 3-4 hours after ingestion) and prior to starting N-acetylcystine (NAC) .
  • Nomogram (helps to determine the likelihood of serious liver damage but does not exclude possible toxicity)
  • N-acetylcystine (NAC)
    140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h x 17 doses
    IV loading dose of 150 mg/kg in 5% dextrose over 15 minutes, thethen a maintenance dose 50 mg/kg IV over the next 4 hours and 100 mg/kg IV over the following 16 hours
    *Promptly begin NAC (beneficial even when administered <48 hours after drug ingestion) in all patients with impending or evolving liver injury due to acetaminophen.
Acute fatty liver of pregnancy/HELLP
  • Early diagnosis and prompt delivery.
  • Adequate supportive care.
  • Consider transplantation for postpartum deterioration
Acute ischemic injury
  • History of cardiac arrest
  • Any period of significant hypovolemia/hypotension, or severe CHF (hypotension is not documented always)
  • Any associated renal dysfunction & muscle necrosis
  • Elevated aminotransferase levels responding to fluid resuscitation
  • Adequate cardiovascular support.
  • Prednisolone (start with 40-60 mg/day, especially in the presence of coagulopathy and mild hepatic encephalopathy)
  • Consider transplantation and do not delay while awaiting response to steroid treatment
  • Liver transplantation (provided underlying malignancy is excluded)
Drug induced
  • History of hepatotoxic drug intake (usually idiosyncratic hepatotoxic drug intake within first 6 months after drug initiation; continuous usage of potentially hepatotoxic drug for more than 1 to 2 years is unlikely to cause de novo liver damage
  • Detailed history taking (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year
    Determine ingredients of non-prescription medications whenever possible
  • Discontinue all but essential medications in the setting of possible drug hepatotoxicity.
  • NAC (may be beneficial for ALF induced by drugs)
Malignant infiltration
  • Malignant infiltration in liver imaging or liver biopsy (confirms or excludes diagnosis)
  • Appropriate management of underlying malignancy
  • Supportive care
Mushroom poisoning
  • History of recent mushroom intake
  • Severe GI symptoms like nausea, vomiting and diarrhea within hours or a day of ingestion (suspected mushroom poisoning in the absence of a positive history)
  • Early gastric lavage and activated charcoal administration
  • Penicillin G 300,000-1 million units/kg/day
  • Silibinin 30-40 mg/kg/day IV or PO, 3-4 days (silymarin in Europe and south America; milk thistle in north America)[11]
  • NAC
  • Liver transplantation (the only lifesaving option)
  • Fluid resuscitation (as needed)
  • Toxically appearing patients with skin lesions (HSV)
  • Positive hepatitis virus serology
  • HSV positive liver biopsy
  • Supportive treatment (no virus specific treatment proven to be effective)
  • Nucleoside and nucleotide analogues (for HBV associated ALF)
  • Acyclovir (5-10 mg/kg every 8 hours for at least 7 days for HSV or VZV)
Wilson's disease
Intermediate etiology
  • Etiology undetermined after all evaluation.


  1. Khadzhidekova VB, Benova DK, Ivanov BA, Mileva MS, Kolev MI (1985). "[Mutagenic effect of the cytostatic drug thaliblastine on rat bone marrow cells when administered alone and in combination with radiation]". Radiobiologiia (in Russian). 25 (5): 656–60. PMID 2933761.
  2. Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC; et al. (2016). "High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial". J Hepatol. 64 (1): 69–78. doi:10.1016/j.jhep.2015.08.018. PMID 26325537.
  3. Demetriou AA, Brown RS, Busuttil RW, Fair J, McGuire BM, Rosenthal P, Am Esch JS, Lerut J, Nyberg SL, Salizzoni M, Fagan EA, de Hemptinne B, Broelsch CE, Muraca M, Salmeron JM, Rabkin JM, Metselaar HJ, Pratt D, De La Mata M, McChesney LP, Everson GT, Lavin PT, Stevens AC, Pitkin Z, Solomon BA (2004). "Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure". Ann. Surg. 239 (5): 660–7, discussion 667–70. PMC 1356274. PMID 15082970.
  4. Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B; et al. (2013). "Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial". Ann Intern Med. 159 (8): 522–31. doi:10.7326/0003-4819-159-8-201310150-00005. PMID 24126646.
  5. Tritto G, Davies NA, Jalan R (2012). "Liver replacement therapy". Semin Respir Crit Care Med. 33 (1): 70–9. doi:10.1055/s-0032-1301736. PMID 22447262.
  6. Stutchfield BM, Simpson K, Wigmore SJ (2011). "Systematic review and meta-analysis of survival following extracorporeal liver support". Br J Surg. 98 (5): 623–31. doi:10.1002/bjs.7418. PMID 21462172.
  7. Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT (2003). "Infection and the progression of hepatic encephalopathy in acute liver failure". Gastroenterology. 125 (3): 755–64. PMID 12949721. Retrieved 2012-10-26. Unknown parameter |month= ignored (help)
  8. Czaja AJ (2012). "Acute and Acute Severe (Fulminant) Autoimmune Hepatitis". Digestive Diseases and Sciences. doi:10.1007/s10620-012-2445-4. PMID 23090425. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  9. Ringe B, Lang H, Oldhafer KJ, Gebel M, Flemming P, Georgii A, Borst HG, Pichlmayr R (1995). "Which is the best surgery for Budd-Chiari syndrome: venous decompression or liver transplantation? A single-center experience with 50 patients". Hepatology (Baltimore, Md.). 21 (5): 1337–44. PMID 7737640. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  10. Ostapowicz, G.; Fontana, RJ.; Schiødt, FV.; Larson, A.; Davern, TJ.; Han, SH.; McCashland, TM.; Shakil, AO.; Hay, JE. (2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States". Ann Intern Med. 137 (12): 947–54. PMID 12484709. Unknown parameter |month= ignored (help)
  11. Enjalbert, F.; Rapior, S.; Nouguier-Soulé, J.; Guillon, S.; Amouroux, N.; Cabot, C. (2002). "Treatment of amatoxin poisoning: 20-year retrospective analysis". J Toxicol Clin Toxicol. 40 (6): 715–57. PMID 12475187.

Template:WH Template:WS