Acute liver failure medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D.  Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S.  Husnain Shaukat, M.D 
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.
- 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.
- The goal is to resuscitate the patient with adequate nutrition and optimization of fluid balance.
- Intubation and mechanical ventilation are indicated for stage 3 or 4 encephalopathy.
- Infections and sepsis are common occurrences with fulminant liver failure. The high standards of infection control should be practiced to minimize the nosocomial sepsis.
- H2 receptor blockers and proton pump inhibitors are indicated to prevent and treat stress gastropathy.
- Early transfer to a liver transplantation center should be considered based on a patient's clinical status.
- 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.
- 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.
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
- Monitoring for increased intracranial pressure in severe encephalopathy, and impending cerebral edema should be done with extradural sensors.
- The goal should be to maintain the intracranial pressure below 20 mm Hg, and the cerebral perfusion pressure above 70 mm Hg.
- Mannitol, 0.5 g/kg, or 100–200 mL of a 20% solution by intravenous infusion over 10 minutes is indicated for reducing sustained cerebral edema.
- Hypothermia (32–34 °C) may reduce intracranial pressure in refractory cases as it affects multiple processes involved in the development of cerebral edema such as slowing of body metabolism, it lowers systemic production, cerebral uptake and metabolism of ammonia as well as hemodynamic stabilizing effects and reducing cerebral blood flow.
- Short-acting barbiturates, propofol, or IV indomethacin can be used for refractory intracranial hypertension.
- The use of antimicrobials as a prophylaxis may reduce infections in a few patients with acute liver failure, but has no survival benefit.
- 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
- Decreased tissue perfusion leading to poor oxygenation and multiorgan failure is a major concern in acute liver failure.
- Patients should be resuscitated with normal saline first, then half normal saline containing 75 mEq/L of bicarbonate should be used in acidotic patients. This fluid should be administered before the use of vasopressors.
- For hypoglycemia, a dextrose solution should be used.
- If a patient is not responding to fluid or vasopressors, the infusion rate should be slowed down to prevent intense vasoconstriction causing ischemia of tissues.
- In patients progressing to acute renal failure, care must be taken to avoid NSAIDs and nephrotoxic agents. Dialysis should be used in a continuous mode rather than intermittent mode.
- Continuous monitoring of glucose and electrolytes is required as they may worsen the condition further.
Renal and pulmonary complications
- Renal failure may develop in more than 50% of patients with acute liver failure, more commonly in the elderly and in patients with acetaminophen induced acute liver failure.
- Pulmonary edema and infections can be seen with acute liver failure. Mechanical ventilation can be required to ensure adequate oxygenation.
- The positive end expiration pressure (PEEP) should be used with caution as it can aggravate cerebral edema in the acute liver failure patients.
Treatment for the Specific Underlying Cause
- Acetylcysteine is used for acetaminophen poisoning for up to 72 hours after ingestion.
- Acetylcysteine can dramatically improve the outcome if administered within eight hours of acetaminophen ingestion.
- Acetylcysteine improves cerebral blood flow and increases transplant free survival in patients with stage 1 or 2 encephalopathy due to the hepatic failure of any cause.
- 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.
- 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
- The drugs other than acetaminophen mostly cause acute liver failure by idiosyncratic reactions.
- No specific antidotes exist for these idiosyncratic drug reactions.
- Corticosteroids are not indicated unless a drug hypersensitivity or an autoimmune reaction is suspected.
- Discontinue all but essential medications.
- 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
- Intravenous acyclovir
- Plasmapheresis + D-penicillamine are used in Wilson's disease.
- Liver transplantaion.
- Patients with autoimmune hepatitis are candidates for corticosteroid therapy.
- These patients should be considered for liver transplantation without delaying assessment to consider steroid therapy.
- 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.
- Treatment of underlying cause of ischemia in shock liver is very important, and determines the prognosis of the condition.
- Transplantation is seldom indicated.
- Transplantation is considered after confirming the diagnosis Budd-Chiari syndrome and excluding malignancy for venous decompression.
|Etiology||Diagnostic Indicators||Management Recommendations|
|Acute fatty liver of pregnancy/HELLP||
|Acute ischemic injury||
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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.