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__NOTOC__
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{{Acute liver failure}}
{{Acute liver failure}}
{{CMG}}
{{CMG}} {{AE}} {{ADI}} {{HS}}
==Overview==
==Overview==
Liver transplantation remains the ultimate therapy for acute liver failure but medical therapy assists in recovery of liver tissue. It acts like a bridge to transplantation. Treatment mainly depends on the underlying etiologies and the complications arising out of it. Liver support systems help in supporting the patients until the liver recovers or can be used as a bridging aid for transplantation.
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 infection|nosocomial sepsis]]. The diagnosis of hepatic injury in [[Hepatic failure|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 antagonist|H2 receptor blockers]] and [[proton pump inhibitors]] are indicated to prevent and treat [[Stress ulcer|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|multiorgan failure.]]
 
==Medical Therapy==
==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.<ref name="pmid2933761">{{cite journal |vauthors=Khadzhidekova VB, Benova DK, Ivanov BA, Mileva MS, Kolev MI |title=[Mutagenic effect of the cytostatic drug thaliblastine on rat bone marrow cells when administered alone and in combination with radiation] |language=Russian |journal=Radiobiologiia |volume=25 |issue=5 |pages=656–60 |year=1985 |pmid=2933761 |doi= |url=}}</ref><ref name="pmid26325537">{{cite journal| author=Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC et al.| title=High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. | journal=J Hepatol | year= 2016 | volume= 64 | issue= 1 | pages= 69-78 | pmid=26325537 | doi=10.1016/j.jhep.2015.08.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26325537  }} </ref><ref name="pmid15082970">{{cite journal |vauthors=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 |title=Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure |journal=Ann. Surg. |volume=239 |issue=5 |pages=660–7; discussion 667–70 |year=2004 |pmid=15082970 |pmc=1356274 |doi= |url=}}</ref><ref name="pmid24126646">{{cite journal| author=Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B et al.| title=Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. | journal=Ann Intern Med | year= 2013 | volume= 159 | issue= 8 | pages= 522-31 | pmid=24126646 | doi=10.7326/0003-4819-159-8-201310150-00005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24126646  }} </ref><ref name="pmid22447262">{{cite journal| author=Tritto G, Davies NA, Jalan R| title=Liver replacement therapy. | journal=Semin Respir Crit Care Med | year= 2012 | volume= 33 | issue= 1 | pages= 70-9 | pmid=22447262 | doi=10.1055/s-0032-1301736 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22447262  }} </ref><ref name="pmid21462172">{{cite journal| author=Stutchfield BM, Simpson K, Wigmore SJ| title=Systematic review and meta-analysis of survival following extracorporeal liver support. | journal=Br J Surg | year= 2011 | volume= 98 | issue= 5 | pages= 623-31 | pmid=21462172 | doi=10.1002/bjs.7418 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21462172  }} </ref>
====General measures====
* 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 blocker]]s 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|hepatic injury]] in [[Hepatic failure|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|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==
===Encephalopathy===
* The goal of management is to limit the severity of [[encephalopathy]] and reduce the risk of [[Cerebral edema|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 [[Hemodynamics|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 [[Dura|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 [[Hemodynamics|hemodynamic]] stabilizing effects and reducing [[cerebral blood flow]].
* Short-acting [[barbiturate]]s, [[propofol]], or IV [[indomethacin]] can be used for [[Intracranial hypertension|refractory intracranial hypertension]].
===Infections===
* The use of [[antimicrobials]] as a [[prophylaxis]] may reduce infections in a few patients with acute liver failure, but has no survival benefit.<ref name="pmid12949721">{{cite journal |author=Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT |title=Infection and the progression of hepatic encephalopathy in acute liver failure |journal=[[Gastroenterology]] |volume=125 |issue=3 |pages=755–64 |year=2003 |month=September |pmid=12949721 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0016508503010515 |accessdate=2012-10-26}}</ref>
* 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 infection|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 [[Mucous membrane|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 inhibitor|proton pump inhibitors]] or [[H2 antagonist|H2 blocking agents]].
===Hemodynamic and Metabolic Disturbances===
* Decreased tissue perfusion leading to [[Oxygenation|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 [[Acidosis|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 [[NSAID]]s and [[Nephrotoxic|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 expiratory pressure|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==
===Acetaminophen Poisoning===
*[[Acetylcysteine]] is used for [[Acetaminophen toxicity|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.
===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===
* The drugs other than [[acetaminophen]] mostly cause acute liver failure by [[Idiosyncratic drug reaction|idiosyncratic reactions]].
* No specific antidotes exist for these [[Idiosyncratic drug reaction|idiosyncratic drug reactions]].
* [[Corticosteroid]]s are not indicated unless a drug [[hypersensitivity]] or an [[autoimmune reaction]] is suspected.
* Discontinue all but essential medications.
===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===
* Intravenous [[acyclovir]]
===Wilson's Disease===
* [[Plasmapheresis]] + [[D-penicillamine]] are used in [[Wilson's disease]].
* [[Liver transplantation|Liver transplantaion]].
===Autoimmune Hepatitis===
* Patients with [[autoimmune hepatitis]] are candidates for [[corticosteroid]] therapy.<ref name="pmid23090425">{{cite journal |author=Czaja AJ |title=Acute and Acute Severe (Fulminant) Autoimmune Hepatitis |journal=[[Digestive Diseases and Sciences]] |volume= |issue= |pages= |year=2012 |month=October |pmid=23090425 |doi=10.1007/s10620-012-2445-4 |url= |accessdate=2012-10-26}}</ref>
* These patients should be considered for [[liver transplant|liver transplantation]] without delaying assessment to consider [[steroid]] therapy.
===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.


===Goal===
===Budd-Chiari Syndrome===
* Metabolic abnormalities
* Transplantation is considered after confirming the diagnosis [[Budd-Chiari syndrome]] and excluding [[malignancy]] for venous decompression.<ref name="pmid7737640">{{cite journal |author=Ringe B, Lang H, Oldhafer KJ, Gebel M, Flemming P, Georgii A, Borst HG, Pichlmayr R |title=Which is the best surgery for Budd-Chiari syndrome: venous decompression or liver transplantation? A single-center experience with 50 patients |journal=[[Hepatology (Baltimore, Md.)]] |volume=21 |issue=5 |pages=1337–44 |year=1995 |month=May |pmid=7737640 |doi= |url= |accessdate=2012-10-26}}</ref>
* Coagulation defects
{| class="wikitable sortable"
* Electrolyte and acid-base disturbances
!Etiology
* Advanced chronic kidney disease
!Diagnostic Indicators
* Hypoglycemia
!Management Recommendations
* Encephalopathy
|-
===Treatment strategies===
|'''Acetaminophen toxicity''' ||
====General measures====
* History of [[acetaminophen]] intake (toxic dose >10 gm/day or >150 mg/kg)<BR>
* Treatment involves admission to hospital; often [[intensive care unit]] admission or very close observation are required.
* [[Acetaminophen]] in blood and/or urine<BR>
* Supportive treatment with adequate nutrition and, optimization of the [[fluid balance]] should be done
* [[Aminotransferase]] levels >3500 IU/L with low [[bilirubin]] levels, in the absence of apparent [[hypotension]] or [[cardiovascular collapse]] (suspected acetaminophen toxicity in the absence of a positive history because acetaminophen is the leading cause of ALF at least in the United States and Europe)<ref name="Ostapowicz-2002">{{Cite journal  | last1 = Ostapowicz | first1 = G. | last2 = Fontana|first2 = RJ. | last3 = Schiødt | first3 = FV. | last4 = Larson | first4 = A. | last5 = Davern | first5 = TJ. | last6 = Han | first6 = SH. | last7 = McCashland|first7 = TM. | last8 = Shakil | first8 = AO. | last9 = Hay | first9 = JE. | title = Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. | journal = Ann Intern Med | volume = 137 | issue = 12 | pages = 947-54 | month = Dec | year = 2002 | doi =  | PMID = 12484709 }}</ref>
* [[Mechanical ventilation]], [[intubation]] is indicated for stage 3 or 4 encephalopathy
|
* [[Sepsis]] and infections are common with [[fulminant liver failure]]. Though prophylactic antibiotic decreases the risk of infection, but is not routinely recommended as no survival benefits have been proved. Nevertheless, broad coverage with antibiotics is recommended for suspected cases of sepsis.  
* '''Activated charcoal:'''<br>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]]) .
* Routine administration of steroids for [[adrenal insufficiency]] is not recommended.
* '''[[Nomogram]]''' (helps to determine the likelihood of serious liver damage but does not exclude possible toxicity)<br>
* [[H2 receptor blocker]] and [[proton pump inhibitors]] are indicated to prevent and treat [[stress gastropathy]].
* Early transfer to a liver transplantation center should be decided based on patient's clinical status.


===2011 AASLD Recommendations : General Measures <ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>(DO NOT EDIT)===
* N-acetylcystine ([[NAC]]) <br>140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h x 17 doses<br>'''or'''<br>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<br>*Promptly begin NAC (beneficial even when administered <48 hours after drug ingestion) in all patients with impending or evolving liver injury due to acetaminophen.<br>
|-
|'''Acute fatty liver of pregnancy/HELLP''' ||
* [[Jaundice]]
* [[Hypertension]]<br>
* [[Coagulopathy]]<br>
* [[Thrombocytopenia]]


{|class=wikitable
* [[Proteinuria]]
* [[Hypoglycemia]]
* [[Steatosis]] in liver imaging or biopsy
|
* Early diagnosis and prompt delivery.<br>
* Adequate supportive care.<br>
* Consider transplantation for postpartum deterioration
|-
|'''Acute ischemic injury''' ||
* History of cardiac arrest<br>
* Any period of significant hypovolemia/hypotension, or severe [[CHF]] (hypotension is not documented always)<br>
* Any associated [[Renal insufficiency|renal dysfunction]] & muscle [[necrosis]]<br>
* Elevated aminotransferase levels responding to fluid resuscitation
|
* Adequate cardiovascular support.
|-
|'''Autoimmune''' ||
* Positive serum [[Autoantibody|autoantibodies]] (may be absent)<br>
* Positive liver biopsy (confirms diagnosis when [[autoimmune hepatitis]] is suspected and autoantibodies are negative)
|
*  [[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
|-
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|'''Budd-Chiari''' ||
* [[Abdominal pain|Abdominal pain<br>]]
*  [[Ascites]]<br>
*  [[Hepatomegaly]]<br>
*  Blood tests positive for [[hypercoagulability]]<br>
*  Positive findings during liver imaging ([[CT]], [[Medical ultrasonography#Doppler sonography|doppler USG]], [[venography]] or magnetic resonance venography) (confirms diagnosis)
|
* Liver transplantation (provided underlying malignancy is excluded)
|-
|-
| '''1.''' Patients with ALF should be hospitalized and monitored frequently, preferably in an ICU.
|'''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 <br>Determine ingredients of non-prescription medications whenever possible
|
* Discontinue all but essential medications in the setting of possible drug hepatotoxicity.<br>
* NAC (may be beneficial for ALF induced by drugs)
|-
|-
| '''2.''' The precise etiology of ALF should be sought to guide further management decisions.
|'''Malignant infiltration''' ||
* Massive [[hepatomegaly]]
 
* Malignant infiltration in liver imaging or liver biopsy (confirms or excludes diagnosis)
|
* Appropriate management of underlying malignancy<br>
* Supportive care
|-
|'''Mushroom poisoning''' ||
* History of recent mushroom intake<br>
* Severe GI symptoms like [[Nausea and vomiting|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<br>
* [[Penicillin|Penicillin G]] 300,000-1 million units/kg/day<br>'''or'''<br>
* [[Silibinin]] 30-40 mg/kg/day IV or PO, 3-4 days (silymarin in Europe and south America; milk thistle in north America)<ref name="Enjalbert-2002">{{Cite journal  | last1 = Enjalbert | first1 = F. | last2 = Rapior | first2 = S. | last3 = Nouguier-Soulé | first3 = J. | last4 = Guillon | first4 = S. | last5 = Amouroux | first5 = N. | last6 = Cabot | first6 = C. | title = Treatment of amatoxin poisoning: 20-year retrospective analysis. | journal = J Toxicol Clin Toxicol | volume = 40 | issue = 6 | pages = 715-57 | month =  | year = 2002 | doi =  | PMID = 12475187 }}</ref><br>
* NAC <br>
* Liver transplantation (the only lifesaving option) <br>
* Fluid resuscitation (as needed)
|-
|'''Viral''' ||
* Toxically appearing patients with skin lesions (HSV)<br>
* Positive hepatitis virus serology<br>
* [[HSV]] positive liver biopsy
|
* Supportive treatment (no virus specific treatment proven to be effective)
* Nucleoside and nucleotide analogues (for [[HBV]] associated ALF) <BR>
* [[Acyclovir]] (5-10 mg/kg every 8 hours for at least 7 days for HSV or VZV)
|-
|'''Wilson's disease''' ||
* [[Kayser-Fleischer ring|Kayser- Fleischer rings]] (KF rings)
* Serum [[bilirubin]] >20 mg/dL,<br>
* Bilirubin:alkaline phosphatase >2.0<br>
* Low serum [[ceruloplasmin]]<br>
* Elevated serum & urine [[copper]]<br>
* High copper levels in liver biopsy
|
* Liver transplantation <br>
* [[Dialysis]] or hemofiltration or [[plasmapheresis]] or plasma exchange
|-
|'''Intermediate etiology''' ||
* Etiology undetermined after all evaluation.
|
* Review drug and toxin intake history<BR>
* Transjugular biopsy (for further evaluation of possible mailgnancy, [[Wilson disease]], [[autoimmune hepatitis]] and [[viral hepatitis]])
|}
|}


====Management of increased intracranial pressure====
==References==
* [[Intracranial pressure]] monitoring in severe encephalopathy and impending cerebral edema should be done with extradural sensors
{{Reflist|2}}


* The goal should be to maintain the intracranial pressure below 20 mm Hg and the cerebral perfusion pressure above 70 mm Hg.
[[Category:Hepatology]]
* [[Lactulose]] is indicated in cases of encephalopathy.
[[Category:Gastroenterology]]
* Mannitol, 0.5 g/kg, or 100–200 mL of a 20% solution by intravenous infusion over 10 minutes for reducing cerebral edema
* [[Mannitol]] should be avoided in patients with advanced chronic kidney diseases.
* Hypernatremia (145-155 mEq/L) through intravenous hypertonic saline infusion  to induce hypernatremia may be used to reduce intracranial hypertension.
* Hypothermia (32–34 °C) may reduce intracranial pressure in refractory cases can be tried.
* Other measures like elevation of head end to 30 degrees, hyperventilation and intravenous prostaglandin E1can also be used.
* Short-acting barbiturate, propofol, or i/v indomethacin for refractory intracranial hypertension.


===Treatment for specific underlying cause===
====Acetaminophen or Paracetamol poisoning====
** [[Acetylcysteine]] for [[paracetamol poisoning]] up to 72 hours after ingestion
** It improves cerebral blood flow and increases transplant-free survival in patients with stage 1 or 2 [[encephalopathy]] due to hepatic failure of any cause.
** Its treatment can increase [[prothrombin time]] giving a false alarm of worsening liver failure.
*** 140 mg/kg orally followed by 70 mg/kg orally every 4 hours for an additional 17 doses or
*** 150 mg/kg in 5% dextrose intravenously over 15 minutes followed by 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours
====Mushroom poisoning====
* Penicillin G - 300,000 to 1 million units/kg/day or
* Silibinin/silymarin/milk thistle (not licensed in the United States)
====Chronic viral hepatitis====
* Nucleoside analogs - Fulminant hepatitis B
====Herpes simplex hepatitis====
* Intravenous acyclovir
====Wilson disease====
* [[Plasmapheresis]] + [[D-penicillamine]]
===[[Liver Support Systems]]===
These are the support devices helping in providing some time to help failing liver to recover. These can also be used as a bridge to transplantation.  There are two kinds of devices sorbent based artificial system and cell based bio-artificial system. There is no good evidence showing low mortality with their use in acute liver failure<ref name="pmid18336699">{{cite journal |author=Freeman RB, Steffick DE, Guidinger MK, Farmer DG, Berg CL, Merion RM |title=Liver and intestine transplantation in the United States, 1997-2006 |journal=[[American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons]] |volume=8 |issue=4 Pt 2 |pages=958–76 |year=2008 |month=April |pmid=18336699 |doi=10.1111/j.1600-6143.2008.02174.x |url=http://dx.doi.org/10.1111/j.1600-6143.2008.02174.x |accessdate=2012-10-26}}</ref>. They are not recommended outside of clinical trials as of now.
==References==
{{reflist|2}}
{{WH}}
{{WH}}
{{WS}}
{{WS}}

Latest revision as of 21:19, 18 December 2017

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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]

Overview

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

Encephalopathy

  • 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

Infections

  • 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
    or
    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.
Autoimmune
  • 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
Budd-Chiari
  • 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
    or
  • 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)
Viral
  • 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.

References

  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.

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