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| ==Management==
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| The management guideline as per the present version of the American Association for the Study of Liver Diseases (AASLD) is as follows<ref name="Lee-2012">{{Cite journal | last1 = Lee | first1 = WM. | last2 = Stravitz | first2 = RT. | last3 = Larson | first3 = AM. | title = Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. | journal = Hepatology | volume = 55 | issue = 3 | pages = 965-7 | month = Mar | year = 2012 |doi = 10.1002/hep.25551 | PMID = 22213561 }}</ref>
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| {{Family tree/start}}
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| {{Family tree |border=2|boxstyle=background: WhiteSmoke;|A1|A1=<div style="float: left; text-align: left; height: 18em; width: 20em; padding: 1em">'''Detailed H/o & PE'''<BR> '''In H/o include''' <br> ❑ Altered mental status <BR> ❑ Exposure to viral infections <BR> ❑ Drug and toxin intake <br> '''In PE include''' <BR> ❑ Mental status <BR> ❑ Stigmata of chronic liver disease</div>}}
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| {{Family tree |!| | | | | | | | | |}}
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| {{Family tree |border=2|boxstyle=background:WhiteSmoke;|)|-|B1|B1=<div style="float: left; text-align: left; height: 54em; width: 41em; padding: 1em">
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| '''Initial Laboratory Analysis'''
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| ----
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| ❑ Prothrombin time/INR<br>
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| ----
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| ''Serum chemistries''<br>❑ Sodium<br>❑ Potassium<br>❑ Chloride<br>❑ Bicarbonate<BR>❑ Calcium<BR>❑ Magnesium<BR>❑ Phosphate<BR>❑ Glucose<BR>❑ Blood Urea Nitrogen<BR>❑ Creatinine<BR>❑ AST<BR>❑ ALT<BR>❑ Alkaline phosphatase<BR>❑ GGT<BR>❑ Total bilirubin<BR>❑ Albumin
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| ❑ Complete blood count<BR>❑ Ammonia <BR>❑ Arterial blood gas<BR>❑ Arterial lactate<BR>❑ Amylase and lipase<BR>❑ Acetaminophen level<BR>❑ Toxicology screen<BR>❑ Viral hepatitis serologies (anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HEV, anti-HCV, HCV RNA, HSV1 IgM, VZV)<BR>❑ Autoimmune markers (ANA, ASMA, Immunoglobulin levels)<BR>❑ Ceruloplasmin level<sup>†</sup><BR>❑ Blood type and screen<BR>❑ Pregnancy test (females)<BR>❑ HIV-1, HIV-2<sup>‡</sup>
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| </div>}}
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| {{Family tree |!| | | | | | | | | |}}
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| {{Family tree |border=2|boxstyle=background:WhiteSmoke;|)|-|C01|C01='''Dx:''' Acute liver failure (ALF)<BR>'''Dx criteria:''' INR ≥1.5 and any degree of alteration in mental status in the absence of pre exisiting [[cirrhosis]] and any illness of <26 weeks duration}}
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| {{Family tree |!| | | | | | | | | |}}
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| {{Family tree |border=2|boxstyle=background:WhiteSmoke;|)|-|D01|D01=Mandatory ICU admission}}
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| {{Family tree |!| | | | | | | | | |}}
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| {{Family tree |border=2|boxstyle=background:WhiteSmoke;|)|-|E01|E01='''ICU management'''<br>'''Etiology specific management'''}}
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| {{Family tree |!| | | | | | | | | |}}
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| {{Family tree |border=2|boxstyle=background:WhiteSmoke;|)|-|E01|E01=Consider transplantation}}
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| {{Family tree/end}}
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| <sup>†</sup>In case of Wilson disease consideration (e.g., in patients less than 40 years without obvious explanation for ALF)<ref name="Roberts-2003">{{Cite journal | last1 = Roberts | first1 = EA. | last2 = Schilsky | first2 = ML. | title = A practice guideline on Wilson disease. | journal = Hepatology | volume = 37 | issue = 6| pages = 1475-92 | month = Jun | year = 2003 | doi = 10.1053/jhep.2003.50252 | PMID = 12774027 }}</ref><br>
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| <sup>‡</sup>Implications for potential liver transplantation
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| <div class="mw-collapsible mw-collapsed">
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| ===Quality of Evidence on Which a Recommendation Is Based===
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| <div class="mw-collapsible-content">
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| The quality of evidence and the based recommendations are as follows<ref name="Woolf-">{{Cite journal | last1 = Woolf | first1 = SH. | last2 = Sox | first2 = HC. |title = The Expert Panel on Preventive Services: continuing the work of the U.S. Preventive Services Task Force. | journal = Am J Prev Med | volume = 7 | issue = 5 |pages = 326-30 | month = | year = | doi = | PMID = 1790039 }}</ref>
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| {|class="wikitable"
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| !Grade !! Definition
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| |-
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| | I|| Randomized controlled trials
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| | II-1|| Controlled trials without randomization
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| | II-2|| Cohort or case-control analytic studies
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| | II-3|| Multiple time series, dramatic uncontrolled experiments
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| | III|| Opinions of respected authorities, descriptive epidemiology
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| |}
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| </div></div>
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| <div class="mw-collapsible mw-collapsed">
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| ===ICU Management===
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| <div class="mw-collapsible-content">
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| {|class="wikitable"
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| !Specific Issues !! Management Recommendations
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| | '''Cerebral edema and intracranial hypertension'''||a) '''Intracranial pressure monitoring: (III)'''<br>ICP monitoring with monitors when patients<br>*Present with high grade hepatic encephalopathy (grade III/IV)<br>*Are in centers with expertise in ICP monitoring<br>*Are awaiting and undergoing liver transplantation<br>Hourly neurological evaluation in the absence of ICP monitors<br>b) '''Prophylactic hypertonic saline: (I)'''<br>Prophylactic induction of [[hypernatremia]] with hypertonic saline to a sodium level of 145-155 mEq/L in patients with<br>*Serum ammonia >150 μM<br>*Grade III/IV hepatic encephalopathy<br>*[[Acute renal failure]]<br>*[[Vasopressors]] requirement to maintain [[Mean arterial pressure|MAP]]<br>c) '''Intracranial hypertension treatment:'''<br>*I line therapy: [[Mannitol]] bolus (0.5-1.0 gm/kg body weight) '''(II-2)'''<br>*II line therapy: [[Secobarbital|Short-acting barbiturates]] and induction of [[hypothermia]] to a core body temperature of 34°-35°C (if refractory to mannitol) '''(II-3)'''
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| | '''Grade I/II encephalopathy'''|| [[Lactulose]] (possibly helpful and may interfere with surgical field by increasing bowel distention during liver transplantation)'''(III)'''
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| | '''Grade III/IV encephalopathy'''||Besides managing the patient similar to grade I/II encephalopathy<br>a) Intubate trachea (might require sedation)'''(III)'''<br>b) Immediate treatment of seizures with [[phenytoin]] and [[benzodiazepines]] with short half-lives '''(III)'''
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| | '''Infection'''||a) Periodic surveillance for prompt initiation of antimicrobial treatment of infections at the earliest sign of active infection or deterioration (progression to high grade hepatic encephalopathy or elements of the [[SIRS]]) '''(III)'''<br>b) Antibiotic prophylaxis possibly helpful (not proven) '''(III)'''
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| | '''Coagulopathy'''||a) In the setting of active bleeding or before invasive procedure, consider replacement therapy for [[thrombocytopenia]] and/or prolonged prothrombin time with platelet and [[FFP]] transfusion respectively '''(III)'''<br>b) '''Prophylaxis for stress ulceration: (I)'''<br>*I line: [[H2 blocker]] or[[PPI]]<br>*II line: [[Sucralfate]]
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| | '''Hemodynamics and renal failure'''||a) Fluid resuscitation and maintenance of adequate intravascular volume (initiate hypotension treatment with intravenous normal saline) '''(III)'''<br>b) Systemic vasopressor support ([[dopamine]], [[epinephrine]], [[norepinephrine]]) as needed '''(II-1)'''<br>c) [[Vasopressin]] or[[terlipressin]] added to norepinephrine in norepinephrine-refractory cases (used cautiously in severely encephalopathic patients with intracranial hypertension)'''(II-1)'''<br>d) '''Goals of circulatory support: (II)'''<br>*MAP ≥75 mmHg<br>*[[CPP]] 60-80 mmHg<br>e) Continuous modes of hemodialysis (if needed) '''(I)'''<br>f) Pulmonary artery catheterization is rarely necessary (it is associated with significant morbidity), instead ensure appropriate volume status with a volume challenge'''(III)'''
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| | '''Metabolic abnormalities'''|| Frequently monitor and correct derangements in glucose, potassium, magnesium and phosphate '''(III)'''
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| |}
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| </div></div>
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| <div class="mw-collapsible mw-collapsed">
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| ===Etiology Specific Management===
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| <div class="mw-collapsible-content">
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| {| class="wikitable sortable"
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| !Etiology
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| !Diagnostic Indicators
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| !Management Recommendations
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| |'''Acetaminophen toxicity''' ||a) H/o: Acetaminophen intake (toxic dose >10 gm/day or >150 mg/kg)<BR>b) Labs: Acetaminophen in blood and urine.<BR>c) Suspected if no H/o but [[aminotransferase]] levels >3500 IU/L with low bilirubin levels, in the absence of apparent hypotension or cardiovascular collapse (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>||a)'''Activated charcoal:'''<br>For patients with known or suspected [[acetaminophen toxicity]], administer [[activated charcoal]] within 4 hours of presentation and prior to starting [[NAC]] '''(I)'''<br>b) '''NAC:'''<br>*Promptly begin NAC in all patients where the ingested quantity of acetaminophen, serum drug level or rising aminotransferases indicate impending or evolving liver injury '''(II-1)'''<br>*NAC may be used in cases of ALF in which acetaminophen ingestion is possible or when knowledge regarding ingestion is inadequate but elevated aminotransferases suggest acetaminophen poisoning '''(III)'''
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| |'''Acute fatty liver of pregnancy/HELLP''' ||a) H/o and PE: Jaundice and hypertension<br>b) Labs: Coagulopathy, thrombocytopenia, proteinuria ± hypoglycemia<BR>c) Liver imaging or biopsy: [[Steatosis]] ||a) Early diagnosis and prompt delivery '''(III)'''<br>b) Consider transplantation for postpartum deterioration '''(III)'''
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| |'''Acute ischemic injury''' ||a) H/o and PE:<br>*Cardiac arrest, any period of significant hypovolemia/hypotension, or severe [[CHF]] (hypotension is not documented always)<br>*Associated renal dysfunction & muscle necrosis<br>b) Labs: Elevated aminotransferase levels responding to fluid resuscitation|| Cardiovascular support is the treatment of choice '''(III)'''
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| |'''Autoimmune''' ||a) Labs: Serum autoantibodies (may be absent)<BR>b) Liver biopsy (confirms diagnosis when [[autoimmune hepatitis]] is suspected and autoantibodies are negative) '''(III)''' ||a) Administer [[prednisolone]] (start with 40-60 mg/day, especially in the presence of coagulopathy and mild hepatic encephalopathy)'''(III)'''<br>b) Consider transplantation and do not delay while awaiting response to steroid treatment '''(III)'''
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| |'''Budd-Chiari''' ||a) H/o and PE: Abdominal pain, ascites and hepatomegaly<BR>b) Labs: Tests to identify hypercoagulability<br>c) Liver imaging: [[CT]], [[Medical ultrasonography#Doppler sonography|doppler USG]], [[venography]] or magnetic resonance venography (confirms diagnosis) || Hepatic vein thrombosis with ALF is an indication for liver transplantation (provided underlying malignancy is excluded) '''(II-3)'''
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| |'''Drug induced''' ||H/o: 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)<BR>* Include details (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 '''(III)'''<br>* Determine ingredients of non-prescription medications whenever possible '''(III)''' ||a) Discontinue all but essential medications in the setting of possible drug hepatotoxicity '''(III)'''<br>b) NAC may be beneficial for ALF induced by drugs '''(I)'''
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| |'''Malignant infiltration''' ||a) PE: Massive hepatomegaly<BR>b) Liver imaging & biopsy: Malignant infiltration (confirms or excludes diagnosis) '''(III)'''||a) Treat the underlying malignancy accordingly<br>b) Supportive care
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| |'''Mushroom poisoning''' ||a) H/o: Recent mushroom intake<BR>b) Suspected if no H/o but severe GI symptoms like nausea, vomiting and diarrhea within hours or a day of ingestion ||a) Consider administration of [[Penicillin|penicillin G]] and NAC in ALF patients with known or suspected mushroom poisoning '''(III)'''<br>b) Patients should be listed for transplantation as it is often the only lifesaving option '''(III)'''
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| |'''Viral''' ||a) PE: Toxically appearing patients with skin lesions in HSV<br>b) Labs: Positive hepatitis virus serology.<BR>c) Liver biopsy: [[HSV]] ||a) Supportive treatment (no virus specific treatment proven to be effective) '''(III)'''<BR>b) '''HBV:'''<BR>Nucleoside and nucleotide analogues should be considered for [[HBV]]associated ALF and for prevention of post-transplant recurrence '''(III)'''<BR>c) '''HSV or VZV:'''<br>[[Acyclovir]] (5-10 mg/kg every 8 hours for at least 7 days) for suspected or documented cases and transplantation may be considered '''(III)'''
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| |'''Wilson's disease''' ||a) PE: KF ring<br>b) Labs: Serum bilirubin >20 mg/dL, bilirubin:alkaline phosphatase >2.0, low serum ceruloplasmin, elevated serum & urine copper<br>c) Liver biopsy: High copper levels '''(III)'''||Promptly consider for liver transplantation '''(III)'''
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| |'''Intermediate etiology''' ||Etiology undetermined after all evaluation||a) Review drug and toxin intake H/o<BR>b) Transjugular biopsy for further evaluation of possible mailgnancy, [[Wilson disease]], autoimmune hepatitis and [[viral hepatitis]] '''(III)'''
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| |}
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| </div></div>
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| <div class="mw-collapsible mw-collapsed">
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| ===Transplantation===
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| <div class="mw-collapsible-content">
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| {|class="wikitable"
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| ! Liver Transplantation!! Recommendations
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| | Prognostic scoring systems|| Currently available prognostic scoring systems (including the widely applied King’s College Hospital criteria-KCH Criteria)<ref name="O'Grady-1989">{{Cite journal | last1 = O'Grady | first1 = JG. | last2 = Alexander | first2 = GJ. | last3 = Hayllar | first3 = KM. | last4 = Williams | first4 = R. | title = Early indicators of prognosis in fulminant hepatic failure. | journal = Gastroenterology | volume = 97 | issue = 2 | pages = 439-45 | month = Aug | year = 1989 | doi = | PMID = 2490426 }}</ref> do not adequately predict outcome and determine candidacy for liver transplantation, thus not recommending the entire reliance entirely upon these guidelines '''(III)'''
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| | Urgent hepatic transplantation|| Urgent hepatic transplantation is indicated when prognostic indicators suggest a high likelihood of death '''(II-3)'''
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| | In the setting of limited organ supply|| In the setting of limited organ supply, either living donor or auxiliary liver transplantation may be considered. But its use remains controversial '''(II-3)'''
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| |Liver support systems|| Currently available liver support systems are not recommended outside clinical trials and their future in management of ALF remains unclear'''(II-1)'''
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| |}
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| </div></div>
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