Sandbox vidit6

Management

The management guideline as per the present version of the American Association for the Study of Liver Diseases (AASLD) is as follows

Detailed H/o & PE In H/o include ❑ Altered mental status ❑ Exposure to viral infections ❑ Drug and toxin intake In PE include ❑ Mental status ❑ Stigmata of chronic liver disease

Initial Laboratory Analysis ❑ Prothrombin time/INR Serum chemistries ❑ Sodium ❑ Potassium ❑ Chloride ❑ Bicarbonate ❑ Calcium ❑ Magnesium ❑ Phosphate ❑ Glucose ❑ Blood Urea Nitrogen ❑ Creatinine ❑ AST ❑ ALT ❑ Alkaline phosphatase ❑ GGT ❑ Total bilirubin ❑ Albumin ❑ Complete blood count ❑ Ammonia ❑ Arterial blood gas ❑ Arterial lactate ❑ Amylase and lipase ❑ Acetaminophen level ❑ Toxicology screen ❑ Viral hepatitis serologies (anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HEV, anti-HCV, HCV RNA, HSV1 IgM, VZV) ❑ Autoimmune markers (ANA, ASMA, Immunoglobulin levels) ❑ Ceruloplasmin level† ❑ Blood type and screen ❑ Pregnancy test (females) ❑ HIV-1, HIV-2‡

Dx: Acute liver failure (ALF) 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

Mandatory ICU admission

ICU management Etiology specific management

Consider transplantation

^†In case of Wilson disease consideration (e.g., in patients less than 40 years without obvious explanation for ALF)
^‡Implications for potential liver transplantation

Quality of Evidence on Which a Recommendation Is Based

The quality of evidence and the based recommendations are as follows

Grade	Definition
I	Randomized controlled trials
II-1	Controlled trials without randomization
II-2	Cohort or case-control analytic studies
II-3	Multiple time series, dramatic uncontrolled experiments
III	Opinions of respected authorities, descriptive epidemiology

ICU Management

Specific Issues	Management Recommendations
Cerebral edema and intracranial hypertension	a) Intracranial pressure monitoring: (III) ICP monitoring with monitors when patients *Present with high grade hepatic encephalopathy (grade III/IV) *Are in centers with expertise in ICP monitoring *Are awaiting and undergoing liver transplantation Hourly neurological evaluation in the absence of ICP monitors b) Prophylactic hypertonic saline: (I) Prophylactic induction of hypernatremia with hypertonic saline to a sodium level of 145-155 mEq/L in patients with *Serum ammonia >150 μM *Grade III/IV hepatic encephalopathy *Acute renal failure *Vasopressors requirement to maintain MAP c) Intracranial hypertension treatment: *I line therapy: Mannitol bolus (0.5-1.0 gm/kg body weight) (II-2) *II line therapy: Short-acting barbiturates and induction of hypothermia to a core body temperature of 34°-35°C (if refractory to mannitol) (II-3)
Grade I/II encephalopathy	Lactulose (possibly helpful and may interfere with surgical field by increasing bowel distention during liver transplantation)(III)
Grade III/IV encephalopathy	Besides managing the patient similar to grade I/II encephalopathy a) Intubate trachea (might require sedation)(III) b) Immediate treatment of seizures with phenytoin and benzodiazepines with short half-lives (III)
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) b) Antibiotic prophylaxis possibly helpful (not proven) (III)
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) b) Prophylaxis for stress ulceration: (I) *I line: H2 blocker orPPI *II line: Sucralfate
Hemodynamics and renal failure	a) Fluid resuscitation and maintenance of adequate intravascular volume (initiate hypotension treatment with intravenous normal saline) (III) b) Systemic vasopressor support (dopamine, epinephrine, norepinephrine) as needed (II-1) c) Vasopressin orterlipressin added to norepinephrine in norepinephrine-refractory cases (used cautiously in severely encephalopathic patients with intracranial hypertension)(II-1) d) Goals of circulatory support: (II) *MAP ≥75 mmHg *CPP 60-80 mmHg e) Continuous modes of hemodialysis (if needed) (I) f) Pulmonary artery catheterization is rarely necessary (it is associated with significant morbidity), instead ensure appropriate volume status with a volume challenge(III)
Metabolic abnormalities	Frequently monitor and correct derangements in glucose, potassium, magnesium and phosphate (III)

Etiology Specific Management

Etiology	Diagnostic Indicators	Management Recommendations
Acetaminophen toxicity	a) H/o: Acetaminophen intake (toxic dose >10 gm/day or >150 mg/kg) b) Labs: Acetaminophen in blood and urine. 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)	a)Activated charcoal: For patients with known or suspected acetaminophen toxicity, administer activated charcoal within 4 hours of presentation and prior to starting NAC (I) b) NAC: *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) *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)
Acute fatty liver of pregnancy/HELLP	a) H/o and PE: Jaundice and hypertension b) Labs: Coagulopathy, thrombocytopenia, proteinuria ± hypoglycemia c) Liver imaging or biopsy: Steatosis	a) Early diagnosis and prompt delivery (III) b) Consider transplantation for postpartum deterioration (III)
Acute ischemic injury	a) H/o and PE: *Cardiac arrest, any period of significant hypovolemia/hypotension, or severe CHF (hypotension is not documented always) *Associated renal dysfunction & muscle necrosis b) Labs: Elevated aminotransferase levels responding to fluid resuscitation	Cardiovascular support is the treatment of choice (III)
Autoimmune	a) Labs: Serum autoantibodies (may be absent) 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) b) Consider transplantation and do not delay while awaiting response to steroid treatment (III)
Budd-Chiari	a) H/o and PE: Abdominal pain, ascites and hepatomegaly b) Labs: Tests to identify hypercoagulability c) Liver imaging: CT, 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)
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) * 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) * Determine ingredients of non-prescription medications whenever possible (III)	a) Discontinue all but essential medications in the setting of possible drug hepatotoxicity (III) b) NAC may be beneficial for ALF induced by drugs (I)
Malignant infiltration	a) PE: Massive hepatomegaly b) Liver imaging & biopsy: Malignant infiltration (confirms or excludes diagnosis) (III)	a) Treat the underlying malignancy accordingly b) Supportive care
Mushroom poisoning	a) H/o: Recent mushroom intake 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 G and NAC in ALF patients with known or suspected mushroom poisoning (III) b) Patients should be listed for transplantation as it is often the only lifesaving option (III)
Viral	a) PE: Toxically appearing patients with skin lesions in HSV b) Labs: Positive hepatitis virus serology. c) Liver biopsy: HSV	a) Supportive treatment (no virus specific treatment proven to be effective) (III) b) HBV: Nucleoside and nucleotide analogues should be considered for HBVassociated ALF and for prevention of post-transplant recurrence (III) c) HSV or VZV: Acyclovir (5-10 mg/kg every 8 hours for at least 7 days) for suspected or documented cases and transplantation may be considered (III)
Wilson's disease	a) PE: KF ring b) Labs: Serum bilirubin >20 mg/dL, bilirubin:alkaline phosphatase >2.0, low serum ceruloplasmin, elevated serum & urine copper c) Liver biopsy: High copper levels (III)	Promptly consider for liver transplantation (III)
Intermediate etiology	Etiology undetermined after all evaluation	a) Review drug and toxin intake H/o b) Transjugular biopsy for further evaluation of possible mailgnancy, Wilson disease, autoimmune hepatitis and viral hepatitis (III)

Transplantation

Liver Transplantation	Recommendations
Prognostic scoring systems	Currently available prognostic scoring systems (including the widely applied King’s College Hospital criteria-KCH Criteria) do not adequately predict outcome and determine candidacy for liver transplantation, thus not recommending the entire reliance entirely upon these guidelines (III)
Urgent hepatic transplantation	Urgent hepatic transplantation is indicated when prognostic indicators suggest a high likelihood of death (II-3)
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)
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)