Acute Liver Failure. Agenda. Natalie H Bzowej, MD, PhD, FRCPC. Case Introduction Definition Diagnosis Initial Laboratory Evaluation Acetaminophen NAC

Transcription

1 Acute Liver Failure Natalie H Bzowej, MD, PhD, FRCPC Agenda Case Introduction Definition Diagnosis Initial Laboratory Evaluation Acetaminophen NAC 1

2 Case 27 year old female presents to ER with N/V Denies fevers or chills, diarrhea Patient had fallen one week ago and twisted her ankle PMHx appendectomy Social Hx +smoking; drinks alcohol 5 x/week for the last 6 mos; no drugs; clerical worker Family history Father is an alcoholic Meds Tylenol x 1 week for her ankle 2 extra strength tablets every 6 hours Case O/E BP 120/65 HR 101 RR 16 O2 sat 96% T 98.6 No stigmata of chronic liver disease; A/O x 3 Anicteric, chest clear, heart sounds normal Abdomen soft, RUQ tenderness No edema Hemglobin 10.3, WBC 5.5, plts 165, INR 1.7 Na 135, K 3.3, BUN 23 Creat 1.2 Tbil 2.3, ALT 3700, AST 2500, ALKP 402 Tylenol level 48 2

3 Case The patient s clinical history is most c/w: A. Chronic liver disease B. Acute hepatitis C. Fulminant liver failure D. Acute liver injury Acute Liver Failure (ALF) Definition Rapid deterioration of liver function resulting in altered mental status (AMS) and coagulopathy in individuals without known pre-existing liver disease If cirrhosis from Wilson disease, vertically-acquired hepatitis B virus (HBV), or autoimmune hepatitis may be included If their chronic liver disease was identified <26 weeks Coagulopathy: INR 1.5 Any degree of altered mental status Illness < 26 week duration NOTE: Patients without AMS do not meet definition of ALF and are more accurately classified as acute liver injury Other terms: hyperacute" (<7 days), "acute" (7-21 days) and "subacute" (>21 days and <26 weeks) are not helpful 3

4 Case Patient diagnosed with acute liver injury What is the next step: A. Send the patient home with labs to be done in a few days B. Arrange for an outpatient liver biopsy C. Admit the patient to hospital D. Perform an outpatient ultrasound Management Principles Patients fulfilling the criteria of ALF: Hospital admission mandatory Patients with any degree of encephalopathy should be transferred to ICU for close monitoring Transplant center should be notified to determine if transfer is appropriate 4

5 Early Diagnostic Testing in ALF CBC Chemistries including LFTs, blood glucose (more frequent BG monitoring if hypoglycemia identified) INR ABG, lactate Ammonia level (arterial) Blood type Acetaminophen level Drug screen (urine and blood) Viral serologies Ceruloplasmin (Wilson s disease) Autoantibodies (autoimmune hepatitis Immunoglobulin G, Anti-smooth muscle antibody AMSA, ANA) Pregnancy test in females Important Viral Serologies in ALF Acute hepatitis A anti-hav IgM Acute hepatitis B Hepatitis B surface antigen (HBsAg) and Hepatitis B core IgM (HBcIgM) Acute hepatitis E anti-hev Acute hepatitis C hepatitis C RNA PCR and anti- HCV Herpes simplex HSV 1 IgM Other less common causes: CMV, EBV, VZV, HIV-1 and HIV-2 5

6 Acetaminophen Hepatotoxicity Leading cause of ALF in United States Dose-related toxin, most ingestions leading to ALF exceed 10gm/day Associated with very high aminotransferase levels (> 3500 IU/L) Activated charcoal may be beneficial within 4 hours of ingestion (1gm/kg) N-Acetylcysteine (NAC) Should be given as early as possible may still be of value 48 hours or more after ingestion Oral dose 140 mg/kg by mouth or nasogastric tube diluted to 5% solution, followed by 70 mg/kg by mouth q 4 h x 17 doses IV administration has replaced oral loading dose mg/kg in 5% dextrose over 15 minutes maintenance dose i-50 mg/kg given over 4 hours followed by 100 mg/kg administered over 16 hours or 6 mg/kg/hr). Controversy exists over when to stop use of NAC standard 72-hour period vs continuation until liver chemistry values have improved 6

7 Acetaminophen Non-Acetaminophen ALF NAC may improve outcomes in nonacetaminophen related ALF In a randomized, control trial NAC improved spontaneous survival in patients with early coma stages (HE grade I or II) in conditions such as acute hepatitis B and drug-induced liver injury Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 2009;137:

8 Common medications leading to druginduced liver injury (DILI) Statins Ciprofloxacin Nitrofurantoin Doxycycline Amoxicillin-clavulanate Trimethoprim-sulfamethazole Ketoconazole Amiodarone Allopurinol Labetalol Herbal medications: kava kava, hydroxycut, herbalife Important to determine ingredients in non-prescription medications Discontinue all non-essential medications Wilson s disease Early diagnosis imperative fulminant form of Wilson s disease is uniformly fatal without transplantation Typically in young patients Associated with Coomb s negative hemolytic anemia (elevated indirect bilirubin) Kaiser-Fleischer rings present in 50% of patients Low ceruloplasmin (may be normal in 15%) Very low alkaline phosphatase and uric acid levels Bilirubin: AP ratio > 2.0 is a rapid and reliable marker Obtain serum and urinary copper levels 8

9 ALF in pregnancy Acute fatty liver of pregnancy HELLP (hemolysis, elevated liver tests, low platelets Often associated with jaundice, coagulopathy and thrombocytopenia May also include features of pre-eclampsia Prompt delivery is critical Rapid recovery after delivery is typical, supportive care Rarely complicated by hepatic rupture or intrahepatic hemorrhage Ischemic injury (shock liver) Generally associated with hypotension Drug-induced hypotension with cocaine, methamphetamines and long-acting niacin Marked elevation of aminotransferases (up to the 10,000s) with rapid normalization Associated elevation of LDH May also be associated with renal dysfunction and muscle necrosis (elevated CK) Treatment with stabilizaion of circulatory problem 9

10 Budd-chiari (acute hepatic vein thrombosis) Typical presentation with abdominal pain, ascites and hepatomegaly Diagnosed with abdominal imaging Should prompt hypercoagulable work-up Prognosis is poor if hepatic failure is present and should prompt consideration of transplantation as opposed to venous decompression Malignant infiltration Not an indication for liver transplant Massive hepatic enlargement common Common malignancies: Breast cancer Small cell lung cancer Lymphoma Myeloma Melanoma 10

11 Case F/u labs Tbil 4.4, ALT 4400, AST 3750, ALKP 556, INR 2.2 Becomes very sleepy and speaks slowly What do you do now? A. Transfer to ICU; start NAC; call transplant center B. Transfer to the ICU; call transplant center C. Keep on the floor D. Transfer to ICU; start NAC; CT head, give Abx; call transplant center Hepatic encephalopathy Grade I/II management principles Brain CT Avoid stimulation and sedation Antibiotics Lactulose Grade III/IV Continue above measures Intubate for airway protection Elevate head of the bed Immediate treatment of seizures Considerations of mannitol, hypertonic saline, hyperventilation and ICP pressure monitoring should be addressed in concert with transplant physician 11

12 Coagulopathy Vitamin K: give at least one dose FFP, platelets, and activated factor VII should only be given for invasive procedures or active bleeding Prophylaxis for stress ulcerations with H2 blocker or PPI recommended Closely monitor: Glucose Potassium Magnesium Phosphorus Metabolic concerns Consider enteral nutrition or TPN early 12

13 Infection All patients with ALF are at increased risk of bacterial and fungal infection Prophylactic surveillance of CXR, blood, urine, sputum and body fluid cultures should be taken Initiate antimicrobial therapy Poor prognostic indicators Etiology of ALF Idiosyncratic drug injury Acute Hepatitis B AIH Mushroom poisoning Wilson s disease Budd-chiari syndrome Indeterminate cause High grade encephalopathy: III/IV Presence of renal dysfunction in nonacetaminophen ALF 13

14 Prognostic models King s College Criteria Acetaminophen-Induced ALF Strongly consider OLT listing if: arterial lactate >3.5 mmol/l after early fluid resuscitation List for OLT if: ph <7.3 - or - arterial lactate >3.0 mmol/l after adequate fluid resuscitation List for OLT if all 3 occur within a 24-hour period: 1. presence of grade 3 or 4 hepatic encephalopathy 2. INR > Creatinine >3.4 mg/dlollege Hospital criteria Case Within 48 hours Grade 3 hepatic encephalopathy Tbil 7.2, INR 7.2, ph 7.2 Creatinine 3.6 and poor urine output Strongly consider liver transplant listing 14

15 Prognostic models King s College Criteria: Non-Acetaminophen-Induced ALF List for OLT if: INR >6.5 and encephalopathy present (irrespective of grade) or any three of the following (encephalopathy present; irrespective of grade): Age <10 or >40 years Jaundice for >7 days before development of encephalopathy INR 3.5 serum bilirubin 17 mg/dl Unfavorable etiology, such as Wilson Disease idiosyncratic drug reaction Transplantation Approximately 40% spontaneous survival with directed and supportive care Overall survival rate of 60% with use of transplantation for those without sufficient recovery Lower 1 year survival than those transplanted for chronic etiologies but after 1 year, patients with ALF have better long-term survival In first 1-3 months most deaths attributable to sepsis or neurologic complications Accounts for < 10% of annual transplants in the United States 15

16 Summary Rapidly progressive, life-threatening condition which occurs when there is massive liver injury Characterisedby coagulopathy and encephalopathy which occurs within days or weeks Often complicated by multi-organ failure Aggressive resuscitation of the circulation ameliorates hepatic parenchymal ischaemic injury and promotes regeneration. Hypoglycaemia must be actively sought, monitored and treated The key to a successful outcome rests intimely recognition, resuscitation and referral to a specialist centre for consideration of transplantation. 16

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