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Chief, Division of Gastroenterology

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Presentation on theme: "Chief, Division of Gastroenterology"— Presentation transcript:

1 Chief, Division of Gastroenterology
ACUTE LIVER FAILURE Milton G. Mutchnick, M.D. Professor of Medicine Chief, Division of Gastroenterology Wayne State University School of Medicine

2 Acute Liver Failure Rapid deterioration of liver function
resulting in altered mentation and coagulopathy in a patient without preexisting cirrhosis and with an illness of less than 26 weeks duration.

3 Acute Liver Failure….AKA
Fulminant hepatic failure Fulminant hepatitis Subfulminant liver failure Subacute hepatic necrosis Subacute liver failure Hyperacute liver failure

4 Index of Suspicion for ALF
Clinical signs of moderate to severe hepatitis Laboratory findings including an increase in the prothrombin time of 4-6sec.(INR ≥ 1.5). Altered sensorium INR ≥ Altered Mental Status = ALF

5 Suspect ALF?..........Admit to ICU

6 Etiology of ALF Acute viral hepatitis (A - E) Mushroom poisoning
Acetaminophen Acute fatty liver of pregnancy Chemical agents

7 Drug-induced hepatitis
Budd-Chiari Syndrome VOD of liver Wilson’s disease AIH

8 ALF Etiologies Viral Drug Poisoning Ischemia VOD Malignant Infiltrate
Wilson’s Disease Microvesicular steatosis AIH Hyperthermia OLT Partial hepatectomy

9 Etiology of ALF in 342 Cases (University Hospital, London UK)
Drugs-Overdose Other Acetaminophen Wilson’s Ecstasy Fatty liver of pregnancy 7 Lymphoma/ Viral Hepatitis malignant infiltrate HAV Sepsis HBV Budd-Chiari Non A-E Ischemia Miscellaneous Idiosyncratic Drug Reactions Lamotrigine, cyproterone, NSAID, chloroguine, rifampin/ INH halothane, flucloxacillin

10 U.S. ALF STUDY GROUP 2003 (308 Patients, 73% Women)

11 Viral Acute Hepatitis A-E Reactivation of HBV Chemotherapy
Immunosuppresion Herpes simplex Varicella-Zoster EBV

12 Acute HAV and ALF Frequency 0.01% - 0.1% in jaundiced patients
ALF uncommon Frequency 0.01% - 0.1% in jaundiced patients ALF occurs early Survival (transplant- free) 75% Age related survival

13 Acute HBV and ALF HBV alone or with HDV co-infection (rare)
Transplant-free survival is 23% Overall survival 77% because of transplantation

14 HBV Markers in ALF IgM Anti HBc 100% HBsAg 90% HBV DNA (Abbott) 10%
*Absence of HBsAg favors better prognosis (47% v 17%). Higher frequency ALF with mutant HBV form

15 Drug Induced ALF Many drugs implicated Acetaminophen
Halothone and derivatives INH/ Rifampin Tricyclics/ MAO inhibitors Phenytoin/ NSAID Increased risk: acetaminophen (as little as 2gms) + ETOH median dose: 13 gm Increased risk if drug continued after jaundice appears

16 Poisoning and ALF Amanita mushrooms (amanatoxins)
- LD = 50 gms (3 mushrooms) - Toxins not destroyed by cooking - Rapid onset of HE in 4-8 days following severe emesis and diarrhea Solvents - chlorinated hydrocarbons Herbal remedies Yellow phosphorus

17 Ischemic Hepatitis and ALF
Liver cell necrosis - massive scale Cardiac tamponade Acute heart failure Pulmonary embolus Hepatic artery thrombosis

18 Obstruction of Hepatic Veins and ALF
Budd-Chiari syndrome and thrombosis of hepatic veins VOD - Post BMT Chemotherapy, Irradiation

19 Massive Malignant Infiltration of the Liver
Attributed to ischemic changes Leukemia, lymphoma Malignant histiocytosis Metastatic Replacement

20 Other Etiologic Causes of ALF
Wilson’s Disease can be presenting feature usually in patients <20 yrs can occur if patient discontinued D-penicillamine for a few years

21 Other Etiologies (2) Microvesicular steatosis
Acute fatty liver of pregnancy Reye’s syndrome Drug Induced - Valproic acid AIH May appear as an acute hepatitis on initial presentation More common if anti-LKMI antibody present ASMA usually not present

22 Other Etiologies (3) Hyperthermia (Heat stroke) Direct thermal injury
Hepatic ischemia due to -DIC -Perfusion defect OLT Poor presentation of donor liver Acute graft rejection Thrombosis - hepatic artery, hepatic vein, portal vein Partial hepatectomy Removal of 80% or more of healthy liver Removal of 50% or less in hepatic dysfunction

23 Evaluation & Diagnosis of Impending ALF
History! History! History! Sexual contacts IDU Risk Factors Pregnancy Mushrooms Medications Travel Toxic exposures

24 HISTORY Family members with liver disease? Recent cold sores
Onset of jaundice Work environment- toxic agents Hobbies Herbal products/dietary supplements

25 Physical Exam Determine presence or absence
of pre-existing liver disease Hepatic tenderness Hepatic decompensation

26 Laboratory Tests (1) ALT, AST, Alk Phos, Glu, Bilirubin
Drug screening ALT, AST, Alk Phos, Glu, Bilirubin Lytes, Albumin, Mg, Phos., CBC with differential Coags: PT, PTT Anti HAV IgM Anti HBc IgM/ Anti HBsAg/ Anti-HCV

27 Laboratory Tests (2) If under 35 years of age Ceruloplasmin
Serum & urine copper Arterial blood gas Arterial lactate Pregnancy test Autoimmune markers – ANA, ASMA, Ig levels HIV status Amylase & lipase

28 Reserved for diagnostic dilemma - (Transjugular approach)
Liver Biopsy Reserved for diagnostic dilemma - AIH, HS (Transjugular approach)

29 Diagnosis of ALF Hallmarks - occurs simultaneously or in succession
Altered mentation Clinical EEG Arterial Ammonia Coagulopathy PT 4 sec prolonged (INR≥ 1.5) Arterial pH<7.3 if acetaminophen ingested (cause for immediate transfer for OLT)

30 Management of ALF (1) Directed towards prevention of complications
ICU setting Central line(s)-10% dextrose Pulmonary artery pressure and CO Inform Transplant Service and transfer with onset of HE Monitor VS and urinary output (Foley) strict I&O Laboratory Testing every 4-6hr electrolytes, BUN, creatinine, CBC, platelets, PT, PTT, ALT, AST, T. bilirubin, Alk Phos, Albumin

31 Management (2) Maintain gastric pH above 5 - protonix IV
Preparation for endotracheal intubation Prepare to initiate monitoring intracranial pressure Enteral feeding tubes for grade 3 or 4 coma

32 Cerebral Edema Cerebral Perfusion Pressure
Mean Arterial Pressure – ICP = Cerebral Perfusion Pressure (CPP) Ideal ICP<20-25mm Hg Ideal CPP>50-60mm Hg Imazaki, et al When CPP<40 for 2 hrs. 0 of 7 patients recovered When CPP>50 6 of 8 patients recovered Improved ICP first sign of spontaneous recovery

33 Management (3) Cerebral Edema & Intracranial Hypertension
(Most serious complications of ALF) Clinical signs of elevated ICP (Intracranial Pressure) -sluggish pupillary response -increased limb-muscle tone -none Monitoring ICP -usually reserved for grade 3 or 4 coma -awaiting OLT

34 Management (4) Cerebral Edema - General Measures -quiet environment
-elevate head 10°-20° -avoid sedation (use restraints) -avoid Valsalva-like maneuvers -mental status assessments q1-2h -mannitol if signs of impending uncal herniation (0.5mg/kg, lolus q4-8h) when ICP<30-40mm -assisted ventilation (in all grade 3 and 4)

35 Multiple Organ Failure
Hepatic damage increased risk of infection Failure of clearance Endotoxemia Gut leak MOF Activation of macrophages Tissue Circulating Release of Hypoxia changes cytokines TNF, IL-1, IL-6 Williams, Sem Liver Dis, Vol 16, No.4, 1996

36 Management (5) Hemodynamic Complications include:
Hypotension, tachycardia, vascular volume decrease with capillary leak and vasodilation Volume expansion (central line) FFP or 4.5% albumin, 10% dextrose Maintain pulmonary capillary wedge pressure 12mm-14mm Hg Minimize salt solutions (ascites, interstitial accumulation) Inotropic/pressor support(epi, norepi, dopamine), but not vasopressin.

37 Management (6) Coagulopathy/Bleeding Diathesis
FFP or platelets given in presence of bleeding Conventional treatment of GI bleeding DIC thrombocytopenia Metabolic Complications Prevent hypoglycemia Phosphate and magnesium levels monitored - replace early Enteral feeding, 60gm protein/24 hrs No role for high branched-chain AA Monitor for lactic acidosis secondary to tissue hypoxia, sepsis

38 (CI = cardiac output/body surface area)
Role of Cardiac Index (CI = cardiac output/body surface area) ALF associated with high CI Presence of low CI (<4.5L/min) is bad prognostic sign Look for - blood loss, pneumothorax lactic acidosis, cardiac tamponade

39 Management (7) Renal Failure - In 42% to 82% of ALF
poor prognostic sign - Rising creatinine and oliguria - Metabolites of acetaminophen are nephrotoxic leading to acute renal failure similar to ATN and loss of phosphate -HRS

40 Additional Complications
ARDS Sepsis - Severe complement deficiency - Decreased PMN motility - Decreased Kupffer cell function and removal of endotoxins - Increased levels of TNF and IL-6

41 Prognostic Factors Dependent on Etiology
Younger patients do better (<40 and >10) Presence of cerebral edema Delay between jaundice and HE of more than 3 weeks - poorer prognosis MOF - poor prognosis

42 Current Treatment Transplantation

43 Temporary Measures Hemodialysis - no proven benefit on survival
Charcoal hemoperfusion - no proven benefit Resins (Cation or anion - exchange) - not proven Extracoporeal liver perfusions - may be bridge to OLT Hepatocyte transplants (peritoneum) - uncertain Capillary hollow-fiber system - unproven, ?bridge



46 Approach to Suspected ALF
Etiology and Pathogenesis Evaluation and Diagnosis Complications Management Prognosis Current and future treatment approaches

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