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Liver Failure

Contents

  1. 1 Definition
  2. 2 Clinical Presentation
    1. 2.1 Figure 2: Pathophysiology of Liver Failure
    2. 2.2 Laboratory Tests
    3. 2.3 Imaging
  3. 3 Treatment
    1. 3.1 Spontaneous Bacterial Peritonitis (SBP)
  4. 4 Complications
  5. 5 References

Definition

  • Fulminant liver failure defined as onset of hepatic encephalopathy and coagulopathy within 8 weeks of liver disease without other preexisting liver disease
  • Characterized by loss of the liver's ability to synthesize proteins such as albumin, coaguloapthy due to impaired production of coagulation factors, defects in bile production and excretion, inability to detoxify organic anions, impaired ammonia elimination, and poor metabolism of glucose and fatty acids
Etiology

  • Viral hepatitis most common cause for all age groups overall (ie echovirus, adenovirus, herpes)
  • Metabolic liver disease (ie OTC deficiency) most common in neonates and infants
  • Drug induced ALF (ie acetaminophen toxicity) most common in adolescents
  • 40-60% of ALF is indeterminant in cause


Clinical Presentation

  • Varies with etiology but some common features
  • Hypoglycemia
  • Coaguloapthy (in addition to impaired production of coagulation factors, there is also impaired production of anticoagulant factors such as protein C and S, hence, an elevated INR does not necessarily mean a predisposition toward bleeding)
  • Encephalopathy
  • Jaundice not always present
Figure 1: Stages of Encephalopathy and Associated Changes



Figure 2: Pathophysiology of Liver Failure


Laboratory Tests

  • LFT's (falling transaminases with increasing bilirubin may indicate hepatic burnout/necrosis rather than improvement)
  • Albumin
  • Basic metabolic panel
  • Ammonia
  • Blood gas analysis
  • Blood glucose
  • CBC
  • Coagulation (INR, PTT)
  • Factor V & VIII (assesses liver's coagulation synthetic capacity and may help differentiate from DIC as in DIC, all factors are consumed while in ALF, the endothelium produces more Factor VIII as an acute phase reactant, leading to typically normal or elevated levels in ALF vs decreased levels of factor VIII in DIC). Factor VII actually has the shortest half life and is produced by the liver but because it is a vitamin K dependent factor, its activity may be decreased as a result of low vitamin K and not over liver failure. (Kerr R. New insights into haemostasis in liver failure. Blood CoagulFibrinolysis. 2003 Jun PMID: 14567536)
  • Type and cross
  • Acetaminophen level
  • Cu, ceruloplasmin (in patients >3 yrs)
  • Autoantibodies (anti smooth muscle, anti liver kidney microsomal, anti soluble liver, anti mitochondrial)
  • Serum amino acids
  • Hepatitis panel
  • EBC, CMV, HSV
  • Urine organic acids
  • Urine reducing substances

Imaging

  • Head CT or MRI
  • Abdominal US with doppler
  • Chest X-ray
  • EEG
  • ICP monitoring controversial and currently institution/surgeon dependent

Treatment

  • Very careful supportive care is the mainstay of treatment for ALF
  • Liver transplant is the only curative therapy for end-stage liver failure-hence, early transfer to a transplant center is recommended
Encephalopathy
  • No sedation (unless required for procedures) as assessment of mental status critical and benzodiazepenes can worsen encephalopathy
  • Restrict protein intake to 1-2 g/kg/day
  • Lactulose for hyperammonemia
  • Neomycin and rifxaimin can also be considered to reduce ammonia production by colonic bacteria
  • CRRT if hyperammonemia and renal insufficiency
  • ICP monitoring controversial and institution/surgeon dependent
  • Elective intubation/mechanical ventilation if concern over airway protection
Fluids and Nutrition
  • Liver failure typically is a catabolic state with a propensity for negative nitrogen balance
  • Blood glucose monitoring
  • Fluid balance ~75% maintenance (reduce risk of cerebral edema)
  • Dextrose to provide GIR of 6-10 mg/kg/min
  • Maintain UOP using diuretics as needed
Coagulation
  • Coagulation blood products (ie FFP) only if clinical bleeding
  • Can consider Factor VIIa to minimize volume loading in bleeding, fluid overloaded patient
  • Vitamin K
  • H2 blockers or PPIs to prevent GI bleeding
Other
  • Broad spectrum antibiotics only if sepsis or other infection suspected or if liver transplantation anticipated (discuss with transplant team)

Spontaneous Bacterial Peritonitis (SBP)

 
Pathophysiology
  • Cirrhosis predisposes bacterial overgrowth in the gut (related to intestinal dysmotility and increased permeability from portal HTN) --> intenstinal translocation of bacteria (most commonly E. coli but also Strep, Kleb, PSA, and other gut bacteria like enterococcus)
Diagnosis
  • >250 cells/mm3 in ascitic fluid (culture commonly negative due to low number of strains)
  • Clinical sxs = fever, abd pain, diarrhea, hepatic encephalopathy
  • Need to distinguish from secondary peritonitis (peritonitis caused by something other than SBP, such as cholecystitis, diverticulitis, gut perf, etc)
    • Confirm by 2 of the following:  low glucose, high LDH, or high protein in ascitic fluid --> obtain CT for further eval
Treatment
  • 5 days of abx + albumin supp at day 1 (1.5 g/kg) and day 3 (1 g/kg)
    • Commonly cefotaxime or cipro used as empiric abx, but use carbapenem or zosyn for pts already on prophy abx, suspected nosocomial SBP, or if immunosuppressed
  • Repeat paracentesis at 48 hrs to document decrease in PMNs if pt does not improve on empiric abx regimen, suspected nosocomial SBP, was already on prophy abx when SBP developed, or atypical bacterial grows from ascitic fluid
Prophylaxis
  • If pts with cirrhosis presents with UGIB, give CTX for 7 days or norfloxacin BID for 7 days to prevent SBP
  • Pts with previous history of SBP should receive long-term prophy with daily norfloxacin because recurrence rate within 1 yr = ~70%

Complications

  • Cerebral edema secondary to hyperammonemia, cytotoxic edema
  • Hepatorenal syndrome characterized by sodium retention, oliguria
    • Thought to be mediated by release of splanchnic vasodilators leading to reduced renal perfusion
    • Renal replacement therapy can temporize but liver transplant is generally the only curative therapy
  • Ascites with subsequent spontaneous bacterial peritonitis (SBP)
    • Paracentesis may be indicated if peritonitis or intraabdominal hypertension/compartment syndrome are suspected
  • Infection (~50% will develop significant infection) typically with gram positive organisms although gram negative bacteria and fungi are also seen: Pipercillin-tazobactam and metronidazole are acceptable first line agents
  • "Citrate lock" can occur when patients with ALF are placed on CRRT. As the regional anticoagulation of the CRRT machine requires citrate and citrate is cleared hepatically, patients with ALF may not be able to effectively clear citrate, leading to higher and higher levels of total calcium (bound to the citrate) despite a normal/low ionized calcium level. Treatment of citrate lock typically includes holding the citrate infusion for 4 hours and restarting at a lower citrate infusion dose (Nephrology will determine the response)

References

1) V. Pineiro-Carrero, E. Pineiro: Liver. Pediatrics. 113(Suppl):1097-1106 2004 15060205

2) W.M. Lee: Acute liver failure. N Engl J Med. 329:1862-1872 1993 8305063

3) R. Wirklund: Preoperative preparation of patients with advanced liver disease. Crit Care Med. 32 (Suppl):S106-S115 2004 15064669

4) R. Squires, B. Shneider, J. Bucuvalas: Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 148:652-658 2006 16737880

5) D. Devictor, et al.: Management of fulminant hepatic failure in children–an analysis of 56 cases. Crit Care Med.21 (Suppl 9):S348-S349 1993 8365219

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