Liver Failure
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