Liver Decompensation

The liver is critical to survival. When injury from viral infection, chemical toxicity, ischemia or autoimmune inflammation damage or kill liver cells, the remaining cells can compensate by doubling their metabolic function. If liver injury or cell loss outstrips its ability to compensate, the liver functions of biotransformation, glycogenolysis, gluconeogenesis, protein synthesis, filtration, etc., will diminish.

As the liver fails, the body will exhibit signs of hepatic insufficiency. Minor signs including: nausea, diarrhea, anorexia and fatigue. More serious liver decompensation is associated systemic signs and symptoms.

  • Central Nervous Systems
    • Altered Mental Status
    • (Encephalopathy)
    • Asterixis
    • Cerebral edema
  • Hematological
    • Thrombocytopenia
    • Coagulopathy
    • Hyperbilirubinemia >2
  • Cardiovascular
    • Hypotension
    • Portal hypertension
      • Varices, Ascites, Edema
  • Metabolic
    • Hypoglycemia
    • Feotor hepaticus
  • Hepatorenal syndrome
    • Splanchic arterial vasodilatation
    • Na+ & H20 retention, ascites
  • Endocrine
    • Testicular atrophy
    • Gynecomastia
    • Menstrual irregularities
  • Respiratory
    • Hepatopulmonary Syndrome
    • Pleural effusion
  • Skin
    • Pruritus
    • Spider angiomas
    • Palmer erythema
  • GI
    • N/V
    • Malnutrition
    • Spontaneous bacterial peritonitis
  • Immunologic
    • Phagocytic dysfunction
    • Complement deficiency
    • Sepsis
  • Liver
    • Hypoproteinemia
    • Cholestasis
    • Jaundice
    • Pain
  • Musculoskeletal
    • Dupuytrens contracture
    • Osteoarthropathy
    • Muscle wasting

Acute Liver Failure

ALF Classification
Causes of ALF in the U.S.*
  • Hyperacute - jaundice to encephalopathy 0-7 days
  • Acute - jaundice to encephalopathy 8-28 days
  • Subacute - jaundice to encephalopathy 29-84 days
  • Acetaminophen overdose 46%
  • Unknown 14%
  • Drug/toxin reactions 12% (antibiotics, NSAIDs, anticonvulsants)
  • Hepatitis B virus 7.7%
  • Autoimmune Hepatitis 5.9%
  • Ischemia 4.6%
  • Hepatitis A virus 2.6%
  • Wilson disease 1.4%
  • Budd-Chiari syndrome 0.9%
  • Pregnancy 0.8%
  • Other 4.8%

Acetaminophen Toxicity

Acetaminophen is oxidized to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).At normal therapeutic dosage any NAPQI produced is rapidly neutralized by the chief hepato-cellular anti-oxidant, glutathione. Neutralizing NAPQI depletes available stores of glutathione. If the amount of NAPQI exceeds available glutathione the hepatocyte is exposed to oxidative damage which can cause inflammation or cell death. Glutathione is also consumed in the process of neutralizing the metabolic by-products of ethanol. Therefore, consuming ethanol with acetaminophen increases the toxicity of acetaminophen or any other source of oxidative stress.*

(ALF) also known as fulminant hepatic failure is a rare life threatening syndrome that can mimic sepsis.
It is characterized by:

The etiology of ALF varies demographically.

Acetaminophen overdose with a jaundice to encephalopathy interval of 0-7 days has a fair likelihood of spontaneous recovery. A jaundice-to-encephalopathy interval of >28 days is usually caused by idiosyncratic drug reactions. It has a very poor prognosis without liver transplantation. Improvements in intensive care and liver transplantation have significantly affected survival rates. Today a U.S. patient receiving care in a liver transplant center has about a 40% chance of spontaneous recovery and about 65% survival rate following liver transplantation.*

Pathology of ALF:



Chronic Liver Disease (CLD) and cirrhosis combined were the 12th most frequent cause of death in the U.S. in 2004.* CLD by definition is a liver illness which has not resolved within 6 months. CLD is characterized by progressive replacement of hepatocytes by fibrosis and eventual cirrhosis. The scar tissue associated with fibrosis and cirrhosis disrupts liver architecture obstructing blood flow and bile excretion. Cirrhotic scarring eventually isolates and encapsulates islands of hepatocytes. Cirrhosis is the common end stage for most chronic liver diseases.

Symptoms of cirrhosis reflect a loss of hepatocyte function resulting in symptoms which include:

Diagnosis of cirrhosis is made based upon:

Cirrhosis is classified by morphology:

Treatment of cirrhosis is focused on slowing progression and the risk of complications associated with the underlying cause: