Difference between revisions of "Hepatic failure"

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*Imaging is not required for diagnosis but it is useful in the correct clinical context, for example:
*Abdominal ultrasound with Doppler to confirm portal and hepatic vein patency
*Abdominal ultrasound with Doppler to confirm portal and hepatic vein patency
*CXR for evaluation of lungs
*Non-contrast computed tomography (CT) scan of the head for patients with Hepatic encephalopathy
*Non-contrast computed tomography (CT) scan of the head for patients with Hepatic encephalopathy

Revision as of 19:31, 2 August 2020

Hepatic failure
ICD-10 K72.9
DiseasesDB 5728
MeSH D017093

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Liver failure; fulminating hepatic failure


Liver failure is the inability of the liver to perform its normal synthetic and metabolic function as part of normal physiology.

Historical Perspective


Three forms are recognized:

  • Chronic liver failure - When liver failure occurs as a result of cirrhosis. It usually means that the liver has been failing gradually for some time (more than 6 months), possibly for years. This is called chronic liver failure or End-stage Liver Disease (ESLD).


Mechanism of hepatic injury:[9]

  • Immune-mediated hepatocellular injury: Viral infections
  • Direct hepatocellular injury:
    • Hepatotrophic virus family(HAV, HBV, HCV)
    • Toxic metabolites: Acetaminophen, metabolic disorders
  • Ischemic hepatocellular injury: Shock, SIRS
  • The pathophysiology of cerebral edema and hepatic encephalopathy is seen in Acute Liver Failure is multi-factorial and includes altered blood-brain barrier secondary to inflammatory mediators leading to microglial activation, accumulation of glutamine secondary to ammonia crossing the BBB and subsequent oxidative stress leading to depletion of adenosine triphosphate (ATP) and guanosine triphosphate (GTP). This ultimately leads to astrocyte swelling and cerebral edema.
  • The pathogenesis of Acute-on-chronic liver failure is unclear but many theories are proposed in such as Neutrophilic dysfunction that increases the risk of infections, Circulating changes, oxidative stress, and Toxin Hypothesis.


Causes for Acute liver failure[5][11]:

Category Etiology of Acute liver failure
Metabolic diseases
Vascular diseases
Malignant Infiltration
Autoimmune disease
  • Unknown

Causes for chronic liver failure:

Differential Diagnosis

Epidemiology and Demographics

Etiology of ALF in Adults.jpg

Natural History, Complications and Prognosis

Natural History

Clinical features in Hepatic failure


  • Hepatic encephalopathy
  • Cerebral edema
  • Intracranial hypertension
  • Seizures


  • Loss of metabolic function
  • Hypoglycemia
  • Hyperammonemia
  • Coagulopathy
  • Lactic acidosis

Kidney and adrenal

  • Hepatorenal syndrome
  • Hepatoadrenal syndrome
  • Electrolyte abnormalities


  • Systemic inflammatory response
  • Immunosuppression
  • Catabolic state


  • High output state
  • Subclinical myocardial injury
  • Hepatocardiac syndrome


  • Pancreatitis


  • Acute lung injury
  • Acute respiratory distress syndrome
  • Hepatopulmonary syndrome

Bone marrow

  • Frequent suppression
  • Anemia
  • Thrombocytopenia


  • Neurological complications, increased intercranial pressure, cerebral edema, Abnormal hemostasis, and bleeding complications, hepatorenal syndrome, multiorgan failure,infection.[17][18]


prognosis of Acute liver failure

  • The prognosis in patients with acute liver failure is highly variable and depends on the etiology, subtypes (hyperacute, acute,...), age, and the degree of coagulopathy. Determining the prognosis for these patients is vital. Liver transplantation has dramatically improved short-term survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment.[19]
  • Identification of patients who will eventually require liver transplantation should be addressed through continuous medical assessment.The King's College Criteria (KCC) may be used.This scoring system is generally quite accurate in predicting poor prognosis and, along with clinical judgment, is useful for ensuring timely transfer to a liver transplant center.[15][20][19]

Prognosis of chronic liver failure

  • Patients with compensated cirrhosis have a median survival of 6–12 years. Decompensation and end stage liver disease occurs in 5%–7% annually; median survival then declines to 2 years.[21]
  • Several retrospectives studies have reported in patients with end-stage liver disease, the MELD score to have similar predictive value to the king's college criteria for mortality associated with ALF.


History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies | Clinical prediction rules

History and symptoms

Social history

  • History of alcohol use:
    • Amount
    • Duration
  • History of illicit drug use
  • History of unprotected sexual intercourse
  • History of recent travel

Past Medical history

Menstrual history

Family history

Medication history

  • History of use of all medications used over the last 6 months, including prescription medications, over-the-counter agents, herbal supplements, wild mushrooms, or other alternatives/complementary therapies;


Physical Examination

  • Complete physical examination should be performed.
  • Assessment of mental status, the neurologic examination, and the fundoscopic examination in patients with Hepatic Encephalopathy of stage 2 or greater.


Laboratory Findings

laboratory tests are recommended for establishing an etiology and determining the prognosis of Acute liver failure:


  • Imaging is not required for diagnosis but it is useful in the correct clinical context, for example:
  • Abdominal ultrasound with Doppler to confirm portal and hepatic vein patency
  • CXR for evaluation of lungs
  • Non-contrast computed tomography (CT) scan of the head for patients with Hepatic encephalopathy


Effective medical Therapies for specific causes of liver failure and hepatic encephalopathy. Medical therapy includes antidotes to reverse the effect of Acute liver failure and various medications to Reduce ICP[15]

  • Acetaminophen intoxication Oral NAC: 140 mg/kg loading dose, then 70 mg/kg every 4 hours until discontinued by hepatology or transplantation surgery attending physician

IV NAC: 150 mg/kg loading dose, then 50 mg/kg IV over 4 hours, then 100 mg/kg IV over 16 hours as a continuous infusion until discontinued by hepatology or transplantation surgery attending physician

  • Amanita phalloides(mushroom intoxication) Charcoal: via NGT every 4 hours alternating with silymarin, Penicillin G: 1 g/kg/day IV and NAC (Dosing as for acetaminophen

overdose.),Silymarin: 300 mg PO/NGT every 12 hours,Legalon-SIL: 5 mg/kg/day IV (given in 4 divided doses) or 5 mg/kg IV loading dose followed by 20 mg/kg/day via continuous infusion

Treatment of complications:

Management of Hepatic Encephalopathy

Even minimal hepatic encephalopathy may benefit from treatment.[24]

Traditionally it has been presumed that excessive protein intake leads to increased generation of ammonia, which, in the setting of severe liver impairment, will accumulate and worsen the hepatic encephalopathy. While very large protein loads (such as gastrointestinal hemorrhage, because blood is rich in protein) are known to precipitate encephalopathy, the need for patients with chronic liver disease patients to be protein restricted has been disproven.[25] Indeed, because chronic liver disease is a catabolic state, a protein restricted diet would lead to protein malnutrition and a negative nitrogen balance.

Concomitant hypokalemia should be corrected as hypokalemia increases renal ammonia production and may promote conversion of ammonium into ammonia which can cross the blood-brain barrier.[26]

Lactulose is a compound that will cause osmotic diarrhea, thus lessening the time available for intestinal bacteria to metabolize protein into ammonia within the bowel. Further, it acidifies the environment in the lumen of the bowel. This promotes the conversion of lumenal ammonia (NH3) to ammonium (NH4+) which, by which virtue of its net charge, should be less readily absorbed into the bloodstream from the bowel lumen. Despite this theoretical and appealing mechanism, a meta-analysis of randomized controlled trials by the international Cochrane Collaboration found benefit, but suggests there is little evidence for its preferred use to treat hepatic encephalopathy.[27] Indeed, any drug (laxative) which speeds up transit through the bowel thereby lessening the time available for bacteria to metabolize protein into ammonia, works just as well.

Lactulose can be given rectally for patients who cannot take oral medications.[28][29][30] One regimen is 300 mL (200 gm) of lactulose syrup (10 gm/15 ml) in 1 L of water which is retained for 1 hour, with the patient in the Trendelenburg position.[31]

Antibiotics may be given to kill bacteria present in the bowel thereby decreasing bacterial conversion of protein to ammonia (and other toxic substances) there. Although effective, neomycin, a non-absorbable aminoglycoside antibiotic, is essentially contraindicated; it has been found that a proportion of the ingested dose is indeed absorbed due to increased gut permeability, thus increasing the risk of renal failure and hearing loss (i.e. two of the potential side effects of neomycin). The former side-effect, in particular, is especially worrisome given the already increased likelihood of renal failure in cirrhosis and portal hypertension (i.e. hepatorenal syndrome). Metronidazole has also been studied.[32]

Rifaximin , receieved orphan drug status in 2005 for the treatment of hepatic encephalopathy. In contrast to neomycin, its tolerability profile is comparable to placebo.[33] Multiple clinical trials have demonstrated that rifaximin at a dose of 400 mg taken orally 3 times a day was as effective as lactulose or lactilol at improving hepatic encephalopathy symptoms.[34] Similarly, rifaximin was as effective as neomycin and paromomycin.[35] Rifaximin was better tolerated than both the cathartics and the other nonabsorbable antibiotics. A number of concerns remain regarding rifaximin's role in the treatment of hepatic encephalopathy. It remains to be determined if rifaximin can improve severe encephalopathy symptoms as rapidly as lactulose. There are also concerns regarding the cost-effectiveness of the medication.

A meta-analysis of randomized controlled trials by the international cochrane collaboration found benefit from flumazenil.[36] The doses of flumazenil varied around a median of 2 milligrams over 10 minutes: flumazenil was given as a continuous infusion (12 trials), preceded by bolus injections in two trials. One trial used only bolus injections. Patients received flumazenil at a total dose ranging from 0.2 to 19.5 milligram (median 2 milligram). The median duration of treatment was 10 minutes (range one minute to 72 hours)'. However, the benefit was short.

L-ornithine-L-aspartate stimulates the urea cycle, and has shown encouraging results in randomized controlled trials.[37][38][39]

Contraindicated medications

Hepatic coma is considered an absolute contraindication to the use of the following medications:

Recommendations for the Treatment of Hepatic Encephalopathy (DO NOT EDIT)

  1. In early stages of encephalopathy, lactulose may be used either orally or rectally to effect a bowel purge, but should not be administered to the point of diarrhea, and may interfere with the surgical field by increasing bowel distention during liver transplantation.
  2. Patients who progress to high-grade hepatic encephalopathy (grade III or IV) should undergo endotracheal intubation.
  3. Seizure activity should be treated with phenytoin and benzodiazepines with short half-lives. Prophylactic phenytoin is not recommended.
  4. Intracranial pressure (ICP) monitoring is recommended in ALF patients with high-grade hepatic encephalopathy, in centers with expertise in ICP monitoring, in patients awaiting and undergoing liver transplantation.
  5. In the absence of ICP monitoring, frequent (hourly) neurological evaluation is recommended to identify early evidence of intracranial hypertension.
  6. In the event of intracranial hypertension, a mannitol bolus (0.5-1.0 gm/kg body weight) is recommended as first-line therapy; however, the prophylactic administration of mannitol is not recommended.
  7. In ALF patients at highest risk for cerebral edema (serum ammonia >150 µM, grade 3/4 hepatic encephalopathy, acute renal failure, requiring vasopressors to maintain mean arterial pressure [MAP]), the prophylactic induction of hypernatremia with hypertonic saline to a sodium level of 145-155 mEq/L is recommended.
  8. Short-acting barbiturates and the induction of hypothermia to a core body temperature of 34-35ºC may be considered for intracranial hypertension refractory to osmotic agents as a bridge to liver transplantation.
  9. Corticosteroids should not be used to control elevated ICP in patients with ALF.

Management of cerebral edema

  • Manitol
  • Hypertonic saline(%3)
  • Hyperventilation
  • Hypothermia
  • phenobarbital and IV Indomethacin
  • Hepatectomy

Treatment of hemodynamic instabilty

  • Invasive hemodynamic monitoring
  • Colloid, crystalloid fluids, and blood products
  • Vassopressors

Monitoring of renal function

  • Early fluid challenge
  • Hemodialysis if needed

Correcting of coagulopathy

Correcting of metabolic disorders

Consider liver transplantation

  • Liver transplantation: One of the most important, yet difficult, aspects of care for patients with Acute Liver failure is the determination of the need for urgent liver transplantation. We recommend early and rapid evaluation for transplantation candidacy. More than half of cases with Acute liver disease need liver transplantation with improved outcomes.[6]
  • For patients with chronic liver failure,the only existing cure is liver transplantation , an option that only a minority of patients will receive it.[21]

Contraindicated medications

Severe hepatic failure is considered an absolute contraindication to the use of the following medications:

The ALFSG index is a newer option that may be more accurate.[40]


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See Also

cs:Jaterní selhání sv:Leversvikt ur:فشل جگری