Acute liver failure medical therapy

Acute liver failure Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Acute Liver Failure from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Acute liver failure medical therapy On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Acute liver failure medical therapy All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Acute liver failure medical therapy
CDC on Acute liver failure medical therapy
Acute liver failure medical therapy in the news
Blogs on Acute liver failure medical therapy
Directions to Hospitals Treating Acute liver failure
Risk calculators and risk factors for Acute liver failure medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2] Husnain Shaukat, M.D [3]

Overview

The management of acute liver failure involves resuscitation of the patient with adequate nutrition and optimization of fluid balance, monitoring and treating the complications and providing nutritional support. The patient should be treated in an appropriate setting preferably a center with liver transplantation facility. Infections and sepsis are common occurrences of fulminant liver failure. The high standards of infection control should be practiced to minimize the nosocomial sepsis. The diagnosis of hepatic injury in hyperacute cases can be a challenge as jaundice can be minimal during that period and confusion or agitation may be the dominant findings. In acute liver failure, the sedative medications should be used with caution as they may mask the worsening encephalopathy and the hepatic clearance may be decreased which can aggravate the sedative effect. However, the short-acting benzodiazepines in low dose can be used during agitation. In acute liver failure patients, opioids are avoided as they decrease the seizure threshold. H2 receptor blockers and proton pump inhibitors are indicated to prevent and treat stress gastropathy. In stage 3 and 4 encephalopathy, intubation and mechanical ventilation are indicated. Acetylcysteine is used for acetaminophen poisoning for up to 72 hours after ingestion. It can dramatically improve the outcome if administered within eight hours of acetaminophen ingestion. The patients with acute liver failure may not have a clear history of acetaminophen intake. Therefore, the threshold for administering acetylcysteine should be low and can also be administered in an acute liver failure of unknown etiology. Every effort should be made to seek out the specific cause of acute liver failure since specific treatments are available for some causes of acute liver failure. However, inappropriately prolonged investigations may make surgery impossible because of progression of sepsis and multiorgan failure.

Medical Therapy

• The management of acute liver failure involves taking care of the patient in an appropriate setting, preferably a center with liver transplantation facility, monitoring and treating the complications and providing nutritional support.

General measures

• The goal is to resuscitate the patient with adequate nutrition and optimization of fluid balance.
• Intubation and mechanical ventilation are indicated for stage 3 or 4 encephalopathy.
• Infections and sepsis are common occurrences with fulminant liver failure. The high standards of infection control should be practiced to minimize the nosocomial sepsis.
• H2 receptor blockers and proton pump inhibitors are indicated to prevent and treat stress gastropathy.
• Early transfer to a liver transplantation center should be considered based on a patient's clinical status.
• The diagnosis of hepatic injury in hyperacute cases can be a challenge as jaundice can be minimal during that period and confusion or agitation may be the dominant findings.
• In acute liver failure, the sedative medications should be used with caution as they may mask the worsening encephalopathy and the hepatic clearance may be decreased which can aggravate the sedative effect. However, the short-acting benzodiazepines in low dose can be used during agitation.
• In acute liver failure patients opioids are avoided as they decrease the seizure threshold.
• Every effort should be made to seek out the specific cause of acute liver failure since specific treatments are available for some causes of acute liver failure. However, inappropriately prolonged investigations may make surgery impossible because of progression of sepsis and multiorgan failure.

Management of complications

Encephalopathy

• The goal of management is to limit the severity of encephalopathy and reduce the risk of cerebral edema.
• Grade I can be managed on the floors with adequate skilled nursing staff in a calm atmosphere, as it helps in reducing agitation.
• Grade II encephalopathy has must be managed in ICU setting.
• For grades III/IV encephalopathy, intubation, and mechanical ventilation are required for management.
• Monitoring and management of hemodynamic and renal parameters as well as glucose, electrolytes and acid-base status is also important.

Increased Intracranial Pressure

• Monitoring for increased intracranial pressure in severe encephalopathy, and impending cerebral edema should be done with extradural sensors.
• The goal should be to maintain the intracranial pressure below 20 mm Hg, and the cerebral perfusion pressure above 70 mm Hg.
• Mannitol, 0.5 g/kg, or 100–200 mL of a 20% solution by intravenous infusion over 10 minutes is indicated for reducing sustained cerebral edema.
• Hypothermia (32–34 °C) may reduce intracranial pressure in refractory cases as it affects multiple processes involved in the development of cerebral edema such as slowing of body metabolism, it lowers systemic production, cerebral uptake and metabolism of ammonia as well as hemodynamic stabilizing effects and reducing cerebral blood flow.
• Short-acting barbiturates, propofol, or IV indomethacin can be used for refractory intracranial hypertension.

Infections

• The use of antimicrobials as a prophylaxis may reduce infections in a few patients with acute liver failure, but has no survival benefit.
• If prophylaxis is not started, there should be ongoing surveillance for the development of infections.
• The antibiotics are administered preemptively in patients with organ failure, encephalopathy or coagulopathy and in whom illness progression is considered likely. The high standards of infection control should be practiced to minimize the nosocomial sepsis.

Coagulopathy and Bleeding Complications

• Coagulopathy constitutes a part of the definition of acute liver failure.
• If there is no evidence of bleeding and INR is not in the normal range, treating the INR with fluids such as plasma may lead to volume overload and may cause transfusion-related lung injury.
• Vitamin K should be administered routinely (5- 10 mg SC) as there is a decreased synthesis of clotting factors from the liver tissue.
• In high-risk procedures or clinically significant bleeding, clotting factor deficiencies should be treated.
• Bleeding mainly occurs from the capillaries, and is usually from mucosal surfaces of the stomach and lung.
• The mucosal surfaces of the gastrointestinal tract are the most common source of bleeding. So, the patient should receive stress ulcer prophylaxis with proton pump inhibitors or H2 blocking agents.

Hemodynamic and Metabolic Disturbances

• Decreased tissue perfusion leading to poor oxygenation and multiorgan failure is a major concern in acute liver failure.
• Patients should be resuscitated with normal saline first, then half normal saline containing 75 mEq/L of bicarbonate should be used in acidotic patients. This fluid should be administered before the use of vasopressors.
• For hypoglycemia, a dextrose solution should be used.
• If a patient is not responding to fluid or vasopressors, the infusion rate should be slowed down to prevent intense vasoconstriction causing ischemia of tissues.
• In patients progressing to acute renal failure, care must be taken to avoid NSAIDs and nephrotoxic agents. Dialysis should be used in a continuous mode rather than intermittent mode.
• Continuous monitoring of glucose and electrolytes is required as they may worsen the condition further.

Renal and pulmonary complications

• Renal failure may develop in more than 50% of patients with acute liver failure, more commonly in the elderly and in patients with acetaminophen induced acute liver failure.
• Pulmonary edema and infections can be seen with acute liver failure. Mechanical ventilation can be required to ensure adequate oxygenation.
• The positive end expiration pressure (PEEP) should be used with caution as it can aggravate cerebral edema in the acute liver failure patients.

Treatment for the Specific Underlying Cause

Acetaminophen Poisoning

• Acetylcysteine is used for acetaminophen poisoning for up to 72 hours after ingestion.
• Acetylcysteine can dramatically improve the outcome if administered within eight hours of acetaminophen ingestion.
• Acetylcysteine improves cerebral blood flow and increases transplant free survival in patients with stage 1 or 2 encephalopathy due to the hepatic failure of any cause.
• Patients with acute liver failure may not have a clear history of acetaminophen intake. Therefore, the threshold for administering acetylcysteine should be low and can also be administered in an acute liver failure of unknown etiology.

Mushroom Poisoning

• In mushroom poisoning, the early administration of activated charcoal is recommended as it is associated with improved survival.
• Aditional therapy include Penicillin G - 300,000 to 1 million units/kg/day

Drug Induced Hepatoxicity

• The drugs other than acetaminophen mostly cause acute liver failure by idiosyncratic reactions.
• No specific antidotes exist for these idiosyncratic drug reactions.
• Corticosteroids are not indicated unless a drug hypersensitivity or an autoimmune reaction is suspected.
• Discontinue all but essential medications.

Viral Hepatitis

• Supportive care
• Viral hepatitis A (and E) related acute liver failure must be treated with supportive care as no virus specific treatment has proven to be effective.
• Nucleoside analogs should be considered for hepatitis B associated acute liver failure and for prevention of post transplant recurrence.

Herpes Simplex Hepatitis

• Intravenous acyclovir

Wilson's Disease

• Plasmapheresis + D-penicillamine are used in Wilson's disease.
• Liver transplantaion.

Autoimmune Hepatitis

• Patients with autoimmune hepatitis are candidates for corticosteroid therapy.
• These patients should be considered for liver transplantation without delaying assessment to consider steroid therapy.

HELLP Syndrome

• Hepatic rupture or hemorrhage are fatal complications of HELLP syndrome requiring immediate resuscitation and intervention.
• Early diagnosis of the complications, and delivery of the baby helps in improving the outcome.
• Transplantation my be considered if there is postpartum deterioration.

Shock Liver

• Treatment of underlying cause of ischemia in shock liver is very important, and determines the prognosis of the condition.
• Transplantation is seldom indicated.

Budd-Chiari Syndrome

• Transplantation is considered after confirming the diagnosis Budd-Chiari syndrome and excluding malignancy for venous decompression.

Etiology	Diagnostic Indicators	Management Recommendations
Acetaminophen toxicity	History of acetaminophen intake (toxic dose >10 gm/day or >150 mg/kg) Acetaminophen in blood and/or urine Aminotransferase levels >3500 IU/L with low bilirubin levels, in the absence of apparent hypotension or cardiovascular collapse (suspected acetaminophen toxicity in the absence of a positive history because acetaminophen is the leading cause of ALF at least in the United States and Europe)	Activated charcoal: 1g/kg PO within 1 hour after drug ingestion (may be beneficial even when administered within 3-4 hours after ingestion) and prior to starting N-acetylcystine (NAC) . Nomogram (helps to determine the likelihood of serious liver damage but does not exclude possible toxicity) N-acetylcystine (NAC) 140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h x 17 doses or IV loading dose of 150 mg/kg in 5% dextrose over 15 minutes, thethen a maintenance dose 50 mg/kg IV over the next 4 hours and 100 mg/kg IV over the following 16 hours *Promptly begin NAC (beneficial even when administered <48 hours after drug ingestion) in all patients with impending or evolving liver injury due to acetaminophen.
Acute fatty liver of pregnancy/HELLP	Jaundice Hypertension Coagulopathy Thrombocytopenia Proteinuria Hypoglycemia Steatosis in liver imaging or biopsy	Early diagnosis and prompt delivery. Adequate supportive care. Consider transplantation for postpartum deterioration
Acute ischemic injury	History of cardiac arrest Any period of significant hypovolemia/hypotension, or severe CHF (hypotension is not documented always) Any associated renal dysfunction & muscle necrosis Elevated aminotransferase levels responding to fluid resuscitation	Adequate cardiovascular support.
Autoimmune	Positive serum autoantibodies (may be absent) Positive liver biopsy (confirms diagnosis when autoimmune hepatitis is suspected and autoantibodies are negative)	Prednisolone (start with 40-60 mg/day, especially in the presence of coagulopathy and mild hepatic encephalopathy) Consider transplantation and do not delay while awaiting response to steroid treatment
Budd-Chiari	Abdominal pain Ascites Hepatomegaly Blood tests positive for hypercoagulability Positive findings during liver imaging (CT, doppler USG, venography or magnetic resonance venography) (confirms diagnosis)	Liver transplantation (provided underlying malignancy is excluded)
Drug induced	History of hepatotoxic drug intake (usually idiosyncratic hepatotoxic drug intake within first 6 months after drug initiation; continuous usage of potentially hepatotoxic drug for more than 1 to 2 years is unlikely to cause de novo liver damage Detailed history taking (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year Determine ingredients of non-prescription medications whenever possible	Discontinue all but essential medications in the setting of possible drug hepatotoxicity. NAC (may be beneficial for ALF induced by drugs)
Malignant infiltration	Massive hepatomegaly Malignant infiltration in liver imaging or liver biopsy (confirms or excludes diagnosis)	Appropriate management of underlying malignancy Supportive care
Mushroom poisoning	History of recent mushroom intake Severe GI symptoms like nausea, vomiting and diarrhea within hours or a day of ingestion (suspected mushroom poisoning in the absence of a positive history)	Early gastric lavage and activated charcoal administration Penicillin G 300,000-1 million units/kg/day or Silibinin 30-40 mg/kg/day IV or PO, 3-4 days (silymarin in Europe and south America; milk thistle in north America) NAC Liver transplantation (the only lifesaving option) Fluid resuscitation (as needed)
Viral	Toxically appearing patients with skin lesions (HSV) Positive hepatitis virus serology HSV positive liver biopsy	Supportive treatment (no virus specific treatment proven to be effective) Nucleoside and nucleotide analogues (for HBV associated ALF) Acyclovir (5-10 mg/kg every 8 hours for at least 7 days for HSV or VZV)
Wilson's disease	Kayser- Fleischer rings (KF rings) Serum bilirubin >20 mg/dL, Bilirubin:alkaline phosphatase >2.0 Low serum ceruloplasmin Elevated serum & urine copper High copper levels in liver biopsy	Liver transplantation Dialysis or hemofiltration or plasmapheresis or plasma exchange
Intermediate etiology	Etiology undetermined after all evaluation.	Review drug and toxin intake history Transjugular biopsy (for further evaluation of possible mailgnancy, Wilson disease, autoimmune hepatitis and viral hepatitis)