Hepatic failure

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

Overview

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

Historical Perspective

• The original definition of Acute liver failure by Trey and Davidson was in 1959.
• In the late 1980s and early 1990s, more terminologies of Acute liver failure proposed in.
• Term of Acute-on-chronic Liver failure suggested by Jalan and willimas in 2002.

Classification

Three forms are recognized:

• Acute liver failure -loss of liver function that occurs rapidly. The most reliable signs of severe acute liver injury are prolonged international normalized ratio ([INR] ≥ 1.5) and any degree of hepatic encephalopathy, in patients without preexisting liver disease and with an illness duration less than 24 weeks.
  • Three types are defined: "Hyperacute " liver failure is said to be present if jaundice to encephalopathy interval is 7 days or less, "Acute" as 8-28 days, "sub-acute" 29days to 12 weeks, "late -onset" 12 -24 weeks.

• Chronic liver failure - Hepatic encephalopathy develps after 6 months and it usually occurs in the context of cirrhosis, itself potentially the result of many possible causes, such as excessive alcohol intake, hepatitis B or C, autoimmune, hereditary and metabolic causes (such as iron or copper overload or non-alcoholic fatty liver disease).Encephalopathy develops after 6 months.

• Acute on Chronic Liver Failure - when acute hepatic decompensation observed in patients with preexisting chronic liver disease characterized by one or more extrahepatic organ failures with a significantly increased risk of death.

Pathophysiology

• The pathophysiology depends on the etiology of the Acute liver failure.
• Most cases of Acute liver failure (except acute fatty liver of pregnancy and Reye syndrome) will have massive hepatocyte necrosis and/or apoptosis leading to liver failure. Hepatocyte necrosis occurs due to ATP depletion causing cellular swelling and cell membrane disruption.

• 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.

• Chronic liver failure is the result of Cirrhosis which is is an advanced stage of liver fibrosis that is accompanied by distortion of the hepatic vasculature.

Causes

Causes for Acute liver failure:

Category	Etiology of Acute liver failure
Viruses	Hepatitis A virus Hepatitis B virus ± delta virus Hepatitis E virus Herpes simplex virus Varicella-zoster virus Cytomegalovirus Epstein-Barr virus Human herpesvirus-6 Adenovirus, Coxsackie B virus, hemorrhagic fever virus
Drugs	Beractant Carfilzomib Caspofungin acetate Cefadroxil Ceftazidime Chlordiazepoxide Dactinomycin diclofenac (patch) Didanosine Diflunisal Efavirenz Fulvestrant gadoxetate Gemcitabine Indinavir Interferon gamma Ixabepilone Meropenem Micafungin sodium Nitisinone Oxaprozin Oxazepam Sorafenib Sulfasalazine Trovafloxacin mesylate
Metabolic diseases	Wilson disease Reye syndrome Acute fatty liver of pregnancy
Toxins	Amanita phalloides toxin Bacillus cereus toxin
Vascular diseases	Right heart failure Budd-Chiari syndrome Ischemic hepatitis
Malignant Infiltration	Metastatic breast cancer Lymphoma
Autoimmune disease	Autoimmune hepatitis

• Chronic liver failure usually occurs in the context of cirrhosis. The most common causes are hepatitis and other viruses, and alcohol abuse.

Differential Diagnosis

• Acute liver failure is a distinctive syndrome that is not confused with other conditions. The major differential diagnosis is in the cause of acute liver failure, whether viral (hepatitis A, B, C, D or E), autoimmune, metabolic (Wilson disease), drug-induced or idiopathic.

Epidemiology and Demographics

• Acute liver failure affects approximately 2,000–3,000 Americans each year.
• Chronic liver disease and Cirrhosis are the 12(th) leading cause of death in the United States.
• Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates.

Natural History, Complications and Prognosis

Natural History

• Acute liver failure (Hyperacute and subacute) is a rare but serious clinical syndrome characterized by the sudden loss of hepatic function in a person without evidence of preexisting liver disease (Exceptions to this definition include Wilson's disease, reactivation of hepatitis B virus infection, and autoimmune hepatitis).

• Signs and symptoms of acute liver failure may include:
  • Sudden jaundice, Hepatic encephalopathy( Mental confusion, difficulty concentrating and disorientation), Muscle tremors, Ascites, Right upper quadrant pain and Tenderness, Abdominal distention, Nausea, Vomiting, malaise, Bleeding easily, Hematemesis, Melena, Tachycardia, Hypotension, Brain herniation, Coma

Complications

• Neurological complications, Abnormal hemostasis, and bleeding complications, Multiorgan failure,infection.

Prognosis

• 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.

Diagnosis

History and Symptoms

• Obtain a detailed medical history from the patient and/or family, including the first onset of the symptom(s); all medications used over the last 6 months, including prescription medications, over-the-counter agents, herbal supplements, wild mushrooms, or other alternatives/complementary therapies;
• Obtain a detailed history of current and prior substance use; current or prior depression (including assessment of suicidality), anxiety, psychosis, or other mental illness; viral prodrome; and recent travel.

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:

Liver function tests Complete blood count with differential Prothrombin time/international normalized ratio Comprehensive metabolic panel Magnesium level Phosphorus level Amylase and lipase levels Toxicology screen (including acetaminophen and salicylate levels) Factor V level a-fetoprotein level Arterial lactate level Arterial blood gas level Arterial ammonia level (in patients with stage 2 or greater hepatic encephalopathy) Viral hepatitis serologies: Hepatitis B surface antigen (hepatitis delta immunoglobulin (Ig)G if the surface antigen is positive), Hepatitis B core IgM, Hepatitis A IgM, Hepatitis E IgG (if positive, ribonucleic acid testing should be ordered in select patients), Hepatitis C antibody HIV antibody Blood and urine cultures Urinalysis Blood type Serum pregnancy test (for patients with childbearing potential) Thromboelastogram Diagnostic transjugular liver biopsy

Imaging

• Abdominal ultrasound with Doppler to confirm portal and hepatic vein patency
• Non-contrast computed tomography (CT) scan of the head for patients with Hepatic encephalopathy

Treatment

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

• 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

• Herpes simplex virus infectionAcyclovir: 10 mg/kg IV every 8 hours (using IBW) adjusted for kidney function

• Cytomegalovirus infection Ganciclovir: 5 mg/kg IV every 12 hours (using IBW) adjusted for kidney function
• Autoimmune hepatitis Methylprednisolone: 60 mg/day IV Kessler WR, et al73
• Hepatitis B virus infection Entecavir (taken on an empty stomach) or tenofovir at standard renal adjusted doses
• Acute fatty liver of pregnancy /HELLP Delivery of the fetus

• Treatment of Hepatic Encephalopathy:

• 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.

Contraindicated medications

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

• Carvedilol
• Conjugated estrogens/bazedoxifene
• Diclofenamide
• Dronedarone
• Nebivolol
• Rosuvastatin
• Simvastatin
• Spironolactone
• Sulfamethoxazole/Trimethoprim
• Doxorubicin Hydrochloride
• Tipranavir

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

See Also

• Hepato-biliary diseases
• Hepatitis

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