Hepatic Failure
- Article Author:
- Daniella Lopes
- Article Editor:
- Hrishikesh Samant
- Updated:
- 10/15/2020 8:42:32 AM
- For CME on this topic:
- Hepatic Failure CME
- PubMed Link:
- Hepatic Failure
Introduction
Acute liver failure (ALF) is a complex clinical syndrome characterized by elevated liver biochemistry, coagulopathy, and hepatic encephalopathy without underlying chronic liver disease. The most frequently used classification is the one that O'Grady and collaborators proposed which divides liver failure into 3 categories based on the interval between the development of jaundice and the onset of encephalopathy as hyperacute liver failure (within 7 days), acute (interval of 1 to 4 weeks ) and subacute (5 to 12 weeks).[1][2][3]
Etiology
The most common etiology of acute liver failure in the U.S. and Western Europe is drug-induced liver injury, while in developing countries it is still viral hepatitis. In the United States, about 2800 cases per year of ALF are identified, with acetaminophen being the main cause.[4] Regarding viral hepatitis, hepatitis A and hepatitis E are frequent causes. Over 1.5 million hepatitis A infections occur worldwide, but less than 1% of them progress to ALF. Better sanitary conditions and the use of the hepatitis A vaccine has led to a decrease in the incidence of acute hepatitis A in developed countries.[5] Hepatitis B is responsible for most of the severe viral ALF cases. Hepatitis C does not appear to cause acute liver failure. Hepatitis D infection can lead to acute liver failure in patients with hepatitis B virus co-infection. Hepatitis E is a rare cause of ALF in the USA but represents around a 20 to 40% of ALF cases in developing countries.[6] Herpes simplex virus (HSV) infection is an uncommon cause of ALF. However, if untreated it carries a mortality rate of 80%. The most commonly affected are immunocompromised and pregnant women. Epstein-Barr virus-related ALF is very rare (less than 1% of all ALF cases).[7][8] Cytomegalovirus is the causal agent of a variety of disease syndromes, including hepatitis.[9] The incidence is low, 19 in 100000 in the general population. Amanita phalloides is the mushroom that most frequently causes hepatotoxicity. Another frequent cause in patients in intensive care is ischemic hepatitis, which occurs when there is a reduction in blood flow and consequently hypoperfusion of hepatocytes leading to liver cell injury. ALF can also result from specific liver diseases of pregnancy as acute fatty liver of pregnancy and HELLP syndrome. Also, Budd-Chiari syndrome, malignancy, and Wilson’s disease can lead to ALF.[10][11]
Epidemiology
The annual incidence of acute liver failure is less than 10 cases per million population in the developed world. In the United States, there are about 2800 cases of ALF per year. The condition is more frequent in developing countries and often affects young people.[12]
Pathophysiology
The pathophysiology will depend on the etiology of acute liver failure. Liver failure occurs due to massive hepatocyte necrosis and/or apoptosis. The mechanism of necrosis characteristically demonstrates ATP depletion, cerebral edema, mitochondrial depolarization, and cell membrane rupture. However, in apoptosis, there is a preservation of ATP with activation of caspases, chromatin condensation, DNA degradation and reabsorption of cellular components.[13]
Histopathology
If the initial evaluation involves a thorough history and examination, a liver biopsy is rarely necessary (usually a transjugular technique is used).[1]
History and Physical
The initial clinical presentation will depend on the etiology of acute liver failure and the time of evolution from the onset of the disease. Signs and symptoms of acute liver failure may include[14]:
- Jaundice
- Pain in the upper right abdomen
- Abdominal swelling
- Nausea
- Vomiting
- Malaise
- Dehydration
Evaluation
The diagnosis of acute liver failure should start with the history and physical examination followed by laboratories tests and abdominal imaging.
History of prior episodes of jaundice, medication and alcohol use, family history of liver disease, risk factors for acute viral hepatitis are clinically relevant.
Laboratory evaluation is required to establish the cause and evaluate the severity. It should include liver blood tests, INR, renal function, metabolic panel, blood count, viral hepatitis serologies and HIV serology, toxicology screen and acetaminophen level, autoimmune markers and arterial blood gas. Ceruloplasmin level should be required when Wilson disease is suspected. In patients with acute or chronic hepatitis, HBV anti-hepatitis D virus antibodies should be requested. In addition, anti-hepatitis E virus antibodies ordered when there is a history of travel to endemic areas. Abdominal imaging evaluation includes studies ultrasonography to rule out underlying chronic liver disease/cirrhosis.[15]
Treatment / Management
Acute liver failure is a complex syndrome, and these patients often succumb to its complications. Patient must be managed in the intensive care unit and transferred to a center with a liver transplant facilities. Treatment should commence as soon as possible along with the diagnostic workup. The therapy must address the underlying cause; for example, administer N-acetylcysteine (NAC) for acetaminophen poisoning, antivirals for acute hepatitis B, steroids for autoimmune flare-ups, penicillamine in Wilson disease, and penicillin in mushroom poisoning.[12] NAC has also shown benefit in non-acetaminophen acute liver failure. The mainstay of treatment of ALF is to prevent cerebral edema regardless of etiology; to achieve this one can employ head elevation, mannitol, hyperventilation, and cerebroprotective measures. Few patients need monitoring of intracranial pressure (ICP) with pressure monitors. Other complications include metabolic acidosis, coagulopathy, hypoglycemia, and renal failure. Coagulopathy should only be corrected if there is active bleeding or the patient needs an invasive procedure. In a patient with renal failure, the institution of early renal replacement therapy is necessary. Hypoglycemia is detrimental in patients with ALF and should be prevented by dextrose infusion. Role of prophylactic antibiotics is still controversial. The management of ALF is with aggressive supportive measures to avoid multiorgan failure until there is recovery or liver transplant.
Differential Diagnosis
- Acute fatty liver of pregnancy
- Amanita phalloides mushroom poisoning
- Acetaminophen poisoning
- Bacillus cereus toxin
- Fructose intolerance
- Galactosemia
- HELLP(hemolysis, elevated liver enzymes, low platelets) syndrome of pregnancy
- Haemorrhage viruses (Ebola virus, Lassa virus, Marburg virus)
- Idiopathic drug reaction
- Neonatal iron storage diseases
- Tyrosinemia
Prognosis
Survival has improved over time with advances in transplant, as identified in an American registry. In 2012 a European registry showed current rates of survival after transplantation of 79% at 1 year and 72% at 5 years. Several clinical factors have prognostic significance in ALF. The presence of encephalopathy is a key indicator, with special attention given to the patient's age and the severity of liver injury, as evaluated by the presence of coagulopathy or jaundice. The most commonly used system for prognosis of ALF prognosis is The King's College Criteria.[16]
Complications
- Cerebral edema: Encephalopathy: Is usually classified based on severity from grade 1 to grade 4.
- Grade 1: change of mood, inappropriate behavior, attention deficit, difficulty in elaborating ideas, irritability, sleep disordered.
- Grade 2: temporary disorientation, lethargy or asterixis.
- Grade 3: marked confusion, unintelligible speech, somnolence.
- Grade 4: coma, unresponsive to verbal or pain stimulus.
- Intracranial pressure above 20 mm Hg usually correlates with cerebral edema. It can progress to intracranial hypertension. It is present in 75% to 80% of patients with ALF and grade 4 hepatic encephalopathy. The first signs suggestive of intracranial hypertension are systolic hypertension and bradycardia.
- Coagulopathy: The most common site of bleeding is from the upper gastrointestinal tract.
- Hematologic manifestations: Hepatitis-associated aplastic anemia (HAA) is a rare but life-threatening condition.
- Infection: Due to a decrease in immunity, ALF patients predispose to multiple infections, which is the leading cause of mortality. Bacterial infections are responsible for 80%, and about 20 to 30% are fungal infections. When ascites is present, unexplained fever and leukocytosis are indications for a diagnostic paracentesis. Prophylactic antibiotics are not a current recommendation.
- Renal failure: Acute renal failure is frequently a complication and is usually the result of hemodynamic alterations. It represents a poor prognosis. The most critical associated entities are hypovolemia, low systemic vascular resistance, acute tubular necrosis, gastrointestinal blood loss, and hepatorenal syndrome.
- Nutritional and metabolic: Due to the high catabolic state of ALF, maintaining adequate nutrition is vital. Early enteral or parenteral feeds should be initiated. Electrolyte abnormalities such as hyponatremia, hypokalemia, hypophosphatemia, hypomagnesemia and acid-base imbalances such as respiratory acidosis are frequent. Hyponatremia is an indicator of poor prognosis.
- Pulmonary complications: Pulmonary edema, pneumonia, and tracheobronchitis are the main complications.[17]
Deterrence and Patient Education
- Hepatitis B and A vaccination
- Avoid self-medication
- Do not eat wild mushrooms
- If receiving a tattoo or piercing, use sterilized material
Pearls and Other Issues
Bioartificial liver systems: Various devices have been created to replace or support liver function. They function as a bridge to transplant. However, these are still in the clinical trial phase.[18]
The use of transplanted hepatocytes infused in the peritoneal cavity or the splenic or hepatic portal system is also under investigation.[19]
High-volume plasma exchange (exchange of 8 to 15% of ideal body weight with fresh frozen plasma), is also treatment under study as a liver support system.
Enhancing Healthcare Team Outcomes
Orthotopic liver transplantation remains the only definitive therapy for patients with irreversible liver injury, with a 5-year survival of more than 70%. The majority of deaths are secondary to neurological complications or sepsis and occur in the first 3 months after transplantation. In Asia, living-related liver transplant (LDLT) is common, with reduced waiting time, and offering better outcomes compared to transplant from a deceased donor. Data from Asia have shown right lobe LDLT improves survival in ALF patients. More frequently, in acute cases, ABO-incompatible grafts are being used. However, in these patients, the graft survival is low (30 to 60% 1-year survival). Auxiliary liver transplant retains the recipient's liver and uses a partial lobe of the donor's liver as temporary liver support. Auxiliary liver transplant has a survival of 60 to 65%.[20]