Acute liver failure
Acute liver failure | |
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Liver transplant |
Acute liver failure is the appearance of severe complications rapidly after the first signs (such as
Signs and symptoms
The main features of acute liver failure are rapid-onset jaundice, weakness, and eventually, changes in mental status that can begin as mild confusion but progress to coma, known as hepatic encephalopathy.[3]
Encephalopathy and cerebral edema
In ALF,
Unfortunately, signs of elevated
Coagulopathy
Kidney failure
Kidney failure is common, present in more than 50% of ALF patients, either due to original insult such as paracetamol resulting in acute tubular necrosis or from hyperdynamic circulation leading to hepatorenal syndrome or functional kidney failure. Because of impaired production of urea, blood urea does not represent the degree of kidney impairment.[citation needed]
Inflammation and infection
About 60% of all ALF patients fulfil the criteria for
Metabolic derangements
Haemodynamic and cardio-respiratory compromise
Late pregnancy
In late pregnancy liver function decreases significantly, which can be easily monitored by blood tests. Early clinical manifestations of ALF in late pregnancy include hypodynamia, decrease in appetite, dark amber urine, deep jaundice, nausea, vomiting, and abdominal distention.[12] Among patients whose deaths were attributed to ALF in late pregnancy, the majority had experienced vaginal deliveries.[13]
Causes
Common causes for acute liver failure are
Pathophysiology
In the majority of acute liver failure (ALF) there is widespread hepatocellular necrosis beginning in the
Zone 1 (periportal) occurs in phosphorus poisoning or eclampsia. Zone 2 (mid-zonal), although rare, is seen in yellow fever. Zone 3 (centrilobular) occurs with ischemic injury, toxic effects, carbon tetrachloride exposure, or chloroform ingestion. In acute acetaminophen overdose,
Diagnosis
All patients with clinical or laboratory evidence of moderate to severe acute hepatitis should have an immediate measurement of prothrombin time and careful evaluation of mental status. If the prothrombin time is prolonged by ≈ 4–6 seconds or more (INR ≥ 1.5), and there is any evidence of altered sensorium, the diagnosis of ALF should be strongly suspected, and hospital admission is mandatory.[22] Initial laboratory examination must be extensive in order to evaluate both the etiology and severity.
- Initial laboratory analysis[22]
- Prothrombin time/INR
- Complete blood count
- Chemistries
- Liver function test:
- Creatinine, urea/blood urea nitrogen, sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate
- Glucose
- Amylase and lipase
- Arterial blood gas, lactate
- Blood type and screen
- Paracetamol (acetaminophen) level, toxicology screen
- anti-HBcIgM, anti-HCV
- LKMA, immunoglobulinlevels
- Ceruloplasmin level (when Wilson's disease suspected)
- Pregnancy test (females)
- Ammonia (arterial if possible)
- transplantation)
History taking should include a careful review of possible exposures to viral infection and drugs or other toxins. From history and clinical examination, the possibility of underlying chronic disease should be ruled out as it may require different management.
A
Definition
Acute liver failure is defined as "the rapid development of hepatocellular dysfunction, specifically coagulopathy and mental status changes (encephalopathy) in a patient without known prior liver disease".[23]page 1557
The diagnosis of acute liver failure is based on physical exam, laboratory findings, patient history, and past medical history to establish mental status changes, coagulopathy, rapidity of onset, and absence of known prior liver disease respectively.[23]page 1557
The exact definition of "rapid" is somewhat questionable, and different sub-divisions exist which are based on the time from onset of first hepatic symptoms to onset of encephalopathy. One scheme defines "acute hepatic failure" as the development of encephalopathy within 26 weeks of the onset of any hepatic symptoms. This is sub-divided into "fulminant hepatic failure", which requires onset of encephalopathy within 8 weeks, and "subfulminant", which describes onset of encephalopathy after 8 weeks but before 26 weeks.[24] Another scheme defines "hyperacute" as onset within 7 days, "acute" as onset between 7 and 28 days, and "subacute" as onset between 28 days and 24 weeks.[23]page 1557
Treatment
King's College Hospital criteria for liver transplantation in acute liver failure[25] |
Patients with paracetamol toxicity pH < 7.3 or serum creatinine level > 3.4 mg/dL (> 300 μmol/L)if in grade III or IV encephalopathy |
Other patients Prothrombin time > 100 seconds or
|
General concerns
Because ALF often involves the rapid deterioration of mental status and the potential for multiorgan failure, patients should be managed in the
Neurologic complications
Patients with grade I–II encephalopathy should be transferred to a liver transplant facility and listed for transplantation. Consider a brain computed tomography (CT) scan to rule out other causes of altered or impaired mental status. Stimulation and overhydration can cause elevations in intracranial pressure (ICP) and should be avoided. Unmanageable agitation may be treated with short-acting benzodiazepines in small doses. Lactulose can be considered at this stage. A preliminary report from the ALFSG on 117 patients suggests that use of lactulose in the first 7 days after diagnosis is associated with a small increase in survival time, but with no difference in severity of encephalopathy or in the overall outcome. For patients who progress to grade III–IV encephalopathy, intubation for airway protection is generally required. Many centers use propofol for sedation because it may reduce cerebral blood. The head of the bed should be elevated to 30 degrees, and electrolytes, blood gasses, glucose, and neurologic status monitored frequently.[28][29]
Cardiovascular complications
Increased cardiac output and low systemic vascular resistance are characteristic of ALF. Pulmonary artery catheterization should be considered. Hypotension should be treated preferentially with fluids, but systemic vasopressor support with agents such as epinephrine, norepinephrine, or dopamine should be used if fluid replacement fails to maintain mean arterial pressure of 50–60 mm Hg. Vasoconstrictive agents (especially vasopressin) should be avoided.[30]
Pulmonary complications
Pulmonary edema and pulmonary infections are commonly seen in patients with ALF. Mechanical ventilation may be required. However, positive end-expiratory pressure can worsen cerebral edema.[31]
Coagulopathy and gastrointestinal bleeding
Impaired liver synthesis of clotting factors, low-grade fibrinolysis, and intravascular coagulation are typical of ALF. Thrombocytopenia is common and may also be dysfunctional. Replacement therapy is recommended only in the setting of bleeding or prior to an invasive procedure. Vitamin K can be given to treat an abnormal prothrombin time, regardless of whether there is poor nutritional status. Administration of recombinant factor VIIa has shown promise; however, this treatment approach requires further study. The use of gastrointestinal hemorrhage prophylaxis with a
Nutrition, electrolytes, and metabolic derangements
In patients with grade I or II encephalopathy, enteral feeding should be initiated early. Parenteral nutrition should be used only if enteral feeding is contraindicated as it increases the risk of infection. Severe restriction of protein is not beneficial; 60 g/day of protein is generally reasonable. Fluid replacement with colloid (e.g. albumin) is preferred rather than crystalloid (e.g. saline); all solutions should contain dextrose to maintain euglycemia. Multiple electrolyte abnormalities are common in ALF. Correction of hypokalemia is essential as hypokalemia increases the kidneys' ammonia production, potentially exacerbating encephalopathy. Hypophosphatemia is especially common in patients with acetaminophen-induced ALF and in those with intact renal function. Hypoglycemia occurs in many patients with ALF and is often due to depletion of hepatic glycogen stores and impaired gluconeogenesis. Plasma glucose concentration should be monitored and hypertonic glucose administered as needed.[33]
Infection
Bacterial and fungal infections are common in ALF, with one study demonstrating culture-proven infection in 80% of ALF patients. Defective cellular and humoral immunity as well as presence of indwelling catheters, coma, broad-spectrum antibiotics, and medications that suppress immunity all predispose to infection. Localizing symptoms of infection such as fever and sputum production are frequently absent and the only clues to an underlying infectious process may be worsening of encephalopathy or renal function. There must be a low threshold for obtaining frequent cultures (blood, urine, and sputum), chest radiographs, and paracentesis. Bacteria that enter through the skin, such as streptococci and staphylococci, tend to predominate. Aggressive surveillance is essential as prophylactic antibiotics have shown little benefit. Fungal infections, particularly in the setting of broad-spectrum antibiotics, are also common, and disseminated fungemia is a poor prognostic sign.[34]
Liver transplantation
The advent of transplantation has changed survival from as low as 15% in the pretransplant era to more than 60% today. Liver transplantation is indicated for many patients with ALF, and survival rates of 56–90% can be achieved. In addition to transplantation, better critical care and the trend toward more benign causes, such as acetaminophen, all contribute to improved survival rates. Spontaneous survival is now around 40%. The application of transplantation among patients with ALF remains low, suggesting that the full potential of this modality may not be realized. Timely availability of an allograft is one of the major factors determining transplant outcomes. In the largest U.S. study, only 29% of patients received a liver graft, while 10% of the overall group (one fourth of patients listed for transplantation) died on the waiting list. Other series have reported death rates of those listed for transplant as high as 40%. In the ALFSG, the transplantation rate was higher in the groups with lower short-term spontaneous survival, making overall survival similar in all groups: acetaminophen, 73%; drug induced, 70%; indeterminate group, 64%; and other causes, 61%. Causes of death for the 101 patients who died within the 3-week period included cerebral edema, multiorgan failure, sepsis, cardiac arrhythmia or arrest and respiratory failure. The median time to death after admission was 5 days.[34]
Acetylcysteine
Intravenous
Prognosis
Historically mortality has been high, being in excess of 80%.[37] In recent years the advent of liver transplantation and multidisciplinary intensive care support have improved survival significantly. At present overall short-term survival with transplant is more than 65%.[38]
Several prognostic scoring systems have been devised to predict mortality and to identify who will require an early liver transplant. These include
Terminology
To date, no universally accepted nomenclature has been adopted. Trey and Davidson introduced the phrase fulminant hepatic failure in 1970, which they described as a "... potentially reversible condition, the consequence of severe liver injury, with an onset of encephalopathy within 8 weeks of the appearance of the first symptoms and in the absence of pre-existing liver disease".[41] Later, it was suggested that the term fulminant should be confined to patients who develop jaundice to encephalopathy within 2 weeks. Phrases subfulminant hepatic failure and late onset hepatic failure were coined for onset between 2 weeks to 3 months and for 8 weeks to 24 weeks, respectively.[42][43] The umbrella phrase of acute liver failure was proposed by King's College group, which has been adopted in this article. Paradoxically, in this classification, the best prognosis is in the hyperacute group.[44]
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