Acute liver failure

Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complications are hepatic encephalopathy and impaired protein synthesis (as measured by the levels of serum albumin and the prothrombin time in the blood). The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes. 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. In ALF, hepatic encephalopathy leads to cerebral edema, coma, brain herniation, and eventually death. Detection of encephalopathy is central to the diagnosis of ALF. It may vary from subtle deficit in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV). Patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral edema and grade IV encephalopathy. The pathogenesis remains unclear, but is likely to be a consequence of several phenomena. There is a buildup of toxic substances like ammonia, mercaptan, serotonin and tryptophan in the brain. This affects neurotransmitter level and neuroreceptor activation. Autoregulation of cerebral blood flow is impaired, and is associated with anaerobic glycolysis and oxidative stress. Neuronal cell astrocytes are susceptible to these changes, and they swell up, resulting in increased intracranial pressure. Inflammatory mediators also play important role. Unfortunately, signs of elevated intracranial pressure, such as papilledema and loss of pupillary reflexes, are not reliable, and occur late in the disease process. CT imaging of the brain is also unhelpful in detecting early cerebral oedema, but is often performed to rule out intra-cerebral bleeding.