Acute liver failure natural history, complications and prognosis
|
Acute liver failure Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Acute liver failure natural history, complications and prognosis On the Web |
|
American Roentgen Ray Society Images of Acute liver failure natural history, complications and prognosis |
|
FDA on Acute liver failure natural history, complications and prognosis |
|
CDC on Acute liver failure natural history, complications and prognosis |
|
Acute liver failure natural history, complications and prognosis in the news |
|
Blogs on Acute liver failure natural history, complications and prognosis |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Natural history, Complications and Prognosis
Complications
- Cerebral oedema and encephalopathy
In ALF, cerebral oedema leads to hepatic encephalopathy, coma, brain herniation and eventually death. Detection of encephalopathy is central to the diagnosis of ALF. It may vary from subtle defecit 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 oedema and grade IV encephalopathy. The pathogenesis remains unclear but is likely to be a consequence of several phenomenon. There is a build up of toxic substances like ammonia, mercaptan, endogenous benzodiazepines and serotonin/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[1][2][3].
Unfortunately, signs of elevated intracranial pressure such as papilloedema 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. Invasive intracranial pressure monitoring via subdural route is often recommended, however the risk of complications must be weighed against the possible benefit (1% fatal haemorrhage).[4] The aim is to maintain intracranial pressures below 25 mmHg, cerebral perfusion pressures above 50 mm Hg[3].
- Coagulopathy
Coagulopathy is another cardinal feature of ALF. Liver has central role in synthesis of almost all coagulation factors and some inhibitors of coagulation and fibrinolysis. Hepatocellular necrosis leads to impaired synthesis of many coagulation factors and their inhibitors. the former produces a prolongation in Prothrombin time which is widely used to monitor severity of hepatic injury.There is significant platelet dysfunction (with both quantitative and qualitative platelet defects). Progressive thrombocytopenia with loss of larger and more active platelet is almost universal. Thrombocytopenia with or without DIC increases risk of intracerebral bleeding[5].
- Renal failure
Renal 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 renal failure. Because of impaired production of urea, blood urea do not represent degree of renal impairment.
- Inflammation and infection
About 60% of all ALF patients fulfil the criteria for systemic inflammatory syndrome irrespective of presence or absence of infection[6]. This often contributes towards multi organ failure. Impaired host defence mechanism due to impaired opsonisation, chemotaxis and intracellular killing substantially increase risk of sepsis. Bacterial sepsis mostly due to gram positive organisms and fungal sepsis are observed in up to 80% and 30% patients respectively[5].
- Metabolic derangements
Hyponatraemia is almost universal finding due to water retention and shift in intracellular sodium transport from inhibition of Na/K ATPase. Hypoglycaemia (due to depleted hepatic glycogen store and hyperinsulinaemia), hypokalaemia, hypophosphataemia and Metabolic alkalosis are often present independent of renal function. Lactic acidosis occurs predominantly in paracetamol overdose.
- Haemodynamic and cardio-respiratory compromise
Hyperdynamic circulation with peripheral vasodilatation from low systemic vascular resistance leads to hypotension. There is a compensatory increase in cardiac output. Adrenal insufficiency has been documented in 60% of ALF and is likely to contribute in haemodynamic compromise[7]. There is also abnormal oxygen transport and utilization. Although delivery of oxygen to the tissues is adequate, there is a decrease in tissue oxygen uptake, resulting in tissue hypoxia and lactic acidosis[8].
Pulmonary complications occur in up to 50% patients[9]. Severe lung injury and hypoxemia result in high mortality. Most cases of severe lung injury is due to ARDS with or withoutsepsis. Pulmonary haemorrhage, pleural effusions, atelectasis, and intrapulmonary shunts also contribute to respiratory difficulty.
Prognosis
Historically mortality has been unacceptably high, being in excess of 80%[10]. 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%[11].
Several prognostic scoring systems have been devised to predict mortality and to identify who will require early liver transplant. These include kings college hospital criteria, MELD score, APACHE II and Clichy criteria.
References
- ↑ Hazell AS, Butterworth RF (1999). "Hepatic encephalopathy: An update of pathophysiologic mechanisms". Proc. Soc. Exp. Biol. Med. 222 (2): 99–112. PMID 10564534.
- ↑ Larsen FS, Wendon J (2002). "Brain edema in liver failure: basic physiologic principles and management". Liver Transpl. 8 (11): 983–9. doi:10.1053/jlts.2002.35779. PMID 12424710.
- ↑ 3.0 3.1
- ↑ Armstrong IR, Pollok A, Lee A (1993). "Complications of intracranial pressure monitoring in fulminant hepatic failure". Lancet. 341 (8846): 690–1. PMID 8095592.
- ↑ 5.0 5.1 Gimson AE (1996). "Fulminant and late onset hepatic failure". British journal of anaesthesia. 77 (1): 90–8. PMID 8703634.
- ↑ Schmidt LE, Larsen FS (2006). "hyperlactatemia". Crit. Care Med. 34 (2): 337–43. PMID 16424712.
- ↑ Harry R, Auzinger G, Wendon J (2002). "The clinical importance of adrenal insufficiency in acute hepatic dysfunction". Hepatology. 36 (2): 395–402. doi:10.1053/jhep.2002.34514. PMID 12143048.
- ↑ Bihari D, Gimson AE, Waterson M, Williams R (1985). "Tissue hypoxia during fulminant hepatic failure". Crit. Care Med. 13 (12): 1034–9. PMID 3933911.
- ↑ Trewby PN, Warren R, Contini S; et al. (1978). "Incidence and pathophysiology of pulmonary edema in fulminant hepatic failure". Gastroenterology. 74 (5 Pt 1): 859–65. PMID 346431.
- ↑ Rakela J, Lange SM, Ludwig J, Baldus WP (1985). "Fulminant hepatitis: Mayo Clinic experience with 34 cases". Mayo Clin. Proc. 60 (5): 289–92. PMID 3921780.
- ↑ Ostapowicz G, Fontana RJ, Schiødt FV; et al. (2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States". Ann. Intern. Med. 137 (12): 947–54. PMID 12484709.