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Acute liver failure



Acute liver failure
Classification & external resources
ICD-10 K72.9
MeSH D017114

Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease (such as jaundice), 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.[1] It reflects the fact that the pace of disease evolution strongly influence prognosis. Underlying aetiology is the other significant determinant of outcome.[2]

Additional recommended knowledge

Contents

Causes

Common causes for acute liver failure are paracetamol (acetaminophen) overdose, idiosyncratic reaction to medication (e.g. tetracycline, troglitazone), excessive alcohol intake (severe alcoholic hepatitis), viral hepatitis (hepatitis A or B - it is extremely uncommon in hepatitis C), acute fatty liver of pregnancy, and idiopathic (without an obvious cause). Reye syndrome is acute liver failure in a child with a viral infection (e.g. chickenpox); it appears that aspirin use may play a significant role. Wilson's disease (hereditary copper accumulation) may infrequently present with acute liver failure.

Pathology

In the majority of acute liver failure (ALF) there is widespread hepatocellular necrosis beginning in the centrizonal distribution and progressing towards portal tracts. The degree of parenchymal inflammation is variable and is proportional to duration of disease[3][4].

Clinical consequence

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[5][6][2].

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).[7] The aim is to maintain intracranial pressures below 25 mmHg, cerebral perfusion pressures above 50 mm Hg[2].

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[4].

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[8]. 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[4].

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[9]. 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[10].

Pulmonary complications occur in up to 50% patients[11]. Severe lung injury and hypoxemia result in high mortality. Most cases of severe lung injury is due to ARDS with or without sepsis. Pulmonary haemorrhage, pleural effusions, atelectasis, and intrapulmonary shunts also contribute to respiratory difficulty.

Evaluation

All patients with clinical or laboratory evidence of moderate to severe acute hepatitis should have 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[12]. Initial laboratory examination must be extensive in order to evaluate both the aetiology and severity.

Initial laboratory analysis[12]

History taking should include careful review of possible exposures to viral infection and drugs or other toxins. From history and clinical examination possibility of underlying chronic disease should be ruled out as it may have different management.

A liver biopsy done via the transjugular route because of coagulopathy is not usually necessary other than in occasional malignancies. As the evaluation continues, several important decisions have to be made such as whether to admit the patient to an ICU, or whether to transfer the patient to a transplant facility. Consultation with the transplant centre as early as possible is critical due to possibility of rapid progression of ALF.

Treatment

King's College Hospital criteria

for liver transplantation in acute liver failure[13]

Patients with paracetamol toxicity

pH <7.3 or
Prothrombin time >100 seconds and
serum creatinine level >3.4 mg/dL (>300 μmol/l)
if in grade III or IV encephalopathy

Other patients

Prothrombin time >100 seconds or
Three of the following variables:

  • Age <10 yr or >40 yr
  • Cause:
    • non-A, non-B hepatitis
    • halothane hepatitis
    • idiosyncratic drug reaction
  • Duration of jaundice before encephalopathy >7 days
  • prothrombin time >50 seconds
  • Serum bilirubin level >17.6 mg/dL (>300 μmol/l)

Treatment involves admission to hospital; often intensive care unit admission or very close observation are required. Supportive treatment is with adequate nutrition, optimalisation of the fluid balance, mechanical ventilation and intracranial pressure monitoring (in severe encephalopathy), and treatment aimed at removing the underlying cause (such as acetylcysteine for paracetamol poisoning). Other supportive measures may include the drainage of ascites.

While many people who develop acute liver failure recover with supportive treatment, liver transplantation is often required in people who continue to deteriorate or have adverse prognostic factors.

"Liver dialysis" (various measures to replace normal liver function) is evolving as a treatment modality and is gradually being introduced in the care of patients with liver failure.

Prognosis

Historically mortality has been unacceptably high, being in excess of 80%[14]. 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%[15].

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.

Terminology

To date no universally accepted nomenclature has been adopted. Trey and Davidson introduced the term fulminant hepatic failure in 1970 to describe "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"[16]. Later it was suggested that the term fulminant should be confined to patients who develop jaundice to encephalopathy within 2 weeks. Terms 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[17][18]. The umbrella term of acute liver failure was proposed by Kings college group which has been adopted in this article. Paradoxically in this classification the best prognosis is in the hyperacute group[19].

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References

  1. ^ O'Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993;342:273-5. PMID 8101303.
  2. ^ a b c O'Grady JG (2005). "Acute liver failure". Postgraduate medical journal 81 (953): 148-54. doi:10.1136/pgmj.2004.026005. PMID 15749789.
  3. ^ Boyer JL, Klatskin G (1970). "Pattern of necrosis in acute viral hepatitis. Prognostic value of bridging (subacute hepatic necrosis)". N. Engl. J. Med. 283 (20): 1063-71. PMID 4319402.
  4. ^ a b c Gimson AE (1996). "Fulminant and late onset hepatic failure". British journal of anaesthesia 77 (1): 90-8. PMID 8703634.
  5. ^ Hazell AS, Butterworth RF (1999). "Hepatic encephalopathy: An update of pathophysiologic mechanisms". Proc. Soc. Exp. Biol. Med. 222 (2): 99-112. PMID 10564534.
  6. ^ 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.
  7. ^ Armstrong IR, Pollok A, Lee A (1993). "Complications of intracranial pressure monitoring in fulminant hepatic failure". Lancet 341 (8846): 690-1. PMID 8095592.
  8. ^ Schmidt LE, Larsen FS (2006). "Prognostic implications of hyperlactatemia, multiple organ failure, and systemic inflammatory response syndrome in patients with acetaminophen-induced acute liver failure". Crit. Care Med. 34 (2): 337-43. PMID 16424712.
  9. ^ 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.
  10. ^ Bihari D, Gimson AE, Waterson M, Williams R (1985). "Tissue hypoxia during fulminant hepatic failure". Crit. Care Med. 13 (12): 1034-9. PMID 3933911.
  11. ^ 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.
  12. ^ a b Polson J, Lee WM (2005). "AASLD position paper: the management of acute liver failure". Hepatology 41 (5): 1179-97. doi:10.1002/hep.20703. PMID 15841455.
  13. ^ O'Grady JG, Alexander GJ, Hayllar KM, Williams R (1989). "Early indicators of prognosis in fulminant hepatic failure". Gastroenterology 97 (2): 439-45. PMID 2490426.
  14. ^ 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.
  15. ^ 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.
  16. ^ Trey C, Davidson CS (1970). "The management of fulminant hepatic failure". Progress in liver diseases 3: 282-98. PMID 4908702.
  17. ^ Bernuau J, Goudeau A, Poynard T, et al (1986). "Multivariate analysis of prognostic factors in fulminant hepatitis B". Hepatology 6 (4): 648-51. PMID 3732998.
  18. ^ Gimson AE, O'Grady J, Ede RJ, Portmann B, Williams R (1986). "Late onset hepatic failure: clinical, serological and histological features". Hepatology 6 (2): 288-94. PMID 3082735.
  19. ^ Sass DA, Shakil AO (2005). "Fulminant hepatic failure". Liver Transpl. 11 (6): 594-605. doi:10.1002/lt.20435. PMID 15915484.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Acute_liver_failure". A list of authors is available in Wikipedia.
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