Acute liver failure pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]
Overview
Acute liver failure results from the loss of normal function of hepatic tissue which occurs over a short period of time. It results in the loss of the metabolic, secretory, and regulatory effects of the liver cells. This results in the rapid accumulation of toxic substances, which then manifests in the patient as an altered sensorium, cerebral edema, hemodynamic abnormalities, and even multiorgan failure.
Pathophysiology
Acute liver failure is caused due to extensive damage to the liver tissue, causing severe compromise of its function. The effects of acute liver failure are due to the loss of its metabolic, secretory and regulatory effects. This results in accumulation of toxic substances and causes deleterious effects. The major cause of morbidity and mortality in patients of liver failure is due to the development of cerebral edema which causes altered sensorium and increased intracranial pressure. Cerebral edema is mediated due to damage to blood brain barrier. Acute liver failure causes increased ammonia concentrations due to the failure of the detoxification system that occurs through the liver. The increased levels of ammonia in combination with the glutamate produced by the astrocytes of brain, causes excess levels of glutamine to be produced through the enzyme glutamine synthetase. The accumulation of glutamine in high concentrations is what causes cerebral edema. In acute liver failure, there are also increased levels of nitric oxide in the circulation. Nitric oxide is a potent vasodilator, and causes a disruption of the cerebral blood flow. This in turn disrupts cerebral auto regulation. Multiorgan failure occurs due to severe hypotension which is caused by the decreased systemic vascular resistance.
Specific Conditions
Acetaminophen Toxicity
- Acetaminophen is the leading cause of acute liver failure.
- Acetaminophen causes dose related toxicity.
- Toxic doses can be as low as 3-4 g/day but most toxic ingestion's are of >10 g/day.
Other Drugs
- Drugs other than acetaminophen also cause acute liver failure.
- These constitute 13% of cases of acute liver failure in US. [1]
- They cause idiosyncratic drug hepatotoxicity.
- They usually present within six months of drug initiation.
Mushroom Poisoning
- This is mainly caused by the genus Amanita (Amanita phalloides).[2]
- Presentations may vary from case to case and it constitutes a medical emergency.
- Patients may recover from traditional medical treatment, or may require transplantation in more severe cases.
Viral Hepatitis
- Hepatitis viruses A, B, D (associated with B), and E (in endemic countries) can cause acute liver failure.
- Viral hepatitis (Hepatitis A and B) constitute to causing 12% of the cases of acute liver failure in US.[1]
- Hepatitis C alone doesn't seem to cause acute liver failure.[3]
- There is a difference in the survival rate of patients with acute liver failure in hepatitis A and hepatitis B which cannot be explained by the severity of dysfunction, but may rather be an inherent feature of the infections themselves.[3]
Autoimmune Hepatitis
- Autoimmune hepatitis may be an unrecognized coexistent condition.
- Autoantibodies are helpful in the diagnosis of the condition. In cases of a negative test for autoantibodies, biopsy may be required.
- A few patients may need transplantation along with steroid therapy.
Ischemic Injury
- This condition is called shock liver. It is a common occurrence in ICU with a prevalence of 10%.[4]
- Shock liver results from severe hypotension due to any cause like heart failure, severe vaso-constriction due to drugs like niacin and cocaine.
- Early recovery is frequent but long term outcome depends on the underlying cause of the ischemia.
HELLP Syndrome
- Few women near the end of pregnancy may develop rapidly progressive liver failure.
- HELLP syndrome is featured by a triad of hemolysis, elevated liver enzymes and low platelets.
- Most of the patients will improve spontaneously with delivery.
- Postpartum deterioration may need transplantation.
Malignancy
- Malignant infiltration may cause acute liver failure.
- Severe acute infiltrations may occur with few malignancies like breast cancer, small cell lung cancer, lymphoma, melanoma, and myeloma.
- Transplantation is not advised in these patients.[5]
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[6].
References
- ↑ 1.0 1.1 Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L, Crippin JS, Blei AT, Samuel G, Reisch J, Lee WM (2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States". Annals of Internal Medicine. 137 (12): 947–54. PMID 12484709. Retrieved 2012-10-27. Unknown parameter
|month=ignored (help) - ↑ Catalina MV, Núñez O, Ponferrada A, Menchén L, Matilla A, Clemente G, Bañares R (2003). "[Liver failure due to mushroom poisoning: clinical course and new treatment perspectives]". Gastroenterología Y Hepatología (in Spanish; Castilian). 26 (7): 417–20. PMID 12887855. Retrieved 2012-10-27.
- ↑ 3.0 3.1 Schiødt FV, Davern TJ, Shakil AO, McGuire B, Samuel G, Lee WM (2003). "Viral hepatitis-related acute liver failure". The American Journal of Gastroenterology. 98 (2): 448–53. doi:10.1111/j.1572-0241.2003.t01-1-07223.x. PMID 12591067. Retrieved 2012-10-27. Unknown parameter
|month=ignored (help) - ↑ Fuhrmann V, Jäger B, Zubkova A, Drolz A (2010). "Hypoxic hepatitis - epidemiology, pathophysiology and clinical management". Wiener Klinische Wochenschrift. 122 (5–6): 129–39. doi:10.1007/s00508-010-1357-6. PMID 20361374. Retrieved 2012-10-27. Unknown parameter
|month=ignored (help) - ↑ Woolf GM, Petrovic LM, Rojter SE, Villamil FG, Makowka L, Podesta LG, Sher LS, Memsic L, Vierling JM (1994). "Acute liver failure due to lymphoma. A diagnostic concern when considering liver transplantation". Digestive Diseases and Sciences. 39 (6): 1351–8. PMID 8200270. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ 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.