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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 18  |  Issue : 4  |  Page : 266-269

Acute liver failure


Department of Gastroenterology, Institute of Gastrosciences and Liver, Apollo Multispeciality Hospitals, Kolkata, West Bengal, India

Date of Submission11-Nov-2021
Date of Decision17-Nov-2021
Date of Acceptance22-Nov-2021
Date of Web Publication23-Dec-2021

Correspondence Address:
Vikash Prakash
Institute of Gastrosciences and Liver, Apollo Multispeciality Hospitals, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_132_21

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  Abstract 


Acute liver failure is an uncommon disease presenting with abrupt failure of liver synthetic and detoxification functions on account of widespread damage to hepatocytes and is associated with high mortality. With advent of emergency liver transplant and tailored critical care its no longer a nontreatable disease.

Keywords: Acute liver failure, Critical care, liver transplant


How to cite this article:
Prakash V. Acute liver failure. Apollo Med 2021;18:266-9

How to cite this URL:
Prakash V. Acute liver failure. Apollo Med [serial online] 2021 [cited 2022 Nov 28];18:266-9. Available from: https://apollomedicine.org/text.asp?2021/18/4/266/333601




  Introduction Top


Very few diseases over past years have seen such a dramatic positive change in outcome as acute liver failure. Emergency liver transplant has made acute liver failure a treatable disease now. Some patients may recover without liver transplant with an efficient critical care support, while others need critical care as a bridge to transplant.

Acute liver failure by definition includes central nervous dysfunction with the presence of encephalopathy and coagulopathy. These along with high prevalence of infection, especially in developing countries like India, make critical care management of these patients till transplanted an important part of treatment.

Acute liver failure is defined by the presence of coagulopathy with an INR of ≥1.5 with altered sensorium in the absence of cirrhosis within 26 weeks of onset of illness. Subclassification is based on time to encephalopathy, namely hyperacute (<7 days), acute (8–28 days) and subacute >28 days to 12 weeks.[1] Hyperacute liver failure has a marked increase in aminotransferases and progresses quickly however has a fair chance of recovery. Acute and subacute liver failure represent similar and overlapping disease patterns and can be seen as a single entity with a greater rise in bilirubin compared to aminotransferases.[2]


  Search Strategy and Study Selection Top


We searched for “acute liver failure” in PubMed, and studies more relevant to the management of neurological and renal complications were chosen. An attempt was made to include more randomized trials rather than expert opinions. The final search was made on October 10, 2021.


  Classifications Based on Time from Jaundice to Encephalopathy Top


Acute liver failure can be classified as in [Figure 1].
Figure 1: Clarification based on time from jaundice to encephalopathy

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  Etiology of Acute Liver Failure Top


Hepatitis E is the most common cause of acute liver failure in India, accounting for 44% of the cases, while hepatitis B ranks second, causing 15% of acute liver failures. In around 31% of patients, etiology cannot be determined.[3]

In developed countries, paracetamol accounts for 40%–60% of the cases.

Pathophysiology

Systemic inflammatory response and raised intracranial pressure are central to acute liver failure, subsequently leading to loss of cerebral autoregulation. Raised ammonia plays a key role; however, multiple other factors contribute to alteration in sensorium of the patient by astrocyte swelling and causing edema in brain.[4] Genome-wide association studies show association of drug-induced liver injury to be associated with multiple genetic risks including single-nucleotide polymorphisms and human leukocyte antigen genes.[5] Extensive hepatocyte necrosis causing massive collapse with just framework remaining is a feature of acute liver failure. Weight of liver can decrease from 1600 mg to 500 mg2 [Table 1].
Table 1: Etiologies of alf

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Acute liver failure phenotypes[1]

  1. In liver cirrhosis


    1. Autoimmune liver disease
    2. Budd–Chiari–acute presentation
    3. Fulminant Wilson disease<
    4. Hepatitis B reactivation.


  2. Acute on chronic liver failure and secondary liver failure.



  Hypoxic/Ischemic Hepatitis Top


  1. Infiltrative liver diseases
  2. Infections like malaria
  3. Lymphoma
  4. Infections (e.g., malaria)
  5. Severe alcoholic hepatitis
  6. Post hepatectomy
  7. Hemophagocytosis.


Determining the etiology of liver failure is important to stratify the patient for the need of urgent liver transplantation. Furthermore, the etiology determines the prognosis of the patient, like hypoxic hepatitis will resolve after restoration of hemodynamics. Patients with (HELLP) hemolysis, elevated liver enzymes, and low platelets and those with acute fatty liver of pregnancy resolve with delivery of fetus, which should be promptly offered with rising LDH and hepatic encephalopathy.[6] Ingestion of multiple doses of paracetamol over more than 8 h for pain resulting in staggered ingestion has a worse prognosis compared to single-point ingestion with more number of organ failures. A sequential organ failure assessment (SOFA) score <6 following staggered ingestion is associated with a favorable outcome.[7] In spite of extensive workup in some of the patients, the cause of liver failure cannot be determined. Drugs are seen in some of these, although many cannot recall them. Some of these patients have a viral picture to start with, although no specific virus can be found out on evaluation. Systemic diseases involving liver and causing liver failure are not an indication emergency liver transplant and require treatment of the systemic disease.[1]

Clinical features

Acute liver failure is a multisystem disease and involves almost all organs. It causes hepatic encephalopathy with cerebral edema and intracranial hypertension and can lead to brainstem herniation. Myocardial injury which is generally subclinical is seen and it is a high cardiac output state. Pancreatitis can occur in viral, drugs, or paracetamol-related injuries. Shock can be accentuated by adrenal insufficiency. Acute renal failure and systemic inflammatory response are often seen at presentation or occurs subsequently. Subacute liver failure may mimic cirrhosis because of rise in portal pressure.

Assessment

  1. Etiology – Paracetamol ingestion with suicidal intent, substance abuse, mushroom ingestion, and pregnancy can help identify a possible etiology
  2. Active alcohol intake, malignancy, and severe comorbidities such as cardiac and pulmonary diseases can preclude an emergency transplant.


Initial laboratory evaluation

Coagulation parameters – INR and prothrombin time are required additionally we can measure factor V and fibrinogen.

Liver tests, urea, creatinine, and urine output should be measured.

Lactate levels and arterial blood gas should be measured.

Search for various etiologies should be made simultaneously.

Blood and urine cultures with ECG and X-ray chest should be done.

Blood glucose should be measured and glucose infusion should be started to avoid hypoglycemia with a target of 140 mg/dl.

Three percent NaCl can be given to maintain a sodium level of 135–145 mg/dl.

Drugs toxic to kidneys and liver and sedatives should be avoided. A low threshold for intubation with onset of encephalopathy and minimal stimulation should be maintained.

N acetylcysteine has a beneficial role both in paracetamol- and nonparacetamol-related acute liver failure cases for up to 48 h after ingestion.[8] Empirical antibiotics should be given.

Tertiary care management

Transfer to a tertiary care unit should be considered because of the unpredictable nature of acute liver failure. Furthermore, there can be a rapid deterioration in sensorium requiring intubation requiring liver transplantation subsequently. Platelets may be low with raised INR, making insertion of central lines and arterial lines little difficult. Global assessment of coagulation with thromboelastography can provide reassurance that may not be deranged.[9]

Management of organ related complications.

Neurological complications

Agitation, hyperreflexia to vomiting, and clonus can be present; however, hepatic encephalopathy is integral to acute liver failure. Intracranial hypertension is seen in fewer cases than was previously thought of. Around 29% of acute cases who progress to grade ¾ coma may have raised intracranial pressure. Hyperacute liver failure, a higher grade of encephalopathy, blood ammonia levels more than 150 μmol/l, low sodium, patients having seizure, and those with shock are likely to have raised intracranial pressure.[10] The presence of sepsis or inflammation without sepsis worsens the neurological outcome. The presence of raised leukocytes and low platelets and presence of infection during encephalopathy are associated with worse outcomes. The more the number of systemic inflammatory components, the worse is the outcome.[11]

Targeting ammonia may not completely reverse brain edema because pathogenesis of hepatic encephalopathy is multifactorial. Changes in expression of genes encoding neuroglial proteins involved in synthesis of neurotransmitter, cell volume regulation, and pro-inflammatory cytokines lead to dysregulation of liver brain pro-inflammatory mechanisms.[12] Antihyperammonemic measures such as lactulose and rifaximin have not been tested for utility in acute liver failure; however, they are worth trying given the mechanism. Hyperventilation induced by raised intracranial pressure leads to respiratory alkalosis. This combined with hypothermia till 32°C helps in the restoration of cerebral autoregulation.[13] Head should be raised to 30° and should be kept in a neutral position. Blood sodium levels have a major impact on astrocyte swelling by promoting inflow of water into it. Patients who are maintained at a sodium level of 137–142 mg/dl have higher intracranial pressure than those who have a sodium level of 145–155 mg/dl over first 24 h.[14] Blood lactate levels increase on account of increased production and reduced clearance. However, it is a poor prognostic marker. Maintaining a temperature of around 33°C–35°C may also help decrease the incidence of raised intracranial hypertension.

Measurement of intracranial pressure directly by intracranial monitoring directly may lead to early aggressive interventions to lower intracranial pressures. The interventions done with direct monitoring and those without does not alter the survival. There are worse outcomes in nonacetaminophen acute liver failure patients. Bleeding risks due to deranged coagulation are there, although it does not increase the mortality; hence, the use of pressure monitors in routine cases has declined.[15] Survival is dismal in patients who have a marked rise in intracranial pressure who are likely to have brainstem herniation post surgery. In these select patients, intensive monitoring of intracranial pressure may help identify patients who are unlikely to benefit from liver transplantation and not have neurological recovery.[16] Mannitol bolus (0.5–1.0 g/kg weight) or hypertonic saline boluses can be given by repeating the boluses if there is no response. The use of dexamethasone, on the other hand, does not provide any survival advantage.[17] Indomethacin has some role in patients who have.[18] Minimal stimulation with deeper sedation with propofol can also be tried.[19],[20],[21]

Renal

Around 30% of patients with acute liver failure require renal replacement therapy. About 70% of patients with acute liver failure have acute kidney injury.[22] Renal injury affects both long- and short-term outcomes but rarely leads to chronicity. Considering the high risk of renal injury, a wise decision on risks and benefits of use of contrast agents should be done. Nephrotoxic medicines should e avoided; prompt treatment of infections and shock if present can prevent renal injury.

Renal replacement therapy may be started for nonrenal indications such as acidosis, high potassium, or fluid overload. Patients with markedly elevated ammonia and increasing hepatic encephalopathy and patients with sodium and other metabolic derangements may require an early start of renal replacement therapy to improve the outcome. Around 22% falls in ammonia levels are seen with the use of hemofiltration.[23]

Females, shock at admission, lower MELD and lower renal failure grades are more likely to have a complete recovery of renal functions post transplant.[24]

Liver devices

Plasma exchange has shown to be of benefit by removing inflammatory mediators and replacement of clotting factors. High-volume plasma exchange helps in ammonia clearance.[25] SOFA scores and inflammatory response scores decrease in patients with the use of plasma exchange.[26] Liver assist devices should only be used as a part of trials.[1]

Liver transplantation

The King's College Criteria have long been used to decide on the need for emergency liver transplant.

Beaujon–Paul Brousse criteria (Clichy) criteria have a higher sensitivity 86 versus 69 than King's College Criteria but lower specificity 76 versus 92. King's College Criteria work best in patients with higher grades of encephalopathy.[27]


  Conclusion Top


With increasing availability of liver transplant, survival has gradually improved over time. Vaccination available for hepatitis B and hepatitis A and improved hygiene is decreasing the incidence of liver failures due to viral hepatitis. Randomized control trials are needed for disease-specific etiologies. In addition, the use of plasmapheresis and utility of liver assist devices need larger trials.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors are on the Editorial Board of Apollo Medicine.



 
  References Top

1.
European Association for the Study of the Liver Electronic Address: [email protected]; Clinical Practice Guidelines Panel; Wendon, J, Panel members, Cordoba J, Dhawan A, et al. EASL clinical practical guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017;66:1047-81.  Back to cited text no. 1
    
2.
Stravitz RT, Lee WM. Acute liver failure. Lancet 2019;394:869-81.  Back to cited text no. 2
    
3.
Bernal W, Wendon J. Acute liver failure. N Engl J Med 2013;369:2525-34.  Back to cited text no. 3
    
4.
Córdoba J, Mínguez B. Hepatic encephalopathy. Semin Liver Dis 2008;28:70-80.  Back to cited text no. 4
    
5.
Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, et al. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology 2017;152:1078-89.  Back to cited text no. 5
    
6.
Westbrook RH, Yeoman AD, Joshi D, Heaton ND, Quaglia A, O'Grady JG, et al. Outcomes of severe pregnancy-related liver disease: Refining the role of transplantation. Am J Transplant 2010;10:2520-6.  Back to cited text no. 6
    
7.
Craig DG, Zafar S, Reid TW, Martin KG, Davidson JS, Hayes PC, et al. The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose. Aliment Pharmacol Ther 2012;35:1408-15.  Back to cited text no. 7
    
8.
Keays R, Harrison PM, Wendon JA, Forbes A, Gove C, Alexander GJ, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: A prospective controlled trial. BMJ 1991;303:1026-9.  Back to cited text no. 8
    
9.
Habib M, Roberts LN, Patel RK, Wendon J, Bernal W, Arya R. Evidence of rebalanced coagulation in acute liver injury and acute liver failure as measured by thrombin generation. Liver Int 2014;34:672-8.  Back to cited text no. 9
    
10.
Shawcross DL, Wendon JA. The neurological manifestations of acute liver failure. Neurochem Int 2012;60:662-71.  Back to cited text no. 10
    
11.
Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, et al. Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology 2003;125:755-64.  Back to cited text no. 11
    
12.
Butterworth RF. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. J Clin Exp Hepatol 2015;5 Suppl 1:S96-103.  Back to cited text no. 12
    
13.
Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A. Restoration of cerebral blood flow autoregulation and reactivity to carbon dioxide in acute liver failure by moderate hypothermia. Hepatology 2001;34:50-4.  Back to cited text no. 13
    
14.
Murphy N, Auzinger G, Bernel W, Wendon J. The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology 2004;39:464-70.  Back to cited text no. 14
    
15.
Karvellas CJ, Fix OK, Battenhouse H, Durkalski V, Sanders C, Lee WM, et al. Outcomes and complications of intracranial pressure monitoring in acute liver failure: A retrospective cohort study. Crit Care Med 2014;42:1157-67.  Back to cited text no. 15
    
16.
Lidofsky SD, Bass NM, Prager MC, Washington DE, Read AE, Wright TL, et al Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure. Hepatology 1992;16:1-7.  Back to cited text no. 16
    
17.
Canalese J, Gimson AE, Davis C, Mellon PJ, Davis M, Williams R. Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure. Gut 1982;23:625-9.  Back to cited text no. 17
    
18.
Wendon J, Lee W. Encephalopathy and cerebral edema in the setting of acute liver failure: Pathogenesis and management. Neurocrit Care 2008;9:97-102.  Back to cited text no. 18
    
19.
Hanid MA, Davies M, Mellon PJ, Silk DB, Strunin L, McCabe JJ, et al. Clinical monitoring of intracranial pressure in fulminant hepatic failure. Gut 1980;21:866-9.  Back to cited text no. 19
    
20.
Forbes A, Alexander GJ, O'Grady JG, Keays R, Gullan R, Dawling S, et al. Thiopental infusion in the treatment of intracranial hypertension complicating fulminant hepatic failure. Hepatology 1989;10:306-10.  Back to cited text no. 20
    
21.
Wijdicks EF, Nyberg SL. Propofol to control intracranial pressure in fulminant hepatic failure. Transplant Proc 2002;34:1220-2.  Back to cited text no. 21
    
22.
Tujios SR, Hynan LS, Vazquez MA, Larson AM, Seremba E, Sanders CM, et al. Risk factors and outcomes of acute kidney injury in patients with acute liver failure. Clin Gastroenterol Hepatol 2015;13:352-9.  Back to cited text no. 22
    
23.
Slack AJ, Auzinger G, Willars C, Dew T, Musto R, Corsilli D, et al. Ammonia clearance with haemofiltration in adults with liver disease. Liver Int 2014;34:42-8.  Back to cited text no. 23
    
24.
O'Riordan A, Brummell Z, Sizer E, Auzinger G, Heaton N, O'Grady JG, et al. Acute kidney injury in patients admitted to a liver intensive therapy unit with paracetamol-induced hepatotoxicity. Nephrol Dial Transplant 2011;26:3501-8.  Back to cited text no. 24
    
25.
Clemmesen JO, Kondrup J, Nielsen LB, Larsen FS, Ott P. Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure. Am J Gastroenterol 2001;96:1217-23.  Back to cited text no. 25
    
26.
Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, et al. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol 2016;64:69-78.  Back to cited text no. 26
    
27.
McPhail MJ, Wendon JA, Bernal W. Meta-analysis of performance of Kings's College hospital criteria in prediction of outcome in non-paracetamol-induced acute liver failure. J Hepatol 2010;53:492-9.  Back to cited text no. 27
    


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