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EASL publishes clinical guide on the management of acute liver failure

AMSTERDAM — EASL recently published their new clinical practice guideline on the assessment and management of acute liver failure, presented recently at the International Liver Congress.

“ALF is frequently, but often incorrectly used to describe both acute deterioration in liver function in patients with chronic liver disease (a condition that should be termed acute-on-chronic liver failure [AoCLF]), or liver involvement in systemic disease processes. Liver injury secondary to alcohol, which presents as alcoholic hepatitis, and other forms of AoCLF, can be difficult to distinguish from ALF on occasion,” the researchers wrote. “However, there are clear differences, and different forms of management are required.”

Clinical features of ALF

Hyperacute liver injury is characterized by severe coagulopathy, markedly increased serum transaminases and only moderate, if any, increased bilirubin; whereas subacute or subfulminant liver injury typically presents with mild to moderate coagulopathy, a mild increase in serum transaminases and deep jaundice. Initial mental alterations may be subtle and require intensive screening at the first sign of hepatic encephalopathy.

“Patients with an acute presentation of chronic autoimmune hepatitis, Wilson disease and Budd-Chiari syndrome are considered as having ALF if they develop hepatic encephalopathy, despite the presence of a pre-existing liver disease in the context of appropriate abnormalities in liver blood tests and coagulation profile,” the researchers wrote.

Assessment and management at presentation

The guideline recommends key steps to follow at initial presentation, the foremost being the clarification of etiology. Exclude the presence of cirrhosis, alcohol-induced liver injury and malignant infiltration of the liver. Screen intensively for signs of hepatic encephalopathy. Begin discussion with a transplant unit, even if transfer is not needed at initial presentation, while also analyzing for contraindications for emergency liver transplant.

Common etiologies that form a possible indication for emergency liver transplant include drug-induced hepatotoxicity, such as paracetamol overdose; viral hepatitis; and other viral infections or autoimmune hepatitis.

Less common etiologies that may determine the need for liver transplant include Budd-Chiari syndrome, Wilson disease, mushroom poisoning, pregnancy-related ALF, ALF induced by hemi-hepatectomy and hyperthermic injury from heat shock. Specific treatment or intervention for these conditions should be started, but in most cases, therapy may be too late to provide full benefits. If patients with these conditions fulfill the criteria for liver transplant, emergency surgery should be considered without delay.

Organ specific management

The guideline includes management recommendations for individual organ systems, divided by the following categories: cardiovascular, respiratory, gastrointestinal, metabolic, acute kidney injury and renal replacement therapy, and coagulation monitoring and management.

Regarding the brain, patients with low levels of hepatic encephalopathy should have regular clinical and specifically neurological examination to detect early signs of progression to the higher grades of 3 and 4. Patients with grade 3 and 4 encephalography should undergo intubation to provide a safe environment and prevent aspiration.

According to the guide, approximately one-third of patients who reach grade 3 or 4 encephalopathy may develop intracranial hypertension (ICH). As CT scans are both insensitive to actual ICH and moving patients with severe hepatic encephalopathy can lead to surges of intrahepatic cholestasis of pregnancy (ICP), scans are not recommended; instead, noninvasive tools, such as trans-cranial Doppler, are recommended. Regarding management, mannitol and hypertonic saline should be administered for surges of ICP with consideration for short-term hyperventilation. Additionally, mild hypothermia and indomethacin may be considered for uncontrolled ICH. Indomethacin should only be used in cases of hyperemic cerebral blood flow.

Artificial and bioartificial liver devices

“Liver assist devices have received much attention over recent years in the hope that they can provide an effective ‘bridge’ to transplantation or recovery of liver function, mitigating the need for transplantation,” the researchers wrote. “Unfortunately, the dream of a mechanical ‘proxy liver’ is a long way from being realized.”

Currently, liver support systems, both biological and absorbent, should only be used in the context of randomized control trials. Plasma exchange in randomized control trials has shown improvement in transplant-free survival in patients with ALF and to modulate immune dysfunction. Considerations for future studies should include randomized control trials of new liver support systems in well-defined patient cohorts, development of dynamic measures of liver function to assess metabolic and synthetic capacity, and analysis of antimicrobial clearance and dosing when using various liver support systems.

Liver transplantation: Ethics, postop and outcome

“During decision making, several factors should be taken into account: the age of the patient, past history of suicide attempts and absence of compliance with any previous medical treatments. It is essential to obtain information from the family and friends of the patient, family doctors, psychiatrists and to solicit input from all members of the multidisciplinary team,” the researchers advise. “The decision to transplant or not based on psychosocial factors is complex and requires clear documentation and rationale. However, the long-term outcome is favorable with high levels of treatment compliance.”

Patients with ALF, patients with the potential for deterioration and patients who may be candidates for liver transplant should be transferred to specialist units prior to onset of hepatic encephalopathy for assessment. Patients with ALF designated for liver transplantation should be afforded the highest priority for donated organs. Irreversible brain injury is a contraindication for transplantation.

HBV recurrence and the need for retransplantation due to organ failure are major concerns in patients with ALF following liver transplantation.

“The quality of life of [liver transplant] survivors is generally good and seems similar to that of patients transplanted for chronic liver disease. The majority of young patients will return to a normal social life and to work. Psychological troubles can be observed in the early postoperative period and are explained mainly by pre-transplant [hepatic encephalopathy] and by the fact that these patients were not prepared psychologically for transplantation,” the researchers wrote. “Long-term survival is generally good; there are few deaths 1 year [post-transplant]. This is due in part to the young age of the patients, the low rate of HBV recurrence in fulminant hepatitis B and the absence of recurrence of hepatic diseases, although chronic rejection remains a risk.” – by Talitha Bennett

References:

European Association for the Study of the Liver, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2016.12.003.

Disclosure: Please see the full guideline for the researchers’ relevant financial disclosures.