Management of Acute Liver Failure and Acute on Chronic Liver Failure: Liver Transplantation and Beyond

Review Article

Austin Liver. 2016; 1(1): 1002.

Management of Acute Liver Failure and Acute on Chronic Liver Failure: Liver Transplantation and Beyond

Malik MU*, Morello F, Ozseker B and Gurakar A

¹Department of Internal Medicine, Conemaugh Memorial Medical Center, USA

²Saint Francis University, USA

³Department of Gastroenterology and Hepatology- Transplant Hepatology, Johns Hopkins University School of Medicine, USA

*Corresponding author: Mohammad U Malik, Department of Internal Medicine, Conemaugh Memorial Medical Center, USA

Received: June 23, 2016; Accepted: August 30, 2016; Published: September 23, 2016


Acute liver failure and acute on chronic liver failure are disease entities with high mortality rate. Urgent referral to the nearest liver transplant center may be lifesaving in the majority of instances. Over the course of several decades, the liver disease burden has continued to expand. This had led to shortage of organ pool. Widespread efforts have been taken over the past few decades to standardize the organ allocation and procurement so that the graft is available to the sickest individual. Efforts are underway to utilize extended criteria donors to match the growing need for organs. Extracorporeal liver support devices were introduced to temporarily provide liver recovery until a donor liver is available. To date the mortality benefit of such devices is unproven. Hepatocyte transplantation has emerged as a safer alternative to liver transplantation. In addition, high flow plasma exchange has recently been proven to treat acute liver failure with mortality benefit. This review aims to summarize the recent advances in the field of Hepatology and transplant Hepatology.

Keywords: Extracorporeal liver support devices; Hepatocyte transplant; Liver transplantation; Organ allocation; Acute liver failure


Acute Liver Failure (ALF) is characterized by an abrupt decrease in liver function as measured by an INR ≥1.5 in a patient without preexisting liver disease with accompanying evidence of hepatic necrosis on histopathology [1]. Hallmark features of ALF are clinical jaundice and hepatic encephalopathy, while ascites may or may not be present. ALF may be categorized as hyperacute (< 1 week), acute (1 to 4 weeks) and subacute (4-26 weeks) [1]. The leading causes in developed countries include drug induced liver injury, followed by viral etiologies. Patients may develop a sudden onset of cerebral edema and multi-system organ failure due to the accumulation of nitrogenous toxins and release of cytokines, eventually leading to death. It is thought that a high level of ammonia is converted to glutamine which results in osmolar swelling of brain cells. A new defined entity, Acute on Chronic Liver Failure (ACLF) is defined as an acute decompensation that occurs in a patient with known cirrhosis or chronic liver disease [2,3]. ACLF includes a subset of cirrhotic patients with high mortality and evidence of new organ failure as a result of complications such as bacterial infection, encephalopathy, or gastrointestinal bleeding [2,3].

Effective management of ALF and ACLF patients is cause specific and requires an experienced multidisciplinary team. Preferably, patients with ALF should be managed in the Intensive Care Unit (ICU). The presence and degree of hepatic encephalopathy is the first step in the decision process to admit the patient to the ICU. Lactulose remains the cornerstone therapy for hepatic encephalopathy. Rifaximin is considered an adjunctive therapy, and has been shown to prevent recurrence, maintain remission, and reduce hospitalization. Efforts should be made to avoid precipitating factors such as electrolyte imbalance, infection, constipation, and bleeding [4]. Intracranial pressure monitoring may be achieved where available and elevated intracranial pressure should be treated accordingly with mannitol. Treatment of ALF should begin before etiology is confirmed, particularly in cases of toxicity. The number of liver-directed therapies in ALF is relatively limited, and it is important to recognize and administer the correct therapy [5]. For example, acetaminophen overdose should be immediately treated with N-acetylcysteine, while supportive care is recommended in cases secondary to hepatitis A and E, and administration of corticosteroids is cornerstone therapy for autoimmune hepatitis. Prompt liver transplantation is considered in cases secondary to Wilson disease, mushroom poisoning, hepatic vein thrombosis without underlying malignancy and in HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelets) syndrome when delivery of a fetus fails to correct hepatic failure [6].

Since the 1960s, Liver Transplantation (LT) has emerged as a cornerstone intervention to cure acute and chronic liver disease [7- 9]. In ALF the hepatocytes may regenerate after removal of acute insult hence, avoiding the need for LT. Hepatocyte self regeneration has become the premise to providing Extracorporeal Liver Support Devices (ECLD) in the interim to bridge patients to LT or selfrecovery (Table 1). ECLD may also provide benefit in instances where LT is contraindicated.

Citation: Malik MU, Morello F, Ozseker B and Gurakar A. Management of Acute Liver Failure and Acute on Chronic Liver Failure: Liver Transplantation and Beyond. Austin Liver. 2016; 1(1): 1002.