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Key Clinical Questions

  • image What is the approach to the hospitalized patient with abnormal liver function tests?

  • image Explain the appropriate diagnostic and therapeutic algorithm for cholestatic liver injury?

  • image What are the causes of acute hepatocellular injury?

  • image What is the treatment algorithm for acetaminophen overdose?

  • image Are there evidence-based interventions for alcoholic hepatitis?

  • image What is the definition of acute liver failure?

  • image When should a patient with acute liver failure be referred for liver transplantation?

Abnormalities in liver function tests (LFTs) commonly occur in the inpatient setting, whether the primary cause for hospital admission, incidentally detected, or a complication of acute illness and its management. Diagnosis of hepatobiliary disorders may include laboratory tests, imaging studies, and liver biopsy. Individual tests, especially those of liver biochemistry, have limited sensitivity and specificity. The cause and severity of disease is often defined by a combination of tests. Certain scores such as Model of End-Stage Liver Disease (MELD), Child-Pugh score, and Maddrey Discriminant Function (mDF), have incorporated clinical and laboratory features to predict survival in patients with significant liver disease including those with decompensated cirrhosis and alcoholic hepatitis (AH).

It is important to discern between liver enzymes and LFTs. Serum aminotransferase levels and alkaline phosphatase (AP) levels are liver enzymes. Their elevation in the serum indicates hepatocyte and bile duct epithelial injury. Albumin, bilirubin, and prothrombin time are actual measures of hepatic function. However, they are affected by extrahepatic factors including nutrition, hemolysis and antibiotic use. For the purpose of this chapter, LFTs will be referred to liver enzymes. Here, we aim to provide a framework for the evaluation of abnormal LFTs in the hospitalized patient to distinguish acute-on-chronic liver injury from acute liver injury, to provide a framework for diagnosis of the many etiologies of liver injury, and to provide evidence-based management where it is available. Early recognition of acute liver failure (ALF), defined by encephalopathy and coagulopathy in a patient without preexisting liver disease, is an important aspect of inpatient care in order to facilitate prompt evaluation for liver transplantation or transfer to a liver transplantation center. Special consideration is given to acetaminophen overdose, the use of N-acetylcysteine (NAC), and the treatment of alcoholic hepatitis. The management of chronic liver disease and decompensated cirrhosis in the hospitalized patient is addressed elsewhere (see Chapter 160 [Cirrhosis and its Complications]).


Abnormal LFTs are a frequent cause for hospitalization, the majority as a consequence of biliary pathology, including cholecystitis and cholangitis, or acute liver injury, in the form of hepatotoxins, such as alcohol and acetaminophen, and viral hepatitides. Approximately 2000 cases of ALF occur annually in the United States. Both ALF and cholangitis, in particular, can confer high mortality of 30% in ALF without transplantation and nearly 100% in untreated acute cholangitis. Acetaminophen overdose continues to be recognized as the most common cause of ALF, accounting for approximately one-third of cases, followed by idiosyncratic drug ...

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