Experts Discuss Hepatic Encephalopathy

Pharmacy Practice in Focus: Health SystemsJuly 2019
Volume 8
Issue 4

Panel members provide information on HE and its symptoms, precipitants, and treatment.

In a Pharmacy Times® peer exchange series, experts Steven L. Flamm, MD; Arun B. Jesudian, MD; David M. Salerno, PharmD; and Elliot B. Tapper, MD, provided an overview of hepatic encephalopathy (HE) and its symptoms, information on a few precipitants, and possible treatment.

HE is a neuropsychiatric complication of chronic liver disease (CLD) that results in significant morbidity and mortality. Most patients may not exhibit symptoms of the disease, and signs when they do present are more nonspecific, such as confusion, fatigue, irritability, itching, and slurred speech.

As CLD levels of occurrence continue to rise, new insights into the pathogenesis of HE and efforts at improving outcomes for patients have resulted in the development and implementation of effective treatment strategies and protocols.

Contrary to popular belief, alcohol consumption is not the only precursor for HE. “Fatty liver infiltration or nonalcoholic steatohepatitis, even cirrhosis in a fraction of patients, is the leading cause of abnormal liver panels,” Flamm said.

Acute liver failure and cirrhosis, which have very different implications, can lead to HE. About 40% of those with cirrhosis have HE. When this is the case, ammonia may be delivered to the brain, which can cause a host of abnormalities, such as dominant inhibitory signaling. Those who have cirrhosis or develop complications because of it should consider a liver transplant, as they can develop ascites, edema, swelling in their legs, or water in their stomach, Flamm said.

Acute liver failure, in which there is severe exacerbation of CLD, can be caused by acetaminophen toxicity, medication, or viral hepatitis. In acute cases, liver failure causes high mortality and requires specialized care, possibly a liver transplant. The difference between acute liver failure and cirrhosis is that those with acute liver failure who have high ammonia levels are also at risk for swelling of the brain.

It is important to keep this disease in mind when counseling patients who may or may not exhibit symptoms. Salerno suggested that providers consider factors that precipitate episodes of HE and look at a patient’s medication list. If patients present with HE, Tapper suggested that they receive hydration therapy.

The panelists indicated that the disease is often a biomarker for an infection, such as spontaneous bacterial peritonitis. Therefore, diagnostic paracentesis is vital to detect an infection in its early stages. The risk is low for this procedure in a patient with cirrhosis with a decreased platelet count or elevated international normalized ratio, Tapper said.

There are 4 prongs for the management of HE, according to the panelists: (1) evaluating consciousness, (2) ruling out other causes of encephalopathy, (3) evaluating for precipitants, and (4) starting the actual empirical treatment for HE.

The standard of care is lactulose, a nonabsorbable disaccharide that is broken down in the colon to prevent the absorption of ammonia. There is also rifaximin, which has been shown to reduce adverse effects when used with lactulose compared with lactulose alone.1 Flamm suggested refraining from the “protein restriction” treatment method.

For more information on the diagnosis, treatment, and management of HE, the authors suggested viewing guidelines from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.


  • Guidelines for the Management of Hepatic Encephalopathy
  • Prevention of Recurrence in Hepatic Encephalopathy


Hudson M, Schuchmann M. Long-term management of hepatic encephalopathy with lactulose and/or rifaximin: a review of the evi- dence. Eur J Gastroenterol Hepatol. 2019 Apr;31(4):434-450. doi: 10.1097/MEG.0000000000001311.

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