Is It Covert or Overt Hepatic Encephalopathy?

Rowen K. Zetterman, MD


November 21, 2016


Hepatic encephalopathy in patients with cirrhosis should be treated as a continuum, which ranges from no impairment to severe hepatic coma.[1]

The diagnosis of hepatic encephalopathy should follow the exclusion of other causes of CNS dysfunction, such as sepsis, hypoxemia, cerebrovascular injury, and intoxication or drug overdose, coupled with appropriate clinical criteria or psychometric testing.

Because overt hepatic encephalopathy is aggravated by electrolyte disturbances, gastrointestinal bleeding, infection, medications, and even dietary indiscretion, these associations should be looked for and corrected. If a patient presents with overt hepatic coma, infection should be excluded with blood, urine, and ascites cultures; pneumonia should be excluded with a chest radiograph; gastrointestinal bleeding should be excluded with stool testing and a nasogastric aspirate; electrolyte disturbances should be excluded with blood testing; and drug or alcohol overdose should be excluded with a careful history, discussions with family members, and testing as needed.

If no single aggravating factor is evident, initial purging of the gastrointestinal tract with polyethylene glycol-containing laxatives, coupled with a broad-spectrum intravenous antibiotic, is recommended until cultures are available. Nonabsorbed disaccharide lactulose is the first choice of therapy; a daily split dose is sufficient to produce two or three soft stools each day. The poorly absorbed antibiotic rifaximin can be used as an add-on therapy when needed.[1] Alternatives to rifaximin include neomycin and metronidazole. Although not considered first-line therapy, oral amino acids, such as branched-chain amino acids and L-ornithine-L-aspartate, have been used in patients who are unresponsive to conventional treatments.[1]

After overt hepatic encephalopathy is clinically controlled, prophylactic therapy includes lactulose (with rifaximin as add-on therapy when needed) coupled with adequate nutrition that provides 35 to 40 kcal and 1.2 to 1.5 g protein/kg ideal body weight daily.[1] Intractable hepatic encephalopathy is an indication for liver transplantation.[1]

"Treatment of minimal hepatic encephalopathy and covert hepatic encephalopathy is not routinely recommended, apart from a case-by-case basis," according to the AASLD and EASL guidelines.[1] However, treatment might be considered in those whose lifestyle is affected by covert encephalopathy or in those with subsequent overt encephalopathy. Some short-term data indicate that medical therapy can improve the neuropsychologic findings of patients with minimal hepatic encephalopathy[25,26], but there is little evidence of long-term benefit, such as a reduction in hospitalization or the prevention of progression to overt encephalopathy.

Probiotics have been used, but they are currently unregulated. Probiotics can decrease intestinal pH and reduce the urease activity of bacteria. An increase of non-urease bacterial species in the colon could also reduce ammonia formation and intestinal pH. Improved health-related quality of life and reversal of minimal hepatic encephalopathy associated with a reduced progression to overt encephalopathy has been described after probiotic intake.[27] In that study, patients who lacked evidence of minimal hepatic encephalopathy on testing were selected. Half of the patients received daily probiotics for 3 months and the other half received a placebo. The rate of eventual overt hepatic encephalopathy was twice as high in the placebo group as in the probiotic group.

Fecal transplantation has been attempted in a single patient,[28] with short-term transient improvement in encephalopathy symptoms.

Other studies have shown that patients with minimal hepatic encephalopathy improve with lactulose[26,29,30] or rifaximin.[25] And in patients with covert hepatic encephalopathy, rifaximin has been shown to improve the ability to operate a motor vehicle.[31]

Patients with overt hepatic encephalopathy before transplantation can have persistent cognitive impairment after liver transplantation[32] and reduced post-transplant survival.[33] Although it seems reasonable that patients with covert encephalopathy who undergo liver transplantation will likely not have persistent postoperative neuropsychiatric dysfunction, this has yet to be studied.

Follow Medscape Gastroenterology on Twitter: @MedscapeGastro


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: