AGA Patient Case: Persistent hepatic encephalopathy

A recent case in the forum involves a patient with cirrhosis and a MELD-Na of 7 who presents for evaluation of uncontrolled hepatic encephalopathy. The current medication regimen includes lactulose titrated to three bowel movements per day, rifaximin 550 mg BID and zinc 220 mg BID. The patient continues to report symptoms of forgetfulness and impaired sleep. An AGA Community expert moderator provides his review of the case. View the full case here.

In this scenario, what management options are available?

Hepatic encephalopathy (HE) can occur in 30 to 40 percent of patients with cirrhosis as a complication of portal hypertension and subsequent portosystemic shunting. The presence of HE is associated with decreased quality of life indices and has been shown to negatively impact patient survival regardless of liver function. Thus, timely and effective control of symptoms is a critical for improvement of patient outcomes.

When evaluating a patient with HE it is important to first determine the frequency of symptoms (episodic, recurrent [up to six months] or persistent) and whether a precipitating event can be identified (i.e. constipation, electrolyte abnormalities, gastrointestinal bleeding, etc.). Proper classification can aid the clinician to best determine management options. This case describes perhaps the most challenging scenario of a patient presenting with persistent and unprecipitated hepatic encephalopathy. The presence of a low MELD score signifies that importance of proper medical management as liver transplantation is not currently an option.


When evaluating a patient with HE it is important to first determine the frequency of symptoms […] and whether a precipitating event can be identified.


For patients with persistent hepatic encephalopathy, it is important to review current prescribed therapies and response to lactulose or other synthetic disaccharides. If possible, confirming these responses with a caretaker or cohabitant would be ideal. Once compliance and adequate treatment response has been confirmed, the medication list should be reviewed to ensure the patient’s condition is not exacerbated by use of sedatives, antidepressants, antipsychotics or opioid therapy. Laboratory testing can also identify other exacerbating factors including infection, electrolyte abnormalities, or anemia.

Up to 50 percent of patients who undergo transjugular intrahepatic portosystemic shunt (TIPS) placement develop hepatic encephalopathy. For those patients who have undergone TIPS placement, a decrease in shunt diameter can be considered once optimization of medical therapy is reached and the patient is cleared of other exacerbating factors. Spontaneous portosystemic shunts (SPSS) can develop in over half of patients with cirrhosis and portal hypertension. These shunts are commonly visualized on CT or MR abdominal imaging with splenorenal shunts occurring most commonly. While most patients with SPSS remain clinically asymptomatic, 71 percent of patients with recurrent and persistent HE are found to have SPSS on imaging. Endovascular closure of these shunts can be considered though it must be noted that closure can lead to increased portal flow and eventual risk of variceal bleeding. Thus, pre-procedure upper endoscopy and proper management of varices is required if SPSS closure is pursued.

Lastly, patients with sarcopenia are at increased risk of persistent HE as skeletal muscle plays a key role in the processing of circulating ammonia. Improvement of nutritional status can potentially alleviate symptoms of HE. Current recommendations include intake of 35 to 40 kcal/kg/day with protein intake of 1.2 to 1.5 g/kg/day. Patients will often require nutritional supplementation to reach these goals. High caloric formulas, rich in vegetable protein and enriched in branched-chain amino acids, are preferred.

In conclusion, management of patients with persistent HE can pose a challenging clinical scenario. Proper sub-classification and identification of patients with persistent-unprecipitated HE is key. Confirmation of compliance is key and in cases where no precipitating factor is identified, evaluation for SPSS should be performed and considered.

The AGA Community is a member-only online forum where you can connect with GIs from around the world. In recent years, it has become a steadfast sounding board for physicians to gain insight into their difficult patient scenarios. AGA members have reached out to their colleagues to determine best practices for therapies, diagnoses and disease-management options for patients spanning the GI spectrum.

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