Diagnosis

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Respond quickly and identify

Managing OHE starts with timely identification

Routinely ask and assess your patients with chronic liver disease (CLD) and cirrhosis for symptoms of OHE

  1. Take a detailed patient history to assess what is new and/or has changed since their last visit. The following can put patients at risk of developing OHE:
    • Recent infections, or procedures requiring hospitalization (eg, banding or TIPS procedures, bariatric surgery)1-3
    • Presence of other CLD complications, such as portal hypertension or varices1
    • Changes in medications (eg, diuretics, beta blockers, opioids)2,4
  2. Check for physical and mental signs of OHE2
  3. Counsel patients and their caregivers on the risk of complications, including signs and symptoms related to OHE2

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Dr. Modi discuss symptoms and assessment of Hepatic Encephalopathy

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You can help patients at risk of overt HE recurrence by screening today: Check for physical and mental changes2

As the burden of CLD/cirrhosis increases, so do hospital readmissions. HE is a common driver for such readmissions.5

Routinely assess patients’ mental, behavioral, and physical state by asking them and their caregivers these simple questions:

  • Have you experienced or has your caregiver reported episodes of reduced cognitive abilities, such as confusion, disorientation, or sleepiness?
  • Have you experienced or has your caregiver reported a change in personality or increase in inappropriate or bizarre behavior?
  • 30% to 40% of patients with cirrhosis will develop OHE2

Reduce the risk of overt HE recurrence and HE-related hospitalization6

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Counsel patients on risks2

Upon diagnosis of cirrhosis, counsel your patients and their caregivers on the risk of complications, including the above signs and symptoms of OHE.

Caregivers can play a critical part in the management of patients with HE

Your patients may not exhibit outward signs of HE at the time of their appointments. Therefore, it is important to ask both patients and their caregivers whether they've experienced (or witnessed) any of the symptoms.7

One study found
caregivers identified 25% of HE episodes8

RECOGNIZE cognitive episodes and behavior changes before they become severe

Part of a holistic approach to managing HE is considering available guidelines

AASLD recommends the following to identify patients at risk for HE and initiate care (GRADE II-2,A,1)2,*:

  • Identify and treat precipitating factors
  • Seek and treat alternative causes of altered mental status
  • Initiate care for patients with altered consciousness
  • Commence empirical HE treatment
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*Per the GRADE System for Evidence: GRADE II-2=cohort or case-control analytic studies; A=evidence is “high quality,” and further research is very unlikely to change our confidence in the estimated effect; and 1=recommendation is “strong,” with factors influencing strength of recommendation including the quality of evidence, presumed patient-important outcomes, and costs.2

Excerpts from guidelines

Diagnosing OHE is a clinical decision based on a clinical examination, requiring the detection of signs suggestive of HE in a patient with severe liver insufficiency and/or portosystemic shunts who does not have obvious alternative causes of brain dysfunction. The recognition of precipitating factors for HE (eg, GI bleeding and infections) supports the diagnosis of HE.3

“Increased blood ammonia alone does not add any diagnostic, staging, or prognostic value for HE in patients with chronic liver disease. A normal value calls for diagnostic reevaluation (GRADE II-3,A,1).”

–Recommendation 93

”Secondary prophylaxis after an episode for OHE is recommended (GRADE I,A,1).”

–Recommendation 113

Ongoing management and team awareness post-discharge is recommended, including educating the patient, caregivers, and providers so that everyone on the care team understands how to manage HE and reduce the risk of repeated HE-related hospitalizations.3

Patient brochure

AASLD/EASL 2014 Guideline Overview

Quickly review some of the recommendations for adult patients with OHE.

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AASLD, American Association for the Study of Liver Diseases; CLD, chronic liver disease; EASL, European Association for the Study of the Liver; GI, gastrointestinal; HE, hepatic encephalopathy; OHE, overt hepatic encephalopathy.

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INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults.

IMPORTANT SAFETY INFORMATION

  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
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INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

IMPORTANT SAFETY INFORMATION

  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
  • There is an increased systemic exposure in patients with severe (Child-Pugh Class C) hepatic impairment. Caution should be exercised when administering XIFAXAN to these patients.
  • Caution should be exercised when concomitant use of XIFAXAN and P-glycoprotein (P-gp) and/or OATPs inhibitors is needed. Concomitant administration of cyclosporine, an inhibitor of P-gp and OATPs, significantly increased the systemic exposure of rifaximin. In patients with hepatic impairment, a potential additive effect of reduced metabolism and concomitant P-gp inhibitors may further increase the systemic exposure to rifaximin.
  • In clinical studies, the most common adverse reactions for XIFAXAN (alone or in combination with lactulose) were:
    – HE (≥10%): Peripheral edema (17%), constipation (16%), nausea (15%), fatigue (14%), insomnia (14%), ascites (13%), dizziness (13%), urinary tract infection (12%), anemia (10%), and pruritus (10%)
    – IBS-D (≥2%): Nausea (3%), ALT increased (2%)
  • INR changes have been reported in patients receiving rifaximin and warfarin concomitantly. Monitor INR and prothrombin time. Dose adjustment of warfarin may be required.
  • XIFAXAN may cause fetal harm. Advise pregnant women of the potential risk to a fetus.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here for full Prescribing Information.

References: 1. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2017;65(1):310-335. doi:10.1002/hep.28906 2. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735. doi:10.1002/hep.27210 3. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357. doi:10.1002/hep.29367 4. Data on file. IQVIA AI 2022. Salix Pharmaceuticals, Bridgewater, NJ. 5. Bajaj JS, Reddy KR, Tandon P, et al. The 3-month readmission rate remains unacceptably high in a large North American cohort of patients with cirrhosis. Hepatology. 2016;64(1):200-208. doi: 10.1002/hep.28414 6. XIFAXAN. Prescribing information. Salix Pharmaceuticals; 2023. Accessed September 19, 2025. https://shared.salix.com/globalassets/pi/xifaxan550-pi.pdf 7. Hameed B. A primary care guide to the diagnosis and management of overt hepatic encephalopathy. Consultant 360. 2018;58(5):e161. 8. Landis CS, Ghabril M, Rustgi V, et al. Prospective multicenter observational study of overt hepatic encephalopathy. Dig Dis Sci. 2016;61(6):1728-1734. doi:10.1007/s10620-016-4031-7

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