Inclusion Criteria:

• Able to provide consent, with signed and dated informed consent form.

• Stated willingness to comply with all study procedures and availability for the duration of the study.

• Male or female, aged 18 years old or older.

• Presenting clinically for an upper endoscopy +/- simultaneous colonoscopy.

Cases must additionally meet the following criteria in order to be eligible:

• Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of clinical decompensation.

• History of at least one episode of overt HE any time in the past, defined as HE requiring hospitalization and initiation or titration of HE therapy.

  • Can be precipitated HE episode

Cirrhosis Controls must additionally meet the following criteria in order to be eligible:

• Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of clinical decompensation2. Childs Pugh Class B or C (marker of liver disease severity.3. Portal hypertension as evidenced by ascites or hydrothorax (current or controlled, in the prior year), varices, or platelet count < 80/nL (without hematological cause)

Exclusion Criteria:

• Gut-absorbable or intravenous antibiotic therapy in the last 4 weeks (rifaximin not included in this list; rifaximin use is permissible in this study)

• History of inflammatory bowel disease, short gut, gastrointestinal tract fistulas, intestinal ischemia, or any form of ongoing colitis.

• Prior diagnosis of dementia or other primary neurocognitive disorder.

• History of any prior gastric or duodenum surgery.

• Any gastrointestinal surgery in the last year.

• Substantial immune compromise/deficiency (e.g., uncontrolled HIV, active immune suppressive therapy including high doses of corticosteroids or medications to prevent graft rejection, recent myeloablative therapy, sustained neutropenia)

• History of liver transplant.

• Pregnancy or breast feeding.

• Platelet count < 30/nL or INR > 2 at enrollment (OK to continue enrollment if these values develop during the study, but would preclude repeat endoscopic biopsy)

• Active hepatitis C, B, or HIV virus viremia (detectable viral load)

Cirrhosis Controls will be excluded if they have a:

• History of overt HE as defined by West Haven Criteria (but then could be study candidates as a “case”)

Healthy Controls will be excluded if they have a:

• Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of portal hypertension.

• Platelet count < 150/nL (as this may indicate portal hypertension and cirrhosis)

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 7/31/2025. Questions regarding updates should be directed to the study team contact.