The objective of this observational study is to compare the differences in proteomics and gut microbiome between the liver cirrhosis group without hepatic encephalopathy and the hepatic encephalopathy group through proteomics and microbiome analysis, screen out the characteristic proteomics and microbiome of patients with hepatic encephalopathy, guide clinical diagnosis and treatment, and conduct in-depth research on the pathogenesis of hepatic encephalopathy. The main questions it aims to answer are:

Are there any differences in serum proteomes between patients with liver cirrhosis without hepatic encephalopathy and those with hepatic encephalopathy? If so, what are the main protein differences? There are differences in the fecal microbiome between patients with liver cirrhosis without hepatic encephalopathy and those with hepatic encephalopathy? If so, what are the main microbial differences?

This study will screen for the differences in proteomes and gut microbiomes between patients with liver cirrhosis without hepatic encephalopathy and those with hepatic encephalopathy, and identify the characteristic proteomes and microbiomes of patients with hepatic encephalopathy to guide clinical diagnosis and treatment.

Inclusion Criteria:

For the NHE (No Hepatic Encephalopathy) Group:

1. Aged between 18 and 85 years, inclusive.
2. Diagnosis of liver cirrhosis.
3. Normal blood ammonia level.
4. West-Haven Criteria grade 0 for Hepatic Encephalopathy.
5. Normal neurological signs.
6. Normal neuropsychological test results.
7. Willing to participate and provides written informed consent.

For the CHE (Covert Hepatic Encephalopathy) Group:

1. Aged between 18 and 85 years, inclusive.

2. Diagnosis of liver cirrhosis.

3. Elevated blood ammonia level.

4. Diagnosis of Covert Hepatic Encephalopathy (West-Haven Criteria grade 0 or I).

   • Grade 0: No personality or behavioral changes but abnormal neuropsychological tests.
   • Grade I: Mild cognitive impairment, lack of awareness, euphoria or anxiety, shortened attention span, or impaired performance of addition/subtraction.

5. Neurological signs are normal or mild asterixis (flapping tremor) may be elicited.

6. Neuropsychological tests are abnormal.

7. Willing to participate and provides written informed consent.

Exclusion Criteria:

1. Diagnosis of any malignant tumor.
2. History of treatment for any malignant tumor.
3. Presence of severe concomitant cardiac, pulmonary, cerebral, or renal diseases, or severe diabetic complications.
4. Use of antibiotics, prebiotics, probiotics, or proton pump inhibitors within the three months prior to enrollment.
5. Pregnancy, lactation, or puerperium.

Study Population: A hospital-based cohort of adult patients (aged 18-85 years) with a confirmed diagnosis of liver cirrhosis, specifically recruited to form two distinct study groups based on the presence or absence of hepatic encephalopathy (HE) and blood ammonia levels.

Sampling Method: Non-Probability Sample. Participants will be consecutively recruited from inpatient units. A purposive sampling strategy will be employed to ensure the successful enrollment of a sufficient number of participants in the Hepatic Encephalopathy (HE) group.

The investigators are currently undecided regarding sharing of Individual Participant Data (IPD). The primary reason for this uncertainty is to ensure full compliance with all regulatory obligations and to uphold the confidentiality commitments made to the study participants during the informed consent process.

Therefore, sharing IPD would require further review and approval by the relevant Institutional Review Board (IRB)/Ethics Committee, and in some cases, may necessitate re-consenting participants, which is not always feasible.

The investigators acknowledge the importance of data sharing for scientific progress. A final decision will be made following the completion of the study and publication of the primary results. The investigators will formally consult with the IRB/Ethics Committee and the data protection officers to determine if and how the data can be shared in a manner that is fully compliant with Chinese regulations and international standards for data privacy.