The goal of this observational study is to develop and test a new questionnaire called the Liver Cirrhosis Cognitive Decline Scale (LiCCoS) for adults with liver cirrhosis. This questionnaire is designed to help identify problems with thinking and daily mental functioning that are common in people with liver cirrhosis but are often missed during routine care.

People with liver cirrhosis may experience problems such as forgetfulness, slowed thinking, trouble paying attention, or difficulty planning everyday tasks. These problems can affect daily life, safety, and treatment adherence. Existing cognitive tests often require special training or equipment and may not fully reflect how people experience these difficulties in daily life. This study aims to create a simple, patient-reported tool that captures these concerns in an easy and practical way.

The main questions this study aims to answer are:

1. Can the LiCCoS questionnaire reliably measure cognitive difficulties in adults with liver cirrhosis?
2. Does the questionnaire correctly reflect differences in cognitive function across levels of liver disease severity?
3. Do LiCCoS scores relate to results from commonly used cognitive screening tests?

Participants will be adults aged 18 to 75 years who have a confirmed diagnosis of liver cirrhosis and are attending outpatient clinics. Participation is voluntary.

Participants will:

Provide basic background information, such as age and medical history

Complete the LiCCoS questionnaire about their thinking and daily mental functioning

Complete standard cognitive screening tests commonly used in clinical care

This study does not involve any treatment or change in medical care. The information collected will be used only for research purposes. The results are expected to help develop a reliable and easy-to-use tool that can support early recognition of cognitive difficulties in people with liver cirrhosis and improve communication between participants and health care providers.

This study is an observational, cross-sectional investigation designed to develop and psychometrically validate a patient-reported outcome measure, the Liver Cirrhosis Cognitive Decline Scale (LiCCoS), for adults with clinically confirmed liver cirrhosis. The study focuses on cognitive difficulties associated with cirrhosis, including attention, psychomotor speed, working memory, executive function, and cirrhosis-related impacts on daily functioning.

Study Rationale and Conceptual Framework

Cognitive impairment related to liver cirrhosis is common and may occur even in the absence of overt hepatic encephalopathy. While several objective tests are used in clinical practice, these tools often require trained personnel or specialized administration and may not adequately reflect participant-perceived cognitive difficulties in everyday life. LiCCoS is intended to address this gap by providing a disease-specific, patient-reported instrument grounded in neurocognitive theory and clinical relevance to cirrhosis.

The conceptual framework for LiCCoS integrates established models of attention, working memory, executive function, and psychomotor processing, together with cirrhosis-specific functional impacts. Items are framed in participant-centered language to enhance interpretability and usability in routine clinical and research settings.

Study Design and Phases

The study will be conducted in multiple sequential phases:

Phase 1: Item Generation An initial pool of items will be generated using a structured literature review and semi-structured interviews with adults living with liver cirrhosis. This process aims to ensure comprehensive coverage of relevant cognitive domains and real-world functional concerns.

Phase 2: Content Validation A multidisciplinary expert panel, including clinicians and cognitive specialists, will evaluate item relevance and clarity. Content validity will be assessed using standard content validity indexing methods to guide item refinement.

Phase 3: Face Validity and Pilot Testing The refined questionnaire will be pilot-tested in a small group of participants to evaluate clarity, comprehension, and feasibility. Feedback from this phase will inform final adjustments before large-scale validation.

Phase 4: Psychometric Validation The finalized LiCCoS will be administered to a larger sample of adults with liver cirrhosis. Psychometric evaluation will include assessment of dimensionality, internal consistency reliability, and construct validity. Factor structure will be examined using exploratory and confirmatory approaches, and relationships with established cognitive screening tools and clinical severity classifications will be evaluated.

Data Collection and Study Procedures

Participants will complete LiCCoS once during a routine outpatient visit or through a secure data collection platform, depending on participant preference. Standard cognitive screening tools used in routine clinical care may also be administered for validation purposes. Sociodemographic and clinical information relevant to disease characterization will be collected from participants and verified through medical records when available.

No experimental intervention, treatment modification, or clinical decision-making is part of this study. All procedures are observational in nature.

Data Management and Quality Assurance

Data will be collected using structured case report forms or secure electronic data capture systems with restricted access. Quality assurance measures will include:

Predefined data entry rules to minimize missing or inconsistent responses

Range and logic checks to identify out-of-range or internally inconsistent data

Periodic review of collected data by the study team for completeness and accuracy

Secure storage of de-identified data using coded participant identifiers

Source data verification may be conducted on a subset of records by comparing collected data with medical records to assess accuracy and completeness.

A data dictionary will be maintained to define all variables, response options, and scoring rules used in the study. Standard operating procedures will guide participant recruitment, data collection, data handling, and analysis activities.

Sample Size Considerations

The planned sample size is based on methodological recommendations for scale development and psychometric validation, using participant-to-item ratios sufficient to support factor analysis and reliability assessment. The total sample will include participants enrolled during pilot testing and the main validation phase.

Statistical Analysis Overview

Statistical analyses will be conducted using standard statistical software. Descriptive statistics will summarize participant characteristics. Psychometric analyses will assess reliability, dimensionality, and construct validity of LiCCoS. Comparative analyses will explore score differences across clinically relevant subgroups defined by disease severity and demographic factors.

Ethical and Regulatory Considerations

The study will be conducted in accordance with the Declaration of Helsinki and applicable national and institutional ethical guidelines. Ethical approval will be obtained prior to participant enrollment. Written informed consent will be obtained from all participants before data collection. LiCCoS scores will not be used for diagnosis or treatment decisions and are intended solely for research validation purposes

Inclusion Criteria:

• Age 18-75 years.
• Documented clinical diagnosis of liver cirrhosis based on imaging, histology, or validated clinical criteria.
• Able to read and understand the language of the cognitive tests.
• Willing and able to provide written informed consent.

Exclusion Criteria:

• Age <18 or >75 years
• Known case of Overt Hepatic Encephalopathy defined as Grade II or higher on the West Haven criteria [25].
• Use of central nervous system depressants, anticholinergics, or psychotropics initiated or changed within the past 4 weeks.
• Known case of Severe uncorrected visual or hearing impairment limiting ability to complete cognitive testing.
• Known case of Any neurological and psychological disorders, substance use disorder and sleep disorders.
• Known case of Severe systemic illness (e.g., end-stage renal disease, decompensated heart failure) that may independently impair cognition or limit participation.

Participants will be recruited from adults receiving outpatient care for liver cirrhosis at the Departments of Gastroenterology and General Medicine of Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR) Hospital, Mullana, Haryana, India. The study population represents individuals with clinically managed chronic liver disease who attend Maharishi Markandeshwar Super Specialty Hospital and are capable of completing questionnaire-based assessments. Recruitment will occur during regular clinic visits without altering standard medical care.

Individual participant data (IPD) will not be shared. The data collected in this study are derived from a newly developed, institution-specific questionnaire and include sensitive health and cognitive information. Data sharing is restricted to protect participant privacy and confidentiality, in accordance with institutional ethics approval, informed consent provisions, and applicable data protection regulations. Only aggregated, de-identified results will be reported through publications and registry postings.