Natural History of Advanced Chronic Liver Diseases

Natural History of Advanced Chronic Liver Diseases and Factors Associated With Hepatic Events - a Registry Study

This is a retrospective-prospective registry cohort study. Patients with advanced chronic liver disease (ACLD) will be prospectively invited to this study. The study follow-up duration will be 10 years. The primary outcome is incident hepatic events and liver-related mortality. Participants will undergo annual transient elastography examination.

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis; Advanced Chronic Liver Disease
• Intervention / Treatment: Diagnostic test: Transient elastography

Detailed Description

Chronic liver diseases (CLD) has burdened the global healthcare system throughout the years. Among all causes of CLD, chronic hepatitis B (CHB) is generally the commonest cause of CLD in the Asia-Pacific region but the prevalence is expected to decline due to effective antiviral treatment. Similarly, with the introduction of direct-acting antiviral (DAA), chronic hepatitis C (CHC) is now readily curable. On the other hand, an increasing trend is observed in metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ARLD) which is likely to change the landscape of CLD both in the region and worldwide.

Advanced chronic liver disease (ACLD) or cirrhosis is a final common pathway of all CLD and was the 9th and 15th leading cause of death in Southeast Asia (0.42 million deaths) in 2019 as reported by the World Health Organization (WHO) Global Health Estimates. It also significantly increases the risk of hepatocellular carcinoma (HCC). With its significant impact on morbidity and mortality, the prognosis of compensated and decompensated states differ drastically and the field is pushing forward ways to prevent hepatic decompensation in order to improve liver-related outcomes. Non-selective beta-blockers (NSBB) has been shown to reduce risk of hepatic decompensation in patients with compensated advanced chronic liver disease (cACLD) and concomitant clinically significant portal hypertension (CSPH). Some other drugs including angiotensin converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB), statin etc. have been shown in retrospective studies to reduce risk of hepatic decompensation but more evidence is required to draw conclusive interpretation.

Apart from medications, non-invasive tests (NIT), including liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) from vibration-controlled transient elastography (VCTE) help prognosticate chronic liver diseases. Yet more validation is required on certain conditions such as in patients with obesity as well as HCC. Biomarkers are also under the spotlights for risk prediction but are yet to reach the stage for widespread clinical practice. Hence these areas deserve further studies.

Hong Kong is an area endemic for chronic hepatitis B as well as expected for an increase with MASLD and ARLD. There has not been an established registry to capture these ACLD patients for systematic monitoring and analysis. Thus, a registry for ACLD is imperative.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Angel Chim, MSc; Phone Number: 85235054205; Email: angelchim@cuhk.edu.hk
• Study Contact Backup: Name: Jimmy CT Lai, MB ChB; Phone Number: 85235054205; Email: jimmyctlai@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital
    • Contact: Angel Chim, MSc; Phone Number: 85235054205; Email: angelchim@cuhk.edu.hk
    • Contact: Jimmy CT Lai, MB ChB; Phone Number: 85235054205; Email: jimmyctlai@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The prospective cohort will comprise of consecutive patients with advanced chronic liver disease attending hepatology clinics or in-patient care in Prince of Wales Hospital in Hong Kong. All patients will be screened if the eligibility criteria are fulfilled.

Description

Inclusion Criteria:

• Aged 18 or above

• Known ACLD, defined by:

  • LSM > 10kPa or
  • Clinical cirrhosis, suggested by 1. ultrasonography of the hepatobiliary system shows features of cirrhosis (e.g. shrunken and nodular liver) and portal hypertension (e.g. dilated portal vein, portal-systemic collaterals or varices, splenomegaly, ascites). 2. Oesophagogastroduodenoscopy (OGD) shows presence of oesophageal varices (OV) and/or gastric varices (GV) and/or portal hypertensive gastropathy.

Exclusion Criteria:

• Current or past history of hepatocellular carcinoma (HCC)
• History of liver transplantation
• Asplenism or history of splenectomy
• Serious medical illness with limited life expectancy of less than 6 months
• Pregnancy
• Unable to obtain or refusal of informed consent from patient

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with advanced chronic liver disease; Adult patients with advanced chronic liver disease	Diagnostic test: Transient elastography; Liver stiffness and spleen stiffness from transient elastography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incident hepatic events and liver-related mortality	Incident hepatic events (including ascites, variceal bleeding and overt hepatic encephalopathy) and liver-related mortality	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of each hepatic event	Hepatic events include ascites, variceal bleeding and overt hepatic encephalopathy	10 years
Incidence rate of hepatocellular carcinoma	Development of hepatocellular carcinoma	10 years
Changes in Child-Pugh and Model for End-stage Liver Disease scores	The minimum and maximum Child-Pugh score are 5 and 15, respectively. The minimum and maximum Model for End-stage Liver Disease score are 6 and 40, respectively. A higher score denotes worse outcome in both scores	10 years
Change in liver and spleen stiffness	Change in liver and spleen stiffness by transient elastography	10 years
Exploratory outcome on identification of novel biomarkers	Novel biomarkers include multi-omics exploration in relation to the primary outcome.	10 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Jimmy CT Lai, MB ChB, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2024
• Primary Completion (Estimated): December 1, 2035
• Study Completion (Estimated): December 1, 2035

Study Registration Dates

• First Submitted: June 17, 2025
• First Submitted That Met QC Criteria: June 25, 2025
• First Posted (Actual): June 29, 2025

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: advanced chronic liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 2024.258

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data may be shared upon reasonable request.
• IPD Sharing Time Frame: 6 months after the first publication until 15 years after the end of the study
• IPD Sharing Access Criteria: By email communication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No