Prospective Cohort Study of Complications and Outcomes in Cirrhosis

The Complications and Outcomes of Acutely Decompensated Cirrhosis: a Multi-center Nested Cohort Study

This is a multi-center, nested cohort study intended to investigate the prevalence, risk factors, and outcomes of complications in patients with acutely decompensated cirrhosis, especially focused on Cytomegalovirus (CMV) reactivation, bacterial infections, hepatic encephalopathy, and Hepatorenal syndrome. Patients diagnosed with acutely decompensated cirrhosis were enrolled. Upon enrollment, detailed baseline data were collected and samples were harvested. Complications were assessed during hospitalization. Post-discharge follow-up was conducted through telephonic interviews at Day 30 and Day 90.

Study Overview

• Status: Recruiting
• Conditions: Decompensated Cirrhosis; Overt Hepatic Encephalopathy; CMV Reactivation
• Intervention / Treatment: Diagnostic test: Test for CMV reactivation

Detailed Description

This is a multi-center, nested cohort study intended to investigate the prevalence, risk factors, and outcomes of complications in patients with acutely decompensated cirrhosis, especially focused on CMV reactivation, bacterial infections, hepatic encephalopathy, and Hepatorenal syndrome. Patients diagnosed with acute decompensated cirrhosis were enrolled. Upon enrollment, detailed baseline data were collected and samples including ascites, feces, plasma, urine and PBMC were harvested. Following enrollment, patients were subjected to a rigorous follow-up regimen extending over a period of 90 days. Complications were assessed every 3-4 days during hospitalization through a combination of laboratory and clinical evaluations. Post-discharge follow-up was conducted through telephonic interviews at Day 30 and Day 90. Upon the emergence of new complications, such as infections (viral, bacterial or fungal) or hepatic encephalopathy, a detailed, complication-specific protocol was activated (Per complications protocols as follows).

Special complications protocols:

Hepatic encephalopathy:

1. The feces, plasma, and urine were collected at hepatic encephalopathy diagnosis before treatment and at Day 4, 7, 14 since hepatic encephalopathy treatment. If patients were discharged before14 days post-hepatic encephalopathy, the sample at discharge were collocated;
2. The treatment strategy for HE is recorded;
3. The HE severity assessments were carried out daily.

CMV reactivation:

1. The patients' plasma were collected twice a week for the assessment of CMV reactivation; The patients' peripheral blood mononuclear cells (PBMC) samples were collected at baseline and at the time of diagnosis of CMV reactivation;
2. The treatment strategy for CMV is recorded.

• Study Type: Observational
• Enrollment (Estimated): 660

Contacts and Locations

• Study Contact: Name: Jinjun Chen; Phone Number: 13902246336; Email: chjj@smu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University
      • Contact: Jinjun Chen, PHD; Phone Number: 86-18588531001; Email: chjj@smu.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All patients with liver cirrhosis, irrespective of time and circumstances of diagnosis, comorbidities and severity of disease will be offered inclusion in the cohort.

Description

Inclusion Criteria:

• Informed written consent
• Age between 18 years and 80 years
• Cirrhosis based on liver histology or a combination of characteristic clinical, biochemical, and imaging features
• Complications of decompensated cirrhosis (ascites, gastrointestinal bleeding and hepatic encephalopathy)

Exclusion Criteria:

• Malignancy
• Acquired immune deficiency syndrome
• Received immunosuppressive drugs for non-hepatic reasons
• Received organ transplantations

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort; Inpatients diagnosed with decompensated cirrhosis form the Hepatology Unit, Nanfang Hospital, China. All patients with clinically verified diagnosis, irrespective of disease stage and etiology is included.	Diagnostic test: Test for CMV reactivation; All enrolled patients are monitored for CMV reactivation and hepatic encephalopathy using regular clinical tests or library test; Other Names: Test and examine the severity of hepatic encephalopathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of CMV reactivation	Cytomegalovirus DNA was quantified in stored plasma samples using real-time PCR (polymerase chain reaction) assay. DNA extraction was performed on 200 µL of plasma using a QIAamp DNA blood kit (Qiagen, German). Then, 25 µL of Tris (10 mM, pH 8.0) was used to elute the DNA, and 10 µL of the DNA was used for each PCR reaction. The minimum detection level was 102 copies/ml of plasma and values over this lower detection limit were considered to be CMV reactivation positive.	From enrollment to 90 days
Incidence of hepatic encephalopathy	Patients meet West Haven criteria (Grade 1-4) were diagnosed of hepatic encephalopathy.	From enrollment to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to anti-CMV therapy	Patients with CMV reactivation may receive anti-CMV therapy; response to anti-CMV therapy was defined as patients' CMV-DNA test negative at more than 2 times.	From CMV reactivation to one week and 90 days after treatment
Response to treatment for hepatic encephalopathy (HE)	Patients with hepatic encephalopathy may receive lactulose and (or) rifaximin; Patients' extent of HE change to Grade 0 (West Haven criteria) or decreased 2 grade from the baseline were be defined to response to the HE treatment.	From HE diagnosis to one week and 90 days after treatment
Survival	Transplantation free survival	From enrollment to 90 days

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): April 4, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Fibrosis; Liver Cirrhosis; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: NFEC-2023-546

Drug and device information, study documents

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