Predicting Acute-on-Chronic Liver Failure After Surgical Intervention in Chronic Liver Disease (PERSEVERE)

Prospective, observational study to define precipitants and predictors of development of Acute-on-Chronic Liver Failure (ACLF) after surgical interventions, allowing to develop a risk stratification for elective procedures in cirrhotic patients. As well as identifying molecular mechanisms of post-interventional ACLF and thus preparing the ground for development of new therapeutic approaches.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Acute-On-Chronic Liver Failure; Surgery; Portal Hypertension; Non-Cirrhotic Portal Hypertension
• Intervention / Treatment: Other: No Intervention

Detailed Description

Background: Acute-on-chronic liver failure (ACLF) is a recently discovered syndrome, which is understood as an acute deterioration of decompen-sated liver cirrhosis. It is defined on the basis of organ failure(s) and associated with high short-term mortality. ACLF is caused by a precipi-tating event that results in excessive systemic inflammation. ACLF is mostly precipitated and associated with bacterial infections but 40-50% of the underlying cause is unclear. Surgery, with or without liver involvement, has been defined as such a precipitating event. It is long known, that surgery in liver cirrhotic patients, depending on stage of cirrhosis as well as on type of surgery, bears a great risk but is still in-evitable in some cases. Child-Turquotte Score has been used for risk stratification of postoperative mortality. The development and out-come of ACLF after surgical interventions have not been characterized yet. In addition, underlying causes as well as molecular mechanism leading to ACLF after surgical intervention have not been identified. The aim of this trial is to further prospectively investigate patients with cirrhosis undergoing surgery to identify clinical markers and molecular mechanisms involved in development of ACLF.

Objectives: Defining precipitants and predictors of development of ACLF after surgical interventions, allowing to develop a risk stratification for elective procedures in cirrhotic patients.

Identifying molecular mechanisms of post-interventional ACLF and thus preparing the ground for development of new therapeutic approaches.

Study design: Prospective, observational study. Patients will be screened according inclusion/exclusion criteria. After informed consent sample processing will be possible from max. 1 week before scheduled surgery.

Primary endpoints: Development of ACLF within 28 and 90 days after visceral or non-visceral surgery in patients with portal hypertension (liver cirrhosis and idiopathic non-cirrhotic portal hypertension)

Secondary endpoints:

1. Mortality at 1 month, 3 months and 1 year.

   Following endpoints will be evaluated:

   " Time to death and mortality (overall and surgery-related) " Time to and rate of unplanned rehospitalizations after surgery " Any Infection and differentiated by site of infection (SBP, pneumonia, urinary tract infection, blood stream infection, Clostridium difficile-associated enterocolitis " Postsurgical acute hepatic decompensation and ACLF

2. To assess the changes in the intestinal microbiota in both groups and evaluate its effect on the primary endpoint.
3. To assess the potential socioeconomic impact.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Michael Praktiknjo, MD; Phone Number: +4922828716375; Email: michael.praktiknjo@ukbonn.de
• Study Contact Backup: Name: Johannes Chang, MD; Email: johannes.chang@ukbonn.de

Study Locations

• Germany
  • Bonn, Germany
    • Recruiting
    • University Hospital Bonn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with and without liver cirrhosis and/or portal hypertension undergoing elective or emergency surgical intervention.

Description

Inclusion Criteria:

• Male or female adult (≥18 years) patient
• With or without liver cirrhosis (diagnosed either histologically or by a combination of clinical, laboratory and radiological signs)
• Or Non-cirrhotic portal hypertension
• Non-pregnant, non-lactating females
• Ability to understand the patient information and to personally sign and date the informed consent to participate in the study
• The patient is co-operative and available for the entire study
• Provided written informed consent
• Indication for surgical intervention

Exclusion Criteria:

• Pregnant or lactating females
• Patients undergoing surgery as form of palliative cancer therapy
• Presence or history of severe extra-hepatic diseases
• HIV-positive patients
• Previous liver or other transplantation
• Patients with acute or subacute liver failure without underlying cirrhosis
• Patients who decline to participate
• Physician´s denial (e.g. the investigator considers that the patient will not follow the protocol scheduled)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Surgery; Patients with and without liver cirrhosis undergoing surgery.	Other: No Intervention; No Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Episodes of Acute-on-Chronic Liver Failure (ACLF)	Development of ACLF after surgery	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year mortality	Death after surgery	12 months
Episodes of Acute Decompensation	Acute hepatic Decompensation after Surgery	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal Microbiota	Intestinal Microbiota will be assessed in stool samples.	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Bonn

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2020
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; Acute-On-Chronic Liver Failure; Surgery; Portal Hypertension; ACLF; Non-Cirrhotic Portal Hypertension
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Liver Failure, Acute; Liver Diseases; End Stage Liver Disease; Fibrosis; Hypertension; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Liver Cirrhosis; Hypertension, Portal
• Other Study ID Numbers: PERSEVERE

Drug and device information, study documents

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