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

Sponsor

University Hospital, Bonn (Other)

Overall Status

Recruiting

CT.gov ID

NCT04578301

Collaborator

(none)

200

Enrollment

Location

75.3

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhosis Portal Hypertension Surgery Acute-On-Chronic Liver Failure Non-Cirrhotic Portal Hypertension	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:

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

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

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Sep 22, 2020

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Surgery

Patients with and without liver cirrhosis undergoing surgery.

Other: No Intervention

No Intervention

Outcome Measures

Primary Outcome Measures

Episodes of Acute-on-Chronic Liver Failure (ACLF) [90 days]
Development of ACLF after surgery

Secondary Outcome Measures

1-year mortality [12 months]
Death after surgery
Episodes of Acute Decompensation [12 months]
Acute hepatic Decompensation after Surgery

Other Outcome Measures

Intestinal Microbiota [12 months]
Intestinal Microbiota will be assessed in stool samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)