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

Surgery Clinical Trial

— PERSEVERE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04578301
• Other study ID #: PERSEVERE
• Status: Recruiting
• Start date: September 22, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2022
• Source: University Hospital, Bonn
• Contact: Michael Praktiknjo, MD
• Phone: +4922828716375
• Email: michael.praktiknjo[@]ukbonn.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Fibrosis
• Hepatic Insufficiency
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Liver Diseases
• Liver Failure
• Non-Cirrhotic Portal Hypertension
• Portal Hypertension
• Surgery

Intervention

Other:
• No Intervention
No Intervention

Locations

Country	Name	City	State
Germany	University Hospital Bonn	Bonn

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Intestinal Microbiota	Intestinal Microbiota will be assessed in stool samples.	12 months
Primary	Episodes of Acute-on-Chronic Liver Failure (ACLF)	Development of ACLF after surgery	90 days
Secondary	1-year mortality	Death after surgery	12 months
Secondary	Episodes of Acute Decompensation	Acute hepatic Decompensation after Surgery	12 months