Clinical trial NCT04578301: Predicting Acute-on-Chronic Liver Failure After Surgical Intervention in Chronic Liver Disease
Official title: Predicting Acute-on-Chronic Liver Failure After Surgical Intervention in Chronic Liver Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Liver Cirrhosis
Portal Hypertension
Surgery
Acute-On-Chronic Liver Failure
Non-Cirrhotic Portal Hypertension
Keywords: ACLF
Acute-On-Chronic Liver Failure
Liver Cirrhosis
Portal Hypertension
Surgery
Non-Cirrhotic Portal Hypertension
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2020-10-08
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with and without liver cirrhosis and/or portal hypertension undergoing elective or emergency surgical intervention.

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Episodes of Acute-on-Chronic Liver Failure (ACLF)
timeFrame: 90 days
Secondary outcomes:
measure: 1-year mortality
timeFrame: 12 months
measure: Episodes of Acute Decompensation
timeFrame: 12 months
Other outcomes:
measure: Intestinal Microbiota
timeFrame: 12 months
Locations:
city: Bonn
country: Germany
facility: University Hospital Bonn
Study officials:
affiliation: University Hospital, Bonn
name: Michael Praktiknjo, MD
role: PRINCIPAL_INVESTIGATOR
References: