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