May the Risk of PHLF be Predicted With Preoperative Liver Gadoxetate MRI (MR-Predict)

November 27, 2023 updated by: Per Sandström, University Hospital, Linkoeping

Is It Possible To Predict PHLF? - Retrospective Analysis of Gadoxetate MRI Prior To Major Liver Resection

Post hepatectomy liver failure (PHLF) is one of the most severe complications after liver re-section. Preoperative evaluation of liver function is complicated and imprecise. The volume and function needed for each individual patient is unknown and the methods used for evaluation are uncertain. Preoperative MRI with Gadolinium may give dynamic information regarding liver function correlating with postoperative liver failure. A retrospective analysis will be performed regarding this topic.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Post hepatectomy liver failure (PHLF) is one of the most severe complications after liver re-section. Preoperative evaluation of liver function is complicated and imprecise. The volume and function needed for each individual patient is unknown and the methods used for evaluation are uncertain. Arbitrary volume limits have been postulated but still there are patients dying of PHLF with volumes well above these limits.

On multivariate analyses, age ≥70 years, pre-operative chemotherapy, steatosis, resection of >3 segments, vascular reconstruction and intraoperative blood loss >300 mL significantly increased the risk of PHLF. Combining ISGLS grades B and C groups resulted in a high sensitivity for predicting mortality compared to the 50-50 rule and Peak bilirubin >7 mg/dL.

For patients with low volume of the future liver remnant (FLR) there are techniques to in-crease the volume prior to resection. Portal vein embolization (PVE) is an established meth-od, whereas associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is relatively new. Augmentation of the volume of the FLR is indicated for patients with FLR less than 20%, provided no intrinsic liver disease exists, 30% after chemotherapy and 40% for patients with compromised liver function, for example liver cirrhosis.

Both methods, PVE and ALPPS, have high risks of morbidity and mortality, especially post hepatectomy liver failure (PHLF), why other alternatives are evaluated. Liver venous depri-vation (LVD), adds liver vein/s occlusion with a plug/plugs when PVE is performed or after PVE. Preliminary data indicate that the growth rate with this percutaneous method is equivalent to ALPPS with function following in parallel. Still all three methods add one extra treatment stage to increase liver volume of the FLR but still suffers the risk of PHLF. Furthermore, a large group of patients is treated with one stage hepatectomy where the volume and function also may be limited.

Liver volume estimation has been the main method to ensure safe resections, but as many studies have explored functional tests with the goal of increasing safety. The most used ones are Indocyanine green (ICG), maximum liver function capacity (LiMax) , Child Pugh (CP) score and Hepatobiliary scintigraphy (HBS). Still, none of these, alone or in combination have been able to completely ameliorate this dreadful complication. In addition, the cut-off levels for resection for each of these methods are arbitrary, mainly because PHLF is relative-ly rare as are major liver resections. Furthermore, all the tests are time consuming, costly and demanding for the patients.

The development of liver gadoxetate (=Primovist) MRI has given hope that this method may provide similar information as that of hepatobiliary scintigraphy (HBS), but with a higher resolution of liver function on a segmental level and at the same time enable liver volume estimation of the FLR as well as tumour burden and anatomy. In addition, MRI may also add quantitative information regarding steatosis, fibrosis (MRE) and iron content, factors previ-ously not included in any test used to estimate liver function.

So, with one modality most of the information gathered with all the other methods could possibly be incorporated into one.

Data regarding the increase in volume, as well as function, during the first week after PVE/ALPPS/LVD is sparse. Previous studies have shown that after PVE the increase in func-tion in the non-embolized lobe is larger than the increase in volume. The opposite has been shown for patients operated with ALPPS where the increase in volume was larger than the increase in function.

HBS has become common in several centers to estimate the liver function prior to major hepatectomy, including TSH and ALPPS. One disadvantage is the relatively poor spa-tial resolution which therefore necessitates another radiological study to assess the tumor burden in the liver. Dynamic gadoxetate MRI has been shown to be comparable with HBS to assess the liver function, with a very strong correlation between the two methods. Also, in PVE patients, it strongly indicates the risk of PHLF after resection when there is no in-creased enhancement in the FLR after 2 weeks.

Liver MRI is increasingly used prior to liver resection for analysis of liver tumour burden and anatomy. The long-term goal of this project is to find simple functional measures that can be obtained from the standard clinical MRI used today in everyday clinical practice. In this way we would ultimately have a method to both evaluate segmental function (gadoxetate), fat and iron storage, fibrosis, volume, tumour burden and anatomy.

Study aim The overall aim of this retrospective study is to evaluate if a preoperative MRI with liver specific contrast agent (gadoxetate, aka Primovist) add segmental functional information and if this information can be used to predict PHLF more accurate than with FLR calculation alone. Thus, the result of the functional analysis will be used to identify factors in the MRI examination that correlates to the risk of PHLF. Based on the gadoxetate MRI data, a pro-spective clinical trial will be designed afterwards to validate the results of this retrospective study. The final goal is to establish a pre-operative workup based on a Primovist MRI proto-col, providing a robust and predictive functional and volumetric measure in all preoperative examinations. This might contribute to a more accurate risk assessment of patients sched-uled for hepatcetomy, thus reducing both post-operative, PHLF related morbidity and mortality.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients who have had a Primovist MRI within 8 weeks before hemihepatectomy or extended hemi-hepatectomy +/- bile duct anastomosis independent of diagnosis.
  2. Patients with cirrhosis who have had a Primovist MRI within 8 weeks before resection of more than one liver segment
  3. Patients who had liver volume augmentation with a pre-operative Primovist MRI less than 2 weeks before resection

  4. Patients who have had a Primovist MRI within 6 weeks be-fore any liver resection where PHLF or death within 90 days occurred.

    -

Exclusion Criteria:

  1. <18 years of age
  2. Resection was not performed -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: experimental arm
Single arm study. All patient who had an MRI performed before liver resection is included
Diagnostic test: MRI
Liver MRI before liver resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Contrast dynamics of Gadoxetate MRI correlation with the risk of PHLF.
Time Frame: 2 years
MRI dynamics correlation with postoperative liver failure. Measurement of gadoxetate uptake pattern in the liver and correlation of this pattern to the risk of developing post hepatectomy liver failure.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between preoprative and postoperative risk factors and PHLF
Time Frame: 2 years
Multivariable analysis of risk factors for Postoperative liver failure including but not limited to: Charlson score, 50:50 rule, CP, MELD, ICG, renal function, thrombocyte count, signs of portal hypertension (portal vein diameter, spleen size), type of resection, bleeding, operation time, diagnosis, neoadjuvant chemo and preoperative liver volume augmentation, MRI contrast dynamics
2 years
MRI protocol description report on method used MRI protocol description
Time Frame: [Time Frame: 2 years
Presentation of protochol and dynamic analysis used to predict postoperative liver failure
[Time Frame: 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Linkoeping

Investigators

  • Principal Investigator: Per Sandström, Prof, Academic study

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 29, 2020

Primary Completion (Estimated)

February 28, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

December 29, 2020

First Submitted That Met QC Criteria

December 30, 2020

First Posted (Actual)

December 31, 2020

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-05708

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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