Impact of Graft Steatosis on Post-operative Complications After Liver Transplantation

NCT ID: NCT02659553

Last Updated: 2016-10-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

271 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-01-31

Study Completion Date

2016-10-31

Brief Summary

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1. Clinical impact of graft steatosis on postoperative complications after OLT.
2. Recommendations to improve outcomes after transplantation of steatotic livers and increase donor pool.

Detailed Description

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Introduction Solid organ transplantation has become the standard of care for selected patients with end-stage organ dysfunction. With improved surgical techniques, more effective immunosuppressive therapies, and better anti-infective medications, outcomes after solid organ transplantation have improved over the last several years.

The excellent survival rates reported after orthotopic liver transplantation (OLT) have increased the demand for liver transplants and have enhanced the disparity between the number of available donor organs and the need for such organs.

The lack of available organs for liver transplantation (LT) associated with the increased death rates among patients on most waiting lists for LT has triggered the use of so-called extended criteria donor (ECD) grafts, previously called ''suboptimal grafts''. Among the wide range of these ECD livers, hepatic steatosis is one of the most frequent disorders, which is mostly related to an increasing prevalence of non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is increasingly significant in healthy individuals for its high worldwide prevalence, an association with the metabolic syndrome such as insulin resistance, diabetes, dyslipidemia and obesity, and an association with liver-related morbidity and mortality.

Clinical evaluation and current imaging modalities, and serological and laboratory tests can be strongly suggestive of the presence of hepatic steatosis, but none of these is capable of distinguishing steatohepatitis (SH) from uncomplicated steatosis; likewise, these evaluations can generally detect advanced liver disease (e.g. portal hypertension), but none can truly assess the degree of liver necroinflammatory injury, lesser stages of fibrosis and architectural remodeling. Liver biopsy evaluation, therefore, remains the 'gold standard' to unequivocally diagnose SH and to document the severity of hepatic injury and fibrosis.

Steatosis is assessed according to the pattern and the amount of fatty infiltration in hepatic tissue sections. Traditionally, fatty accumulation has been classified morphologically as macrovesicular or microvesicular. Macrovesicular steatosis is characterized by a single, bulky fat vacuole in the hepatocyte that displaces the nucleus to the edge of the cell. The less conspicuous microvesicular steatosis, usually related to toxins or metabolic disorders, is characterized by accumulation of tiny lipid vesicles in the cytoplasm of hepatocytes without nuclear dislocation. Current quantification and grading of liver steatosis originates from studies performed in the early 1990s, when steatosis was classified as mild, moderate, or severe if, less than 30%, 30-60%, or more than 60% of hepatocytes, respectively, display fatty infiltrations.

Although usually benign, fatty liver may associate with serious injury, with inflammation and hepatocyte necro-apoptosis, non-alcoholic steatohepatitis (NASH), in 20-30% of subjects. Those patients are at risk of developing fibrosis, one fifth progressing to liver cirrhosis. It is apparently more slowly progressive than other chronic liver diseases, such as alcohol or viral-induced disease. Moreover, the problem of hepatocytes being fatty, overcomes the liver itself, as it increases the risk for cardiovascular disease and death and duplicates the risk for type 2 diabetes mellitus (T2DM), independently of the severity of liver injury.

Severe fatty livers are more susceptible to warm and cold ischemia reperfusion injury than normal ones. The type of damage is not through the pathway of cellular apoptosis, but necrosis.

The use of steatotic grafts for orthotopic liver transplantation (OLT) is associated with a high rate of primary graft dysfunction and decreased graft and patient survival particularly with macro-steatosis.

Conditions

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Post-operative Complications

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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mild steatosis

5% - 30% of hepatocytes have fatty infiltration

steatosis

Intervention Type PROCEDURE

Liver Transplantation with graft steatosis

moderate steatosis

30% - 60% of hepatocytes have fatty infiltration

steatosis

Intervention Type PROCEDURE

Liver Transplantation with graft steatosis

No steatosis

No or less than 5% of hepatocytes have fatty infiltration

steatosis

Intervention Type PROCEDURE

Liver Transplantation with graft steatosis

Interventions

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steatosis

Liver Transplantation with graft steatosis

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* All adult patients candidates for liver transplantation are included in this study

Exclusion Criteria

* Pediatric patients are excluded.
* Re- transplanted patients.
* cases with no histopathological examination records
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Università Politecnica delle Marche

OTHER

Sponsor Role collaborator

Sohag University

OTHER

Sponsor Role lead

Responsible Party

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Emad Ali Ahmed Ali

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alaa A. Redwan, Professor

Role: STUDY_DIRECTOR

Sohag University

Marco Vivarelli, Professor

Role: STUDY_DIRECTOR

Università Politecnica delle Marche

Locations

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Polytechnic university of Marche

Ancona, AN, Italy

Site Status

Countries

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Italy

References

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Nocito A, El-Badry AM, Clavien PA. When is steatosis too much for transplantation? J Hepatol. 2006 Oct;45(4):494-9. doi: 10.1016/j.jhep.2006.07.017. Epub 2006 Jul 31. No abstract available.

Reference Type RESULT
PMID: 16919359 (View on PubMed)

El-Badry AM, Jang JH, Elsherbiny A, Contaldo C, Tian Y, Raptis DA, Laczko E, Moritz W, Graf R, Clavien PA. Chemical composition of hepatic lipids mediates reperfusion injury of the macrosteatotic mouse liver through thromboxane A(2). J Hepatol. 2011 Dec;55(6):1291-9. doi: 10.1016/j.jhep.2011.04.019. Epub 2011 May 19.

Reference Type RESULT
PMID: 21703192 (View on PubMed)

Trevisani F, Colantoni A, Caraceni P, Van Thiel DH. The use of donor fatty liver for liver transplantation: a challenge or a quagmire? J Hepatol. 1996 Jan;24(1):114-21. doi: 10.1016/s0168-8278(96)80195-4. No abstract available.

Reference Type RESULT
PMID: 8834034 (View on PubMed)

Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589 consecutive liver biopsies in a single center. J Hepatol. 2007 Aug;47(2):239-44. doi: 10.1016/j.jhep.2007.02.007. Epub 2007 Mar 6.

Reference Type RESULT
PMID: 17400323 (View on PubMed)

McCormack L, Dutkowski P, El-Badry AM, Clavien PA. Liver transplantation using fatty livers: always feasible? J Hepatol. 2011 May;54(5):1055-62. doi: 10.1016/j.jhep.2010.11.004. Epub 2010 Nov 13.

Reference Type RESULT
PMID: 21145846 (View on PubMed)

Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol. 2013 May;58(5):1007-19. doi: 10.1016/j.jhep.2012.11.021. Epub 2012 Nov 23.

Reference Type RESULT
PMID: 23183525 (View on PubMed)

Other Identifiers

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28/9/2014

Identifier Type: -

Identifier Source: org_study_id

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