Trial Outcomes & Findings for Hepatic Vein Flow During Orthotopic Liver Transplantation as Predictive Factor for Postoperative Graft Function (NCT NCT03814031)

Results Overview

Primary outcome was early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on postoperative day 7. and ALT/AST \> 2,000 IU/L Systolic and diastolic hepatic vein flow index was assessed intraoperatively in neohepatic phase in both of EAD and non EAD group, and reported.

Recruitment status

COMPLETED

Target enrollment

97 participants

Primary outcome timeframe

EAD met at any point within the first 7 days status post OLT

Results posted on

2024-09-23

Participant Flow

Participant milestones

Participant milestones
Measure	EAD After Orthotopic Liver Transplantation Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation No EAD noted after orthotopic liver transplantation NO intervention
Overall Study STARTED	26	71
Overall Study COMPLETED	26	71
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EAD After Orthotopic Liver Transplantation n=26 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=71 Participants No EAD noted after orthotopic liver transplantation NO intervention	Total n=97 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=26 Participants	0 Participants n=71 Participants	0 Participants n=97 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=26 Participants	41 Participants n=71 Participants	51 Participants n=97 Participants
Age, Categorical >=65 years	16 Participants n=26 Participants	30 Participants n=71 Participants	46 Participants n=97 Participants
Age, Continuous	58 years n=26 Participants	55 years n=71 Participants	56 years n=97 Participants
Sex: Female, Male Female	11 Participants n=26 Participants	28 Participants n=71 Participants	39 Participants n=97 Participants
Sex: Female, Male Male	15 Participants n=26 Participants	43 Participants n=71 Participants	58 Participants n=97 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	26 participants n=26 Participants	71 participants n=71 Participants	97 participants n=97 Participants

PRIMARY outcome

Timeframe: EAD met at any point within the first 7 days status post OLT

Primary outcome was early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on postoperative day 7. and ALT/AST \> 2,000 IU/L Systolic and diastolic hepatic vein flow index was assessed intraoperatively in neohepatic phase in both of EAD and non EAD group, and reported.

Outcome measures

Outcome measures
Measure	EAD After Orthotopic Liver Transplantation n=26 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=71 Participants No EAD noted after orthotopic liver transplantation NO intervention
EAD HV flow systolic index	1.23 L/kg/min Interval 0.85 to 1.73	2.19 L/kg/min Interval 1.28 to 3.7
EAD HV flow diastolic index	0.87 L/kg/min Interval 0.62 to 1.32	1.54 L/kg/min Interval 1.07 to 2.34

SECONDARY outcome

Timeframe: Acute rejection noted at any point within 6-8 weeks post transplant

Population: Adult patients undergoing the orthotopic liver transplant piggy-back technique with TEE-measured HV flow

Acute rejection noted with biopsy at any point within 6 to 8 weeks post-transplant

Outcome measures

Outcome measures
Measure	EAD After Orthotopic Liver Transplantation n=8 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=5 Participants No EAD noted after orthotopic liver transplantation NO intervention
Acute Rejection HV flow systolic index	0.738 L/kg/min Interval 0.69 to 1.341	1.535 L/kg/min Interval 0.844 to 2.57
Acute Rejection HV flow diastolic index	0.571 L/kg/min Interval 0.57 to 1.024	1.101 L/kg/min Interval 0.708 to 1.644

SECONDARY outcome

Timeframe: postoperative day 7 assessment

Population: Adult patients undergoing the orthotopic liver transplant piggy-back technique with TEE-measured HV flow

Normal total bilirubin \< 1.2 mg/dL

Outcome measures

Outcome measures
Measure	EAD After Orthotopic Liver Transplantation n=52 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=45 Participants No EAD noted after orthotopic liver transplantation NO intervention
Prolonged (>Seven Days) Time to Normalize Total Bilirubin (TIME T-bil) HV flow systolic index	1.086 L/kg/min Interval 0.691 to 1.438	2.051 L/kg/min Interval 1.077 to 2.868
Prolonged (>Seven Days) Time to Normalize Total Bilirubin (TIME T-bil) HV flow diastolic index	0.806 L/kg/min Interval 0.469 to 1.04	1.351 L/kg/min Interval 0.954 to 2.186

SECONDARY outcome

Timeframe: postoperative day 7 assessment

Population: Adult patients undergoing the orthotopic liver transplant piggy-back technique with TEE-measured HV flow

Normal INR \< 1.16

Outcome measures

Outcome measures
Measure	EAD After Orthotopic Liver Transplantation n=35 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=62 Participants No EAD noted after orthotopic liver transplantation NO intervention
Prolonged (>Seven Days) Time to Normalize INR (TIME Inr) HV flow systolic index	1.081 L/kg/min Interval 0.639 to 1.604	1.484 L/kg/min Interval 0.736 to 2.518
Prolonged (>Seven Days) Time to Normalize INR (TIME Inr) HV flow diastolic index	0.954 L/kg/min Interval 0.526 to 1.222	1.050 L/kg/min Interval 0.666 to 1.526

SECONDARY outcome

Timeframe: postoperative day 7 assessment

Population: Adult patients undergoing the orthotopic liver transplant piggy-back technique with TEE-measured HV flow

Normal platelet count \> 140 B/L

Outcome measures

Outcome measures
Measure	EAD After Orthotopic Liver Transplantation n=75 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=22 Participants No EAD noted after orthotopic liver transplantation NO intervention
Prolonged (>Seven Days) Time to Normalize Platelet Count (TIME Plt). HV flow systolic index	1.341 L/kg/min Interval 0.69 to 2.243	1.379 L/kg/min Interval 0.867 to 2.553
Prolonged (>Seven Days) Time to Normalize Platelet Count (TIME Plt). HV flow diastolic index	0.829 L/kg/min Interval 0.713 to 1.98	1.024 L/kg/min Interval 0.58 to 1.47

POST_HOC outcome

Timeframe: Timing is postoperatively at any point 6-8 weeks. Duration is a day.

Population: Randomly chosen 30 patients among enrolled patients

Intra-rater and inter-rater reliability analyses of HVFi are performed using intraclass correlation coefficient (ICC). We randomly pick up 30 images and obtain consistency ICC for inter-observer variability using all three investigators (A, B, and C), and absolute-agreement ICC for intra-observer variability using investigator C, who measure all images twice with an interval between 6 and 8 weeks. For inter-observer variability, 3 investigators post-hoc determine HVFi based on the pulse-wave Doppler signal.

Outcome measures

Outcome measures
Measure	EAD After Orthotopic Liver Transplantation n=30 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=30 Participants No EAD noted after orthotopic liver transplantation NO intervention
Intra-rater Reliability Analyses of HVFi	0.998 ICC Interval 0.997 to 0.999	0.998 ICC Interval 0.996 to 0.999

POST_HOC outcome

Timeframe: Timing is postoperative at any point. Duration is a day.

Population: Randomly chosen 30 patients among enrolled patients

Intra-rater and inter-rater reliability analyses of HVFi are performed using intraclass correlation coefficient (ICC). We randomly pick up 30 images and obtain consistency ICC for inter-observer variability using all three investigators (A, B, and C). For inter-observer variability, 3 investigators post-hoc determine HVFi based on the pulse-wave Doppler signal.

Outcome measures

Outcome measures
Measure	EAD After Orthotopic Liver Transplantation n=30 Participants Early allograft dysfunction (EAD), which was defined by the presence of one or more of the following: total bilirubin (t-bil) ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days. NO intervention	No EAD After Orthotopic Liver Transplantation n=30 Participants No EAD noted after orthotopic liver transplantation NO intervention
Inter-rater Reliability Analyses of HVFi	0.997 ICC Interval 0.995 to 0.998	0.993 ICC Interval 0.988 to 0.996

Adverse Events

EAD After Orthotopic Liver Transplantation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

No EAD After Orthotopic Liver Transplantation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Yoshihisa Morita

Henry Ford Hospital

Phone: 3059784358

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place