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Multidisciplinary approach to study of patients with Severe Alcoholic Hepatitis Undergoing Liver Transplantation

Award Number: P50AA027054
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Summary Alcoholic liver disease is among the most common indications for liver transplant (LT), accounting for over ¼ of LTs performed annually in the United States. Given concerns of post-transplant recidivism and also the possibility for clinical improvement pre-transplant with abstinence, transplant centers have required 6 months of documented sobriety prior to LT. However, a subset of patients present for medical care with severe alcoholic hepatitis (SAH), requiring urgent and aggressive medical management. If they are unresponsive to steroid-based medical treatment, LT is the only life-saving option. Without LT, SAH patients have a 70-80% three-month mortality, therefore a 6-month sobriety rule precludes these patients from life-saving LT. We have demonstrated through a pilot study and the largest series in the world, that LT for SAH provides excellent short-term survival and similar recidivism rates in comparison to LT for alcoholic cirrhotics with 6 months sobriety. LT for SAH is rare and controversial, because at most centers, the standard 6-month sobriety period is a transplant candidacy requirement. However, critics of the 6 month criteria emphasize that it is an arbitrary length of time and an unreliable predictor of recidivism. In order to minimize risk to the public perception of organ donation, careful analysis of LT selection criteria is crucial to ensure allocation to those with the greatest survival benefit and highest chance of maintained sobriety. Appropriate candidate selection criteria, in an ethical manner, is paramount to identify select SAH patients who would significantly benefit from LT. In this grant proposal we will quantify outcomes and identify risk factors for poor survival after LT in SAH. We will compare outcomes of LT in SAH patients with other end-stage liver disease patients, and determine the ethical issues and evaluate public opinion regarding early LT in SAH patients in an effort to determine a more rational national policy. Further, we propose to more rigorously examine recidivism in our patients post-transplant and compare differing behavioral and pharmacologic interventions to identify best practice care. We also propose to study explanted livers from patients undergoing transplant to characterize at the protein, antibody, and molecular level changes that may help articulate the pathophysiology of SAH. Lastly, we seek to utilize small animal models of liver transplantation in conjunction with alcohol exposure to answer questions about liver regeneration, stem cells, and the immune system that cannot be answered directly from our patients. This work is now being conducted under the auspices of our newly formed “DELTA Center” (Delivery of Early Liver Transplant for Alcoholic Hepatitis) at Johns Hopkins. The quantification of survival benefit of LT in SAH compared to other LT recipients will provide a context for support in the medical community for LT expansion in this population. These clinical aspects in addition to the identification of public opinion regarding early LT for SAH will allow for advancement in the treatment of SAH patients at a national level.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $1,736,736 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	002	5	9/6/2023	SUPPLEMENT FOR EXPANSION	$132,949
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	003	5	9/14/2023	NON-COMPETING CONTINUATION	$0
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	001	5	2/6/2023	NON-COMPETING CONTINUATION	$1,603,787
2023	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	000	4	11/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,736,736

Issue Date FY: 2022 ( Subtotal = $1,621,184 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	000	4	2/1/2022	NON-COMPETING CONTINUATION	$1,459,063
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	001	4	6/23/2022	NON-COMPETING CONTINUATION	$162,121
														Subtotal = $1,621,184

Issue Date FY: 2021 ( Subtotal = $1,635,108 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	001	3	9/28/2021	NON-COMPETING CONTINUATION	$0
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	000	3	2/18/2021	NON-COMPETING CONTINUATION	$1,635,108
														Subtotal = $1,635,108

Issue Date FY: 2020 ( Subtotal = $1,665,534 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	001	2	5/13/2020	NON-COMPETING CONTINUATION	$0
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	000	2	1/31/2020	NON-COMPETING CONTINUATION	$1,665,534
														Subtotal = $1,665,534

Issue Date FY: 2019 ( Subtotal = $1,682,041 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Alcohol Research Programs	000	1	1/21/2019	NEW	$1,682,041
														Subtotal = $1,682,041

Grand Total All Awards = $8,340,603

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Multidisciplinary approach to study of patients with Severe Alcoholic Hepatitis Undergoing Liver Transplantation

Award Number: P50AA027054

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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