TY - JOUR
T1 - Controversies in clinical trials for alcoholic hepatitis
AU - Lieber, Sarah R.
AU - Rice, John P.
AU - Lucey, Michael R.
AU - Bataller, Ramon
N1 - Publisher Copyright:
© 2017 European Association for the Study of the Liver
PY - 2018/3
Y1 - 2018/3
N2 - Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease, contributing to significant morbidity and mortality. Yet, the only available therapies that improve survival are corticosteroids and liver transplantation, with no new drugs successfully developed for decades. This article briefly describes the current state of affairs in AH therapy and examines the practical and ethical challenges of conducting controlled trials in patients with severe AH. While prednisolone is considered standard of care in severe AH, this recommendation remains controversial given the marginal benefits and questionable long-term safety of steroids. Placebo-controlled trials without steroids may be necessary and ethically justified in certain populations with AH who have not been adequately investigated. Ultimately, we suggest that the field will advance with the development of a plausible animal model of true AH, a consensus on a composite clinical endpoint that does not rely solely on mortality, as well as the adoption of the NIAAA Alcoholic Hepatitis Consortia recommendations regarding standard definitions and when to request a liver biopsy prior to study entry.
AB - Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease, contributing to significant morbidity and mortality. Yet, the only available therapies that improve survival are corticosteroids and liver transplantation, with no new drugs successfully developed for decades. This article briefly describes the current state of affairs in AH therapy and examines the practical and ethical challenges of conducting controlled trials in patients with severe AH. While prednisolone is considered standard of care in severe AH, this recommendation remains controversial given the marginal benefits and questionable long-term safety of steroids. Placebo-controlled trials without steroids may be necessary and ethically justified in certain populations with AH who have not been adequately investigated. Ultimately, we suggest that the field will advance with the development of a plausible animal model of true AH, a consensus on a composite clinical endpoint that does not rely solely on mortality, as well as the adoption of the NIAAA Alcoholic Hepatitis Consortia recommendations regarding standard definitions and when to request a liver biopsy prior to study entry.
KW - Alcohol use disorder
KW - Alcoholic liver disease
KW - Ethics of placebo-controlled trials
KW - Prednisolone
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U2 - 10.1016/j.jhep.2017.09.013
DO - 10.1016/j.jhep.2017.09.013
M3 - Short survey
C2 - 28966126
AN - SCOPUS:85035136587
SN - 0168-8278
VL - 68
SP - 586
EP - 592
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -