title: The course of galactose elimination capacity in patients with alcoholic cirrhosis: possible use as a surrogate marker for death.
abstract: There is increasing interest for the use of surrogate end points in the evaluation of treatments in patients with liver disease, but adequate validation is seldom available. This study aimed to describe the different course of galactose elimination capacity in patients with alcoholic cirrhosis who continued to drink or abstained from alcohol consumption during follow-up, and to validate changes in galactose elimination as a surrogate end point for death from liver-related causes. Forty-five patients with alcoholic cirrhosis (22 who continued drinking throughout the study period, and 23 who stopped drinking and were abstinent throughout the study period) were retrospectively selected among patients who had galactose elimination capacity measured at 6-month intervals. During follow-up 10 drinkers and 3 abstainers died of liver-related causes (P = .025). Abstainers showed a transient improvement in galactose elimination capacity, followed by a decrease. Continuous drinkers showed a reduction from the beginning. According to Cox's regression analyses, persistent alcohol abuse and galactose elimination capacity were separately related to the risk of death, but, when a time-dependent model was fitted containing galactose elimination capacity and persistent alcohol abuse, only the former remained significant. This implies that variations in the risk of death occurring as a consequence of abstinence from alcohol consumption may be predicted from changes in galactose elimination capacity, and that the mechanisms through which abstinence influences survival are strictly linked to the mechanisms responsible for the changes in the test. Because of the strict association of decrease in galactose elimination capacity and short survival, as proved in several series, this observation represents adherence to the criteria requested for adequacy of a surrogate end point. In conclusion, in alcoholic cirrhosis the decrease in galactose elimination capacity is an adequate surrogate end point for death from liver-related causes, which is worth testing in other conditions and in response to other treatments.
authors.affiliation: Centro di Spleno-Epatologia, Dipartmento di Medicina Clinica e Sperimentale, Università di Padova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Merkel
authors.forename: G
authors.initials: G
authors.lastname: Marchesini
authors.forename: A
authors.initials: A
authors.lastname: Fabbri
authors.forename: S
authors.initials: S
authors.lastname: Bianco
authors.forename: G
authors.initials: G
authors.lastname: Bianchi
authors.forename: E
authors.initials: E
authors.lastname: Enzo
authors.forename: D
authors.initials: D
authors.lastname: Sacerdoti
authors.forename: M
authors.initials: M
authors.lastname: Zoli
authors.forename: A
authors.initials: A
authors.lastname: Gatta
mesh_terms: D000437:Alcoholism / Q000517:prevention & control; D015415:Biomarkers; D003643:Death; D005260:Female; D005500:Follow-Up Studies; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D005690:Galactose