The course of galactose elimination capacity in patients with alcoholic cirrhosis: Possible use as a surrogate marker for death

✍ Scribed by C Merkel; G Marchesini; A Fabbri; S Bianco; G Bianchi; E Enzo; D Sacerdoti; M Zoli; A Gatta

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 183 KB
• Volume: 24
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510240412

✦ Synopsis

ditions and in response to other treatments. (HEPATOL-

There is increasing interest for the use of surrogate OGY 1996;24:820-823.) end points in the evaluation of treatments in patients with liver disease, but adequate validation is seldom

Recent research in clinical epidemiology focused on the valavailable. This study aimed to describe the different idation of surrogate end points to be used instead of the true, course of galactose elimination capacity in patients with clinically relevant events which need a long time to take alcoholic cirrhosis who continued to drink or abstained place. 1,2 Before a surrogate end point may be used in the from alcohol consumption during follow-up, and to valiclinical practice, its adequacy must be proven in the clinical date changes in galactose elimination as a surrogate end problem, and with the therapeutic options under study. 3 The point for death from liver-related causes. Forty-five pamore stringent method to validate a surrogate end point is tients with alcoholic cirrhosis (22 who continued drinkthe analysis of a trial or a series of trials performed on the ing throughout the study period, and 23 who stopped clinical problem under study, to verify if (or to what extent) drinking and were abstinent throughout the study pethe surrogate end point meets the criteria proposed by Prenriod) were retrospectively selected among patients who tice. 4 In particular, the first criterion requests that the occurhad galactose elimination capacity measured at 6-month rence of the surrogate end point is linked to the occurrence intervals. During follow-up 10 drinkers and 3 abstainers of the true end point; the second criterion requests that the died of liver-related causes (P Å .025). Abstainers showed mechanism(s) through which treatment influences the true a transient improvement in galactose elimination capacend point is directly and at the same time related to the ity, followed by a decrease. Continuous drinkers showed occurrence of the surrogate end point. a reduction from the beginning. According to Cox's re-Preliminary data have suggested a possible use of changes gression analyses, persistent alcohol abuse and galacin quantitative liver function tests as surrogate markers for tose elimination capacity were separately related to the survival in patients with chronic liver disease. 5 The first risk of death, but, when a time-dependent model was Prentice's criterion is proven by the strict association of defitted containing galactose elimination capacity and percrease in quantitative liver function tests and survival shown sistent alcohol abuse, only the former remained signifiin many series. [6][7][8] The adherence to the second criterion is cant. This implies that variations in the risk of death more difficult to prove, and should be assessed for any single occurring as a consequence of abstinence from alcohol treatment. Unfortunately, in patients with chronic liver disconsumption may be predicted from changes in galacease, the lack of effective treatments improving liver function tose elimination capacity, and that the mechanisms and survival makes this second criterion difficult to fulfill. through which abstinence influences survival are Abstinence from alcohol in alcoholic cirrhosis may be considstrictly linked to the mechanisms responsible for the ered a model treatment improving survival through improvechanges in the test. Because of the strict association of ment in liver function, and the different course of values decrease in galactose elimination capacity and short of a quantitative liver function test in patients who start survival, as proved in several series, this observation abstinence, compared with that of patients who continue represents adherence to the criteria requested for adedrinking, may mimic the effect of a drug treatment in a cliniquacy of a surrogate end point. In conclusion, in alcocal trial. Very few data are available on the course of quantiholic cirrhosis the decrease in galactose elimination catative liver function tests during follow-up in patients with pacity is an adequate surrogate end point for death from cirrhosis in relation to persistent alcohol abuse or abstiliver-related causes, which is worth testing in other connence. 9 In the present study we described the course of galactose elimination capacity (GEC) in a group of cirrhotics with alcohol abuse, divided into a group who abstained during follow-Abbreviation: GEC, galactose elimination capacity. up and a group who continued drinking, and analyzed the From