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

Abstract

ditions and in response to other treatments. (HEPATOLThere 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 vali-clinical 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 pa-more stringent method to validate a surrogate end point is tients with alcoholic cirrhosis (22 who continued drink-the 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 pe-the 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 capac-end 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 rePreliminary data have suggested a possible use of changes gression analyses, persistent alcohol abuse and galac-in 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 per-crease in quantitative liver function tests and survival shown sistent alcohol abuse, only the former remained signifi-in 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 galac-ease, the lack of effective treatments improving liver fun...

Review article: alcoholic liver disease – pathophysiological aspects and risk factors

“…In clinically compensated alcoholic cirrhosis, the 5‐year survival is about 90% in persistent abstainers, while lower than 70% in persistent drinkers. Once decompensated liver disease develops, the 5‐year survival falls to 30% at best in patients who continue drinking 23–26 …”

Breath testing for human liver function assessment

“…For some 40 years, the galactose elimination capacity (GEC) test has been performed as a quantitative liver function test, 11 showing a significant correlation with the severity of chronic liver disease, 141 , 142 and a usefulness for the prognosis of liver cirrhosis 143–145 …”

[13C]‐Galactose breath test: correlation with liver fibrosis in chronic hepatitis C

“…Since the work of Tygstrup [1] in the early 1960s, the galactose elimination capacity test (GEC) has been widely used in various liver diseases. Recently, the GEC has been proposed as a possible surrogate marker of death in advanced liver diseases such as alcoholic cirrhosis or primary biliary cirrhosis [2][3][4]. To date, however, no quantitative liver function test has been demonstrated to be significantly altered in the early stages of liver diseases; the GEC has been shown to be of no value in chronic hepatitis without cirrhosis [5,6], and similar results have been observed with more recent tests, such as the monoethylglycinexilidide formation from lidocaine metabolism (MEGX test) [7].…”