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.

The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study

“…Our findings are consistent with the existing studies of GEC and mortality of cirrhosis patients [6-12,26,27], but our study extends them by being sufficiently large to examine subgroups; by examining both cirrhosis-related mortality and mortality from other causes; by having complete long-term follow-up; by presenting a near-continuous relationship between GEC and short- and long-term mortality; and by adjusting for relevant confounders.…”

Alcoholic liver disease and the potential role of plasminogen activator inhibitor-1 and fibrin metabolism

“…7,8 Abstinence is also effective in the more severe stages of ALD, and increases survival even in decompensated cirrhotics. 3,9 However, the high rate of recidivism in alcoholics prevents abstinence from being generally effective for ALD. Liver transplantation is also an effective means to treat ALD; however, issues such as organ shortage and costs limit this therapy.…”

Determination of hepatic galactose elimination capacity using 2-[18F]fluoro-2-deoxy-d-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model

“…When corrected for the amount of galactose excreted in urine, an approximate estimate of the hepatic V max for galactose is achieved from the blood disappearance curve using blood concentrations ensuring near-saturation of the enzymatic system [1–4]. The GEC accurately assessed survival prognosis of patients with acute liver failure [5], chronic liver disease [6,7], and patients undergoing liver resection [8]. More interestingly, it has been shown that quantitative liver function tests such as the GEC are far more predictive of the remaining liver function following partial hepatectomy than measurements of liver volumes [9–11].…”