Abstract
BackgroundThe cirrhosis complications hepatic encephalopathy, ascites, and variceal bleeding increase mortality but develop in random sequence. Therefore prognoses based on the presence or absence of these clinical complications are inherently inaccurate, and other determinants of the clinical course should be identified. Here we present our study of patho-etiological factors that may be causally involved in the development of specific complications to alcoholic cirrhosis; it was based on a model of cirrhosis pathophysiology encompassing hepatic metabolic capacity, continued alcohol consumption, and circulatory dysfunction.MethodsWe followed a Danish community-based cohort of 466 patients with alcoholic cirrhosis. Stratified Cox regression was used to examine the effects of GEC (a measure of hepatic metabolic capacity), alcohol consumption, and plasma sodium concentration (a measure of circulatory dysfunction) on the hazard rates of first-time hepatic encephalopathy, first-time ascites, first-time variceal bleeding, and mortality. We adjusted for confounding by comorbidity, gender, and age. Data on risk factors and confounders were updated during follow-up.ResultsA low GEC increased the risk of first-time hepatic encephalopathy (hazard ratio [HR] 1.21 per 0.1 mmol/min GEC loss, 95% CI 1.11-1.31), but was unassociated with other adverse events. Alcohol consumption increased the risk of first-time ascites (HR 3.18, 95% CI 1.19-8.47), first-time variceal bleeding (HR 2.78, 95% CI 1.59-4.87), and mortality (HR 2.45, 95% CI 1.63-3.66), but not the risk of first-time hepatic encephalopathy. Hyponatremia increased the risk of all adverse events.ConclusionsReduced hepatic metabolic capacity, alcohol consumption, and hyponatremia were causally involved in the development of specific complications to alcoholic cirrhosis.
Highlights
The cirrhosis complications hepatic encephalopathy, ascites, and variceal bleeding increase mortality but develop in random sequence
We recently described the development of hepatic encephalopathy, ascites, and variceal bleeding in Danish patients with alcoholic cirrhosis [1]
Cirrhosis patients have reduced hepatic metabolic capacity, and the residual capacity can be measured with the galactose elimination capacity (GEC) test [2], the result of which is a strong predictor of mortality [3]
Summary
The cirrhosis complications hepatic encephalopathy, ascites, and variceal bleeding increase mortality but develop in random sequence. We present our study of patho-etiological factors that may be causally involved in the development of specific complications to alcoholic cirrhosis; it was based on a model of cirrhosis pathophysiology encompassing hepatic metabolic capacity, continued alcohol consumption, and circulatory dysfunction. We recently described the development of hepatic encephalopathy, ascites, and variceal bleeding in Danish patients with alcoholic cirrhosis [1] The appearance of these complications increased mortality, but they developed in random sequence. Cirrhosis is accompanied by renal dysfunction and water dyshomeostasis causing hyponatremia which is associated with increased mortality [5] We examined whether those three pathoetiological factors—reduced hepatic metabolic capacity, continued alcohol consumption, and circulatory dysfunction—are causally involved in the development of specific complications to alcoholic cirrhosis, and not merely predictors of an elevated mortality. Our study was based on a model of cirrhosis pathophysiology restricted to the three patho-etiological factors and relevant confounders, and we aimed to establish causal links between the pathophysiology and the clinical course of alcoholic cirrhosis
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