Should impaired liver function be held responsible for cognitive impairment and poor health-related quality of life in alcoholic cirrhosis?
Authors: Thomas Paparrigopoulos, Elias Tzavellas, Dimitris Karaiskos, Ioannis Liappas
Journal: Hepatology (2007)

In their study in HEPATOLOGY, Prasad et al.1 showed that lactulose administered to patients with cirrhosis who have minimal hepatic encephalopathy considerably improves cognitive functions and consequently health-related quality of life. In this context, the authors suggested that ammonia plays the key role in the observed cognitive deficits. However, in the description of their sample, approximately 60% of the studied population is reported as having cirrhosis due to alcohol abuse. It is well established that chronic alcohol abuse produces measurable and often long-lasting cognitive/neuropsychological deficits and morphological brain damage, through the intricate direct and indirect toxic effects of alcohol on the central nervous system,2 that are independent of liver function impairment3; therefore, these deficits should not be attributed primarily to high ammonia levels. It remains an unresolved issue whether these deleterious functional, metabolic, and structural effects are quickly and fully reversible, as recently proposed by various researchers4, 5; instead, everyday clinical practice and research evidence show that several months or maybe years of abstinence are necessary for the recovery of neurocognitive functions. Furthermore, the frequent comorbidity of alcohol abuse/dependence with various psychiatric conditions, that is, mood and anxiety disorders, psychotic disorders, and personality disorders,6 which may at least transiently compromise the mental state and, consequently, a neuropsychological assessment, is a potential influencing factor that needs to be minutely screened for and ruled out before conclusions are reached. For instance, it has been repeatedly reported that 30%–40% of alcohol-dependent individuals fulfill the criteria for a major depressive episode at some time in their lives.6, 7 Moreover, it has been emphasized that there is a complex relationship between alcohol dependence and mood disorders and that the clinical distinction between alcohol-induced and independent major depressive episodes may be difficult to make without the necessary expertise and follow-up assessments.7 Depression is characterized by, among other things, psychomotor agitation or retardation and impaired concentration and thinking, which cause significant distress and functional impairment. Consequently, depression, especially if untreated, may be heavily implicated in poor mental performance reflected in neuropsychological tests. In addition, there is some recent evidence for continuing subtle neuropsychological impairments even in fully remitted patients with a history of major depressive disorder.8 Last but not least, we should be reminded that a large proportion of patients suffering from chronic illnesses, in this case serious hepatopathy, are especially prone to developing symptoms of depression that compromise mental functioning and well-being.9, 10 Therefore, we believe that none of the aforementioned parameters should be underestimated when speculative pathogenetic propositions are advanced regarding cognitive impairment and poor health-related quality of life in patients with alcoholic cirrhosis. Thomas Paparrigopoulos*, Elias Tzavellas*, Dimitris Karaiskos*, Ioannis Liappas*, * Drug and Alcohol Addiction Clinic, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece.