Mean platelet volume and mortality in patients with alcohol use disorder.

Several recent studies have pointed out the relationship of platelet size with increased mortality or adverse clinical course. Most studies show that increased mean platelet volume (MPV) may be associated with a deleterious outcome in different settings such as sepsis or neoplasia, whereas other researchers have found the opposite. In inflammatory conditions there is an altered secretion of several cytokines, some of them exerting a marked influence on platelet biogenesis and/or on platelet activation and aggregation. Alcohol use disorder is a chronic situation characterized by a protracted low-grade inflammation. In this study we analyze the relationship between proinflammatory cytokines and MPV and their relationships with mortality in patients with alcohol abuse. We determined serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 and routine laboratory variables among 184 patients with alcohol use disorder admitted to our hospital and followed-up for a median of 42 months. We found that MPV was inversely related to TNF-α (ρ=-0.34), and directly to IL-8 (ρ=0.32, p<0.001 in both cases) and to IL-6 (ρ=0.15; p = 0.046). Reduced MPV was related both with short-term (<6 months) and long-term mortality. Conclusion: These results suggest that inflammatory cytokines are strongly related to MPV. A low MPV is associated with a poor prognosis among patients with alcohol use disorder.

Incidence of cancer and mortality among heavy alcoholics.

BACKGROUND AND AIMS: Cancer risk is increased in alcoholics. Heavy ethanol consumption is also associated with other potentially lethal conditions such as cirrhosis, diabetes, hypertension, dyslipidemia or malnutrition, that increase mortality. The aim of the present study is to analyze the impact on mortality of new cancer development in a cohort of heavy alcoholics. METHODS: Three hundred and thirty nine heavy alcoholics (about 200 g ethanol/daily during more than 15 years), initially admitted for organic problems to our service (reference hospital) were prospectively followed up for a maximum period of 120 months (median = 26, interquartile range = 12-60 months), either as outpatients or during successive admissions. Clinical and laboratory evaluation including incidence of new cancer and drinking habits were recorded at each appointment, as well as mortality. RESULTS: During the study period 57 patients developed cancer and 151 died. Only 75 did not relapse in alcohol drinking. Mortality was related to deranged liver function, relapse of alcohol drinking, and malnutrition, whereas age, the development of new cancer, or the presence of diabetes, dyslipidemia or hypertension did not influence on mortality, especially in cirrhotics and among those who did not quit drinking. Cancer was related to mortality only among non-cirrhotics, together with ethanol abstention and age. CONCLUSIONS: Heavy drinking is associated with high mortality among alcoholic patients admitted to the hospital. If a patient is already cirrhotic or if there is drinking relapse, the development of a new cancer, the concurrent presence of diabetes, hypertension, dyslipidemia, or advanced age have no impact on survival. Mortality is only related to deranged liver function, relapse of alcohol drinking, and malnutrition.

Prognostic Value of Serum Iron, Ferritin, and Transferrin in Chronic Alcoholic Liver Disease.

Ethanol increases iron absorption. Therefore, increased amount of iron reaches the liver, and exerts pro-oxidant effects and stimulates ferritin synthesis and hepatic stellate cell activation, promoting fibrosis and inflammation. These mechanisms would theoretically support a role of ferritin as a marker of the transition to liver cirrhosis, and, consequently, as a prognostic factor, but there is controversy regarding its behavior in alcoholics. We analyzed among 238 severe alcoholics the prognostic value of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC), and the relationships of these variables with liver function, proinflammatory markers (C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor α), and the presence of cirrhosis. Patients showed higher serum ferritin (Z = 2.50, p = 0.031) but lower transferrin (t(264) = 4.81, p < 0.001), TIBC (t(262) = 4.44, p < 0.001), and iron (Z = 3.19, p = 0.001) values compared with 32 age- and sex-matched controls. Ferritin was related to inflammatory cytokines such as IL-8 (ρ = 0.18, p = 0.012) and to IL-6 (ρ = 0.16, p = 0.016), but not to liver function. On the contrary, cirrhotics showed lower transferrin (t(234) = 4.77, p < 0.001) and TIBC (t(232) = 4.67, p < 0.001), but higher TSI (Z = 3.35, p < 0.001) than non-cirrhotics. Transferrin, TSI, and TIBC were related to liver function impairment (marked differences among the Child's groups regarding transferrin (KW (2) = 22.83, p < 0.001), TSI (KW (2) = 15.81, p < 0.001), and TIBC (KW (2) = 21.38, p < 0.001) but only weakly to inflammation (inverse relationships between IL-6 and total iron (ρ = - 0.16, p = 0.017), TIBC (ρ = - 0.20, p = 0.002), and transferrin (ρ = - 0.20, p = 0.003). In accordance, albumin, IL-6, alcohol quitting, and TSI, in this order, were independently related to mortality, but not ferritin or iron.