Research ArticleStatin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients
Introduction
Since their introduction in the late 1980’s, 3-hydroxyl-3-methyl-glutaryl coenzyme A reductase inhibitors, commonly referred to as statins, have become one of the most frequently prescribed drugs in developed countries [1], [2]. Statins are among the most potent lipid-lowering agents, and their efficacy in reducing the incidence of coronary events has been repeatedly demonstrated [3], [4], [5]. Statin use is recommended in current guidelines for treatment of hypercholesterolemia [6] and coronary heart disease [7].
Apart from their lipid-lowering capacities, statins exert pleiotropic effects that may contribute to the beneficial features. Experimental models suggest that statins improve hepatic microcirculation and endothelial function [8], [9], reduce platelet recruitment [10], [11], decrease vascular [12] and systemic inflammation [13], and attenuate hepatic ischemia/reperfusion (I/R) injury [14], [15], [16]. Recently, it has been shown that treatment with simvastatin attenuated lipopolysaccharide-induced hepatic sinusoidal dysfunction in rodents [9]. Additionally, simvastatin and atorvastatin attenuated hepatic injury and fibrosis following bile-duct-ligation in rats [17], [18]. These experimental data indicate that statins have beneficial effects on hepatic perfusion and may have potential effects in preventing and treating ischemic liver injury.
Hypoxic hepatitis (HH), also known as shock liver or ischemic hepatitis, is a life-threatening event associated with high morbidity and mortality [19], [20], [21], [22], [23]. HH is characterized by diffuse hepatic injury resulting from cardio-circulatory or respiratory impairment [19], [20], and its presence is suggested by a marked, transient and potentially reversible increase of aminotransferase levels in the appropriate clinical setting [19], [20], [21], [22], [23]. In critically ill patients at the medical intensive care unit (ICU), incidence rates of up to 11% with an ICU-mortality rate of 57% were observed [22]. Treatment of the underlying condition is currently the only therapy. As ischemia/reperfusion injury, inflammation, and endothelial/sinusoidal dysfunction are cardinal factors contributing to development of HH [24], statins may influence incidence and course of HH in critically ill patients.
Therefore, we investigated whether statin treatment prior to ICU admission affects incidence rates, severity and complications of HH in this prospective study in critically ill patients at the medical ICU.
Section snippets
Patients and methods
This prospective study was performed at 3 medical ICUs located at the Medical University Vienna (Vienna, Austria). All patients admitted to the 3 ICUs, between December 2008 and December 2009, were eligible for inclusion in the study. A total of 851 consecutive patients were included and studied prospectively.
All patients were prospectively screened for new onset of HH within 48 h after ICU admission. This observation window was chosen due to the reported time frame of rise of aminotransferase
Patients’ characteristics
Clinical characteristics of the total study cohort stratified to statin use are illustrated in Table 1. 851 patients were included in the study. Primary reasons for ICU admission were cardiogenic events and/or cardiopulmonary resuscitation (n = 274, 32%), infections/sepsis (n = 192, 23%), post-operative care (n = 144, 17%), respiratory insufficiency (n = 98, 11%), neurologic diseases (n = 58, 7%), bleeding (n = 25, 3%), and other (n = 60, 7%). 155 (18%) patients were on statin therapy prior to ICU admission.
Discussion
Liver dysfunction is associated with high morbidity and mortality at the ICU [22], [23], [39]. Hypoxic liver injury is one of the leading types of hepatic impairment in critically ill patients with reported incidence rates exceeding 10 percent [22]. Short-term-mortality in these patients is extremely high exceeding 50% by far. However, apart from treatment of the underlying condition, there are no established therapeutic opportunities or prophylactic measures. We report results of the first
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
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2018, Clinics in Liver DiseaseCitation Excerpt :Biopsy, although not usually performed, demonstrates centrilobular (zone 3) necrosis.79 Statins have been noted to be a protective factor against developing ischemic hepatitis, whereas active alcohol consumption is a risk factor.80 Ischemic hepatitis accounts for 0.3% to 6% of ALF cases.81,82
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