Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD.

Sex differences in thrombosis are well described, but their underlying mechanism(s) are not completely understood. Coagulation proteins are synthesized in the liver, and liver gene expression is sex specific and depends on sex differences in growth hormone (GH) secretion -males secrete GH in a pulsatile fashion, while females secrete GH continuously. Accordingly, we tested the hypothesis that sex-specific GH secretion patterns cause sex differences in thrombosis. Male mice were more susceptible to thrombosis than females in the thromboplastin-induced pulmonary embolism model and showed shorter clotting times ex vivo. GH-deficient little (lit) mice were protected from thrombosis, and pulsatile GH given to lit mice restored the male clotting phenotype. Moreover, pulsatile GH administration resulted in a male clotting phenotype in control female mice, while continuous GH caused a female clotting phenotype in control male mice. Expression of the coagulation inhibitors Proc, Serpinc1, Serpind1, and Serpina5 were strongly modulated by sex-specific GH patterns, and GH modulated resistance to activated protein C. These results reveal what we believe to be a novel mechanism whereby sex-specific GH patterns mediate sex differences in thrombosis through coordinated changes in the expression of coagulation inhibitor genes in the liver.

Introduction and aim. Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has seen a rapid increase in incidence in the United States. Racial and ethnic differences in HCC incidence have been observed, with Latinos showing the greatest increase over the past four decades, highlighting a concerning health disparity. The goal of the present study was to compare the clinical features at the time of diagnosis of HCC in Latino and Caucasian patients. Material and methods. We retrospectively screened a total of 556 charts of Latino and Caucasian patients with HCC. Results. The mean age of HCC diagnosis was not significantly different between Latinos and Caucasians, but Latinos presented with higher body mass index (BMI). Rates of hypertension, diabetes, and hyperlipidemia were similar in the two groups. The most common etiology of liver disease was alcohol drinking in Latinos, and chronic hepatitis C in Caucasian patients. Non-Alcoholic Steatohepatitis (NASH) was the associated diagnosis in 8.6% of Latinos and 4.7% of Caucasians. Interestingly, alpha-fetoprotein (AFP) levels at time of diagnosis were higher in Latino patients compared to Caucasians, but this difference was evident only in male patients. Multifocal HCC was slightly more frequent in Latinos, but the two groups had similar cancerous vascular invasion. Latino patients also presented with higher rates of both ascites and hepatic encephalopathy. Conclusion. Latino and Caucasian patients with HCC present with a different profile of etiologies, but cancer features appear to be more severe in Latinos.

To explore the effect(s) of growth hormone signaling on thrombosis, we studied signal transduction and transcription factor 5 (STAT5)-deficient mice and found markedly reduced survival in an in vivo thrombosis model. These findings were not explained by a compensatory increase in growth hormone secretion. There was a modest increase in the activity of several procoagulant factors, but there was no difference in the rate or magnitude of thrombin generation in STAT5-deficient mice relative to control.However, thrombin-triggered clot times were markedly shorter, and fibrin polymerization occurred more rapidly in plasma from STAT5-deficient mice. Fibrinogen depletion and mixing studies indicated that the effect on fibrin polymerization was not due to intrinsic changes in fibrinogen, but resulted from changes in the concentration of a circulating plasma inhibitor. While thrombin-triggered clot times were significantly shorter in STAT5-deficient animals, reptilase-triggered clot times were unchanged. Accordingly, while the rate of thrombin-catalyzed release of fibrinopeptide A was similar, the release of fibrinopeptide B was accelerated in STAT5-deficient plasma versus control. Taken IntroductionThrombosis-related diseases such as myocardial infarction, stroke, and venous thromboembolism account for substantial morbidity and mortality worldwide. We recently demonstrated that thrombosis susceptibility is mediated, in part, by sex-specific patterns of growth hormone (GH) secretion and subsequent effects on expression of coagulation-related genes in the liver. 1 GH is a pleiotropic hormone that is synthesized and secreted by the anterior pituitary gland and has diverse effects on its target tissues. 2,3 Hepatic GH signaling occurs via the type I cytokine receptor, growth hormone receptor, and activation of its primary downstream effectors, the Janus kinase 2 (JAK2) and signal transduction and transcription factor 5 (STAT5). Mice deficient in both STAT5A and STAT5B are largely insensitive to GH and consequently, have an impaired insulin-like growth factor 1-mediated feedback inhibition and dysregulated GH secretion. [4][5][6][7][8] STAT5 is also an integral component of interleukin, erythropoietin, and prolactin signaling pathways. Furthermore, STAT5 can be activated independently of JAK2 by receptor tyrosine kinases and other mechanisms. 9,10 STAT5 has thus been shown to be a central component of GH signaling, as well as other important cytokine signaling pathways.Previously, we demonstrated that GH-deficient little mice are protected from thrombosis in vivo. 1 Considering the important role of STAT5 in GH signaling, we aimed to study the role of STAT5 in thrombosis. In this study, we characterized 2 mouse models of STAT5 deficiency. We predicted that mice deficient in STAT5 would have a decrease in thrombosis susceptibility, as seen in GH-deficient little mice. Surprisingly, we found that the genetic loss of STAT5 resulted in increased susceptibility to thrombosis, in vivo, and shortened clotting times, in vitro. These...