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Liangpunsakul S.,Indiana University | Liangpunsakul S.,Roudebush Veterans Administration Medical Center
American Journal of the Medical Sciences | Year: 2014

BACKGROUND:: The association between hepatitis B and metabolic syndrome (MetS) has not been well described. Overall epidemiologic evidences for this association have suggested conflicting results. The aim this study was to determine the association between hepatitis B infection and MetS using large U.S. population database, the Third National Health and Nutrition Examination Survey. METHODS:: Individuals aged ≥18 years were included in this study. MetS was defined according to the Third Report of the National Cholesterol Education Program Adult Treatment Panel guideline. The chronic hepatitis B was defined as the presence of hepatitis B surface antigen. The presence of hepatitis B core antibody with/without surface antibody, in the absence of surface antigen, was considered as past exposure to hepatitis B. To represent national estimates, weighted frequencies for chronic hepatitis B and past exposure to hepatitis B are reported. Multivariate logistic regression analysis accounting for age, gender, race, smoking and alcohol status was conducted to identify the independent predictor(s) of MetS. RESULTS:: This study cohort consisted of total population of 593,594 with chronic hepatitis B and 7,280,620 with past exposure to hepatitis B. Prevalence of MetS among included study cohort was 25.7%. Inverse association was observed between MetS and chronic hepatitis B (adjusted odds ratio, 0.32; 95% confidence interval, 0.12-0.84). Among individual components of MetS, waist circumference was inversely associated with chronic hepatitis B (adjusted odds ratio, 0.31; 95% confidence interval, 0.14-0.71). No significant association was noted between past exposure to hepatitis B and MetS or its individual components. CONCLUSIONS:: In this study, the authors noted significant inverse association between MetS and chronic hepatitis B. © 2013 Lippincott Williams and Wilkins.


Liangpunsakul S.,Indiana University | Liangpunsakul S.,Roudebush Veterans Administration Medical Center | Haber P.,University of Sydney | McCaughan G.W.,University of Sydney
Gastroenterology | Year: 2016

Alcoholic liver diseases comprise a spectrum of clinical disorders and changes in liver tissue that can be detected by pathology analysis. These range from steatosis to more severe signs and symptoms of liver disease associated with inflammation, such as those observed in patients with alcoholic hepatitis or cirrhosis. Although the relationship between alcohol consumption and liver disease is well established, severe alcohol-related morbidities develop in only a minority of people who consume alcohol in excess. Inter-individual differences in susceptibility to the toxic effects of alcohol have been studied extensively - they include pattern of alcohol consumption, sex, environmental factors (such as diet), and genetic factors, which vary widely among different parts of the world. Alcoholic liver disease is becoming more common in many parts of Asia, but is decreasing in Western Europe. Treatment approaches, including availability of medications, models of care, and approach to transplantation, differ among regions. © 2016 AGA Institute.


Liangpunsakul S.,Indiana University | Liangpunsakul S.,Roudebush Veterans Administration Medical Center | Chalasani N.,Indiana University
Digestive Diseases and Sciences | Year: 2011

Background: Low serum levels of vitamin D are associated with metabolic syndrome. Participants in NHANES III with unexplained elevation in ALT levels have high prevalence of metabolic syndrome. We hypothesized that the serum concentrations of vitamin D were inversely associated with unexplained elevation in ALT. Methods: A total of 6,826 fasting subjects underwent morning physical examination and met the inclusion and exclusion criteria. From these participants, we have constructed cases with unexplained elevation in ALT (n = 308) and compared their serum vitamin D concentrations to matched controls with normal ALT (N = 979). We examined the prevalence of unexplained elevation in ALT level across different quartiles of vitamin D levels. Results: Participants with unexplained elevation in ALT had significantly lower serum vitamin D levels compared to controls (61.8 ± 26.0 nmol/l vs. 66.8 ± 27.1 nmol/l, P < 0.01). The unadjusted prevalence of unexplained elevation in ALT in patients with highest to lowest quartiles of serum vitamin D levels were 21.4, 21.4, 25.6, and 31.5%, respectively. Compared to lowest quartile, patients with top two quartiles of serum vitamin D levels had significantly lower prevalence of unexplained elevation in ALT (OR, 95% CI for highest quartile 0.62 [0.43-0.89] and for third quartile 0.61 [0.42-0.86]). This relationship persisted even after controlling for metabolic syndrome, insulin resistance, and serum triglycerides. Conclusions: This study suggests a significant inverse relationship between serum vitamin D levels and unexplained elevation in ALT. Further studies are needed to confirm this observation and to understand the basis for and implications of this observation. © 2011 Springer Science+Business Media, LLC.


Debella Y.T.,University of Indianapolis | Giduma H.D.,University of Indianapolis | Light R.P.,University of Indianapolis | Agarwal R.,University of Indianapolis | Agarwal R.,Roudebush Veterans Administration Medical Center
Clinical Journal of the American Society of Nephrology | Year: 2011

Summary Background and objectives Whether chronic kidney disease (CKD) should also be considered a coronary disease equivalent like diabetes is not clear. Design, setting, participants, & methods Veterans with and without diabetes and with and without CKD were prospectively recruited. A competing Cox regression model was used to describe the risk of myocardial infarction (MI) in the two groups (CKD and diabetes) over a decade of follow-up. Results The incidence rate of MI in those without CKD was 0.047/yr and in those with CKD was 0.206/yr. Multivariate adjustment revealed the incident rate ratio for MI in CKD as 3.5 and for diabetes mellitus as 2.5. The cumulative incidence for MI was influenced by CKD and diabetes. CKD was associated with a subhazard ratio for MI of 3.74; in contrast, diabetes was associated with a subhazard ratio for MI of 2.6. For the outcome of all-cause mortality, after multivariate adjustment, CKD was associated with a hazard ratio (HR) of 1.86, which was similar to the HR of 2.27 for prevalent coronary artery disease. The HR for diabetes was NS at 1.35. Conclusions CKD is associated with a risk of death similar to that of established coronary artery disease and higher than that of diabetes mellitus. CKD is associated with a risk of MI that is at least as much as that from diabetes mellitus. Among veterans, CKD appears to be a coronary disease equivalent. ©2011 by the American Society of Nephrology.


Ringer J.M.,Roudebush Veterans Administration Medical Center | Lysaker P.H.,Indiana University
Journal of Nervous and Mental Disease | Year: 2014

Heightened levels of anger and dysregulated expression of anger have been associated with poorer outcomes and treatment response for persons with schizophrenia spectrum disorders. Less is known, however, about the psychological processes that determine the extent to which anger is expressed in a more versus less adaptive manner. To explore this issue, this study gathered reports of anger expression style in 88 persons with schizophrenia or schizoaffective disorder using the State-Trait Anger Expression Inventory, Second Edition. The authors additionally assessed anxiety, suspiciousness, emotion recognition, self-esteem, and cumulative trauma history. Correlations and multiple regression analyses showed that outward anger control, that is, the suppression of anger, was predicted by lower levels of suspiciousness, poorer emotion recognition, and reduced anxiety. Participants who endorsed greater anxiety and had experiencedmore traumatic events reported a heightened tendency to express anger both inwardly and outwardly. © 2014 by Lippincott Williams & Wilkins.


Supakul R.,Indiana University | Liangpunsakul S.,Roudebush Veterans Administration Medical Center
Translational Research | Year: 2011

The mechanisms underlying alcohol-induced hepatic steatosis are complex, involving the disturbance of several signaling pathways. We have gained a better understanding of the role of the innate immune system in the liver and its effects on lipid metabolism and uncovered a number of circulating factors that can influence the response of the liver to ethanol. In this report, we will focus on the potential role of ceramide on AMP-activated protein kinase, as a mediator of alcohol-induced hepatic steatosis. © 2011 Mosby, Inc. All rights reserved.


Chayanupatkul M.,Albert Einstein Medical Center | Liangpunsakul S.,Indiana University | Liangpunsakul S.,Roudebush Veterans Administration Medical Center
World Journal of Gastroenterology | Year: 2014

Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Jinjuvadia R.,Ford Motor Company | Liangpunsakul S.,Indiana University | Liangpunsakul S.,Roudebush Veterans Administration Medical Center
Journal of Clinical Gastroenterology | Year: 2015

Background: Alcoholic hepatitis (AH) is the most florid manifestation of alcoholic liver disease which accounts for significant morbidity, mortality, and financial burden. Aim of this study is to evaluate temporal trend of hospitalizations from AH and evaluate its financial impact. Methods: The National Inpatient Sample databases (from 2002 to 2010) which are collected as part of Healthcare Cost and Utilization Project by Agency for Healthcare Research and Quality were utilized. Individuals aged 21 years and older were included. The hospitalizations with primary diagnosis of AH were captured by ICD-9 codes. The national estimates of hospitalization were derived using sample weights provided by National Inpatient Sample. Simple linear regression method was used to assess trends in mortality and length of stay over time. Results: We observed the increased in total cases of AH-related hospitalization from 249,884 (0.66% of total admission in 2002) to 326,403 (0.83% of total admission in 2010). The significant increase in the total admission rate was attributable mainly to the rise in inpatient hospitalization for secondary diagnosis of AH (0.48% in 2002 to 0.67% in 2010). Most of the AH-related hospitalization were males. Hepatic encephalopathy was found to be the most common admitting diagnosis for individuals hospitalized with secondary diagnosis of AH (8.9% in 2002 and 8.6% in 2010). There was a significant decrease in inpatient mortality for primary diagnosis of AH from 10.07% (in 2002) to 5.76% (in 2010) (absolute risk reduction: 4.3%). Average cost of hospitalization related to primary diagnosis of AH was $27,124 and $46,264 in 2002 and 2010, respectively. After adjusting for inflation, the additional cost of each hospitalization seemed to increase by 40.7% in 2010 compared with 2002 (additional cost per hospitalization $11,044 in 2010 compared with 2002). Federal (Medicare) or state (Medicaid) supported health insurance program are the main primary expected payers for these AH hospitalizations (∼25% to 29%). Despite increase in cost per hospitalization, length of stay for hospitalization due to primary diagnosis of AH was not observed to decrease substantially over time (6.7 d in 2002 to 6.1 d in 2010). Conclusions: AH-related hospitalization continued to increase during the study period, despite the decrease in the in-hospital mortality rate. Substantial increases in health care cost and utilization among hospitalized AH patients were observed. © 2014 Wolters Kluwer Health, Inc.


Bellido T.,Indiana University | Bellido T.,Roudebush Veterans Administration Medical Center
Calcified Tissue International | Year: 2014

Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet-to-be-identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone-resorbing osteoclasts. Osteocytes are also the source of molecules that regulate the generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function or to altered expression of either molecule in osteocytes markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling. © 2013 Springer Science+Business Media New York.


Moorthi R.N.,Indiana University | Kandula P.,Indiana University | Moe S.M.,Indiana University | Moe S.M.,Roudebush Veterans Administration Medical Center
Current Opinion in Nephrology and Hypertension | Year: 2011

Purpose of review Patients with chronic kidney disease (CKD) are often insufficient in 25(OH) vitamin D and are almost uniformly deficient in 1,25(OH)2 vitamin D, because of decreased renal hydroxylation resulting from hyperphosphatemia and elevated fibroblast growth factor- 23 (FGF-23) levels. These same abnormalities lead to secondary hyperparathyroidism for which the administration of ca\lcitriol or vitamin D analogs has been the mainstay of therapy for decades. This review summarizes new trials of vitamin D, calcitriol, and its analogs over the last 2 years. Recent findings In addition to the endocrine effects of the vitamin D axis on bone and mineral metabolism, studies have demonstrated there is also extrarenal conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D in multiple cells leading to autocrine effects. This advance has led to the speculation that CKD patients may also need to be supplemented with ergocalciferol or cholecalciferol. Unfortunately, to date, the majority of interventional studies have focused on biochemical end points. There are no randomized controlled trials demonstrating that therapy with any formulation of vitamin D results in improved patient level outcomes. Summary Despite the physiologic importance of vitamin D in health and disease, more research is required to determine which vitamin D derivative is required for optimal health in CKD patients. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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