A STUDY ON SERUM URIC ACID AND LIVER ENZYMES IN THE GERIATRIC AGE GROUP IN A TERTIARY CARE HOSPITAL

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1 Biochemistry Original Article International Journal of Clinical And Diagnostic Research ISSN Volume 6, Issue 3, May-June 2018 A STUDY ON SERUM URIC ACID AND LIVER ENZYMES IN THE GERIATRIC AGE GROUP IN A TERTIARY CARE HOSPITAL Abstract Elteza T J 1*, Nirmali M 2, Tridip K 3 Hyperuricemia has long been considered as a cause of gouty arthritis and kidney stones but more recently it has also been implicated in the development of liver dysfunction, hypertension, kidney disease, metabolic syndrome, and cardiovascular disease. It has been suggested that hyperuricaemia can lead to oxidative stress, endothelial dysfunction, insulin resistance and systemic inflammation. This study is done with a view to measure the levels of uric acid and liver enzymes(ast, ALT, GGT) in the geriatric age group and to analyse the results statistically. Case group comprised of 30 person of age>60 years attending geriatric OPD while30 healthy subjects of age<60 years were taken as control. Uric acid, AST, ALT and GGT levels were analysed in both case and control group in Vitros 5600 fully automated analyser. The mean values of uric acid, AST, ALT and GGT were significantly higher in case group as compared with the control.the elevation of serum uric acid levels along with the classical liver enzymes might be a risk factor for incidence of chronic liver disease in the elderly. Author Affiliations: 1,2 Department of Biochemistry, Gauhati Medical College & Hospital, Assam. 3 Department of Biochemistry, Tezpur Medical College & Hospital, Assam. Keywords: Uric acid, Aspartate transaminase, Alanine transaminase, Gamma glutamyl transpeptidase *Corresponding Author: Dr. Nirmali Mattack, Demonstrator, Department of Biochemistry, Gauhati Medical College & Hospital, Guwahati, Assam nirmalimattack@gmail.com

2 INTRODUCTION Uric acid (UA) is an endogenous and final oxidation end product of purine metabolism. Humans lack the gene encoding for the enzyme uricase, due to which uric acid cannot be converted to soluble allantoin leading to a rise in the levels of serum UA in humans compared to other mammals that have uricase encoding genes. [1] Till now, hyperuricemia has been considered as a cause of gouty arthritis and kidney stones but recent studies have revealed the fact that it has role to play in the development of liver dysfunction, kidney disease, hypertension,metabolic syndrome, and cardiovascular disease. [2] Liver is a complex and largest organ of the body with interdependent metabolic, excretory and defence functions. [3] Liver abnormalities can be detected easily nowadays with the advent of several screening tests which includes measuring levels of serum Alanine and Aspartate amino transferases (ALT and AST), Gamma glutamyl transpeptidase (GGT) and others. Serum enzyme levels fluctuate widely from normal to moderately abnormal depending on the nature of liver injury. [4,5] Oxidative stress, insulin resistance, and systemic inflammation are now considered to be important risk factors for the development or progression of the most important liver diseases. These conditions also play a vital role in the pathogenesis of non alcoholic fatty liver disease (NAFLD). [6] Over the past few decades, there has been a dramatic increase in the percentage of older people in the general population. In India 60 years and above is considered as geriatric population. Health care professionals should be aware of the changes that distinguish older from younger patients, as these changes bring new challenges in clinical care resulting from the special needs associated with both normal aging and its related chronic illnesses. Various authors and researchers have suggested that hyperuricemia which strongly reflects or may even cause oxidative stress and systemic inflammation, is a risk factor for the development of cirrhosis or the presence of hepatic necro inflammation in the elderly. AIMS & OBJECTIVE: To analyse the levels of UA and liver enzymes (AST,ALT,GGT) in the geriatric group and to correlate the findings statistically. MATERIALS AND METHODS: It was a case- control study conducted in Dept. of Biochemistry and department of geriatric medicine, GMCH after obtaining institutional ethical clearance. The study was conducted for a period of six months from March-September

3 subjects attending Geriatric OPD of age>60 years were taken as case while 30 healthy subjects of age<60 years comprised the control group. Informed written consent was obtained from all the participants. Patients with past history of chronic alcohol intake, any chronic illness like diabetes, cardiovascular disease, gout, liver carcinoma, hepatitis B, C infection were excluded from the study. Sample collection and storage: Taking all aseptic and antiseptic precautions, 5ml of blood was drawn from the median cubital vein. The vials containing separated serum sample were labeled properly and stored at C, if estimations were not done within 8 hours of collection of the blood. However, all estimations were completed within 24 hours of collection of blood sample. Method of evaluation: UA, AST, ALT and GGT were measured in VITROS 5600 fully automated analyser. After all the calculations and the biochemical estimations, the results obtained were statistically analyzed and compared between different groups of the study. Baseline characteristics of the study participants are expressed in mean ± SD (standard deviation). Student t test was used whenever applicable to analyze differences in baseline characteristics between the control and the test group. Correlations were observed by using Pearson correlation coefficient. The results were considered significant when the probability (p value) was less than 0.05 %.Statistical analysis was done using GraphPad InStat version All the statistical graphs were prepared using Microsoft Excel RESULTS: The mean age for case group is years with a standard deviation of 4.53 while in control group it was years with a standard deviation of The case group comprised of 57% male subjects and 43% female subject. The mean value of UA, AST, ALT and GGT were higher in the case group than the control(p<0.0001){table 1}.On doing Pearson correlation UA correlated positively with Age, AST ALT (Table 2). Parameter Uricacid (mg/dl) Control (mean±sd) and GGT Case (mean±sd) Table 1: Showing mean±sd of uric acid, AST, ALT & GGT in both case and control group p value 4.50± ± AST(U/L) 21.8± ± ALT(U/L) 24.43± ± GGT(U/L) 31.06± ±

4 Parameter Parameter r 2 P value Age Uric acid AST ALT GGT Table 2: Showing Pearson s correlation of uric acid with Age, AST, ALT and GGT in the case group DISCUSSION: A significant increase in AST, ALT and GGT levels along with an increase in the UA level is found in the case group. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicate the concentration of hepatic intracellular enzymes that have leaked into the circulation. They are considered as markers for hepatocellular injury and are most helpful in recognizing acute hepatocellular diseases. [7] We also found a significant positive association of rise in UA along with AST, ALT and GGT. These associations are largely independent of other known liver disease. Various studies have pointed to the fact UA level might be a risk factor for the incidence of chronic liver disease like NAFLD.The progression NAFLD is very complex and its exact mechanism is not well understood. Many factors, including genetic, metabolic, and dietary risk factors, are postulated to contribute to the development of NAFLD. Various authors have suggested the two hit theory first hit is the development of hepatic steatosis caused by an imbalance of hepatic lipid metabolism and the second hit is a concurrent inflammatory process from oxidative process. Raised serum UA level is also known to produce pro-inflammatory and pro oxidative effects.[8]. Another study by Ruggerio et al have shown a positive significant relationship between serum UA and many inflammatory markers in Italian men. [9] Related studies are also done in this area that showed that serum UA levels are associated with the progression of chronic liver diseases such as NAFLD and hyperuricemia is independently associated with the severity of liver damage among NAFLD patients.[10] In an experimental study done by Khoshla UM et al it was seen that hyperurecemia caused endothelial dysfunction and reduced bioavailability of nitric oxide in rats. [11] An another study done by Mercuro G et al it was seen that treatment with allopurinol improved endothelial function in patients with hyperuricemia. [12] A similar study done by Benerji et al found novel association between serum UA levels and the incidence of cirrhosis-related hospitalization

5 or the presence of elevated serum ALT or GGT. [13] Whether hyperuricemia is a cause or a consequence of conditions that helps in the progression of liver disease is of utmost importance as the reduction of UA level by pharmacological means will only be useful if it is a cause rather than a result of these conditions. [14] CONCLUSION From the study we found a significant rise in the levels of ALT,AST,GGT and UA in the geriatric age group. Hence the elevation of serum UA levels along with the classical liver enzymes might be considered a risk factor for incidence of chronic liver disease in the elderly. Further studies on this topic are required to investigate whether this association is independent or has clinical utility in the prediction of the presence or incidence of liver disease. Appropriate measures should be taken to keep serum UA levels under control especially in the geriatric population so as to prevent development of liver dysfunction due to elevated liver enzymes. Conflict of Interest Statement- There is no conflict of interest. REFERENCES: 1. Oda M, Satta Y, Takenaka O, Takahata N. Loss of urate oxidase activity in hominoids and its evolutionary implications. Mol Biol Evol. 2002;19(5): Edwards NL. The role of hyperuricemia in vascular disorders. Curr Opin Rheumatol 2009;21: Al-Jumaily E F,. Khaleel F M.The effect of Chronic liver diseases on some biochemical parameters in patients serum. Current Res. Jr. Biological Sc, 2012;4(5): Boker KH, Dalley G, Bahr M J. Long term outcome of hepatitis C virus infection after liver transplantation. Hepatology. 1997; 52(1): Hoofnagle JH, Di Bisceglie AM. The treatment of chronic viral hepatitis. New Engl J Med, 1997:336(5): Li Y, Xu C, Yu C, Xu L, Miao M. Association of serum uric acid level with non-alcoholic fatty liver disease: a cross-sectional study. J Hepatol 2009; 50: Han N, Htoo H K, Aung H.Determinants of abnormal Liver function test in Diabetes patients in

6 Myanmar. Int. Jr. Diabetes Res. 2012, 1(3): Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen activated protein kinase and cyclooxygenase-2. Hypertension 2003;41: Ruggiero C, Cherubini A, Ble A, Bos AJ, Maggio M, Dixit VD, et al. Uric acid and inflammatory markers. Eur Heart J 2006; 27: Petta S, Camma C, Cabibi D, Di Marco V, Craxi A. Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2011;34: Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal C, Mu W, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int 2005; 67: Mercuro G, Vitale C, Cerquetani E, Zoncu S, Deidda M, Fini M, et al. Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk. Am J Cardiol 2004; 94: Benerji GV, Babu MF, Kumari R D, Saha A. Comparative study of ALT,AST,GGT and uric acid levels in liver diseases. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) 2013; 7(5): Edwards NL. The role of hyperuricemia in vascular disorders. Curr Opin Rheumatol 2009; 21:132-7.