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Original Research Article

A comparative study of effect of alcohol on , LFT and GGT in a tertiary care hospital

B V Mamatha1, Samalad S Vijay Mahantesh2*, D S ShankarPrasad3, S V Kashinakunti4, R Manjula5

1Associate Professor, Department of Biochemistry, Subbaiah Institute of Medical Sciences, Shimoga, Karnataka, INDIA. 2Consultant Paediatric surgeon and Paediatric Urologist, Nanjappa hospital, Kuvempu Road, Shimoga, INDIA. 3,4Professor, Department of Biochemistry, S.N. Medical College, Bagalkot, Karnataka, INDIA. 5Associate Professor, Department of Community Medicine, Bagalkot, Karnataka, INDIA. Email: [email protected]

Abstract Background: Alcoholism is a serious health issue in majority of developing countries. Oxidative stress due to alcoholism leads to injury. Ferritin is an acute phase reactant. The levels of ferritin are found to be elevated in alcoholism. GGT is a marker of alcoholic liver disorders. Objective: To analyse and compare the levels of serum ferritin, LFT markers and GGT in alcoholics and non-alcoholics. Materials and Methods: The study group included 50 patients of alcoholic liver disease and 50 healthy controls who are age and sex matched with cases. Serum ferritin, LFT markers like serum , total protein, albumin, AST, ALT, ALP and GGT were estimated in both cases and controls. Results: The study showed that alcoholic patients have significantly increased levels of ferritin, GGT, serum bilirubin, AST, ALT, ALP compared to controls. Serum proteins and albumin levels were significantly lower in cases compared to controls. Serum ferritin showed positive pearson correlation with AST, ALT and GGT. Conclusion: The increased serum levels of ferritin in cases show that oxidative stress in alcoholics is the main cause of liver injury and associated complications with it. Frequent follow up should be done along with the treatment of the disease. It is necessary to give antioxidant supplements to prevent the complications. Key Word: Alcoholic liver disease, Ferritin, LFT markers, GGT, Oxidative stress

*Address for Correspondence: Dr. Samalad S Vijay Mahantesh, Consultant Paediatric surgeon and Paediatric Urologist, Nanjappa Hospital, Kuvempu Road, Shimoga, Email: [email protected] Received Date: 12/02/2019 Revised Date: 02/04/2019 Accepted Date: 09/06/2019 DOI: https://doi.org/10.26611/10021215

structural and functional derangements.2Alcohol at low Access this article online doses is beneficial in decreasing the incidence of Quick Response Code: myocardial infarction, stroke, and alzheimer’s disease, Website: but consumption more than two standard drinks-per day

www.medpulse.in increases the risk of healthproblems.3Harmful effects of alcohol are encountered with regular consumption of

7.5 units (60 g) of alcohol per day in men and5 units (40g) per day in women.4The identification of Accessed Date: alcoholics, especially in the early stages of alcohol 16 October 2019 abuse is important in preventing adverse health effects

and socioeconomic consequences. Many biochemical parameters in blood and urine have been proposed as INTRODUCTION the biomarkers of alcoholism. The major biomarkers Alcoholic liver disease (ALD)includes wide range of include alanine amino transferase (ALT), aspartate clinical and morphological changes that range from aminotransferase (AST), γ-glutamyl transferase (GGT), fatty liver to hepatic inflammation and alcoholic and carbohydrate deficient and many more. hepatitis to progressive cirrhosis.1 Alcoholism is a plays an important role in various essential cell serious health issue with socioeconomic consequences functions. However, excess iron is toxic and causes .The chronic consumption of alcohol causes multiple lipid peroxidation and tissue damage. Its absorption and

How to cite this article: B V Mamatha, Samalad S Vijay Mahantesh, D S ShankarPrasad, S V Kashinakunti, R Manjula. A comparative study of effect of alcohol on Serum Ferritin, LFT and GGT in a tertiary care hospital. MedPulse International Journal of Biochemistry. October 2019; 12(1): 21-24. https://www.medpulse.in/Biochemistry/ MedPulse International Journal of Biochemistry, Print ISSN: 2550-763X, Online ISSN: 2636-4573, Volume 12, Issue 1, October 2019 pp 21-24 transport therefore needs to be tightly regulated. It is a liver function test markers. We also hypothesized that known fact that iron stores are increased in alcoholics. serum ferritin may be acting as a marker of acute phase Iron accumulation has been proved as one of the reactant, reflecting the inflammatory status of patients mechanisms involved in chronic liver disease. Both iron of chronic alcohol abuse, rather than as a marker of iron and alcohol can initiate free radical formation and overload. produce oxidative stress within liver and hence fasten the progression toward cirrhosis.5 ,6 Ferritin is a positive AIMS AND OBJECTIVES: acute-phase protein. High serum ferritin is found in a To estimate and compare the levels of Serum ferritin, large spectrum of conditions including LFT and GGT in alcoholics and non alcoholics. haemochromatosis, alcoholic liver disease etc... Serum ferritin is frequently reported to be elevated in chronic MATERIALS AND METHODS alcoholics. The liver contains much of the iron stored in This study was conducted in Medicine OPD and the body, and any process that damage liver cells will inpatients admitted in SNMC and HSK hospital, release ferritin. It is also possible that liver damage may Navanagar, Bagalkot, over a period of 6 months. Serum interfere with clearance of ferritin from the circulation. levels of ferritin, LFT and GGT were estimated in 50 Liver injury due to oxidative stress causes hepatic male alcoholic patients who are considered as cases endothelial cells to release ferritin into circulation. and50 controls who are age and sex matched healthy Ferritin may amplify the toxic effects of alcohol non-alcoholic subjects. Study design was case control towards fibrosis and cirrhosis. The leakage of tissue study. Detailed clinical history was taken regarding ferritin which is an intracellular iron storage protein, number of drinks, type of drink and duration of alcohol 7 causes increase in serum ferritin. Serum gamma drinking. glutamyl transferase (GGT), is often the first marker to Inclusion criteria: be elevated in alcoholics. It increases in a dose- 1. 50 alcoholic male patients aged between 25 to dependent manner in alcohol misuse. It is less sensitive 60 years in women than men. The enzyme may be released by 2. Alcohol abuse was determined by CAGE hepatic cell injury or by induction following exposure to questionnaire, which is a screening test for alcohol. Hepatocyte cholestasis and hepatocytedamage problem drinking and its potential problems in alcoholic liver disease causes increase in GGT. It 3. Alcohol consumption more than 2 or more increases after five weeks of drinkingmore than 50 g per drinks per day for more than 1 year duration. day. It usually increases to three times the upper Exclusion criteria: reference limit, but will normalise within five weeks of patients with 8 abstinence. It has a half-life of 26days. Serum GGT 1. viral Hepatitis levels rise in response to the acute hepatocellular 2. Chronic inflammatory diseases damage. The levels are especially high in patients with 3. Malignancies severe alcoholic liver disease. These are more likely to 4. cirrhosis of liver due to other causes be elevated in the regular rather than the episodic 5. iron therapy drinkers. The (ALT) and aspartate 6. evidence of gastrointestinal bleeding transaminase (AST) levels are elevated in patients with 7. evidence of disorders associated with iron viral hepatitis, toxic hepatitis, cholestasis, cirrhosis, liver carcinoma, and alcoholic liver disease. The serum 8. diabetes mellitus, thyroid disorders. AST and ALT levels are often raised in patients who are Written informed consent was taken. Institutional alcoholics although generally not to more than 2-4 times ethical committee approval was taken before starting the the upper limits of the normal range. An AST/ALT ratio study. A sample of 5 ml venous blood was collected which is > 1.5, strongly suggests an alcohol- induced under standard aseptic precautions. Sample was damage to the liver, and a ratio which is > 2.0 confirms centrifuged to obtain clear serum. Serum ferritin was 2 this diagnosis. Several studies have reported elevated estimated by chemiluminescence method. LFT were serum ferritin, LFT and GGT levels in patients with measured spectrophotometrically using A25 Biosystems ALD. There are not many studies in India which show Autoanalyser. GGT was estimated by SZASZ method association of alcohol with ferritin, although incidence using semiautoanalyser 3300. of alcohol abuse is quite high in India compared to other Statistical Analysis: Data obtained was tabulated and developing countries. Hence, the present study was analysed by applying appropriate statistical tests using undertaken to evaluate the effects of alcoholic liver SPSS package version 17. Results were expressed as disease on the serum levels of ferritin, GGT and other mean ±SD. Comparison of variables between two

MedPulse International Journal of Biochemistry, Print ISSN: 2550-763X, Online ISSN: 2636-4573, Volume 12, Issue 1, October 2019 Page 22 B V Mamatha, Samalad S Vijay Mahantesh, D S ShankarPrasad, S V Kashinakunti, R Manjula groups performed with student t-test. The p value < 0.05 Table 3: Total protein, albumin and globulin levels in both the were considered statistically significant. groups: Characteristics Groups Mean ±SD t p RESULTS Cases 5.9±0.7 Protein -1.9 0.53 Table 1 shows mean age in both the groups and it is Controls 6.3±0.6 statistically insignificant. We have compared liver Cases 3.1±0.5 Albumin -4.9 0.0001 function parameters like Total bilirubin, direct and Controls 3.8±0.5 Cases 2.8±0.4 indirect bilirubin, total proteins, albumin and globulin, Globulin 2.7 0.08 and liver enzymes like ALT and AST in both cases and Controls 2.5±0.5 controls. Table 2 shows statistically significant increased total bilirubin levels in cases. Serum albumin, Table 4: SGOT, SGPT and ALP levels in cases and controls: Globulin, ALT, AST, GGT and ferritin were Characteristics Groups Mean ±SD t p Cases 68.5±30.4 significantly increased in cases when compared to SGOT 8.8 0.0004 Controls 19.0±6.6 controls with p<0.05as shown in tables 3,4,5 Cases 54.7±39.9 SGPT 5.1 0.0006 respectively. Controls 17.4±6.0 Table 1: Mean age in both the groups: Cases 102.4±62.0 ALP 4.8 0.0009 Characteristics Groups Mean ±SD t p Controls 47.4±10.1 Age Cases 44.2±7.7 0.048 0.96 Controls 44.09±9.0 Table 5: Comparison of serum GGT and Ferritin levels in cases

Table 2: Total bilirubin, direct and indirect bilirubin levels in both and controls: the groups: Characteristics Groups Mean ±SD t p Cases 103.0±12.9 Characteristics Groups Mean ±SD t p GGT 22.5 0.0007 Cases 1.7±2.2 Controls 32.1±11.4 Total bilirubin 2.72 0.09 Cases 585.5±481.9 Controls 0.5±0.19 Ferritin 5.6 0.0004 Cases 1.0±1.9 Controls 94.7±53.4 Direct bilirubin 1.88 0.65 Controls 0.35±0.11 The levels of SGOT, SGPT and GGT showed positive Cases 0.69±0.5 correlation with serum ferritin levels but did not show Indirect bilirubin 4.99 0.0005 controls 0.2±0.08 statistical significance (fig 1,2,3).

Figure 1: Pearson correlation of SGOT and ferritin; Figure 2: Pearson correlation of SGPT and ferritin; Figure 3: Pearson correlation of GGT and ferritin

Table 6: Pearson’s Correlation between Ferritin with SGOT, SGPT and GGT in cases Cases p value r value Ferritin vs SGOT 0.374 0.168 Ferritin vs SGPT 0.276 0.205 Ferritin vs GGT 0.548 0.11

DISCUSSION marker. That is why we had excluded patients who were Our study provides striking evidence that alcohol taking iron therapy, who had history of bleeding in the consumption has effects on iron status. Increase in recent past and persons with other inflammations and serum iron and ferritin may be useful in individuals who infections. Alcoholic liver disease is commonly are iron deficient but not in all patients. Excess iron may associated with . The possible mechanisms lead to oxidative stress and generation of free radicals explained for iron overload are, taking iron in and may lead to harmful effects on liver. Our aim in this hepatocytes in specific way through increased levels of study was to show serum ferritin as oxidative stress (TfR) and increased intestinal iron

Copyright © 2019, Medpulse Publishing Corporation, MedPulse International Journal of Biochemistry, Volume 12, Issue 1, October 2019 MedPulse International Journal of Biochemistry, Print ISSN: 2550-763X, Online ISSN: 2636-4573, Volume 12, Issue 1, October 2019 pp 21-24 absorption from decreasing hepcidin.9 The results and GGT in Liver associated Diseases. Euro. J. Exp. Bio., explain that concentrations of Ferritin and GGT in the 2013,3(2), 280-284. serum of alcoholics are significantly higher when 2. Shivashankara A.R., et al., A Correlative Study on the Aminotransferases and Gamma Glutamyl Transferase in the compared with non alcoholics (p < 0.05)This is in Saliva and Serum of Chronic Alcoholics Before and After accordance with studies by Suneetha N et al,T.E.Meyer Alcohol Deaddiction , Journal of Clinical and Diagnostic et al, J. B. Whitfield et al.7,10,11 Total bilirubin, Serum Research. 2011 June, Vol-5(3): 512-515 albumin, Globulin, SGOT, SGPT, GGT and ferritin 3. Schuckit MA. Alcohol and alcoholism. In: Kasper DL, were significantly increased in cases when compared to Braunwald E,Fauci AS, editors. Harrison’s Principles of controls with p<0.05.similar findings were obtained in Internal Medicine. 16th ed.New York, NY: McGraw Hills; 12,13,14 2005. p. 2562-6. other studies. The levels of SGOT and SGPT, 4. P aivikki Alatalo, Heidi Koivisto,Katri Puukka, Johanna GGT showed positive correlation with serum ferritin Hietala, Petra Anttila,Risto Bloigu, Onni Niemel . levels but did not show statistical significance. Alcohol Biomarkers of Liver Status in Heavy Drinkers, Moderate consumption causes changes in oxidant-antioxidant Drinkers and Abstainers .Alcohol and AlcoholismVol. 44, system. Alcohol metabolism generates reactive oxygen No. 2, pp. 199–203, 2009 species and lipid peroxidation products. Due to liver 5. Ishii H, Kurose I, Kato S. Pathogenesis of alcoholic liver diseasewith particular emphasis on oxidative stress. J injury, hepatic endothelial cells release ferritin into GastroenterolHepatol1997;12:S272-82 circulation, in response to increased oxidative stress. 6. Mane M, Mane P, Prajapati P, Afzalpurkar S, Aundhakar A. Alcohol-mediated oxidative stress is involved in the Effect of Alcohol Consumption on Indices of Serum Iron and inhibition ofhepcidin promoter activity and transcription Ferritin in a Tertiary Care Hospital of Rural, Maharashtra. Int in the liver. The combination of both agents may add up J Sci Stud 2016;3(12):160-165. to exacerbate oxidativeinjury and fibrogenesis in the 7. Suneetha N, , Devika Rani K, Padma Rupa, ShrutiMohanty, Pragna Rao , Syndrome of Malnutrition-Inflammation liver. It is possible that the elevations in serum markers Complex in Chronic Alcoholics. of iron stores that we observed among alcohol users do 8. Harriet Gordon , Detection of alcoholic liver disease. World J not reflect a true elevation in body iron stores. It is also Gastroentero, 2001;7(3):297 – 302. possible that alcohol consumption itself provokes 9. Mohamed Abdel-HalemHelaly, El-Sayed ZakiHatata , Ehab changes in acute-phase proteins, of which ferritin is El-Sayed Abdel-Khalek, Ibrahim AhmedAbdel Aal, Elevated one.15 Levels of Serum Ferritin May be Related to Non-Alcoholic Steatohepatitis. Eur J Basic Med Sci 2011;1(1):13-20. 10. T.E.Meyer,C.Kassianides,T.H.Bothwell,A.Green Effects of CONCLUSION heavy alcoholconsumption on serum ferritin concentrations S In our study we found that serum ferritin is A Medical Journal Volume 66, 13 October1984. significantly increased in alcoholics. Serum ferritin 11. J. B. Whitfield, G. Zhu, A. C. Heath, L. W. Powell, and N. 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MedPulse International Journal of Biochemistry, Print ISSN: 2550-763X, Online ISSN: 2636-4573, Volume 12, Issue 1, October 2019 Page 24