Seroprevalence and Clinical Profile of Hepatitis C in Type 2 Diabetes Mellitus Patient

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1 Seroprevalence and Clinical Profile of Hepatitis C in Type 2 Diabetes Mellitus Patient Dr N BIPLAB SINGH 1, Professor,Department Of Medicine, Regional Institute Of Medical Science, Imphal, Manipur. Nbiplab@Rediffmail.Com Dr KARAM ROMEO 3. Consultant Gastroenterologist, Associate Professor, Department Of Medicine, Rims,Imphal, Manipur. Karamdr@Gmail.Com Dr ANIL P KUMAR 2, Post Graduate Student, Department Of Medicine, Rims, Imphal, Manipur. anil.pk4922@gmail.com Dr Th BHIMO SINGH 4, Professor, Department Of Medicine, Rims,Imphal,Manipur. bhimoth@yahoo.co.in. Dr SACHIN DEBA SINGH 5, Professor,Department Of Medicine, Rims,Imphal, Manipur. ABSTRACT Hepatitis C virus (HCV) infection and Type 2 diabetes mellitus (T2DM) are two major public health problems associated with increasing complications and mortality rates worldwide. Meta-analysis have showed that HCV increases the risk of T2DM. With India having the largest number of Diabetic patients, combined infection of HCV poses significant challenge in patient management. This study was thus undertaken to know the prevalence of HCV sero positivity and clinical profile of HCV in Type 2 Diabetes Mellitus patients. Key Words: Hepatitis C Virus, Type 2 Diabetes Mellitus, Fibroscan, HbA1c, HCV RNA PCR. 1. INTRODUCTION Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) are two major public health problems associated with increasing complications and mortality rates worldwide [1][2]. Hepatitis C is a contagious liver disease that results from infection with the hepatitis C virus. It can range in severity from a mild illness lasting a few weeks to a serious, lifelong illness. About 150 million people are chronically infected and at risk of developing liver cirrhosis and/or liver cancer. More than 350,000 people die from hepatitis C-related liver diseases every year [3]. Hepatitis C is found worldwide with some countries having chronic infection rates as high as 5% and above. The prevalence of hepatitis c in India is 1.5% [4]. About 75 85% of newly infected persons develop chronic infection and 60 70% of chronically infected people develop chronic liver disease; 5 20% develop cirrhosis and 1 5% die from cirrhosis or liver cancer. In 25% of liver cancer patients, the underlying cause is hepatitis C [3]. Infection with HCV has been shown to produce both hepatic and extra hepatic manifestations, the various extra hepatic manifestations including insulin resistance, essential mixed cryoglobulinemia, glomerulonephritis, porphyria cutaneous tarda and benign monoclonal gammopathy [5, 6]. A metaanalysis showed that HCV increases the risk of type 2 diabetes mellitus (T2DM) by 1.8 times in excess of that posed by relative degree of liver pathology [7]. 124

2 Various studies have shown high HCV seropositivity among patients with T2DM as compared to the control group, prevalence being two to seven times higher in the diabetic group [8-10]. The mechanism of pathogenesis of diabetes in patients with HCV infection remains unclear though it has been implicated that insulin resistance plays an important role and is related to fibrosis score [11-13]. An increase of the fasting insulin and a decrease in insulin sensitivity have been observed in HCVinfected subjects with a moderate or severe degree of hepatic fibrosis (16). However, HCV-infected patients without fibrosis (fibrosis stage 0) also present higher insulin resistance than patients with primary biliary cirrhosis with different degrees of hepatic fibrosis (fibrosis stages 1 3) and healthy individuals (15). These data suggest that HCV is capable of producing an increase in insulin resistance, even before a minimal degree of hepatic fibrosis is present. Alternatively, insulin resistance has been described as an independent factor in predicting the presence of hepatic fibrosis in HCVinfected patients (15). After controlling for potential confounders, Mehta et al. reported that HCV infected individuals were 3.77 times more likely (95%CI = ) to have T2DM as compared to those without the infection [14]. India leads the world with largest number of diabetic subjects earning the dubious distinction of being termed the "diabetes capital of the world". According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. With the presence of combined Hepatitis c infection and type 2 diabetes it poses important challenge clinically to obtain a good glycaemic control which is necessary to prevent further complications of diabetes. 2.MATERIALS AND METHODS STUDY DESIGN and PATIENTS: A cross sectional study was conducted in the department of Medicine, REGIONAL INSTITUTE OF MEDICAL SCIENCE, IMPHAL for a duration of six months from March 2013 to August A total of 300 patients were enrolled in this study who were between the age group of years, diagnosed case of type 2 DM on treatment with no previous history of Hepatitis infection willing to give a valid consent were included and those with already diagnosed hepatitis C or B patients with HIV were excluded. DATA COLLECTION: All the patients were explained about the purposes of the study and written consent was taken from each patient. Patients were advised to undergo HCV antibody detection which was performed using Fourth generation Enzyme Immunoassay [ELISA] in the plasma or serum. Patients with positive status were then subjected to HCV RNA quantitative analysis performed using Real time PCR by COBAS AMPLIPREP and TAQMAN. Fibroscan was performed using FIBROSCAN 402 with M probe based on Controlled Pulse Vibration Elastography Technique.HBA1c was estimated by High Performance Liquid Chromatography (HPLC) Method. STATITICAL ANALYSIS: Analysis was carried out using SPSS v20 software. Descriptive analysis was performed and results were expressed as mean and percentages. 3. RESULTS Of the total 300 patients enrolled 140(46.66%) were male and 160(53.34%) were females. Male: Female ratio of 0.87:1. The mean age of the study population was years with 48(16%) patients 40 years and 252(84%) patients >41 years. By religion 206(68.66%) patients were Hindu and 94(31.33%) patients were Christian. District wise distribution showed 176(58.7%) were from Imphal West, 32(10.7%) from Imphal East, 26(8.7%) from churachandpur, 22(7.3%) from Bishnupur, 22(7.3%) from Thoubal, 10(3.3%) from chandel, 6(2.0%) from Senapati and 6(2.0%) from Tamenglong districts. Fig-1; Table-1. Screening for HCV antibody for 300 patients showed reactive for 32 patients with a prevalence of 10.66%. Further sub grouping (table-2) shows of 32 HCV positive 8(16.60%) are patients with age 125

3 40 years and 24 (9.53%) with age >41 years. 18(12.80%) patients are males and 14 (8.75%) are females. Based on religion 18(8.73%) were Hindu and 14(14.80%) were Christian. P values of all the subgroups were statistically insignificant. Genotype 3 was found in 16(50.00%) patients, genotype 1 in 14(43.8%) patients and genotype 6 in 2(6.3%) patients. Mean SGOT 151±101.21, SGPT ±121.35, FBS ±91.43, PPBS ±150.21, HBA1c 13.52±2.41. Mean viral load of patients was IU. Fibroscan of HCV-ab positive showed 2/32(6.3%) patients with no fibrosis (<8Kpa), 16/32(50%) had moderate fibrosis (8-13 Kpa), 8/32(25%) had severe fibrosis (13-18 Kpa) and 6/32(18.8%) had cirrhosis (>18 Kpa) table DISCUSSION AND CONCLUSIONS In this study, the seroprevalance of HCV infection was found to be 10.66% in patients of type 2 DM. This is in accordance with various other studies conducted in other part of the world such as NaoufelKaabia, et al [17] showed a prevalence of 17%, Nauman A Jadoon et al [18] showed 13.7%, Nwankiti OO et al showed 14.36%, Ndako JA et al [20] showed 11.00%, Mehta SH et al [14] showed 11.58%, Mason AL et al [8] showed 4.2%. Various meta-analysis [7, 21] have also shown similar findings. The study also shows the prevalence of genotype 3 in 50% of the HCV positive patients followed by genotype 1 (43.8%), this pattern holds good to the general prevalence of genotype in the Indian subcontinent [22]. It can also be seen that the prevalence of Genotype-1 is almost equal to that of Genotype-3 which is different to that of general population with HCV positive in whom Genotype- 1 was shown to be present in 30.98%, Genotype-6 was found in 6.3% of patients which is very rare in Indian subcontinent [22]. Lalhriatpuii et al showed the seroprevalence of HCV in voluntary blood donors in RIMS hospital for the year 2012 of 1.09% which was much less compared to the prevalence of 10.66% in this study among T2DM [23]. The study also shows the increased prevalence of HCV positive in patients 40 compared with those >41 years (16.60% vs 9.53%), this may be because of associated presence of other high risk behaviour. Christians had a higher prevalence than Hindu 14.80% vs 8.73% as most of the Christian in the state of Manipur are tribal in origin and there is an increased prevalence of high risk behaviour including IV drug abuse, multiple sex partners, tattooing. 58.7% of the study population is from Imphal West as REGIONAL INSTITUTE OF MEDICAL SCIENCE Hospital is situated in Imphal West. The study also shows the mean value of fibroscan which falls in the category of severe fibrosis (13-18 kpa), of the 32 patients16(50%) patients had moderate fibrosis (8-13 Kpa), the mean SGOT , SGPT , showing the presence of chronicity and ongoing necrosis of the hepatocytes respectively. All the patients in the study group had poor glycaemic control with mean HBA1c of inspite of patients being under treatment. The mean Fasting and Post Prandial sugars of these patients were and showing uncontrolled Type 2 DM. It can be concluded that there is a high prevalence of HCV Ab positivity in T2DM patients, with younger patients <40 years being more prone to get infected. High prevalence of Genotype 1 and Genotype 6 in this study population compared to general population. It is difficult to achieve good glycaemic control in HCV Ab positive patient s inspite of treatment. 5. REFERENCES [1]. Zimmet P, Alberti K, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001; 414: [2]. Lauer G M, Walker B D. Hepatitis C virus infection. New Engl J Med 2001; 345:

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5 Manipur,International Journal of Innovative Research and Development, Volume 3, Issue 1, January 2014; p TABLE-1 IMPHAL EAST IMPHAL WEST SENAPATI TAMENGLONG CCPUR BISHNUPUR CHANDEL THOUBAL TOTAL FREQUENCY PERCENTAGE TABLE -2 Baseline characteristics of patients with HCV Sero-positivity POSITIVE n (%) HCV STATUS NEGATIVE n (%) AGE 40 8 (16.60) 40 (83.40) >41 24 (9.53) 228 (90.47) SEX MALE 18 (12.80) 122 (87.20) FEMALE 14 (8.75) 146 (91.25) CASTE HINDU 18 (8.73) 188 (91.27) CHRISTIAN 14 (14.80) 80 (85.20) ISLAM 0 0 P VALUE TABLE-3 Fibroscan SGOT SGPT FBS PPBS HbA1c Mean Std. Error of Mean Std. Deviation Minimum Maximum

6 TABLE - 4 Grading Frequency Percentage (%) No Fibrosis ( <8 Kpa) Moderate Fibrosis (8-13 Kpa) severe Fibrosis (13-18 Kpa) Cirrhosis (>18 Kpa) Total Fig.1 Author s Brief Biography:. Prof Dr N Biplab Singh, MD, John Hopkins Medical Fellow, is professor at the Regional Institute Of Medical Science, Imphal, Manipur. He has published 52 papers in National Journals and 12 in International Journals. He is a life member of API India, RSSDI and Indian AIDS society 129