SUMMARY Journal of Islamabad Medical & Dental College (JIMDC); 2016:5(4):168-171 168 Original Article Correlation of Duration of Hepatitis C Infection with Triglycerides and Total Cholesterol Muhammad Imran Khan Almani1, Ahsan Kazmi2, Imtiaz Haider3, Tariq Afzal3, Muhammad Ammar Khan4, Rahat Farwa5, Aziz Bangish6, and Imran Haider7 1 Blood Unit, Benazir Bhutto Hospital Rawalpindi. 2 ,3&7Department of Pathology Rawalpindi Medical College Rawalpindi. 4.Department of Pathology Sargodha Medical College Sargodha. 5. Department of Medicine Nishtar Medical College Multan. 6. Shaheed Zulfiqar Ali Bhutto Medical University, PIMS G-8 Islamabad Abstract Objective: To study the correlation of duration of chronic HCV infection with total cholesterol and triglycerides. Patients & Methods: In this cross-sectional observational study we recruited 37 HCV infected patients who were diagnosed at least 6 months ago. Seven patients were excluded due to hyperglycemia. Patients suffering from metabolic disorders affecting total cholesterol and triglycerides were also excluded. Serum triglycerides, total cholesterol, and plasma glucose were measured by enzymatic method. Data was entered on SPSS version 16. Mean, standard deviation was calculated for numerical data. Pearson correlation was used to find association of duration of HCV with Total Cholesterol and Triglycerides. Results: Mean age of 30 subjects was 39.9±9.5 years, duration of HCV infection was 4.1±3.4 years and mean fasting plasma glucose was 81.7±6.4mg/dl. Total cholesterol and triglycerides were 107±30mg/dl and 72.3±23.5mg/dl respectively. Triglycerides showed a significant correlation with duration of HCV infection (p=0.024) and total cholesterol (p=0.001). Conclusion: There is a significant correlation of triglycerides with duration of HCV infection (p=0.024) and total cholesterol (p=0.001). Key words: Chronic hepatitis C, total cholesterol, triglycerides and correlation Introduction Hepatitis C virus (HCV) was identified and was named as non-A Non-B hepatitis in 1970 and as HCV in 1989. 1, 2 Chronic Hepatitis C virus (CHCV) infection is an important cause of hepatitis causing liver cirrhosis and end stage liver disease.3 Prevalence rate of HCV infection ranged from 0.1% to 12%, in different populations.1 Globally estimated carrier state rate has been reported 3% (175 millions).1 About 200 million people (3.3% of the world’s population) were infected with HCV worldwide in 2009.2 In one study, about 10 million people (5% of worldwide HCV infected patients) have been reported in Pakistan.2 In developing countries overuse and unsafe injection practices causes 2 to 5 million hepatitis C virus infections and these infections lead to high burden of chronicity, disability and death.4 Liver is a vital organ and plays a key role in metabolism and synthesis of serum lipoproteins.5 Impaired lipid metabolism is closely associated with chronic liver disease which result in low levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL) regardless of degree of fibrosis.5 Several mechanisms have been proposed to alter cholesterol homeostasis in HCV infected patients. One of the proposed mechanism is through its interference with the mevalonate pathway, resulting in decreased cholesterol synthesis. This diminished synthesis may then subsequently upregulate LDL-receptor expression, ultimately lowering LDL levels.6-8 Hepatitis C viral proteins have also been shown to directly activate the PI3-K/AKT sign align pathway, resulting in activation of the master regulator sterol response element binding protein (SREBP), which plays a critical role in activation of genes essential to fatty acid and cholesterol biosynthesis.9-12 Additionally, infection with HCV is associated with reduced microsomal triglyceride transfer protein (MTTP), an enzyme critical for VLDL synthesis, and whose inhibition results in decreased circulating LDL and cholesterol levels.13Hypolipidemias have thus been found associated with CHCV infection through several mechanisms.14 Very few studies have been conducted in our setup, on the correlation of metabolic variables like total cholesterol and triglycerides in CHCV patients. Present study was planned Corresponding author: Muhammad Imran Khan Almani Email: imran_almani@yahoo.com. Received: May 28, 2016; Accepted: Dec 29,2016 mailto:imran_almani@yahoo.com Journal of Islamabad Medical & Dental College (JIMDC); 2016:5(4):168-171 169 to study the correlation between duration of CHCV infection and serum total cholesterol and triglycerides. Patients and Methods This cross-sectional study was conducted at Pathology department Holy Family Hospital. About 37 anti-HCV antibodies positive patients of both genders and all ages, who were in fasting state were enrolled in the study. Sampling was done by non-probability convenience sampling. Only diagnosed cases of HCV with at least 6 months’ post-diagnosis were included. Patients with known hyperlipidemias, dyslipidemia, diabetes mellitus or hyperglycemia, endocrine disorders affecting lipid metabolism and myocardial infarction were excluded from this study.Out of 37 patients 7 were excluded due to fasting hyperglycemia. Informed consent was obtained from each patient prior to enrolment in this study. Fasting venous blood sample collected in a gel tube for total cholesterol and triglycerides and into sodium fluoride tube for plasma glucose measurement. Samples were centrifuged after about half an hour. We analyzed these samples for serum triglycerides (TG), serum total cholesterol (TC) and fasting plasma glucose (FPG). TC, TG and glucose were measured by enzymatic method. Statistical package for social sciences (SPSS) version 16 was used for statistical analysis. Mean, standard deviation (SD), variance and skewness of, duration of HCV infection after diagnosis, with T.C, and TG were measured. Duration of HCV (DHCV) infection was considered by the time when the patient came to know about his infection first time after that the patient got advise to screen himself for viral hepatitis and was declared reactive for anti HCV antibodies by either immunochrmatography, enzyme linked immunosorbent assay (ELISA), or polymerase chain reaction (PCR). Pearson’s correlation was applied to see the correlation between duration of HCV infection, triglycerides, and total cholesterol. P. Value less than 0.05 was considered significant. Results Baseline characteristics of total 30 patients are presented below in Table 1.Age of these patients ranged from 22-60 years with mean of 38.90 years+9.488SD. Mean duration of HCV infection was 4.13 years+3.431 SD. Mean fasting plasma glucose was 81.7mg/dl±6.4 SD. Total cholesterol and triglycerides were 107±30 mg/dl and 72.3±23.5mg/dl respectively. As shown in table 2, TG showed a significant correlation with duration of HCV infection (P=0.024), however correlation of cholesterol with duration of HCV was not significant (p value.606) The correlation between TG and TC was also significant (P=0.001). Table 1: Statistical Analysis of biographic and biochemical Variables (n=30) Variable Mean SD Age (in years) 38.90 9.488 Duration of HCV (in years) 4.13 3.431 FBS (mg/dl) 81.70 6.439 Total Cholesterol(mg/dl) 107.30 30.268 Triglycerides (mg/dl) 72.30 23.511 Table 2: Correlations different variables with duration of hepatitis C infection (n=30) Pearson Correlation P value Total Cholesterol (TC) 0.098 0.606 Triglycerides (TG) 0.412 0.024 TC vs TG 0.581 0.001 Correlation is significant < 0.05. Discussion Lipoproteins are closely connected to the process of hepatitis C virus (HCV) infection. In our study Triglycerides were low in majority of the patients and showed a significant correlation with duration of HCV infection (P=0.024).Our results are comparable with findings of the Perlemuter, et al, who also reported that the levels of triglycerides in HCV infected patients were moderately low.15 In 2006, D. Siagriset al. reported Serum TC (P < 0.0005), HDL-C (P < 0.0005) and LDL-C (P < 0.0005) were lower in chronic hepatitis C patients compared with controls. They also reported that this finding is more pronounced in patients infected with HCV genotype 3a. Patients with HCV genotype 3a had significantly lower levels of TC, HDL-C, LDL-C, higher viral load and higher frequency of hepatic steatosis than those with other genotypes. They proposed that further studies are needed to define the pathophysiology of the relationship between lipid metabolism and HCV infection.16 In a study done by Corey KE et al, it was observed hepatitis C is associated with decreased cholesterol and LDL levels. This hypolipidemia resolves with successful hepatitis C treatment but persists in nonresponders.08Other studies have also reported that Hepatitis C virus infected patients with HCV viremia have significantly low serum TG and cholesterol levels.17,18 Single nucleotide polymorphism in interleukin 28B gene have been found and reported in Journal of Islamabad Medical & Dental College (JIMDC); 2016:5(4):168-171 170 HCV positive patients with lower levels of triglycerides.19 Skowroński et al observed that there was a significant correlation of duration of HCV infection with total cholesterol which is in agreement with our study. 20 In the same study Skowroński et al. found that there was no significant correlation of duration of HCV infection with triglycerides,20 while in our study we observed that there is significant correlation of duration of HCV infection with triglycerides. Circulating lipid levels are altered in patients with HCV, regardless of the duration of infection. In a cohort of patients with acute HCV, early infection was associated with reduction in LDL and total cholesterol levels and following successful anti-HCV treatment, the lipids of these patients returned to pre-infection levels.7Patients with CHC also have also demonstrated reduced levels of circulating LDL, apolipoprotein B100 (apoB) and total cholesterol, compared to healthy controls and seem to resolve after successful clearance of CHC, supporting the hypothesis that HCV has a direct cytopathic effect upon host lipid metabolism. The presence and degree of hypocholesterolemia carries important prognostic implications for patients with CHC. Elevated LDL and high-density lipoprotein (HDL) levels have thus been associated with improved rates of sustained virologic response.6 Conclusion Serum triglycerides have a significant correlation with the duration of HCV infection. Chronic HCV infection is associated with hypotriglyceridemia. Limitations and Recommendations This was a small sample sized study and included only triglycerides and total cholesterol as target variables in our study. It is thus suggested that studies may be conducted with large sample size and other variables of lipid profile like very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein cholesterol (HDL). Moreover it is suggested that studies are conducted to find out various mechanisms leading to Hypolipidemias, association with genotypes and effect of their treatment response. Conflict of Interest This study has no conflict of interest as declared by any author. References 1. Houghton,M. The long and winding road leading to the identification of the hepatitis C virus. Journal of Hepatology. 2009;5: 939–948. 2. Waheed, Y., Shafi, T., Safi, S.Z. and Qadri, I. Hepatitis C virus in Pakistan: A systematic review of prevalence, genotypes and risk factors. World J Gastroenterol. 2009;15:5647-5653. 3. 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Skowroński, M., Ziółkiewicz, D.Z., Juszczyk, J. and Wysocka, B.W. 2009. Intermediate clinical manifestation of diabetes in patients with hepatitis C virus infection. E&C Hepatology, 5: 34-39. .. Authorship Contribution: Author 1: Conception, Synthesis and Planning of the research, Active participation in active methodology Interpretation, analysis and discussion Author 2: Conception, Synthesis and Planning of the research, Active participation in active methodology Interpretation, analysis and discussion Author 3: Conception, Synthesis and Planning of the research, Interpretation, analysis and discussion Author 4,5,6: Active participation in active methodology, Interpretation, analysis and discussion