Study of Frequency of Prediabetes in Patients with Chronic Hepatitis C Virus Infection

Subjects and Methods: A crosssectional study was performed on 60 HCV patients. Twenty healthy persons were taken as controls. Full history taking, clinical examination, routine laboratory and radiological investigations were done Body mass index (BMI), Waist Hip ratio, serum fasting glucose and fasting insulin were determined. IR was calculated by the Homeostasis Model for Assessment of Insulin Resistance (HOMA-IR), where values less than 2 has been considered completely normal and higher than 2 as a prediabetic state.


INTRODUCTION
Hepatitis C virus (HCV) infection is one the main causes of chronic liver disease worldwide.The number of chronically infected persons worldwide is estimated to be about 160 million, but most are unaware of their infection [1].Approximately 700,000 persons die each year from HCV related complications, which include cirrhosis, hepatoceullar carcinoma (HCC) and liver failure [2].The most recent epidemiological survey done in Egypt revealed that 10% of the population had HCV antibody and 7% had positive HCV-RNA [3].

Number of studies have demonstrated a strong association between HCV infection and insulin resistance (IR), providing a possible link between this infection and diabetes mellitus [4].
Prediabetes mellitus is defined as a state of abnormal glucose homeostasis in which deficiency or resistance to insulin is the hallmark.Prediabetes mellitus precedes the development of overt type 2 diabetes mellitus (T2DM).It is associated with increased mortality and morbidity, and thus fits well with the criteria of a disease condition [5].The gold standard for the assessment of IR is the euglycemic hyperinsulinemic clamp technique.Another more practicable and also well-accepted method of measuring systemic IR is the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).It is calculated by the following formula: fasting glucose (mmol/L) × fasting insulin (μU/L)/22.5[6].In previous reports, HOMA less than 2 has been considered 'completely' normal and higher than 2 as prediabetic state [7].The progression of prediabetes to T2DM has been examined in a number of populations with varying results.In general, epidemiological studies indicate that approximately 25% of individuals progress to T2DM in 5 years, whereas about 50% remain prediabetic and about 25% revert to normal [8].The aim of this study was to assess the frequency of prediabetes assessed by (HOMA-IR) in patients with chronic HCV infection.

Subjects :
This study was conducted on 80 subjects attending or admitted to the Department of Hepatology, Gastroenterology and Infectious Diseases and outpatient clinic at Benha University hospital during the period from May 2016 to April 2017 after approval of Benha University ethical committee.They were classified into 3 groups.Group I: included thirty patients with chronic HCV with no evidence of cirrhosis, group II: included thirty patients with HCV related cirrhosis and group ІIІ: twenty apparently healthy volunteers of matched age, sex and BMI were included as control group.Exclusion criteria included clinical evidence of diabetes mellitus, family history of T2DM, non HCV related liver disease, e.g (HBV, alcohol abuse, hepatic schistosomiasis, autoimmune hepatitis, hemochromatosis, Wilson disease, hepatocellular carcinoma, any endocrinal disorder, diabetogenic drugs e.g.(steroids), severe systemic diseases (cardiac, respiratory or renal diseases), obese patients (BMI>30) & waist hip ratio (for men above 0.9 and for women above 0.85).

Materials :
All the patients and controls were subjected to full history taking, complete clinical examination including (1) BMI: measured as weight in Kg/ height m 2  were used to compare differences between more than two groups regarding parametric and nonparametric data respectively, followed by posthoc test using the Bonferroni method to detect differences in pairs.The person correlation coefficient (r) and the Spearman Correlation coefficient (rho; ρ) were used to test for the correlation between estimated parameters as appropriate.[14].In this study we aimed to assess the frequency of prediabetes assessed by (HOMA-IR) in patients with chronic HCV infection.

RESULTS
In this study, statistical analysis revealed significant difference between the studied groups as regard fasting blood glucose; it was higher in both of group I and group II than controls, and there was no significant difference between group I and group II.In addition, in this study statistical analysis revealed significant difference between the studied groups as regard fasting insulin level; it was higher in both of group I and group II than controls and there was no significant difference between group I and group II.In addition, statistical analysis revealed significant difference between the studied groups as regard HOMA-IR; it was higher in both of group I and group II than controls and there was no statistically significant difference between group I and group II.

CONCLUSION
This study showed that the frequency of prediabetes among non-diabetic chronic HCV patients was 63.33%.In addition, prediabetes in chronic HCV patients was not connected with the severity of liver disease and insulin resistance is a direct viral feature.Also this study concluded that HCV patients should be assessed for IR and prediabetes in their routine evaluation, to avoid the double burden of DM and HCV.

2]. The following laboratory investigations were done: Sampling:
milliliters whole blood was put in EDTA vacutainer (violet cap) and mixed up & down gently which was used to measure CBC.b-2 ml on Na Fluoride serum test tubes, centrifuged at (1500 rpm for 10 minutes).The separated serum is used for the assay of fasting blood sugar.c-2 plain test tubes without anticoagulant.The plain test tubes were left till coagulation.After coagulation, samples were centrifuged (at 1500 rpm for 15 minutes).The separated serum was used for the assay of Bilirubin, albumin and Insulin.
2. Liver Function Tests: Alanine Transaminase, Aspartate Transaminase applying kinetic method, serum albumin, Prothrombine time and activity, Alkaline phosphatase-Bilirubin (total and direct).3.Fasting blood sugar applying glucose enzymatic colorimetric method All biochemical tests were done using Biosystem A15 auto-analyzer Specific Laboratory Investigations : 1-Fasting insulin level : using ELISA kit supplied from BioTina GmbH.Alter Weg 18, 79112 Freiburg, Germany according to manufacturers' instructions.2-HOMA-IR(Homeostasis Model Assessment of Insulin Resistance) it was calculated using the equation HOMA-IR = fasting glucose (mmol/L) x fasting insulin (μU/L)/22.5.Cutoff point to define insulin resistance is ≥ 2.--Child-Pugh score: To assess the degree

Table 1
Table (1):Distribution of the studied groups regarding their sex, age, BMI and Waist/Hip ratio F: One way Analysis Of Variance (ANOVA) S: Significant (P<0.05)HS: Highly Significantly (P<0.001) †: Significant differences compared to Group I ‡: Significant differences compared to Group II

Table ( 3
): Frequency of prediabetes among the studied groups

Table ( 4
): Correlation between Child score & FBS, fasting insulin and HOMA-IR in group II disease.In euglycemic individuals the estimation of HOMA-IR level helps to quantify IR [13].Diabetes can adversely affect the course of CHC

26] who
[28]nstrated that prediabetes in HCV is not connected with the severity of liver disease, and no correlation between liver fibrosis and HOMA-IR values and IR is a direct vial feature.It agreed also with Lecube et al.[27]who studied groups of patients with CHC and chronic hepatitis B matched by age, sex, BMI and fibrosis stage, HOMA index was found higher in hepatitis C patients.On the other hand these results disagreed with Jason et al.[18]who assessed the extent of IR in relation to the severity of liver disease and hepatic fibrosis and found that, increased HOMA-IR values was associated with a higher rate of fibrosis progression and more advanced stages of hepatic fibrosis.Also theses results disagreed with Furutani et al.[28]who concluded that IR was connected with impaired glucose tolerance and the severity of the liver disease in non-diabetic patients with HCV infection.