A true and definite connection between impaired glucose tolerance and HCV was confirmed by the high prevalence of high fasting serum glucose and diabetes in CHC patients, thus basic screening for glucose abnormalities is indicated [1]. CHC infected patients had a higher risk of developing type 2 diabetes compared with uninfected controls [2].That may be attributed to the HCV encoded proteins that might alter insulin signaling, thus impaired insulin sensitivity and finally the glycaemic dysregulation may occur even before the cirrhotic stage [3].

Advances in HCV cell culture have enabled a better understanding of HCV virology, which has led to development of many new direct-acting antiviral drugs (DAAs) that target the key components involved in the process of viral replication. These DAAs favour a simplified and shortened therapy that can be administered orally with higher tolerability and efficacy than the former regimen i.e. IFN and RBV [4]. They led to a major shift in HCV clinical management i.e. a significantly higher SVR, and shortened total treatment duration from 48 to 24–36 weeks. Yet, adverse side effects, problematic dosing schedules, and potential drug-drug interactions pose challenges for clinical management [5].

DAAs have also improved the glycemic control in diabetic patients with CHC as evidenced by decreased mean HbA1c and decreased insulin use. Therefore, DAAs are considered an additional justified antiviral treatment in all patients with diabetes [6]. HbA1c was statistically significantly reduced regardless the type of DAA regimen, HCV genotype, body mass index (BMI) and human immune deficiency virus (HIV) status. Accordingly, diabetic patients receiving DAAs should be closely monitored for hypoglycaemic events [7].

This study aimed to evaluate influence of DM on pretreatment status of HCV infected patients and to assess the mutual relation between DM and DAAs, i.e. the influence of DM on the virologic response of CHC diabetic patients, and conversely, the influence of DAAs on the control of DM.

This is a multicentric retrospective cohort study where database from all national medical centers providing treatment of viral hepatitis, affiliated to the Ministry of Health and Population (MOHP), and following the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH), were collected.

The recruited patients were adult patients (≥18 years), with documented CHC by serology (3rd generation ELISA antibody test, and direct HCV virologic assay i.e. quantitative polymerase chain reaction (PCR) test including compensated cirrhosis (Child Pugh score ≤ 6) [8].

All enrolled patients were subjected to: 1]a) Full history taking including diabetes, drugs, medical comorbidity, and b) thorough clinical examination, 2] Basic laboratory tests prior to initiation of treatment; complete blood count (CBC), liver biochemical profile (LBP) [bilirubin, transaminases; aspartate transaminase (AST),and alanine aminotransferase (ALT), albumin and international normalized ratio (INR)], kidney functions (urea, creatinine), glycaemic status (glycosylated haemoglobin (HbA1C) such that value <6 denotes the well-controlled and values ≥6 and <8 denotes the fairly controlled ones, 3]Virologic study; a) for HCV: i. anti HCV according to the manufacturer’s instructions with a second-generation enzyme immunoassay (EIA; Abbott GmbH, Delkenheim, Germany), and ii. for HCV RNA, amplified directly without isolation of RNA, by use of 1-step reverse transcriptase– polymerase chain reaction (RT-PCR), b) for HBV by hepatitis B surface antigen (HBsAg) via Enzyme Immune Assay (Abbott GmbH, Delkenheim, Germany), Other tests; Antinuclear antibody (ANA), Thyroid stimulating hormone (TSH), and tumour marker;α faeto protein (α FP), 4] Imaging study; a) Abdominal Ultrasound (US), b)Liver stiffness measurement (LSM) via Fibroscan,to assess the hepatic fibrosis, whenever possible according to its availability in the treating centre, 5] Fibrosis score (Fib-4)that was calculated, 6] Endoscopic examination is done in cirrhotic patients to check esophageal ± gastric varices,7] Histopathologic examination of liver biopsy that was performed under US guidance after checking the adequacy of the patients’ coagulation profile. It was done before the extending fibroscan examination to assess the hepatitis activity (HAI), fibrosis stage (by applying the Metavir scoring method [9]), and severity of steatosis by Brunt scoring system [10]. Only liver biopsy samples with at least 10 mm long or had six portal tracts were examined to allow for adequate interpretation.

Patients with inadequate liver biopsy samples were sent for re-biopsy. 8] Statistical analysis: Data were exported from National Database in excel format. Data analysis was performed with a statistical package for personal computer (SPSS, version 17; SPSS, Inc., Chicago, IL).

The included patients are divided into 2 groups; the diabetic and the non-diabetic ones. Diabetic patients were further subdivided into the well and the fairly controlled ones according to their HbA1c. All patients were evaluated clinically, biochemically, and virologically prior to therapy and monitored in the same items along treatment to identify their achieved virologic response.

Patients were compared by means (Student’s t-test) and proportions (chi-square) when appropriate. The descriptive statistics were provided with mean standard deviation (SD) or median for nonparametric data. The χ2 test and student t-test were employed for analysis of qualitative or quantitative variables, respectively. Pearson correlation was done to correlate HBAC variables with other continuous variables. Logistic regression analysis was applied first, to assess predictors of response including diabetes as cofactor. Another logistic regression analysis was applied for diabetic patients only to assess independent factors for response to treatment. In all tests, P values were significant if < 0.05.

Inclusion criteria: Adult patients (≥18 years old) with CHC diagnosed by positive serology (anti HCV antibody) and detected viraemia by HCV RNA test. Women of childbearing potential or men with a female partner of childbearing potential must agree to use effective form of contraception. Patients must have a negative pregnancy test prior to therapy.

Exclusion criteria: Patients with decompensated liver disease (Child B and C defined by total serum Bilirubin ≥2 mg/dL, albumin ≤2.8 gm/dL, INR ≥ 1.7, presence of ascites or encephalopathy), thrombocytopenia (<50,000 cells/mm3), patients with hepatocellular carcinoma (HCC), patients with severe psychiatric disease, and patients with serious co-morbid conditions. Poorly controlled diabetic patients were not included until controlling their glycaemic status.

All the procedures carried out in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.