Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients

Background and AimsChronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies.MethodsWe screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients’ baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment.ResultsHigh IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039).ConclusionsThere were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.

Special Issue “Chronic HCV Infection: Clinical Advances and Eradication Perspectives”

The latest report of global hepatitis estimated 58 million people with Hepatitis C virus (HCV) chronic disease and 1 [...]

A Review on Extrahepatic Manifestations of Chronic Hepatitis C Virus Infection and the Impact of Direct-Acting Antiviral Therapy

Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin’s lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.

Neurocognitive Dysfunctions in Adolescents with Chronic HCV infection

Introduction Globally, in 2015, an estimated 71 million people represented 1% of the world’s population including 5 million children, were living with chronic HCV infection, with the highest prevalence in the WHO Eastern Mediterranean region and the European region. Aim Primary objective was to assess the frequency of neurocognitive dysfunctions in children and adolescent with chronic HCV infection. Subject and Methods This prospective case–control study included forty adolescents with HCV recruited from the regular attendants of the Pediatrics Hospital, Ain Shams University and 20 healthy children from outpatient clinic. Psychiatric interviews and assessments were conducted by experienced qualified psychologist. Results Twenty adolescent with chronic HCV infection who fulfilled the inclusion criteria, were treatment naïve were recruited (Group1). They were five girls (25%) and fifteen boys (75%), their mean ages were 13.6 ± 2.37 years, were assessed before receiving Daclatasvir/Sofosbuvir, orally direct antiviral agents. They had statistically significant lower performance IQ and its subsets, verbal IQ and its subsets and total IQ as well as higher level of conduct, socializes aggression, attention problem, psychotic behavior, depression inventory and anxiety scale than control. Conclusion HCV may play a major role in cognition affection and the effect was more pronounced on the untreated HCV patients.

In Egyptian Patients with Hepatocellular Carcinoma the role of MicroRNA-215

Introduction/Objective MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs which are make a contribution in the regulation of gene expression and protein translation, and they play vital roles in differentiation, cell growth, and the development of diverse types of cancers. Methods/Case Report Our research was done in hepatology and gastroenterology department at the National Liver Institute, Menoufia University. It included 135 patients and 60 healthy subjects serving as control group. We have 3 groups: Group I (Control) This group included 60 apparently healthy individuals. They were 32 males and 28 females, whose ages ranged from 39 to 67 years old (mean ±SD= 51.67 ± 6.40 years). Group II (Cirrhosis) This group included 75 patients with liver cirrhosis due to chronic HCV infection. They were 41 males and 34 females whose ages ranged from 41 to 68 years old (mean ±SD= 54±6.73 years). Group III (HCC) Sixty patients with HCC were included. They were 35 males and 25 females, whose ages ranged from 41 to 70 years old (mean ±SD= 53.97±6.15 years). Laboratory Investigations Complete blood count (CBC), Liver tests: aspartate transaminase (AST) and alanine transaminase (ALT), serum albumin, total and direct bilirubin, alkaline phosphatase and INR were measured. Serum creatinine was also measured. The analysis of serum alpha fetoprotein (AFP) (ng/ml) was done. Chronic HCV infection was diagnosed by detection of HCV antibody and HCV RNA by real time PCR. Anti-HCV antibody was detected by means of a third generation enzyme immunoassay. Quantification of HCV RNA level was performed by means of COBAS Taqman 84 (Roche) real time HCV RNA Assay with lower detection limit 15 IU/ml. Results (if a Case Study enter NA) In control group, miRNA-215 ranged from 1.60 to 21.30 with a median value of 6.89. In cirrhotic patients group, it ranged from 0.70 to 14.65 with a median value of 2.85. In patients with HCC group, it ranged from 0.03 to 10.95 with a median value of 0.52 (pg/ml). MiRNA-215 and AFA mean levels showed a statistically significant difference (p <0.001) between the three studied groups. Conclusion In conclusion, MicroRNA-215 was proved to be significantly lower in HCC patients compared to cirrhotic patients and control group. This marker might be used as a potential serologic marker for HCC and a complementary diagnostic tool in monitoring cirrhotic patients for detection of HCC.

Effect of Sustained Virological Response with Direct Acting Antiviral Agents on Insulin Resistance in Patients with Chronic HCV Infection

Background Infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. Liver disease is not the only problem caused by chronic HCV infection; many extra-hepatic complications such as insulin resistance (IR) can be associated with HCV infection as well. Objective To assess the effect of sustained virological response on insulin resistance in patients with chronic hepatitis C infection. Patients and methods This study was conducted in New Cairo Viral Hepatitis Treatment Center (NCVHTC), in the period between December 2017 and December 2018. The current study was conducted on 46 enrolled HCV patients with type 2 Diabetes Mellitus (T2DM). Fasting Insulin (FI) and fasting blood glucose (FBG) as well as lipid profile were assessed in all patients at three time points; before treatment, at the end of treatment (EOT) and 12 weeks after the EOT. Results Despite using 4 different DAA regimens, all patients achieved SVR regardless of the regimen used. As a measurement of IR, HOMA-IR was calculated at the three time points using FI & FBG, it was found that HOMA-IR decreased significantly at the EOT; however, when calculated at week 12 after EOT, the reduction of HOMA-IR was not significant compared to the baseline levels. on the other hand, total cholesterol & LDL increased at the EOT and continued to increase at 12 weeks after the EOT. Conclusion Improvements in IR and glycemic control were not statistically significant after achieving sustained virologic response (SVR) with DAAs in patients with chronic HCV infection. Changes in the lipid profile such as an increase in the levels of total cholesterol and LDL can be expected after treatment with DAAs.

Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan

Introduction: Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are incretin-based oral antidiabetic drugs. Previous studies have shown an association between increased plasma activity of DPP-4 and chronic hepatitis C virus (HCV) infection. Dipeptidyl peptidase 4 inhibitors may be associated with preventing the development of chronic HCV infection. The aim of this study was to investigate whether the use of DPP-4 inhibitors is associated with a decreased risk of hepatocellular carcinoma (HCC) in patients with diabetes mellitus (DM) and chronic HCV infection.Methods: In this retrospective cohort study, we enrolled patients with type 2 diabetes and chronic HCV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The patients were divided into two groups (DPP-4 inhibitor cohort and non-DPP-4 inhibitor cohort) according to whether or not they received DPP-4 inhibitor treatment.Results: Multivariate Cox proportional hazard regression analysis showed a significantly lower risk of HCC in the patients who took DPP-4 inhibitors compared to those who did not. Kaplan-Meier survival analysis demonstrated a significantly higher HCC-free rate in the DPP-4 inhibitor cohort than in the non-DPP-4 inhibitor cohort.Conclusion: The use of DPP-4 inhibitors was associated with a lower risk of HCC in patients with type 2 DM and chronic HCV infection.

IMPLEMENTATION OF MICROELIMINATION STRATEGY IN ERADICATION OF CHRONIC HEPATITIS C INFECTION IN PATIENTS WITH HEMOPHILIA IN THE NORTHERN REGION OF SERBIA

Background: Treating HCV in people with hemophilia not only prevents the development of ESLD and HCC, but it also greatly increases the quality of life for people living with hemophilia. There are many obstacles in reaching the WHO goal of globally eradicating HCV by the year 2030., mainly its scale, complexity and implementation. That is why many countries have implemented a micro-elimination strategy: a pragmatic elimination approach in populations with the most efficacy. The aim of this publication is to present the morbidity and mortality rates, the clinical course and treatment outcomes of chronic HCV infection in PWH, as well as to show an example of a successfully conducted HCV micro-elimination strategy among people with hemophilia in the Province of Vojvodina. Methods: A retrospective, single-center study, performed using medical documentation of all registered PWH in the Clinical center of Vojvodina from 1994. until 2020. It included 74 hemophilia patients, out of which 32 were patients with hemophilia and chronic HCV infection. Results: The mean age of HCV positive PWH was 42.3 years, with the duration of infection of 30-35 years. Co-infection with HIV was observed in 6.25% of cases. Furthermore, 18.75% of patients had spontaneous HCV elimination and 75% patients were treated with antiviral protocols. Cirrhosis developed in 21.87% with an incidence rate of 0.6 per 100 patient-years. After treatment with Pegylated IFN and ribavirin (RBV), 58.3% achieved SVR. Side effects of IFN-based therapy regiment were recorded in 20.8% of treated PWH. In 37.5% PWH, DAA protocols were administered, and these patients achieved SVR. HCV positive PWH have a statistically higher mortality rate than non-infected people with hemophilia. Among the HCV positive PWH, hemophilia-related deaths were 6.25%, and HCV-related deaths were 9.37%. Currently, in the Registry of PWH in Vojvodina, there are no patients with active HCV infection. Conclusion: The micro-elimination strategy in subpopulation of PWH was successfully implemented in the Province of Vojvodina in close collaborations of hematologist and infectious diseases specialist.