HCV co-infection is related to acute ischemic severity and outcome

Background and aim HCV infection is associated with increased risk of ischemic cerebral stroke. HCV stroked patients are younger with a lower burden of classical risk factors and higher levels of systemic inflammation. The present study aimed to discover the association between HCV infection functional outcome of stroke. Patients and methods The present prospective study included 60 patients with acute ischemic stroke. All patients were subjected to careful history taking and through clinical and neurological examination. Stroke severity at presentation was assessed using National Institute of Health Stroke Scale (NIHSS). Quantitative HCV RNA test was used to diagnose HCV infection. The prognosis of the studied patients was 3 months after treatment using modified Rankin scale (mRS) for neurologic disability. Results The present study was conducted on 60 patients with ischemic stroke. They comprised 13 patients (21.7%) with HCV and 47 patients without. Stroke patients with HCV had significantly higher frequency of carotid artery stenosis, higher NIHSS (17.9 ± 6.9 versus 9.9 ± 5.3, p < 0.001) and higher frequency of severe stroke (46.1% versus 4.3%, p = 0.001) when compared with patients without HCV. Logistic regression analysis identified patients’ sex, NIHSS and HCV as significant predictors of outcome in univariate analysis. However, in multivariate analysis, only NIHSS proved to be significant. Conclusions The present study suggests a significant link between chronic HCV infection and ischemic stroke severity and poor outcome. This is probably related to the pathogenic effects of the chronic inflammatory state induced by HCV infection on the cerebral microvasculature.

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) &gt;25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score &gt;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 &lt; 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 [...]

Performance of HCV Antigen Testing for the Diagnosis and Monitoring of Antiviral Treatment: A Systematic Review and Meta-Analysis

Background and Aims. Active hepatitis C virus (HCV) infection is based on the detection of HCV RNA that it is effective but presents high cost and the need to hire trained personnel. This systematic review and meta-analysis is aimed at evaluating the diagnostic accuracy of HCV Ag testing to identify HCV cases and to monitor antiviral treatment including DAA treatment. Methods. The studies were identified through a search in PubMed, Lilacs, and Scopus from 1990 through March 31, 2020. Cohort, cross-sectional, and randomized controlled trials were included. Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Our primary outcome was to determine the accuracy of HCV Ag detection for the diagnosis, which we estimated using random-effects meta-analysis. Results. Of 3,062 articles identified, 54 met our eligibility criteria. The studies described cohorts from 20 countries, including 14,286 individuals with chronic HCV individuals. Studies for ECLIA technology demonstrated highest quality compared to studies that used ELISA. The pooled sensitivity and specificity (95% CI) for HCV Ag detection of active HCV infection were 98.82% ( 95 % CI = 98.04 %; 99.30%) and 98.95% ( 95 % CI = 97.84 %; 99.49%), respectively. High concordance was found between HCV Ag testing and HCV RNA detection 89.7% and 95% to evaluate antiviral treatment. Conclusions. According to our findings, HCV Ag testing could be useful to identify HCV active cases in low-resource areas. For antiviral treatment, HCV Ag testing will be useful at the end of treatment.

Transfusion Transmissible Infections in Blood Donors in the Province of Bié, Angola, during a 15-Year Follow-Up, Imply the Need for Pathogen Reduction Technologies

Transfusion transmissible infections (TTIs), caused by hepatitis B virus (HBV), human immunode-ficiency virus (HIV), hepatitis C virus (HCV), and syphilis, have a high global impact, especially in sub-Saharan Africa. We evaluated the trend of these infections over time in blood donors in Angola. A retrospective cross-sectional study was conducted among blood donors in Angola from 2005 to 2020. Additionally, frozen samples obtained from blood donors in 2007 were investigated to identify chronic HCV carriers and possible occult HBV infection (OBI). The overall prevalence of HBV, HCV, HIV, and syphilis was 8.5, 3, 2.1, and 4.4%, respectively, among 57,979 blood donors. HBV was predominant among male donors, while the remaining TTIs were predominant among women. Donors >50 years had a significantly high prevalence for all TTIs. Chronic HCV infection was ab-sent in 500 samples tested and OBI was present in 3%. Our results show the continued high prev-alence of TTIs among blood donors in Angola. Most infections showed a significantly low preva-lence in years with campaigns seeking voluntary blood donors, thus, reinforcing the importance of this type of donor to ensure safe blood. Africa, with a high prevalence of diverse pathogens, should consider cost-effective pathogen reduction technologies, once they are commercially accessible, to increase the availability of safe blood.

Motives and risk perceptions of participants in a phase 1 trial for Hepatitis C Virus investigational therapy in pregnancy

Limited research has been done among pregnant people participating in investigational drug trials. To enhance the ethical understanding of pregnant people’s perspectives on research participation, we sought to describe motives and risk perceptions of participants in a phase 1 trial of ledipasvir/sofosbuvir (LDV/SOF) treatment for chronic Hepatitis C virus (HCV) during pregnancy. Pregnant people with chronic HCV infection enrolled in an open-label, phase 1 study of LDV/SOF participated in semi-structured, in-depth interviews to explore their reasons for participation and experiences within the study. Pregnant people took 12 weeks of LDV/SOF and were interviewed at enrollment and at the end of study. We recorded the interviews, transcribed them verbatim, coded them using NVivo software, and performed inductive thematic analysis. Nine women completed the study yielding 18 interview transcripts. We identified two themes regarding motives and one regarding risk perception. Motives—(1) Women conceptualized study participation as part of the caregiving role they associate with motherhood; participating was viewed as an act of caregiving for their infants, their families, themselves, and other pregnant women with chronic HCV. (2) Women also noted that they faced multiple barriers to treatment prior to pregnancy that created a desire to receive therapy through trial participation. Risk perception—(3) Women acknowledged personal and fetal risk associated with participation. Acceptance of risk was influenced by women’s concepts of motherhood, preexisting knowledge of HCV and medical research, family members, intimate partners, or by the study design. Women enrolled in a phase 1 trial for chronic HCV therapy during pregnancy acknowledged risks of participation and were motivated by hopes for fetal and personal benefit and by lack of prenatal access to treatment. Ethical inclusion of pregnant people in research should acknowledge structural factors that contribute to vulnerability and data deficiencies for treatment in pregnancy.

Late Recurrence of Hepatocellular Carcinoma in a Patient 10 Years after Liver Transplantation Unrelated to Transplanted Organ

Liver transplantation (LTx) is an accepted method of hepatocellular carcinoma (HCC) treatment in cirrhotic patients; however, it has many limitations, and there is a substantial risk of recurrence. Most relapses occur within the first 2 posttransplant years. We aimed to present a late extrahepatic recurrence of HCC 10 years after LTx, and we discuss the possible risk factors and ways to improve transplantation results. A 68-year-old patient with liver cirrhosis and HCC on the background of chronic HCV and past HBV infection was transplanted urgently due to the rapid decompensation. Anti-HCV treatment before surgery was unsuccessful. Pretransplant computed tomography showed 1 focal 4.5 cm lesion consistent with HCC. Histopathology of the explanted organ showed 2 nodules outside the Milan criteria. Angioinvasion was not found. The patient achieved a sustained viral response to pegylated interferon and ribavirin 2 years post-LTx. Eight years were uneventful. CT of the abdomen performed occasionally was normal. Ten years after LTx, the patient unexpectedly presented with shortness of breath, fatigue, and weight loss. Two metastatic nodules of HCC in the lungs and pelvis were found. Although late HCC recurrence post-LTx is rare, it should be always considered, especially when risk factors such as viral infections and underestimation of tumor advancement were identified. We advocate that oncological surveillance of HCC relapse has to be continued during the whole posttransplant period. High AFP levels, the unfavorable neutrophil to lymphocyte ratio, and better estimation of primary tumor size seem to be useful in the identification of good candidates for transplantation.

Fibrin Monomer in Chronic HCV ‎Cirrhotic Patients

Background: Cirrhosis is a diffuse pathophysiological state of the liver that is thought to be the final stage of various liver injuries. It is characterized by chronic necroinflammatory and fibrogenetic processes, which result in the conversion of normal liver architecture into structurally abnormal nodules, dense fibrotic septa, concomitant parenchymal exaustment, and liver tissue collapse. Aim of this Work is to study fibrin monomer in chronic HCV patients with and without portal hypertension aiming to investigate its value in these patients and if it aides in early detection of thrombus formation.‎ Patients and Methods: They were fifty chronic HCV cirrhotic patients with and ‎without portal hypertension. Patients of these study were selected from Tropical and internal medicine departments and investigated at Clinical Pathology department in Tanta University hospitals, Faculty of Medicine, Tanta University during the period from July 2018 to January 2020. Results: The individuals included in this study were comprised as: Group 1: Twenty-five healthy volunteers (matched for age and gender) were investigated as a control group. Group 2: Twenty-five diagnosed cirrhotic patients without portal hypertension. Group 3: Twenty-five diagnosed cirrhotic patients with portal hypertension. The result of the present study was statistically analyzed, summarized and presented in tables. Conclusion: It may be concluded that soluble fibrin monomer complex could represent a useful marker ‎for early detection of thrombus generation in chronic HCV cirrhotic patients. It may enable ‎us to pick up vulnerable patients in early stages to start early management.

Angiopoietin-2 as a predictor of fibrosis regression in chronic hepatitis C virus patients after direct-acting antiviral drugs

Background HCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level. Results Statistically significantly higher levels of baseline Ang-2 were detected with the progression of fibrosis stages with a p-value of <0.001. The best cutoff value of baseline Ang-2 in discrimination of liver cirrhosis (F4) from F0-F3 was > 630 pg/ml with 85.71% sensitivity and 84.85% specificity. A statistically significant decline of Ang-2 (from 464.3±237.2 pg/ml to 401.3±277.1 pg/ml) was noted after the achievement of SVR12 with a p-value < 0.001. Regression of liver fibrosis in this study is defined as a decrease of more than or equal to one stage in liver fibrosis. Lower baseline fibrosis stages and other non-invasive scoring systems (FIB-4 and APRI scores) were associated with regression of fibrosis following successful DAAs treatment. However, higher baseline Ang-2 levels were significantly associated with non-regression of fibrosis, and at a cutoff of >680 pg/ml, it might predict non-regression of fibrosis after successful eradication of HCV with DAAs with 93.33% sensitivity and 70% specificity. Conclusions Angiopoietin-2 can be a useful predictor of fibrosis regression in chronic HCV patients receiving direct-acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced fibrosis stages may predict non-regression of liver fibrosis.