Fifty-eight million people worldwide are chronically infected with hepatitis C virus (HCV) and are at risk of developing cirrhosis and hepatocellular carcinoma (HCC). Direct-acting antivirals are highly effective; however, they are burdened by high costs and the unchanged risk of HCC and reinfection, making prophylactic countermeasures an urgent medical need. HCV high genetic diversity is one of the main obstacles to vaccine development. The protective role of the humoral response directed against the HCV E2 glycoprotein is well established, and broadly neutralizing antibodies play a crucial role in effective viral clearance.

This review explores the HCV targets and the different vaccination approaches, encompassing different expression systems, antigen selection strategies, and delivery methods, focusing on those aimed at eliciting a broad and effective humoral response. Our search criteria included the keywords 'HCV,' 'Hepatitis C,' and 'vaccine' using publicly available databases. Following the screening, 54 papers were selected.

The investigation of novel vaccine platforms beyond traditional approaches is necessary. While progress has been made in this direction, continued investigations on the HCV virology, immunology, and vaccinology are essential to surmount associated obstacles, heling in the development of an HCV vaccine that can benefit the global public health.

The ReLink project aims to reintegrate diagnosed-but-untreated hepatitis-C-positive patients into medical care and initiate a therapy.

A retrospective search within the practice management system of a single center in Germany identified among 1965 hepatitis-C-positive patients 100 untreated patients with available contact details and meeting all inclusion criteria. Patients were contacted by 2 contact rounds.

Out of 100 patients, 64% were male. Most patients (81%) were aged between 30 and 59 years. The patients belonged to high-risk groups for hepatitis C virus infections or had other comorbidities. The majority of patients injected drugs (21%) and/or were currently or had been on substitution therapy (44%); alcohol addiction was also frequent (21%). Out of 25 patients who agreed to an appointment, 10 patients (40%) started therapy and 5 additional patients (20%) agreed to therapy but were not yet able to start or had not yet made a decision. One‑third of patients who agreed to an appointment did not show up.

Diagnosed-but-untreated patients are an important subgroup of hepatitis-C-positive patients; their recall to the clinic for direct-acting antiviral therapy is possible. However, inaccurate contact information, unresponsiveness to outreach, and further reluctance to attend doctor appointments limited the overall impact of this program. Regular review of the patients' contact details may facilitate both follow-up and recall.

Background: This study evaluated titers and amplitudes of anti-E2 antibodies (anti-E2-Abs) and neutralizing antibodies against hepatitis C virus (HCV; anti-HCV-nAbs) in HIV/HCV-coinfected individuals over five years after successful HCV treatment completion. Methods: We retrospectively analyzed 76 HIV/HCV-coinfected patients achieving sustained virologic response post-HCV treatment. Plasma levels of anti-E2-Abs and anti-HCV-nAbs against five HCV genotypes (Gt1a, Gt1b, Gt2a, Gt3a, and Gt4a) were determined using ELISA and microneutralization assays, respectively. Statistical analyses comparing the three follow-up time points (baseline, one year, and five years post-HCV treatment) were performed using generalized linear mixed models, adjusting p-values with the false discovery rate (q-value). Results: Compared to baseline, anti-E2-Abs titers decreased at one year (1.9- to 2.3-fold, q-value < 0.001) and five years (3.4- to 9.1-fold, q-value < 0.001) post-HCV treatment. Anti-HCV-nAbs decreased 2.9- to 8.4-fold (q-value < 0.002) at one year and 17.8- to 90.4-fold (q-value < 0.001) at five years post-HCV treatment. Anti-HCV-nAbs titers against Gt3a were consistently the lowest. Nonresponse rates for anti-E2-Abs remained low throughout the follow-up, while anti-HCV-nAbs nonresponse rates increased 1.8- to 13.5-fold (q-value < 0.05) at five years post-HCV treatment, with Gt3a showing the highest nonresponse rate. Conclusions: Humoral immune responses against HCV decreased consistently one and five years post-HCV treatment, regardless of HCV genotype and previous HCV therapy or type of treatment (IFN- or DAA-based therapy). This decline was more pronounced for anti-HCV-nAbs, particularly against Gt3.

The combination of ledipasvir and sofosbuvir (LDV/SOF) has been licensed to treat genotype 1 hepatitis C virus infection (HCV) with a 12-week regimen. However, there is scant data from Yemen regarding this combination regimen. Here, we investigate sustained virologic responses (SVR) 12 weeks after HCV treatment with LDV/SOF regimens and the factors that contribute to SVR failure.

A retrospective cross-sectional study was conducted at Althora General Hospital in Ibb, Yemen, from June 1, 2019, to October 31, 2022, on 53 cases with HCV genotype 1 infection who received combined therapy of LDV/SOF and completed treatment for 12 weeks. The clinical characteristics and treatment follow-up were obtained from patient medical records. Factors associated with SVR failure were investigated in univariate analysis with odds ratio (OR) and 95% confidence interval (CI).

The mean age was 50 ± 15.3 years, and most cases were female (n=36, 67.9%). Comorbidities were diabetes, hypertension, and fatty liver, which were represented in 12 (22.6%), nine (17.0%), and eight (15.1%) cases, respectively. A total of 13 (24.5%) patients had compensated liver cirrhosis, while the remaining 40 patients (75.5%) were non-cirrhotic healthy individuals. The baseline viral load (HCV RNA) was more than 800000 IU/mL in 21 patients (39.6%). Early virological response (ERV) was achieved in 51 patients (96.2%). After treatment, 46 of the patients (86.8%) achieved SVR at Week 12, while failure occurred in two patients (3.8%) and relapse occurred in five patients (9.4%). Blood liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, returned to normal, with statistically significant improvements in non-cirrhotic healthy persons than compensated liver cirrhosis individuals (p= 0.006, 0.006, and 0.010; respectively). Factors associated with SVR failure were older age (OR:1.13; 95% CI: 1.03-1.30, p=0.009), presence of liver cirrhosis (OR: 5.48; 95% CI: 1.04-28.98, p=0.031), having diabetes (OR: 6.33; 95% CI: 1.19-37.93, p= 0.019), baseline higher viral load (OR: 2.27; 95% CI: 0.45-12.73, p<0.001), and not achieving EVR (OR:7.63; 95% CI: 3.77- 17.78, p= 0.009).

In this study, we found that LDV/SOF regimens are effective against HCV genotype one infection, allowing for the expansion of 12-week treatment for suitable patients in clinical settings. Additionally, older age, liver cirrhosis, diabetes, higher pretreatment viral load, and non-completion of EVR were associated with SVR failure. However, due to the small number of HCV genotype 1 infected individuals in this study, more corporate data is required to get a clear conclusion.

Background: The disease burden of hepatitis C virus (HCV) infection in HIV-positive and HIV-negative men who have sex with men (MSM) is changing. We aim to provide an updated comprehensive estimate of HCV prevalence and incidence among the HIV-positive and HIV-negative MSM population at the country, regional, and global levels and their changing trends over time. Methods: PubMed, Embase, PsycINFO, CINAHL, and conference databases were searched and eligible records on the prevalence and incidence of HCV antibodies were selected and pooled via a random-effects model. Meta-regression was performed to demonstrate the association between the pooled rates and study year. Results: A total of 230 articles reporting 245 records from 51 countries with 445,883 participants and 704,249 follow-up person-years were included. The pooled prevalence of HCV in MSM was 5.9% (95% CI: 5.1-6.8), with substantial differences between countries and regions. Low- and lower-middle-income countries (12.3 and 7.0%) manifested a larger disease burden than high- and upper-middle-income countries (5.8 and 3.8%). HCV prevalence in HIV-positive MSM was substantially higher than in HIV-negative MSM (8.1 vs. 2.8%, p < 0.001). The pooled incidence of HCV was 8.6 (95% CI: 7.2-10.0) per 1,000 person-years, with an increasing trend over time, according to meta-regression (p < 0.05). Conclusion: Global HCV prevalence in MSM varies by region and HIV status. Behavior counseling and regular HCV monitoring are needed in HIV-positive subgroups and high-risk regions. Given the upward trend of HCV incidence and sexual risk behaviors, there is also a continued need to reinforce risk-reduction intervention. Systematic Review Registration: PROSPERO, identifier CRD42020211028; https://www.crd.york.ac.uk/prospero/.

Background and objectives: this study assessed variations in the blood parameters of patients with hematological disorders infected with HCV throughout a 12-week interferon-free treatment regimen. Materials and methods: We followed a total of 344 patients suffering from chronic hepatitis C, infected with the 1b genotype and concomitant hematological disorders, who benefited from the direct-acting antiviral (DAA) therapy in our clinic. Seven of the most routinely checked blood parameters were analyzed, namely, hemoglobin, leucocyte count, neutrophils, erythrocyte count, platelet count, ALT, and total bilirubin level. In total, 129 patients received a treatment scheme comprising ombitasvir, paritaprevir, ritonavir, and dasabuvir, while the 215 other patients received a sofosbuvir and ledipasvir regimen. Results: Patients enrolled in the study showed remarkably increased ALT levels in the first four weeks of DAA treatment, normalizing to levels below 40 U/L by the end of regimen. There were no other blood parameters that worsened throughout the 12-week regimen to levels below our laboratory's normal range. After 12 weeks of DAA therapy, 309 patients (90%) achieved SVR. Conclusions: Our findings are consistent in evaluating the efficacy and tolerability of direct-acting antivirals for 1b genotype HCV infected patients with associated hematological malignancies under remission, and other hematological disturbances, that were previously unsuccessfully treated with a pegylated interferon regimen. Thus, paving a pathway for government-funded programs being implemented in this direction.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted an urgent need to identify effective medicines for the prevention and treatment of the disease. A comparative analysis between SARS-CoV-2 and Hepatitis C Virus (HCV) can expand the available knowledge regarding the virology and potential drug targets against these viruses. Interestingly, comparing HCV with SARS-CoV-2 reveals major similarities between them, ranging from the ion channels that are utilized, to the symptoms that are exhibited by patients. Via this comparative analysis, and from what is known about HCV, the most promising treatments for COVID-19 can focus on the reduction of viral load, treatment of pulmonary system damages, and reduction of inflammation. In particular, the drugs that show most potential in this regard include ritonavir, a combination of peg-IFN, and lumacaftor-ivacaftor. This review anaylses SARS-CoV-2 from the perspective of the role of ion homeostasis and channels in viral pathomechanism. We also highlight other novel treatment approaches that can be used for both treatment and prevention of COVID-19. The relevance of this review is to offer high-quality evidence that can be used as the basis for the identification of potential solutions to the COVID-19 pandemic.

There is no published study from India on hepatitis C virus (HCV) treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR). A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15-67) years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 10(6) copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54%) patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80%) patients required increase in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment-limiting). Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy.

To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells (DCs) in chronic hepatitis C (CHC) patients infected with genotype 3 virus.

This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c (BDCA1)(+) DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus (HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR.

Non-responders [sustained virological response (SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1 (6-fold) and negative regulators of JAK-STAT pathway such as SOCS (6-fold) as compared to responders (SVR+ve) to antiviral therapy. The down-regulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex (MHC) Class-II family as HLA-DP, HLA-DQ (2-fold) and superoxide dismutase (2-fold). Cells grown in the presence of HCV viral proteins had genes down-regulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors (4-fold) were up-regulated as compared to cells grown in absence of viral proteins.

Underexpressed MHC class-II genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.