A Synopsis of Hepatitis C Virus Treatments and Future Perspectives

Abstract

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN–RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

“…Interferons type I and HBV reactivation: Interferons type I (IFN-1) plays a crucial role in orchestrating the immune response during the reactivation of HBV. When viral components are recognized by PRRs such as Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors, and melanoma differentiation-associated protein 5, in liver cells known as hepatocytes and hepatic DCs, it leads to a reduced response to PAMPs and a compromised production of IFN-I, which include IFN-alpha and IFN-beta[ 27 , 28 ]. According to a report by Faure-Dupuy and Baumert[ 29 ], it has been found that HBV infection leads to an increase in the expression of microRNA-146a (miR-146a) in liver cells.…”

Contemporary Insights into Hepatitis C Virus: A Comprehensive Review

“…Innovative therapeutic strategies are being explored as well, to expand the treatment options for HCV especially for challenging cases (e.g., patients with HCC) as reviewed comprehensively by Medina et al [ 343 ]. For example, agents such as ezetimibe that target cellular cholesterol, which is critical for viral entry, can offer a novel mechanism to prevent HCV entry into hepatocytes [ 344 ].…”

“…Moreover, clinical trials incorporating statins with DAAs or IFN are underway [ 345 ]. These trials aim to enhance the antiviral response by taking advantage of the effects of statins on lipid metabolism, which may also boost IFN effectiveness [ 343 ].…”

“…Moreover, clinical trials incorporating statins with DAAs or IFN are underway [345]. These trials aim to enhance the antiviral response by taking advantage of the effects of statins on lipid metabolism, which may also boost IFN effectiveness [343]. Glecaprevir/Pibrentasvir (Mavyret) SVR12 of 99.7% for genotype 1 [331] SVR12 of 91% for genotype 3 [332] SVR12 of 99-100% for genotypes 4, 5, and 6 [333,334] Headache and fatigue [331] Sofosbuvir/Velpatasvir (Epclusa) SVR12 of 98.1% for subtype 1a, 99.2% for subtype 1b, 100% for genotypes 2, 4, and 6, and 97.1% for genotype 5 [335] SVR12 of 95% for genotype 3 [336] Headache, fatigue, nasopharyngitis, and nausea [335] Ledipasvir/Sofosbuvir (Harvoni) SVR12 of 95-98.6% for genotype 1 [337,338] SVR12 of 98.4% for genotype 2 [338] SVR12 of 98% for genotype 4 [339] SVR12 of 92.9% for genotype 5 [340] SVR12 of 95% for genotype 6 [341] Fatigue, insomnia, headache, and nausea [340,341] Elbasvir/Grazoprevir (Zepatier) SVR12 of 92% for subtype 1a, 99% for subtype 1b, 100% for genotype 4, and 80% for genotype 6 [342] Headache, fatigue, and nausea [342]…”

Investigating the role of killer cell immunoglobulin‐like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection

“…To avoid potential confounding effects from known genetic backgrounds, we included interferon lambda 4 (IFNL4) in our considerations, which has been confirmed to be closely associated with HCV infection and the response to treatment. 28 Specifically, IFNL4 rs12979860 and IFNL4 rs8099917 are significantly associated with spontaneous virus clearance and response to peg-IFN-a/RBV treatment. 29 Therefore, these two SNPs were also included in the study, and their genetic typing results were incorporated as confounding factors in the final analysis to avoid the possible effect of the proven IFNL4 genotype on the HCV infection outcome.…”