Hepatitis C Virus Therapy Research Articles

Characteristics and prognosis of hepatocellular carcinoma patients after direct-acting antiviral hepatitis C virus therapy in a single medical center in Egypt

Objective: Hepatocellular carcinoma (HCC) incidence has increased dramatically over the previous two decades and is anticipated to rise further in some countries, notably the United States, by 2030. HCC is most widespread in Asia and Africa, where hepatitis B and C are ubiquitous and lead to the development of chronic liver disease and, finally, HCC. In this study, we examined changes in the characteristics and prognosis of HCC patients, as well as the risk of developing HCC after direct-acting antiviral (DAA) medication.Methods: The study enrolled all individuals who attended the Clinical Oncology and Nuclear Medicine Department, Suez Canal University Hospital, Ismailia, Egypt, with a proven diagnosis of HCC in the period between January 2020 and December 2021. HCC is diagnosed based on radiographic appearance (arterial enhancement phase and delayed washout phase) or compatible histology.Results: This retrospective cohort included 254 HCC patients, separated into three groups. Kaplan-Meier curves with log-rank analysis revealed that hepatitis C virus (HCV) treatment therapy considerably reduced the time to HCC development following hepatitis diagnosis (p < .001). HCV therapy had a substantial impact on progression-free survival and overall survival in HCC patients (p < .001).Conclusions: The emergence of DAA medication has greatly altered the management of HCV patients in the context of HCC. DAAs have been shown to be both safe and beneficial in these individuals, particularly in terms of lowering the risk of hepatic decompensation. DAAs have been reported to enhance overall survival in patients with cirrhotic HCV-related HCC, most likely due to decreased hepatic decompensation.

Single-center retrospective review of standard versus minimal monitoring for hepatitis C direct-acting antiviral therapy

BackgroundHighly effective direct-acting antiviral (DAA) therapies have transformed the landscape of hepatitis C virus (HCV) treatment. However, there continues to be limited data regarding the efficacy and safety of required in-person clinic visits (standard monitoring) versus completely telehealth clinic visits (minimal monitoring) during HCV therapy, which could delay practice adoption. ObjectivesThis study aimed to assess the rates of undetectable HCV ribonucleic acid (RNA) in sustained viral load 12 weeks after therapy (SVR12) in standard versus minimal monitoring approaches during DAA. MethodsA 12-month, single-center retrospective cohort study was conducted in treatment-naïve HCV-infected adults who received DAA therapy between May 1, 2020, and April 30, 2021. The standard monitoring group had ≥1 in-person clinic visit with HCV RNA laboratory monitoring during DAA treatment. The minimal monitoring group had entirely telehealth visits without HCV RNA laboratory monitoring during treatment. Both groups received telephonic touchpoints throughout DAA treatment from a clinical pharmacist practitioner and a nurse care coordinator. The primary outcome was SVR12. ResultsFrom May 2020 to April 2021, 133 patients with HCV met inclusion criteria and were treated with DAA (standard, n = 56; minimal, n = 77), with no differences in baseline demographics. Overall, total encounters during DAA treatment remained significantly higher in the standard than minimal monitoring group (standard, 2.1 ± 0.8, vs. minimal, 1.7 ± 0.9; P < .01). Although minimal monitoring had higher loss to follow-up rates (standard, 7.1%, vs. minimal, 18.2%; P = 0.06), the modified intention-to-treat analysis showed no differences in sustained virologic response (SVR) between standard and minimal monitoring approaches (standard, 98.1%, n = 51, vs. minimal, 95.3%, n = 60; P = 0.41). ConclusionsThis single-center retrospective cohort study demonstrated that minimal monitoring during HCV treatment was as effective in achieving SVR cure rates as standard monitoring. Eliminating required in-person clinic visits during DAA therapy alongside a collaborative approach may play a major role in overcoming barriers to HCV care in select patients.

Extrahepatic Cancer Risk in Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antivirals.

Chronic hepatitis C virus (HCV) infection is associated with an increased risk of extrahepatic cancers, particularly non-Hodgkin lymphoma. The introduction of direct-acting antivirals (DAAs) has revolutionized HCV therapy, resulting in high cure rates. However, concerns have been raised about potential effects on cancer risk. This review summarizes the current evidence on extrahepatic cancer risk in HCV-infected patients treated with DAAs. We examined epidemiologic data on HCV-associated extrahepatic cancers and explored potential mechanisms linking HCV to carcinogenesis outside the liver. Studies evaluating cancer outcomes after DAA therapy were critically reviewed while considering methodological challenges. While some studies suggested a reduced risk of extrahepatic cancers after DAA therapy, others showed no significant change. Limitations included short follow-up periods and confounding variables. Immunological changes following rapid HCV clearance may have complex effects on cancer risk. Long-term prospective studies and mechanistic investigations are needed to fully elucidate the relationship between DAA therapy and extrahepatic cancer risk in HCV patients. Clinicians should remain vigilant for extrahepatic malignancies in this population.

HIV and hepatitis C virus-related misinformation may contribute to rising rates of infection and suboptimal clinical outcomes among persons with substance use

ABSTRACT HIV and hepatitis C virus (HCV) infection rates among persons, who use drugs, have risen during the US overdose crisis. We elicited patient perspectives about these interconnected infections to identify the areas of misinformation that might prevent appropriate management. We used in-depth interviews and thematic analysis of coded data collected from patients (N = 24) at detox and from key informants (N = 10). Seventy-one per cent reported injecting drugs. We found that patient narratives included misinformation about HIV and HCV transmission, natural history and treatment. Some participants thought that activities such as sharing drinkware or food with persons with HIV could lead to infection, while others believed that mainly men who have sex with men were at risk. Despite significant improvements in treatment, some participants still believed that HIV was a fatal condition, while others noted that treatment was only necessary at later stages. Some participants thought that HCV was a common, mild infection that might not need immediate attention, and others stated that individuals who were actively using drugs were ineligible for treatment. The current study exposes a considerable level of misinformation about HIV prevention and about the importance and benefits of HCV therapy. Educational interventions are necessary to counter misinformation identified.

HCV 5-Methylcytosine Enhances Viral RNA Replication through Interaction with m5C Reader YBX1.

Hepatitis C virus (HCV) is a positive-stranded RNA virus that mainly causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Recently we confirmed m5C modifications within NS5A gene of HCV RNA genome. However, the roles of the m5C modification and its interaction with host proteins in regulating HCV's life cycle, remain unexplored. Here, we demonstrate that HCV infection enhances the expression of the host m5C reader YBX1 through the transcription factor MAX. YBX1 acts as an m5C reader, recognizing the m5C-modified NS5A C7525 site in the HCV RNA genome and significantly enhancing HCV RNA stability. This m5C-modification is also required for YBX1 colocalization with lipid droplets and HCV Core protein. Moreover, YBX1 facilitates HCV RNA replication, as well as viral assembly/budding. The tryptophan residue at position 65 (W65) of YBX1 is critical for these functions. Knockout of YBX1 or the application of YBX1 inhibitor SU056 suppresses HCV RNA replication and viral protein translation. To our knowledge, this is the first report demonstrating that the interaction between host m5C reader YBX1 and HCV RNA m5C methylation facilitates viral replication. Therefore, hepatic-YBX1 knockdown holds promise as a potential host-directed strategy for HCV therapy.

Care Integration for Hepatitis C Virus Treatment Through Facilitated Telemedicine Within Opioid Treatment Programs: Qualitative Study.

Telemedicine has the potential to remove geographic and temporal obstacles to health care access. Whether and how telemedicine can increase health care access for underserved populations remains an open question. To address this issue, we integrated facilitated telemedicine encounters for the management of hepatitis C virus (HCV), a highly prevalent condition among people with opioid use disorder (OUD), into opioid treatment programs (OTPs). In New York State, OTPs are methadone-dispensing centers that provide patient-centered, evidence-based treatment for OUD. We investigated the integration and impact of facilitated telemedicine into OTP workflows in these settings. This study aims to understand OTP staff experiences with integrating facilitated telemedicine for HCV treatment into OTPs, including best practices and lessons learned. We conducted semistructured interviews with 45 OTP staff members (13 clinical, 12 administrative, 6 physicians, and 14 support staff members) at least one year after the implementation of facilitated telemedicine for HCV management. We used hermeneutic phenomenological analysis to understand OTP staff experiences. We identified 4 overarching themes illustrating the successful integration of facilitated telemedicine for HCV care into OTPs. First, integration requires an understanding of the challenges, goals, and values of the OTP. As OTP staff learned about new, highly effective HCV therapies, they valued an HCV cure as a "win" for their patients and were excited about the potential to eliminate a highly prevalent infectious disease. Second, the integration of facilitated telemedicine into OTPs fosters social support and reinforces relationships between patients and OTP staff. OTP staff appreciated the ability to have "eyes on" patients during telemedicine encounters to assess body language, a necessary component of OUD management. Third, participants described high levels of interprofessional collaboration as a care team that included the blurring of lines between disciplines working toward a common goal of improving patient care. Study case managers were integrated into OTP workflows and established communication channels to improve patient outcomes. Fourth, administrators endorsed the sustained and future expansion of facilitated telemedicine to address comorbidities. OTP staff were highly enthusiastic about facilitated telemedicine for an underserved population. They described high levels of collaboration and integration comparable to relevant integrative frameworks. When situated within OTPs, facilitated telemedicine is a high-value application of telemedicine that provides support for underserved populations necessary for high-quality health care. These experiences support sustaining and scaling facilitated telemedicine in comparable settings and evaluating its ability to address other comorbidities. ClinicalTrials.gov NCT02933970; https://clinicaltrials.gov/study/NCT02933970.

Programmed cell death-1 is involved with peripheral blood immune cell profiles in patients with hepatitis C virus antiviral therapy.

Mutations in the non-structural protein regions of hepatitis C virus (HCV) are a cause of a non-sustained virological response (SVR) to treatment with direct-acting antivirals (DAAs) for chronic hepatitis; however, there are non-SVR cases without these mutations. In this study, we examined immune cell profiles in peripheral blood before and after ombitasvir/paritaprevir/ritonavir treatment and screened for genes that could be used to predict the therapeutic effects of DAAs. Fluorescence-activated cell sorting analysis indicated that the median frequencies of programmed cell death-1-positive (PD-1+) effector regulatory T cells (eTregs), PD-1+CD8+ T cells, and PD-1+Helper T cells were decreased significantly in SVR cases, but without significant changes in non-SVR cases. The frequency of PD-1+ naïve Tregs was significantly higher in the SVR group than in the non-SVR group before and after treatment. Similar results were found in patients treated with other DAAs (e.g., daclatasvir plus asunaprevir) and supported an immune response after HCV therapy. RNA-sequencing analysis indicated a significant increase in the expression of genes associated with the immune response in the SVR group, while genes related to intracellular and extracellular signal transduction were highly expressed in the non-SVR group. Therefore, we searched for genes associated with PD-1+ eTregs and CD8+ T cells that were significantly different between the SVR and non-SVR groups and found that T-box transcription factor 21 was associated with the non-SVR state. These results indicate that PD-1-related signaling pathways are associated with a non-SVR mechanism after DAAs treatment separate from mutation-related drug resistance.

Therapeutic Intervention of Serine Protease Inhibitors against Hepatitis C Virus.

Hepatitis C virus (HCV) is a globally prevalent and hazardous disorder that is responsible for inducing several persistent and potentially fatal liver diseases. Current treatment strategies offer limited efficacy, often accompanied by severe and debilitating adverse effects. Consequently, there is an urgent and compelling need to develop novel therapeutic interventions that can provide maximum efficacy in combating HCV while minimizing the burden of adverse effects on patients. One promising target against HCV is the NS3-4A serine protease, a complex composed of two HCV-encoded proteins. This non-covalent heterodimer is crucial in the viral life cycle and has become a primary focus for therapeutic interventions. Although peginterferon, combined with ribavirin, is commonly employed for HCV treatment, its efficacy is hampered by significant adverse effects that can profoundly impact patients' quality of life. In recent years, the development of direct-acting antiviral agents (DAAs) has emerged as a breakthrough in HCV therapy. These agents exhibit remarkable potency against the virus and have demonstrated fewer adverse effects when combined with other DAAs. However, it is important to note that there is a potential for developing resistance to DAAs due to alterations in the amino acid position of the NS3-4A protease. This emphasizes the need for ongoing research to identify strategies that can minimize the emergence of resistance and ensure long-term effectiveness. While the combination of DAAs holds promise for HCV treatment, it is crucial to consider the possibility of drug-drug interactions. These interactions may occur when different DAAs are used concurrently, potentially compromising their therapeutic efficacy. Therefore, carefully evaluating and monitoring potential drug interactions are vital to optimize treatment outcomes. In the pursuit of novel therapeutic interventions for HCV, the field of computational biology and bioinformatics has emerged as a valuable tool. These advanced technologies and methodologies enable the development and design of new drugs and therapeutic agents that exhibit maximum efficacy, reduced risk of resistance, and minimal adverse effects. By leveraging computational approaches, researchers can efficiently screen and optimize potential candidates, accelerating the discovery and development of highly effective treatments for HCV, treatments.

Effect of Mutation of RNA-dependent RNA Polymerase (RdRp) of Hepatitis C Virus on Affinities of Dasabuvir: Computational Study

Hepatitis C Virus (HCV) is one of the infectious diseases that has posed a serious threat to global public health for the past few decades. HCV is an RNA virus that infects the human liver and can lead to chronic liver damage, cirrhosis, and even liver cancer. Treatment for HCV infection has made rapid advancements in recent years, particularly with the development of more effective antiviral drugs. One of the drugs used in HCV therapy is dasabuvir. Dasabuvir is an RNA-dependent RNA polymerase (RdRp) inhibitor that functions to inhibit the replication of the HCV virus. The RdRp enzyme in HCV is represented by NS5B, and dasabuvir specifically targets this enzyme. Several reports have revealed mutations in HCV NS5B due to the use of dasabuvir. This study conducted a computational mutation analysis on NS5B of HCV resulting from dasabuvir usage. The research findings indicate that mutations in the HCV polymerase induced by dasabuvir usage lead to changes in dasabuvir's conformation and binding energy. Some mutations decrease binding energy, such as mutations C316N, C451S, and N411S. However, on the other hand, there are mutations that increase binding energy, such as M414V, A553V, and C445F. The decrease in binding energy is supported by increased hydrogen bonding interactions with Asp318, Gln446, and Tyr448, as well as the formation of new hydrogen bonds, such as hydrogen bonding with Ser288 in C451S and Arg200 in C451S. Meanwhile, the increase in binding energy is supported by decreased binding interactions with Asp318 and pi-pi interactions with Phe193. Hydrogen bonding with Asn291 also decreases, as seen in A553V, and is even lost in C445F. Future work will be devoted for designing new dasabuvir derivatives which having better affinited to NS5B of HCV.

Коморбидные состояния как внепеченочные проявления хронической HCV-инфекции

Chronic hepatitis C virus (HCV) infection is a serious public health problem. In 2022, more than 33.8 thousand cases of chronic hepatitis C virus (HCV) were registered in the Russian Federation, with a total economic burden of RUB 60.9 billion. In addition to liver damage, a significant number of patients with CHC have various comorbid conditions, the development of which may be due to extrahepatic replication of HCV. In clinical practice, it is difficult to prove the association of comorbid pathology with extrahepatic manifestations of HCV. This literature review presents the results of meta-analyses and systematic studies that demonstrate the development of extrahepatic manifestations in chronic HCV infection. The data on cardiovascular and endocrine system damage, development of mixed cryoglobulinemia, neurological disorders are discussed. The analysis of scientific studies on the influence of HCV therapy with direct antiviral drugs on the course of comorbid pathology is carried out, personalized approaches to antiviral therapy for HCV patients with comorbid pathology and the prospects of clinical research to study this problem are substantiated. Key words: chronic HCV infection, chronic hepatitis C, extrahepatic manifestations, comorbid conditions, direct antiviral drugs

Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis

Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n= 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n= 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122mm2, p <0.001). The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased. There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop.

Self-awareness of hepatitis C infection in the United States: A cross-sectional study based on the National Health Nutrition and Examination Survey.

Hepatitis C virus (HCV) is a global health issue with an estimated prevalence of 2.4 to 3 million people in the US and 58 million worldwide. Previous reports from the US have shown that close to half of those with the infection are unaware of their status. Although the current therapy for HCV is very effective, the primary barrier has been the inability to diagnose a large fraction of those infected. We studied public awareness of HCV in the US using National Health Nutrition and Examination Survey data from 2013 to 2020. Our aim was to measure awareness of infection in individuals with HCV and identify possible barriers to diagnosis. In total, 206 individuals with HCV were included in the weighted analysis. The weighted awareness of infection was 60.1%, suggesting that over 0.8 million are unaware nationally. Awareness was significantly low in the Mexican American and Asian populations. Non-US citizens and non-US-born individuals also had poor awareness. The transaminases were more elevated in those unaware of the infection, suggesting their higher risk of liver fibrosis. Although the proportion of infected people aware of their illness has been rising, over 0.8 million are still unaware of their infection and their risk of liver damage. We believe policy measures focused on further intense screening and educational campaigns, particularly in high-risk groups, are vital in realizing the World Health Organization's goal of eliminating HCV as a global health threat.

Hepatitis C and heart transplantation: An update.

There are limited data regarding heart transplantation in the setting of hepatitis C virus (HCV) infection in either recipients or donors, as the practice was infrequent, given concerns of worse post-transplant outcomes. This changed dramatically after the development of highly effective HCV therapies, namely direct-acting antivirals (DAAs). Additionally, nucleic acid testing currently in use establishes more precisely the risk of HCV transmission from donors. As a result, chronic HCV infection in itself is no longer a barrier for heart transplant candidates, and the use of HCV-positive organs for HCV-infected and non-infected transplant candidates has increased dramatically. A review of the literature revealed that in the pre-DAA era, HCV seropositive heart transplant patients had a higher mortality than their seronegative counterparts. However, short-term data suggest that the differences in survival have been erased in the DAA era. Heart transplantation from HCV-viremic donors to HCV-uninfected recipients has become increasingly common as the number of deceased donors with HCV viremia has increased over the past years. Preliminary outcome reports are very encouraging, although further data are needed with regard to long-term safety. New information continues to be incorporated to optimize protocols that guide this practice.

Incidence of Hepatocellular Carcinoma in Hepatitis C Patients Treated with Direct-Acting Antivirals and Its Relation to Hepatic Fibrosis Stage

Abstract Introduction Significant advances in understanding of the molecular virology, life cycle, and pathogenesis of Hepatitis C Virus (HCV) led to the Direct-Acting Anti-viral (DAA) era of HCV therapy in 2011 (Hezode et al.,2015). It can be expected that rates of HCV-associated hepatocellular carcinoma (HCC) will decrease significantly after the widespread adoption of DAAs, However Hepatitis C patients with cirrhosis who were treated with direct-acting antivirals had increased likelihood of developing HCC (Tayyab et al., 2020) (Kozbial et al., 2016). HCC was also associated with greater liver stiffness according to transient elastography and lower platelet counts (Conti et al., 2016). The aim of this study is to investigate incidence of HCC in Egyptian HCV patients in whom other predominant HCV genotypes are prevalent and different treatment protocols followed. Methods This was a retrospective study including 400 chronic HCV patients who were following up their medical condition at Kobri El-Koba Military Hospital hepatology outpatient clinic from January 2018 to September 2019. Patients were divided into two main equal groups regarding either received HCV direct acting antivirals or not. Incidence of HCC after 18 months of follow up were compared between two groups. Its relation to hepatic fibrosis stage was calculated in both groups. Results DAA receiving group had significantly lower incidence of HCC than non DAA receiving group (control group). Eleven patients in DAA receiving group developed HCC (5.5%) compared to twenty-two patients in control group (11%) with P- value 0.04. Although there was no significant difference between two groups regarding pre-treatment prevalence of ascites, splenomegaly, or esophageal varices, DAA receiving group had statistically significant advanced hepatic fibrosis when compared to control group. Before starting treatment, DAA Receiving group shows (4.5% F0, 14% F1, 7% F2, 11.5% F3 and 63% F4) versus (20.5% F0, 14% F1, 18.5% F2, 6.5% F3 and 40.5% F4) in control group with highly significant P value 0.00. Conclusion Incidence of HCC decreased significantly after DAA in chronic HCV patients. Decreased incidence occurred despite advanced hepatic fibrosis in this group of patients.

Treating Hepatitis C Before Total Knee Arthroplasty is Cost-Effective: A Markov Analysis

BackgroundPatients who have the hepatitis C virus (HCV) have increased mortality and complication rates following total knee arthroplasty (TKA). Recent advances in HCV therapy have enabled clinicians to eradicate the disease using direct-acting antivirals (DAAs); however, its cost-effectiveness before TKA remains to be demonstrated. The aim of this study was to perform a cost-effectiveness analysis comparing no therapy to DAAs before TKA. MethodsA Markov model using input values from the published literature was performed to evaluate the cost-effectiveness of DAA treatment before TKA. Input values included event probabilities, mortality, cost, and health state quality-adjusted life-year (QALY) values for patients who have and do not have HCV. Patients who have HCV were modeled to have an increased rate of periprosthetic joint infection (PJI) infection (9.9 to 0.7%). The incremental cost-effectiveness ratio (ICER) of no therapy versus DAA was compared to a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to investigate the effects of uncertainty associated with input variables. ResultsTotal knee arthroplasty in the setting of no therapy and DAA added 8.1 and 13.5 QALYs at a cost of $25,000 and $114,900. The ICER associated with DAA in comparison to no therapy was $16,800/QALY, below the willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses demonstrated that the ICER was affected by patient age, inflation rate, DAA cost and effectiveness, HCV-associated mortality, and DAA-induced reduction in PJI rate. ConclusionDirect-acting antiviral treatment before TKA reduces risk of PJI and is cost-effective. Strong consideration should be given to treating patients who have HCV before elective TKA. Level of EvidenceCost-effectiveness Analysis; Level III.

KIR Genotypes Impact Progression to Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Infection

In Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was to study the potential role of the 16 KIR genes in the outcome of individuals with chronic hepatitis C virus (HCV) infection in Egypt. The study was carried out under an IRB-approved protocol. Sequence-Specific-Primer-PCR (SSP-PCR) was used for KIR genotyping of germline DNA extracted from peripheral blood leukocytes or from the non-tumor liver of 83 HCC patients, 100 patients with chronic HCV infection without HCC, and 120 matched healthy controls. Out of the 83 HCC patients, only 7 (8.4%) were treated by interferon and/or interferon Ribavirin combination, while for the remaining patients 50 (60.2%) received no prior HCV therapy and 26 (31.3%) were treated with direct-acting antiviral (DAA). Our results showed that KIR haplotype AA that contains more inhibitory KIR genes and fewer activating genes was observed with a significantly lower frequency in HCC patients (6/83, 7.2%) compared to chronic HCV (27/100, 27.0%) (p = 0.0005, OR = 0.21 [0.08–0.53]) and healthy controls (29/119, 24.4%) (p = 0.001, OR = 0.24 [0.09–0.61]). In addition, the frequency of genotype 6 (G6) which contains all the KIR genes was significantly high in the HCC patients (16/83, 19.3%) compared to chronic HCV (8/100, 8.0%) (p = 0.02, OR = 2.7 [1.11–6.79]) and healthy controls (8/119, 6.7%) (p = 0.006, OR = 3.31 [1.35–8.16]). Activating KIR genes 2DS1 and 3DS1 were significantly higher in HCC patients (48/83, 57.83% and 45/83, 54.22%) compared to the chronic HCV patients (36/100, 36% and 34/100, 34%), p = 0.028, 0.027, respectively. Our results are contrary to a prior work on HCC from patients with HCV who were mostly treated by interferon-based therapies. In conclusion, KIR haplotype AA has an important role in host defense against HCC progression especially in patients treated by DAA, suggesting an important role of the KIR genotype status on the outcome of chronic HCV infection.

Improving the model of payment for medical care for chronic viral hepatitis C in the framework of the implementation of the Program of State Guarantees of Free Provision of Medical Care to Citizens for 2023 and for the planned period of 2024–2025

Background. In 2021, new clinical guidelines for the treatment of chronic hepatitis C virus (HCV) in adults were published that did not contain interferon drug therapy regimens. Current therapy of chronic HCV is based on modern drugs of direct-acting antivirals (DAA). In this regard, the model of diagnosis-related groups (DRG) with the use of interferon-containing drugs as etiotropic therapy, which has been in effect until now, has lost its relevance and cannot be used to pay for cases of medical care for chronic HCV within the framework of the Program of State Guarantees of Free Medical Care to Citizens for 2023 and for the planning period of 2024–2025 (PSG). Objective: to improve the DRG model to pay for medical care for chronic HCV in a day hospital based on current clinical recommendations.Material and methods. Regulatory legal documents on the subject of the study, proposals and expert opinions of specialists, as well as feedback from public organizations, including patients, regarding the payment of medical care for chronic HCV, sent as part of a public discussion of the draft PSG, were studied. For the calculations were used: the current version of the clinical recommendations "Chronic viral hepatitis C"; impersonal personalized information of the database of registers of bills for payment for medical care for 2020–2021; the state register of manufacturers' maximum selling prices for medicines included in the list of vital and essential drugs.Results. A DRG model was developed to pay for medical care during drug therapy of chronic HCV, including for children. When calculating the model, the cost of medicines, patient days and the principles of accounting for the duration of hospitalization were updated.Conclusion. The developed DRG model to pay for medical care for chronic HCV in a day hospital with the use of drug therapy regimens with DAA recommended by clinical guidelines, including for children with HCV, contributes to improving the effectiveness of the system of payment for medical care provided as part of the implementation of the PSG and accessibility of medical care for this contingent of patients.

Investigation of novel HCV therapies: Boscia angustifalia &Boscia senegalensis extracts loaded on galactosylated chitosan nanoparticles synthesized by eco-friendly method for HCV treatment

Hepatitis C virus (HCV) is a major causative agent of chronic liver diseases including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Treatment of HCV has evolved from early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C after receiving therapy with direct-acting antivirals (DAA) with a 0.5 % chance of the hepatitis C virus recurrence, similar to other chronic viral infections. So, retreatment options following treatment failure have become crucial issues. Hence, this study aims to investigate a new promising therapy for HCV. In the field of nanomedicine, chitosan nanoparticles are well-known delivery systems that are frequently used as polymeric carriers. Galactosylated chitosan nanoparticles have been widely applied in HCV treatment. In this study, we have modified galactosylation by an eco-friendly method using l-ascorbic instead of hazardous reagents and we have loaded it with newly tested two Boscia extracts each in three different concentrations. The synthesized chitosan nanoparticles showed two dispersion peaks, at 196 ± 29 nm and 1.33 ± 0.36 μm, with a zeta potential of +3.3 ± 0.4mV with high stability in a range of 40.7 mV. The percentage of encapsulation of Boscia angustifalia extract was found to be 46.58 ± 1.33 % and for Boscia senegalensis extract was 9.77 ± 0.33 %. The release of Boscia angustifalia extract from the nanoparticles was about 40 % in acidic media after 180 min and about 60 % in normal pH. However, the release of Boscia senegalensis extract was 20 % in acidic media and 56 % in normal media after 24 h. Testing of these two newly developed composites against HCV was carried out using an in vitro system for the production of hepatitis C virus (HCV) which was established by infection of human hepatoma cells. Evidence for persistent virus production was monitored by the ELISA technique using an anti-HCV-specific antibody. Results obtained showed that all samples had an anti-HCV activity that increased by increasing concentration, and Boscia angustifalia had remarkable anti-HCV activity compared to Boscia senegalensis.

Current Therapy of Chronic Viral Hepatitis B, C and D.

The majority of chronic viral hepatitis cases are induced via infection with the hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). These patients are at increased risk for progressive liver disease leading to cirrhosis as well as hepatocellular carcinoma (HCC). HBV infection is well controlled by the currently available nucleosides as well as nucleotides, and the development of cirrhosis can be prevented. Additionally, it has been shown that HBV-induced liver fibrosis can regress during successful antiviral treatment; however, a "functional cure", i.e., loss of HBsAg, is a rare event when these drugs are used. Therefore, novel therapeutic strategies are aiming at the selective suppression of HBsAg levels in combination with immunostimulation. The development of directly acting antivirals (DAAs) has revolutionized HCV therapy, as almost all patients can be cured via this treatment. Additionally, DAA therapy has few, if any, side effects, and is generally well tolerated by patients. HDV remains the most challenging type of chronic viral hepatitis. Although novel therapeutic options have recently been approved, response rates are still less favorable compared to HBV and HCV. This review discusses current and future options for the treatment of chronic HBV, HCV, and HDV infection.

Predictive plasma biomarkers of long-term increase in hepatic steatosis index after HCV eradication in HIV/HCV-coinfected patients

Hepatic steatosis is a common condition found in the liver of hepatitis C virus (HCV)-infected patients, contributing to more severe forms of liver disease. In addition, the human immunodeficiency virus (HIV) may accelerate this process. Alternatively, several immune checkpoint proteins have been reported to be upregulated and correlated with disease progression during HCV and HIV infections. In steatosis, a detrimental immune system activation has been established; however, the role of the immune checkpoints has not been addressed so far. Thus, this study aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before antiviral therapy) with hepatic steatosis index (HSI) increase at the end of follow-up (∼ five years after sustained virologic response (SVR)). We performed a multicenter retrospective study in 62 patients coinfected with HIV/HCV who started antiviral therapy. Immune checkpoint proteins were analyzed at baseline using a Luminex 200TM analyzer. The statistical association analysis was carried out using Generalized Linear Models (GLM) and Partial Least Squares Discriminant Analysis (PLS-DA). Fifty-three percent of the patients showed HSI increase from baseline to the end of follow-up. Higher immune checkpoint protein levels of BTLA, CD137(4–1BB), CD80, GITR, LAG-3, and PD-L1 before HCV therapy were associated with a long-term increase in HSI after successful HCV therapy, suggesting a potential predictive role for early detection of progression towards steatosis in HIV/HCV-coinfected patients.