Molecular characterization of the nonstructural 5A (NS5A) region of hepatitis C virus in Thai blood donors.

Direct acting antivirals (DAAs) have been developed for hepatitis C virus (HCV) therapy, and they are usually effective, however resistance to DAA regimens has also been reported to have a significant impact. Resistance associated substitutions (RASs) in the NS5A region are known to be correlated with failure of DAA therapy. HCV genotypes 3a and 1 are the most prevalent genotypes in Thailand. This study analyzed the type and frequency of RASs associated with DAA failure, focusing on the NS5A region. Serum samples of HCV genotype 3a, 1a, and 1b infection from Thai blood donors were selected. The NS5A region was amplified using reverse transcription-polymerase chain reaction (RT-PCR). A phylogenetic tree was constructed to identify the genotypes of HCV. Nucleotide sequencing and amino acid sequencing were conducted to determine the prevalence of RASs. Construction of the phylogenetic tree indicated that 29 samples were genotype 3a, 11 samples were genotype 1a, and 9 were genotype 1b. Both HCV genotypes 1a and 3a can be categorized into two subclades. Results showed that the NS5A substitutions A30V/K, A62T/V/I/M/P/S/L, and S98G were present in HCV genotype 3a. In HCV genotype 1a, only NS5A RASs H54Y was detected. NS5A amino acid substitutions Q54H and P58L were found in HCV genotype 1b. In conclusion, NS5A RASs at amino acid positions 30, 62, 54, 58, and 98 are present within HCV genotypes 3a and 1. While keeping in mind that additional information was not available on the anonymous blood donors tested in this study, these findings can contribute to understand the NS5A mutation. Further study with known patients under drug treatment is recommended.

Clinical significance of viral markers testing by ELISA and Individual Donation Nucleic Acid Testing (ID-NAT) for blood screening in blood bank: Single center study in Egypt.

Prevention of transfusion-transmitted viral infections and insurance of safe blood transfusion are the main goals of all blood banks worldwide. Despite the high sensitivity and specificity of currently used enzyme linked immunosorbent assay (ELISA) for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) testing, viral transmission could still occur during the window period. Introducing viral individual donation nucleic acid testing (ID-NAT) can greatly decrease such risk providing an additional layer in securing blood transfusion. We aimed to assess the clinical significance of viral markers testing by ELISA and ID-NAT for blood screening in the Blood Bank of Suez Canal University Hospital. We studied all donations (2132) collected during a two-months period. Blood donor samples were screened by ELISA and ID-NAT tests for HBV, HCV, and HIV. Serological testing results for HCV by ELISA revealed 2,122 (99.5 %) negative donations compared to 2,131 (99.95 %) negative donations by ID-NAT testing. Of the positive ELISA samples, only one was NAT positive. For HBV ELISA testing, 2,115 (99.2 %) donations were negative, also by ID-NAT testing 2,115 (99.2 %) donations were HBV DNA negative. Out of the negative ELISA samples, two samples were ID-NAT reactive donors which were missed by serology assay being in the window period. HIV ELISA testing revealed negative 2,130 (99.9 %) donations while ID-NAT testing showed 2,131 (99.95 %) negative donations and one positive donation. In conclusion, this is the first study carried out in the Suez Canal and Sinai region, Egypt to assess the importance of ID-NAT implementation. The introduction of ID-NAT in blood banks is an effective method for increasing safety of the blood transfusion.

The burden of HCV among prevalent hemodialysis patients after the National Egyptian HCV Eradication program.

In the first phase of its treatment program, Egypt aimed to treat 250,000 people annually until 2020, thereby reducing the number of viremic patients and limiting hepatitis C virus (HCV) transmission. Egypt strives to eradicate HCV and HCV-associated morbidity by 2030. This study aimed to determine the prevalence of HCV infection among end-stage renal disease patients and the reasons for non-treatment among those offered free medication. This multi-center cross-sectional study was conducted during the period from November 2022 to April 2023. The study included 500 patients receiving hemodialysis (HD) sessions on a regular basis for more than three months in Dakahlia Governorate. According to patients` medical history, we found that 23.4% of patients had previous HCV infection. Of these, 12.6% received treatment, and 10.8% did not receive treatment due to a variety of reasons. For instance, some patients were unaware of the drug's availability, five patients (1%) feared side effects, 43 patients (8.6%) did not require treatment, and five patients (1%) had other causes as contraindications of drugs, noncompliance and deterioration of health status. In addition, 20.4% of patients were reported to have fully recovered, while 0.8% had a recurrence. After investigations, 1% of patients had positive hepatitis B surface antigen (HbsAg), 23.4% positive HCV Ab, and 4.2% positive HCV by the polymerase chain reaction. In conclusion, the low prevalence of HCV among HD patients confirms that HCV infection is not currently a significant health concern among patients on maintenance HD.

Serum microRNA-16 as a potential biomarker for HCV-induced hepato-cellular carcinoma in Egyptian patients.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Two risk factors that cause 80-90% of HCC cases globally are chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The diagnostic value of circulating microRNAs (miRNAs) in numerous tumors has been described. Our research assessed microRNA-16 (miR-16) as a novel biomarker in patients with HCV-induced HCC. The study included three groups. Group 1 included 55 individuals with cirrhosis caused by liver HCV infection in addition to HCC. Group 2 included 55 individuals with cirrhosis brought on by HCV infection. Group 3 included 55 normal control individuals. Expression of miR-16 in blood was assessed by real-time polymerase chain reaction (RT-PCR). The mean level of miR-16 was significantly different in the three groups, with group 1 having the greatest value (1.098 ± 0.647), followed by group 2 (1.1035 ± 0.8567) and group 3 (control subjects) having the lowest value (0.3842 ± 0.21485). The receiver operating characteristic (ROC) curve analysis showed that miR-16 had a higher diagnostic value at area under the curve (AUC) of 0.935 than alpha-feto protein (AUC of 0.859) to differentiate between HCC and control subjects. MiR-16 has a sensitivity of 81.82 % and a specificity of 69.09%, to distinguish between patients with liver cirrhosis and HCC patients. Our findings illustrated that circulating miR-16 can be proposed as a marker for detection of patients with HCV-induced HCC.

Advancing Hepatitis C Elimination through Opt-Out Universal Screening and Treatment in Carceral Settings, United States.

Incarcerated persons are infected with hepatitis C virus (HCV) at rates ≈10 times higher than that of the general population in the United States. To achieve national hepatitis C elimination goals, the diagnosis and treatment of hepatitis C in incarcerated persons must be prioritized. In 2022, the Centers for Disease Control and Prevention recommended that all persons receive opt-out HCV screening upon entry into a carceral setting. We review recommendations, treatments, and policy strategies used to promote HCV opt-out universal HCV screening and treatment in incarcerated populations in the United States. Treatment of hepatitis C in carceral settings has increased but varies by jurisdiction and is not sufficient to achieve HCV elimination. Strengthening universal HCV screening and treatment of HCV-infected incarcerated persons is necessary for HCV elimination nationwide.

Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder.

Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be triggered by viral infection of the brain is unknown. We used a target-enrichment, deep sequencing platform and bioinformatic pipeline named "ViroFind", for the unbiased characterization of DNA and RNA viruses in brain samples obtained from the National Neuro-AIDS Tissue Consortium. We analyzed fresh frozen post-mortem prefrontal cortex from 72 individuals without known viral infection of the brain, including 16 HIV+/SUD+, 20 HIV+/SUD-, 16 HIV-/SUD+, and 20 HIV-/SUD-. The average age was 52.3 y and 62.5% were males. We identified sequences from 26 viruses belonging to 11 viral taxa. These included viruses with and without known pathogenic potential or tropism to the nervous system, with sequence coverage ranging from 0.03 to 99.73% of the viral genomes. In SUD+ people, HIV-infection was associated with a higher total number of viruses, and HIV+/SUD+ compared to HIV-/SUD+ individuals had an increased frequency of Adenovirus (68.8 vs 0%; p<0.001) and Epstein-Barr virus (EBV) (43.8 vs 6.3%; p=0.037) as well as an increase in Torque Teno virus (TTV) burden. Conversely, in HIV+ people, SUD was associated with an increase in frequency of Hepatitis C virus, (25 in HIV+/SUD+ vs 0% in HIV+/SUD-; p=0.031). Finally, HIV+/SUD- compared to HIV-/SUD- individuals had an increased frequency of EBV (50 vs 0%; p<0.001) and an increase in TTV viral burden, but a decreased Adenovirus viral burden. These data demonstrate an unexpectedly high variety in the human brain virome, identifying targets for future research into the impact of these taxa on the central nervous system. ViroFind could become a valuable tool for monitoring viral dynamics in various compartments, monitoring outbreaks, and informing vaccine development.

Treatment initiation rates of patients with positive anti-hepatitis C virus results in tertiary hospitals in Turkey.

INTRODUCTION: The aim of this national, multicenter, cross-sectional, retrospective chart review study was to determine the proportion of patients in Turkey who received hepatitis C virus (HCV) treatment after receiving positive anti-HCV results during HCV screening. METHODOLOGY: Data related to patients' demographics, laboratory results, time interval from obtaining a positive anti-HCV result to treatment initiation, specialty of the physician requesting anti-HCV screening, and type of hospital were analyzed. RESULTS: Among 1,000 patients who received a positive anti-HCV result, 50.3% were male and 78.5% were screened for HCV-RNA. Among HCV-RNA screened patients, 54.8% (n = 430) had a positive result. Among patients who tested positive for HCV-RNA, 72.8% received HCV treatment in line with their positive anti-HCV results. The median time from obtaining a positive anti-HCV result to initiation of HCV treatment was 91.0 days (interquartile range 42.0 to 178.5). Non-surgical branches requested HCV-RNA testing more frequently than surgical branches (p < 0.001). The rate of access to HCV treatment was higher among patients screened in university hospitals than among patients screened in training and research hospitals (p < 0.001). CONCLUSIONS: Our results indicate a higher rate of treatment initiation among patients with HCV infection than is described in the published literature. Furthermore, the time from screening to treatment initiation was considerably shorter compared with other international studies. However, since HCV-RNA testing was not requested in a significant portion of patients with a positive anti-HCV test result, there might be a large patient population with HCV who do not receive treatment.

Distribution and genotyping of hepatitis C virus (HCV) infection in Gansu province, China.

INTRODUCTION: The distribution of common subtypes of hepatitis C virus (HCV) in Gansu province were analyzed. This information provided a theoretical basis for the selection of appropriate antiviral treatment regimens. METHODOLOGY: We collected data on HCV antibody screening tests from 421,802 outpatients and inpatients at the Second Clinical Hospital of Lanzhou University from January 2018 to June 2022. Ribonucleic acid (RNA) viral load, HCV genotypes, and HCV quantification were analyzed retrospectively. The results of HCV positive detection rate, copy number, and genotype distribution were statistically analysed using SPSS 26.0. RESULTS: A total of 421,802 HCV antibody screenings were performed resulting in 4,558 positive cases (1.081%). In addition, 2,345 cases (1.302%) were positive with quantitative HCV antibodies in 180,157 outpatients and inpatients. Quantitative HCV virus RNA was further measured in 2592 outpatients and inpatients. There were 825 positive cases for HCV, with a positivity rate of 31.83%. High-sensitivity quantification of HCV-RNA was performed in 6538 patients, among which 1336 were HCV-RNA positive infections (positivity rate of 20.43%). Among the 1484 genotype tests, 4 genotypes and 10 subtypes were detected, including 4a, 1b, 2a, 2b, 3a, 3b, 6a, 6n, 1b/2a, and 2a/6a, with the majority of results from 2a (51.89%) and 1b (42.72%). CONCLUSIONS: The most prevalent genetic subtype in HCV-positive patients in Gansu was 2a, followed by 1b. In addition, 8 genotype subtypes appeared: 1a, 2b, 3a, 3b, 6a, 6n, 1b/2a and 2a/6a. Understanding the distribution of HCV genes in Gansu province is of significance for the optimization of virus treatment.

Hepatitis C prevalence and cascade of care among patients in the decentralised opioid agonist therapy programme of the canton of St Gallen, Switzerland: a cross-sectional study.

BACKGROUND: To eliminate chronic hepatitis C virus (HCV) infection by 2030, 90% of those infected must be diagnosed and 80% treated. In Switzerland, >40% of the estimated 32,000 infected people are still undiagnosed. In the canton of St Gallen, HCV prevalence and cascade of care have only been studied in the centralised opioid agonist therapy (OAT) setting (institutions), although about 80% of OAT patients are treated decentrally (general practitioner [GP] or pharmacy). AIM: To describe HCV prevalence and cascade of care among patients in the decentralised OAT programme of the canton of St Gallen, Switzerland, and compare it to contemporaneous data from the centralised setting. METHODS: For each patient receiving his/her OAT from a GP or pharmacy on 1 April 2021, the cantonal medical office sent a questionnaire to the prescribing GP. Patient characteristics, HCV antibody (Ab)/RNA screening uptake, HCV Ab/RNA prevalence and HCV treatment uptake were obtained and compared to those of patients of the Medizinisch-soziale Hilfsstelle 1 in St Gallen (centralised setting). RESULTS: Of the 563 OAT patients under the care of 127 GPs, 107 patients from 41 GPs could be analysed (median age: 48 years [IQR: 40-56]; ongoing intravenous drug use: 25%; OAT provider: 66% GP, 34% pharmacy). HCV Ab screening uptake was 68% (73/107) with an HCV Ab prevalence of 68% (50/73) among those tested. Of the HCV Ab-positive patients, 84% (42/50) were HCV RNA-tested, among whom 57% (24/42) were viraemic. HCV treatment uptake was 83% (20/24), with 95% (19/20) achieving a sustained virological response. Non-uptake of HCV screening and treatment tended to be higher among patients receiving OAT at the pharmacy vs at the GP's office: 37% vs 26% (p = 0.245) for screening and 30% vs 7% (p = 0.139) for treatment. The proportion never HCV Ab-tested and the proportion of HCV Ab-positives never HCV RNA-tested was significantly higher in the decentralised compared to the centralised setting: 32% vs 3% (p <0.001) never Ab-tested and 16% vs 0% (p = 0.002) never RNA-tested. In contrast, HCV treatment uptake (83% vs 78%), sustained virological response rate (95% vs 100%) and residual HCV RNA prevalence among the HCV Ab-positive (12% vs 14%) were comparable for both settings. CONCLUSION: In the decentralised OAT setting of the canton of St Gallen, HCV Ab prevalence is high. Since HCV Ab and RNA screening uptake are markedly lower than in the centralised setting, potentially >40% of patients with chronic HCV are not diagnosed yet. HCV screening in the decentralised setting needs improvement, e.g. by increasing awareness and simplifying testing. High HCV treatment uptake and cure rates are possible in centralised and decentralised settings.

Biosensor-based multiple cross displacement amplification platform for visual and rapid identification of hepatitis C virus.

Hepatitis C remains a global health problem, especially in poverty-stricken areas. A rapid and sensitive point-of-care (POC) diagnostic tool is critical for the early detection and timely treatment of hepatitis C virus (HCV) infection. Here, for the first time, we reported a novel molecular diagnostic assay, termed reverse transcription multiple cross displacement amplification integrated with a gold-nanoparticle-based lateral flow biosensor (RT-MCDA-AuNPs-LFB), which was developed for rapid, sensitive, specific, and visual identification of HCV. HCV-RT-MCDA induced rapid isothermal amplification through a specific primer set targeting the 5'untranslated region gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a that are prevalent in China. The optimal reaction temperature and time for RT-MCDA-AuNPs-LFB were 68°C and 25 min, respectively. The limit of detection of the assay was 10 copies per test, and the specificity was 100% for the experimental strains. The whole detection procedure, including crude nucleic acid isolation (~5 min), RT-MCDA (68°C, 25 min), and visual AuNPs-LFB result confirmation (less than 2 min), was performed within 35 min. The preliminary results indicated that the HCV-RT-MCDA-AuNPs-LFB assay could be a valuable tool for sensitive, specific, visual, cost-saving, and rapid detection of HCV and has potential as a POC diagnostic platform for field screening and early clinical detection of HCV infection.

Integration of Hepatitis C and Addiction Treatment in People Who Inject Drugs: The San Patrignano HCV-Free and Drug-Free Experience.

Injection drug use represents an important contributor to hepatitis C virus (HCV) transmission, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected persons who inject drugs (PWIDs). We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC; we applied the cascade of care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered 811 PWIDs (aged 18+ years) residing in San Patrignano TC at the beginning of the observation period (January 2018-March 2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct-acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. A total of 481 of these 503 individuals (95.6%) underwent HCV RNA testing. Out of the 331 participants positive for HCV RNA, 225 were ultimately prescribed a DAA treatment with a sustained viral response (SVR), which was achieved by 222 PWIDs (98.7%). Of the 222 PWIDs, 186 (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in the care of individuals, which aligns with the therapeutic goals of addiction treatment.

Ongoing Gaps in the Hepatitis C Care Cascade during the Direct-Acting Antiviral Era in a Large Retrospective Cohort in Canada: A Population-Based Study.

To achieve hepatitis C virus (HCV) elimination, high uptake along the care cascade steps for all will be necessary. We mapped engagement with the care cascade overall and among priority groups in the post-direct-acting antivirals (DAAs) period and assessed if this changed relative to pre-DAAs. We created a population-based cohort of all reported HCV diagnoses in Quebec (1990-2018) and constructed the care cascade [antibody diagnosed, RNA tested, RNA positive, genotyped, treated, sustained virologic response (SVR)] in 2013 and 2018. Characteristics associated with RNA testing and treatment initiation were investigated using marginal logistic models via generalized estimating equations. Of the 31,439 individuals HCV-diagnosed in Quebec since 1990 and alive as of 2018, there was significant progress in engagement with the care cascade post- vs. pre-DAAs; 86% vs. 77% were RNA-tested, and 64% vs. 40% initiated treatment. As of 2018, a higher risk of not being RNA-tested or treated was observed among individuals born <1945 vs. >1965 [hazard ratio (HR); 95% CI; 1.35 (1.16-1.57)], those with material and social deprivation [1.21 (1.06-1.38)], and those with alcohol use disorder [1.21 (1.08-1.360]. Overall, non-immigrants had lower rates of RNA testing [0.76 (0.67-0.85)] and treatment initiation [0.63 (0.57-0.70)] than immigrants. As of 2018, PWID had a lower risk of not being RNA tested [0.67 (0.61-0.85)] but a similar risk of not being treated, compared to non-PWID. Engagement in the HCV care cascade have improved in the post-DAA era, but inequities remain. Vulnerable subgroups, including certain older immigrants, were less likely to have received RNA testing or treatment as of 2018 and would benefit from focused interventions to strengthen these steps.

Occult HBV Infection in Patients Infected by HIV or HCV: Comparison between HBV-DNA and Two Assays for HBsAg.

We investigated the frequency and serological correlates of occult hepatitis B virus infection (OBI) and the potential impact of a highly sensitive assay for HBsAg in subjects infected by human immunodeficiency virus (HIV) or hepatitis C virus (HCV), who are also at risk for hepatitis B virus (HBV) infection, often in an occult form. Samples from 499 patients with HIV, all HBsAg negative and anti-HBc positive, and 137 patients with HCV were tested for HBV-DNA, anti-HBc, anti-HBs, and HBsAg by a conventional and highly sensitive assay. HBV biomarkers were detected in 71.5% of HCV-RNA-positive, with a higher prevalence of cases positive only for anti-HBc in patients with HCV than in those with HIV. HBV-DNA was detectable in 0.6% of HIV-positive and 7.3% of HCV-RNA-positive patients. Among patients with HCV, four were positive for HBsAg and negative for HBV-DNA, bringing the rate of HBV-active infection in this group to 10.2%. Active HBV infection was not related to gender or specific patterns of HBV biomarkers but was higher in HCV patients coinfected by HIV compared to those infected only by HCV. Monitoring patients at high risk for HBV infection and reactivation may require testing for both HBV-DNA and HBsAg.

Determination of IL-6 Gene Promoter Polymorphism in Patients with Hepatitis C and Its Impact on RNA Secondary Structure.

Background and Objectives: A polymorphism in the promoter region of the IL-6 gene would influence the level of IL-6 expression in patients with HCV, resulting in a pro-inflammatory response. Few studies have shown the association between -174G>C (rs1800795) and -1363G>T (rs2069827) polymorphisms and HCV infection, and their results have been contradictory. There are no data published in our population to study such an IL-6 stimulus against HCV infection and its impact on RNA secondary structure. Therefore, we isolated human subjects from the province of Punjab, Pakistan. The objective was to screen for IL-6 gene promoter polymorphisms -174G/C and -1363G/T and those correlated with serum concentrations of IL-6 in patients with HCV and compared with a control. Materials and Methods: In conventional PCR, measurement of serum IL-6 by CLIA and statistical analysis were performed to observe the genotype association studies. By integrating bioinformatics and computational tools, our study aimed to provide a comprehensive understanding of how variations in the promoter region of IL-6 may have functional implications on gene expression. Results: The -174G>C and -1363G>T genotypes in the promoter region of patients with HCV were in strong allelic association (Δ = 0.97, p < 0.001). Interestingly, the bioinformatics analysis was well aligned with our experimental data. Conclusions: Based on the data, it can be inferred that IL-6 gene promoter polymorphisms are important in the dysregulation of IL-6 levels in patients with HCV.

No gender differences in the 24-month course of non-invasive liver fibrosis markers after DAA therapy in HCV-mono and HCV/HIV-coinfected patients.

Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.

Systematic integration of molecular and clinical approaches in HCV-induced hepatocellular carcinoma.

BACKGROUND: MicroRNAs (miRNAs) play a crucial role in gene expression and regulation, with dysregulation of miRNA function linked to various diseases, including hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). There is still a gap in understanding the regulatory relationship between miRNAs and mRNAs in HCV-HCC. This study aimed to investigate the function and effects of persistent HCV-induced miRNA expression on gene regulation in HCC. METHODS: MiRNA array data were used to identify differentially expressed miRNAs and their targets, and miRNAs were analyzed via DIANA for KEGG pathways, gene ontology (GO) functional enrichment, and Ingenuity Pathways Analysis (IPA) for hepatotoxicity, canonical pathways, associated network functions, and interactive networks. RESULTS: Seventeen miRNAs in L-HCV and 9 miRNAs in S-HCV were differentially expressed, and 5 miRNAs in L-HCV and 5 miRNAs in S-HCV were significantly expressed in liver hepatocellular carcinoma (LIHC) tumors. Grouped miRNA survival analysis showed that L-HCV miRNAs were associated with survival in LIHC, and miRNA‒mRNA targets regulated viral carcinogenesis and cell cycle alteration through cancer pathways in LIHC. MiRNA-regulated RCN1 was suppressed through miRNA-oncogene interactions, and suppression of RCN1 inhibited invasion and migration in HCC. CONCLUSION: Persistent HCV infection induced the expression of miRNAs that act as tumor suppressors by inhibiting oncogenes in HCC. RCN1 was suppressed while miRNAs were upregulated, demonstrating an inverse relationship. Therefore, hsa-miR-215-5p, hsa-miR-10b-5p, hsa-let-7a-5p and their target RCN1 may be ideal biomarkers for monitoring HCV-HCC progression.

Effects of sustained viral response on lipid in Hepatitis C: a systematic review and meta-analysis.

BACKGROUND: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. METHODS: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. RESULTS: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. CONCLUSIONS: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. REGISTRATION: PROSPERO CRD42020180793.

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy.

BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.