Therapy For Hepatitis C Virus Infection Research Articles

Biomarkers in Detection of Hepatitis C Virus Infection.

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).

Sociodemographic Profile, Genotype, and Response to Therapy in Hepatitis C Virus Infection: A Brief Report from Himachal Pradesh

Introduction Hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. There is no data on sociodemographic profile, risk factors, genotype, and response to therapy of HCV infection from Himachal Pradesh. Methods In this single-center study, we retrospectively analyzed data from HCV-infected patients treated with new oral direct-acting antiviral drugs from September 2019 to March 2022. Data on the sociodemographic profile of HCV-infected patients, along with risk factors for its transmission, HCV genotype, and response to therapy, was analyzed. Results A total of 189 patients were included, with a mean age of 30.9 ± 13.8 years. Most were males and were students. Predominant risk factor for HCV transmission was intravenous drug use (61.4%), tattooing (11.7%), and hemodialysis (11.1%). A majority of the patients were students (72%). The predominant genotype was GT 3. Most (95.2%) patients were without cirrhosis, so sofosbuvir plus daclatasvir for 12 weeks was the most common regimen used. Sustained virological response was achieved in 94.7% of patients. Conclusion This study, alarmingly, shows that intravenous drug users and tattooing are important risk factors for HCV infection in Himachal Pradesh. Further, students were the most frequently infected group.

Comparison of the Efficacies of Direct-Acting Antiviral Treatment for HCV Infection in People Who Inject Drugs and Non-Drug Users.

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

Modern Treatment of Hepatitis C Infection

Abstract In 2016, the World Health Organization set „Viral hepatitis elimination by 2030” as a goal, which is predicated upon 2 advances: on the one hand, the efficacy of hepatitis B vaccine and, on the other, the sustained viral response to direct-acting antiviral (DAA) therapy for infection with hepatitis C virus (HCV). Romania also adopted this initiative considering the available results confirming the efficiency of this policy. Viral clearance results in reduced morbidity and mortality by liver injury and also by any associated HCV infection manifestations. In order to fulfill the target stated by the WHO any patient with detectable viremia must be treated. Unlike interferon-based regimes, DAA therapy for HCV infection is applicable to all groups of patients, regardless of the severity of their liver injury. Other advantages are high efficiency levels, proved in clinical trials as well as in the real world, oral administration route, good safety profile, a very good rate of sustained virological response in patients with decompensated cirrhosis and the possibility of prescribing them to children older than 8. Despite the remarkable progress, an ideal antiviral therapy has not yet been discovered. The direct-acting antiviral therapy in use today has 3 targets: NS3/4A, NS5A, NS5B. None of the drugs is designed to be used alone. For convenience, the pharmaceutical industry has developed pills containing combinations of 2 or 3 active drugs, which completely changed the hepatitis C treatment paradigm.

Using Power of Calculated Electrons to Cut, Analyze and Exterminate the Outer and the Inner Biological Elements of Hepatitis C Virus without Blood Parameters Disorders: In Vitro Study

Recently, the prevention and treatment of hepatitis C virus (HCV) complications consider as major obstacles to reducing HCV outbreaks worldwide. Therefore, it is crucial to develop a new alternative therapy for HCV infection with low cost and low side effects. A smart device termed a Life Restoration Device (LRD) was designated to produce a low potential codified amount of ions. The specified codified amount of ions produced from LRD are designated to exterminate HCV. To investigate our hypothesis, we designated an experimental system for in-vitro studies. This system is composed of a glass tube that can be filled with HCV polymerase chain reaction (PCR)-positive serum. The result of this study showed that LRD can decrease the viral load of HCV PCR-positive serum to 99% after 2 hrs treatment. The viral load reduction of the LRD against low HCV PCR count was almost similar to that of high HCV PCR count. Furthermore, the efficacy of LRD to reduce the serum viral load after 30 min or 60 min treatment was 74%or 95% respectively while the viral load after2 hrs treatment was about 91%. The electron microscopy investigation of HCV PCR-positive serum after treatment with LRD showed degenerated HCV particles compared with the non-treated virus. The in vitro treatment of the HCV PCR-positive serum with LRD didn’t affect the blood contents such as red blood cells count, white blood cells count and hemoglobin levels. The sincerity of the codified amount of ions produced by LRD may affect the fragile fluidity of the viral envelope. Treatment of hepatitis viruses with a codified amount of ions is a new alternative therapy but needs more studies. It is crucial to develop an effective alternative viral therapy using such kind of technology to reduce the antiviral drugs side effects.

A nurse practitioner model of care in the era of direct acting antiviral therapy for hepatitis C virus infection.

Background and AimDirect‐acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has resulted in high rates of successful disease cure; however, not enough healthcare providers are available to deliver treatment to the population living with chronic HCV. To demonstrate that a nurse practitioner (NP) model of care is non‐inferior to specialist gastroenterologist (SG) management of HCV infection, as measured by sustained viral response at 12 weeks (SVR12) after initiation of DAA therapy.DesignRetrospective cohort database study.SettingSingle‐center outpatient study, Central Coast Local Health District (CCLHD).ParticipantsAll patients with chronic HCV treated in the CCLHD Liver Clinic in the period 3rd March 2016 to 31st May 2019 were retrospectively analyzed. In this time period, a total of 1638 patients with chronic HCV had completed treatment. Seven hundred and thirty‐four patients were excluded (733 pre‐PBS listing for DAAs and 1 not treated with DAA). Nine hundred and four patients were eligible for the study, of which 541 were managed by an SG, and 363 managed by an NP.Main outcome measuresData were collected on patient demographics, genotype, fibrosis score, and presence of cirrhosis. Primary end point was number of patients achieving SVR12.ResultsOf the 904 patients treated with DAA, 764 (84.5%) achieved SVR12. There was no statistical difference (P > 0.05) in achieving SVR12 between patients treated by an SP (n = 481, 88.9%) and those treated by an NP (n = 281, 77.4%).ConclusionAn NP model of care is non‐inferior to SG management of HCV infection, as evidenced by equivocal success in achieving SVR12 between the two treatment groups. Therefore, an NP model of care is a viable option in the era of DAA therapy for HCV infection. Ongoing investment into the delivery of NP care could increase treatment uptake of HCV, with the aim of decreasing overall burden of disease.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4years and post-LT survival was 87.9% at 5years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems.

Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.

HCV Core Antigen as an alternative test to Quantitative HCV RNA for assessment of SVR in Chronic HCV infected patients treated with Direct Acting Antiviral agents

Abstract Background and aims Widespread use of direct-acting antiviral (DAA) agents to treat patients with hepatitis C virus (HCV) infection has reduced the need for monitoring of HCV-RNA levels, because viral kinetics do not predict sustained virologic response (SVR) to these drugs. However, the performance of cheaper tests, such as the assay to quantify HCV core antigen (HCV Ag), has not been determined. This study was aimed at investigating the accuracy of the HCV Ag test in predicting which patients receiving DAAs will achieve SVR at week 12 (SVR12). Methods We performed a prospective study on 90 patients, chronically infected with HCV, receiving DAAs therapy from different NCCVH centers in Cairo during the period from August 2017 to June 2018. We collected blood samples and measured the levels of HCV core Ag and HCV-RNA at baseline and 12 weeks after end of treatment. We compared the ability of these assays to predict which patients would have SVR12. Results The median baseline level of HCV-RNA was 1688529.6 ± 994697.3 IU/ml (range, 312700 IU/ml to 3491100 IU/ml) and HCV Ag was 179.2 ± 83.5 pg/ml (range, 33.5 pg/ml to 315.6 pg/ml). HCV Ag became undetectable in 92.2% 12 weeks after the end of treatment. HCV-RNA became undetectable in 87.8% at the end of treatment (P<.0001). 79 out of 90 patients (87.8%) achieved an SVR12; the test for HCV Ag identified 63.6% of these patients. Conclusions Tests that measure HCV Ag monitor efficacy of DAA therapy for HCV infection as well as assays that measure HCV-RNA, and hence could be recommended for clinical practice.

Recommendations of the Polish Group of Experts for HCV for the treatment of hepatitis C in 2020.

The recommendations set out the principles of diagnosis and treatment of hepatitis C virus (HCV) infections according to the most recent knowledge. The main goal of therapy for HCV infection is to eliminate the virus from the body, which consequently leads to arrest of progress or regression of changes in the liver. Current version of the recommendations prioritise pangenotypic regimens and provide guidelines in special populations of patients, such as children, cirrhotics, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfected, those with renal failure, hepatic decompensation and non-responders to previous therapies.

Can hepatitis C virus core antigen replace quantitative RNA in the assessment of a sustained virologic response?

BackgroundThe widespread use of direct-acting antivirals (DAAs) in the treatment of hepatitis C virus (HCV) infection has reduced the need for monitoring HCV-RNA levels because viral kinetics do not predict a sustained virologic response (SVR). However, the performance of cheaper tests, such as the assay to quantify hepatitis C virus core antigen (HCV Ag), has not been determined. Our aim was to assess the accuracy of the HCV core Ag test in predicting the achievement of SVR and its predictive value as a monitoring test in the course of treatment.Patients and methodsThis prospective study was carried out on 90 patients, chronically infected with HCV, who received DAA therapy. Blood samples were collected and the levels of HCV core Ag and HCV-RNA were measured at baseline and at 12 weeks after the end of treatment. We compared the ability of these assays to predict which patients would achieve SVR12.ResultsThe baseline level of HCV-RNA was 1 688 529.6±994 697.3 IU/ml (range: 312 700–3 491 100 IU/ml) and HCV core Ag was 179.2±83.5 pg/ml (range: 33.5–315.6 pg/ml). HCV Ag became undetectable in 92.2% 12 weeks after the end of treatment, whereas HCV-RNA became undetectable in 87.8% at the end of treatment (P<0001). Seventy-nine out of 90 (87.8%) patients achieved SVR12; the test for HCV Ag identified 63.6% of these patients.ConclusionMeasurement of HCV core Ag can monitor the efficacy of DAA therapy for HCV infection. Thus, it can be applied in clinical practice.

Analysis of drug-induced hearing loss by using a spontaneous reporting system database.

Many drugs can cause hearing loss, leading to sensorineural deafness. The aim of this study was to evaluate the risk of drug-induced hearing loss (DIHL) by using the Japanese Adverse Drug Event Report (JADER) database and to obtain profiles of DIHL onset in clinical settings. We relied on the Medical Dictionary for Regulatory Activities preferred terms and standardized queries, and calculated the reporting odds ratios (RORs). Furthermore, we applied multivariate logistic regression analysis, association rule mining, and time-to-onset analysis using Weibull proportional hazard models. Of 534688 reports recorded in the JADER database from April 2004 to June 2018, adverse event signals were detected for platinum compounds, sulfonamides (plain) (loop diuretics), interferons, ribavirin, other aminoglycosides, papillomavirus vaccines, drugs used in erectile dysfunction, vancomycin, erythromycin, and pancuronium by determining RORs. The RORs of other aminoglycosides, other quaternary ammonium compounds, drugs used in erectile dysfunction, and sulfonamides (plain) were 29.4 (22.4–38.6), 18.5 (11.2–30.6), 15.4 (10.6–22.5), and 12.6 (10.0–16.0), respectively. High lift score was observed for patients with congenital diaphragmatic hernia treated with pancuronium using association rule mining. The median durations (interquartile range) for DIHL due to platinum compounds, sulfonamides (plain), interferons, antivirals for treatment of hepatitis C virus (HCV) infections, other aminoglycosides, carboxamide derivatives, macrolides, and pneumococcal vaccines were 25.5 (7.5–111.3), 80.5 (4.5–143.0), 64.0 (14.0–132.0), 53.0 (9.0–121.0), 11.0 (3.0–26.8), 1.5 (0.3–11.5), 3.5 (1.3–6.8), and 2.0 (1.0–4.5), respectively. Our results demonstrated potential risks associated with several drugs based on their RORs. We recommend to closely monitor patients treated with aminoglycosides for DIHL for at least two weeks. Moreover, individuals receiving platinum compounds, sulfonamides (plain), interferons, and antivirals for HCV infection therapy should be carefully observed for DIHL for at least several months.

Short Course of Treatment for Hepatitis C in Adolescents

Source: El-Khayat H, Kamal EM, Yakoot M, et al. Effectiveness of 8-week sofosbuvir/ledipasvir in the adolescent chronic hepatitis C-infected patients. Eur J Gastroenterol Hepatol. 2019; 31(8): 1004– 1009; doi: 10.1097/MEG.0000000000001360Investigators from multiple institutions in Egypt conducted a randomized trial assessing the efficacy and safety of sofosbuvir/ledipasvir (SOF/LVD) for 8 weeks, compared to 12 weeks, for treatment of genotype 4 hepatitis C virus (HCV) infection in adolescents 12–17 years old. Study patients were randomized to a single daily dose of a combination of SOF 400 mg and LVD 90 mg for either 8 or 12 weeks. At baseline, participants underwent a FibroScan to assess liver fibrosis using a standardized classification system. Laboratory screening was conducted at baseline and throughout the 12-week study period to measure HCV RNA and assess for possible adverse events; study participants reported adverse events. The primary study outcome was the sustained virologic response (SVR) rate, defined as undetectable HCV RNA at week 12. Secondary outcomes included SVR rates at 4 weeks and adverse events.A total of 157 patients were enrolled in the study: 73 were randomized to 8 weeks of SOF/LVD treatment and 84 to 12 weeks of treatment. The mean age of study patients was 14 years, the mean (standard deviation) HCV RNA at baseline was 5.80 (0.17) IU/L, and 68% had no to mild liver fibrosis at baseline. The source of HCV infection was considered to be perinatal infection in 73% of patients, surgical or dental procedures in 10%, and unknown in 17%. Patient characteristics were similar in the 2 treatment groups.The SVR rate at 12 weeks was 98.6% (95% CI, 93%–100%) for those treated for 8 weeks and 97.6% (95% CI, 96%–100%) for patients treated for 12 weeks. SVR rates at 4 weeks were 63% and 58%, respectively, for adolescents in the 8-week and 12-week treatment groups. Adverse events were reported by 7% of those in the 8-week group, including fatigue (2 patients), and headache, epigastric tenderness, and nausea in 1 patient each. Among patients randomized to 12 weeks of treatment, 8.3% reported an adverse event, including fatigue (1 patient), epigastric tenderness (1 patient), diarrhea (2 patients), nausea (1 patient), and rash (2 patients). Laboratory screening did not reveal any significant adverse events.The authors conclude that 8 weeks of SOF/LVD is as effective as 12 weeks of treatment in adolescents with HCV infection.Dr Rosenthal has disclosed the following financial relationships relevant to this commentary: Research grant support from Gilead, AbbVie, and Merck. This commentary does contain a discussion of an unapproved/investigative use of a commercial product/device.With the advent of highly effective direct-acting antiviral (DAA) drugs for HCV therapy, chronic HCV infection is no longer the leading indication in adults requiring liver transplant.1 Although therapies for HCV in children lag behind the regimens approved in adults, all oral DAA regimens in children are also now approved by the US Food and Drug Administration (FDA) and available.2 Regimens are so effective that cure can be anticipated in 8–12 weeks of therapy. The current investigators found that an 8-week course of SOF/LVD therapy was as effective and safe as the classic 12-week course in curing adolescents of genotype 4 HCV.In the United States, approximately 75% of chronic HCV infections are caused by HCV genotype 1; 15%–20% by genotype 2 or 3; and <5% by genotypes 4, 5, or 6.3 The FDA has approved 12-week combination SOF/LVD for the treatment of pediatric patients ≥12 years of age who weigh at least 35 kg and have HCV genotype 1 infection; they can be treatment naive without cirrhosis or with compensated cirrhosis or treatment experienced without cirrhosis.4 The FDA also approved its use for 12 weeks of therapy in adolescents with genotypes 4, 5, or 6 who are treatment naive or who are treatment experienced without cirrhosis or with compensated cirrhosis.4 In treatment-experienced adolescents with genotype 1 HCV and compensated cirrhosis, therapy should consist of 24 weeks of SOF/LVD. If SOF/LVD is used, 2 warnings need to be heeded.4 Patients with HCV and hepatitis B virus coinfection need to be monitored for hepatitis B virus reactivation and hepatitis flare during HCV treatment and posttreatment follow-up. Coadministration of amiodarone with SOF/LVD is not recommended because serious bradycardia with symptoms may occur.4DAA therapies for HCV infection are approved for use in adolescents. Regimens are effective and safe.At first glance, it would appear that therapy for HCV infection is solely within the purview of gastroenterologists. Pediatricians, however, can ensure that HCV screening is performed in patients at high risk, such as children of mothers who are HCV positive, and that potentially hepatotoxic agents (eg, alcohol) are avoided in those with HCV infection. (See AAP Grand Rounds. 2019;41[4]:45.5)

Anti-viral activity of compounds from Agrimonia pilosa and Galla rhois extract mixture

Hepatitis C virus (HCV) infection is a significant health problem, with a worldwide prevalence of about 170 million. Recently, the development of direct acting antiviral (DAA) as a therapeutic agent for HCV has been rapidly increasing. However, DAA has a side effect and is costly. Therefore, it is still necessary to develop a therapeutic agent to treat HCV infection using products.Agrimonia pilosa (AP) and Galla rhois (RG) are traditional medicines and are known to display therapeutic activity on various diseases. Notably, they have been reported to have an anti-viral effect on HBV and influenza virus infections. It is expected that anti-viral activity will increase when two extracts are mixed.To investigate their anti-viral activity, the expression level of HCV Core 1b and NS5A was measured. Remarkably, AP, RG, and their mixed compound (APRG64) strongly inhibited the expression of viral proteins, which led us to identify their metabolites. A total of 14 metabolites were identified using liquid chromatography mass spectrometry (LC-MS). These metabolites were evaluated for their anti-HCV activity to identify active ingredients.In conclusion, our results unveiled that anti-HCV activity of Agrimonia pilosa and Galla rhois extract mixture could lead to the development of a novel therapy for HCV infection.

Elimination of hepatitis C virus infection among people who use drugs: Ensuring equitable access to prevention, treatment, and care for all

There have been major strides towards the World Health Organization goal to eliminate hepatitis C virus (HCV) infection as a global public health threat. The availability of simple, well-tolerated direct-acting antiviral therapies for HCV infection that can achieve a cure in >95% of people has provided an important tool to help achieve the global elimination targets. Encouragingly, therapy is highly effective among people receiving opioid agonist therapy and people who have recently injected drugs. Moving forward, major challenges include ensuring that new infections are prevented from occurring and that people who are living with HCV are tested, linked to care, treated, receive appropriate follow-up, and have equitable access to care. This editorial highlights key themes and articles in a special issue focusing on the elimination of HCV among people who inject drugs. An overarching consideration flowing from this work is how to ensure equitable access to HCV treatment and care for all. This special issue maps the field in relation to: HCV prevention; the cascade of HCV care; strategies to enhance testing, linkage to care, and treatment uptake; and HCV treatment and reinfection. In addition, papers draw attention to the ‘risk environments’ and socio-ecological determinants of HCV acquisition, barriers to HCV care, the importance of messaging around the side-effects of new direct-acting antiviral therapies, the positive transformative potential of treatment and cure, and the key role of community-based drug user organizations in the HCV response. While this special issue highlights some successful efforts towards HCV elimination among people who inject drugs, it also highlights the relative lack of attention to settings in which resources enabling elimination are scarce, and where elimination hopes and potentials are less clear, such as in many low and middle income countries. Strengthening capacity in areas of the world where resources are more limited will be a critical step towards ensuring equity for all so that global HCV elimination among PWID can be achieved.

Process of selecting and educating HCV-uninfected kidney waiting-list candidates for HCV-infected kidney transplantation.

Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)-infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV-infected donors has increased significantly. With the development of direct-acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used direct-acting antiviral therapy to treat HCV infection in HCV-uninfected transplant recipients of kidneys from HCV-viremic donors. To date, HCV has been eradicated in all cases. Though these strategies will potentially increase the donor pool of available kidneys, shorten waitlist times, and ultimately decrease mortality in patients waiting for KT, identifying the ideal candidates and educating them about a protocol to utilize direct-acting antiviral therapy to cure HCV after it is transmitted is essential. We present our approach to patient selection and education for a clinical trial in transplantation of HCV viremic kidneys into uninfected recipients.

Direct-acting antiviral therapy slows kidney function decline in patients with Hepatitis C virus infection and chronic kidney disease

Hepatitis C virus (HCV) infection is common and can accelerate chronic kidney disease (CKD) progression. Direct-acting antiviral (DAA) therapies against hepatitis C have consistently shown rates of sustained viral remission. However, the effect on kidney function is unknown. In a retrospective observational cohort study of HCV-infected patients receiving DAA therapies from 2013 to 2017, the slopes of estimated glomerular filtration rate (eGFR) decline were compared in the three years before DAA therapy to the slope after therapy. Pre- and post-treatment albuminuria values were also compared. In all, 1,178 patients were included; mean age of 56, 64% male, 71% white, 21% were diabetic, and 42% with cirrhosis. In patients with eGFR less than 60ml/min per 1.73m2, the annual decline in eGFR in the three years prior to treatment was -5.98 ml/min per year (95% confidence interval -7.30 to -4.67) and improved to -1.32 ml/min per year (95% confidence interval -4.50 to 1.88) after DAA therapy. In patients with eGFR greater than 60ml/min per 1.73m2 the annual decline in eGFR in the three years prior to treatment was -1.43 ml/min per year (95% confidence interval -1.78 to -1.08) and after DAA therapy was -2.32 ml/min per year (95% confidence interval -3.36 to -1.03). Albuminuria improved significantly in patients without diabetes, but not in those with diabetes. Predictors of eGFR improvement included having CKD at baseline and being non-diabetic. Events of acute kidney injury were rare, occurring in 29 patients, and unrelated to antiviral therapy in 76% of cases. Thus, DAA therapy for HCVs infection may slow CKD progression.

Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients

BackgroundHearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.MethodsWe conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir–velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.ResultsA total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.ConclusionsIn patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.)

Identification of a New HCV Subtype 6xg Among Injection Drug Users in Kachin, Myanmar.

Characterizing hepatitis C virus (HCV) genetic diversity not only allows us to trace its origin and evolutionary history, but also provides valuable insights into diagnosis, prevention and therapy of HCV infection. Although eight HCV genotypes and 86 subtypes have been classified, there are still some HCV variants that need to be assigned. The genotype 6 is the most diverse HCV genotype and mainly prevalent in Southeast Asia. In this study, we identified a new HCV subtype 6xg from injection drug users (IDUs) in Kachin, Myanmar. A distinctive feature of 6xg from other subtypes of the genotype 6 was a Lys insertion in NS5A gene, which changes the RRKR/K motif into RRKKR/K. Bayesian analyses showed that HCV 6xg originated during 1984–1988, and experienced a rapid population expansion during 2005–2009. We characterized HCV subtype profile among IDUs in this region, and detected six HCV subtypes, including 1a (12.0%), 3a (12.0%), 3b (24.0%), 6n (16.0%), 6xa (20.0%), and 6xg (12.0%). Importantly, we found that HCV subtype distribution in Kachin was very similar to that in Dehong prefecture of Yunnan, but very distinct from those in other regions of Myanmar and Yunnan, indicating that the China–Myanmar border region shared a unique HCV subtype pattern. The appearance of 6xg and the unique HCV subtype profile among IDUs in the China–Myanmar border region have significant epidemiological and public health implications.

Review on chemogenomic approaches towards hepatitis C viral targets.

Hepatitis C virus (HCV) is the most prevalent viral pathogen that infects more than 185 million people worldwide. HCV infection leads to chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma. Direct-acting antivirals (DAAs) are the recent combination therapy for HCV infection with reduced side effects than prior therapies. Sustained virological response (SVR) acts as a gold standard marker to monitor the success of antiviral treatment. Older treatment therapies attain 50-55% of SVR compared with DAAs which attain around 90-95%. The current review emphasizes the recent chemogenomic updates that have been unfolded through structure-based drug design of HCV drug target proteins (NS3/4A, NS5A, and NS5B) and ligand-based drug design of DAAs in achieving a stable HCV viral treatment strategies.