Sustained Virological Response Rates Research Articles

DAA - directly acting antivirals - as a new, more efficient solution of the chronic hepatitis C treatment and theirs various application.

Introduction Cirrhosis is a condition in which the liver becomes fibrotic following damage to the liver and transforms the architecture of the organ into regenerative nodules. The disease is caused 30% by HCV infection, resulting in a risk of severe complications and death. Since the use of direct-acting antivirals ( DAAs) for the treatment of chronic HCV, sustained virological response (SVR) rates have begun to increase, even in treatment-resistant cases. Studies have also shown that DAAs may have applications in other viral diseases and even In the treatment of breast cancer. Aim of the study The purpouse of our study was to review scientific articles to show the efficiency and potential use of DAAs in the treatment of chronic HCV, and to identify possible directions for further research. Methods and materials We reviewed the English literature in the PubMed, using the key words: "simeprevir" ; "sofosbuvir" ; "velpatasvir" ; "telaprevir" ; "chronic hepatitis C". Results Studies have shown that the therapeutic regimens currently being designed with (DAAs) offer the possibility of treating almost the entire population with hepatitis C, while reducing side effects of interferon therapy such as increased AST, ALT activities, diarrhoea, vomiting, nausea and depression. They remain effective and tolerable, regardless of the stage of cirrhosis and associated serious co-morbidities. Analysis of studiem shows, that DAAs also show efficacy against other disease such as breast cancer, MRSA infections, SARS-CoV-2 or flavivirus infection. Conclusion All (DAAs) are effective in the treatment of patients with HCV, including cirrhosis. They result in significant improvements in prognosis and clinical outcomes. Promising results have been obtained in published data on the effect of DAAs against disease entities other than HCV, suggesting the rationale for future clinical trials to further the hypothesis of the increased potential of these drugs.

Real-world treatment outcomes of sofosbuvir-based regimens for treatment of chronic hepatitis C with and without human immunodeficiency virus co-infection.

The efficacy of sofosbuvir (SOF)-based regimens in the treatment of chronic hepatitis C (HCV) patients with and without human immunodeficiency virus (HIV) co-infected patients in real-world setting is limited. This was a retrospective cohort study, conducted between 1 January 2017 and 31 December 2021 at Bamrasnaradura Infectious Disease Institute, Thailand. All HCV patients received 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) at 12 weeks after the end of treatment. Treatment outcomes were compared between HCV patients with and without HIV co-infection. A total of 163 patients were included in the study, 130 (79.8%) were HCV/HIV co-infected, and 33 (20.2%) were HCV mono-infected. Of all, 106 (64%) patients received SOF and ledipasvir. Genotype 1 (GT1) was predominant at 66.4%, followed by GT3 at 22.2%, and GT6 at 11.4%. Overall SVR was 96.9%. SVR in HCV mono-infected was 96.9% and SVR in HIV-HCV co-infected patients was 96.9%. The factor associated with SVR was HCV genotype (P=0.001). Patients with HCV GT6 had lower SVR rates compared with GT1 and GT3 patients (83.3%, 100%, and 97.1% [P=0.000] respectively). There was no association between SVR and other factors such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history (all P > 0.05). All patients completed 12-week SOF-based treatment. In real-world setting, HCV treatment with SOF-based regimens between patients with and without HIV co-infection showed high rates of SVR. SOF-based regimens were highly efficacious and tolerated.

Effectiveness of elbasvir/grazoprevir plus ribavirin for hepatitis C virus genotype 1a infection and baseline NS5A resistance

Introduction and ObjectivesIn clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin. Materials and MethodsThis was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who were prescribed 16 weeks of elbasvir/grazoprevir and ≥ 1 prescription for ribavirin were included. SVR was defined as HCV RNA below the lower limit of quantification ≥ 70 days after end of treatment. ResultsThe primary analysis included patients with baseline RASs at positions 30, 31, or 93 (n = 76); a secondary analysis included patients with RASs at positions 28, 30, 31, or 93 (n = 93). SVR was achieved by 77.6% (59/76) of patients in the primary analysis and 80.6% (75/93) of those in the secondary analysis. Of the 18 (19.4%) patients in the secondary cohort who failed to achieve SVR, 8 relapsed (4 with treatment-emergent NS5A substitutions) and 10 did not have viral sequencing to distinguish relapse from reinfection. ConclusionsThis analysis highlights the opportunities in leveraging real-world data to further understand treatment outcomes in smaller, discrete subgroups of patients with HCV infection who cannot be thoroughly evaluated in clinical trials.

Effectiveness of pangenotypic retreatment of chronic hepatitis C after prior failure of pangenotypic therapies.

Despite the overall excellent efficacy of pangenotypic direct‑acting antiviral (DAA) options, there is still a small percentage of patients with hepatitis C virus (HCV) infection who do not respond to the therapy. This analysis was designed to evaluate the effectiveness of pangenotypic retreatment in the cases of pangenotypic therapy failure. The study included patients treated with the pangenotypic regimen, selected from the EpiTer‑2 database, a real‑world project evaluating DAA‑based treatment in Poland. Of a total 15 123 patients, 4345 received 1 course of the pangenotypic treatment (PAN group) and 48 patients were retreated with pangenotypic regimens after a failure of the pangenotypic therapy (PAP group). The patients from the PAP group were more often men (79% vs 53%; P <0.001), had higher median (interquartile range [IQR]) body mass index (27.5 [25.7-30.1] vs 25.7 [22.9-28.7] kg/m2; P <0.001), were more often infected with genotype 3 (58% vs 27%; P <0.001), and more frequently had liver cirrhosis (46% vs 21%; P <0.001) than the patients in the PAN group. Importantly, no significant difference in the treatment effectiveness was found between the PAP and PAN groups with sustained virologic response (SVR) rate of 89.6% vs 93.7% (P = 0.39) in intention‑to‑treat, and 91.5% vs 97.6% (P = 0.17) in the per-protocol analysis. The selection of a specific retherapy regimen did not affect SVR. Our study demonstrated the excellent effectiveness of pangenotypic regimens and confirmed that most DAA nonresponders could be successfully retreated with another pangenotypic regimen. The best retreatment strategy is a triple pangenotypic regimen, especially in patients with unfavorable response factors, such as genotype 3 infection, cirrhosis, and male sex.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil.

Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

Результаты исследования “Deti-2”: эффективность комбинации глекапревир/пибрентасвир в реальной клинической практике у подростков 12–17 лет с хроническим гепатитом С в России

The introduction of interferon-free combinations made it possible to effectively conduct antiviral therapy of chronic infection caused by hepatitis C virus (HCV) first in adults and later in adolescents. Glecaprevir/pibrentasvir (GLE/PIB) allowed to achieve sustained virological response (SVR12) in 100% (47/47) of adolescents in the DORA clinical trial. In the meantime there is insufficient data describing the effectiveness of GLE/PIB in adolescents in real clinical practice in Russia. Objective. Evaluation of the effectiveness of GLE/PIB in the treatment of chronic hepatitis C in adolescents 12–17 years of age in real clinical practice in the Russian Federation. Patients and methods. This prospective multicenter observational study enrolled adolescents (12–17 years old) chronically infected with HCV who were prescribed GLE/PIB for 8–16 weeks according to the label approved in the Russian Federation. Efficacy was evaluated based on the sustained virological response rate (SVR12), defined as the HCV RNA level &lt; 50 IU/ml (or undetectable) 12 weeks after the last dose of GLE/PIB. Results. Of the 99 patients enrolled in the study, 92 received GLE/PIB for 8 weeks and 7 for 16 weeks. The overall SVR12 rate was 96.77% (90/93). In subgroups receiving 8- and 16-week courses of therapy, the efficacy was 96.51% (83/86) and 100% (7/7), respectively. SVR was achieved in 96.43% (81/84) of treatment-naive patients, and in 100.00% (9/9) of treatmentexperienced patients. Adverse events (AEs) were reported in 7.07% of patients (7/99), while no AEs of the 3rd degree of severity were observed, as well as no serious adverse events. All patients who did not achieve SVR12 had been diagnosed with stage 4 HIV infection. Conclusion. GLE/PIB was highly effective and well tolerated by adolescents infected with HCV in real clinical practice in Russia, which corresponds to the results previously obtained in the DORA clinical trial. Key words: hronic hepatitis C, hepatitis C virus, glecaprevir, pibrentasvir, SVR12, adolescents

Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals.

Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population. The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023. The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively. A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.

Real World Efficacy and Safety of Sofosbuvir + Velpatasvir + Voxilaprevir in Romanian Patients with Genotype 1b HCV Infection Non-reponders to DAAs Therapy

The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy. In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/ VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered. Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/ grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%). SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction.

1536. Hepatitis C Care Cascade Before and After Lifted Insurance Restrictions In Birth Cohort and Non-Birth Cohort Patients

Abstract Background In 2016, the MetroHealth System implemented a system-wide hepatitis C (HCV) screening initiative in novel settings. We previously showed that those born 1945–1965 (birth cohort, BC) had higher rates of linkage to care (LTC) and sustained virologic response (SVR) rates compared to non-BC (not born 1945–1965). Since 2019, restrictions on fibrosis, sobriety and prescriber have been loosened. We hypothesized that gaps in care cascade between BC and non-BC patients (including LTC rates) would lessen in those diagnosed after 2019. Methods We compared the HCV LTC rates and care cascade in patients diagnosed from Jan 1, 2016 to June 30 2017 (early group) to those diagnosed July 1, 2019 to Dec 31, 2020 (late group) as well between BC and non-BC patients. We performed logistic regression to evaluate the impact of race, gender, known prior HCV positivity, site of HCV diagnosis, HIV, insurance, active injection drug use (IDU), remote IDU, psychiatric disorder, BC status and early/late diagnosis on LTC. Results The study population comprised 2103 HCV+ patients (1349 non-BC, 754 BC). There were 1026 patients in the early group and 1077 patients in the late group. 1353 patients were HCV RNA+. Of those, 914 (67.6%) were white, 306 (22.6%) African American; 872 (64.4%) male; 990 (74.5%) Medicaid; 822 (60.7%) outpatient diagnosis. On multivariable analysis, factors affecting. LTC were: BC (aOR 1.71, 95%CI 1.19–2.45, p=0.003); diagnosed inpatient (aOR 0.45 (0.32–0.66), p&amp;lt; 0.0001), emergency department (aOR 0.55, (0.35–0.89), p=0.0142) or jail (aOR 0.23, (0.13–0.4), p=0.23); active IDU (aOR 0.22, (0.14–0.35),p&amp;lt; 0.0001); remote IDU (aOR 0.60, (0.4–0.89)p=0.01); and diagnosis in the late group (aOR 0.67, (0.51–0.8), p=0.005). The care cascade improved in the late group, but gaps remained in non-BC vs BC (Table). Conclusion The non-BC continued to have lower rates of LTC compared to BC in the late group.Overall LTC was decreased in the late group for both non-BC and BC likely due to COVID-19. However, improvement in medication approval was shown in the late group, and most patients who were prescribed treatment completed it. Active IDU remained a barrier to non-LTC, but did not fully explain the differences between BC and non-BC patients. Disclosures Melissa O. Jenkins, Meliisa Jenkins, Gilead Sciences: Grant/Research Support.

Fibrosis Changes Following Viral Clearance and its Relation to HCC

Globally, about 290 000 people died from hepatitis C (HCV) in 2019, mostly from cirrhosis and hepatocellular carcinoma (HCC). Less than a decade, direct-acting antivirals (DAAs) replaced interferon-based therapies in treatment protocols and sustained virologic response (SVR) rates exceeded 95%. However, it is not clear yet whether HCV eradication by DAAs can reverse fibrosis or cirrhosis substantially, reduce the risk of developing HCC in the long term. In this review was aimed to summarizes the evidence for reversibility or progression of fibrosis following HCV clearance by DAAs, subsequently its impact on developing de nova HCC. For this purpose, cohorts in which patients achieved SVR, have paired liver stiffness measurements obtained by transient elastography were reviewed and results discussed.

Hepatocellular carcinoma and hepatitis C virus treatments: The bold and the beautiful.

The occurrence of hepatocellular carcinoma (HCC) is one of the most serious complications of hepatitis C virus (HCV) infection. Recently, effective antiviral medications have made sustained viral response (SVR) or cure a realistic therapeutic goal for most chronic HCV patients. Given HCV's tumorigenic propensity, it is not surprising that achieving SVR is helpful in preventing HCC. This review briefly summarizes and discusses the existing evidence on the relationship between hepatic carcinogenesis and viral eradication by antivirals, which is mainly divided into interferon-based and direct-acting antivirals (DAAs) based therapy. DAAs have changed the treatment landscape of chronic HCV, reaching high rates of SVR even in patients with advanced cirrhosis, with few contraindications and little side effects. Although some early reports suggested that DAA treatment increased the chance of HCC occurrence, more subsequent observational studies have refuted this theory. The probability of HCC recurrence after HCV eradication appears to be decreasing over time following SVR. Despite virological suppression/cure, individuals with liver cirrhosis are still at risk of HCC and should be monitored. There is a considerable need for markers/scores to predict the long-term risk of HCC in patients with HCV-related liver disease who attain SVR with direct-acting antivirals.

Evaluation of a pilot emergency department linkage to care program for patients previously diagnosed with Hepatitis C.

There is a significant number of Emergency Department (ED) patients with known chronic hepatitis C virus (HCV) infection who have not been treated with directly acting antivirals. We implemented a pilot ED-based linkage-to-care program to address this need and evaluated the impact of the program using the HCV Care Continuum metrics. Between March 2015 and May 2016, dedicated patient care navigators identified HCV RNA-positive patients in an urban ED and offered expedited appointments with the on-site viral hepatitis clinic. Patient demographics and care continuum outcomes were abstracted from the EMR and analysed to determine significant factors influencing linkage-to-care (LTC) and treatment initiation rates. The ED linkage-to-care program achieved a 43% linkage-to-care rate (165/384), 22% treatment rate (84/384) and 16% sustained virologic response rate (63/384). Significant associations were found between linkage-to-care and increasing age (OR=1.03), Medicare insurance (OR=2.21) and having a primary care physician (PCP) (OR=4.03). For patients who were linked, the odds of initiating treatment were also positively significantly associated with increasing age (OR=1.04) and having a PCP (OR=2.77). For patients who initiated treatment, the odds of sustained virologic response were marginally associated with having a PCP (OR=4.92).Our ED linkage-to-care program utilized care coordination to successfully link nearly half of approached HCV RNA-positive patients to care. This design can be feasibly replicated by other EDs given limited non-clinical training required for linkage-to-care staff. Adoption of similar programs in other EDs may improve the rates of LTC and treatment initiation for previously diagnosed HCV patients.

Sustained virological response after treatment with direct antiviral agents in individuals with HIV and hepatitis C co-infection.

Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing. We included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment. A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered. Our estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.

Understanding the effect of direct-acting antiviral therapy on weight in patients with chronic hepatitis C

Direct-acting antivirals (DAAs) have revolutionized treatment for HCV. Compared to interferon-based therapies, DAAs achieve higher rates of sustained virologic response, with more tolerable side effects. Nonetheless, interferon-based therapies have the potential to cause weight loss, and literature documenting the impact of DAAs on weight is limited. Appetite suppression may occur with chronic HCV. It is plausible that DAAs may indirectly cause weight gain given their ability to cause rapid virologic suppression, leading to improved hepatic function. A retrospective chart review identified 220 patients who initiated DAA therapy between 1 February 2019, and 29 February 2020. Patients 18years and older who completed therapy with a DAA were included in the study if they had a documented initial weight (weight on the day therapy was initiated) and final weight (weight 12weeks after therapy completion). Change in weight was assessed as the primary outcome. Comorbidities with the potential to impact weight were assessed as confounders. Multiple variables were analyzed and baseline BMI was the only factor that influenced a change in weight (P = 0.016). Patients with a higher BMI at baseline experienced statistically significant weight gain. Weight was increased by 0.14kg per unit of BMI (95% CI: 0.026, 0.25). Patient demographics relating to age and gender, progression of cirrhosis and concurrent comorbidities had no statistically significant impact on change in weight. Weight changes after treatment with a DAA may be related to the individual's weight prior to treatment.

Sustained virological response (SVR) and safety of two direct acting anti-viral (DAA) combination therapies in Chronic Hepatitis-C infected patients of Lahore, Pakistan. A Randomized Controlled Trial

Chronic Hepatitis C (HCV) is a deadly infection affecting &gt; 185 million people worldwide and led to liver cirrhosis, hepatocellular carcinoma, or liver failure. Recently, treatment regimens of chronic HCV have entered the era of direct acting anti-virals (DAAs). Sustained virological response (SVR) rate is one of the best available tools to evaluate the efficacy of DAA treatments. Objective: To compare SVR rate and safety of two combinations of DAA treatments (Sofosbuvir and Daclatasvir vs Sofosbuvir and Velpatasvir) in chronic HCV infected patients of Lahore, Pakistan. Methods: Present randomized controlled trial was conducted at Mayo Hospital, Lahore, Pakistan and recruited 76 chronic HCV infected patients according to Consort guidelines. Registered patients were allocated in two groups by lottery method. Group A received sofobuvir with daclatasvir (SOFO + DCV) while group B received sofobuvir with velpatasvir (SOFO + VEL) treatment for 12 weeks. Response to therapy was evaluated in terms of SVR after 24 weeks and safety profile of the drug. Results: Both treatment groups showed high SVR 24 weeks after the completion of therapy. Group A (SOFO + DCV) presented 92% SVR while group B showed 97% SVR rate. Both DAA combination therapies presented good efficacy and safety profile. Few contraindications noted during the treatment included fatigue, arthritis, headache, loss of appetite and anemia. Conclusions: The efficacy of both DAA combination therapies was comparably high with &gt; 90% SVR rate. Group A proved safer as compared to group B. Studied DAA combinations are effective treatment options for chronic HCV treatment planning.

Real-world impact of a subsidy decision of sofosbuvir-velpatasvir for treatment of chronic hepatitis C on clinical practice and patient outcomes.

Sofosbuvir-velpatasvir was recommended for subsidy to treat chronic hepatitis C in Singapore in 2018. We measured the impact of the subsidy decision on clinical practice and patient outcomes. Specifically, we looked at pre- and post-subsidy changes in the utilization and prescribing pattern of chronic hepatitis C treatment and the real-world clinical effectiveness. Utilization trends and prescribing patterns were assessed using aggregated drug utilization data from public hospitals' dispensing systems and clinical data from the national electronic health record database, respectively. An audit was conducted to evaluate sustained virological response rate 12 weeks post treatment (SVR12). Use of sofosbuvir-velpatasvir increased sharply since its subsidy listing and dropped subsequently, whereas the utilization of comparator drugs remained low. Prescribing rate of sofosbuvir-velpatasvir increased from 13.7% in the pre-subsidy period to 90.2% in the post-subsidy period; 39.1% of patients previously on pegylated interferon and ribavirin switched to sofosbuvir-velpatasvir following its subsidy listing. In the audit, 365 out of 375 patients (97.3% [95% confidence interval: 95.1-98.6%]) achieved SVR12. The subsidy decision led to increased accessibility to patients and intended changes in clinical practice. Sofosbuvir-velpatasvir was also clinically effective in the real world. These findings augur well for the continued eradication of chronic hepatitis C infection in Singapore.

Poor linkage to care may compromise the Brazilian plan for hepatitis C elimination.

Hepatitis C Virus (HCV) seroprevalence was shown to vary from 0.7% to 1.38%. Most of those results were obtained in baby boomers tested during HCV screening campaigns, but little is known about the frequencies of linkage to care (LTC) and sustained virological response (SVR) of those HCV+ tested patients. The aim of this work was to evaluate HCV seroprevalence in two large HCV screening campaigns and the frequency of LTC and SVR obtained from those HCV+ patients. The results of this initiative are presented in this short communication. HCV seroprevalence was shown to vary according to HCV testing venue, possibly related to socioeconomic status and access to healthcare. Poor LTC and SVR rates were observed in those HCV+ tested patients, reflecting the existence of not readily detectable barriers, probably related to direct non-medical costs, that needs to be taken into consideration in order to accomplish WHO goals for disease elimination.

Barriers and Facilitators of Hepatitis C Care in Persons Coinfected with Human Immunodeficiency Virus.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are often co-transmitted. Viral coinfection results in worse outcomes. Persons who inject drugs (PWIDs) face barriers to medical treatment, but HCV treatment is indicated and effective even with ongoing active drug use. We aimed to assess access to HCV care and treatment results in patients coinfected with HIV-HCV. This is a real-world retrospective single-center study of patients followed in the HIV clinic between 2002 and 2018. Linkage to care was defined as achieving care cascade steps: (1) hepatology clinic visit, (2) receiving prescription of anti-HCV treatment, and (3) documentation of sustained virologic response (SVR). Of 1660 patients with HIV, 254 with HIV-HCV coinfection were included. Only 39% of them achieved SVR. The rate limiting step was the engagement into hepatology care. Being a PWID was associated with ~50% reduced odds of achieving study outcomes, active drug use was associated with ~90% reduced odds. Older age was found to facilitate treatment success. Once treated, the rate of SVR was high in all populations. HCV is undertreated in coinfected young PWIDs. Further efforts should be directed to improve access to care in this marginalized population.

Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders.

Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.

Ritonavir Blocks Hepatitis E Virus Internalization and Clears Hepatitis E Virus In Vitro with Ribavirin.

Hepatitis E virus (HEV) is increasingly recognized as the leading cause of acute hepatitis. Although HEV infections are mostly self-limiting, a chronic course can develop especially in those with immunocompromised state. Ribavirin is currently used to treat such patients. According to various reports on chronic HEV infections, a sustained virological response (SVR) was achieved in approximately 80% of patients receiving ribavirin monotherapy. To increase the SVR rate, drug combination might be a viable strategy, which we attempted in the current study. Ritonavir was identified in our previous drug screening while searching for candidate novel anti-HEV drugs. It demonstrated potent inhibition of HEV growth in cultured cells. In the present study, ritonavir blocked HEV internalization as shown through time-of-addition and immunofluorescence assays. Its combination with ribavirin significantly increased the efficiency of inhibiting HEV growth compared to that shown by ribavirin monotherapy, even in PLC/PRF/5 cells with robust HEV production, and resulted in viral clearance. Similar efficiency was seen for HEV genotypes 3 and 4, the main causes of chronic infection. The present findings provide insight concerning the advantage of combination therapy using drugs blocking different steps in the HEV life cycle (internalization and RNA replication) as a potential novel treatment strategy for chronic hepatitis E.