Pangenotypic Direct-acting Antivirals Research Articles

Economic evaluation of pan-genotypic generic direct-acting antiviral regimens for treatment of chronic hepatitis C in Iran: a cost-effectiveness study

IntroductionLow-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent...

Retreatment for hepatitis C virus direct acting antiviral therapy virological failure in primary and tertiary settings: the REACH-C cohort.

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct‐acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real‐world cohort. REACH‐C is an Australian observational study (n = 10,843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n = 56) and tertiary (n = 157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p = 1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11–0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64–11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15–0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralized models may increase retreatment uptake and reduce HCV‐related mortality.

High Proportion of Blood-Borne and Sexually Transmitted Infections Among People Deprived of Liberty in a Central Male Prison in Thailand: A Cross-Sectional Study 2018-2019.

Data are lacking or outdated on burden of HIV, viral hepatitis infection, and sexually transmitted infections such as syphilis among people deprived of liberty in the Asia-Pacific region. We aimed to evaluate the proportion of viral hepatitis B (HBV), hepatitis C (HCV), HIV, and syphilis infections, and factors associated with HCV, HBV, and HIV infection in a central male prison. A cross-sectional study was performed among 1,028 people deprived of liberty from a central male prison in Bangkok, Thailand. People deprived of liberty were screened for HIV, HBV, HCV, and syphilis infections during 2018-2019. HBV and HCV were defined as positive hepatitis B surface antigen and positive anti-HCV antibody, respectively. Proportions (95% confidence interval [CI]) of infections were calculated based on the binomial distribution. HBV proportion was reported for different age groups. Risk factors associated with HCV infections were evaluated by logistic regression model. The median age was 38 (interquartile range, 32-50) years, and 6.9% reported use of injection drugs. The proportion of HIV, HBV, anti-HCV, HCV RNA, and syphilis was 2.9% (95% CI, 1.9-4.1), 6.4% (5-8.1), 5.9% (4.6-7.6), 4.2% (3-5.6), and 4.8% (3.5-6.3), respectively. One (0.1%), 7 (0.6%), and 2 (3%) were co-infected with HIV/HBV, HIV/HCV, and HDV/HBV, respectively. HBV proportion differed across age groups: 3.7% in <30 years, 7% in 31-40 years, 9.7% in 41-50 years, and 5.5% in >50 years. Factors associated with HCV infection were older age, lower education level, previous incarceration, and injection drug use. In multivariable models, older age was associated with HBV infection, and men having sex with men was associated with HIV infection. The proportion of blood-borne infections was higher among males than among the general population. HBV vaccination, routine HCV screening, and treatment with pan-genotypic direct-acting antivirals with minimal specialist requirements should be implemented in Thai prisons.

Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis.

Although the pan-genotypic direct-acting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. We evaluated the real-world safety and efficacy of two pan-genotypic regimens (Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir) for HCV-infected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua Christian Care System that commenced treatment between August 2018 and December 2020. This retrospective study evaluated the efficacy and safety of pan-genotypic direct-acting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment. Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow-up during treatment and one more patient after treatment. A total of four patients died. However, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%). Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotype-undetermined HCV infection real-world settings.

Impact of polypharmacy and aging on the risk of multiple drug-drug interactions (DDIs) in HCV patients treated with pangenotypic direct-acting antivirals (pDAA)

Background: Recent studies suggest that sofosbuvir-based regimens are preferred in HCV elderly patients for their slightly more user-friendly DDI profile compared to protease inhibitor-based regimens. Our aim was to explore the impact of polymedication and aging on multiple DDIs prevalence in patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB).

Risk of multiple drug interactions potentially linked to safety in patients receiving pangenotypic direct-acting antivirals for the treatment of hepatitis C

Background: Previous studies evaluated the risk of drug-drug interactions (DDIs) in HCV patients receiving pangenotypic direct-acting antivirals (pDAA) on pairwise interaction. We aimed at describing the risk prevalence of potential multiple-DDI (multi-DDI) and its clinical impact in patients treated with pDAAs.

Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for treating patients with hepatitis C virus reinfection following direct‐acting antiviral‐induced sustained virologic response

AbstractData regarding the patient characteristics of hepatitis C virus (HCV) reinfection following viral eradication by a prior course of direct‐acting antivirals (DAAs) and the clinical performance of pangenotypic DAAs to retreat such patients are lacking. The demographics and potential routes of transmission were shown in 22 patients with confirmed reinfection following HCV clearance by a prior course of DAAs. Twenty patients received retreatment with pangenotypic sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) according to label recommendations. The sustained virologic response (SVR12) rates and the tolerance following treatment were reported. The incidence rates of reinfection among human immunodeficiency virus (HIV)‐positive and HIV‐negative patients were 8.33 per 100 person‐years (95% CI: 5.33‐12.78) and 0.30 per 100 person‐years (95% CI: 0.12‐0.77), respectively. Eighteen (81.8%) patients had HIV coinfection. The elapsed time between SVR12 and reinfection ranged from 3 to 36 months. Twenty (90.9%) patients had different viral genotypes/subtypes before and after HCV reinfection. Prior to reinfection, 15 (68.2%) patients achieved SVR12 using SOF/VEL or GLE/PIB. Twelve and eight patients were retreated with SOF/VEL for 12 weeks and GLE/PIB for 8 weeks, respectively, in whom SVR12 was all achieved. All patients completed the assigned course of retreatment without interruption and all had excellent tolerance. The risk of HCV reinfection is higher in HIV‐positive patients than HIV‐negative patients following DAA‐induced SVR. Treating reinfected patients with SOF/VEL or GLE/PIB as DAA‐naïve patients has excellent effectiveness and tolerance, irrespective of the type of prior DAA exposure or viral genotypes/subtypes.

Outreach onsite treatment with a simplified pangenotypic direct-acting anti-viral regimen for hepatitis C virus micro-elimination in a prison.

BACKGROUNDPrisoners are at risk of hepatitis C virus (HCV) infection, especially among the people who inject drugs (PWID). We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals (DAA) regimen, 12 wk of sofosbuvir/velpatasvir, in a PWID-dominant prison in Taiwan.AIMTo implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in Taiwan.METHODSHCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen, 12 wk of sofosbuvir/ velpatasvir, from two cohorts in Penghu Prison, either identified by mass screen or in outpatient clinics, in September 2019. Another group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control group. The primary endpoint was sustained virological response (SVR12, defined as undetectable HCV ribonucleic acid (RNA) 12 wk after end-of-treatment).RESULTSA total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign; 91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/ pibrentasvir before mass screening were enrolled as a control. The HCV micro-elimination group had significantly lower proportion of diabetes, hypertension, hyperlipidemia, advanced fibrosis and chronic kidney diseases, but higher levels of HCV RNA. The SVR12 rate was comparable between the HCV micro-elimination and control groups, 95.8% (203/212) vs 94.5% (86/91), respectively, in intent-to-treat analysis, and 100% (203/203) vs 98.9% (86/87), respectively, in per-protocol analysis. There was no virological failure, treatment discontinuation, and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination group.CONCLUSIONOutreach mass screening followed by immediate onsite treatment with a simplified pangenotypic DAA regimen, sofosbuvir/velpatasvir, provides successful strategies toward HCV micro-elimination among prisoners.

A simplified algorithm for managing hepatitis C infection by leveraging telemedicine

Background: The utilization of alternative modalities to deliver patient care during the coronavirus disease of 2019 (COVID-19) pandemic has catalyzed the widespread adoption and integration of telemedicine into routine practice. These shifts have afforded a pivotal moment to analyze existing guidelines, such as for hepatitis C (HCV), identify opportunities, and streamline algorithms for optimizing disease management in remote settings. Methods and findings: Toward furthering momentum for targeting global HCV elimination, our cross-specialty expert panel collaborated to develop a simplified treatment algorithm for use in telemedicine environments by non-specialist providers (Figure 1). This algorithm includes a framework for delivery of HCV treatment and recommendations for screening, pre-treatment evaluation, on-treatment monitoring, and post-cure follow-up. The use of telemedicine for HCV management is supported by multiple studies demonstrating similar cure rates, measured by sustained virologic response at 12weeks post treatment (SVR12), compared to standard, in-person clinic visits. No laboratory monitoring is necessary for the majority of patients taking pan-genotypic direct-acting antivirals (DAAs), further reinforcing the ease of remote management of HCV treatment. Touchpoints to support medication adherence can be conducted through a variety of technologies, including bidirectional text messaging, electronic portals, and telephone and/or video conferencing. Conclusion: Telemedicine thus offers a critical opportunity to expand identification, link to care, and treat persons living with HCV.

Place of therapeutic patient education in chronic hepatitis C treated with direct-acting antivirals

Objective: Today, with the availability of direct-acting antivirals (DAAs), the value of therapeutic patient education (TPE) in chronic hepatitis C needs to be redefined, as these drugs have made treatment simple. The study presented here in sought to define what role TPE plays today in hepatitis C management along with what factors are associated with such programs being used. Methods: We included 786 patients mono-infected with hepatitis C virus (HCV) who underwent treatment with DAAs. 284 of whom benefited from a TPE program (36.1%). The characteristics of HCV and how it was treated were compared retrospectively between TPE+ and TPE- patients. The TPE program was overseen by a nurse. Results: The following factors were associated with TPE on multivariate analysis: migrant status (OR=3.63, 95%CI: 2.24-5.96, p &lt;0.001), advanced fibrosis (OR=1.73, 95%CI: 1.08-2.76, p=0.022), tobacco use (OR=1.84, 95%CI: 1.10-3.08, p=0.020) and pangenotypic DAA treatment (OR=0.42, 95%CI: 0.26-0.68, p &lt;0.001). Sustained virological response at 12 weeks (SVR 12) was 96% in both groups. Conclusion: Overall, TPE was primarily followed by migrants during their HCV management as part of overall medico-psycho-social care, and primarily those with severe disease. Practice implication: TPE could help reduce the impact of social inequality on health.

Sofosbuvir/Velpatasvir for HepatitisC Virus Infection: Real-World Effectiveness and Safety from a Nationwide Registry in Taiwan.

IntroductionPangenotypic direct-acting antivirals are expected to cure hepatitis C virus (HCV) in more than 95% of treated patients. However, data on the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) in Taiwan are limited. This study aims to characterize the patient population in the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry and evaluate treatment outcome in Taiwanese patients receiving SOF/VEL.MethodsThis study was a retrospective-prospective, observational, multicenter, real-world analysis. Adults with chronic hepatitis C were treated with SOF/VEL 400/100 mg ± ribavirin for 12 weeks. The primary outcome was sustained virologic response 12 weeks after end of therapy (SVR12). Factors associated with not achieving SVR12 were evaluated using logistic regression and covariate analysis. Safety was also assessed.ResultsIn total, 3480 patients were included: 86.8% genotype 1/2, 2.8% genotype 3, 0.1% genotype 4/5, 9.6% genotype 6; unclassified, 0.8%; 12.2% compensated cirrhosis; 3.3% decompensated cirrhosis; and 15.8% chronic kidney disease. Overall SVR12 rate was 99.4% (genotype 1, 99.5%; genotype 2, 99.4%; genotype 3, 96.9%; genotype 4, 100%; genotype 6, 99.7%). SVR12 rates among patients with compensated cirrhosis, decompensated cirrhosis, and chronic kidney disease stages 4–5 were 99.5%, 100%, and 100%, respectively. There were 21 patients (0.6%) who did not achieve SVR12. Factors associated with failure were treatment adherence below 60%, high viral load, and genotype 3 (p < 0.001, p = 0.028, and p = 0.001, respectively). Adverse events occurred in 10% of patients; 0.6% were serious and one was related to treatment. Treatment discontinuation occurred in 0.3% of patients; none were treatment related. The estimated glomerular filtration rate remained stable throughout treatment and follow-up, regardless of baseline values and cirrhosis status.ConclusionSOF/VEL was highly effective and well tolerated in Taiwanese patients, irrespective of viral genotype, liver disease severity, and comorbidities.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00576-7.

Treatment of Hepatitis C virus among people who inject drugs at a syringe service program during the COVID-19 response: The potential role of telehealth, medications for opioid use disorder and minimal demands on patients.

BackgroundHealthcare delivery was disrupted during the COVID-19 pandemic, requiring minimized in-person contact between patients and clinicians. During the pandemic, people with opioid use disorder (OUD) were not only at elevated risk for COVID-19, but had markedly reduced access to treatment for OUD, Hepatitis C virus (HCV) and HIV due to recommended decreased in-person visits.MethodsFrom March 15-June 15, 2020 at the syringe services program (SSP) in New Haven, Connecticut, USA, a differentiated care model evolved with reduced clinical demands on people who inject drugs (PWID) to ensure screening and treatment for HCV, HIV and OUD, with a focus on HCV treatment. This model involved a single, bundled screening, evaluation, testing (SET) and monitoring strategy for all three conditions, minimal in-person visits, followed by tele-health communication between patients, outreach workers and clinicians. In-person visits occurred only during induction onto methadone and phlebotomy at baseline and phlebotomy 12 weeks post-treatment for HCV to measure sustained virological response (SVR). Patients received supportive texts/calls from outreach workers and clinicians.ResultsOverall, 66 actively injecting PWID, all with OUD, underwent bundled laboratory screening; 35 had chronic HCV infection. Participants were 40 years (mean), mostly white (N = 18) men (N = 28) and 12 were unstably housed. Two were lost to-follow-up and 2 were incarcerated, leaving 31 who started pan-genotypic direct-acting antivirals (DAAs). The mean time from referral to initial phlebotomy and initiation of DAAs was 6.9 and 9.9 days, respectively. Fourteen additional patients were newly started on buprenorphine and 6 started on methadone; three and four, respectively, were on treatment at baseline. Overall, 29 (93.5%) PWID who initiated DAAs achieved SVR; among unstably housed persons the SVR was 83.3%.ConclusionsIn response to COVID-19, an innovative differentiated care model for PWID at an SSP evolved that included successful co-treatment for HCV, HIV and OUD using a client-centered approach that reduces treatment demands on patients yet supports ongoing access to evidence-based treatments.

Treating chronic hepatitis C in general practice.

Hepatitis C virus (HCV) infection continues to result in significant morbidity and mortality in Australia. Eradication of HCV remains a challenge, with many patients unaware of their infection. With the new era of direct-acting antivirals (DAAs), higher viral eradication rates are attainable, and access to treatment can be expanded bytreating most patients with HCV in general practice, moving away from the traditional model of treatment by a gastroenterologist, hepatologist or infectious diseases physician. Currently available DAAs are pan-genotypic, well tolerated and safe; hence, HCV treatment can be easily undertaken in general practice. The aim of this article is to highlight how to use pan-genotypic DAAs and when to consider referral for a specialist opinion. Most patients with HCV can be treated ingeneral practice, increasing the number of patients who have access totreatment and hence reducing the likelihood of progression to advanced liver disease in these patients, as well asadvancing progress towards HCV eradication in Australia.

Seroprevalence, Genotyping, and Monitoring of Hepatitis C Viral Loads in Patients on Antivirals in Burkina Faso

Introduction: Hepatitis C virus (HCV) infection remains a major public health problem worldwide. In Burkina Faso, nearly 720,000 people are living with HCV, and each year about 900 people die from complications of cirrhosis or hepatocellular carcinoma. This study was planned to determine the HCV seroprevalence, characterize circulating genotypes, and monitor HCV viral loads in patients under treatment with antivirals. Methods: A total of 4,124 individuals and 167 patients in the pre-therapy program were recruited. The “SD Bioline HCV” kit was used for rapid screening of anti-HCV antibodies. Viral load and genotyping were performed in 167 HCV patients on antivirals using the “Iontek HCV Quant” and “Iontek genotyping” kits. Results: Prevalence of HCV was 1.65% (68/4,124), and the median viral load of participants was 5.37 log10/mL (1.32–7.67 log10/mL). Genotype 2 was predominant with a frequency of 86.23% (144/167) and appeared to be more active with higher viral load compared to 13.77% (23/167) for genotype 1 (p < 0.001). After 24 weeks of pan-genotypic direct-acting antivirals, such as sofosbuvir/daclatasvir and sofosbuvir/velpatasvir, the viral loads of all patients became undetectable. Conclusion: The responses to antivirals by the circulating genotypes indicate that the results are very satisfactory. Therefore, the prevalence of HCV in the population can be reduced through identification of cases and treatment.

Hepatitis C Virus Infection: What Are We Currently Doing in Latin America About WHO's Proposals for 2030?

Hepatitis C Virus Infection: What Are We Currently Doing in Latin America About WHO's Proposals for 2030?

Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan

Clinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

Prevalence of drug-drug interactions with pangenotypic direct-acting antivirals for hepatitis C and real-world care management in the United States: a retrospective observational study.

BACKGROUND: Direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) have varying potentials for drug-drug interactions (DDIs). OBJECTIVES: To (1) identify prevalence of potential DDI with glecaprevir-pibrentasvir (GLE-PIB) and sofosbuvir-velpatasvir (SOF-VEL) and (2) describe health care provider actions in response to pharmacist recommendations based on potential interactions with GLE-PIB or SOF-VEL, using 2 complementary data sources. METHODS: Possible interacting drugs were identified among adult patients in a United States electronic medical record database covering 21 health care organizations and 26 million patients in 2018. DDIs were categorized as potential weak interaction (Level 1), potential interaction (Level 2), or contraindicated (Level 3). Real-world recommendations and resultant actions regarding DDIs with GLE-PIB and SOF-VEL were obtained from a specialty pharmacy database. Categorical variable comparisons were done via chi-square analysis with subsequent z-tests of column proportions. RESULTS: DDI prevalence was higher for patients prescribed GLE-PIB (317/769 [41%]) compared with those prescribed SOF-VEL (170/633 [27%]), and the prevalence of a Level 3 (contraindicated) interaction was higher with GLE-PIB than SOF-VEL (61/769 [8%] vs 2/633 [< 1%]). Across all DDI levels, analgesics (139/317 [44%]), proton-pump inhibitors (129/317 [41%]), and lipid-lowering agents (59/317 [19%]) were the top drug classes for the GLE-PIB group with potential for DDI. For SOF-VEL prescribed patients, the top drug classes were proton-pump inhibitors (83/170 [49%]), histamine-2 blockers (42/170[25%]), and lipid-lowering agents (42/170 [25%]). In real-world care management, the overall prevalence of pharmacist recommendations regarding DDIs was significantly lower for SOF-VEL (28/419 [7%]) relative to GLE-PIB (151/1,216 [12%]). Recommended guidance from pharmacists was not followed for 39% (69/179) of patients, 36% (54/151) for GLE-PIB, and 54% (15/28) for SOF-VEL. CONCLUSIONS: The potential for DDIs with pangenotypic HCV DAAs is frequent and may be more frequent with GLE-PIB than SOF-VEL. Physician responses to pharmacist alerts regarding potential interaction can be highly variable, even in cases of contraindication. DISCLOSURES: Funding for this study was provided by Gilead Sciences, Inc. Trio Health Analytics received funding from Gilead Sciences, Inc., to conduct research for this study. Tsai consults for and has received grants and honoraria from Gilead, AbbVie, Merck, and Bristol Myers Squibb; he has also received lecture fees from Gilead and AbbVie. Curry consults for Trio Health Analytics and Gilead and has also consulted for and received grants from Mallinckrodt. Flamm consults for and has received lecture fees from Gilead and AbbVie; he has also received grants from Gilead and AbbVie. Milligan and Wick are employed by Trio Health Analytics and have received research support from Gilead, Merck, and AbbVie. Younossi has received grants from Gilead, Intercept, Bristol Myers Squibb, GlaxoSmithKline, and Novo Nordisk. Afdhal is a paid consultant/advisory board member for Gilead, Echosens, Ligand, Shionogi, and Trio Health; owns stock in Spring-Bank and Allurion and has stock options in SpringBank; receives royalty income from UpToDate; and is on the board of directors for the nonprofit Liver Institute for Education and Research. Data from this study were presented at the American Association for the Study of Liver Disease (AASLD) Liver Meeting 2019; November 8-12, 2019; Boston, MA, and the European Association for Study of the Liver (EASL) International Liver Congress 2020; August 27-29, 2020; virtual.

Impact of Coronavirus Disease 2019 Pandemic on Viral Hepatitis Elimination: What Is the Price?

In 2016, the World Health Organization developed a plan for viral hepatitis elimination by 2030. Globally, control of hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most challenging aspects of viral hepatitis elimination. In many developed countries elimination of HBV could be targeted to special populations mostly immigrants from low resource settings. Elimination of HCV, however, remains a challenge globally. Barriers to HCV elimination include high cost of medications and the ability to engage specific at-risk populations as well as individuals who are out of medical care. In the context of the coronavirus disease 2019 (COVID-19) pandemic, treatment access and screening have been further negatively impacted by social distancing rules and COVID-19-related anxieties. This threatens to throw most countries off course in their elimination efforts. Before the pandemic, some states in the United States had scaled up their elimination efforts with plans to ramp up testing and treatment using Netflix-like payment models for HCV direct acting antiviral drugs. Most of these efforts have stalled on account of the health system's focus on COVID-19 control. To prevent further delays in achieving elimination targets, programs would need to explore new models of care that address COVID-19-related access hurdles. Systems that leverage technologies such as telemedicine and self-testing could help maintain treatment levels. Mathematical models estimate that COVID-19-related delays in 2020 could lead to 44,800 hepatocellular cancers and 72,300 liver-related deaths for the next decade.

Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C.

Direct-acting antiviral (DAA) drugs are associated with high (>95%) sustained virological response at 12 weeks (SVR12) in chronic hepatitis C (CHC) patients. There is a paucity of data regarding the characteristics and re-treatment outcomes of DAA treatment failure patients. In a retrospective analysis of the prospectively collected database, we assessed the outcomes of re-treatment among patients with previous DAA failure. Patients' characteristics, viral characteristics, including resistance-associated substitutions (RAS) in a subgroup of patients, SVR12, and clinical outcomes were studied. Of 40 patients with DAA failure, among whom 36 were retreated, mean age was 45.7 years, 63.9% (n = 23) were male, 63.9% (n = 23) had agenotype-3 infection and 63.9% (n = 23) were cirrhotic. The re-treatment regimens included a combination of pan-genotypic DAA, mainly sofosbuvir and velpatasvir with or without ribavirin. Three patients who declined retreatment and one who was still on treatment was excluded. For patients who completed re-treatment, SVR12 was 100% irrespective of genotypes. SVR12 among genotype 3 was 75% (15 of 20) when lost to follow-up was considered a treatment failure. Six patients died due to liver-related causes, including five (83.3%) with hepatocellular carcinoma. RAS analysis in 17 randomly selected patients did not reveal any dominant substitutions in NS5A or NS5B region affecting SVR12, though several novel mutations were observed. In conclusion, re-treatment of CHC patients with prior DAA failure using pan-genotypic DAA is associated with high SVR12 rates irrespective of genotype or the presence of RAS.

Genotype 3-hepatitis C virus' last line of defense.

Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.