Pangenotypic Regimen Research Articles

Hepatitis C Retreatment With First-Line Direct Acting Antiviral Drugs

Sofosbuvir (S), daclatasvir (D), ledipasvir, or velpatasvir (V) containing first-line hepatitis C virus (HCV) treatment regimens fail to cure viremia in 5-10%. We report our experience of HCV retreatment using these first-line drugs, in a setting where second-line anti-HCV drugs are not available. Adults, who had relapsed after first complete course of a sofosbuvir-containing first-line, pegylated interferon free, anti-HCV treatment regimen with or without ribavirin (Riba) were included. Retreatment regimen, tailored to the failed anti-HCV regimen, was based on principle of using first-line drugs for 24 weeks with ribavirinand swapping between pangenotypic and genotype-specific regimens. Retreatment outcome was categorized as successful (achieved undetectable HCV RNA at the end of treatment [ETR] and sustained viral response at week 12 [SVR12]), non-responder (failed to achieve ETR), or relapse (achieved ETR but not achieved SVR12). Twelve patients (9 male; 7 cirrhosis; all genotype 3) who had relapsed to prior anti-HCV treatment (4 SD12, 4 SD24, 1 SDRiba12, 1 SDRiba24, 2 SV12) were included. Following retreatment (2 SDRiba24, 10 SVRiba24), all achieved ETR but only 9 (75%) achieved SVR12. Two among three, in whom retreatment failed, achieved SVR12 following another course of sofosbuvir/velpatasvir/ribavirin for 24 weeks. Overall, 11/12 (92%) patients achieved SVR12 following retreatment with the first-line anti-HCV drugs. HCV retreatment could be a treatment option if second-line anti-HCV drugs are not available. Successful retreatment could be achieved, in a large proportion, with the use of first-line drugs for 24 weeks with ribavirinand swapping of pangenotypic/genotype-specific regimens (NCT03483987).

Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens.

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.

Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C.

Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.

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 of genotype-specific and pangenotypic direct-acting antivirals in HCV-infected patients with renal failure.

The aim is to summarize the effectiveness and safety of genotype-specific and pangenotypic hepatitis C virus (HCV) treatments in patients with renal failure. In the EpiTer-2 database, which includes data from 22 hepatology centers in Poland, 593 patients with HCV infection and kidney failure were identified. According to KDIGO 2022, they fulfilled the criteria of chronic kidney disease. Patients were divided into two groups: treated with genotype-specific regimens (n = 428) and pangenotypic options (n = 165), in relation to the stage of kidney disease determined using the glomerular filtration rate (GFR) (Cockcroft and Gault equation). Two separate groups were created for hemodialyzed patients (n = 134) and patients after kidney transplantation (n = 89). In a total of 593 patients, 78.7% were treatment-naïve and 23.9% had liver cirrhosis, in 27.5% of cases decompensated. In both groups, the dominant genotype was GT1b. Among patients treated with genotype-specific regimens, LDV/SOF ± RBV, OBV/PTV/r + DSV ± RBV, and GZR/EBR ± RBV treatments were given to 31.5%, 31.5%, and 34.8% of patients respectively. In pangenotypic regimens, GLE/PIB was chosen in 50.3%. Ninety-six percent and 98.8% of patients in the genotype-specific regimen and 88.5% and 94.8% in the pangenotypic regimen achieved a sustained virologic response at 12 weeks (SVR12) in the intention-to-treat and per protocol population respectively. Liver cirrhosis was identified as a risk factor for virological failure. During the study, 14 patients died, 7 in each of the two groups, none related to the antiviral treatment. Both types of treatment regimens are equally effective and safe in patients with renal failure. The stage of renal failure or transplant does not influence the antiviral response.

Recommendations of the Polish Group of Experts for HCV for the treatment of hepatitis C in 2023.

The recommendations define the principles of diagnosis and treatment of hepatitis C virus (HCV) infection according to the latest knowledge. The main goal of the treatment of HCV infection is to eliminate the virus from the body, which in turn leads to stopping the progression or causes the regression of previously formed changes in the liver. The current version of the guidelines prioritizes pangenotypic regimens and includes guidelines for special patient populations such as children, patients with cirrhosis, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection, patients with renal failure, liver failure and lack of response to previous therapies as well as patients in the peri-transplant period.

Direct-Acting Antiviral Treatment in Albanian Patients With Chronic Hepatitis C and Advanced Liver Fibrosis.

Background Treating chronic hepatitis C (CHC) with direct-acting antiviral (DAA) is very effective at clearing the infection. In Albania treatment with DAA is limited to patients with liver stiffness F3-F4, and with other co-infections. The objective of this study was to evaluate the efficacy of DAA in Albanian patients with genotypes 1-5, who mostly suffer from advanced liver fibrosis. Material and Methods This is a retrospective study carried out at the University Hospital Center "Mother Teresa", Tirana, during 2014-2019, including treatment-naïve and treatment-experienced patients with genotypes 1-5. All patients were evaluated with elastography and most of them were F3-F4. The primary endpoint involved the patients achieving SVR-12, or undetectablehepatitis C virus/ribonucleic acid (HCV RNA) 12 weeks after the end of treatment. In patients without a genotype, we have used a pangenotypic regimen. Results This study included 207 patients with a mean age of 48.9 ± 13.1 years, 56% male and 44% female; 152 (73%) were genotype 1, 24 were (11.5%) genotype 2, nine were (4.3%) genotype 3, 14 were (6.7%) genotype 4, one was (0.4%) genotype 5, and seven (3.8%) unassigned genotypes. The sustained virologic response (SVR) percentage according to genotype is discussed in the article. The overall SVR score of all the patients in our study was>93%. According to elastography, 127 (66%) were F3-F4, and 80 (38.6%) were F1-F2. Conclusion Treatment with DAA proved to be very effective in our patients; most of them had advanced liver fibrosisas well as compensatedor decompensated liver cirrhosis. The overall SVR score ofthe patients in our study was>93%. Our country needs to treat all patients with chronic hepatitis C without limitations to attain the WHO objectiveof eradicating this disease by 2030.

Hepatitis C virus care cascade for children in Moscow Region

Background. Children and adolescents with infection caused by the hepatitis C virus (HCV) have not been given sufficient attention due to mild forms of HCV and delays in approval of antiviral treatment regimens. Omissions in the studies of pediatric cohorts and shortcomings of management policies aimed at children should be eliminated by improving screening coverage and access to treatment.&#x0D; The aim of the study was to present the results of the cascade sequence of diagnostic testing, care and treatment of children with HCV in the Moscow Region (MR).&#x0D; Materials and methods. The study included all HCV seropositive children of MR (n = 175), who underwent screening tests, and it did not include patients living with HIV/HCV coinfection. Children were observed from 2017 to 2022. The HCV RNA was detected in 164 children and HCV genotypes were identified in 99 children. The stage of liver fibrosis was assessed in 73 children by transient elastography and by FIB-4 index calculation.&#x0D; Results. In MR, 93.7% of seropositive children were tested for HCV RNA; 71.2% of adolescents over 12 years of age received treatment. The prevalence of HCV seropositivity was estimated at 0.113/1,000 children population; the prevalence of chronic HCV infection was at least 0.059/1,000. The dominant HCV subtypes were GT 1b (43.4% [the 95% confidence interval, 33.553.8%]), GT 3a (23.2% [15.332.8%]) and GT 3a/3b (20.2% [12.829.5%]). The incidence of viremic HCV infection per 100,000 children was 3.3 among children under 3 years of age; 7.0 among children aged 36 years; 7.7 among children aged 711 years, 4.4 among adolescents older than 12 years. Natural HCV clearance was reported at the frequency of 19.5% [13.826.4%]. Extrahepatic manifestations were of rare occasion 2.9% [0.96.5%]. Vertical transmission was the primary route of HCV transmission (78.3% [71.484.2%]); infection is assumed to occur during medical invasive procedures 7.4% [4.012.4%], drug using 0.6% [0.013.10%], in the family household 0.6% [0.013.10%]. New cases of HCV infection were more frequently detected during routine examination of children prior to hospitalization or children born to mothers with HCV. Viremic HCV was confirmed in 90.2% [84.694.3%], including HCV infection in 53.4% [45.061.6%], chronic liver disease in 35.8% [28.144.1%] having low activity and occasional consequences (the fibrosis METAVIR score of F1 and F1-2 17.8% [9.828.5%]). No significant clinical and epidemiological differences between the natural course of chronic HCV infection and the liver disease caused by HCV have been found. The burden of pediatric HCV in MR is aggravated by a significant proportion of socially vulnerable patients and patients with comorbid conditions.&#x0D; Conclusion. One of the solutions for detection of new pediatric cases of HCV infection in MR can be offered by improvement of collaboration and continuity of care among healthcare organizations and early treatment of women of childbearing age. Further research is required to evaluate the effectiveness of routine testing of all socially vulnerable pediatric groups. Early application of pan-genotypic antiviral treatment regimens can contribute significantly to control of the HCV infection incidence in children.

Changes in renal function in patients with chronic hepatitis C treated with sofosbuvir‐velpatasvir

AbstractDirect‐acting antivirals (DAAs) have become an effective first‐line treatment for chronic hepatitis C (CHC), and the fixed‐dose combination of sofosbuvir (SOF) and velpatasvir (VEL) is one of the most important pangenotypic DAA regimen according to present treatment guideline. The association between SOF‐based regimens and renal toxicity remains controversial. A total of 953 patients including 130 with estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m2 and 823 with eGFR &gt; 60 mL/min/1.73m2 receiving SOF/VEL therapy for 12 weeks were enrolled in this study. The eGFR was assessed at baseline, end of treatment (EOT), and 12 weeks after completion of the therapy (end of follow‐up, EOF). The eGFR in patients with eGFR ≤ 60 mL/min/1.73m2 increased from baseline (47.89 ± 10.25 mL/min/1.73m2) to EOT (51.65 ± 15.92; P &lt; .001) and EOF (51.51 ± 14.46 mL/min/1.73m2; P &lt; .05). The eGFR in patients with eGFR &gt; 60 mL/min/1.73m2 at baseline (91.52 ± 22.06 mL/min/1.73m2) was lower at EOT (90.37 ± 22.3; P &lt; .05), with no difference between EOT and EOF (P = .06). Multivariable analysis showed that a higher serum albumin level was associated with a lower risk of eGFR decrease at EOT, and the patients with baseline eGFR &gt; 60 mL/min/1.73m2 were associated with a higher risk of eGFR decrease at EOF. The rates of sustained virologic response 12 weeks after treatment cessation (SVR12) were 99.2% in per‐protocol analysis, and the most common adverse events were fatigue (4.7%), abdominal discomfort (4.5%), and skin itching (3.7%). In conclusion, renal function improved after the SOF/VEL treatment in patients with CHC and chronic kidney disease. Thus, SOF/VEL was safe, effective, and tolerable in these patients.

National trends in retreatment of HCV due to reinfection or treatment failure in Australia

Population-level uptake of direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, including retreatment, can be estimated through administrative pharmaceutical dispensation data. However, the reasons for retreatment are not captured in these data. We developed a machine learning model to classify retreatments as reinfection or treatment failure at a national level. Retreatment data from the REACH-C cohort (n= 10,843 treated with DAAs; n= 320 retreatments with known reason), were used to train a random forest model. Nested cross validation was undertaken to assess model performance and to optimise hyperparameters. The model was applied to data on DAA retreatment dispensed during 2016-2021 in Australia, to identify the reason for retreatment (treatment failure or reinfection). Average predictive accuracy, precision, sensitivity, specificity and F1-score for the model were 96.3%, 96.5%, 96.3%, 96.3% and 96.3%, respectively. Nationally, 95,272 individuals initiated DAAs, with treatment uptake declining from 32,454 in 2016 to 6,566 in 2021. Of those treated, 6,980 (7%) were retreated. Our model classified 51.8% (95% CI 46.7-53.6%; n= 3,614) of cases as reinfection and 48.2% (95% CI 46.4-53.3%; n= 3,366) as treatment failure. Retreatment for reinfection increased steadily over the study period from 14 in 2016 to 1,092 in 2020, stabilising in 2021. Retreatment for treatment failure increased from 73 in 2016 to 1,077 in 2019, then declined to 515 in 2021. Among individuals retreated for treatment failure, 50% had discontinued initial treatment. We used a novel methodology with high classification accuracy to evaluate DAA retreatment patterns at a national level. Increases in retreatment uptake for treatment failure corresponded to the availability of pangenotypic and salvage regimens. Increasing retreatment uptake for reinfection likely reflects increasing reinfection incidence. This study used machine learning methodologies to analyse national administrative data and characterise trends in HCV retreatment due to reinfection and treatment failure. Retreatment for reinfection increased over time, reflecting increasing numbers of people at risk for reinfection following HCV cure. Increased retreatment for treatment failure corresponded to the availability of pangenotypic and salvage DAA regimens. The findings of this study can be used by public health agencies and policy makers to guide and assess HCV elimination strategies, while the novel methodology for monitoring trends in HCV retreatment has the potential to be used in other settings, and health conditions.

Treatment of hepatitis C in children and adolescents: how far have we reached?

Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens. This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords. Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing. The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.

Defer no more: advances in the treatment and prevention of chronic hepatitis C virus infection in children.

Direct-acting antiviral (DAA) regimens targeting hepatitis C virus (HCV) are now approved for young children. This review examines recent DAA experience in children, current treatment recommendations and challenges, and potential treatment-as-prevention strategies. In 2021, the US FDA extended approval of two pan-genotypic DAA regimens, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, to children as young as age 3 years based on high success rates and reassuring safety profiles in registry trials. Similar performance has been replicated with real-world DAA use in thousands of adolescents and in limited reports of children with high-risk conditions, including cirrhosis, cancer, thalassemia and HIV-coinfection. Treatment without delay is now recommended in the USA for viremic children aged 3 years and up to prevent disease progression and future spread. To date, treatment expansion is limited by high rates of undiagnosed paediatric infection. Universal prenatal screening will aid identification of perinatally exposed newborns, but new strategies are needed to boost testing of exposed infants and at-risk adolescents. Postpartum treatment programmes can prevent subsequent vertical transmission but are hampered by low rates of linkage to care and treatment completion. These challenges may be avoided by DAA use in pregnancy, and this warrants continued study. Paediatric HCV is now readily curable. Substantial clinical and public health effort is required to ensure widespread uptake of this therapeutic breakthrough.

FRI404 - High efficacy and safety of pan-genotypic direct-acting antiviral regimens in adolescents and children: a global systematic review to inform new World Health Organization recommendations

FRI404 - High efficacy and safety of pan-genotypic direct-acting antiviral regimens in adolescents and children: a global systematic review to inform new World Health Organization recommendations

Clinical characteristics and antiviral therapy in patients infected with hepatitis C virus in the interferon‑free era.

The highly effective and safe interferon (IFN)-free options were a breakthrough in the treatment of patients infected with hepatitis C virus (HCV). The current analysis was designed to evaluate changes in the patient profile and antiviral treatment characteristics over time. The study population consisted of 963 consecutive HCV‑infected patients who started IFN‑free regimens between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce, Poland. The analysis was carried out for 5 time intervals. The studied group was sex‑balanced, with the median (interquartile range) age changing from 58 (44.8-63) in 2015-2016 to 43 (35-61) in 2020. The proportion of patients with comorbidities decreased over the years. The rate of treatment‑naïve individuals increased from 40.9% in 2015-2016 to 91% in 2020, while the percentage of patients with liver cirrhosis decreased from 51.1% in 2015-2016 to 13.3% in 2020. Genotype‑specific regimens dominated in the years 2015-2017, while pangenotypic options gained an advantage in 2019 and reached 91% in 2020. Overall effectiveness achieved 98.4% in the per‑protocol analysis and was comparable over the years with lower efficacy among patients with liver cirrhosis and those infected with genotype 3. The therapy was well‑tolerated, and the safety profile improved over time. The median age of HCV‑infected patients decreased over the years. They were less burdened with comorbidities and comedications, more likely to be treatment‑naïve, and had less advanced liver disease. The genotype‑specific regimens, predominantly used at the beginning of the IFN‑free era, were superseded by the pangenotypic regimens.

SAFETY AND EFFICACY OF DIRECT ACTING ANTIVIRALS FOR CHRONIC HEPATITIS C IN PATIENTS WITH CHRONIC KIDNEY DISEASE ON MAINTENANCE HEMODIALYSIS

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and is associated with increased morbidity and mortality. Aim of the study is to assess the safety and efficacy of pangenotypic DAA regimens in patients with chronic disease on maintenance hemodialysis. In thisMATERIALS AND METHODS: prospective observational study, hemodialysis patients with chronic hepatitis C infection were identified and treatment initiated with appropriate pangenotypic regimen. Totally 74 patients diagnosed with chronic hepatitis C and treated with DAAs for 12 weeks. The sustained virologic response (SVR) rate obtained 12 weeks post-treatment (SVR12) was evaluated. Laboratory indices and adverse reactions during the treatment process were also assessed. All theRESULTS: patients enrolled completed 12 weeks of treatment. 12 out of 74(16.2%) patients had compensated liver disease. SVR was achieved in 12 out of 12 patients (100%) receiving sofosbuvir/velpatasvir, and 60 of 62 patients (96.7%) receiving sofosbuvir/daclatasvir. No serious or significant adverse reactions were reported. PangenotypicCONCLUSION: regimens containing sofosbuvir are safe and well tolerated in patients with chronic kidney disease on maintenance hemodialysis. Sofosbuvir/daclatasvir based regimens at full dose can be used as an alternative pan genotypic regimen in patients with chronic kidney disease on hemodialysis.

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...

Safety and Effectiveness Using 8 Weeks of Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis: The CREST Study.

IntroductionIn clinical trials with hepatitis C virus-infected treatment-naïve (TN) patients with compensated cirrhosis (CC), glecaprevir/pibrentasvir (G/P), a fixed-dose, once-daily, pangenotypic regimen, has demonstrated sustained virologic response at posttreatment Week 12 (SVR12) > 95%. We evaluated the real-world safety and effectiveness of 8-week G/P therapy in TN patients with CC, including certain subgroups of interest.MethodsThe CREST study is a real-world, noninterventional, multicenter study retrospectively assessing data from Canada, Germany, Israel, Italy, and Spain. The full analysis set (FAS) designated all patients in the study; the modified analysis set (MAS) excluded patients who discontinued G/P for nonvirologic failure or who had missing SVR12 data. The primary endpoint was SVR12; safety endpoints were also assessed.ResultsA total of 386 patients were included in the FAS, 375 patients completed the study, and 325 patients were included in the MAS; 51 patients had missing SVR12 data. Overall, in the MAS and FAS, SVR12 was achieved in 99.1% and 84.2% of patients, respectively. In subgroups of interest, the percentage of patients achieving SVR12 in the MAS (and FAS) was: genotype (GT)3: 97.5% (80.6%); FibroScan® ≥ 12.5 kPa: 98.9% (89.3%); platelet count < 100 × 109/l: 100% (88.2%); both platelets < 150 × 109/l and FibroScan® > 20 kPa: 100% (88.9%); aspartate aminotransferase-to-platelet ratio index > 1.09: 98.7% (83.1%); fibrosis-4 index > 3.25: 98.6% (84.0%); albumin < 3 g/dl: 100% (91.7%); people who use drugs: 97.7% (84.3%); psychiatric disorders: 96.6% (84.8%); and human immunodeficiency virus coinfection: 100% (95.0%). Overall, 26.9% (104/386) of patients experienced an adverse event, none of which were classed as serious.ConclusionIn this real-world cohort, 8 weeks of G/P therapy was well tolerated in TN patients with CC. SVR12 rates were similar to clinical trials, supporting 8-week treatment in TN patients with CC, including those with signs of advanced liver disease and GT3 infection.

DAA treatment failures in a low-resource setting with a high burden of hepatitis C infections: a case series

ABSTRACTGlobally, 58 million people are living with hepatitis C virus (HCV) infection and 1.5 million new patients are infected every year. The advent of direct acting antivirals (DAAs) has revolutionized the treatment of HCV, opening the door to the ambitious World Health Organization HCV infection elimination strategy by 2030. However, emerging resistance to DAAs could jeopardize any hope of achieving these targets. We discuss a series of 18 patients within a resource-limited setting, who after failing standard sofosbuvir-daclatasvir-based regimen also failed to respond to advanced pan-genotypic treatment regimens, i.e. sofosbuvir-velpatasvir, sofosbuvir-velpatasvir-ribavirin and sofosbuvir-velpatasvir-voxilaprevir. To avoid the spread of refractory HCV strains within the existing epidemic, we call for increased attention and research regarding patients failing treatment on standard pan-genotypic regimens and the spread of HCV-resistant strains within the communities.

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.

Cost-utility analysis of four WHO-recommended sofosbuvir-based regimens for the treatment of chronic hepatitis C in sub-Saharan Africa

BackgroundAlthough direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d’Ivoire and Senegal.MethodsUsing modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country’s predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo ‘no DAA treatment’ as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d’Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves.ResultsWith slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country’s per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to significantly lower costs. ICERs ranged from US$139 to US$216/QALY according to country i.e. a 95% probability of being cost-effective. Furthermore, this regimen was cost-effective (probability> 95%) for all CET higher than US$281/QALY, US$223/QALY and US$195/QALY in Cameroon, Côte d’Ivoire and Senegal, respectively, corresponding to 0.14 (Côte d’Ivoire and Senegal) and 0.2 (Cameroon) times the country’s per-capita GDP.ConclusionsGeneric sofosbuvir/daclatasvir is very cost-effective for treating chronic hepatitis C in sub-Saharan Africa. Large-scale use of generics and an increase in national and international funding for hepatitis C treatment must be priorities for the HCV elimination agenda.