RESUMEN
This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33-53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Masculino , Embarazo , Femenino , Humanos , Hepacivirus , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Estudios Retrospectivos , Antivirales/uso terapéutico , Pandemias , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiologíaRESUMEN
BACKGROUND & AIMS: HCV test and treat campaigns currently exclude pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine. METHODS: Country-specific probabilistic decision models were developed to simulate a cohort of pregnant women. We compared five strategies: S0, targeted risk-based screening and deferred treatment (DT) to after pregnancy/breastfeeding; S1, World Health Organization (WHO) risk-based screening and DT; S2, WHO risk-based screening and targeted treatment (treat women with risk factors for HCV vertical transmission [VT]); S3, universal screening and targeted treatment during pregnancy; S4, universal screening and treatment. Maternal and infant HCV outcomes were projected. RESULTS: S0 resulted in the highest proportion of women undiagnosed: 59% and 20% in Egypt and Ukraine, respectively, with 0% maternal cure by delivery and VT estimated at 6.5% and 7.9%, respectively. WHO risk-based screening and DT (S1) increased the proportion of women diagnosed with no change in maternal cure or VT. Universal screening and treatment during pregnancy (S4) resulted in the highest proportion of women diagnosed and cured by delivery (65% and 70%, respectively), and lower levels of VT (3.4% and 3.6%, respectively). CONCLUSIONS: This is one of the first models to explore HCV screening and treatment strategies in pregnancy, which will be critical in informing future care and policy as more safety/efficacy data emerge. Universal screening and treatment in pregnancy could potentially improve both maternal and infant outcomes. IMPACT AND IMPLICATIONS: In the context of two lower middle-income countries with high HCV burdens (Egypt and Ukraine), we designed a decision analytic model to explore five different HCV testing and treatment strategies for pregnant women, with the assumption that treatment was safe and efficacious for use in pregnancy. Assuming direct-acting antiviral treatment during pregnancy would reduce vertical transmission, our findings indicate that the provision of universal (rather than risk-based targeted) screening and treatment would provide the greatest maternal and infant benefits. While future trials are needed to assess the safety and efficacy of direct-acting antivirals in pregnancy and their impact on vertical transmission, there is increasing recognition that the elimination of HCV cannot leave entire subpopulations of pregnant women and young children behind. Our findings will be critical for policymakers when developing improved screening and treatment recommendations for pregnant women.
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Hepatitis C Crónica , Hepatitis C , Complicaciones Infecciosas del Embarazo , Niño , Humanos , Embarazo , Femenino , Preescolar , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Egipto/epidemiología , Ucrania/epidemiología , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Tamizaje Masivo , Transmisión Vertical de Enfermedad Infecciosa/prevención & controlRESUMEN
BACKGROUND & AIMS: The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial. METHODS: We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. RESULTS: Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002). CONCLUSION: This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS. GOV NUMBER: NCT04695769. IMPACT AND IMPLICATIONS: HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy.
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Hepatitis C Crónica , Hepatitis C , Masculino , Humanos , Femenino , Sofosbuvir/efectos adversos , Antivirales/efectos adversos , Hepatitis C Crónica/tratamiento farmacológico , Ribavirina/efectos adversos , Resultado del Tratamiento , Quimioterapia Combinada , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Retratamiento , GenotipoRESUMEN
BACKGROUND & AIMS: Prisons are key venues for scaling-up hepatitis C virus (HCV) testing and treatment. Complex clinical pathways and frequent movements of people in prison remain barriers to HCV care. This study evaluated the impact of a 'one-stop-shop' point-of-care HCV RNA testing intervention on treatment uptake compared with standard of care among people recently incarcerated in Australia. METHODS: PIVOT was a prospective, non-concurrent, controlled study comparing HCV treatment uptake during 'standard of care' (n = 239; November 2019-May 2020) and a 'one-stop-shop' intervention (n = 301; June 2020-April 2021) in one reception prison in Australia. The primary endpoint was uptake of direct-acting antiviral treatment at 12 weeks from enrolment. Secondary outcomes included the time taken from enrolment to each stage in the care cascade. RESULTS: A total of 540 male participants were enrolled. Median age (29 vs. 28 years) and history of injecting drug use (48% vs. 42%) were similar between standard of care and intervention phases. Among people diagnosed with current HCV infection (n = 18/63 in the standard of care phase vs. n = 30/298 in the intervention phase), the proportion initiating direct-acting antiviral treatment within 12 weeks from enrolment in the intervention phase was higher (93% [95% CI 0.78-0.99] vs. 22% [95% CI 0.64-0.48]; p <0.001), and the median time to treatment initiation was shorter (6 days [IQR 5-7] vs. 99 days [IQR 57-127]; p <0.001) compared to standard of care. CONCLUSIONS: The 'one-stop-shop' intervention enhanced treatment uptake and reduced time to treatment initiation among people recently incarcerated in Australia, thereby overcoming key barriers to treatment scale-up in the prison sector. IMPACT AND IMPLICATIONS: This study provides important insights for policymakers regarding optimal HCV testing and treatment pathways for people newly incarcerated in prisons. The findings will improve health outcomes in people in prison with chronic HCV infection by increasing testing and treatment, thereby reducing infections, liver-related morbidity/mortality, and comorbidities. The findings will change clinical practice, clinical guidelines, and international guidance, and will inform future research and national and regional strategies, in particular regarding point-of-care testing, which is being rapidly scaled-up in various settings globally. The economic impact will likely include health budget savings resulting from reduced negative health outcomes relating to HCV, and health system efficiencies resulting from the introduction of simplified models of care. CLINICAL TRIALS REGISTRATION: This study is registered at Clinicaltrials.gov (NCT04809246).
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Prisioneros , Abuso de Sustancias por Vía Intravenosa , Humanos , Masculino , Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Sistemas de Atención de Punto , Pruebas en el Punto de Atención , Prisiones , Estudios Prospectivos , ARN , Abuso de Sustancias por Vía Intravenosa/complicacionesRESUMEN
BACKGROUND: Several HCV patients in Brazil were lost to follow-up (LTFU) in the last two decades before achievement of sustained virological response (SVR). Strategies to recall those diagnosed but untreated patients have been used elsewhere with different success rates. AIM: To identify and retrieve LTFU patients in order to offer them the treatment with the current highly effective direct acting antiviral agents (DAAs). METHODS: Registries ofall HCV patients from three large reference centers in Brazil were retrospectively reviewed to identify those with no registry of SVR. Reasons for non-achievement of SVR were elicited in HCV-RNA + patients. All patients who were not treated or cured were contacted to offer the therapy with DAAs. RESULTS: 10,289 HCV patients (50% males, mean age 52 ± 11 years) were identified. Only 4,293 (41.7%) had been successfully treated previously. From the remaining 5,996 most were LTFU (59%), were not treated for other reasons (14.7%) or were non-responders (26.3%). After revision of the charts 3,559 were considered eligible to be retrieved. The callback success of phone calls was 18%, 13% to cellphone messages (SMS or WhatsApp) and 7% to regular mail. Five-hundred sixty patients had been already treatedor were on treatment and 234 were reported to be dead or transplanted. Finally, 201 had made an appointment and initiated antiviral treatment. CONCLUSION: Even considering the low callback rate, retrieval of LTFU patients was shown to be an important strategy forhepatitis C micro-elimination in Brazil.
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Hepatitis C Crónica , Hepatitis C , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Antivirales/uso terapéutico , Brasil/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Estudios Retrospectivos , Perdida de Seguimiento , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepacivirus/genéticaRESUMEN
Host regulatory immune response is involved in the hepatic inflammatory process caused by the hepatitis C virus (HCV). We aimed to determine if HCV clearance with direct-acting antivirals (DAAs) changes the hepatic fibrosis stage, biochemical parameters of liver injury, and inflammatory/immune responses. Sample: 329 chronic hepatitis C (CHC) patients, 134 of them treated with DAAs. Liver fibrosis was evaluated by transient elastography (FibroScan), biochemical and cellular parameters were determined by standard methods, cytokine concentration by enzyme-linked immunoabsorbent assay (ELISA), and genetic polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or endpoint genotyping. Before DAA treatment, severe fibrosis or cirrhosis (F3/4) was associated with higher values of tumor necrosis factor-alpha (TNF-α) and genotypes transforming growth factor-beta-509 C/T_CC (TGF-ß-509 C/T_CC), interleukine-10-1082 T/C_CC (IL-10-1082 T/C_CC), and IL-10-592 G/T_GT. After DAA treatment, fewer F3/4 patients and lower values of TNF-α were found. Patients with TNF-α-308 G/A_GG and IL-10-592 G/T_GT were at risk for F3/4. Lack of improvement of liver fibrosis was associated with lower baseline values of platelet count for genotypes TNF-α-308 G/A_GG and haplotype TT/GG of IL-10-1082 T/C and IL-10-592 G/T. Our study showed decreased liver fibrosis/inflammation and normalization of liver injury biomarkers after DAA treatment. It also points to the importance of suppressing the pro-inflammatory response by DAAs in the resolution of hepatitis C, contributing to the improvement of liver damage evaluated by transient elastography.
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Hepatitis C Crónica , Hepatitis C , Humanos , Antivirales/uso terapéutico , Citocinas/genética , Citocinas/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Hepatitis C Crónica/complicaciones , Interleucina-10/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/uso terapéutico , Polimorfismo Genético , Cirrosis Hepática/genética , Cirrosis Hepática/complicaciones , Hepatitis C/complicaciones , Factor de Crecimiento Transformador beta/genética , Hepacivirus/genética , InmunidadRESUMEN
INTRODUCTION: There is limited research about HBV reactivation (HBVr) due to direct-acting antivirals (DAA) for HCV and most are limited by short duration of follow-up, small sample size, and absence of baseline HBV DNA. We aimed to determine the incidence and clinical course of HBVr in HBsAg and/or anti-HBcIgG positive patients treated with DAA for HCV. METHODS: Seven centers retrospectively analyzed their database on HCV patients treated with DAA between 2015 and 2019. Patients with HBV coinfection or resolved HBV infection were enrolled. Serum transaminases, HBsAg, HBeAg, and HBV DNA were followed every 4 weeks during DAA treatment and every 12 weeks 1 year after treatment. Entecavir or tenofovir disoproxil fumarate was started in case of HBVr. The development of HBVr, HBV flare, liver failure, and mortality were determined. RESULTS: 852 patients received DAA treatment for HCV. Among them, 35 (4.1%) had HBV coinfection and 246 (28.9%) had resolved HBV infection. 257 patients (53.3% male, mean age: 63 ± 9) constituted the study group (29 with coinfection and 228 with resolved infection). Three patients with coinfection were HBV DNA positive. HBVr developed in 10 (34.5%) HBsAg positive patients, either during (n = 3) or 12-48 weeks after finishing DAA treatment. HBV flare and acute liver failure developed in 1 patient (3.4%), each. Two patients with resolved infection developed HBVr (0.87%) and one (0.44%) had HBV flare. Overall, none of the patients died or underwent liver transplantation due to HBVr. CONCLUSION: Patients with HBV/HCV coinfection have a high risk of HBVr after DAA treatment and should receive antiviral prophylaxis. Patients with resolved infection have a low risk of HBVr and can be monitored by serial ALT measurements.
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Coinfección , Hepatitis B , Hepatitis C Crónica , Hepatitis C , Anciano , Antivirales/farmacología , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , ADN Viral/farmacología , ADN Viral/uso terapéutico , Femenino , Hepacivirus/genética , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/fisiología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Activación ViralRESUMEN
BACKGROUND: Despite the current highly effective therapies with direct-acting antiviral agents (DAAs), some patients with chronic hepatitis C virus (HCV) infection still do not achieve sustained virological response (SVR) and require retreatment. Sofosbuvir/velpatasvir/voxilaprevir (SVV) is recommended as the first-line retreatment option for most patients. The aim of this study was to evaluate the efficacy of SVV as salvage therapy after at least one course of DAA. METHODS: Data were collected on all HCV-infected patients who failed DAAs and were prescribed SVV from a prospective Canadian registry (CANUHC) including 17 sites across Canada. Factors associated with failure to achieve SVR with SVV therapy and the utility of RAS testing and ribavirin use were evaluated. RESULTS: A total of 128 patients received SVV after non-SVR with DAA treatment: 80% male, median age 57.5 (31-86), 44% cirrhotic, and 17 patients post liver transplant. First line regimens included: sofosbuvir/velpatasvir (27.3%), sofosbuvir/ledipasvir (26.5%), grazoprevir/elbasvir (12.5%), other (33.5%). Ribavirin was added to SVV in 26 patients due to past sofosbuvir/velpatasvir use (nâ =â 8), complex resistance associated substitution profiles (nâ =â 16) and/or cirrhosis (nâ =â 9). Overall SVR rate was 96% (123/128). Of 35 patients who previously failed sofosbuvir/velpatasvir, 31 (88.5%) achieved SVR compared to 92 of 93 (99%) among those receiving any other regimen (Pâ =â .01). CONCLUSIONS: Similar to reports from phase 3 clinical trials, SVV proved highly effective as salvage therapy for patients who failed a previous DAA therapy. Those who failed SVV had at least 2 of the following factors: genotype 3, presence of cirrhosis, past liver transplantation, past exposure to sofosbuvir/velpatasvir and/or complex resistance profiles.
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Antivirales , Hepatitis C Crónica , Ácidos Aminoisobutíricos , Antivirales/uso terapéutico , Canadá , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Persona de Mediana Edad , Prolina/análogos & derivados , Estudios Prospectivos , Quinoxalinas , Sistema de Registros , Terapia Recuperativa , Sofosbuvir/uso terapéutico , SulfonamidasRESUMEN
BACKGROUND & AIMS: Direct-acting antivirals (DAA) lead to high sustained virological response (SVR) rates and decrease the risk of disease progression. We compared SVR rates and all-cause, liver- and non-liver-related deaths, liver-related events, and non-liver-related cancers in HIV/HCV-coinfected and HCV-monoinfected participants from 2 French cohort studies after initiation of DAA treatment. METHODS: Up to 4 HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to each HIV/HCV-coinfected patient from the ANRS CO13 HEPAVIH cohort; both are nationwide, prospective, multicentre, and observational. Participants were initiated on DAAs between March 2014 and December 2017. Cox proportional hazards models adjusted by age, sex, duration since HCV diagnosis, HCV transmission routes, HCV genotypes, cirrhosis, tobacco, alcohol consumption, and SVR (time dependent) were used. RESULTS: A total of 592 HIV/HCV-coinfected and 2,049 HCV-monoinfected participants were included; median age was 53.3 years (inter-quartile range: 49.6-56.9) and 52.9 years (49.6; 56.7), 1,498 (73.1%) and 436 (73.6%) were men, and 159 (28.8%) and 793 (41.2%) had cirrhosis, respectively. SVR was observed in 92.9% and 94.6%, respectively. HIV coinfection was associated with higher risk of all-cause death (hazard ratio [HR] 1.93; 95% CI 1.01-3.69), non-liver-related death (HR 2.84; 95% CI 1.27-6.36), and non-liver-related cancer (HR 3.26; 95% CI 1.50-7.08), but not with liver-related-death (HR 1.04; 95% CI 0.34-3.15) or liver-related events (HR 0.66; 95% CI 0.31-1.44). CONCLUSIONS: After DAA treatment, HIV-coinfected individuals had similar SVR rates and risk of liver-related deaths and events compared with HCV-monoinfected individuals, but had a higher risk of all-cause and non-liver-related deaths and non-liver-related cancers. LAY SUMMARY: We compared the risk of several clinical events in participants infected by human immunodeficiency virus and hepatitis C virus with those infected with hepatitis C virus alone, matched on age and sex, after treatment with contemporary direct-acting antivirals. We found a higher risk of all-cause deaths, non-liver-related deaths, and non-liver-related cancers in participants coinfected with the human immunodeficiency virus and hepatitis C virus, and no differences for the risk of liver-related deaths or events.
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Causas de Muerte , Infecciones por VIH , VIH , Hepacivirus , Hepatitis C Crónica , Oligopéptidos , Prolina/análogos & derivados , Antivirales/administración & dosificación , Progresión de la Enfermedad , Femenino , Francia/epidemiología , VIH/efectos de los fármacos , VIH/aislamiento & purificación , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Prolina/administración & dosificación , Prolina/efectos adversos , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología , Respuesta Virológica SostenidaRESUMEN
OBJECTIVES: Sustained virological response (SVR) decreases the risk of hepatitis C virus (HCV)-related events. Nevertheless, a substantial risk of events persists. We estimated incidences and identified factors associated with severe clinical events after SVR following treatment with a direct-acting antiviral (DAA) in HIV/HCV-coinfected patients. METHODS: Participants from the ANRS CO13 HEPAVIH were included if they reached SVR. Incidence rates of overall mortality, liver-related events, AIDS-defining events, ischaemic events and non-liver non-AIDS-defining cancers (NLNA) were estimated. Factors associated with the risk of those events were identified using Poisson models adjusted on age at SVR and sex. RESULTS: In all, 775 participants were included. Incidence rates (95% confidence interval) of liver-related events, overall mortality, AIDS-defining events, ischaemic events and NLNA cancers per 1000 person-years were 5.9 (3.3-10.3), 22.2 (16.8-29.5), 0.6 (0.1-4.5), 7.3 (4.4-12.2) and 13.7 (9.4-20.0), respectively. For all events, incidence rates were higher in cirrhotic than in non-cirrhotic participants. Cirrhosis, liver stiffness and CD4 count were associated with liver-related events. Factors associated with overall mortality were age, cirrhosis, liver stiffness and gamma-glutamyl transferase (GGT). For ischaemic events and NLNA cancers, associated factors were total cholesterol and CD4 count, respectively. CONCLUSIONS: After SVR following a DAA treatment, liver-related and AIDS-defining events were observed less frequently than NLNA cancers. Severity of liver disease was associated with the risk of liver-related events and of overall mortality but not with ischaemic events and NLNA cancers. Factors reflecting HIV infection were associated with NLNA cancers and liver-related events.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Coinfección/complicaciones , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/epidemiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: HIV-coinfected patients experience higher incidences of non-liver-related cancers than HCV-monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfection on the risk of non-liver-related cancers in HCV participants treated with direct-acting antivirals (DAAs). METHODS: Up to four HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to HIV/HCV-coinfected participants from the ANRS CO13 HEPAVIH cohort. Participants were followed from DAA initiation until the occurrence of a non-liver-related cancer. Counterfactual mediation analysis was carried out to estimate the direct (chronic inflammation and immunosuppression), indirect (tobacco and alcohol consumption and metabolic syndrome) and total effect of HIV coinfection on the risk of non-liver-related cancers. RESULTS: 548 HIV/HCV-coinfected and 2016 monoinfected participants were included. Overall, HIV coinfection was associated with a 3.7-fold [95% confidence interval (CI): 1.7-7.0] higher risk of non-liver-related cancers in HCV participants. This increased risk was explained by significant direct effect [hazard ratio (HR) = 3.4, 95% CI: 1.7-6.6] but not indirect effect (HR = 1.1, 95% CI: 0.8-1.5) of HIV coinfection. CONCLUSIONS: In HCV participants treated with DAAs, the direct effect of HIV coinfection, reflecting chronic inflammation and immunosuppression, was associated with a 3.7-fold higher risk of non-liver-related cancer. By contrast, the indirect effect of HIV coinfection, reflecting higher tobacco and alcohol consumption and metabolic dysregulation, was not significantly associated with the risk of non-liver-related cancers.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Neoplasias , Antivirales/farmacología , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Análisis de Mediación , Neoplasias/complicaciones , Neoplasias/epidemiología , Respuesta Virológica SostenidaRESUMEN
Long-term effects on cirrhosis and portal hypertension of direct antiviral agent (DAA)-based eradication of hepatitis C virus (HCV) are still under debate. We analysed dynamics of liver and spleen elastography to assess potential regression of cirrhosis and portal hypertension 3 years post-treatment. Fifty-four patients with HCV-associated cirrhosis and DAA-induced SVR were included. Liver and spleen stiffness were measured at baseline (BL), end of treatment (EOT), 24 weeks after EOT (FU24) and 1, 2 and 3 (FU144) years post-treatment by transient liver elastography (L-TE) and point shear wave elastography (pSWE) using acoustic radiation force impulse (ARFI) of the liver (L-ARFI) and spleen (S-ARFI). Biochemical, virological and clinical data were also obtained. Liver stiffness assessed by L-TE decreased between BL [median (range), 32.5(9.1-75) kPa] and EOT [21.3(6.7-73.5) kPa; p < .0001] and EOT and FU144 [16(4.1-75) kPa; p = .006]. L-ARFI values improved between EOT [2.5(1.2-4.1) m/s] and FU144 [1.7(0.9-4.1) m/s; p = .001], while spleen stiffness remained unchanged. Overall, L-TE improved in 38 of 54 (70.4%) patients at EOT and 29 of 38 (76.3%) declined further until FU144, whereas L-ARFI values decreased in 30/54 (55.6%) patients at EOT and continued to decrease in 28/30 (93.3%) patients at FU144. Low bilirubin and high albumin levels at BL were associated with improved L-ARFI values (p = .048) at EOT or regression of cirrhosis (<12.5 kPa) by L-TE at FU144 (p = .005), respectively. Liver stiffness, but not spleen stiffness, continued to decline in a considerable proportion of patients with advanced liver disease after HCV eradication.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica , Hepatitis C , Hipertensión Portal , Antivirales/uso terapéutico , Estudios de Seguimiento , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Humanos , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/patología , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Estudios Longitudinales , Estudios Prospectivos , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.
Asunto(s)
Antivirales , Coinfección , Infecciones por VIH , Hepatitis C Crónica , Adulto , Anciano , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Nigeria , Portugal , Calidad de Vida , Sofosbuvir/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
The impact of direct-acting antiviral (DAA) therapies on fibrosis regression remains uncertain. In the current study, we prospectively evaluated dynamics of liver stiffness by transient elastography (TE) in patients with chronic HCV infection receiving DAA-based treatment. Patients (260) were enrolled in the German Hepatitis C-Registry (DHC-R), a national multicentre real-world cohort. Liver stiffness (LS) was assessed at baseline, end of treatment (EOT) and 24 weeks after EOT (FU24) by TE. Biochemical, virological and clinical data were obtained in parallel. In patients with SVR, there was a significant improvement of LS between baseline (median [range], 8.6 [1.7-73.5] kPa) and FU24 (7.9 [1.7-75 kPa]; P < .0001) as well as between EOT (8.4 [1.7-73.5 kPa]) and FU24 [P < .0001]. Stratified by fibrosis stage, patients classified into F4 had higher magnitude of LS reduction between BL (median [range], 25.1 [13.5-73.5] kPa) and FU24 (21.5 [3.1-75] kPa; P = .002) compared to those with F2-F3 (8.9 [7.1-12.4] kPa and 8.8 [4.2-29.1]; P = .060) or F0-F1 (5.3 [1.7-7] kPa and 5.2 [1.7-7.7]; P = .064). In cirrhotic patients, low platelets were significantly associated with lack of liver stiffness improvement, both at EOT (P = .018) and at FU24 (P = .012). LS significantly correlated with ALT (r = .371), AST (r = .552), platelets (r = -.499), GGT (r = .250), bilirubin (r = .230), APRI score (r = .512), FIB-4 score (r = .517) and FORNS index (r = .562); P < .0001. Liver elastography improved significantly in our real-world cohort after DAA-based therapy. As LS correlates similarly with transaminase levels and serum fibrosis markers, it might reflect both reduction of necroinflammation and fibrosis regression.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica , Hígado , Antivirales/uso terapéutico , Alemania , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Hígado/patología , Cirrosis Hepática/patología , Sistema de Registros , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (p < .0001) and in HIV-HCV group there were more men (p < .0001). Prevalence of genotype 1a (p = .002), as well as of genotypes 3 and 4 (p < .0001) was higher in HIV-HCV-coinfected patients. Genotype 1b was more frequent (p < .0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p = .0004) and lower proportion of fibrosis F2 (p < .0001). HIV-HCV-coinfected individuals were more often treatment-naïve (p < .0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p > .05). They were, however, influenced by HCV genotype (p < .0001), stage of hepatic fibrosis (p < .0001), male sex (p < .0001), BMI (p = .0001) and treatment regimen modifications (p < .0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations.
Asunto(s)
Coinfección , Infecciones por VIH , Hepatitis C , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Hepatitis C virus (HCV) is highly prevalent among homeless persons, yet barriers continue to impede HCV testing and treatment in this population. We studied the experiences of homeless individuals related to accessing HCV care to inform the design of a shelter-based HCV prevention and treatment program. METHODS: Homeless shelter clients (10 women and 10 men) of a large shelter in San Francisco participated in gender segregated focus groups. Focus groups followed a semi-structured interview format, which assessed individual, program/system, and societal-level barriers and facilitators to universal HCV testing and linkage to HCV care. Focus group interviews were transcribed, coded, and analyzed using thematic analysis. RESULTS: We identified key barriers to HCV testing and treatment at the individual level (limited knowledge and misconceptions about HCV infection, mistrust of health care providers, co-morbid conditions of substance use, psychiatric and chronic medical conditions), system level (limited advocacy for HCV services by shelter staff), and social level (stigma of homelessness). Individual, system, and social facilitators to HCV care described by participants included internal motivation, financial incentives, prior experiences with rapid HCV testing, and availability of affordable direct acting antiviral (DAA) treatment, respectively. CONCLUSIONS: Interrelated individual- and social-level factors were the predominant barriers affecting homeless persons' decisions to engage in HCV prevention and treatment. Integrated models of care for homeless persons at risk for or living with HCV address many of these factors, and should include interventions to improve patient knowledge of HCV and the availability of effective treatments.
Asunto(s)
Implementación de Plan de Salud , Hepacivirus/inmunología , Hepatitis C/epidemiología , Hepatitis C/psicología , Personas con Mala Vivienda , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Personal de Salud , Hepatitis C/complicaciones , Hepatitis C/prevención & control , Anticuerpos contra la Hepatitis C/sangre , Vivienda , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , San Francisco/epidemiología , Estigma Social , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
BACKGROUND: Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF). METHODS: Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month. Left ventricular function was measured with both EF and GLS. RESULTS: From March 2015 to December 2016, 82 patients were enrolled. Fifty-six percent patients were males. Mean age was 66.12 (SD: 9.25) years. About 20% patients did not present any cardiovascular risk factors or comorbidities. A worsening trend of GLS was observed. Variations were not found to be statistically significant when EF was studied along the follow-up. However, when GLS was studied, its variations were found to be statistically significant indicating a worsening effect, albeit with different trends in patients who underwent treatment for three months compared to six months. Worsening of GLS was found to be statistically significant even after adjusting for body mass index and liver fibrosis, independently from treatment duration. CONCLUSIONS: Our results showed unexpected worsening of left ventricular function when measured through GLS after HCV treatment response induced by DAAs including sofosbuvir. Although this result is not proven to be clinically significant, the safety profile of sofosbuvir-based regimens needs to be studied further.
Asunto(s)
Pruebas de Función Cardíaca/métodos , Hepatitis C/tratamiento farmacológico , Sofosbuvir/administración & dosificación , Sofosbuvir/efectos adversos , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico , Función Ventricular Izquierda/efectos de los fármacos , Anciano , Cardiotoxicidad/diagnóstico , Enfermedad Crónica , Quimioterapia Combinada/efectos adversos , Ecocardiografía , Femenino , Hepatitis C/fisiopatología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Disfunción Ventricular Izquierda/virología , Función Ventricular Izquierda/fisiologíaRESUMEN
AIM: Hepatitis C virus (HCV) recombinant form RF1_2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 by standard genotyping. We aimed to identify RF1_2k/1b strains among genotype 2 patients and assess its impact on treatment outcomes. METHODS: The study included 148 patients with HCV genotype 2 as determined by 5-untranslated region/core genotyping assay. RF1_2k/1b was identified by sequencing the non-structural protein 5B region. Patients were treated within the national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon (IFN)/SOF/RBV, or ledipasvir (LDV)/SOF/RBV. RESULTS: Of 148 patients, 103 (69.5%) had RF1_ 2k/1b. Sustained virologic response (SVR) data was available for 136 patients (RF1_ 2k/1b, n = 103; genotype 2, n = 33). Sustained virologic response was achieved in more genotype 2 patient than in RF1_2k/1b patients (97.0% vs. 76.7%, P = 0.009). Twelve weeks of LDV/SOF/RBV treatment was highly effective (100% SVR) in both genotypes. Among RF1_2k/1b patients, LDV/SOF/RBV for 12 weeks was superior (100% SVR) to SOF/RBV for 12 weeks (56.4%, P < 0.0001) or 20 weeks (79.2%, P = 0.05). Twelve weeks of IFN/SOF/RBV also showed better response than SOF/RBV for 12 weeks (88.9% vs. 56.4%, P = 0.02) in these patients. CONCLUSIONS: High prevalence of the RF1_2k/1b strain can significantly affect treatment outcomes. Treatment with IFN/SOF/RBV and especially LDV/SOF/RBV ensured significantly higher SVR in patients infected with RF1_2k/1b strain compared to standard HCV genotype 2 treatment with SOF/RBV. There is a need to reassess existing methods for the management of HCV genotype 2 infections, especially in areas with high prevalence of the RF1_2k/1b strain.
RESUMEN
BACKGROUND & AIMS: Little is known about the epidemiology and frequency of recombinant HCV genotype 2/1 strains, which may represent a challenge for direct antiviral therapy (DAA). This study aims to identify the epidemiology and phylogeny of HCV genotype 2/1 strains and encourages genotype screening, to select the DAA-regimen that achieves the optimal sustained virologic response. METHODS: Consecutive samples from HCV genotype 2 infected patients, according to commercial genotyping, from Germany, Italy and Israel were re-genotyped by Sanger-based sequencing. Virologic, epidemiological, and phylogenetic analyses including other published chimeras were performed. RESULTS: Sequence analysis of 442 supposed HCV genotype 2 isolates revealed 61 (genotype 2k/1b (n=59), 2a/1b (n=1) or 2b/1a (n=1)) chimeras. No chimeras were observed in Italy, but the frequency was 14% and 25% in Germany and Israel. Treatment of viral chimera with sofosbuvir/ribavirin led to virologic relapse in 25/27 patients (93%). Nearly all patients treated with genotype 1-based DAA-regimens initially (n=8/9), or after relapse (n=13/13), achieved a sustained virologic response. Most patients with 2k/1b chimeras (88%) were originally from eight different areas of the former Soviet Union. All known 2k/1b chimeras harbour the same recombination breakpoint and build one phylogenetic cluster, while all other chimeras have different phylogenies. CONCLUSIONS: The HCV genotype 2k/1b variant derives from one single recombination event most likely in the former Soviet Union, while other chimeras are unique and develop independently. A relatively high frequency has been observed along the migration flows, in Germany and Israel. In countries with little migration from the former Soviet Union the prevalence of 2k/1b chimeras is expected to be low. Treatment with sofosbuvir plus ribavirin is insufficient, but genotype 1-based regimens seem to be effective. Lay summary: The frequency of recombinant HCV is higher than expected. A novel recombinant variant (HCV genotype 2a/1b) was identified. Screening for recombinant viruses would contribute to increased response rates to direct antiviral therapy.