Late Relapse and Reinfection in HCV Patients Treated with Direct-Acting Antiviral (DAA) Drugs.
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ABSTRACT:
SUBMITTER: Minosse C
PROVIDER: S-EPMC8235384 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDirect-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV). The impact of DAAs on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains uncertain.ObjectiveWe aimed to evaluate the risk of HCC recurrence in LT recipients cleared of HCV with DAAs at the time of LT compared to a control group of LT recipients who were viremic at the time of LT.MethodsThe study was a single-center, retrospective cohort study of patients undergoing LT for HCV-related HCC from 2002 to 2017. We compared time to post-LT HCC recurrence in patients with a sustained virological response (SVR) from DAAs prior to LT (DAA group) to patients who were viremic at LT (HCV+ group) using Kaplan-Meier analysis. We performed a secondary analysis comparing post-LT HCC recurrence in the DAA group to LT recipients with SVR from interferon-based treatment prior to LT (IFN group).ResultsOne hundred fifty-one patients underwent LT for HCC related to HCV: 34 patients in DAA group, 95 patients in HCV+ group, and 22 in IFN group. Kaplan-Meier estimates of being HCC free were 96.2, 96.2, and 78.8% at 6, 12, and 24 months in DAA group, respectively, and 100, 98.6, and 95.8% at 6, 12, and 24 months in the HCV+ group, respectively; p = 0.08. There was no difference observed for HCC recurrence between the DAA and IFN groups. In a multivariate Cox proportional hazards model, DAA use increased the risk of post-LT HCC recurrence (HR 5.2, 95% CI 0.9-29.81, p = 0.07).ConclusionsA strong trend was observed on both Kaplan-Meier and multivariate analyses toward increased post-LT HCC recurrence in patients who achieved SVR prior to LT with DAAs compared to patients who were viremic at LT. Caution is required when considering pre-LT treatment of HCV with DAAs in patients with HCC.
| S-EPMC7590751 | biostudies-literature
Project description:Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12. At baseline, genotypes were determined as HCV1a (41.5%), HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%), while six cases revealed to be discordantly assigned by phylogeny and commercial assays. Overall, 60.4% was co-infected with HIV. The large majority was classified as people who inject drugs (78.6%), often co-infected with HIV. Transmission was sexual in seven cases, of which five in HIV-positive men-who-have-sex-with-men. Overall, relapse was defined for 44 patients, while no conclusion was drawn for four patients. Five patients were reinfected with a different HCV strain, of which three with a different genotype, showing that phylogeny is needed not only to determine the genotype, but also to distinguish between relapse and intra-subtype reinfection. Of note, phylogenies are more reliable when longer fragments of the viral genome are being sequenced.
| S-EPMC6059487 | biostudies-literature
Project description:IntroductionClinical trials have demonstrated the efficacy of all-oral direct-acting antiviral (DAA) regimens in the treatment of patients infected with hepatitis C virus (HCV). This study assessed real-world effectiveness of two recently approved regimens; paritaprevir/ritonavir/ombitasvir; dasabuvir (3D), and sofosbuvir/ledipasvir (SOF/LDV) in patients with HCV genotype 1.MethodsA retrospective analysis of administrative claims data (IMS Health Patient-Centric Data Warehouse/Medivo database) from October 1, 2013 to August 14, 2015 was conducted. Patients ≥19 years of age with a HCV genotype 1 infection, a prescription fill for 3D or SOF/LDV, and ≥1 HCV viral load (VL) assessment from weeks 4-30 post-treatment were selected for analysis. Percentages of patients achieving sustained virologic response (SVR; defined as HCV RNA ≤43 IU/mL) were determined. Unadjusted SVR rates were compared between treatment groups using Fisher's exact tests. SVR rates were also assessed using multivariate regression with adjustment for age group, sex, and treatment history. Analyses were repeated for a subset of patients with VL assessment from 12 to 30 weeks post-treatment.ResultsA total of 1707 (44 3D and 1663 SOF/LDV) patients were included. The majority (60%) were male, 49% were aged 55-64 years, and 97% were treatment-naïve 1 year prior to index. The unadjusted relative risk (RR) for achieving SVR in patients treated with SOF/LDV compared with 3D was 0.98%, 95% confidence interval (CI): 0.93-1.02. After adjusting for the baseline covariates, the RR was 0.98%, 95% CI: 0.94-1.03.ConclusionsIn this early view of real-world data, effectiveness of all-oral DAA regimens in HCV genotype 1 patients was concordant with results from registration trials. SVR rates were similar for the two regimens. Further studies are needed to confirm these results.FundingAbbVie, Inc.
| S-EPMC4662718 | biostudies-literature
Project description:HIV/HCV infection is supposed to substantially reduce survival as compared to HIV mono-infection. Here, we compared longtime-survival and causes of death in a cohort of HIV- and HIV/HCV-co-infected patients on combined antiretroviral therapy (cART), before introduction of HCV direct acting antivirals (DAA). 322 Caucasian patients with HIV (n?=?176) and HIV/HCV-infection (n?=?146) were enrolled into this study. All patients were recruited between 2003 and 2004 and followed until 01.01.2014. We compared overall survival between the two groups by the Kaplan-Meyer method and identified independent factors associated with long-time survival by conditional Cox regression analysis. In total 46 (14.3%) patients died during the observation period (HIV infection: n?=?23 (13.1%), HIV/HCV infection: n?=?23 (15.8%) but overall-survival did not differ significantly between HIV/HCV-infected and HIV mono-infected patients (p?=?0.619). Survival was substantially better in patients with complete suppression of HIV replication below the level of detection than in those with residual viremia (p?=?0.001). Age (p?=?0.008), ?-glutamyltranspeptidase (p?<?0.0001) and bilirubin (p?=?0.008) were significant predictors of survival irrespective from HCV co-infection. Complete repression of HIV replication on cART is the key factor determining survival both in HIV- and HIV/HCV-co-infected patients, while HCV co-infection and therapy without DAAs seem to affect survival to a lesser extent. Thus, patients with HIV/HCV co-infection require particularly intensive cART.
| S-EPMC6715635 | biostudies-literature
Project description:Despite the excellent efficacy of direct acting antivirals (DAA) for hepatitis C virus (HCV), treatment failures do occur. Until recently, retreatment decisions after DAA failure were influenced by the number of available agents, concerns about HCV drug resistance, and lack of data regarding retreatment. Recommended treatment approaches previously depended on limited clinical trials and expert opinion. In this article, we review the current state of the evidence for HCV retreatment after DAA failure. Based on recent clinical trial data, most patients who fail HCV treatment with DAA agents now have excellent retreatment options. While some patients may benefit from resistance testing after DAA therapy failure to select the optimal treatment and duration, newly approved salvage therapies are not significantly impacted by common mutations and have been approved by the Food and Drug Administration for HCV retreatment without regard for the presence of resistance associated substitutions. While prior retreatment efforts were limited to longer courses of therapy, the addition of ribavirin, or novel combinations of approved therapies based on expert guidance, current DAA options make HCV retreatment in the DAA era more streamlined and evidence-based.
| S-EPMC5726279 | biostudies-literature
Project description:Torque Teno virus (TTV) is a ubiquitous virus that causes chronic infection in humans with unknown clinical consequences. Here, we investigated the influence of TTV infection on HCV direct-acting antiviral (DAA) efficacy in HIV/HCV coinfected and HCV monoinfected patients as controls. Of 92 study patients, 79.3% were TTV DNA positive; untreated patients exhibited a significantly higher proportion of TTV DNA-positivity vs. sustained virological response (SVR) patients (100.0% vs. 65.2%, p < 0.001), while TTV positivity was not significant in DAA failure patients vs. SVR patients despite HIV/HCV coinfection. TTV DNA viral load was higher among HCV monoinfected patients vs. HIV/HCV coinfected, although marginally significant (p = 0.074) and no significant viral load difference was detected between DAA failures and SVR patients, while untreated vs. SVR patients had a significantly higher viral load (19,884, IQR 5977-333,534, vs. 469, IQR 10-4124, p = 0.004). Alpha-genogroup 3 TTV was the most prevalent genetic group, and no specific strain or genogroup was observed in relapser patients. Among HIV/HCV patients with HCV RNA detectable at end of treatment (EOT), TTV DNA was detected in 9/17 treatment responder patients and 3/5 relapser patients, thus, TTV infection does not appear to influence the control HCV viremia after EOT. Levels of IL-6 IL-4, and CD14 were not significantly different between TTV PCR-positive and -negative patients. These results suggest no association between TTV DNA positivity or viral load and HCV DAA failure whether patients were HIV/HCV coinfected or HCV monoinfected.
| S-EPMC8152458 | biostudies-literature
Project description:Background and aimsMixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium-term to long-term period.Approach and resultsDirect-acting antiviral-treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated. Cumulative incidence Kaplan-Meier curves were reported for response, clinical deterioration, relapse and relapse-free survival rates. Cox regression analysis evaluated factors associated with different outcomes. A clinical response was reported in at least one follow-up point for 373 of 423 (88%) patients with CV who achieved SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A full complete response (FCR) was reached by 164 (38.8%) patients in at least one follow-up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration, 19 months). In patients who achieved FCR and had an available follow-up (137 patients) a relapse was observed in 13% and it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving SVR, a clinical nonresponse was associated with older age and renal involvement; a clinical deterioration/relapse was associated with high pretreatment rheumatoid factor values, and FCR was inversely associated with age, neuropathy, and high cryocrit levels.ConclusionIn patients with CV, HCV eradication may not correspond to a persistent clinical improvement, and clinical response may fluctuate. This implies an attentive approach to post-SVR evaluation through prognostic factors and tailored treatment.
| S-EPMC9305531 | biostudies-literature
Project description:We have carried out a longitudinal study of PBMC's miRNA profile in HIV/HCV coinfected patients (n=28) after HCV eradication with DAA and SVR achivement. HIV monoinfected patients (n=16) were used as control. Briefly, peripheral venous blood samples were collected in EDTA tubes, and PBMCs were isolated within the first 4 hours after extraction.Total RNA including miRNAs were isolated from PBMCs with the miRNeasy Mini kit (Qiagen). Quality and integrity were evaluated by the Bioanalyzer 2100 with Agilent RNA 6000 Nano kit (Agilent). Only those samples with RIN > 7.5 were sequenced. Small RNA library synthesis and sequencing were performed at Centre for Genomic Regulation (CRG) at Barcelona (Spain). Small RNA libraries were constructed with Illumina’s TruSeq Small RNA kit v.4 (Illumina) and 50nts (1x50) were sequenced in an Illumina HiSeq2500, with a single read approach.
2021-11-23 | E-MTAB-10566 | biostudies-arrayexpress
Project description:Background & aimsWe determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID).MethodsA dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment.ResultsThe most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage.ConclusionsTreating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high.
| S-EPMC4914770 | biostudies-literature
Project description:Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV-HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV-HCV patients. Methods: Non-cirrhotic HIV-HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders). Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = -0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = -0.713) significantly differentiated between nonresponders from responders in HIV-HCV coinfected patients and was able to predict the failure of treatment response. Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV-HCV coinfected patients.
| S-EPMC8784690 | biostudies-literature