Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients

Background: Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment.

Methods: 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment.

Results: Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL.

Conclusion: DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.     

Coste-efectividad del desfibrilador automático implantable para la prevención primaria de la muerte súbita cardiaca

Introduction and objectiveImplantable cardioverter-defibrillators (ICD) are a cost-effective alternative for secondary prevention of sudden cardiac death, but their efficiency in primary prevention, especially among patients with nonischemic heart disease, is still uncertain.MethodsWe performed a cost-effectiveness analysis of ICD plus conventional medical treatment (CMT) vs CMT for primary prevention of cardiac arrhythmias from the perspective of the national health service. We simulated the course of the disease by using Markov models in patients with ischemic and nonischemic heart disease. The parameters of the model were based on the results obtained from a meta-analysis of clinical trials published between 1996 and 2018 comparing ICD plus CMT vs CMT, the safety results of the DANISH trial, and analysis of real-world clinical practice in a tertiary hospital.ResultsWe estimated that ICD reduced the likelihood of all-cause death in patients with ischemic heart disease (HR, 0.70; 95%CI, 0.58-0.85) and in those with nonischemic heart disease (HR, 0.79; 95%CI, 0.66–0.96). The incremental cost-effectiveness ratio (ICER) estimated with probabilistic analysis was €19 171/quality adjusted life year (QALY) in patients with ischemic heart disease and €31 084/QALY in those with nonischemic dilated myocardiopathy overall and €23 230/QALY in patients younger than 68 years.ConclusionsThe efficiency of single-lead ICD systems has improved in the last decade, and these devices are cost-effective in patients with ischemic and nonischemic left ventricular dysfunction younger than 68 years, assuming willingness to pay as €25 000/QALY. For older nonischemic patients, the ICER was around €30 000/QALY.Full English text available from:www.revespcardiol.org/en     

Cost-Effectiveness of a Community-Based Exercise Programme in COPD Self-Management

Introduction: Information regarding cost-effectiveness of community-based exercise programmes in COPD is scarce. Therefore, we have investigated whether a community-based exercise programme is a cost-effective component of self-management for patients with COPD after 2 years of follow-up.

Methods: All included COPD patients participated in four self-management sessions. Additionally, patients in the COPE-active group participated in an 11-month community-based exercise programme led by physiotherapists. Patients trained 3 times/week for 6 months and two times/week during the subsequent 5 months. In both periods, one of these weekly training sessions was home-based (unsupervised). No formal physiotherapy sessions were offered to COPE-active patients in the second year. A decision analytical model with a 24-month perspective was used to evaluate cost-effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated and cost-effectiveness planes were created.

Results: Data of 77 patients participating in the exercise programme and 76 patients in the control group were analysed. The ICER for an additional patient prevented from deteriorating at least 47.5 meters on the ISWT was €6257. The ICER for an additional patient with a clinically relevant improvement (≥ 500 steps/day) in physical activity was €1564, and the ICER for an additional quality-adjusted life year (QALY) was €10 950.

Conclusion: Due to a lack of maintenance of beneficial effects on our primary outcome exercise capacity after 2 years of follow-up and higher costs of the programme, the community-based exercise programme cannot be considered cost-effective compared to self-management programmes only. Nevertheless, the ICERs for the secondary outcomes physical activity and QALY are generally considered acceptable.     

Colonoscopic surveillance – a cost-effective method to prevent hereditary and familial colorectal cancer

Objective: Approximately 20–30% of all colorectal cancer (CRC) cases may have a familial contribution. The family history of CRC can be prominent (e.g., hereditary colorectal cancer (HCRC)) or more moderate (e.g., familial colorectal cancer (FCRC)). For family members at risk, colonoscopic surveillance is a well-established method to prevent both HCRC and FCRC, although the evidence for the exact procedures of the surveillance is limited. Surveillance can come at a high price if individuals are frequently examined, as this may result in unnecessary colonoscopies in relation to actual risk for CRC. This study analyses the cost-effectiveness of a surveillance programme implemented in the Northern Sweden Health Care Region.

Methods: The study includes 259 individuals prospectively recorded in the colonoscopic surveillance programme registry at the Cancer Prevention Clinic, Umeå University Hospital. We performed a cost–utility analysis with a contrafactual design: we compared observed costs and loss of quality-adjusted life years (QALYs) due to CRC with the surveillance programme to an expected outcome without surveillance. The main measure was the incremental cost-effectiveness ratio (ICER) between surveillance and non-surveillance. Scenario analysis was used to explore uncertainty.

Results: The ICER between surveillance and non-surveillance in the base model was 3596€/QALY. The ICER varied from ?4620€ in the best-case scenario to 33,779€ in the worst-case scenario.

Conclusion: Colonoscopic surveillance is a very cost-effective method to prevent HCRC and FCRC compared to current thresholds for cost-effectiveness and other cancer preventive interventions.     

Retreatment with sofosbuvir,ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy

Background

The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy.

Methods

This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12 weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated.

Results

Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7% (13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.

Conclusions

This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.

     

Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience

Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles.Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed.ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree.ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.     

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil

Introduction and objectivesDirect antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil.Materials and methodsAll Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR).Results3939 patients (60% males, mean age 58 ± 10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation.ConclusionSOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.     

Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway

Abstract

Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5–10%) at baseline in direct-acting antiviral agents (DAA) treatment-naïve genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014–2017.

Patients/Methods: Treatment in the intervention group (n?=?130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (n?=?78) received recommended standard DAA-treatment.

Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (p?=?.06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment.

Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.     

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

Background and aimsTreatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs.Patients and methodsInstitutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included.ResultsAs previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions.ConclusionThe retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.     

Cost‐effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis

To evaluate the cost‐effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment‐naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0‐F1) versus advanced fibrosis (F2‐F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality‐adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0‐F1 compared with F2‐F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real‐world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0‐F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2‐F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0‐F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver‐related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2‐F4 patients. In CHC treatment‐naïve GT1 patients, starting treatment with LDV/SOF in patients with F0‐F1 compared to those with F2‐F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings.     

NS5A resistance-associated variants undermine the effectiveness of ledipasvir and sofosbuvir for cirrhotic patients infected with HCV genotype 1b

Background

Little real-world cohort data has been reported for Asians who have received interferon-free regimens with sofosbuvir (SOF) for chronic hepatitis C virus (HCV) infection. We evaluated the effectiveness and safety in clinical practice of ledipasvir (LDV) plus SOF for Japanese patients infected with HCV genotype 1.

Methods

This large, multicenter, real-world cohort study consisted of 772 patients treatment-naive or -experienced, with or without compensated cirrhosis, who were treated with LDV (90 mg)/SOF (400 mg) for a fixed 12-week duration. Direct sequence analysis of the NS5A genes (L31 and Y93) was performed at baseline.

Results

Almost all (99.6%) were infected with HCV genotype 1b. The overall sustained virological response 12 weeks after the end of treatment (SVR12) rate was 98.8% (763/772). Multivariable logistic regression analysis extracted male (odds ratio [OR] 6.62, p = 0.024), cirrhosis (OR 20.1, p = 0.0054), and baseline NS5A resistance-associated variants (RAVs) (OR 29.3, p = 0.0018) as independently associated with treatment failure. Notably, the SVR12 rate for cirrhosis patients with baseline NS5A RAVs (87.5%, 49/56) was statistically lower than for the other groups. This tendency was found except for patients with prior daclatasvir/asunaprevir failure. All patients with treatment failure had NS5A Y93H at relapse, whether or not they had NS5A RAVs at baseline. Serious adverse effects were very rare, and discontinuation was required for only five (0.6%) patients.

Conclusions

LDV/SOF for HCV genotype 1b was exceptionally effective, however, NS5A RAVs undermined the virological effect for cirrhosis patients. Moreover, LDV/SOF was shown to be safe, irrespective of age or fibrosis status.

     

Treatment of Chronic HCV Infection with the New Direct Acting Antivirals (DAA): First Report of a Real World Experience in Southern Brazil

Introduction and aimThere is almost no data regarding the efficacy of direct acting antivirals (DAAs) therapy in Brazil. The aim of this historical cohort study is to describe the sustained virologic response (SVR) rate among real-world compensated chronic hepatitis C patients in three hepatology centers from Southern Brazil.Materials and methodsPatients were included if they had at least 12 weeks follow-up after the end of therapy. Patients that were lost to follow-up or had treatment prematurely interrupted for any reason were considered treatment failure in this intention to treat analysis.Results219 patients were analyzed. Mean age was 57.4 ± 10.9 years and 142/219 (64.8%) were male. Genotype 1 was present in 166 patients (75.8%; 1a 29.2%, 1b 46.6%); Genotypes 2, 3 and 4 in 8 (3.7%), 43 (19.6%) and 2 (0.9%), respectively. 96 (43.8%) were cirrhotic. 134 (59.5%) were treatment experienced. DAA therapies were: sofosbuvir (SOF) + ribavirin (RBV) in 10 patients; SOF + simeprevir (SMV) ± RBV in 73; SOF + pegylated interferon (PEG-IFN) + RBV in 6; SOF + daclatasvir (DCV) ± RBV in 51, SOF + ledipasvir (LDV) ± RBV in 61, and par-itaprevir/ritonavir + ombitasvir + dasabuvir (PTVr/OBV/DSV) ± RBV in 18 patients. SVR-12 was achieved in 208/219 (95%). Ten patients had virologic failure: 6 cirrhotic, 7 treatment experienced, and 6 either genotype 3 or 1a. No adverse event was attributed to the DAA therapy.ConclusionsReal world experience with DAA therapy in Southern Brazil showed a high rate of SVR and excellent tolerability. Failure to achieve SVR was mainly observed among patients with at least one negative predictor of response: cirrhosis and/or genotypes 1a or 3.     

Pharmacoeconomic analysis of Metoject(®) in the treatment of rheumatoid arthritis in Spain

ObjectivesThe aim of this study was to compare the clinical and economic consequences of using subcutaneous methotrexate (Metoject^®) with respect to oral methotrexate in the management of rheumatoid arthritis (RA) in Spain.MethodsA cost-effectiveness analysis was performed to compare early treatment of RA using a Markov model. The model allowed us to estimate long term efficacy of RA treatment based on data from the literature and expert opinion, and to combine this data with costs of managing RA in Spain. The perspective of the study was from the National Health System point of view, using a time horizon of 5 years and patient lifetime. All costs were expressed in 2009 euros and a 3% discount rate was applied.ResultsThe cost (only pharmacologic costs) per quality-adjusted life year (QALY) gained with Metoject^® went from 25,173 to 35,807 € at 5 years and from 19,056 to 25,351 € for patient lifetime. When direct costs in RA treatment were considered, it was observed that cost-effectiveness at 5 years went from 29,682 to 42,175 €/QALY gained, and for patient lifetime from 22,514 to 29,848 €/ QALY gained.ConclusionsAdditional costs of Metoject^® with respect to oral methotrexate would be offset by their improved effectiveness, expressed in QALY, showing that Metoject^® could be a cost-effective treatment option for RA in the Spanish Health System assuming a spanish threshold.     

Changes in serum lipid profiles caused by three regimens of interferon‐free direct‐acting antivirals for patients infected with hepatitis C virus

Aim

Serum low‐density lipoprotein cholesterol (LDL‐C) increases during treatment of chronic hepatitis C (CHC) with interferon‐free direct‐acting antivirals (DAAs). We sought to compare the changes of serum lipid profiles caused by three regimens.

Methods

A total of 216 CHC patients were enrolled. Among 170 patients infected with hepatitis C virus (HCV) genotype 1b, 85 received daclatasvir plus asunaprevir (DCV/ASV) and 85 received sofosbuvir plus ledipasvir (SOF/LDV). Forty‐six infected with HCV genotype 2 received sofosbuvir plus ribavirin (SOF/RBV). Serum total cholesterol (TC), LDL‐C, high‐density lipoprotein cholesterol, and triglyceride were measured at baseline and 4, 8, 12 (for all regimens), and 24 weeks (for DCV/ASV) during treatment (4w, 8w, 12w, and 24w, respectively) and 12 and 24 weeks after treatment (p12w and p24w, respectively).

Results

In 69 (81.2%) patients who received DCV/ASV and achieved a sustained virologic response at 24 weeks after the end of treatment (SVR24), TC and LDL‐C increased significantly from baseline to p24w. In 84 (98.8%) treated with SOF/LDV who achieved SVR24, TC and LDL‐C increased significantly from baseline to 8w, and TC decreased significantly from 8w to p12w. The 45 (97.8%) who received SOF/RBV and achieved SVR24 showed no significant changes. At 12w, TC and LDL‐C increased to a greater degree in patients receiving SOF/LDV than in those receiving DCV/ASV or SOF/RBV.

Conclusion

During treatment with DAAs, the serum lipid profile may reflect not only recovery from the disruption of lipid metabolism induced by HCV, but also the pharmacological effects of DAAs. Further investigations are needed to elucidate the effect of DAAs on serum lipid profiles.     

SVR 24 Achievement Two Weeks After a Tripled Dose of Daclatasvir in an HCV Genotype 3 Patient

Directly-acting antivirals (DAA) have changed the chronic hepatitis C virus (HCV) infection therapeutic scenario allowing virus eradication in more than 95% of patients, independently from the genotype, with 12 to 24-week treatment regimens. We describe a 51-year-old Pakistani man with a chronic HCV-genotype 3 (GT3a) infection with moderate liver fibrosis, who achieved sustained virological response (SVR) 24 after a tripled dose of Daclatasvir (DCV) taken erroneously associated to Sofosbuvir (SOF). The patient had a concomitant intestinal TB infection whose treatment had been delayed in order to firstly eradicate HCV to reduce the liver toxicity of anti-mycobacterial drugs. Thanks to the cultural mediator support, we explained to the patient the correct posology of each drug to take during the day consisting of 12 week SOF (400 mg daily) plus DCV (60 mg daily) regimen. He returned 13 days after for a programmed visit and we were surprised to learn that he had taken 3 pills of DCV (180 mg/daily) instead of one, thus ending DCV assumption after only 9 days while SOF was taken correctly. He complained no symptoms. We immediately performed blood test that showed alteration of lactate dehydrogenase, creatine phosphokinase, and creatin kinase MB activity. At day 15 we stopped SOF closely monitoring the patient. Blood test alterations returned normal after one week of treatment suspension, HCV viremia remained suppressed after 4, 12 and 24 weeks proving HCV eradication. If confirmed, these data could suggest that higher doses of DCV, if tolerated, might be employed in short-time HCV-GT3 treatment.     

High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study

ABSTRACT

Aim: Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment.

Methods: Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point.

Results: We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis.

Conclusion: SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.     

Hepatitis C virus genotype 3: Meta-analysis on sustained virologic response rates with currently available treatment options

AIM: To address the therapeutic efficacy of various treatment regimens in genotype 3 selecting randomized clinical trials and prospective National Cohort Studies.METHODS:(1) PEG-INF-based therapy including sofosbuvir(SOF) + RBV for 12 wk vs SOF + RBV 24 wk;(2) SOF + RBV therapy 12 wk/16 wk vs 24 wk; and(3) the role of RBV in SOF + daclatasvir(DCV) and SOF + ledipasvir(LDV) combinations. This metaanalysis provides robust information with the intention of addressing treatment strategy for hepatitis C virus genotype 3.RESULTS: A combination treatment including SOF + RBV + PEG-IFN for 12 wk notes better SVR than with only SOF + RBV for 12 wk, although its association with more frequent adverse effects may be a limiting factor. Longer duration therapy with SOF + RBV(24 wk) has achieved higher SVR rates than shorter durations(12 or 16 wk). SOF + LDV are not an ideal treatment for genotype 3. CONCLUSION: Lastly, SOF + DCV combination is probably the best oral therapy option and the addition of RBV does not appear to be needed to increase SVR rates substantially.     

High sustained virologic response in genotypes 3 and 6 with generic NS5A inhibitor and sofosbuvir regimens in chronic HCV in myanmar

Exclusive HCV therapy clinical trials with genotype 6 patients in high prevalence areas have been sparse. We analysed the safety and efficacy of two generic, pangenotypic NS5A/NS5B combination oral DAA regimens, primarily in genotypes 3 and 6, in a real‐world setting: (a) daclatasvir/sofosbuvir (DCV/SOF) ± ribavirin (RBV) and (b) Velpatasvir/sofosbuvir (VEL/SOF ± RBV). Between December 2015 and November 2017, data from 522 patients were analysed, 311 of whom were treated with DCV/SOF ± RBV for 12/24 weeks (genotype 3: n = 193, genotype 6: n = 89) and 211 were treated with VEL/SOF ± RBV for 12/24 weeks (genotype 3: n = 83, genotype 6: n = 77). Overall SVR rates were high for both DCV/SOF ± RBV (96.1%, n = 299/311) and VEL/SOF ± RBV (95.3%, n = 201/211), and there was a good adverse event profile. Treatment naïve status and inclusion of RBV (in advanced fibrosis/cirrhosis) were significant independent predictors of achieving SVR12, while type of DAA regimen was not predictive. In this large cohort of genotypes 3 (n = 276) and 6 (n = 166; n = 127 unique subtype of 6c‐l), high SVR rates of 94.9% (n = 262/276) and 95.2% (n = 158/166), respectively, were noted. In conclusion, generic and pangenotypic DCV/SOF and VEL/SOF ± RBV regimens were highly effective and safe, in genotypes 3 and 6 chronic HCV in Myanmar. These efficacious pangenotypic regimens suggest that baseline genotype testing can be eliminated moving forward. While RBV may still be needed for those with advanced fibrosis/cirrhosis, in a global elimination strategy it would not be practical even if it does compromise SVR in a minority with difficult to treat characteristics.     

An economic evaluation of pregabalin versus usual care in the management of community-treated patients with refractory painful diabetic peripheral neuropathy in primary care settings

ObjectiveTo estimate the cost-effectiveness of pregabalin versus usual care (UC) in the management of community-treated patients with refractory painful diabetic peripheral neuropathy (pDPN) in primary care settings (PCS) in Spain.MethodsData was extracted from a 12-week registry study assessing costs of neuropathic pain in Spain. Pregabalin-naïve outpatients treated with UC or newly prescribed pregabalin were selected for inclusion in the cost-effectiveness analysis. Effectiveness was expressed as quality-adjusted life years (QALY) gain. Perspectives of the Spanish National Health System (NHS) and society (2006) were applied for cost calculations. Results were expressed as incremental cost-effectiveness ratio (ICER). Bootstrapping techniques (10,000 re-samples) were used to obtain the probabilistic ICER and the cost-effectiveness acceptability curve.ResultsA total of 189 patients were included in the economic analysis. Compared with UC, pregabalin was associated with higher QALY gain in a period of 12-weeks; 0.0406 ± 0.0343 versus 0.0285 ± 0.0350 (p = 0.167). Overall total costs (€1368 ± 1229 vs. €1258 ± 1474; p = 0.587) and healthcare costs (€628 ± 590 vs. €469 ± 420; p = 0.134) were similar for both pregabalin and UC, respectively. ICERs for pregabalin varied from €5302 (95% CI: dominant; €144,105) for total costs to €14,381 (dominant; €115,648) for healthcare costs. Probabilistic sensitivity analyses showed that 79–84% of ICERs were below the threshold of €30,000/QALY.ConclusionThis study suggests that pregabalin may be cost-effective in the management of community-treated refractory outpatients, with pDPN when compared with usual care in the primary care setting in Spain. These findings may help policy makers when making health decision in the management of diabetes in the community.     

Cost-utility analysis of second-generation direct-acting antivirals for hepatitis C: a systematic review

ABSTRACT

Introduction: High prices of second-generation direct-acting antivirals (DAAs) in the treatment of chronic hepatitis C virus (HCV) patients led to reimbursement decisions based on cost per quality-adjusted life year (QALY).

Areas covered: We performed a systematic review of cost-utility analyses (CUA) comparing interventions with second-generation DAA therapies with no treatment, and with previous therapies for chronic HCV patients until July 2017. A total of 36 studies were included: 30 studies from the perspective of the healthcare payer, 3 from the societal perspective, and 3 did not report the perspective. For genotype 1, the highest number of ICER comparison corresponds to sofosbuvir (SOF) triple therapy and SOF-based combinations which reported a cost per QALY systematically ranging from negative to lower than US$100,000 when compared with no treatment or dual therapy or Simeprevir triple therapy.

Expert commentary: Selected studies may be overestimating the true cost per QALY of second-generation DAAs in the treatment of HCV, mainly because of neglecting non-healthcare costs, using official list prices which are higher than actual transaction prices and not adopting the long run drug price in a dynamic approach. In addition, the impact of important price reductions of several DAAs in recent years on cost per QALY should be considered.