DAA Combination Research Articles

Impact of Direct Acting Antivirals therapy on metabolic profiles and adiponectin serum level in Egyptian patients with chronic hepatitis C infection

Abstract Background and Objectives Hepatitis C Virus (HCV) infection is a major global health challenge. Chronic hepatitis C viral infection is associated with wide metabolic disarrangements. HCV interacts with lipid metabolism leading to steatosis, causing wide adipocytokines changes and impairs glucose metabolism leading to increased prevalence of insulin resistance (IR) and type 2 diabetes. Several oral anti-HCV drugs (direct acting antivirals; DAAs) have been developed over the last several years. Now, HCV can be eliminated from the infected host within 12 weeks of DAA combination therapy. As, there is limited data on the effects of DAA therapy on metabolic profiles, lipid profile and adiponectin level. Hence, this study was carried out to evaluate the Impact of Direct Acting Antivirals therapy on metabolic profiles and adiponectin serum level in Egyptian patients with chronic hepatitis C infection. Methods This study was performed on 100 patients who have chronic infection with hepatitis C, patients were divided into two groups, Group I was 50 patients were treated with (Sofosbuvir/Daclatasvir/Ribavirin) for 3 months. Group II was 50 patients were treated with (Ombitasvir, Paritaprevir, Ritonavir/Ribavirin) for 3 months. With follow up changes were occurred in Fasting Lipid profile (total cholesterol, triglyceride, HDL and LDL), metabolic profile (fasting blood sugar, Fasting Insulin, HOMA-IR and HBA1C) and Serum adiponectin level before and after end of treatment. Results One hundred patients met inclusion criteria were reviewed, (56%) were males in group I while (46%) were males in group I, Mean age in group I was 47.4 ± 5.3 years while in group II was 43.2 ± 6.6 years, statistical analysis of data showed significant difference in the lipid profile in group I before and after treatment .As, we found significant reduction in serum triglycerides after treatment (113.2 ± 22.9 mg/dL vs 105.6 ± 23.2 mg/dL, P < 0.001) and a significant elevation of serum Total Cholesterol, LDL and HDL after treatment (TC: 153.2 ± 20.1 mg/dL vs 174.1 ± 19 mg/dL, P < 0.001, LDL: 74.7 ± 9.9 mg/dL vs 93.3 ± 12 mg/dL, P < 0.001, HDL: 54.6 ± 10.1 mg/dL vs 57.2 ± 10.3 mg/dL, P 0.010) But in group II there was no significant difference in the lipid profile before and after treatment, Also, We found significant reduction in fasting insulin, HOMAIR and HBA1C after treatment in group I (Fasting Insulin: 11.4 ± 3.3 (uU/L)/ml vs 9.7 ± 2.2 (uU/L)/ml, P < 0.001, HOMA-IR: 2.7 ± 0.9 vs 2.2 ± 0.6, P < 0.001, HBA1C: 5.6 ± 0.4 vs 5.4 ± 0.3, P 0.003) But in group II there was no significant difference in fasting insulin, HOMA-IR and HBA1C before and after treatment. Also, we found that there was no significant changes in the serum adiponectin level in the both group before and after treatment. Conclusion Eradication of chronic hepatitis C viral infection with DAAs may affect the lipid and the metabolic profile of patients after the end of treatment according to the type of DAAs used in the treatment and according to the stage of the liver disease of patients. But not affect the serum Adiponectin level.

Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia.

Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.

The outcome of re-treatment of relapsed hepatitis C virus infection in a resource-limited setting.

The aim of this study was to compare efficacy and safety of different combination regimens in re-treatment of HCV in the setting of inaccessibility of resistance testing. This real-life prospective study included 86 chronic HCV infected patients who experienced failure of treatment treated at Faculty of Medicine Ain shams Research Institute (MASRI) since 2018. 64% of the patients were males, with median age 50.2years. They were re-treated using 1 of 3 proposed regimens of DAA combinations. One group received PAR/OMB/SOF/RBV for 12weeks, another group received SOF/DAC/SIM/RBV for 12weeks and a third received SOF/DAC/RBV for 24weeks. Response to different regimens was assessed by comparing sustained virologic response (SVR) of each. Monitoring the occurrence of adverse events was performed. SVR was achieved in all but 3 patients (96.5% SVR), one in the SOF/DAC/SIM/RBV group and two in the SOF/DAC/RBV group. The group receiving RBV had more anaemia and hyperbilirubinemia. The first treatment regimen used was a significant predictor to SVR achievement. This study presents alternative treatment regimens for re-treatment of HCV patients in areas with limited resources in the case of non-availability of other regimens as velpatasvir, voxilaprevir, grazoprevir, elbasvir.

Assessing the impact of a combination of sofosbuvir and daclatasvir treatment for hepatitis C virus infection on heart rate, rhythm and heart rate variability using 24-hour ECG monitoring

BackgroundDirect-acting antiviral agents (DAAs) cure patients with hepatitis C virus (HCV) infection. Concerns have arisen the occurrence of significant bradyarrhythmias during treatment with DAAs. The aim of this study was to assess the impact of a DAA combination for the treatment of HCV infection on heart rate, rhythm, and heart rate variability (HRV) using 24-h ECG monitoring.ResultsA prospective randomized study of 50 treatment-naïve patients with HCV infection treated with a combination of sofosbuvir 400 mg daily and daclatasvir 60 mg daily for 12 weeks. Surface ECG and 24-h ECG monitoring were performed at baseline and after completion of therapy to assess PR interval, corrected QT interval (QTc), minimum heart rate (HR), maximum HR, average HR, HRV time-domain and frequency-domain measures, significant pauses, tachycardias, bradycardias, premature atrial contractions (PACs), and premature ventricular contraction (PVCs).No differences were detected in all examined parameters between baseline and after completion of treatment. PR interval was 154 ± 25.95 vs 151.4 ± 23.82 ms, respectively (p = 0.124). QTc interval was 397.34 ± 29.38 vs 395.04 ± 30.23 ms, respectively (p = 0.403). No differences were detected for minimum HR, maximum HR, average HR, HRV time-domain and frequency-domain measures, the occurrence of significant pauses, sinus tachycardia episodes, sinus bradycardia episodes, PACs, and PVCs. No episodes of bradyarrhythmias, syncope, and atrial fibrillation, supraventricular, or ventricular tachycardias were reported or detected.ConclusionIn non-cardiac patients receiving no cardioactive medications, the combination of sofosbuvir and daclatasvir for the treatment of HCV infection has no effect on HR, rhythm, conductivity, or HRV. No symptomatic bradycardias, tachycardias, or syncope were reported or detected using 24-h ECG monitoring.

Effect of Using Direct Acting Anti-Virals In Treatment of HCV Naive Patient with and without Portal Hypertension

Abstract Background Hepatitis C Virus (HCV) infection is a major global health challenge; it is estimated that more than 80 million people are chronically infected worldwide. Egypt has the highest prevalence of HCV in the world (predominantly genotype 4) secondary to the previous schistosomiasis eradication campaigns with very high incidence rates among elderly, rural areas and in lower social classes. However, several oral anti-HCV drugs (direct acting antivirals; DAAs) have been developed over the last several years. Now, HCV can be eliminated from the infected host within 12 wk of DAA combination therapy without noticeable side effects Aims: to evaluate the Effect of presence of portal hypertension on the results of treatment of chronic HCV infected naive patient with direct acting antivirals Patients and Methods 200 subjects were divided into 2 groups: group I: including 100 cirrhotic patients with HCV infection and portal hypertension, group II: including 100 cirrhotic patients with HCV infection without portal hypertension. Diagnosis of portal hypertension was confirmed by presence of esophageal varices in endoscopy. Both group received combination of IFN-free DAAs. Results CK-18 was significantly elevated in patients of group I in comparison to group 11, with mean ± SD: 460 ± 279, 167 ± 56 and 149 ± 57, respectively, and P value: 0.001. with mean ±SD: 59.6± 28, when compared with control group (with 23±8) P value < 0.001. ROC curve between Cases and Control as regards CK18 with Area Under the Curve (AUC): 0.925. Cutoff > 30 ug/l With Sensitivity: 86.67% & Specificity: 83.33%. Ck-18 was found to be correlated with steatosis and fibrosis assessed by fibroscan with P value< 0.001. Conclusion treatment of 200 patients with HCV and compensated cirrhosis, HCV eradication reduced risk for liver decompensation, regardless of whether the patients had EVs.

From the Editor’s Desk: September 2019

From the Editor’s Desk: September 2019

Viral dynamics among HCV infected patients with different genotypes treated with genotypic specific or pan-genotypic direct-acting antiviral agent combinations.

BackgroundNew hepatitis C virus (HCV) therapies have improved efficacy, allowed pangenotypic applications, increased barriers to drug resistance and shortened therapy duration.MethodsPatients infected with different HCV genotypes were divided into two groups: group 1 included 169 patients receiving genotypic specific regimens (GSR), while group 2 included 186 patients receiving pan-genotypic regimens (PGR). Patient’s HCV RNA was quantified and sequenced.ResultsComparable sustained viral response (SVR) rates were observed in both GSR and PGR treated patients. Nevertheless, even if not significant, a greater proportion of non-detectable levels (NDL) of HCV RNA was observed in patients treated with PGR as compared with GSR. Overall, among patients in the GSR and PGR groups with residual viremia, 124/169 (73.4%) and 125/186 (67.2%) at four weeks, and 66/169 (39.1%) and 58/186 (31.2%) at eight weeks, achieved SVR. No difference was observed in the clinical outcome comparing patients in the GSR and PGR groups according to genotype. While, comparing patients between the two groups, the proportion of patients with NDL HCV RNA at four and eight weeks was higher in patients infected with genotype 1b treated with PGR (p=0.0015). A significantly higher number of patients infected with 1b had RASs at baseline (p=0.0001). In addition, the proportion of patients with treatment failure was higher in patients with RASs at baseline compared with those without (p=0.012). Overall, 2.5% patients failed to achieve SVR after DAA treatment.ConclusionA sharp HCV RNA decrease was observed in patients treated with both GSR and PGR. However, even if comparable, a slightly greater number of patients treated with PGR achieved NDL HCV RNA as compared with GSR. A significant difference was observed in patients with baseline RASs, both in relation to treatment failure and genotype. In conclusion, the use of new DAA combinations helps patients achieve a more rapid virologic response.

A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety

BackgroundDirect-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems.Case presentationA 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved.ConclusionsAlthough DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.

Evolution of HCV patient characteristics and DAA regimens in the German Hepatitis C Registry (DHC-R) in 2014 and 2015.

The urgent need in HCV-infected patients with liver disease mandated the rapid implementation of IFN-free DAA combination therapies following their regulatory approval in 2014 and 2015 without full knowledge of the optimal combinations and regimens. Investigating the evolution of the DAA utilization patterns and treatment outcomes could provide learnings for future situations. This was an analysis of a prospective observational database from the German Hepatitis C Registry (DHC-R) covering a period from May 2014 to September 2015. Adult patients had evidence of chronic HCV GT1 or GT4 infection and were treated with an IFN-free combination regimen of simeprevir (SMV) + sofosbuvir (SOF) or other IFN-free regimens: daclatasvir + sofosbuvir (DCV + SOF), ledipasvir/sofosbuvir (SOF/LDV), paritaprevir/r + ombitasvir ± dasabuvir (PrOD), with or without ribavirine (R). A total of 5496 subjects were followed during the period. During this period, clinical recommendations and treatment patterns evolved rapidly in response to new evidence from clinical trials and clinical routine and regulatory approval of additional regimens. High SVR12 rates were seen in this cohort, even in hard-to-treat patient subgroups. In the multivariate analysis, gender, age, advanced cirrhosis, and intensified treatment for cirrhotics were associated with treatment outcome. Despite limited knowledge of the optimal utilization of the newly approved DAA combinations and treatment durations as well as their comparative efficacy and safety profiles, high SVR rates were achieved regardless of the DAA combination. These outcomes were facilitated by the rapid adaptation of clinical recommendations. Future situations with high unmet medical need may follow a similar approach.

Letter: Management of patients with chronic hepatitis C failing repeated courses of interferon‐free DAA combination therapy: a translational research perspective with clinical impact—author's reply

Letter: Management of patients with chronic hepatitis C failing repeated courses of interferon‐free DAA combination therapy: a translational research perspective with clinical impact—author's reply

Letter: management of patients with chronic hepatitis C failing repeated courses of interferon‐free DAA combination therapy: a translational research perspective with clinical impact

Letter: management of patients with chronic hepatitis C failing repeated courses of interferon‐free DAA combination therapy: a translational research perspective with clinical impact

THU-122-Sofosbuvir/velpatasvir ± ribavirin for retreatment of patients with chronic hepatitis C virus infection and advanced fibrosis failing to a previous DAA combination regimen

THU-122-Sofosbuvir/velpatasvir ± ribavirin for retreatment of patients with chronic hepatitis C virus infection and advanced fibrosis failing to a previous DAA combination regimen

Treatment of hepatitis C virus infection with direct-acting antiviral agents: 100% cure?

Around 71 million people are chronically infected with HCV worldwide. HCV antiviral drug development has been remarkable. The availability of pangenotypic direct-acting antivirals with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. IFN-free DAA combinations can now cure HCV in more than 95% of patients with HCV infection after 8-12weeks of treatment. Programmes to eliminate HCV must include increased screening (risk-based and universal), linkage to care, as well as increased access to treatment worldwide. In this paper, we will review the available data on recently approved direct-acting antiviral agents, with sustained virological response that reaches almost 100%.

Long-term follow-up of ribavirin-free DAA-based treatment in HCV recurrence after orthotopic liver transplantation.

Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT. A total of 62 OLT recipients (male: 50%/81%; age: 60.7±8.5years [mean±SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%. Data of at least 96weeks of FUP after treatment cessation (mean: 120; up to 167weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N=1, SVR12: N=3, after SVR96: N=1 respectively). Reasons for death were: multi-organ failure (N=4), impaired graft function (N=1) and unknown (N=1). RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome.

Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response

BackgroundNovel direct-acting antiviral DAA combination therapies tremendously improved sustained virologic response (SVR) rates in patients with chronic HCV infection. SVR is typically accompanied by normalization of liver enzymes, however, hepatic inflammation, i.e. persistently elevated aminotransferase levels may persist despite HCV eradication. Aim: To investigate prevalence and risk factors for ongoing hepatic inflammation after SVR in two large patient cohorts.MethodsThis post-hoc analysis was based on prospectively collected demographic and clinical data from 834 patients with SVR after HCV treatment with either PegIFN- or DAA-based treatment regimens from the PRAMA trial (n = 341) or patients treated at our outpatient clinic (n = 493).ResultsWe observed an unexpected high prevalence of post-SVR inflammation, including patients who received novel IFN-free DAA-based therapies. Up to 10% of patients had ongoing elevation of aminotransferase levels and another 25% showed aminotransferase activity above the so-called healthy range. Several baseline factors were independently associated with post-SVR aminotransferase elevation. Among those, particularly male gender, advanced liver disease and markers for liver steatosis were strongly predictive for persistent ALT elevation. The use of IFN-based antiviral treatment was independently correlated with post-SVR inflammation, further supporting the overall benefit of IFN-free combination regimens.ConclusionThis is the first comprehensive study on a large patient cohort investigating the prevalence and risk factors for ongoing liver inflammation after eradication of HCV. Our data show a high proportion of patients with ongoing hepatic inflammation despite HCV eradication with potential implications for the management of approximately one third of all patients upon SVR.

FRI-260 - Efficacy of therapy against chronic hepatitis C virus genotype 1 infection in HIV-coinfected patients with several interferon-free DAA combinations: real life data from the HEPAVIR-DAA Cohort

FRI-260 - Efficacy of therapy against chronic hepatitis C virus genotype 1 infection in HIV-coinfected patients with several interferon-free DAA combinations: real life data from the HEPAVIR-DAA Cohort

Ultrasensitive HCV RNA Quantification in Antiviral Triple Therapy: New Insight on Viral Clearance Dynamics and Treatment Outcome Predictors.

ObjectivesIdentifying the predictive factors of Sustained Virological Response (SVR) represents an important challenge in new interferon-based DAA therapies. Here, we analyzed the kinetics of antiviral response associated with a triple drug regimen, and the association between negative residual viral load at different time points during treatment.MethodsTwenty-three HCV genotype 1 (GT 1a n = 11; GT1b n = 12) infected patients were included in the study. Linear Discriminant Analysis (LDA) was used to establish possible association between HCV RNA values at days 1 and 4 from start of therapy and SVR. Principal component analysis (PCA) was applied to analyze the correlation between HCV RNA slope and SVR. A ultrasensitive (US) method was established to measure the residual HCV viral load in those samples which resulted “detected <12IU/ml” or undetectable with ABBOTT standard assay, and was retrospectively used on samples collected at different time points to establish its predictive power for SVR.ResultsAccording to LDA, there was no association between SVR and viral kinetics neither at time points earlier than 1 week (days 1 and 4) after therapy initiation nor later. The slopes were not relevant for classifying patients as SVR or no-SVR. No significant differences were observed in the median HCV RNA values at T0 among SVR and no-SVR patients. HCV RNA values with US protocol (LOD 1.2 IU/ml) after 1 month of therapy were considered; the area under the ROC curve was 0.70. Overall, PPV and NPV of undetectable HCV RNA with the US method for SVR was 100% and 46.7%, respectively; sensitivity and specificity were 38.4% and 100% respectively.ConclusionHCV RNA “not detected” by the US method after 1 month of treatment is predictive of SVR in first generation Protease inhibitor (PI)-based triple therapy. The US method could have clinical utility for advanced monitoring of virological response in new interferon based DAA combination regimens.

DAA-based antiviral treatment of patients with chronic hepatitis C in the pre- and postkidney transplantation setting.

DAA-based regimens for chronic hepatitis C infection encourage treatment of "difficult-to-treat" cohorts. This study investigated efficacy and safety of DAA-based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty-five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir-based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV-RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty-four (96%) patients achieved SVR 12/24 (ITT-analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely - both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re-infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient - SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real-life cohorts.

Safety and efficacy of IFN/RBV-free DAA-based regimens in HCV-recurrence after Orthotopic Liver Transplantation

Background & Aim: Interferon-free DAA combinations allow an effective treatment of HCV recurrence after orthotopic liver transplantation (OLT), but the role of ribavirin (RBV) in the post transplant setting is still under debate. So far published data gained from IFN/RBV-free DAA-based regimens are sparse. We thus aimed to analyze safety and efficacy of IFN/RBV-free DAA-based regimens in HCV-recurrence after OLT.

Cost-effectiveness and budget impact of interferon-free direct-acting antiviral-based regimens for hepatitis C treatment: the French case.

We evaluated the cost-effectiveness and the budget impact of new DAA-based regimen use in France. A Markov model simulated chronic hepatitis C (CHC) treatment interventions with IFN-based and IFN-free regimens at stage of fibrosis ≥F3, ≥F2 or regardless of fibrosis stage, and treatment either with the least or the most expensive combination. It estimated quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). It also assessed the budget impact over 5 years of treating all CHC-screened patients, regardless of fibrosis, assuming ≤20 000 patients treated/year and priority to ≥F3. Sensitivity analyses were also conducted. For genotypes (G) 1-4, the initiation of IFN-free regardless of fibrosis was a cost-effective strategy compared to prior standard of care (SOC) initiated at stage F2: €40 400-88 300/QALY gained in G1; similar results were obtained for patients infected with G4. Considering G2-3, the most cost-effective strategy was IFN-based regimens regardless of fibrosis compared to prior SOC initiated at stage F2: €21 300 and €19 400/QALY gained, respectively; the strategy with IFN-free regimens being more effective but not cost-effective at current costs. The budget impact of treating all CHC-screened patients over 5 years would range between 3.5 and 7.2 billion €, depending on whether one considers the least or the most expensive combination of new DAAs and whether one treats G2-3 with IFN-based or IFN-free new DAAs. In France, treatment initiation with new DDAs regardless of fibrosis stage is cost-effective, but would add 3.5-7.2 billion € to an already overburdened medical care system.