Paritaprevir/ritonavir, Ombitasvir, And Dasabuvir Research Articles

Drug-Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral PrOD Combination Regimen of Paritaprevir/Ritonavir-Ombitasvir and Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or Cirrhosis.

The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir-ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated. Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD. The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration-time curve from time 0-12 hours (AUC0-12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed. Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.

Long-term Risk of Hepatocellular Carcinoma Following Direct-Acting Antiviral Therapy in Compensated Liver Cirrhosis Induced by Hepatitis C Virus Infection

Background: Considering the excellent safety profile and the high efficacy rates, great benefits were expected with the availability of the new direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV) infection. Following the publication of two articles in 2016 on the high incidence rates of hepatocelullar carcinoma (HCC) following DAAs, several papers revealed contradictory results, thereby casting shadows on the role of DAAs in hepatocarcinogenesis. Objectives: The present study aimed to assess the incidence and risk factors of HCC in patients with HCV genotype 1b infection and compensated cirrhosis with the sustained virological response (SVR) following DAAs. Methods: This multicentric prospective study encompassed 479 patients with HCV genotype 1b compensated cirrhosis treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) +/- ribavirin (RBV) for 12 weeks in two tertiary centers in Northeastern Romania. The patients were prospectively followed up in the Institute of Gastroenterology Iasi, Romania, from November 2015 to December 2020. Results: During the follow-up period (mean 60.11 ± 3.87 months), 23 patients (4.8%) developed HCC. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 1.1, 1.9, and 2.6%, respectively. At the time of the diagnosis, 15 patients (65%) had a single tumor, 12 patients (52.2%) were within the Milan criteria, and nine persons (39%) had Barcelona liver cancer stage 0-A. In this regard, the mean AFP level was 35.3 ± 93.1 ng/mL. A multivariate analysis, age above 65 years, and a cutoff point of AFP ≥ 10 ng/mL at the end of treatment were independent factors associated with HCC. A majority of the patients (n = 11, 47.8%) received curative treatment by surgical resection. In this study, histopathological examination identified a moderately differentiated tumor (G2) in 5 patients, five patients had a poorly differentiated tumor (G3), and only one patient had a well-differentiated tumor (G1). Conclusions: Our study revealed no evidence of the high incidence rate of HCC after the long-term follow-up of patients with HCV-related liver cirrhosis and SVR following DAA treatment. However, the cumulative 5-year risk remained above the cutoff point, and this makes the HCC screening cost-effective. The HCC occurrence appears to be associated with aging and a moderately increased AFP level at EOT (≥ 10 ng/mL).

HBsAg Loss Due to Tenofovir Treatment for HBV Reactivation Following DAAs Therapy in One Patient with HBV-HCV Coinfection

Abstract Hepatitis B virus (HBV) reactivation induced by administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported in previous studies, the subsequent clinical outcomes varied from no symptom to liver failure or death, however, the timing of anti-HBV treatment is controversial. We report the clinical HBV reactivation in a 51 years old female fibrotic patient with chronic HBV-HCV infection during the paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) therapy. Her baseline HCV RNA, HBV DNA, alanine aminotransferase (ALT), and liver stiffness measurement levels were 5,560,000 IU/mL, <15 IU/mL, 48 U/L, and 11.8 kPa, respectively. At 8 weeks of PrOD treatment, her HCV RNA, HBV DNA, and ALT levels were <15 IU/mL, 2,880,000 IU/mL, and 837 U/L, respectively, and clinical reactivation was diagnosed. Meanwhile, tenofovir was immediately used for anti-HBV treatment. Fortunately, HBV DNA and ALT were undetectable and normalized after 16 weeks of anti-HBV therapy, and unexpectedly, hepatitis B surface antigen loss occurred at 80 weeks of anti-HBV treatment. This study may extend our understanding of the timing of anti-HBV therapy to prevent potential HBV reactivation during DAAs treatment in HBV-HCV coinfected patients, and proper initiation timing may lead to functional cure of chronic HBV infection.

The risks of hepatocellular carcinoma and variceal bleeding after HCV eradication with direct-acting antiviral therapy: a propensity score analysis

The combination paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD), which achieves a high sustained virologic response (SVR) rate and few side effects, has dramatically changed the outcome of hepatitis C virus (HCV) infection. The risk of hepatocellular carcinoma (HCC) and variceal bleeding in patients treated with interferon (IFN)-free direct-acting antivirals (DAAs) is unknown. The aim of this prospective study was to evaluate the rate of HCC and variceal bleeding and identify prognostic factors for decompensation/complications in HCV-1b-infected patients with compensated liver cirrhosis following treatment with PrOD with or without ribavirin. Material and methods: A total of 483 HCV patients received PrOD treatment. Patients with a history of HCC were excluded from the study. Prior antiviral therapy was identified in 59% of patients. Patient data were collected at baseline, at the end of treatment (EoT), at 3 months after EOT (SVR) and during an 18-month surveillance period. Patients were divided into two age groups: <60 years (233 patients) and ≥60 years (250 patients). Results: The median observation period was 540 days. During this period, HCC developed in 18 patients (3.7%) and variceal bleeding developed in 9 patients (1.9%). A Propensity score matching analysis found no significant difference in the incidence of HCC (p= 0.078) or variceal bleeding (p=0.426) between the two groups. The mean serum AFP levels decreased in the young group (baseline=19.44 ng/dL, SVR=4.57 ng/dL) and the elderly group (baseline=4.52 ng/dL, SVR=10.69 ng/dL). Edge of decompensation and previous esophageal varices were significantly associated with the risk of variceal bleeding. Conclusions: The risk of HCC (5.3%) and variceal bleeding (2%) development in elderly patients (≥60years) following viral eradication by IFN-free DAA therapy may follow a specific pattern.

Precipitating factors causing hyperbilirubinemia during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir.

Hepatic decompensation is a fatal on-treatment side effect during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Prompt bilirubin testing can reveal hepatic failure in susceptible patients, and clinical parameters precipitating early elevation of bilirubin can warn clinicians to avoid PrOD prescription. This retrospective study included 169 Hepatitis C virus (HCV)-genotype 1b patients who underwent a 12-week course of PrOD with or without ribavirin. Laboratory data underwent χ analysis with Fisher's exact test to determine the precipitating factors causing hyperbilirubinemia in patients who had received 1 week of treatment. Sustained viral response was achieved in 164 patients (97.0%). Total bilirubin was ≥2 mg/dL (21.3%) in 36 patients after 1 week of treatment. Pretreatment white blood cell (WBC) <4500/µL and platelet <100,000/µL correlated with total bilirubin ≥2 mg/dL (relative risk [RR]: 21.64, 95% CI: 5.23-89.64, p < 0.001) after 1 week of treatment. Pretreatment platelet ≥100 000/µL and WBC <4500/µL correlated with direct bilirubin ≥0.45 mg/dL (RR: 6.56, 95% CI: 1.42-30.38, p = 0.016) and indirect bilirubin ≥0.6 mg/dL (RR: 4.77, 95% CI: 1.03-22.15, p = 0.046). Pretreatment platelet <100,000/µL with F3/F4 fibrosis correlated with first week total bilirubin ≥2 mg/dL (RR: 3.57, 95% CI: 1.35-9.09, p = 0.010). PrOD is an effective antiviral regimen for HCV genotype 1b patients. Total bilirubin ≥2 mg/dL after 1 week of treatment serves as an early warning of irreversible progression toward hepatic decompensation, and the current study provides a guide by which to monitor chronic hepatitis C patients undergoing PrOD treatment.

Clinical utility of hepatitis C virus core antigen assay in the monitoring of direct-acting antivirals for chronic hepatitis C.

BackgroundHepatitis C virus core antigen (HCV Ag) assay has been proposed as a more economical alternative to HCV RNA detection. This study aimed to investigate the clinical utility of HCV Ag assay in the monitoring of direct-acting antivirals (DAAs) for chronic hepatitis C patients.MethodsWe analyzed serum samples from 110 patients treated with paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin. The levels for both HCV Ag and HCV RNA assessed by COBAS TaqMan HCV (CTM) Test or Abbott RealTime HCV (ART) assay were evaluated at baseline, week 2, 4, and 12 during treatment and 12 weeks after completion.ResultsBaseline HCV Ag levels showed good correlations with HCV viral load (r = 0.879; p<0.001); whereas the correlation was slightly stronger with CTM test than with ART assay (p = 0.074). The concordance of HCV Ag and HCV RNA undetectability was significantly better in CTM test than in ART assay at week 2 (p = 0.003) and week 4 (p = 0.003). A sustained viral response 12 weeks off therapy (SVR12) was achieved in 108 patients (98%); the HCV Ag assay identified 99% of these patients. Both undetectability of serum HCV Ag and HCV RNA had high positive predictive value at week 2 (98% vs. 100%) and at week 4 (97% vs. 99%) in predicting SVR12.ConclusionsHCV Ag assay may be a feasible alternative to HCV RNA for the determination of SVR12 in patients treated with DAAs.

Real-world safety and efficacy of paritaprevir/ritonavir/ombitasvir plus dasabuvir\u2009\xb1\u2009ribavirin in patients with hepatitis C virus genotype 1 and advanced hepatic fibrosis or compensated cirrhosis: a multicenter pooled analysis

Paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin shows favorable results in hepatitis C virus genotype 1 (HCV-1) patients in terms of safety and efficacy, but real-world data remain limited for those with advanced hepatic fibrosis (fibrosis 3, F3) or compensated cirrhosis (F4). A total of 941 patients treated in four hospitals (the Keelung, the Linkuo, the Chiayi and the Kaohsiung Chang Gung Memorial Hospital) through a nationwide government-funded program in Taiwan were enrolled. Patients with HCV and advanced hepatic fibrosis or compensated cirrhosis received 12 weeks of PrOD in HCV-1b and 12 or 24 weeks of PrOD plus ribavirin therapy in HCV-1a without or with cirrhosis. Advanced hepatic fibrosis or compensated cirrhosis was confirmed by either ultrasonography, fibrosis index based on 4 factors (FIB-4) test, or transient elastography/acoustic radiation force impulse (ARFI). The safety and efficacy (sustained virologic response 12 weeks off therapy, SVR12) were evaluated. An SVR12 was achieved in 887 of 898 (98.8%) patients based on the per-protocol analysis (subjects receiving ≥1 dose of any study medication and HCV RNA data available at post-treatment week 12). Child-Pugh A6 (odds ratio: 0.168; 95% confidence interval (CI): 0.043–0.659, p = 0.011) was the only significant factor of poor SVR12. Fifty-four (5.7%) patients were withdrawn early from the treatment because of hepatic decompensation (n = 18, 1.9%) and other adverse reactions. Multivariate analyses identified old age (odds ratio: 1.062; 95% CI: 1.008–1.119, p = 0.024) and Child-Pugh A6 (odds ratio: 4.957; 95% CI: 1.691–14.528, p = 0.004) were significantly associated with hepatic decompensation. In conclusion, this large real-world cohort proved PrOD with or without ribavirin to be highly effective in chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis. However, Child-Pugh A6 should be an exclusion criterion for first-line treatment in these patients.

A 12-week rescue therapy by PrOD-based regimen for advanced fibrotic genotype-1 CHC patients who failed to pegylated interferon plus ribavirin

Treatment of chronic hepatitis C (CHC) evolved rapidly due to the invention of interferon-free direct antiviral agents. Previous clinical trials showed combination therapy with paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin (RBV) can cure over 95% of genotype 1 CHC patients, regardless with cirrhosis or not. However, real-world data regarding the efficacy and safety of PrOD-based therapy in Asian HCV genotype 1 CHC patients are limited, especially for advanced-fibrotic patients who failed previous therapy with pegylated interferon (PEG-IFN) plus RBV. Between January and October 2017, 60 advanced fibrotic (≥F3) genotype 1 CHC patients who failed previous therapy with PEG-IFN and received PrOD-based therapy for 12 weeks were retrospectively enrolled. Weight-based RBV 800 to 1200 mg/d was added for genotype 1b patients with cirrhosis and all genotype 1a patients. Sustained virological response (SVR) was defined by undetectable HCV RNA at the end and 12 weeks after the completion of therapy. The mean age was 63.2 ± 9.3 years, 26 (43.3%) of them were males and 20 (33.3%) were diagnosed to have liver cirrhosis. The mean baseline HCV RNA level was 6.19 ± 0.88 log10 IU/mL and 86.7% (52/60) of patients were infected by HCV genotype 1b. After PrOD-based therapy, the rates undetectable HCV RNA (<15 IU/mL) at week 2, 4, and 12 were 61.7%, 90.0%, and 100%, respectively; 69.6% (16/23) of patients with detectable HCV RNA at week 2 were < 100 IU/mL. Pruritus, fatigue, headache, insomnia, and dizziness were the most common patient-reported adverse events. Grade 2 hyperbilirubinemia were found in 21.6% (13/60) of patients during study period and all belonged to unconjugated hyperbilirubinemia. After posttherapy follow up, all 60 patients (100%) achieved SVR. Our real-world data in Taiwan revealed that PrOD-based rescue therapy is well-tolerated and highly effective for genotype 1 CHC patients with advanced fibrosis failing previous therapy with PEG-IFN plus RBV.

Hepatic decompensation during paritaprevir/ritonavir/ombitasvir/dasabuvir treatment for genotype 1b chronic hepatitis C patients with advanced fibrosis and compensated cirrhosis.

Background and aimHepatic decompensation is a severe on-treatment adverse event for chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Till now, few papers regarding on-treatment hepatic decompensation have been reported. The study aims to analyze the general feature and predictive factors of on-treatment hepatic decompensation in hepatitis C virus (HCV) genotype 1b-infected patients with advanced fibrosis and compensated cirrhosis who receive treatment with PrOD.MethodsA real-word cohort enrolled 189 HCV genotype 1b patients with advanced fibrosis and compensated cirrhosis treated with 12-week PrOD. Clinical and laboratory data were analyzed between patients with and without on-treatment hepatic decompensation.ResultsThe sustained virologic response rate at 12 weeks after treatment was 97.3% in HCV subtype 1b patients with advanced fibrosis and cirrhosis. On-treatment hyperbilirubinemia (total bilirubin >2 mg/dL) occurred in 27 (14.3%) patients, and the incidence of the increase of total and direct form bilirubin was significantly different during treatment between patients with Child-Turcotte-Pugh score 5 and score 6. Five (18.5%) hyperbilirubinemia patients progressed to hepatic decompensation. Older age (adjusted OR: 1.2, 95% CI: 1.0–1.4) and albumin ≤3.6 g/dL (adjusted OR: 10.4, 95% CI: 1.3–81.2) may be two predictors for on-treatment hepatic decompensation by multivariate analysis.ConclusionsPrOD is an effective direct-acting antiviral agent for antiviral therapy in HCV genotype 1b patients with advanced fibrosis and cirrhosis. Hyperbilirubinemia is possibly the early warning feature of on-treatment hepatic decompensation. This serious adverse event of on-treatment hepatic decompensation is not common. Older age and low baseline albumin level may be predictive factors.

Real‐world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for patients with chronic hepatitis C virus genotype 1b infection in Taiwan

The real-world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) remain limited for East Asian hepatitis C virus genotype 1b (HCV-1b) patients. The study aimed to evaluate the antiviral responses of PrOD-based regimens for HCV-1b patients in Taiwan. The study performed a retrospective analysis of 103 HCV-1b patients receiving PrOD with or without ribavirin (RBV) for 12weeks. Data were analyzed to assess the on-treatment and off-therapy HCV viral load and on-treatment adverse events. The pre-specified characteristics related to sustained virologic response 12weeks off therapy (SVR12 ) were compared. At treatment week 4, 100 of 102 patients (98.0%) had serum HCV RNA level <25IU/mL. The SVR12 was achieved in 101 of 103 patients (98.1%, [95% confidence interval: 93.2-99.5%]). All except one (99.0%) patients tolerated treatment well without treatment interruption. One cirrhotic patient discontinued treatment at week 1 due to hepatic decompensation. Twenty-four patients (23.3%) had ≥ grade 2 elevation in total bilirubin levels, and 21 of them (87.5%) had indirect type hyperbilirubinemia. The stratified SVR12 rates were comparable in terms of sex, age, body mass index, prior treatment experience, hepatitis B virus surface antigen status, RBV usage, baseline and week 2 viral load, renal function, and hepatic fibrosis stage. Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without RBV are efficacious and generally well tolerated for treatment of HCV-1b patients in Taiwan.

Efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with ribavirin for the treatment of HCV genotype 1b compensated cirrhosis in patients aged 70 years or older.

Advanced age has been a major limitation of interferon-based treatment for chronic hepatitis C virus (HCV) infection because of its poor response and tolerability. Direct-acting antiviral (DAA) drug regimens are safe and highly effective, allowing administration of treatment also in elderly. This study aims to assess the efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with ribavirin for the treatment of patients aged ≥70 years with HCV genotype 1b compensated cirrhosis.A total of 1008 patients with HCV genotype 1b compensated cirrhosis were prospectively treated with PrOD + ribavirin for 12 weeks, between December 2015 and July 2016. Sustained virologic response 12 weeks after the end of treatment (SVR12), adverse effects (AEs), comorbidities, discontinuation, and death rates were recorded. Efficacy and safety of therapy were assessed in patients aged ≥70 years and compared with data from patients <70 years.There were 117 patients aged ≥70 years, preponderantly females (58.9%), mean age 73.3 ± 2.8 years (range 70–82), and 37 (31.6%) were treatment-experienced. Comorbidities were reported in 60.6% of patients ≥70 years and in 39.8% of those <70 years (P < .001). SVR12 rates based on intention-to-treat and per-protocol analyses were 97.4% and 100%, respectively, in patients ≥70 years, compared to 97.8% and 99.6%, respectively, in patients <70 years (P = ns and P = ns). Severe AEs were reported in 4 (3.4%) patients ≥70 years, compared to 23 (2.6%) in those <70 years (P = ns). One death was recorded in a patient aged 79 years (0.9%) and 6 deaths (0.8%) in those <70 years (P = ns).Treatment with PrOD + ribavirin in patients 70 years of age or older with HCV genotype 1b compensated cirrhosis proved as effective, safe, and well tolerated, as it did in younger patients.

The effect of curing hepatitis C with direct-acting antiviral treatment on endothelial function.

Epidemiological data suggest that chronic HCV infection (CHC) is associated with increased cardiovascular risk, but it is unknown if it is associated with endothelial dysfunction. We aimed to assess the effect of antiviral treatment on endothelial function in non-cirrhotic adults with CHC. Self-controlled before and after study. All patients had genotype-1 CHC and were treated with 12 weeks of paritaprevir/ritonavir, ombitasvir and dasabuvir (PrOD), with ribavirin added for those with genotype-1a infection. Endothelial function was assessed at three time points before antiviral treatment, at treatment weeks 1, 4, 8 and 12, and 12 weeks after the end of treatment. The main assessment tools were reactive hyperaemia peripheral arterial tonometry (RHPAT) and serum concentrations of angiopoietin-2 (Ang-2) and E-selectin. A total of 16 patients were enrolled. Mean (sd) age was 51.4 (6.9) years and 11 participants (69%) were male. All 16 patients achieved a sustained virological response. The mean (sd) baseline RHPAT index was 2.05 (0.48), and there was no significant change during treatment (mean within-patient change from baseline to end of treatment =-0.23 [0.45]; P= not significant). There was a significant improvement in both mean Ang-2 (baseline 2.44 [0.79] ng/ml, within-patient change -0.60 [0.44]; P<0.001) and E-selectin (baseline 48.7 [21.5] ng/ml, within-patient change -14.4 [13.0]; P<0.001). Removing HCV viraemia is associated with a significant improvement in endothelial function as measured by serum markers, but not in bedside microvascular reactivity. Chronic HCV viraemia may be associated with endothelial cell dysfunction and therefore long-term cardiovascular risk.

Real-life efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir in chronic hepatitis C patients in Hong Kong.

In registration studies, combination therapy of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with and without ribavirin for 12-24weeks can achieve >90% sustained virological response (SVR) for genotype 1 hepatitis C virus (HCV) infection. However, data in Asia is scanty. We aimed to study the efficacy and safety of this combination therapy in chronic hepatitis C patients in Hong Kong. We retrospectively analyzed data from six local hospitals that have prescribed PrOD with and without ribavirin to patients with genotype 1 chronic HCV infection as part of a global compassionate program. Among 41 patients treated, 35 (85%) patients had genotype 1b HCV infection, 6 (15%) had co-infection with human immunodeficiency virus, 35 (85%) failed previous peginterferon and ribavirin therapy, 25 (61%) had compensated liver cirrhosis, and 3 (7%) had liver transplantation. Thirty-five (85%) patients received 12-week treatment and six patients received 24-week treatment; 26 (63%) patients received ribavirin combination. Thirty-nine (95%; 95% confidence interval 88.5-100%) patients had undetectable HCV RNA at 12-week post-treatment, that is, SVR. The two patients who did not develop SVR discontinued treatment prematurely; both of them were treatment experienced with liver cirrhosis complicated by acute renal failure unrelated to the treatment of PrOD and ribavirin. No patient had hepatic decompensation. Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin is effective and safe in patients with genotype 1 HCV infection in real-life clinical setting in Hong Kong.

Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the Veterans Affairs National Health Care System

We investigated the real-world effectiveness of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) in treatment of different subgroups of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, or4. We performed a retrospective analysis of data from 17,487 patients with HCV infection (13,974 with HCV genotype 1; 2131 with genotype 2; 1237 with genotype 3; and 135 with genotype 4) who began treatment with sofosbuvir (n= 2986), ledipasvir/sofosbuvir (n= 11,327), or PrOD (n= 3174), with or without ribavirin, from January 1, 2014 through June 20, 2015 in the Veterans Affairs health care system. Data through April 15, 2016 were analyzed to assess completion of treatments and sustained virologic response 12 weeks after treatment (SVR12). Mean age of patients was 61 ± 7 years, 97% were male, 52% were non-Hispanic white, 29% were non-Hispanic black, 32% had a diagnosis of cirrhosis (9.9% with decompensated cirrhosis), 36% had a Fibrosis-4 index score >3.25 (indicator of cirrhosis), and 29% had received prior antiviral treatment. An SVR12 was achieved by 92.8% (95% confidence interval [CI], 92.3%-93.2%) of subjects with HCV genotype 1 infection (no significant difference between ledipasvir/sofosbuvir and PrOD regimens), 86.2% (95% CI, 84.6%-87.7%) of those with genotype 2 infection (treated with sofosbuvir and ribavirin), 74.8% (95% CI, 72.2%-77.3%) of those with genotype 3 infection (77.9% in patients given ledipasvir/sofosbuvir plus ribavirin, 87.0% in patients given sofosbuvir and pegylated-interferon plus ribavirin, and 70.6% of patients given sofosbuvir plus ribavirin), and 89.6% (95% CI 82.8%-93.9%) of those with genotype 4 infection. Among patients with cirrhosis, 90.6% of patients with HCV genotype 1, 77.3% with HCV genotype 2, 65.7% with HCV genotype 3, and 83.9% with HCV genotype 4 achieved an SVR12. Among previously treated patients, 92.6% with genotype 1; 80.2% with genotype 2; 69.2% with genotype 3; and 93.5% with genotype 4 achieved SVR12. Among treatment-naive patients, 92.8% with genotype 1; 88.0% with genotype 2; 77.5% with genotype 3; and 88.3% with genotype 4 achieved SVR12. Eight-week regimens of ledipasvir/sofosbuvir produced an SVR12 in 94.3% of eligible patients with HCV genotype 1 infection; this regimen was underused. High proportions of patients with HCV infections genotypes 1-4 (ranging from 75% to 93%) in the Veterans Affairs national health care system achieved SVR12, approaching the results reported in clinical trials, especially in patients with genotype 1 infection. An 8-week regimen of ledipasvir/sofosbuvir is effective for eligible patients with HCV genotype 1 infection and could reduce costs. There is substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections.

Paritaprevir/ritonavir/ombitasvir and dasabuvir for the treatment of chronic hepatitis C virus infection

Introduction: The use of direct-acting antiviral (DAA) agents against chronic hepatitis C virus (HCV) infections can result in the successful treatment of nearly all patients. Effective antiviral treatments can prevent the progression to cirrhosis and hepatocellular malignancy, and decrease liver-related morbidity and mortality.Areas covered: Paritaprevir–ritonavir–ombitasvir and dasabuvir (PrOD), with or without ribavirin, is an all-oral regimen approved for the treatment of HCV genotype 1 infections, including patients with compensated cirrhosis. Phase 2 and 3 clinical trials demonstrated the safety and efficacy of this regimen in HCV genotype 1-infected patients who are treatment-naïve and those who have failed peginterferon/ribavirin therapy. Additional studies evaluated the use of PrOD with or without ribavirin among special populations, including patients co-infected with human immunodeficiency virus-1 and HCV, liver transplant recipients with HCV recurrence, and patients with severe renal impairment. Additionally, the combination of paritaprevir-ritonavir-ombitasvir plus ribavirin is found to be highly efficacious, and is now approved in the US, for the treatment of HCV genotype 4 infections.Expert opinion: The availability and use of interferon-free DAA combination regimens has resulted in a major paradigm shift in the treatment of HCV. PrOD, with or without ribavirin, is an effective, safe and tolerable treatment option.