BACKGROUND & AIMS The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure. METHODS We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12. RESULTS The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%–98%), 97% receiving the drugs for 12 weeks (95% CI, 96%–98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%–97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%–99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%–99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%–99% vs 98%; 95% CI, 95%–99%). Factors that predicted SVR12 were higher albumin (≤3.5 g/dL), lower total bilirubin (≥1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use. CONCLUSIONS Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.

Background Data outside of clinical trials with direct acting antiviral (DAA) regimens with or without ribavirin as treatment of chronic HCV in solid organ transplant recipients is limited. Methods Liver transplant (LT), kidney transplant (KT) and dual liver kidney (DLK) transplant recipients from the HCV-TARGET database, a multicenter, longitudinal clinical care treatment cohort, treated with DAA regimens between January 1 2014 and February 15, 2016 were included to assess safety and efficacy. Results 443 post-transplant patients were included (KT=60, LT =347, DLK=36); 42% had cirrhosis, 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% G1a, 27% G1b, and 8% G1 no subtype) and were treated with sofosbuvir/ledipasvir (SOF/LDV) ± RBV (85%) followed by sofosbuvir + daclatasvir (SOF + DAC) ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir (PrOD) ± RBV (6%). SVR12 rates were available on 415 patients and 397 patients (95.7%) achieved SVR12: 96.3%, 94.6% and 90.9% among LT, KT and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher eGFR and lower creatinine. Female gender, baseline albumin ≥ 3.5 g/dL, baseline total bilirubin ≤ 1.2 mg/dL, the absence of cirrhosis and hepatic decompensation predicted SVR12. Six episodes of acute rejection (n=2 KT, 4 LT) occurred during HCV treatment in 4 and after cessation of treatment in 2. Conclusion In a large prospective observational cohort study, DAA therapy with SOF/LDV, PrOD and SOF plus DAC was efficacious and safe in, LT, KT, and DLK transplant recipients. Ribavirin did not influence SVR. Graft rejection was rare.

Ovarian cancer is the most lethal gynecologic malignancy in both African-American and white women. Although prevalences of many ovarian cancer risk factors differ markedly between African Americans and whites, there has been little research on how the relative contributions of risk factors may vary between racial/ethnic groups. Using data from a North Carolina case-control study (1999-2008), the authors conducted unconditional logistic regression analyses to calculate odds ratios and 95% confidence intervals for ovarian cancer risk factors in African-American (143 cases, 189 controls) and white (943 cases, 868 controls) women and to test for interactions by race/ethnicity. They also calculated attributable fractions within each racial/ethnic group for the modifiable factors of pregnancy, oral contraceptive use, tubal ligation, and body mass index. Many risk factors showed similar relations across racial/ethnic groups, but tubal ligation and family history of breast or ovarian cancer showed stronger associations among African Americans. Younger age at menarche was associated with risk only in white women. Attributable fractions associated with tubal ligation, oral contraceptive use, and obesity were markedly higher for African Americans. The relative importance of ovarian cancer risk factors may differ for African-American women, but conclusions were limited by the small sample. There is a clear need for further research on etiologic factors for ovarian cancer in African-American women.

ObjectiveDue to a high efficacy in clinical trials, sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infection. We investigated safety and effectiveness of these regimens for GT2 in HCV-TARGET participants.DesignHCV-TARGET, an international, prospective observational study evaluates clinical practice data on novel antiviral therapies at 44 academic and 17 community medical centres in North America and Europe. Clinical data were centrally abstracted from medical records. Selection of treatment regimen and duration was the investigator's choice. The primary efficacy outcome was sustained virological response 12 weeks after therapy (SVR12).ResultsBetween December 2013 and April 2015, 321 patients completed 12 weeks (n=283) or 16 weeks (n=38) of treatment with SOF and RBV. Prior treatment experience and cirrhosis was more frequent among patients in the 16-week regimen compared with 12 weeks (52.6% vs 27.6% and 63.2% vs 21.9%, respectively). Overall, SVR12 was 88.2%. The SVR12 in patients without cirrhosis was 91.0% and 92.9% for 12 or 16 weeks of therapy, respectively. In patients with cirrhosis treated for 12 or 16 weeks, SVR12 was 79.0% and 83%. In the multivariate analysis, liver cirrhosis, lower serum albumin and RBV dose at baseline were significantly associated with SVR12. Common adverse events (AEs) included fatigue, anaemia, nausea, headache, insomnia, rash and flu-like symptoms. Discontinuation due to AEs occurred in 2.8%.ConclusionsIn this clinical practice setting, SOF and RBV was safe and effective for treatment of patients with HCV GT2 infection.Trial registration numberNCT01474811.

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