High post-transplant virological response in hepatitis C virus infected patients treated with pretransplant protease inhibitor-based triple therapy.

BACKGROUND & AIMS: Prevention of recurrent hepatitis C virus (HCV) following liver transplant (LT) with pre-LT antiviral therapy is limited by poor tolerability and efficacy. We aimed to evaluate the safety and efficacy of NS3/4A protease inhibitor (PI)-based triple therapy in patients awaiting LT. METHODS: Consecutive patients treated with triple therapy pre-LT from two centers were prospectively enrolled in an observational cohort. Overall 12 week sustained virological response (SVR12) was the primary outcome. Pre- and post-LT (pTVR) virological response rates and safety were secondary outcomes. RESULTS: Twenty-nine patients (mean age 57.9, 79% male, 66% prior non-responders) were treated with telaprevir (93%) or boceprevir-based (7%) triple therapy for a median (range) of 27 (3-50) weeks, including a pegylated-interferon and ribavirin lead-in in 18%. Median (range) MELD at treatment was 8 (6-16), 39% had hepatocellular carcinoma and all patients were Child-Turcotte-Pugh class A (62%) or B (38%). Twelve patients underwent LT, 75% with undetectable viral load. The overall SVR12 rate was 52%, including pre-LT SVR12 of 41% in patients who completed treatment and follow-up on the wait list and pTVR12 of 67% among transplanted patients. The pTVR12 rate was 89% among those patients with undetectable viral load at LT. Serious adverse events occurred in nine (31%) patients including one (3%) on-treatment death and eight (28%) hospitalizations. CONCLUSIONS: Overall SVR12 and pTVR12 rates are high among patients treated with PI-based triple therapy while awaiting LT, even in this difficult to treat population. However, caution is needed as early discontinuation and serious adverse events are common.

Arterial spin-labeling MR imaging of renal masses: correlation with histopathologic findings.

PURPOSE: To assess the value of arterial spin-labeling (ASL) perfusion magnetic resonance (MR) imaging in the characterization of solid renal masses by using histopathologic findings as the standard of reference. MATERIALS AND METHODS: This prospective study was compliant with HIPAA and approved by the institutional review board. Informed consent was obtained from all patients before imaging. Forty-two consecutive patients suspected of having renal masses underwent ASL MR imaging before their routine 1.5-T clinical MR examination. Mean and peak tumor perfusion levels were obtained by one radiologist, who was blinded to the final histologic diagnosis, by using region of interest analysis. Perfusion values were correlated with histopathologic findings by using analysis of variance. A linear correlation model was used to evaluate the relationship between tumor size and perfusion in clear cell renal cell carcinoma (RCC). P < .05 was considered indicative of a statistically significant difference. RESULTS: Histopathologic findings were available in 34 patients (28 men, six women; mean age ± standard deviation, 60.4 years ± 11.7). The mean perfusion of papillary RCC (27.0 mL/min/100 g ± 15.1) was lower than that of clear cell RCC (171.6 mL/min/100 g ± 61.2, P = .001), chromophobe RCC (152.9 mL/min/100 g ± 80.7, P = .04), unclassified RCC (208.0 mL/min/100 g ± 41.1, P = .001), and oncocytoma (373.9 mL/min/100 g ± 99.2, P < .001). The mean and peak perfusion levels of oncocytoma (373.9 mL/min/100 g ± 99.2 and 512.3 mL/min/100 g ± 146.0, respectively) were higher than those of papillary RCC (27.0 mL/min/100 g ± 15.1 and 78.2 mL/min/100 g ± 39.7, P < .001 for both), chromophobe RCC (152.9 mL/min/100 g ± 80.7 and 260.9 mL/min/100 g ± 61.9; P < .001 and P = .02, respectively), and unclassified RCC (208.0 mL/min/100 g ± 41.1 and 273.3 mL/min/100 g ± 83.4; P = .01 and P = .03, respectively). The mean tumor perfusion of oncocytoma was higher than that of clear cell RCC (P < .001). CONCLUSION: ASL MR imaging enables distinction among different histopathologic diagnoses in renal masses on the basis of their perfusion level. Oncocytomas demonstrate higher perfusion levels than RCCs, and papillary RCCs exhibit lower perfusion levels than other RCC subtypes.

Hyperpolarized HHe 3 MRI of the lung in cystic fibrosis: assessment at baseline and after bronchodilator and airway clearance treatment.

RATIONALE AND OBJECTIVES: The purpose of this study is to determine hyperpolarized helium 3 (HHe) magnetic resonance (MR) findings of the lung in patients with cystic fibrosis (CF) compared with healthy subjects and determine whether HHe MR can detect changes after bronchodilator therapy or mechanical airway mucus clearance treatment. MATERIALS AND METHODS: Thirty-one subjects, 16 healthy volunteers and 15 patients with CF, underwent HHe lung ventilation MR imaging and spirometry at baseline. Eight patients with CF then were treated with nebulized albuterol, after which a follow-up HHe MR scan was obtained. Subsequently, recombinant human deoxyribonuclease (DNase) treatment and chest physical therapy were performed in these eight subjects, followed by a third HHe MR scan. For each MR study, the number of ventilation defects was scored by a human reader. RESULTS: Patients with CF had significantly more HHe MR ventilation defects per image than healthy subjects (mean, 8.2 defects in patients with CF vs 1.6 defects in healthy subjects; P < .05). Even the four subjects with CF with a normal forced expiratory volume in 1 second had significantly more ventilation defects than healthy subjects (mean, 6.5 defects in these patients with CF; P = .0002). After treatment with albuterol, there was a small, but statistically significant, decrease in number of ventilation defects (mean, 9.6-8.0 defects; P = .025). After DNase and chest physical therapy, there was a trend toward increasing ventilation defects (mean, 8.3 defects; P = .096), but with a residual net improvement relative to baseline. CONCLUSION: In patients with CF, HHe MR ventilation defects correlate with spirometry, change with treatment, and are elevated in number in patients with CF with normal spirometry results. Thus, HHe MR appears to possess many of the characteristics required of a biomarker for pulmonary CF and may be useful in the evaluation of CF pulmonary disease severity or progression.