Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C.

BACKGROUND AND AIMS: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting. METHODS: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment. RESULTS: A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m2, and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x103/mm3 and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes. CONCLUSIONS: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks. LAY SUMMARY: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.

Acute portal venous injury after microwave ablation in an in vivo porcine model: a rare possible complication.

PURPOSE: To evaluate the damage caused by microwave ablation to vessels inside and outside the ablation zone in an in vivo swine model. MATERIALS AND METHODS: Four pigs underwent microwave liver ablation with a 2.45-GHz generator and a 14-gauge water-cooled antenna with a miniature choke. Each animal underwent four 15-minute microwave ablations (two at 40 W, two at 60 W). Mean minimum and maximum diameters of ablation areas were calculated on gross pathologic and histologic examination. At minimum, a whole-mount section and two to four specimens were obtained from each ablation and stained with hematoxylin and eosin. Specimens were analyzed to verify the presence of damaged vessels in and outside the ablation area. RESULTS: Mean ablation diameters at gross pathologic examination, including the hemorrhagic halo, were 3.1 cm ± 0.5 at 40 W and 3.6 cm ± 1.1 at 60 W. All ablation zones presented a characteristic pattern consisting of three concentric zones: (i) a central area consisting of coagulative necrosis (mean maximum diameter, 8.5 mm ± 2.6), (ii) a larger area characterized by irreversibly damaged hepatocytes (mean maximum thickness, 11.7 mm ± 3.4), and (iii) a hemorrhagic halo. Twenty-one veins outside the ablation zone were evaluated (mean diameter, 5.6 mm), three of which (14%) showed diffuse endothelial damage. All three represented a continuation of a portal vein within the ablation area. CONCLUSIONS: In a small percentage of microwave ablation cases, endothelial damage can extend from a portal vessel included in the ablation zone to a segment of the vessel situated outside the ablation zone. Further investigation of the clinical significance of this finding is needed.

Surveillance for hepatocellular carcinoma at the community level: Easier said than done.

Surveillance for hepatocellular carcinoma (HCC) in high-risk patients with semiannual ultrasound examinations is advocated by all international guidelines. However, as long as the identification of the population to be screened and the surveillance programs are not well implemented, the real-life impact of HCC surveillance in reducing mortality for HCC cannot be known. We propose a new approach that promotes the identification of cirrhotic patients by primary care physicians (PCPs) and referral of patients to the hepatologist for surveillance. Surveillance should be incorporated, when feasible, in a hub and spoke model of comprehensive hepatology care. Training PCPs to identify cirrhotic patients and performing surveillance in a subspecialist setting are equally important to improve the effectiveness of real-life surveillance and to decrease HCC mortality over time.

Renal safety in 3264 HCV patients treated with DAA-based regimens: Results from a large Italian real-life study.

BACKGROUND: Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are lacking. AIM: To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD). METHODS: All HCV patients treated with DAA in Lombardy (December 2014-November 2017) with available kidney function tests during and off-treatment were included. RESULTS: Among 3264 patients [65% males, 67% cirrhotics, eGFR 88 (9-264) ml/min], CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33-45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively). CONCLUSIONS: During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.

Follow-up after percutaneous radiofrequency ablation of renal cell carcinoma: contrast-enhanced sonography versus contrast-enhanced CT or MRI.

OBJECTIVE: The purpose of this study was to assess, with contrast-enhanced CT or MRI as the reference imaging technique, the diagnostic performance of low-mechanical-index contrast-enhanced sonography in detecting local tumor progression after percutaneous radiofrequency ablation of renal tumors. MATERIALS AND METHODS: Twenty-nine patients with 30 renal tumors (18 men, 11 women; mean age, 73 years; range, 53-83 years) underwent percutaneous radiofrequency ablation at a single center between March 1998 and January 2007. The imaging follow-up schedule was both contrast-enhanced sonography and CT or MRI 4 months after completion of treatment and every 4 months for the first year. Thereafter, the follow-up schedule was contrast-enhanced sonography every 4 months with CT or MRI every 8 months. The chi-square test with Yates correction was used to evaluate positive and negative predictive values and accuracy. RESULTS: One patient was scheduled to undergo surgical resection, and another patient was lost to follow-up. Twenty-seven patients with 28 renal tumors participated in follow-up. The concordance between contrast-enhanced sonographic and CT or MRI findings was 100% for 27 of 28 tumors (96.4%) that had a hypervascular pattern before treatment. In the case of the tumor that was hypovascular at imaging performed before percutaneous radiofrequency ablation, local tumor progression was missed at contrast-enhanced sonography. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of contrast-enhanced sonography were 96.6%, 100%, 100%, 95.8%, and 98.1%. CONCLUSION: Contrast-enhanced sonography is an effective alternative to CT and MRI in the follow-up of renal tumors managed with percutaneous radiofrequency ablation.

Radiofrequency ablation of liver tumors: the role of microbubble ultrasound contrast agents.

Radiofrequency ablation (RFA) is currently indicated for the treatment of primary and metastatic hepatic malignancies. Real-time ultrasound (US) is generally used during the procedure to guide electrode placement, but for evaluating the results of treatment, contrast-enhanced computed tomography and magnetic resonance imaging have traditionally been considered more effective. This view has changed, however, with the recent development of contrast-enhanced ultrasound (CEUS) (eg, using sulfur hexafluoride microbubbles), which can provide valuable information on the effects of RFA more rapidly and economically than computed tomography or magnetic resonance imaging without exposing the patient to ionizing radiation. In our center, CEUS is performed in patients with liver tumors before and immediately after RFA, in selected cases during the procedure as well, and in the follow-up. Between January 2003 and June 2005, we performed CEUS on 350 patients scheduled for RFA of primary or metastatic liver tumors. In 14 (13.4%) of the 96 patients whose disease was metastatic, CEUS revealed lesions that had been missed on the conventional US examination. In most of these cases, the result was a more complete treatment performed under CEUS guidance. In the remaining 2 (14%) of 14, the results of the examination allowed us to avoid subjecting the patient to useless treatment. In our experience, the use of CEUS also improved the management and follow-up of patients undergoing interstitial therapy.

Treatment with stem cell differentiation stage factors of intermediate-advanced hepatocellular carcinoma: an open randomized clinical trial.

There is no standard treatment for patients with advanced hepatocellular carcinoma (HCC). We developed a product containing stem cells differentiation stage factors (SCDSF) that inhibits tumor growth in vivo and in vitro. The aim of this open randomized study was to assess its efficacy in patients with HCC not suitable for resection, transplantation, ablation therapy, or arterial chemoembolization. A total of 179 consecutive patients were enrolled. We randomly assigned the patients to receive either SCDSF or only conservative treatment. Primary end points were tumor response and survival. Secondary end points were performance status and patient tolerance. Randomization was stopped at the second interim analysis (6 months) of the first 32 patients recruited when the inspection detected a significant difference in favor of treatment (p = 0.037). The responses to the therapy obtained in 154 additional patients confirmed previous results. Evaluation of survival showed a significant difference between the group of patients who responded to treatment versus the group with progression of disease (p < 0.001). Of the 23 treated patients with a performance status (PS) of 1, 19 changed to 0. The study indicated the efficacy of SCDSF treatment of the patients with intermediate-advanced HCC.

Contrast enhanced ultrasound: Should it play a role in immediate evaluation of liver tumors following thermal ablation?

PURPOSE: To compare the accuracy of immediate CEUS with results of 24-h CEUS and MDCT in early evaluation of liver tumors following thermal ablation, using the combined results of a 3 month follow-up MDCT and CEUS as a reference standard. SUBJECTS AND METHODS: From our database, we selected patients who underwent a thermal ablation immediately followed by CEUS (within 5-10min) between February 2009 and February 2011. There were 92 patients (median age 73 years), two of whom had repeat ablation during the study period for a total of 94 tumors. Sixty tumors were treated with radiofrequency and 34 with microwave ablation. All patients underwent CEUS and CT examinations at 24h. For patients with more than one treated tumor in the same session, the lesion imaged post-procedural and at 24-h with CEUS in all vascular phases was selected. All measurements of the necrotic zone, as an avascular zone, were performed during the portal-venous phase. Immediate post-procedural CEUS and 24h CEUS and MDCT were blindly reviewed by two radiologists. One radiologist blindly reviewed the follow-up imaging. The mean diameters of the necrotic zone at post-procedural CEUS, and CEUS and MDCT at 24h were compared and diagnostic accuracy to detect residual tumor calculated for each index tests compared to 3-months follow-up imaging. RESULTS: The mean diameter of the necrotic zone was: 29±9mm at post-procedural CEUS, 34±10mm at 24h CEUS and 35±11mm at 24h MDCT. Mean diameter of the necrotic zone was significantly smaller at post-procedural CEUS compared to either CEUS or MDCT at 24h (p<0.001 for all). With a 95% confidence interval, the sensitivity was 25% (11-47%) for immediate CEUS, 20% (8-42%) for CEUS at 24-h, and 40% (22-61%) for CT at 24-h. Specificity was 96% (89-99%) for immediate CEUS, 97% (91-99%) for CEUS at 24-h, and 97% (91-99%) for CT at 24-h. CONCLUSIONS: Diagnostic accuracy of post-procedural CEUS in early evaluation of liver tumors following thermal ablation is comparable to both CEUS and MDCT performed at 24h. Therefore, post-procedural CEUS can be used to detect and retreat residual viable tissue in the same ablation session.