Reply to: "Built-in bias in HCV clearance in acute HCV infection"

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Effect of wounding intensity on physiological and quality changes of strawberry fruit

Wounding makes fresh-cut product more perishable than whole fruit. The effect of wounding intensity on respiration rate and nutritional quality of fresh-cut ‘Candonga’ strawberries was investigated. Fruit were submitted to six levels of cutting intensity - whole fruit (WHO), 4, 16, 64, and 128 pieces and chopped (CHO) samples. Respiration rate, and the main nutritional parameters were evaluated at the processing day and after 2 days of storage at 5°C. Results showed that wounding intensity significantly influenced respiration rate, ascorbic and dehydroascorbic acids, total phenolic content, and antioxidant capacity. Respiration rate increased with wounding intensity up to the level of 64 pieces (10.01 µg kg-1 s-1) compared to WHO (5.5 µg kg-1 s-1) and then decreased in the CHO samples (2.81 µg kg-1 s-1). At Day 2, the stress caused by the high intensity of cutting (64 pieces and CHO) induced a higher degradation of ascorbic acid, phenolic compounds, and antioxidant capacity. Stress-related changes decrease when the wounding damage was so high that it completely compromises the functionality of the cells (from 64 pieces up). These results should be considered for processing and packaging optimization of minimally processed strawberries-based products

Overall efficacy and safety results of sofosbuvir-based therapies in Phase II and III studies

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Noninvasive Diagnosis of NAFLD and NASH

The aim of this review is to outline emerging biomarkers that can serve as early diagnostic tools to identify patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) and, among them, the subgroup of best candidates for clinical trials on emerging compounds. Regarding possible predictors of NAFLD, a number of studies evaluated a combination of serum biomarkers either available in routine practice (or investigational) or proprietary and expensive. So far, magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) appears to be the most accurate for fatty liver diagnosis. In clinical practice, the main question is how to diagnose NASH early. There are new promising biomarkers that can help in diagnosing early stages of NASH, yet they include variables not routinely tested. In the setting of NASH, most studies confirm that, in spite of several well-known limitations, transient elastography or point shear wave elastography can help in enriching the pool of patients that should be screened for investigational treatments. Newer multiomics biomarkers including those focusing on microbiota can be useful but require methods to be standardized and implemented. To date, one biomarker alone is not able to non- or minimally invasively identify patients with NASH and mild to moderate fibrosis

Nonalcoholic Steatohepatitis: A 9-Year Follow Up Cohort Study

Background and aim: Non-alcoholic fatty liver disease (NAFLD) may progress to severe liver fibrosis and cirrhosis. A limited number of studies with a long follow up assessed fibrosis progression and related predictors in untreated patients with a histological diagnosis of NAFLD. This study aims to investigate rate and predictors of NAFLD progression. Methods: For 9 (2–16.7) years, we followed up a cohort of patients histologically diagnosed. Disease progression was defined by a composite endpoint as evidence of cirrhosis in patients without cirrhosis at baseline, evidence of de novo occurrence of cirrhosis complications, histologically established worsening of stage 1 of fibrosis or increase of 20% in liver stiffness by transient elastography in patients rejecting a second liver biopsy. Results: A total of 91 patients were enrolled. Of them, 31 had NAFL and 60 NASH. A second liver biopsy was performed in 22 NASH patients and in 4 NAFL. Disease progression was observed in 38.5% NASH and in 12.0% NAFL (p = 0.034). Patients with portal inflammation had a higher risk of progression (66.7% vs 26%, p = 0.021). High triglycerides levels, advanced fibrosis at baseline and the duration of follow-up predict disease progression (p = 0.021; OR = 6.93, 95% CI 1.33–36.08, p = 0.43; OR 8.37; 95% CI 1.07–65.58 and p = 0.034; OR = 0.88; 95% CI 0.78–0.99, respectively). Conclusions: Our results reinforce the evidence that, in the absence of pharmacologic treatment, NASH progresses in about 40% of patients. Liver biopsy is the only mean to discriminate NAFL from NASH. The prognostic role of portal inflammation needs to be explored in larger series

SVR12 Higher than 97% in GT3 Cirrhotic Patients with Evidence of Portal Hypertension Treated with SOF/VEL without Ribavirin: A Nation-Wide Cohort Study

In clinical trials, a sofosbuvir/velpatasvir (SOF/VEL) pangenotypic single-tablet regimen was associated with high sustained virological response (SVR) rates at 12 weeks (SVR12) after the end of treatment, regardless of genotype and fibrosis stage. No real-life data on genotype 3 (GT3) cirrhotic patients with portal hypertension are available. The aim of this study was to assess the effectiveness of SOF/VEL in GT3 cirrhotics with portal hypertension. Patients with GT3 and advanced cirrhosis were treated for 12 weeks with SOF/VEL without ribavirin at five different centers in Italy from June 2017 to August 2018 and their SVR12 was assessed. Of the 227 GT3 cirrhotics evaluated, 205 met the inclusion criteria and 111 had transient elastography results ≥20 KPa. SVR12 was 97.6% (95% CI 94.4–98.9), rates were 99.1% (95% CI 95.7–99.8) in patients with ≥20 KPa and 95.8% (95% CI 89.5–98.3) in those with <20 KPa (p = 0.18). Analyzed by presence of esophageal varices, the SVR12 rates were 98.4% (95% CI 91.4–99.7) and 97.1% (95% CI 92.9–98.9) in patients without and with varices, respectively (p = 1.0). In real life, SOF/VEL GT3 cirrhotic patients with evidence of portal hypertension can achieve SVR12 levels comparable to those of patients without portal hypertension. These SVR12 rates are similar to what is reported in compensated cirrhosis treated within clinical trials

Overall efficacy and safety results of sofosbuvir-based therapies in Phase II and III studies

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