Comparison of three therapeutic regimens for genotype-3 hepatitis C virus infection in a large real-life multicentre cohort.

BACKGROUND & AIMS: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. METHODS: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression. RESULTS: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10 HCV-RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12. CONCLUSIONS: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <> genotype.

Dysmetabolism, Diabetes and Clinical Outcomes in Patients Cured of Chronic Hepatitis C: A Real-Life Cohort Study.

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2 , 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20-3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16-6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11-0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi-disciplinary management approach may improve cardiovascular and possibly liver-related outcomes.

An observational, prospective, open-label, multicentre evaluation of aliskiren in treated, uncontrolled patients: a real-life, long-term, follow-up, clinical practice in Italy.

INTRODUCTION: The addition of the direct renin inhibitor aliskiren is demonstrated to improve blood pressure (BP) control rate and reduce progression of organ damage in treated hypertensive patients in clinical trials with a relatively short follow-up period. AIM: The objective of this study was to assess the effectiveness, safety and tolerability of aliskiren as an add-on antihypertensive therapy in high-risk, treated, hypertensive patients, who were not controlled with concomitant treatment with at least two antihypertensive drugs under 'real-life' conditions, during a planned observation and treatment period of at least 12 months in Italy. METHODS: Clinical data were derived from medical databases of treated, uncontrolled, hypertensive patients followed by specialized physicians operating in different clinical settings (hospital divisions or outpatient clinics) in Italy. Aliskiren was added to stable antihypertensive treatment, including at least two drug classes (independently of class or dosage) and unable to achieve BP control. Follow-up visits for measuring clinic BP levels and collecting data on drug safety and tolerability were planned at time intervals of 1, 6 and 12 months. At each predefined follow-up visit, aliskiren could be up-titrated from 150 to 300 mg daily if BP control was not achieved. RESULTS: From May 2009 to June 2011, a total of 1186 treated, uncontrolled, hypertensive patients (46.3% female, aged 65.2 ± 11.7 years, mean duration of hypertension 13.2 ± 9.3 years, mean clinic BP levels 156.5 ± 15.9/90.3 ± 9.5 mmHg) were enrolled. Systolic and diastolic BP levels were 141.1/82.4, 134.9/79.8 and 133.6/78.9 mmHg at 1-, 6- and 12-month follow-up visits, respectively (p < 0.0001 vs baseline for all comparisons). These effects were consistent in all predefined subgroups, including those with left ventricular hypertrophy, renal disease, diabetes mellitus, coronary artery disease or cerebrovascular disease. Reduced levels of microalbuminuria were also reported, without affecting other renal and electrolyte parameters. Overall, compliance to study medication was high (93.0%), with a very low proportion of patients experiencing adverse events leading to drug discontinuation (3.6%). CONCLUSIONS: In this observational, prospective, open-label, multicentre study, we reported the 12-month clinical effectiveness, safety and tolerability of adding aliskiren to treated, uncontrolled, hypertensive patients in a 'real-life' setting in Italy. This strategy leads to a significantly improved BP control rate and low incidence of drug-related side effects or discontinuations.