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•Glecaprevir/pibrentasvir combination has demonstrated excellent SVR rates (99.2%) in this real-world study in Italy.•Male gender (0.022) and HCV genotype3 (0.046) were associated ...with the lowest rates of SVR after 8-week G/P treatment.•8.3% of the patients reported mild adverse events and 0.7% of them prematurely withdrew antiviral treatment.
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.
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.
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.
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.
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.
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•SOF/VEL/VOX demonstrated excellent effectiveness in patients with HCV and previous DAA failure in a real-life study.•Cirrhosis (p = 0.005) and hepatocellular carcinoma onset ...(p = 0.02) were the only features associated with treatment failure.•Treatment failures (4%) occurred in patients with cirrhosis, with genotypes HCV-1a and 3 the most represented.
Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting.
All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment.
A total of 179 patients were included: median age 57 (18–88) years, 74% males, median HCV-RNA 1,081,817 (482–25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%).
SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting.
This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.
Background and Aims
Metabolic dysfunction (MD)‐associated fatty liver disease has been proposed to identify individuals at risk of liver events irrespectively of the contemporary presence of other ...liver diseases. The aim of this study was to examine the impact of MD in patients cured of chronic hepatis C (CHC).
Patients and Methods
We analysed data from a real‐life cohort of 2611 Italian patients cured of CHC with direct antiviral agents and advanced liver fibrosis, without HBV/HIV, transplantation and negative for hepatocellular carcinoma (HCC) history (age 61.4 ± 11.8 years, 63.9% males, median follow‐up 34, 24–40 months). Information about ultrasonographic steatosis (US) after sustained virological response was available in 1978.
Results
MD affected 58% of patients, diagnosed due to the presence of diabetes (MD‐diabetes, 19%), overweight without diabetes (MD‐overweight, 37%) or multiple metabolic abnormalities without overweight and diabetes (MD‐metabolic, 2%). MD was more frequent than and not coincident with US (32% MD‐only, 23% MD‐US and 13% US‐only). MD was associated with higher liver stiffness (p < 0.05), particularly in patients with MD‐diabetes and MD‐only subgroups, comprising older individuals with more advanced metabolic and liver disease (p < 0.05). At Cox proportional hazard multivariable analysis, MD was associated with increased risk of HCC (HR 1.97, 95% CI 1.27–3.04; p = 0.0023). Further classification according to diagnostic criteria improved risk stratification (p < 0.0001), with the highest risk observed in patients with MD‐diabetes. Patients with MD‐only appeared at highest risk since the sustained virological response achievement (p = 0.008), with a later catch‐up of those with combined MD‐US, whereas US‐only was not associated with HCC.
Conclusions
MD is more prevalent than US in patients cured of CHC with advanced fibrosis and identifies more accurately individuals at risk of developing HCC.
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 Log10HCV‐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 <<difficult‐to‐treat>> genotype.
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.
To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD).
All HCV patients treated with DAA in Lombardy (December 2014–November 2017) with available kidney function tests during and off-treatment were included.
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).
During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.
In routine clinical practice, hepatitis C virus‐infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological ...response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE‐Lombardia Network database from January 2015, who discontinued DAAs before the predefined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5 years, and 53 (14.5%) patients were HIV‐co‐infected. Liver cirrhosis was observed in 251 (68.8%) subjects, and the most represented genotypes were 1b (n = 168, 46%) and 3 (n = 59, 16.2%). DAA was discontinued a median of 1 (IQR 1–4) weeks before the predefined EOT, with 164 (44.9%) patients stopping DAAs at least 2 weeks before the planned schedule. In patients with F0–F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for <4 weeks: 50% (n = 2/4) vs. 99.1% (n = 109/110) for ≥4 weeks, p = 0.003. In patients with liver cirrhosis, lower rates of SVR12 were observed in patients treated <8 weeks: 83.3% (n = 25/30) vs. 94.6% (n = 209/221) for ≥8 weeks, p = 0.038. Despite premature discontinuation of DAA, high SVR12 rates were observed in a real‐life setting for treatment lasting at least 4 weeks in patients with liver fibrosis F0–F3 and 8 weeks in those with liver cirrhosis. On this basis, feasibility of reducing DAA treatment duration should be explored in randomized clinical trials.
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