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Background: Glecaprevir and Pibrentasvir (G/P) determine high rates of sustained virological response (SVR) with optimal safety profile in patients with chronic hepatitis C virus (HCV) infection. The efficacy and safety of G/P in Caucasian patients aged 75 years and older have not been widely analysed. Methods: This is a retrospective multicentre real‐world study enrolling all consecutive patients 75 years and older who received G/P between October 2017 and January 2022 at five referral centres in Italy. SVR was analysed by intention‐to‐treat (ITT) and per‐protocol analyses (PP). Results: A total of 570 patients met the inclusion criteria and were analysed: mean age was 80 (75–97) years, 356 (62%) were females, 52% (298/570) had HCV‐1, 44% (252/570) had HCV‐2 and 137 (24%) patients had liver cirrhosis. Four hundred and sixty‐three (81%) patients were taking at least one concomitant drug, with 144 (25%) taking ≥5 concomitant drugs. G/P was given for 8 weeks in 488 patients (86%). During treatment, 48 patients (8%) reported side effects, with 10 (2%) patients discontinuing treatment prematurely. Two patients developed treatment‐unrelated serious adverse events. Overall, the SVR rate was 97.9% (558/570) by ITT analysis and 99.6% (558/560) by PP analysis. SVR rates remained consistently high among subgroup analysis stratified by genotype, treatment duration, fibrosis stage and concomitant medications. Conclusions: Treatment with G/P achieved 97.9% SVR rates in HCV patients older than 75 years of age. Safety was optimal with only 2% of patients discontinuing early. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAAs) revolutionized the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), even in advanced cirrhosis, with modest contraindications and a low rate of adverse events. However, the risk of hepatocellular carcinoma (HCC) persists due to the underlying chronic liver disease, both in patients with and without history of HCC. Although some initial studies reported a presumptive high risk of HCC development after DAA therapy, more recent observational studies denied this hypothesis. The residual risk for HCC occurrence after HCV eradication seems being progressively reduced with time after SVR. Data on recurrence of HCC after DAA exposure in patients with previously treated carcinoma initially reported conflicting results too, this being also due to methodological issues in analysis of retrospective multicenter studies. Anyway, current evidence support the use of DAAs in HCV-HCC treated patients, without any higher risk of tumor recurrence linked to antiviral therapy. Less effort has been made to evaluate the efficacy of DAA therapy in patients with untreated active HCC and it has been questioned whether a lower rate of SVR would be obtained among patients with active HCC. Studies conducted in this perspective concluded that HCC status does not influence the likelihood to obtain SVR with DAAs, making DAAs appropriate in HCC-active patients. As far as survival is concerned, recent studies conducted in cirrhotic HCV-related early-stage HCC found that DAAs improved overall survival, a benefit probably due to the reduction of hepatic decompensation. [ABSTRACT FROM AUTHOR]

Background and Aims: Beyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort.Methods and Results: In this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19-34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148-1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44-53.95; p = 0.016).Conclusions: HCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors. [ABSTRACT FROM AUTHOR]

Aim: To assess the effect of hepatitis C virus (HCV) eradication on type 2 diabetes mellitus (T2DM). incidence. Methods: A prospective multicentre case–control study was performed, which included 2426 patients with HCV, 42% of whom had liver fibrosis stage F0‐F2 and 58% of whom had liver fibrosis stage F3‐F4. The study population consisted of a control group including 1099 untreated patients and 1327 cases treated with direct‐acting antivirals (DAAs). T2DM incidence was assessed during a median (interquartile range) follow‐up period of 30 (28–42) months. Risk factors for T2DM were assessed using a Cox regression model (relative risk [RR], hazard ratio [HR], Kaplan–Meier analysis). Insulin sensitivity was evaluated by homeostatic model assessment (HOMA) and changes by repeated‐measures ANOVA. Factors independently associated with T2DM were assessed by multivariate analysis. Results: The absolute incidence of T2DM for controls and cases was 28 and 7/1000 person‐years, respectively (P = 0.001). In cases compared to controls, HCV clearance reduced the RR and HR of T2DM by 81% and 75% to 93%, respectively (P = 0.001). It was calculated that, for every 15 patients who obtained HCV clearance, one case of T2DM was saved. HCV clearance was associated with significant reductions in HOMA‐insulin resistance and HOMA‐β‐cell function and an increase in HOMA‐insulin sensitivity, as assessed in 384 patients before and after HCV clearance. At multivariate analysis, HCV clearance emerged as independently associated with a reduced T2DM risk. Conclusion: The results showed that HCV clearance by DAA treatment reduces T2DM incidence probably by restoring the HCV‐induced alteration of glucose homeostasis mechanisms. [ABSTRACT FROM AUTHOR]

Background and aims: HCV eradication improves non‐hepatic outcomes such as cardiovascular diseases, although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction in systemic oxidative stress after viral clearance. Methods: We studied a retrospective cohort of 105 patients (age 62.4 ± 11.2 years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow‐up. Levels of 8‐iso‐prostaglandin F2α (F2‐isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative stress markers (exposures) and change in carotid intima‐media thickness (cIMT) (outcome) was examined using multiple linear regression. Results: Subclinical atherosclerosis, defined as the presence of carotid plaque and/or cIMT ≥ 0.9, was present in 72% of the cohort. All patients achieved SVR that led to reduction in cIMT (0.92 ± 0.20 vs 0.83 ± 0.21 mm, P <.001). HCV eradication markedly decreased serum levels of F2‐isoprostanes (620.5 [143.2; 1904.1] vs 119.51 [63.2; 400.6] pg/mL, P <.0001), lipid hydroperoxides (13.8 [6.3; 20.7] vs 4.9 [2.3; 9.6] nmol/μl, P <.0001) and 8‐hydroxy‐2'‐deoxyguanosine (558.9 [321.0; 6301.2] vs 294.51 [215.31; 408.95] pg/mL, P <.0001), whereas increased serum GPx activity (10.44 [4.6; 16.3] vs 13.75 [9.42; 20.63] nmol/min/mL, P =.001). By multiple linear regression analysis ΔcIMT was independently associated with ΔF2‐isoprostanes (β: 1.746 [0.948; 2.543]; P <.0001) after adjustment for age, baseline F2‐isoprostanes and baseline IMT. Conclusions: Besides association of lipid peroxidation with severity of liver disease, the reduction in F2‐isoprostanes may be involved in the improvement of atherosclerosis after HCV eradication. [ABSTRACT FROM AUTHOR]

Background & Aims: In patients with hepatitis C virus (HCV)‐related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13C‐aminopyrine breath test (ABT) to assess whether its changes can predict liver‐related outcomes after DAA treatment in patients with HCV cirrhosis. Methods: Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation – defined as Child A6 (N = 22, 44%) or previous decompensation (N = 7, 14%) – or Child B cirrhosis (N = 21, 42%) eligible for DAA‐based antiviral therapy. ABT was performed at baseline and 12 weeks after the end of antiviral therapy. Patients received sofosbuvir‐based regimens. Results: Aminopyrine breath test was available for all 50 patients at baseline. The 120' cumulative dose was directly associated at regression analysis only with albumin levels (P =.001). ABT was available at follow‐up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2 months (range 12.2‐32.1 months). Lower Ʌ ABT – defined as changes of 120' cumulative dose from FUW12 to baseline – (HR 0.97, 95% CI 0.94‐0.99; P =.02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16‐310.3; P =.03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of Ʌ ABT was good (0.87, 95% CI 0.75‐0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver‐related events/death (P <.001). Conclusions: In patients with advanced HCV cirrhosis who achieve SVR with DAA, Ʌ ABT assists in assessing the residual likelihood of liver‐related events and deaths after viral cure. [ABSTRACT FROM AUTHOR]

HCV‐RNA assessment during therapy with Direct‐Acting Antiviral (DAA) regimens still relies on assays requiring blood collection and transport to a specialised laboratory, which may compromise linkage to care. GeneXpert‐HCV Viral Load (GXHVL) (Cepheid) is a plasma‐based assay used at point of care (POC) with a sensitivity of ≤10 IU/mL, and, results available within 2 hours. Fifty‐nine consecutive HCV‐patients ready for DAAs treatment were enrolled. HCV‐RNA was simultaneously tested using Roche TaqMan RT‐PCR (venous blood sample) and GXHVL (capillary blood collected by fingerstick), at baseline (BL), week 4 (W4) of therapy, end of therapy (EOT) and week 12 of follow‐up (W12FU). Both assays demonstrated undetectable HCV‐RNA in all patients at EOT and identified the single case of HCV‐relapse at W12FU. GXHVL used as a point‐of‐care assay in the outpatient setting provides results fully comparable to the laboratory‐based test. Its excellent performance and ease of use suggest its adoption in non‐specialist settings where simplicity of care is paramount to implement HCV eradication campaigns. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) remains a significant public health problem and is one of the major causes of chronic liver disease worldwide. In recent years many new tools to facilitate widespread HCV screening and new therapeutic options with excellent efficacy and tolerability profiles and cost lowering policies have become available. To fully utilise these new tools, the link between local and specialist centres for the management of HCV infection must be reinforced. In order to GAIN further insight into these aspects, with a particular focus on the Italian scenario, a group of experts met to discuss relevant aspects and open issues on chronic HCV. As a summary of that meeting, the following aspects are here overviewed: (i) global situation of HCV; (ii) screening, diagnosis and indications for the treatment of HCV; (iii) the Italian situation of HCV referrals; (iv) 'hard to reach' patients; (v) treatment of HCV with extrahepatic manifestations; (vi) treatment of patients with advanced cirrhosis. It is the intention of the expert panel to further promote widespread screening and eradication policies that should be accompanied by greater interaction, by attempting to involve all healthcare providers in an organised process to facilitate linkage to care of patients with HCV infections. [ABSTRACT FROM AUTHOR]

Background Few studies examined the outcome of patients with hepatitis C virus ( HCV)-related cirrhosis who developed hepatocellular carcinoma ( HCC). The relative weight as determinant of death for cancer vs end-stage liver disease ( ESLD) and the benefit of HCV eradication remain undefined. This multicentre, retrospective analysis evaluates overall survival ( OS), rate of decompensation and tumour recurrence in compensated HCC patients treated with interferon ( IFN) according to HCV status since HCC diagnosis. Methods Two groups of patients with HCV-related cirrhosis and HCC were followed since HCC diagnosis: (i) compensated cirrhotics with prior sustained virological response ( SVR) on IFN-based regimens (N=19); (ii) compensated cirrhotics without SVR (viraemic) (N=156). RESULTS Over a median follow-up of 3.0 years since the onset of HCC, OS was longer for HCC patients with SVR than for viraemic patients (log-rank P=.004). The 5-year OS rate was 65.9% in patients with SVR vs 31.9% in viraemic patients. Similar trends were reported for hepatic decompensation (log-rank P=.01) and tumour recurrence (log-rank P=.01). These findings were confirmed at multivariable and propensity score analysis. At propensity analysis, 0/19 compensated patients with SVR died for ESLD vs 7/19 (37%) viraemic patients ( P=.004). HCC mortality was similar in the two groups. Conclusions Hepatocellular carcinoma patients with prior SVR and compensated cirrhosis at the time of tumour diagnosis have prolonged OS than viraemic patients. Given the lack of cirrhosis progression, no SVR patient ultimately died for ESLD while this condition appears the main cause of death among viraemic patients. [ABSTRACT FROM AUTHOR]

Background & Aims Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. Methods The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age- and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population. Results Overall, 28/181 patients followed-up for a median period of 9.6 years (range 1–25 years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3–94.8) and 62.9% (95% CI, 45.9–75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR = 1.00 (95% CI, 0.72–1.35), with an SMR for non-SVR patients of 3.85 (95% CI, 3.43–4.30), for untreated of 3.01 (95% CI, 2.64–3.42) and for decompensated of 6.70 (95% CI, 5.39–8.22). Conclusions Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable. [ABSTRACT FROM AUTHOR]

Background & Aims: The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. Methods: In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. Results: Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637–7.101), low (<400,000IU) viremia (OR 2.907; CI 2.111–4.004), F0–F2 fibrosis (OR 1.631; CI 1.122–2.372) and type 2 diabetes (OR 0.528; CI 0.286–0.972). In the alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274–9.208), IL28B CC genotype (OR 3.306; CI 2.301–4.751), low viremia (OR 2.175; CI 1.542–3.070), and F0–F2 fibrosis (OR 1.506; CI 1.012–2.242). Combining the favorable baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66 patients (6.3%, overall) with all predictors could be anticipated to reach the >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. Conclusions: A consistent subset of naïve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin. [Copyright &y& Elsevier]

Abstract: Background: The aetiological factors of hepatocellular carcinoma may vary over time. Aims: The study assessed the potential impact of the aetiological factors on the effectiveness of surveillance in real-world patients. Methods: Multicentre, cross-sectional study enrolling consecutive hepatocellular carcinoma cases during a six month period. Results: 1733 cases (1311 prevalent and 422 incident) were recruited (mean age 68.6 years; 46.1% cases over 70 years; 73.9% males; 95.3% with cirrhosis); 63.0% were hepatitis C virus positive and 23.7% were virus negative. Amongst incident HCCs, 34.5% were single ≤3cm and 54.4% met the Milan criteria; 61.6% were diagnosed during surveillance; virus negative patients showed the lowest rate of surveillance (51.0%). Surveillance was an independent predictor of detecting single HCCs ≤2cm (O.R.=5.4; 95% C.I.=2.4–12.4) or HCCs meeting the Milan criteria (O.R.=3.1; 95% C.I.=1.9–5.2). Compared with an earlier Italian survey, there was a higher proportion of elderly subjects (P <0.01), Child-Pugh class A cases (P <0.01), of virus-negative patients (P <0.01) and with single tumours ≤3cm (P <0.01) and a lower prevalence of hepatitis C virus positive individuals (P <0.01). Conclusion: HCC is characterised by a growing prevalence of elderly patients and cases unrelated to hepatitis virus infections. The application of surveillance must be implemented, particularly amongst non-viral patients. [Copyright &y& Elsevier]

Background/Aims: Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertension are poorly known. Methods: We performed a randomized controlled trial in 102 HCV patients with compensated cirrhosis and portal hypertension: 51 received 1μg/kg/week of Pegylated-interferon α-2b and 51 Pegylated-interferon plus 800mg/day of ribavirin up to 52 weeks. Results: By intention-to-treat analysis, five patients on monotherapy and eleven on combination therapy achieved a sustained virological response (9.8% vs. 21.6%, p =0.06). The response was more frequent for genotypes 2 or 3 than genotype 1 (66.6% vs. 11.3%, p =0.001). Genotype 1, who had low viral load at start of therapy, were HCV–RNA negative at 4 weeks, and were adherent to the scheduled therapy had a higher probability of sustained virological response. Patients with sustained virological response had less disease events compared to nonresponders (6.2% vs. 38.3%, p =0.03 by log rank test) during follow-up. Conclusions: In HCV cirrhosis with portal hypertension Peg-interferon plus ribavirin is a feasible treatment. Although the rate of viral eradication is modest, tailoring by genotype and early viral response allows to keep patients on treatment who are more likely to have viral eradication. Patients with viral eradication have fewer disease complications during follow-up. [Copyright &y& Elsevier]

Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with β-thalassemia]. Resistance-associated-substitutions (RAS) were analysed by Geno2pheno-algorithm. Nucleotide-sequence-variability (NSV, at 1%, 2%, 5%, 10% and 15% NGS-cutoffs) and Shannon entropy were estimated. Phylogenetic analysis was performed by Mega6-software and Bayesian-analysis. Results: Phylogenetic analysis showed five transmission-clusters: one involving four HCV-acute onco-hematologic-patients; one involving three HCV-chronic β-thalassemia-patients and three involving both HCV-acute and chronic β-thalassemia-patients. The NS5A-RAS Y93H was found in seven patients, distributed differently among chronic/acute patients involved in the same transmission-clusters, independently from the host-genetic IL-28-polymorphism. The intra-host NSV was higher in chronic-patients versus acute-patients, at all cutoffs analyzed (p < 0.05). Even though Shannon-entropy was higher in chronic-patients, significantly higher values were observed only in chronic β-thalassemia-patients versus acute β-thalassemia-patients (p = 0.01). Conclusions: In nosocomial HCV transmission-clusters, the intra-host HCV quasispecies divergence in patients with acute-infection was very low in comparison to that in chronic-infection. The NS5A-RAS Y93H was often transmitted and distributed differently within the same transmission-clusters, independently from the IL-28-polymorphism. [ABSTRACT FROM AUTHOR]

Highlights: [•] Resistance-associated variants is found in 14% of naÁPve HCV-1b patients. [•] HCV has a low barrier of resistance to PIs. [•] The presence of polymorphisms affects the HCV-1b genetic barrier to PIs. [•] A single transition is required for selection of low to medium resistance mutations. [•] NS3 sequencing is a useful tool for the best use of PIs in future IFN-free regimens. [ABSTRACT FROM AUTHOR]

HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events. In a prospective multicentre study, 2204 HCV patients (F0–F2:29.5%, F3–F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59–74) years and BMI 25.9 (23.1–28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels >200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24–39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral stroke (ICS), were recorded. An overall of 2204 patients were evaluated as control group and 1668 patients after HCV elimination were followed as a case group. Factors associated with CV events were evaluated by uni- and multi-variate analyses. Incident CV rates per 100 patient years in pre-treatment and untreated controls and treated cases were 1.12, 1.14 and 0.44 (p = 0.0001 vs. controls), respectively, and a decreased of relative risk (RR = 0.379; p = 0.0002) was observed. CV risk was 2.0–3.5 times lower then in controls (HR 3.671; 95%C.I.:1.871–7.201; p < 0.001). The calculated number of patients to be treated to get a benefit in a patient was 55.26. The annual incidence reduction of CV events was 0.68%. HCV clearance was independently associated with CV events reduction (OR, 4.716; 95% C.I.:1.832–12.138; p = 0.001). HCV clearance by DAA reduces CV events (IHD and ICS) with both clinical and socio-economic benefits. • HCV clearance by direct-acting antivirals (DAA) significantly reduces the annual incidence of cardio vascular events by 0.68%. • Incident cardiovascular events (CV) rates for 100 patient years in controls was 1.14 and in cases 0.44. • The CV risk after HCV clearance was reduced by 2.0–3.5 folds. • The calculated number of patients to be treated to get a benefit in a patient was 55.26. • HCV clearance was independently associated with CV events reduction. [ABSTRACT FROM AUTHOR]

Background and Aims Recent studies suggest an association between hepatitis C virus (HCV) infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct-acting antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. Materials and methods One hundred eighty-two consecutive patients with HCV and advanced fibrosis or compensated cirrhosis were evaluated. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT ≥1 mm) and carotid plaques, defined as focal thickening of ≥1.5 mm at the level of the common carotid, were evaluated by ultrasonography (US) at baseline and 9–12 months after the end of therapy. Fifty-six percent of patients were male, mean age 63.1 ± 10.4 years, and 65.9% had compensated cirrhosis. One in five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. At baseline, mean IMT was 0.94 ± 0.29 mm, 42.8% had IMT ≥1 mm, and 42.8% had carotid plaques. Results All patients achieved a 12-week sustained virological response. IMT significantly decreased from baseline to follow-up (0.94 ± 0.29 mm vs. 0.81 ± 0.27, p  <0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p  <0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p  = 0.34). These results were confirmed in subgroups of patients stratified for cardiovascular risk factors and liver disease severity. Conclusion HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis with or without additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term. Lay summary Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels. [ABSTRACT FROM AUTHOR]

: Background/AimsHVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN α2b or STD-IFN α2b plus RBV.: MethodsHVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees.: ResultsNo correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients.: ConclusionsBaseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18. [Copyright &y& Elsevier]