Clinical Study Cirrhosis and Rapid Virological Response to Peginterferon Plus Ribavirin Determine Treatment Outcome in HCV-1 IL28B rs12979860 CC Patients

Background. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphism is associated with high rates of sustained virological response (SVR) to peginterferon (PegIFN) and ribavirin (Rbv) in hepatitis C virus genotype-1 (HCV-1) patients. The impact of baseline predictors of treatment outcome and their interplay with viral kinetics in HCV-1 CC patients has not been fully evaluated. Aim. To identify baseline and on-therapy predictors of treatment failure in HCV-1 IL28B CC patients. Methods. Treatment-naïve HCV-1 patients, compliant to PegIFN and Rbv who did not discontinue treatment for nonvirological reasons, were analyzed. Results. 109 HCV-1 IL28B CC were studied. Sixty were males, 39 with BMI >25, 69 with >600,000 IU/mL HCV RNA, 15 with HCV1a, and 30 with cirrhosis. Overall, 75 (69%) achieved an SVR; cirrhosis was the only baseline predictor of treatment failure (OR: 2.58, 95% CI: 1.07-6.21) as SVR rates were 53% in cirrhotics versus 75% in noncirrhotics ( = 0.03). HCV RNA undetectability (<50 IU/mL) at week 4 (RVR) was achieved by 58 patients (53%). The SVR rates were independent of RVR in noncirrhotics, 76% (34/45) RVR (+) and 74% (25/34) RVR (−) ( = 0.9). In cirrhotic patients, SVR rates were significantly higher in RVR (+) compared to RVR (−) (10/13 (77%) versus 6/17 (35%) = 0.03). Conclusions. In HCV-1 IL28B CC patients, cirrhosis is the only clinical baseline predictor of PegIFN and Rbv treatment failure. However, in IL28B CC cirrhotics, the achievement of RVR identifies those patients who still have high rates of SVR to Peg-IFN/Rbv therapy

Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients

Background/Aims The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. Methods cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. Results One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB. Conclusions Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

The beginning of the Neolithic in the Po Plain (northern Italy): Problems and perspectives

The Po Valley is one of the major physiographic units of northern Italy. It can be considered as a key area for the interpretation of long-term historical events and processes because of its location midway between the Mediterranean world and continental Europe. This paper is an updated summary of our knowledge of the Early Neolithic farming communities of the region. In particular it discusses data derived from radiocarbon dated sites. Its aim is to provide the international audience with an updated view of the topic, based on the discussion of a new series of AMS radiocarbon results, to frame the earliest producing communities of the Po Valley into the more general picture of the Neolithization of Italy. To achieve the goal, apart from radiocarbon assays, we have taken into consideration material culture remains, subsistence economy, environmental resources, and data gathered from archaeometric analyses and technology

New Evidence of Ancestral Landscape in Trentino in the Copper and Bronze Ages: the Ritual Sites of Cles-Campi Neri and La Vela di Trento

Recent investigations (1999-2007) carried out at the site of Cles-Campi Neri in the Valle di Non have brought to light a circular stone structure which can be attributed to a period between the Late Copper Age and the initial phase of the Early Bronze Age. Two structural phases have been identified. The earlier one saw the presence of a large enclosure made up of large blocks enclosing a smaller structure. The items found at the upper levels are made up of flint tools altered by heat. There are also small agglomerations of calcined human bones. In the subsequent phase the area inside the large enclosure was filled in with a platform made up of stones and pebbles, covered and surrounded by organic soil, in which hundreds of flint tools and flakes have been found, along with rarer fragments of pottery. The agglomerations of calcined human bones continue in this phase. Other circular stone structures are positioned along the external perimeter of the platform. Initial analysis of the structural context and the overall material culture, the presence of probable food offerings, suggested by palaeobotanical analysis, and of cremated human remains, make it possible to surmise that the site may have been linked to ritual practices or complex funeral rites. There are considerable similarities between the site of Cles-Campi Neri and the funeral and cult complex dating back to the Copper Age discovered in 2006 at La Vela di Trento (sector Vela IX) in the Adige valley. The cult area developed diachronically according to the principle of horizontal stratigraphy, illustrating the progressive extension of the structure from the centre towards the outside. It was made up of a series of stone rings delimiting the structured platforms. The placing of the remains of human skeletons and animal remains, mostly calcined, on these has been documented, along with archaeological material including flint tools, parts of copper and stone ornaments and occasional pottery sherds. It has also been ascertained that fires were lit. A baby was found buried in a jar (pithos burial) in the southern part of the area investigated. This can be attributed to the Early Bronze Age. The structure brought to light at La Vela very probably represents evidence of more extensive rites and funeral practices linked to the cult of ancestors, according to a practice also documented in other alpine areas.Endrizzi Lorenza, Mottes Elisabetta, Nicolis Franco, Degasperi Nicola. New Evidence of Ancestral Landscape in Trentino in the Copper and Bronze Ages: the Ritual Sites of Cles-Campi Neri and La Vela di Trento. In: Ancestral Landscape. Burial mounds in the Copper and Bronze Ages (Central and Eastern Europe – Balkans – Adriatic – Aegean, 4th-2nd millennium B.C.) Proceedings of the International Conference held in Udine, May 15th-18th 2008. Lyon : Maison de l'Orient et de la Méditerranée Jean Pouilloux, 2012. pp. 511-522. (Travaux de la Maison de l'Orient et de la Méditerranée. Série recherches archéologiques, 58

New Evidence of Ancestral Landscape in Trentino in the Copper and Bronze Ages: the Ritual Sites of Cles-Campi Neri and La Vela di Trento

Recent investigations (1999-2007) carried out at the site of Cles-Campi Neri in the Valle di Non have brought to light a circular stone structure which can be attributed to a period between the Late Copper Age and the initial phase of the Early Bronze Age. Two structural phases have been identified. The earlier one saw the presence of a large enclosure made up of large blocks enclosing a smaller structure. The items found at the upper levels are made up of flint tools altered by heat. There are also small agglomerations of calcined human bones. In the subsequent phase the area inside the large enclosure was filled in with a platform made up of stones and pebbles, covered and surrounded by organic soil, in which hundreds of flint tools and flakes have been found, along with rarer fragments of pottery. The agglomerations of calcined human bones continue in this phase. Other circular stone structures are positioned along the external perimeter of the platform. Initial analysis of the structural context and the overall material culture, the presence of probable food offerings, suggested by palaeobotanical analysis, and of cremated human remains, make it possible to surmise that the site may have been linked to ritual practices or complex funeral rites. There are considerable similarities between the site of Cles-Campi Neri and the funeral and cult complex dating back to the Copper Age discovered in 2006 at La Vela di Trento (sector Vela IX) in the Adige valley. The cult area developed diachronically according to the principle of horizontal stratigraphy, illustrating the progressive extension of the structure from the centre towards the outside. It was made up of a series of stone rings delimiting the structured platforms. The placing of the remains of human skeletons and animal remains, mostly calcined, on these has been documented, along with archaeological material including flint tools, parts of copper and stone ornaments and occasional pottery sherds. It has also been ascertained that fires were lit. A baby was found buried in a jar (pithos burial) in the southern part of the area investigated. This can be attributed to the Early Bronze Age. The structure brought to light at La Vela very probably represents evidence of more extensive rites and funeral practices linked to the cult of ancestors, according to a practice also documented in other alpine areas.Endrizzi Lorenza, Mottes Elisabetta, Nicolis Franco, Degasperi Nicola. New Evidence of Ancestral Landscape in Trentino in the Copper and Bronze Ages: the Ritual Sites of Cles-Campi Neri and La Vela di Trento. In: Ancestral Landscape. Burial mounds in the Copper and Bronze Ages (Central and Eastern Europe – Balkans – Adriatic – Aegean, 4th-2nd millennium B.C.) Proceedings of the International Conference held in Udine, May 15th-18th 2008. Lyon : Maison de l'Orient et de la Méditerranée Jean Pouilloux, 2012. pp. 511-522. (Travaux de la Maison de l'Orient et de la Méditerranée. Série recherches archéologiques, 58

L’anagrafe dell’handicap della Provincia autonoma di Trento: aggiornamento dei dati al 31 dicembre 2016

[The register of the handicap of the Autonomous Province of Trento: updating the data as of December 31, 2016] The Authors, examining the Italian welfare system and the contents of Law 104/92 (“Framework Law for assistance, social integration, and rights of the handicapped”), present a statistical analysis of the handicap database in Province of Trento.The Law 104/92 aims, among others, at guaranteeing the respect for human dignity, as well as the rights to freedom and autonomy of persons with disabilities, while promoting their integration in families, schools, work and society; preventing and removing negative conditions that stop the human development, the highest possible level of autonomy and participation in social life, as well as the enjoyment of civil, political and patrimonial rights; achieving a functional and social rehabilitation of people with physical and sensory impairment, while ensuring adequate services and prevention, care and rehabilitation measures, as well as a legal and economic protection; preparing adequate initiatives to overcome marginalization and social exclusion

12 weeks ombitasvir/paritaprevir\u2013ritonavir\u202f+\u202fribavirin achieve high SVR rates in HCV-4 patients with advanced fibrosis

Background: Ombitasvir/paritaprevir-ritonavir (OBT/PTV-r) plus ribavirin (RBV) for 12 weeks in hepatitis C virus (HCV) genotype 4 patients with advanced fibrosis has been only investigated in clinical trials. Aims: To assess safety and efficacy of OBT/PTV-r + RBV for 12 weeks in real-life HCV-4 patients with advanced fibrosis. Methods: HCV-4 patients with advanced fibrosis consecutively receiving OBT/PTV-r + RBV for 12 weeks in a single center were enrolled. Fibrosis was staged by transient elastography (TE) (F3: >= 10 kPa; F4 >= 11.9 kPa) or histologically. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks post-treatment. Results: Between January 2016 and February 2017, 49 HCV-4 patients were included: median age 54 (39-72) years, 84% males, 59% Egyptians, 35% fibrosis F3 and 65% F4, all Child Pugh class A. Median RBV dose was 1200 (200-1200) mg/day. At ITT analysis, 47 (96%) patients achieved an SVR (100% at PP analysis). SVR was not affected by ancestry (Egyptian vs. Italian 97% vs. 95%, p = 1.0), fibrosis stage (F3 vs. F4 100% vs. 94%, p = .53), presence of baseline resistance associated substitutions (RASs) or RBV reduction. Conclusions: We report 100% SVR with 12-weeks of OBT/PTV-r + RBV in HCV-4 patients with advanced liver disease, including compensated cirrhotics