Advanced liver disease outcomes after hepatitis C eradication by human immunodeficiency virus infection in PITER cohort

Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated

Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Optimization of a buffer layer for cubic silicon carbide growth on silicon substrates

abstract A procedure for the optimization of a 3C–SiC buffer layer for the deposition of 3C–SiC/(001) Si is described. After a standard carbonization at 1125 1C, SiH4 and C3H8 were added to the gas phase while the temperature was raised from 1125 1C to the growth temperature of 1380 1C with a controlled temperature ramp to grow a thin SiC layer. The quality and the crystallinity of the buffer layer and the presence of voids at the SiC/Si interface are related to the gas flow and to the heating ramp rate. In order to improve the buffer quality the SiH4 and C3H8 flows were changed during the heating ramp. On the optimized buffer no voids were detected and a high-quality 1.5 μm3C–SiC was grown to demonstrate the effectiveness of the described buffe

Optimization of a buffer layer for cubic silicon carbide growth on silicon substrates

abstract A procedure for the optimization of a 3C–SiC buffer layer for the deposition of 3C–SiC/(001) Si is described. After a standard carbonization at 1125 1C, SiH4 and C3H8 were added to the gas phase while the temperature was raised from 1125 1C to the growth temperature of 1380 1C with a controlled temperature ramp to grow a thin SiC layer. The quality and the crystallinity of the buffer layer and the presence of voids at the SiC/Si interface are related to the gas flow and to the heating ramp rate. In order to improve the buffer quality the SiH4 and C3H8 flows were changed during the heating ramp. On the optimized buffer no voids were detected and a high-quality 1.5 μm3C–SiC was grown to demonstrate the effectiveness of the described buffe

HeteroSiC & WASMPE 2013

We describe a procedure for the optimization of a 3C-SiC buffer layer for the deposition of 3C-SiC on (001) Si substrates. A 100 - 150 nm thick SiC buffer was deposited after a standard carbonization at 1125 °C, while increasing the temperature from 1125 °C to 1380 °C.Ramp time influenced the quality and the crystallinity of the buffer layer and the presence of voids at the SiC/Si interface. After the optimization of the buffer, to demonstrate its effectiveness, a high- quality 3C-SiC was grown, with excellent surface morphology, crystallinity and low stress

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort

Background and aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. Methods: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. Results: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. Conclusions: The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection

A prospective study of DAA Effectiveness and Relapse Risk in HCV Cryoglobulinemic Vasculitis by the Italian PITER Cohort

none33noBackground & aims: Mixed cryoglobulinemia (MC) is the most common Hepatitis C Virus (HCV) extrahepatic manifestation. We aimed to prospectively evaluate the Cryoglobulinemic Vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium-long term period. Approach: Direct Acting Antiviral (DAA) treated cryoglobulinemic patients, consecutively enrolled in the multicentric PITER cohort, were prospectively evaluated. Cumulative incidence, Kaplan Meier curves were reported for response, clinical deterioration or relapse and survival free rates. Cox regression analysis evaluated factors associated with different outcomes. Results: A clinical response was reported in at least one follow-up point for 373 of 423 (88%) CV patients who achieved a SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A Full Complete Response (FCR) was reached by 164 (38.8%) patients in at least one follow-up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration: 19 months). In patients who achieved a FCR and had an available follow-up (137 patients) a relapse was observed in 13%; it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving a SVR, a clinical non-response was associated with age and renal involvement; a clinical deterioration/relapse was associated with high pre-treatment rheumatoid factor values and a FCR was inversely associated with age, neuropathy, and high cryocrit levels. Conclusions: In CV patients, HCV eradication may not correspond to a persistent clinical improvement and clinical response may fluctuate. This implies an attentive approach to post-SVR evaluation through prognostic factors and tailored treatment.noneKondili, Loreta A; Monti, Monica; Quaranta, Maria Giovanna; Gragnani, Laura; Panetta, Valentina; Brancaccio, Giuseppina; Mazzaro, Cesare; Persico, Marcello; Masarone, Mario; Gentile, Ivan; Andreone, Pietro; Madonia, Salvatore; Biliotti, Elisa; Filomia, Roberto; Puoti, Massimo; Fracanzani, Anna Ludovica; Laccabue, Diletta; Ieluzzi, Donatella; Coppola, Carmine; Rumi, Maria Grazia; Benedetti, Antonio; Verucchi, Gabriella; Coco, Barbara; Chemello, Liliana; Iannone, Andrea; Ciancio, Alessia; Russo, Francesco Paolo; Barbaro, Francesco; Morisco, Filomena; Chessa, Luchino; Massari, Marco; Blanc, Pierluigi; Zignego, Anna LindaKondili, Loreta A; Monti, Monica; Quaranta, Maria Giovanna; Gragnani, Laura; Panetta, Valentina; Brancaccio, Giuseppina; Mazzaro, Cesare; Persico, Marcello; Masarone, Mario; Gentile, Ivan; Andreone, Pietro; Madonia, Salvatore; Biliotti, Elisa; Filomia, Roberto; Puoti, Massimo; Fracanzani, Anna Ludovica; Laccabue, Diletta; Ieluzzi, Donatella; Coppola, Carmine; Rumi, Maria Grazia; Benedetti, Antonio; Verucchi, Gabriella; Coco, Barbara; Chemello, Liliana; Iannone, Andrea; Ciancio, Alessia; Russo, Francesco Paolo; Barbaro, Francesco; Morisco, Filomena; Chessa, Luchino; Massari, Marco; Blanc, Pierluigi; Zignego, Anna Lind

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort

Background and aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. Methods: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. Results: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. Conclusions: The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection