The burden of hepatocellular carcinoma in non-alcoholic fatty liver disease: Screening issue and future perspectives

In recent decades, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the Western world, and the occurrence of its complications, such as hepatocellular carcinoma (HCC), has rapidly increased. Obesity and diabetes are considered not only the main triggers for the development of the disease, but also two independent risk factors for HCC. Single nucleotide polymorphisms (such as PNPLA3, TM6SF2 and MBOAT7) are related to the susceptibility to the development of HCC and its progression. Therefore, an appropriate follow-up of these patients is needed for the early diagnosis and treatment of HCC. To date, international guidelines recommend the use of ultrasonography with or without alpha-fetoprotein (AFP) in patients with advanced fibrosis. Furthermore, the use of non-invasive tools could represent a strategy to implement surveillance performance. In this review, we analyzed the main risk factors of NAFLD-related HCC, the validated screening methods and the future perspectives

Pharmacological therapy of non-alcoholic fatty liver disease: What drugs are available now and future perspectives

The non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease as well as the first cause of liver transplantation. NAFLD is commonly associated with metabolic syndrome (MetS), and this is the most important reason why it is extremely difficult to treat this disease bearing in mind the enormous amount of interrelationships between the liver and other systems in maintaining the metabolic health. The treatment of NAFLD is a key point to prevent NASH progression to advanced fibrosis, to prevent cirrhosis and to prevent the development of its hepatic complications (such as liver decompensation and HCC) and even extrahepatic one. A part of the well-known healthy effect of diet and physical exercise in this setting it is important to design the correct pharmaceutical strategy in order to antagonize the progression of the disease. In this regard, the current review has the scope to give a panoramic view on the possible pharmacological treatment strategy in NAFLD patients

Systemic treatment for hepatocellular carcinoma beyond milan criteria on the waitlist: is it time for a neoadjuvant therapy?

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Pyroprocess Experiments at ENEA Laboratories

A new facility, known as Pyrel III, has been installed at ENEA laboratories for pyrochemical process studies under inactive conditions. It is a pilot plant which allows electrorening and electroreduction experiments to be conducted on simulated fuel. The main component of the plant is a zirconia crucible. The crucible is heated by a furnace which is supported in an externally water-cooled well under the oor of a steel glove-box, where an argon atmosphere is maintained by a continual purge of about 10 L·min-1. The vessel is loaded with LiCl-KCl eutectic salt (59-41 mol%) and is currently operated at 460 °C. Several improvements on Pyrel II (the previous operating plant) have been introduced into Pyrel III. They are described in detail, together with the results from the rst experimental campaign which used lanthanum metal.Moreover, studies about the treatment of chloride salt wastes from pyroprocesses have been conducted in parallel. They follow two main routes: on one hand, a matrix termed sodalite, a naturally occurring mineral containing chlorine, has been synthesized from a mix of nepheline, simulated exhausted salts and glass frit; on the other hand, a novel method proposed by Korea Atomic Energy Research Institute (KAERI) is under assessment. The nal waste forms have been fully characterized with the support of the Politechnique of Milan, by means of density measurements, thermal analysis, and stereomicroscopy observations, FTIR, XRD, and RAMAN spectra, as well as leach tests under static condition

First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. Methods: A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Sequences starting with first-line ATEZO plus BEVA followed by 5 second-line treatments (sorafenib [SORA], lenvatinib [LENVA], regorafenib, cabozantinib, and ramucirumab) were compared. The probability of transition between states (initial treatment, cancer progression, and death) was derived from RCTs. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥ grade 3) were calculated. The incremental safety-effectiveness ratio (ISER) was calculated as the difference in probability of SAEs divided by LYG between the 2 most effective sequences. Results: ATEZO plus BEVA followed by LENVA (median OS, 24 months) or SORA (median OS, 23 months) was the most effective sequence, producing a LYG of 0.50 and 0.42 year, respectively. ATEZO plus BEVA followed by SORA was the safest sequence (SAEs 63%). At a willingness-to-risk threshold of 10% of SAEs for LYG, ATEZO plus BEVA followed by second-line SORA was favored in 72% of cases, while at a threshold of 30% of SAEs for LYG, ATEZO plus BEVA followed by second-line LENVA was favored in 69% of cases. Conclusion: Our simulation model provides a strong rationale to support ongoing trials evaluating second-line tyrosine-kinase inhibitors after first-line ATEZO plus BEVA. Future evidence from ongoing RCTs and prospective real-world studies are needed to prove the net health benefit of sequential treatment options for advanced HCC

Effect of Treatment, during Primary Infection, on Establishment and Clearance of Cellular Reservoirs of HIV-1

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatmen

Impact of biliary stents on the diagnostic accuracy of EUS-guided fine-needle biopsy of solid pancreatic head lesions: A multicenter study

There is no clear evidence of a negative impact of biliary stents on the diagnostic yield of EUS-guided fine-needle biopsy (EUS-FNB) for diagnosing pancreatic head lesions. We aimed to evaluate the association between the presence of biliary stents and the diagnostic accuracy of EUS-FNB. Materials and Methods: A multicenter retrospective study including all jaundiced patients secondary to pancreatic head masses was performed. Patients were divided into two groups according to the presence of a biliary stent placed before EUS-FNB. Pathological results were classified according to the Papanicolaou classification and compared against the final diagnosis. Diagnostic measures in the two groups were compared. Multivariate logistic regression analyses including potential factors affecting EUS-FNB accuracy were performed. Results: Overall, 842 patients were included, 495 (58.8%) without and 347 (41.2%) with biliary stent. A plastic or a metal stent was placed in 217 (62.5%) and 130 (37.5%) cases, respectively. Diagnostic sensitivity and accuracy were significantly higher in patients without biliary stent than in those with stent (91.9% and 92.1% vs. 85.9% and 86.4%, P = 0.010 At multivariate analyses, lesion size (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.02-1.09, P = 0.01) and presence of biliary stent (OR: 0.51, 95% CI: 0.32-0.89, P = 0.01) were independently associated with diagnostic accuracy. In the subgroup of patients with biliary stent, the type of stent (plastic vs. metal) did not impact EUS-FNB yield, whereas the use of larger bore needles enhanced diagnostic accuracy (OR: 2.29, 95% CI: 1.28-4.12, P = 0.005). Conclusions: In this large retrospective study, an indwelling biliary stent negatively impacted the diagnostic accuracy of EUS-FNB. Preferably, EUS-FNB should precede endoscopic retrograde cholangiopancreatography, especially in the case of small tumors

Biofertilización: experiencias realizadas en la provincia del Chaco en cultivos intensivos y extensivos

Rural Extension fosters innovation which is an important tool for solving problems associated with rural producers' needs, for the loss of natural and social capital and for the lack of productive structure diversification. In this work, actions were articulated among AgroTechnical Institute, Directorate of Agriculture, Chaco Directorate of Rural Soil and Water, Institute of Rural Development and Small-size Family Producers (IDRAF) and Chaco Directorate of Territory Support and Agencies. To achieve the aim, participatory methodology was selected. Three major decisions were made as regards place, participants and working method. Biofertilization technology is an efficient alternative in sustainable production, achieving important results as a plant growth promoter and in soil phytopathogens control. The producers were open-minded and determined to implement this technology at the time of carrying out inoculation and different measurements. None of them had previously applied biofertilizers, so training and working cooperatively between producers and technicians was important. It is crucial to continue researching in the field of biofertilizers in different local crops as biological products are influenced by environmental conditions. Socializing about biofertilization and products that are currently on the market is one of the aims shared by the different institutions that work in Chaco.La Extensión Rural, como promotora de la innovación, es una herramienta importante para la resolución de problemas asociados a las necesidades de los productores rurales, la pérdida del capital natural y social, o la falta de diversificación de la estructura productiva. En este trabajo se articularon acciones entre el Instituto Agrotécnico, la Dirección de Agricultura, Dirección de Suelos y Agua Rural del Chaco, Instituto de Desarrollo Rural y Agricultura Familiar (IDRAF) y la Dirección de Apoyo Territorial y Agencias de la provincia del Chaco. Para lograr el objetivo se utilizó un método participativo en donde se definieron 3 grandes decisiones: dónde trabajar, con quién trabajar y cómo trabajar con los participantes. La tecnología de biofertilización es una alternativa eficiente en producción sustentable, logrando resultados importantes como promotora de crecimiento vegetal y en el control de fitopatógenos del suelo. Los productores con los que se trabajó en estas experiencias se mostraron abiertos y dispuestos a probar esta tecnología, siendo ellos los que llevaron adelante la inoculación y las distintas mediciones en los ensayos. Ninguno había aplicado biofertilizantes anteriormente, por lo que fue importante la capacitación y el trabajo en conjunto productor-técnico. Es importante seguir generando información de la respuesta de los biofertilizantes en los distintos cultivos regionales, ya que al ser productos biológicos están influenciados con las condiciones ambientales. La difusión de la biofertilización y de los productos que actualmente se encuentran en el mercado es uno de los objetivos compartidos con las distintas instituciones que trabajamos articuladamente en la provincia del Chaco

Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib

Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline