Value of Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) in Assessing Liver Fibrosis in Metabolic Dysfunction-Associated Liver Disease: A Comprehensive Review of its Serum Biomarker Role.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a broad condition characterized by lipid accumulation in the liver tissue, which can progress to fibrosis and cirrhosis if left untreated. Traditionally, liver biopsy is the gold standard for evaluating fibrosis. However, non-invasive biomarkers of liver fibrosis are developed to assess the fibrosis without the risk of biopsy complications. Novel serum biomarkers have emerged as a promising tool for non-invasive assessment of liver fibrosis in MAFLD patients. Several studies have shown that elevated levels of Mac-2 binding protein glycosylation isomer (M2BPGi) are associated with increased liver fibrosis severity in MAFLD patients. This suggests that M2BPGi could serve as a reliable marker for identifying individuals at higher risk of disease progression. Furthermore, the use of M2BPGi offers a non-invasive alternative to liver biopsy, which is invasive and prone to sampling errors. Overall, the usage of M2BPGi in assessing liver fibrosis in MAFLD holds great promise for improving risk stratification and monitoring disease progression in affected individuals. Further research is needed to validate its utility in clinical practice and establish standardized protocols for its implementation.

Changes in Cerebrospinal Fluid, Liver and Intima-media-thickness Biomarkers in Patients with HIV-associated Neurocognitive Disorders Randomized to a Less Neurotoxic Treatment Regimen.

The prevalence of neurocognitive impairment in people living with HIV is estimated between 30 and 50%. The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. Aim of the study was to measure the change in CSF biomarkers, Fibroscan and IMT measurements in PLWH with HAND randomized to a less neurotoxic regimen, or continuing their treatment. Adult patients with HAND were screened and enrolled if presenting no major resistance associated mutations, no HIV viral replication, not on efavirenz or darunavir, with R5-tropic HIV and without major confounding conditions. Lumbar puncture, IMT and Fibroscan measurements were performed. After 1:1 randomization to a less neurotoxic regimen consisting of darunavir/cobicistat plus emtricitabine plus maraviroc, or mantaining actual care, tests were repeated after 24 weeks: CSF biomarkes (HIV RNA, tau, p-tau, Beta-amyloid1-42, S100Beta and neopterin) were included. Non-parametric tests (Mann-Whitney and Wilcoxon's) were used. 28 participants completed the study. Male and European ancestry were prevalent; median age was 55 years (51-60). All patients were virally suppressed; median CD4 + count was 626 cell/uL (469-772). Baseline characteristics were similar between the study arms. A significant decrease in CSF p-tau and an increase in CSF neopterin and NFL were observed. We observed a significant reduction in liver stiffness at W24. Despite a small sample size we observed changes in neuromarkers and in hepatic stiffness in patients randomized to the experimental arm. We observed changes in CSF biomarkers (lower phosphorylated-tau and higher neopterin and NFL) that need to be replicated in large cohorts. Subclinical neurotoxicity may be observed in patients with HAND and warrants prospective studies.

Application of Noninvasive Tools to Decide the Need for Beta-Blockers for Variceal Bleeding Prophylaxis in Compensated Advanced Liver Disease: A Decision Curve Analysis.

Background and aims: Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up. Methods: This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy. Results: A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9-35) months. The 1-year and 3-year rate of VB with all NITs was 5.7-7.4% and 13.2-16.4% among high-risk and 0-2.3% and 0-5% among low-risk subgroups, respectively (P < 0.001) in both viral and nonviral aetiologies. Among patients classified as low risk on Baveno-VI criteria, none developed VB on follow-up. At thresholds of <3% event rate of VB, Baveno-VI (NNT-176), platelet-albumin (NNT-576) and anticipate platelet (NNT-233) criteria were superior, whereas endoscopic stratification was superior above this event rate on DCA. Conclusions: The use of both elastography and blood-based NITs at baseline can accurately identify the need for NSBB for VB prophylaxis in patients of cACLD on follow-up.

Non-invasive diagnosis of nonalcoholic fatty liver disease in patients with type 2 diabetes.

Liver disease has emerged as a significant cause of death in people with type 2 diabetes (T2D). Due to a common underlying pathogenic mechanism, namely insulin resistance, T2D represents the main risk factor for nonalcoholic fatty liver disease (NAFLD), characterized by a buildup of fat in the liver. Globally, NAFLD is the most common liver disease, affecting a quarter of the general adult population. The development of nonalcoholic steatohepatitis (NASH) signifies an increased risk of liver fibrosis progression that can result in cirrhosis, hepatocellular carcinoma (HCC), and death. Liver fibrosis progression and development of cirrhosis is mostly asymptomatic until complications from decompensated end-stage liver disease arise. Traditionally, liver biopsy is used to diagnose NASH and stage fibrosis, however, it is invasive and costly. Non-invasive diagnostic alternatives include serum biomarkers and imaging techniques. Early identification of advanced liver fibrosis is pivotal to prompt initiation of targeted surveillance, including screening for HCC, as well as providing options for current and investigational therapeutic interventions to reduce fibrosis progression. This review gives an update on non-invasive diagnostic tools for NAFLD and liver fibrosis in the specific context of T2D, providing clinicians a pragmatic diagnostic approach to this frequent comorbidity in diabetes medicine.

Brazilian Society of Hepatology and Brazilian College of Radiology practice guidance for the use of elastography in liver diseases.

In 2015 the European Association for the Study of Liver Diseases (EASL) and the Asociación Latinoamericana para el Estudio del Hígado (ALEH) published a guideline for the use of non-invasive markers of liver disease. At that time, this guideline focused on the available data regarding ultrasonic-related elastography methods. Since then, much has been published, including new data about XL probe use in transient elastography, magnetic resonance elastography, and non-invasive liver steatosis evaluation. In order to draw evidence-based guidance concerning the use of elastography for non-invasive assessment of fibrosis and steatosis in different chronic liver diseases, the Brazilian Society of Hepatology (SBH) and the Brazilian College of Radiology (CBR) sponsored a single-topic meeting on October 4th, 2019, at São Paulo, Brazil. The aim was to establish specific recommendations regarding the use of imaging-related non-invasive technology to diagnose liver fibrosis and steatosis based on the discussion of evidence-based topics by an organizing committee of experts. It was submitted online to all SBH and CBR members. The present document is the final version of the manuscript that supports the use of this new technology as an alternative to liver biopsy.

Exosomes: A Source for New and Old Biomarkers in Cancer.

Clinical oncology needs reliable tumor biomarkers to allow a follow-up of tumor patients who do not necessarily need invasive approaches. To date, the existing biomarkers are not sufficiently reliable, and many of them have generated more problems than facilitating the commitment of clinical oncologists. Over the last decades, a broad family of extracellular vesicles, with size ranging between micro to nano, has been raised as a new hope for potential sources of new tumor biomarkers. However, while knowledge in the field is increasing, we do not currently have definitive information allowing a clinical use of extracellular vesicles in cancer clinics. Recent evidence provides new perspective in clinical oncology, based on data showing that circulating nanovesicles called exosomes may represent a valuable source of tumor biomarkers. In this review, we discuss the existing clinical data supporting a key role of exosomes as a source of tumor biomarkers, including proteins and miRNAs, but also discuss the importance of the expression of known tumor biomarkers when expressed on exosomes.

Circadian health differs between boys and girls as assessed by non-invasive tools in school-aged children.

BACKGROUND & AIMS: Assessment of circadian health is confined to adults. However, understanding circadian status of school-aged children is necessary due to its health implications. The aim was to develop 1) a protocol to assess circadian function in school-aged children by combining the best non-invasive tools previously validated in adults; 2) a score to capture circadian function in children including food timing. This protocol will allow to explore gender differences and to compare the circadian function of school-aged children with adults from the same Mediterranean area. METHODS: Healthy children (8-12 y) from 3 schools in a Mediterranean area of Spain were recruited (n = 248; 125 males and 123 females). Several non-invasive tools were used: a) 7-day-diaries of food timing and food intake, physical-activity and sleep, b) Munich-chronotype-self-reported-questionnaire; c) cortisol and melatonin saliva determinations; d) 7-day-rhythms of wrist temperature (T), activity (A), position (P) and the integrative variable TAP e) 7-day-light exposure. RESULTS: We have constructed the first school-aged children population for the assessment of circadian function (ONTIME-Jr) and a new circadian score has been developed. Among circadian-related measures, TAP was the most suitable and reliable to determine circadian system characteristics. Circadian function was better in girls than in boys [circadian score (AU) Mean ± SD (girls, 1216 ± 153 vs. 1159 ± 173 boys, P = 0.012)], and also in school-aged children than in adults from the same Mediterranean area (Circadian-Function-Index: children 0.47 ± 0.06 vs. adults 0.45 ± 0.06 P = 0.001). CONCLUSIONS: A new protocol, including TAP and food timing, demonstrated to be reliable in assessing circadian function in children. These non-invasive techniques provide the wherewithal for paediatricians to assess circadian function in clinical practice. TRIAL REGISTRATION: Chronobiology and childhood obesity (ONTIME-Jr: Obesity, Nutrigenetics, Timing and Mediterranean, Junior). ClinicalTrials.gov ID: NCT02895282, October 2014.

Herramientas invasivas y no invasivas para el diagnóstico de cáncer oral: revisión de la literatura / Invasive and non-invasive tools for the diagnosis of oral cancer: review of the literature

El cáncer oral es una neoplasia frecuente a nivel mundial; su diagnóstico se realiza de forma tardía por lo menos en un 50-60 por ciento de los casos, lo que empeora el pronóstico de los pacientes, ya que a mayor estadio, mayor es la tasa de mortalidad. Por lo tanto, es fundamental contar con herramientas que permitan realizar un diagnóstico temprano y tratamiento oportuno, sobre todo cuando existen lesiones premalignas clínicamente identificables. En el presente estudio se revisan las herramientas invasivas y no invasivas (modernas y antiguas) que han demostrado utilidad para el diagnóstico de cáncer oral; se basan tanto en técnicas ampliamente disponibles en la práctica clínica como en otras aún no disponibles, pero que podrían implementarse con una apropiada coordinación entre el profesional dedicado a la clínica y los investigadores.

Oral cancer is a neoplasm that is frequent on a worldwide level andis diagnosed late in at least 50-60% of the cases. Its late detection worsens the prognosis of patients because it is associated with a greater mortality. Therefore, it is essential to have tools that allow a timely diagnosis when premalignant lesions present and when there are noclinically identifi able premalignant lesions. In the present study, wereview the invasive and non-invasive tools (modern and old) that haveproven useful for the diagnosis of oral cancer; they are based bothon techniques widely available in clinical practice and on techniques not yet available, but that could be implemented with appropriate coordination between the clinic professional and the researchers.

PD-L1 expressing circulating tumour cells in head and neck cancers.

BACKGROUND: Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a promising immunotherapeutic approach for the management and treatment of head and neck cancer patients who do not respond to 1st/2nd line therapy. However, as checkpoint inhibitors are cost intensive, identifying patients who would most likely benefit from anti PD-L1 therapy is required. Developing a non-invasive technique would be of major benefit to the patient and to the health care system. CASE PRESENTATION: We report the case of a 56 year old man affected by a supraglottic squamous cell carcinoma (SCC). A CT scan showed a 20 mm right jugulodigastric node and suspicious lung lesions. The lung lesion was biopsied and confirmed to be consistent with SCC. The patient was offered palliative chemotherapy. At the time of presentation, a blood sample was taken for circulating tumour cell (CTC) analysis. The dissemination of cancer was confirmed by the detection of CTCs in the peripheral blood of the patient, measured by the CellSearch System (Janssen Diagnostics). Using marker-independent, low-shear spiral microfluidic technology combined with immunocytochemistry, CTC clusters were found in this patient at the same time point, expressing PD-L1. CONCLUSION: This report highlights the potential use of CTCs to identify patients which might respond to anti PD-L1 therapy.