Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(8), P. 487 - 503

Published: March 17, 2023

Language: Английский

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Obese visceral fat tissue inflammation: from protective to detrimental?

BMC Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Dec. 27, 2022

Abstract Obesity usually is accompanied by inflammation of fat tissue, with a prominent role visceral fat. Chronic in obese tissue lower grade than acute immune activation for clearing the from an infectious agent. It loss adipocyte metabolic homeostasis that causes resident cells supporting functions and regaining homeostasis. Initially, excess influx lipids glucose context overnutrition met growth proliferation. Eventual lipid overload hypertrophic adipocytes leads to endoplasmic reticulum stress secretion variety signals causing increased sympathetic tone, lipolysis adipocytes, uptake macrophages, matrix remodeling, angiogenesis, cell activation. Pro-inflammatory signaling system release amounts pro-inflammatory other mediators resulting enhanced tissue-protective responses. With chronic overnutrition, these protective actions are insufficient, death as well senescence several types seen. This structural damage expression or immunostimulatory components monocytes many types, contribution stromal cells. Matrix remodeling angiogenesis further intensified possibly detrimental fibrosis. The accumulation senescent also may be via eventual spread state affected neighboring microRNA-containing vesicles. Obese can viewed initially response order cope ambient nutrients restore but contribute at later stage.

Language: Английский

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Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(4), P. 294 - 311

Published: Feb. 29, 2024

Language: Английский

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Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

ESMO Open, Journal Year: 2022, Volume and Issue: 7(6), P. 100591 - 100591

Published: Oct. 6, 2022

A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy.We carried out a retrospective analysis prospectively collected data consecutive patients with advanced HCC, treated atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers 4 countries (Italy, Japan, Republic Korea, and UK). The primary endpoint was overall survival (OS) bevacizumab versus lenvatinib. Secondary endpoints were progression-free (PFS) OS PFS sorafenib. For the secondary endpoints, we on whole population first, then divided cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) non-NAFLD/NASH population.One hundred ninety received 569 210 In population, multivariate showed treatment lenvatinib associated longer [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] (HR 0.67; CI 0.51-0.86; 0.002) compared to bevacizumab. NAFLD/NASH confirmed 0.46; 0.26-0.84; 0.0110) 0.55; 0.38-0.82; 0.031) subgroup patients, no difference observed between those All these results following propensity score matching analysis. By comparing receiving statistically significant observed.The present conducted large number HCC for first time is particular NAFLD/NASH-related HCC.

Language: Английский

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Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 95, P. 101231 - 101231

Published: Dec. 5, 2023

Liver fibrosis, as an excess deposition of extracellular matrix (ECM) components, results from chronic liver injury well persistent activation inflammatory response and fibrogenesis. fibrosis is a major determinant for disease (CLD) progression in the last two decades our understanding on molecular cellular mechanisms underlying fibrogenic CLD has dramatically improved, boosting pre-clinical studies clinical trials designed to find novel therapeutic approaches. From these several critical concepts have emerged, starting reveal complexity pro-fibrotic microenvironment which involves very complex, dynamic interrelated interactions between different hepatic extrahepatic cell populations. This review will offer first recapitulation established pathophysiological basic principles by intentionally focus attention NAFLD/NASH, metabolic-related form with high impact general population emerging leading cause worldwide. NAFLD/NASH-related pro-inflammatory profibrogenic be analysed information cells, mediators signalling pathways taken advantage methodological approaches techniques (single genomics, imaging mass cytometry, vitro two- three-dimensional models, etc.). We next overview recent advancement diagnostic prognostic tools, including serum biomarkers polygenic scores, support analysis biopsies. Finally, this provide current therapies treatment NAFLD/NASH patients.

Language: Английский

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Nonalcoholic fatty liver disease and hepatocellular carcinoma:Insights in epidemiology, pathogenesis, imaging, prevention and therapy

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 93, P. 20 - 35

Published: May 4, 2023

Language: Английский

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Inflammatory processes involved in NASH-related hepatocellular carcinoma

Bioscience Reports, Journal Year: 2023, Volume and Issue: 43(1)

Published: Jan. 1, 2023

Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. In recent years nonalcoholic fatty liver disease (NAFLD) becoming a growing HCCs and incidence NAFLD-related expected to further dramatically increase by next decade. Chronic inflammation regarded as driving force NAFLD progression key factor in hepatic carcinogenesis. Hepatic results from persistent stimulation innate immunity response hepatocellular injury gut dysbiosis well activation adaptive immunity. However, relative roles processes HCC are still incompletely characterized. This due complex interplay between different cell populations, which also strongly influenced gut-derived bacterial products, metabolic/nutritional signals. Furthermore, carcinogenic mechanisms NAFLD/NASH appear involve signals mediated hypoxia inducible factors. review discusses data regarding contribution inflammatory cells their possible impact on patient current treatments.

Language: Английский

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SGLT2 inhibitor promotes ketogenesis to improve MASH by suppressing CD8+ T cell activation

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(10), P. 2245 - 2261.e6

Published: Sept. 6, 2024

Language: Английский

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Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity

Nutrients, Journal Year: 2024, Volume and Issue: 16(9), P. 1388 - 1388

Published: May 3, 2024

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by accumulation of lipid species hepatocytes, leading inflammation that can progress steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing encompass genetic variations metabolic disorders such obesity, diabetes, insulin resistance. Moreover, transgenerational influences, resulting an imbalance gut microbial composition, epigenetic modifications, dysregulated hepatic immune responses offspring, play a pivotal role development. Maternal nutrition shapes profile microbiota-derived metabolites exerting significant influence on system regulation development syndrome offspring. In this review, we summarize evidence elucidating intricate interplay between microbiota, epigenetics, immunity fetuses exposed maternal nutrition, its impact onset Furthermore, potential therapeutic strategies targeting network are also discussed.

Language: Английский

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Tumor biology and immune infiltration define primary liver cancer subsets linked to overall survival after immunotherapy

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(6), P. 101052 - 101052

Published: May 23, 2023

Primary liver cancer is a rising cause of deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces potent response subset patients, rates vary among individuals. Predicting which patients will respond to great interest field. In retrospective arm National Cancer Institute Cancers Liver: Accelerating Research Immunotherapy by Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples profile transcriptome and genomic alterations 86 hepatocellular carcinoma cholangiocarcinoma prior following inhibitor treatment. Using supervised unsupervised approaches, identify stable molecular subtypes linked overall survival distinguished two axes aggressive tumor biology microenvironmental features. Moreover, responses treatment differ between subtypes. Thus, heterogeneous may be stratified status indicative inhibitors.

Language: Английский

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