114 research outputs found

    Mechanisms of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma

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    Simple Summary Immune checkpoint inhibitors (ICIs) are now a cornerstone of systemic treatment for hepatocellular carcinoma (HCC). However, their efficacy is blunted by mechanisms of tumour resistance in many patients. This review reports on the state of the art of resistance to ICIs, focusing on HCC, with the aim to provide clear and direct information to clinicians and researchers. Growing knowledge on the mechanisms of resistance to immunotherapy can indeed guide the choice of and expand the application of novel combined treatments. Hepatocellular carcinoma (HCC) is the most common liver cancer and a relevant global health problem. Immune checkpoint inhibitors (ICIs) represent the most effective systemic treatment for HCC. However, due to primary resistance, approximately 40% of HCC patients do not achieve a disease control with ICIs. Moreover, a similar proportion will experience disease progression after an initial response caused by secondary resistance. This review describes the mechanisms of primary and secondary resistance and reports the ongoing therapeutic strategies to overcome these obstacles

    Intestinal Microbiota, Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma: The Potential Role of Dysbiosis in the Hepatocarcinogenesis

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    Introduction: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Approximately 5–30% of HCC patients lack a readily identifiable risk factor for their cancer, and most of these cases are attributed to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)

    A Case of Advanced Hepatocellular Carcinoma with Bone Metastases Managed with Tyrosine Kinase Inhibitors and Aggressive Palliative Radiation Therapy: Role of Combination Therapy for Extending Survival

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    We report the case of a 68-year-old man with advanced hepatocellular carcinoma (HCC) with multiple bone metastases (BM) treated with tyrosine kinase inhibitors. Despite an insufficient disease control on BM with a progression free survival (PFS) of 6 months, sorafenib was not discontinued and multiple radiation therapy (RT) sessions with a palliative purpose were performed. Thanks to this aggressive radiotherapy approach in order to control the bone tumor burden, the patient has continued sorafenib for 34.6 months achieving an overall survival (OS) of 41.3 months. This result highlights the importance of a tailored management of patients with advanced HCC and the role of the RT for BM control, even if at lower cumulative radiation dose, for extending patient survival

    autoimmune liver disorders and small vessel vasculitis four case reports and review of the literature

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    Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjogren's syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation

    Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis

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    The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk factors such as obesity, type2-diabetes mellitus, and dyslipidemia has led to a worldwide diffusion of NAFLD. In parallel to the increased availability of effective anti-viral agents, NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries in the next years. This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis, management, and treatment of NAFLD. Different scientific societies from Europe, America, and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD. These guidelines are consistent with the key elements in the management of NAFLD, but still, show significant difference about some critical points. We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences. We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions. Differences were noted in: the definition of NAFLD, the opportunity of NAFLD screening in high-risk patients, the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis, in the follow-up protocols and, finally, in the treatment strategy (especially in the proposed pharmacological management). These difference have been discussed in the light of the possible evolution of the scenario of NAFLD in the next years

    Multiple abdominal abscesses complicated by severe sepsis as a result of occult Crohn's disease

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    Intra-abdominal infections represent an important cause of mortality in worldwide population and often require both rapid diagnostic work-up and swift therapeutic decisions. In this paper a relatively frequent pathologic condition in industrialized countries is described as a potential cause of multiple abdominal abscesses with severe sepsis. In the subsequent review of the literature, first-line diagnostic examinations and therapeutic options, both medical and surgical, are discussed according to the most recent guidelines and recommendations

    Management of adverse events with tailored sorafenib dosing prolongs survival of hepatocellular carcinoma patients

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    Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. The impact of the physicians experience on the management of these AEs and the relative implications on clinical outcomes are unknown. We verified if the AEs management changed over time and if these modifications impacted on treatment duration and overall survival (OS)

    Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial.

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    The search for systemic therapies for hepatocellular carcinoma has been characterized by difficulties and failures. Despite recent progresses, many issues are still to be settled. In particular, the development of drugs inhibiting different neoplastic pathways remains a priority for patients intolerant or resistant to antiangiogenic drugs. This task may be daunting, as previous failures extensively demonstrated. We aimed to identify the future perspective of postsorafenib trials analyzing the strengths and the critical points of past and currently undergoing studies, in the light of the most recent evidences in the field. We identified various points (including stratification, biomarkers, end points, radiologic criteria of response, treatment beyond radiologic progression) that should be considered by future trials to reduce the risks of failure

    RANK-RANKL-OPG Axis in MASLD: Current Evidence Linking Bone and Liver Diseases and Future Perspectives

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    Metabolic dysfunction-associated steatotic liver disease (MASLD)-and its worse form, metabolic-associated steatohepatitis (MASH), characterised by inflammation and liver damage-corresponds to the liver's involvement in metabolic syndrome, which constitutes an economic burden for healthcare systems. However, the biomolecular pathways that contribute to steatotic liver disease are not completely clear. Abnormalities of bone metabolism are frequent in people affected by metabolic liver disease, with reduced bone density and an increased risk of fracture. Receptor activator of NF-kappa B (RANK), receptor activator of NF-kappa B ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication
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