1,721,144 research outputs found
c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma
No full textc-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical -investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC
DAAs for HCV and risk of hepatocellular carcinoma: current standpoint
No full textIt is a commentary on a hot topic and according it does not have an abstrac
Stereotactic body radiotherapy for patients with hepatocellular carcinoma and intermediate grade cirrhosis – Authors' reply
No full textNon-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis
No full textUnderlying liver cirrhosis is present in most patients with hepatocellular carcinoma, and liver transplantation is the only treatment strategy to cure both diseases. All other hepatocellular carcinoma treatment strategies have to take into account residual liver function that concurs with the patient's prognosis and might limit their feasibility. In patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B (CPT-B), owing to borderline liver function, any intervention might be offset by liver function deterioration. In this setting, the decision for hepatocellular carcinoma treatment requires a comprehensive assessment of liver function, not restricted to the CPT classification, in addition to a careful evaluation of the prognostic effect of hepatocellular carcinoma compared with cirrhosis. In this Review, we provide an overview of the literature regarding the benefits and harms of non-transplant therapies in patients with hepatocellular carcinoma and CPT-B cirrhosis
Surrogate Markers for Antimitochondrial Antibody-Negative Primary Biliary Cholangitis
No full textNew Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) has been reported by Reig et al as potential biomarkers in primary biliary cholangitis (PBC). They also reported changes of these
antibodies over time, and described the association with clinical outcomes. The authors found that anti-HK1 and anti-KLHL12 were positive in 46.1% and 22.8% of patients, respectively, and changed
overtime in 13.3% and 5.5% of patients, respectively. Interestingly, anti-HK1 or antiKLHL12 antibodies were detected in 6 (37.5%) of the 16 patients with antimitochondrial antibody (AMA), and in 4
(40%) of the 10 AMA, anti-gp210– and anti-sp100–seronegative patients. Moreover, a lower response to ursodeoxycholic acid was observed in antiHK1–positive patients according only to
Toronto criteria (74% vs 87%, P , 0.02).
It is well known that antinuclear antibodies (ANA) demonstrated high PBC specificity and high diagnostic value in AMA-negative PBC patients, particularly the anti-sp100 and anti-gp210 antibodies corresponding to the immunofluorescence PBC-specific ANA patterns of multiple nuclear dots (MND) and rim-like membranous (RL/M), respectively.
It would therefore be relevant to test the new antibodies described by Reig et al. in multicenter studies in different geographical areas on a subgroup of patients who are negative for both AMA and all
ANAs as detected by immunofluorescence and/or by immunoenzymatic assays with recombinant antigens
Radiologic criteria of response to systemic treatments for hepatocellular carcinoma
No full textSorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed
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
Full text linkWe 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
Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure
No full textBackground: No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Methods: Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Results: Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500. mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3). Conclusions: Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study
The importance of liver functional reserve in the non-surgical treatment of hepatocellular carcinoma
No full textThe aim of any oncological treatment is not just to eliminate the tumour, but to maximise patient survival and quality of life. Since the liver has a vital function, any radical treatment that severely compromises liver function will result in a shortening of life expectancy, rather than a prolongation. Furthermore, even non-severe liver damage may prevent the delivery of further effective therapies. This is particularly important in the case of hepatocellular carcinoma (HCC), as it is associated with underlying cirrhosis in most patients - cirrhosis itself is not only a potentially lethal disease and independent prognostic factor in HCC, but it also makes liver function fragile. Accordingly, some information about liver dysfunction is included in most staging systems for HCC and can be used to guide the selection of treatments that the functional liver reserve can tolerate. Unfortunately, the prediction of functional damage to the liver in the case of antitumor treatments is very challenging and still suboptimal in any given patient. Moreover, while the assessment of functional reserve can now be used to avoid postoperative liver failure in the surgical setting, its use has been less well clarified for non-surgical therapies, which is of particular relevance today, as several lines of effective non-surgical treatments, including systemic therapies, have become available. The present article will a) critically review the implications of the assessment of liver functional reserve in patients with HCC, b) illustrate the available tools to assess liver functional reserve and c) discuss the role of functional assessment for each type of non-surgical therapy for HCC. (C) 2021 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver
Clinical impact of non-organ-specific autoantibodies on the response to combined antiviral treatment in patients with hepatitis C
No full textBACKGROUND: Hepatitis C virus (HCV)-related chronic hepatitis is frequently associated with non-organ-specific autoantibodies (NOSAs), but available data about the relationship between NOSA positivity and the effect of antiviral therapy in persons with hepatitis C are few and controversial. Our aim was to evaluate the impact of NOSA positivity on the outcome of combined antiviral therapy in HCV-positive patients. METHODS: A total of 143 consecutive adult patients with hepatitis C were studied. Antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomal antibody type 1 (LKM1) were detected by indirect immunofluorescence. All patients were treatment naive and received combined antiviral therapy (interferon [IFN]-ribavirin) after enrollment in the study. Patients were classified as nonresponders if HCV RNA was detectable after 6 months of therapy, as relapsers if abnormal transaminase levels and reactivation of HCV replication were observed after the end of treatment, and as long-term responders if transaminase levels were persistently normal and HCV RNA was undetectable 6 months after the end of treatment. RESULTS: Thirty-seven patients (25%) were NOSA positive (SMA was detected in 19 patients, ANA in 10, ANA and SMA in 4, LKM1 in 3, and SMA and LKM1 in 1). The prevalence of long-term response was similar between NOSA-positive patients and NOSA-negative patients (48.6% vs. 56.6%; P=not significant). Compared with HCV genotype 1 (HCV-1), HCV genotypes other than 1 were more often associated with long-term response among NOSA-positive patients (93.3% vs. 30%; P=.0017). The overall rate of long-term response, irrespective of NOSA status, was 54.5%. Detection of HCV-1 and elevated gamma-glutamyl transpeptidase serum levels were independent negative prognostic factors of treatment response (P=.007 and P=.026, respectively). CONCLUSIONS: Combined antiviral treatment (IFN-ribavirin) is safe and effective in NOSA-positive patients with hepatitis C, even if long-term response is less likely in those infected with HCV-1
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