Predictive biomarkers of the response of hepatocellular carcinoma (HCC) to Lenvatinib therapy have not yet been clarified. The aim of this study was to identify clinically significant biomarkers of response to Lenvatinib therapy, to target strategies against HCC. Levels of circulating angiogenic factors (CAFs) were analyzed in blood samples collected at baseline and after introducing lenvatinib, from 74 Child-Pugh class A HCC patients who received lenvatinib. As CAF biomarkers, serum vascular endothelial growth factor (VEGF), fibroblast growth factor 19 (FGF19), FGF23, and angiopoietin-2 (Ang-2) were measured using enzyme-linked immunosorbent assays. Results: Significantly increased FGF19 (FGF19-i) levels and decreased Ang-2 (Ang-2-d) levels were seen in Lenvatinib responders as compared to non-responders (ratio of FGF19 level at 4 weeks/baseline in responders vs. non-responders: 2.09 vs. 1.32, respectively, p = 0.0004; ratio of Ang-2 level at four weeks/baseline: 0.584 vs. 0.810, respectively, p = 0.0002). Changes in FGF23 and VEGF levels at four weeks versus baseline, however, were not significantly different in responders versus non-responders. In multivariate analysis, the combination of serum FGF19-i and Ang-2-d was the most independent predictive factor for Lenvatinib response (Odds ratio, 9.143; p = 0.0012). Furthermore, this combination biomarker showed the greatest independent association with progression-free survival (Hazard ratio, 0.171; p = 0.0240). Early changes in circulating FGF19 and Ang-2 levels might be useful for predicting clinical response and progression-free survival in HCC patients on Lenvatinib therapy.
Fusion imaging with CEUS appears to be a useful method for the early evaluation of the efficacy of RFA for the treatment of HCCs with iso-echoic or unclear margins on conventional US.
Fatty changes are frequently observed in small, well-differentiated hepatocellular carcinomas (HCCs), but are rarely observed in large (over 30 mm in diameter) lesions. Here, we report a 76-year-old man who developed a large (58 mm in diameter), well-differentiated HCC with diffuse extensive fatty changes in the right lobe of the liver. He had no history of alcohol abuse, obesity, or hepatitis B or C infection, and no autoantibodies, but he did have type 2 diabetes. The serum alpha-fetoprotein level was within the normal range, and ultrasonography showed a round hyperechoic lesion. Dynamic contrast-enhanced computed tomography revealed a tumor with inhomogeneous low attenuation in the arterial, portal, and venous phases, mimicking an angiomyolipoma. The patient underwent central bisegmentectomy of the liver, and the histological diagnosis was well-differentiated HCC with diffuse extensive fatty changes. The surrounding non-cancerous area was normal. A review of the published literature found six published cases of large, well-differentiated HCC with extensive fatty changes. Unlike the patients in most previous reports, our patient did not have any underlying liver disease and had no history of alcohol abuse.
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