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Purpose: To evaluate safety and efficacy of degradable starch microspheres (DSMs) TACE in a large clinical cohort of patients with unresectable HCC., Materials and Methods: This is a single-center consecutive patients cohort study. The study was approved by local institutional ethics committee. Written informed consent was obtained. From December 2013 to March 2018, 137 cirrhotic patients with unresectable HCC were enrolled. For DSMs-TACE, a mixture of 4 mL of DSMs, 6 mL of non-ionic contrast and doxorubicin at a dose of 50 mg/m 2 were used. Primary end point was long-term outcome, in terms of time to progression (TTP) and overall survival (OS). Secondary endpoints were: safety, liver toxicity, 1-month percentage of tumor necrosis according to the modified RECIST criteria., Results: Two hundred and sixty-seven DSMs-TACE were performed in 137 HCC patients (33 patients in BCLC stage A, 84 patients in BCLC stage B, and 20 in stage C). Patients had a mean nodule number of 3.5 ± 1.2 (SD). Major complications were observed in 6.8% of cases. Post-embolization syndrome was common (101 patients 73.7%). According to mRecist criteria, a high objective response rate was obtained even after just one treatment (84.3% of patients showed complete response or partial response). The median TTP and OS after DSMs-TACE were 12 months and 36 months, respectively. OS at 6 months, 1 year, 2 and 3 years was 98%, 81.3%, 57.9%, 34.9%, respectively., Conclusion: DSMs-TACE is a safe and effective therapy for patients with HCC, allowing to obtain a good rate of OS with excellent local tumor control.

Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment., (© 2018 John Wiley & Sons Ltd.)

Background: An impaired HBsAg-secretion can increase HBV oncogenic-properties. Here, we investigate genetic-determinants in HBsAg correlated with HBV-induced hepatocellular carcinoma (HCC), and their impact on HBsAg-secretion and cell-proliferation., Methods: This study included 128 chronically HBV-infected patients: 23 with HCC (73.9% D; 26.1% A HBV-genotype), and 105 without cirrhosis/HCC (72.4% D, 27.6% A) as reference-group. The impact of mutations on HBsAg-secretion was assessed by measuring the ratio [secreted/intracellular HBsAg] until day 5 post-transfection. The impact of mutations on cell-cycle advancement was assessed by flow-cytometry., Results: Two HBsAg mutations significantly correlated with HCC: P203Q (17.4% [4/23] in HCC vs 1.0% [1/105] in non-HCC, P=0.004); S210R (34.8% [8/23] in HCC vs 3.8% [4/105] in non-HCC, P <0.001); P203Q+S210R (17.4% [4/23] in HCC vs 0% [0/110] in non-HCC, P=0.001). Both mutations reside in trans-membrane C-terminal domain critical for HBsAg-secretion. In in-vitro experiments, P203Q, S210R and P203Q+S210R significantly reduced the ratio [secreted/intracellular HBsAg] compared to wt at each time-point analysed (P <0.05), supporting an impaired HBsAg-secretion. Furthermore, P203Q and P203Q+S210R increased the percentage of cells in S-phase compared to wt, indicating cell-cycle progression (P203Q:26±13%; P203Q+S210R:29±14%; wt:18%±9, P <0.01. Additionally, S210R increased the percentage of cells in G2/M-phase (26±8% for wt versus 33±6% for S210R, P <0.001)., Conclusions: Specific mutations in HBsAg C-terminus significantly correlate with HBV-induced HCC. They hamper HBsAg-secretion and are associated with increased cellular proliferation, supporting their involvement in HCC-development. The identification of viral genetic markers associated with HCC is critical to identify patients at higher HCC-risk that may deserve intensive liver monitoring, and/or early anti-HBV therapy.

Aim: To assess the diagnostic performance of magnetic resonance imaging (MRI) with gadoxetic acid in the identification of hepatocellular carcinoma (HCC) nodules by comparison with histological findings., Methods: In a cohort of patients suffering from cirrhosis of various etiologies (chronic hepatitis C virus (HCV) or hepatitis B virus (HBV), alcohol abuse, cryptogenic forms), we selected 17 patients affected by HCC who were eligible for liver transplantation on the basis of a computed-tomography (CT) total-body examination. Such patients also underwent an MRI examination under basal conditions, and with four dynamic phases, as well as a hepatobiliary phase acquired after at least 20 min and recognized by the excretion of contrast agent into the bile duct, following intravenous administration of 0.05 mol/kg of gadoxetic acid (gadoxetate disodium, Primovist(®); Bayer, Osaka, Japan). The MRI images were then evaluated in a double-blinded experimental setup by two radiologists experienced in imaging of the liver. The diagnosis of HCC was made in the presence of nodular lesions that showed typical or atypical enhancement patterns. The liver was subsequently explanted (on average 47.4 days after MRI evaluation), dissected into 1-cm samples, and histologically evaluated according to the classification of Edmondson-Steiner., Results: At the histopathological examination, 46 nodules were identified, on average 2.7 nodules for each patient. Of these, 37 were hepatocellular carcinomas, 3 were characterized by histologically unrecognizable complete necrosis, and 6 showed high-grade dysplasia. MRI with hepatospecific contrast medium showed inter-observer average values of sensitivity, specificity, and diagnostic accuracy of 94.6, 90, and 93.6 %, respectively. In one case, a nodule was not identified by MRI with gadoxetic acid, even in the hepatospecific phase (false negative (FN)). This result could be implicated to the long time interval between the analysis and the explant (88 days). In another case, there was an overdiagnosis of a HCC with a typical nodular pattern (false positive (FP)), but which most likely should have been attributed to a previous echinococcus cyst. MRI analysis, in combination with the study of the hepatobiliary phase, also showed a greater sensitivity, the same specificity, and a greater diagnostic accuracy compared to MRI evaluated only in the dynamic phases (with an average percentage between the two operators, respectively, of 75.7, 90, and 78 %)., Conclusions: MRI with gadoxetic acid shows a diagnostic accuracy superior to contrast-enhanced MRI, allowing for the diagnosis of additional lesions, and it could be considered as an imaging method to carry out a more appropriate management of waiting lists for liver transplants.