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Background: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is progressively increasing. The aim of this study was to determine the safety and efficacy of conventional transarterial chemoembolization (TACE) in elderly HCC patients compared with younger adults., Methods: A consecutive cohort of unresectable HCC patients treated with TACE as a first-line treatment was retrospectively analyzed. Patients were categorized into "elderly" (≥ 70 years, 80 patients) and "younger" (< 70 years, 145 patients). Liver-related death and progression-free survival after TACE were compared before and after propensity score matching. A competing risk regression analysis was used for univariate/multivariate survival data analysis., Results: cTACE was well tolerated in both groups. The cumulative risk of both liver-related death and progression-free survival after cTACE was comparable between "elderly" and "younger" (death: 73.8% vs 69.4%, P = 0.505; progression-free survival: 48.2% vs 44.8%, P = 0.0668). Propensity model matched 61 patients in each group for gender and Barcelona Clinic Liver Cancer staging. Even after matching, the cumulative risk of liver-related death and of progression-free survival did not differ between the two groups. At multivariate analysis, Child-Pugh class, tumor gross pathology and alpha-fetoprotein were independently associated with the liver-related mortality risk., Conclusions: This study confirms that TACE is well tolerated and effective in patients aged 70 years or more with unresectable HCC as it is for their younger counterparts (< 70 years). Liver-related mortality was not associated with age ≥ 70 years and primarily predicted by tumor multifocality, Child-Pugh class B and an increased alpha-fetoprotein value (> 31 ng/ml).

Objective: Many improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging., Design: Our study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology., Results: A classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN., Conclusion: Our new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. As α-fetoprotein (AFP) is considered a poor surveillance test, we tested the performance of its changes over time., Methods: Eighty patients were diagnosed with HCC (cases) during semiannual surveillance with ultrasonography and AFP measurement were recruited and matched for age, gender, etiology and Child-Pugh class with 160 contemporary cancer-free controls undergoing the same surveillance training group (TG). As a validation group (VG) we considered 36 subsequent patients diagnosed with HCC, matched 1 : 3 with contemporary cancer-free controls. α-Fetoprotein values at the time of HCC diagnosis (T0) and its changes over the 12 (Δ12) and 6 months (Δ6) before cancer detection were considered., Results: In both TG and VG, >80% of HCCs were found at an early stage. In TG, AFP significantly increased over time only in cases. T0 AFP and a positive Δ6 were independently associated with HCC diagnosis (odds ratio: 1.031 and 2.402, respectively). The area under the curve of T0 AFP was 0.76 and its best cutoff (BC) was 10 ng ml(-1) (sensitivity 66.3%, specificity 80.6%). The combination of AFP >10 ng ml(-1) or a positive Δ6 composite α-fetoprotein index (CAI) increased the sensitivity to 80% with a negative predictive value (NPV) of 86.2%. Negative predictive value rose to 99%, considering a cancer prevalence of 3%. In the VG, the AFP-BC was again 10 ng ml(-1) (sensitivity 66.7%, specificity 88.9%), and CAI sensitivity was 80.6% with a NPV value of 90.5%., Conclusions: CAI achieves adequate sensitivity and NPV as a surveillance test for the early detection of HCC in cirrhosis.

The early detection of bacterial infections and hepatocellular carcinoma (HCC) could ameliorate the prognosis of cirrhosis. C-reactive protein and procalcitonin are under investigation in the setting of cirrhosis as markers of sepsis. In the attempt to discriminate bacterial infection from systemic inflammation, the role of novel biomarkers such as lypopolysaccharide binding-protein, mid-regional fragment of pro-adrenomedullin and delta neutrophil index are currently in development. Concerning HCC, many studies attempted to evaluate biomarkers in the hope of ameliorating the accuracy of the surveillance based on ultrasound. The use of α-fetoprotein (AFP) has been extensively investigated, as well as other biomarkers expressed in the serum of HCC patients like lens culinaris agglutinin-reactive fraction of AFP, des-γ-carboxy prothrombin, glypican-3, α-l-fucosidase and their combined use.

We report here two cases of hepatocellular carcinoma (HCC) 90 and 70 months, respectively, after successful treatment with interferon (IFN) and ribavirin for hepatitis C virus (HCV)-related cirrhosis. A 50-year-old Caucasian man and a 66-year-old Caucasian woman with HCV-related cirrhosis were treated with IFN and ribavirin and in both cases a sustained virological response (SVR) was obtained with persistent normalization of serum aminotransferases and continuous disappearance of serum HCV-RNA. Both patients were subsequently followed up within an HCC surveillance programme based on biochemical and ultrasound (US) evaluation every 6 months and the appearance of HCC was detected 90 and 70 months, respectively, after discontinuation of therapy. We introduce these two cases to call attention to the importance of not underestimating the risk of HCC development even many years after complete HCV eradication, especially in the presence of established cirrhosis and concomitance of other risk factors for HCC.

Background & Aims: Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival., Methods: Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care., Results: The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis., Conclusions: TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.

The emergence of drug-resistant virus in hepatitis B virus patients treated with lamivudine is well documented. However, its clinical impact in the long-term treatment of anti-HBe positive compensated cirrhotic patients is not well known. In this study, we treated 22 consecutive patients with anti-HBe compensated cirrhosis with lamivudine for a median period of 42 months. All patients responded to lamivudine, but viral breakthrough occurred in 13 patients (59%) between 9 and 42 months of therapy due to the emergence of a mutant strain. During the follow-up, 11 developed hepatocellular carcinoma. Of these, 10 occurred soon after the emergence of viral resistance, generally showing aggressive behaviour, and one in the nine long-term responder patients (P = 0.013). Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development (risk ratio: 10.4; 95% CI: 1.3-84.9). Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti-HBe positive cirrhosis and warrants further research.

Background/aims: To evaluate the tolerability and therapeutic potential of the immunostimulating adjuvant alpha-1-thymosin in patients with hepatocellular carcinoma., Methodology: Twelve patients with hepatocellular carcinoma were treated with alpha-1-thymosin (900 micrograms/m2 subcutaneously twice per week for 6 months) and transcatheter arterial chemoembolization and compared to a historical control group (matched for gender, age, Okuda staging, Child's score, alpha-fetoprotein serum levels and viral infection) treated with transcatheter arterial chemoembolization alone., Results: No severe side effects were recorded in the 2 treatment groups. The combination of alpha-1-thymosin plus transcatheter arterial chemoembolization resulted in a longer survival that reached statistical significance 7 months after the end of treatment (p < 0.05). Patients receiving combined treatment demonstrated a significant increase in peripheral blood mononuclear cells expressing CD3 (p < 0.05) and CD8 (p < 0.025) 3 months after beginning treatment. They also had a significant increase (p < 0.05) in CD16+ and CD56+ cells after 1 month, and a slight reduction in mononuclear cells expressing CD25, a marker for cell activation. No alterations in the response to phytohemagglutinin stimulation were seen during the alpha-1-thymosin treatment., Conclusions: The absence of toxicity and the favourable effects observed in this open study call for a double blind control study to confirm the efficacy of the combined treatment.

Background: Age is considered one of the important contraindications to surgery for hepatocellular carcinoma (HCC) in cirrhosis patients. We therefore evaluated the safety and prevalence of side effects in endoarterial therapy (EAT) in subjects aged over 65 years compared with younger treated patients., Methods: Thirty-eight patients with HCC aged 65 years and over underwent transcatheter arterial chemoembolization (TACE) (n = 28) or intraarterial chemotherapy (IAC) (n = 10). The survival rate was calculated using Kaplan-Meier's method with respect to a control group consisting of younger treated subjects (44 TACE; 21 IAC) comparable for stage of HCC and severity of the underlying cirrhosis., Results: The comparison between the two groups regarding side effects, procedure-related death, and survival did not show any difference considering the whole EAT procedure. TACE in elderly subjects reached a statistically lower outcome with respect to younger patients (p < .025) but remained statistically superior in survival versus both older and younger patients treated with IAC (p < .05, respectively). Stratifying the patients following the degree of Lipiodol uptake of tumor mass in the three groups (Group I, > 75%; Group II, 50-75%; Group III, < 50%), in the young subjects a higher probability of survival was strictly correlated to a degree of uptake over 75%, while in the elderly patients an impregnation over 50% was sufficient to obtain a satisfactory survival curve., Conclusions: EAT is a reliable and safe therapeutic option for the geriatric patient with HCC, with TACE showing a better efficacy than IAC, requiring a lesser degree of Lipiodol uptake to achieve an improvement of outcome.

Background: Most patients with hepatocellular carcinoma (HCC) are not suitable for surgical therapy. Systemic chemotherapy, immunotherapy, and hormonotherapy have not had convincingly acceptable results. Therefore, transarterial catheter-targeted therapies such as intraarterial chemotherapy (IAC), possibly followed by transcatheter arterial chemoembolization (TACE), have been proposed., Methods: A survival analysis curve was drawn using the Kaplan-Meier method for 164 patients, 100 with HCC who underwent TACE (69) or IAC (31), and a matched historic group of 64 who did not receive specific antineoplastic treatment., Results: A significantly more favorable survival was observed for TACE-treated patients compared with IAC-treated patients (P < 0.001); TACE- and IAC-treated patients had a statistically superior survival than that of untreated patients (P < 0.001 and P < 0.025, respectively). This difference was still significant (P < 0.001) when the patients were subdivided into Classes A and B and Stages I and II following Child's and Okuda's criteria. The TACE- and IAC-treated groups had a good relationship between technical efficacy of therapy and survival. Stratifying the patients according to the degree of iodized oil (Lipiodol Ultrafluid, Guerbet, Aulnay-Sous-Bois, France) uptake in the three groups with Group 1 having an uptake greater than 75% of tumor mass, Group 2 having an uptake of 50%-75%, and Group 3 having an uptake less than 50%, survival at 6, 12, 24, 36, and 48 months was calculated as 94%, 88%, 67%, 53%, and 30%, respectively, for Group 1; 86%, 68%, 13%, 13%, and 0% for Group 2, and 43%, 23%, 6%, 6%, and 0% for Group 3 (Group 1 vs. Group 2: P < 0.001; Group 1 vs. Group 3: P < 0.001; Group 2 vs. Group 3: P < 0.001, respectively). The most important side effects after the intraarterial procedure were fever (46.2%), abdominal pain (36.6%), chemical cholecystitis (8%), and pancreatitis (1.7%). Death strictly related to treatment occurred in two patients; one had massive bleeding due to ruptured esophageal varices, and the other had a subphrenic abscess of a superficial HCC of the VIII segment., Conclusions: Transcatheter arterial chemoembolization and IAC were effective and relatively safe, and the authors believe that they have a primary role in treating patients with unresectable HCC larger than 5 cm; iodized oil uptake can be considered a suitable prognostic marker.