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Aims: Sorafenib is the only systemic treatment shown to be effective against advanced hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) has been selected as an alternative therapeutic option for advanced HCC. We investigated the efficacy and safety of HAIC as an alternative treatment for sorafenib in advanced HCC. Methods: Between May 2008 and March 2011, 20 consecutive patients were treated with sorafenib monotherapy as a first-line treatment and 21 consecutive patients who could not take sorafenib because of cost were treated with HAIC monotherapy as an alternative. Sorafenib was administered in 400 mg b.i.d. doses. For HAIC, daily cisplatin (7 mg/m2 on days 1-5) and 5-FU (170 mg/m2 on days 1-5) were infused every 4 weeks. We assessed overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and toxicity. Results: Median OS was 4.9 months (95% CI, 3.4-6.4) for sorafenib and 7.3 months (95% CI, 4.5-10.2) for HAIC ( P = 0.599). Median PFS was 2.0 months (95% CI, 1.96-2.05) versus 3.0 months (95% CI, 1.98-4.02) for sorafenib and HAIC, respectively ( P = 0.303). ORR and disease control rate (DCR) for sorafenib were 10.0 and 35.0% versus 19.0 and 38.1% for HAIC (ORR, P = 0.413; DCR, P = 0.837). Patients treated with HAIC more frequently exhibited grade 3/4 neutropenia (23.8 vs 0% for sorafenib), whereas sorafenib therapy showed grade 3/4 hand-foot skin reaction in 10% of patients. Conclusion: HAIC is a useful alternative treatment for advanced HCC and further prospective investigations are required. [ABSTRACT FROM AUTHOR]

Simple Summary: Further information is necessary regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). When we compared the HCC incidence in non-cirrhotic CHB patients receiving BSV with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model, the standardized incidence ratio (SIR) was significantly reduced to 0.128 at 7 years. The incidence of HCC in patients with cirrhosis was compared using the GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, and the SIR was significantly decreased to 0.371 at 7.5 years. HCC prediction was available for BSV-treated patients using existing models. We concluded that BSV decreases the risk of HCC in patients with CHB, and HCC risk prediction models are applicable. No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) recurrence after liver resection depends upon the stage and histological grade of the tumor and the expression of certain biomarkers. However, it remains unclear which of these factors has the highest predictive value regarding HCC recurrence after surgical resection. Methods: This study investigated the associations among clinicopathological characteristics, expression of biomarkers, and HCC recurrence after liver resection. Fifty-four patients having undergone liver resection for HCC were enrolled prospectively, and their data were analyzed retrospectively. Evaluated variables were clinical data, laboratory findings, modified Union for International Cancer Control (UICC) stage, vascular invasion, histological differentiation, and immunohistochemical staining for fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor, and tumor-necrosis-factor-related apoptosis-inducing ligand receptors 1 and 2. Results: Mean patient age was 58.6 years (range, 30–71), and the mean and SD for follow-up duration were 51.2 ± 34.8 months. Cumulative 1-, 3-, and 5-year recurrence rates were 32.9%, 53.6%, and 68.1%, respectively. In univariate analysis, FGFR2 (p = 0.026) and Edmonson-Steiner grade (E-S grade) (p = 0.030) were associated with recurrence after resection in HCC patients. In multivariate analyses, increased FGFR2 expression (p = 0.017) was the only significant predictor of HCC recurrence. Conclusions: High FGFR2 expression had marginal association with poor E-S grade (p = 0.056). More intensive surveillance of HCC recurrence is warranted in HCC patients with increased FGFR2 expression. [ABSTRACT FROM AUTHOR]

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p < 0.001). With matched analysis, the decrease in LS value was significantly larger in DAA group than peg-IFN group at both 48 weeks (29% vs. 9%) and 96 weeks (39% vs. 17%). The incidence of HCC was not significantly different between DAA and peg-IFN groups (5.5% vs. 5.4%) at 144 weeks. HCV eradication with DAA can lead to improvement of liver stiffness over time. The regression of fibrosis was greater in the group with DAA than peg-IFN. Clinical trials registration: ClinicalTrials.gov (NCT02865369). [ABSTRACT FROM AUTHOR]

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)‐induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low‐level viremia HBV‐HCC receiving non‐curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low‐level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV‐HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non‐antiviral group). The definition of low‐level viremia was an HBV DNA level <2000 IU/ml. Kaplan‐Meier curves, log‐rank tests and Cox regression analysis were used for statistical analyses. The median follow‐up duration was 39 months (1–174 months). Overall survival (OS) did not differ between groups (P =.227). Barcelona Clinic Liver Cancer stage (BCLC), Child‐Pugh (CP) class and α‐fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P =.022) was a prognostic factor for 2‐year survival. On subgroup analysis, antiviral therapy improved short‐term survival in patients with BCLC stage 0 and A (P =.037) and CP class A (P =.04). In patients with low‐level viremia, antiviral therapy yielded short‐term survival benefits, particularly in patients with early‐stage HCC. [ABSTRACT FROM AUTHOR]

Background and Aims: Sorafenib is a proven first-line treatment recommended for hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). However, multiple treatment modalities are used in clinical practice as a first-line option. This study is a prospective, observational, multicenter, cohort study evaluating patterns of treatment modalities and outcomes for HCC patients with PVI. Methods: The baseline characteristics, treatment modalities, and outcomes were prospectively collected for 287 newly diagnosed HCC patients with PVI between August 2015 and July 2016 from 16 sites in Korea. Results: During a median 7.8 months of follow-up (range 0.3–24.6 months), mortality was observed in 123 (42.9%) patients. Decision tree analysis classified patients into five subgroups with different outcomes. The patterns of treatment were very heterogeneous, and there was no dominant treatment modality. The most commonly used treatment modality was transarterial chemoembolization (TACE) (20.2%) followed by TACE plus external beam radiation therapy (17.8%) and sorafenib (12.5%). When stratified according to the extent of PVI, sorafenib treatment showed comparable outcomes when the PVI extent was lobal or main/bilateral, yet showed worse outcomes when the PVI extent was limited to the segmental level compared to those who received treatment other than sorafenib. Conclusions: HCC patients with PVI comprise a heterogeneous population and are treated with various treatment modalities with diverse clinical outcomes in clinical practice. Subclassification of HCC patients with PVI is required to minimize heterogeneity and should be considered for the selection of treatment modalities and future clinical trials. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis and hepatocellular carcinoma (HCC) are often ineligible for resection or local ablation therapy due to poor liver function and/or difficult location. The aim of this study is to evaluate therapeutic outcomes of stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) compared with TACE alone for HCC measuring less than 5 cm. From March 2011 to December 2016, 85 patients underwent SBRT with TACE (SBRT-TACE group) and 114 underwent TACE (TACE group) at 4 tertiary hospitals. Local control rate (LCR), progression-free survival (PFS) and overall survival (OS) were compared after propensity-score matching (1:1 ratio). The SBRT-TACE group showed significantly higher 1- and 3-year LCR than the TACE group (91.1% and 89.9%, respectively vs 69.9% and 44.8%, respectively; P < 0.001). The SBRT-TACE group showed better 1- and 3-year PFS than the TACE group (56.5% and 32.3%, respectively vs 42.2% and 21.6%, respectively; P = 0.022). However, 1-, 3- and 5-year OS was not different between the SBRT-TACE and TACE groups (98.8%, 89.1% and 80.7%, respectively vs 99.7%, 83.3% and 71.0%, respectively; P = 0.206). In multivariate analysis, the overall SBRT added to TACE did not contribute to extend PFS. However, in patients with less than 2 tumors, the combined therapy was effective (HR 0.590, 95% CI 0.392–0.889, P = 0.012). SBRT-TACE is superior to TACE in terms of LCR. Particularly, SBRT-TACE may be an effective alternative in patients with HCC number (≤2), which is not indicated for resection or local ablation. [ABSTRACT FROM AUTHOR]

Convincing data that support routine use of preventive therapy against hepatitis B virus (HBV) reactivation in radiotherapy (RT) for hepatocellular carcinoma (HCC) are lacking. The aim of this study was to investigate the incidence, clinical significance, and risk factors of HBV reactivation after RT. Medical records of 133 HBsAg (+) HCC patients who received radiotherapy from March 2009 to February 2016 were reviewed. Patients were divided into two groups: 1) non-antiviral group, those who did not receive antiviral therapy before RT (n = 27); and antiviral group (those who underwent antiviral therapy before RT) (n = 106). Factors related to HBV reactivation in HCC patients were evaluated. 17 (12.7%) of 133 patients developed HBV reactivation after RT. Patients in the antiviral group had significantly lower rates of HBV reactivation than those in the non-antiviral group (7.5% vs. 33.3%, p<0.001). HBV related hepatitis was also lower in the antiviral group (3.8% vs. 14.8%, p = 0.031). In multivariate analysis, absence of antiviral treatment (OR: 8.339, 95% CI: 2.532–27.470, p<0.001) and combined treatment of RT with transarterial chemoembolizatoin (TACE) (OR: 5.313, 95% CI: 1.548–18.232, p = 0.008) were risk factors for HBV reactivation. HBV reactivation can occur after radiotherapy. Combination treatment of RT with TACE and non-antiviral treatment are major risk factors for HBV reactivation during or after RT. Therefore, preventive antiviral therapy should be recommended for patients with HCC who are scheduled to receive RT. [ABSTRACT FROM AUTHOR]

Background and Aims: Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. Methods: A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. Results: The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. Conclusions: In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB. [ABSTRACT FROM AUTHOR]