It has been proved that nucleos(t) ide analogues (NAs) therapy could improve underlying liver disease and reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the difference of effectiveness in reducing HCC occurrence between tenofovir (TDF) and enticavir (ETV), two first-line NAs drugs, is still little known. This meta analysis aims to assess the efficacy in reducing incidence of HCC comparing tenofovir monotherapy with entecavir monotherapy among chronic hepatitis B (CHB) patients by analyzing their long-term clinical outcomes. Databases including PubMed, Embase, Cochrane Central Register of Controlled Trial, and ISI Web of Science were fully investigated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the included articles, two of the authors independently extracted and confirmed relevant data. Review Manager software (RevMan 5.3) was using for meta analysis. Seven articles with 3698 patients were finally included in this research, 1574 in tenofovir group and 2124 in entecavir group. For meta analysis, the incidence of HCC was significantly lower among the tenofovir group than entecavir group [rate ratio (95% CI) of 0.66 (0.49, 0.89), P = 0.008], while there was no statistical significance in incidence of death or transplantation [rate ratio (95% CI) of 0.78 (0.55, 1.13), P = 0.19], encephalopathy [risk ratio (95% CI) of 0.72 (0.45, 1.13), P = 0.15] or variceal bleeding [risk ratio (95% CI) of 0.71 (0.34, 1.50), P = 0.37] between the two groups. There is a better effect of tenofovir in reducing HCC incidence than entecavir, which indicates tenofovir should be used more widely while treating chronic hepatitis B patients. However before applying, randomized controlled trial and large prospective cohort study should be performed in the future.

Background: In the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial.Methods: ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated.Results: There was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19–9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS andP = 0.8004 in OS).Conclusion: PNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy.

Objective: Microvascular invasion (MVI) has been proved to be an independent risk factor for the recurrence of HCC. If promptly treated, the recurrence rate can be reduced and the total survival time can be prolonged. The aim of this study is to analyze the effect of sorafenib on the clinical outcomes in HCC patients with MVI after curative hepatectomy. Methods: HCC patients who underwent hepatectomy and were pathologically diagnosed with MVI were retrospectively analyzed. Patients were divided into sorafenib group and control group. Sorafenib 400 mg, twice daily, was administered orally after surgery in the sorafenib group. The recurrence-free survival (RFS) and overall survival (OS) were observed during follow-up, and associated factors were analyzed using univariate and multivariate COX regression. Results: There was no significant difference in demographics, clinical staging, and tumor index between sorafenib group (16 patients) and control group (33 matched patients). The RFS and OS were both longer in the sorafenib group, and the 3-years RFS rates of the sorafenib group and control group were 56.3% (9 of 16) and 24.2% (8 of 33), respectively (P=0.027). The 3-year OS rate of the sorafenib group was 81.3% (13 of 16), which was significantly higher than that of the control group (39.4%, P=0.006). The results of multivariate COX regression indicated that treatment with sorafenib was an independent associated factor for RFS and OS. Conclusion: We believe that using sorafenib therapy after curative hepatectomy in HCC patients with MVI is effective and beneficial as it can reduce recurrence and prolong the survival time.

Introduction: Intrahepatic cholangiocarcinoma (ICC) stands as the second most common malignant tumor in the liver with poor patient prognosis. Increasing evidences have shown that inflammation plays a significant role in tumor progression, angiogenesis, and metastasis. However, the prognosis significance of inflammatory biomarkers on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is poorly recognized. Methods: ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were investigated. Results: Receiver operating characteristic (ROC) curves showed no significance in NLR, PLR, and LMR in RFS and OS, while significant results were shown on SII in both RFS (P = 0.035) and OS (P = 0.034) with areas under ROC curve as 0.63 (95%CI 0.52–0.74) and 0.62 (95%CI 0.51–0.72), respectively. Kaplan-Meier curves revealed a statistically significant better survival data in SII-low groups on both RFS (P < 0.001) and OS (P < 0.001). The univariate and multivariate analyses revealed that higher level of SII was independently associated with both poorer RFS time and OS time. However, no significant result was shown on NLR, PLR, or LMR. Conclusion: SII is an effective prognostic factor for predicting the prognosis of ICC patient undergone curative hepatectomy, while NLR, PLR, and LMR are not associated with clinical outcomes of these patients.

Background and Aim: Although the treatment effect and availability of therapeutic options for advanced hepatocellular carcinoma (HCC) are limited, the downstaging strategy may improve patient prognosis. This study aimed to investigate the potential of combination therapy as a downstaging strategy for treating advanced HCC with portal vein tumor thrombus (PVTT).Methods: This retrospective case series included patients having advanced HCC with PVTT, who received the combination therapy of sorafenib, camrelizumab, transcatheter arterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) from January 2019 to December 2019 in Xiangya Hospital, Central South University. The downstaging rate, treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated.Results: Of the 13 patients, HCC downstaging was achieved in 4 (33.3%) patients who later received hepatectomy. The overall response rate was 41.7%, and the disease control rate was 50.0%. The median PFS time was 15.7 months, with a 1-year PFS rate of 58.3%, whereas the median OS was not reached after 1 year (1-year OS, 83.3%). No severe adverse events or grade 3–4 adverse effect was observed in 12 of the 13 enrolled patients; therapy had to be discontinued in only one patient due to adverse events, who was excluded from the study. The most common adverse effect was fever (n = 4, 33.3%), followed by skin reaction (n = 3, 25%).Conclusion: A combination therapy comprising sorafenib, camrelizumab, TACE, and SBRT is an effective downstaging strategy for advanced HCC with PVTT and is associated with few adverse events.

Background: Immunotherapy has gradually played a significant role in treating cancer over the past 10 years. Meanwhile, significant connections have been found between infiltrating immune cells and prognosis, as well as the development of immunotherapy in hepatocellular carcinoma (HCC). Thus, analyses of the immune cell landscape are urgently needed for the future development of immunotherapy in HCC. Methods: Expression data of HCC and normal liver tissue were searched and downloaded from The Cancer Genome Atlas. The fraction of various immune cells was estimated by CIBERSORT, which is a computational analysis tool. Comparisons of the fractions of 22 types of immune cells were performed between HCC and normal tissues, as well as survival analyses and clinical significance. xCell was used to validate the results. Results: The fractions of 12 types of immune cells, including follicular helper T (Tfh) cells, monocytes, M0, and M2 macrophages, were significantly different between tissues. In survival analyses, higher fractions of Tfh cells (P=0.037), M0 (P=0.001), and M2 macrophages (P=0.045) were associated with a poorer prognosis, and monocytes with a better prognosis (P=0.040). Furthermore, a higher fraction of M0 macrophages (P=0.001), lower fraction of monocytes (P=0.031), and M2 macrophages (P=0.018) were found as risk factors of a poorer histological grade of HCC. Only M0 macrophages showed a significant association with the clinical stage of HCC. Meanwhile, xCell showed monocytes and M2 macrophages significantly reduced in tumor tissues, which validated the results. Conclusion: Tfh cells, monocytes, M0 and M2 macrophages may play an indicator role in carcinogenesis, progression, and clinical outcomes of HCC. Our research can serve as a reference contributing to future immunotherapy strategies of HCC.