Partial hepatectomy versus interventional treatment in patients with hepatitis B virus-related hepatocellular carcinoma and clinically significant portal hypertension: a randomized comparative clinical trial

Background:The widely accepted view that portal hypertension(PHT)is a con-traindication to hepatectomy for patients with hepatocellular carcinoma(HCC)is being increasingly challenged.The long-term survival outcomes and safety of partial hepatectomy versus interventional treatment using ablation with or without pre-ablation transarterial chemoembolization(TACE)in patients with HBV-related HCC within the Milan criteria and with clinically significant PHT were compared in this study.Methods:This open-label randomized clinical trial was conducted on consecu-tive patients with clinically PHT and hepatitis B virus(HBV)-related HCC with tumors which were within the Milan criteria.These patients were randomized 1:1 to receive either partial hepatectomy or interventional treatment between December 2012 and June 2018.The primary endpoint was overall survival(OS);secondary endpoints included recurrence-free survival(RFS)and therapeutic safety.Results:Each of the 2 groups had 80 patients.The 1-,3-and 5-year OS rates in the partial hepatectomy group and the interventional treatment group were 95.0%,86.2%,69.5%versus 93.8%,77.5%,64.9%,respectively(P=0.325).The corresponding RFS rates were 78.8%,55.0%,46.2%versus 71.3%,52.5%,45.0%,respectively(P=0.783).The partial hepatectomy group had a higher compli-cation rate compared to the interventional group(67.5%vs.20%,P<0.001).However,the differences were mainly in Clavien-Dindo Grade Ⅰ complications(P<0.001),while not significant in Grade Ⅱ/Ⅲ/Ⅳ/Ⅴ(All P>0.05).Conclusions:This study shows that partial hepatectomy treatment did not meet prespecified significance for improved OS and RFS compared to interventional treatment for patients with HBV-related HCC within the Milan criteria and with clinically significant PHT.However,partial hepatectomy is still a safe procedure and should be considered as a treatment option rather than a contraindication.

Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma

Background and Aims:Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma(HCC)patients while the underlying mechanism of metastasis remains elusive.In our study,procollagen-lysine,2-oxoglutarate 5-dioxygenase 2(PLOD2)was shown to be involved in the process of metastasis in HCC.Methods:The Cancer Genome Atlas(TCGA)database and HCC tissue microarrays were used to evaluate the expression of genes.In vitro migration,invasion,in vivo subcutaneous tumor model and in vivo lung metastasis assays were used to determine the role of PLOD2 in tumor growth and metastasis in HCC.RNA sequencing and gene set enrichment analysis were performed to uncover the downstream factor of PLOD2 in HCC cells.A luciferase reporter assay was performed to evaluate the interaction between PLOD2 and interferon regulatory factor 5(IRF5).Results:The expression of PLOD2 in HCC tissues was higher than that in adjacent tissues,and increased PLOD2 expression was often found in advanced tumors and was correlated with poor prognosis in HCC patients.In vitro experiments,knockdown of PLOD2 reduced the migration and invasion of human HCC cells.Loss of PLOD2 suppressed human HCC growth and metastasis in a subcutaneous tumor model and a lung metastasis model.Baculoviral IAP repeat containing 3(BIRC3)was proven to be the downstream factor of PLOD2 in human HCC cells.In addition,PLOD2 was transcriptionally regulated by IRF5 in HCC cells.Conclusions:High expression of PLOD2 was regulated by IRF5,which was correlated with the poor survival of HCC patients.PLOD2 enhanced HCC metastasis via BIRC3,suggesting that PLOD2 might be a valuable prognostic biomarker for HCC treatment.