Comparison of laparoscopic hepatectomy and percutaneous radiofrequency ablation for the treatment of small hepatocellular carcinoma: a meta-analysis.

AIM: The purpose of this study was to compare the long-term outcomes of laparoscopic hepatectomy (LH) and percutaneous radiofrequency ablation (PRFA) for the treatment of small hepatocellular carcinoma. METHODS: We systematically searched PubMed, Embase, Web of Science, and Medline from January 2000 to May 2022 for literature comparing the efficacy of LH and PRFA in the treatment of small hepatocellular carcinoma (largest tumour diameter ≤ 3 cm, number of intrahepatic tumours ≤3, or diameter of a single intrahepatic lesion ≤5 cm. ). We assessed overall survival (OS), recurrence-free survival (RFS), local recurrence and complication rates. RESULTS: A total of 1886 patients with small HCC were included in the 8 studies included in this study, of which 839 underwent LH and 1047 underwent PRAF. The results of the meta-analysis showed that the two groups had the same 3-year (HR: 0.99, 95% CI: 0.67 to 1.47) and 5-year (HR: 1.30, 95% CI: 0.90 to 1.87) OS rates, and the LH group had better 3-year (HR: 0.58, 95% CI: 0.49 to 0.68) and 5-year (HR: 0.56, 95% CI: 0.37 to 0.85) RFS rates. The LH group had a lower local recurrence rate (OR: 0.19, 95% CI: 0.12 to 0.32), but the PRFA group had a lower complication rate (OR: 2.49, 95% CI: 1.76 to 3.54). CONCLUSION: There was no difference in OS between LH and PRFA in the treatment of small HCC. LH had a higher RFS rate and a lower local recurrence rate, but PRFA had a lower complication rate. In general, the long-term efficacy of LH in the treatment of small HCC is better than that of PRFA. Considering the advantages of less trauma and a low complication rate of PRFA, a large number of RCT studies are needed for further verification in the future.

Fatty acid activates NLRP3 inflammasomes in mouse Kupffer cells through mitochondrial DNA release.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in many developed and developing countries worldwide. It has been well established that the chronic sterile inflammation caused by the NLRP3 inflammasome is closely related to NAFLD development. Kupffer cells (KCs) are involved in the pathogenesis of various liver diseases. We used methionine choline-deficient diets to establish a mouse nonalcoholic steatohepatitis (NASH) model. The expression and formation of the NLRP3 inflammasome in the KCs from the mouse and cell models were determined by Western blotting and co-immunoprecipitation. Evidence of mitochondrial DNA (mtDNA) release was determined by live cell labeling and imaging. KCs and the NLRP3 inflammasome exerted proinflammatory effects on the development and progression of NASH through secretion of the proinflammatory cytokine IL-1ß. NLRP3, ASC and Caspase-1 protein expression levels in KCs from NASH mouse livers were significantly higher than those in KCs from NLRP3-/- mice, and the number of NLRP3 inflammasome protein complexes was significantly higher in KCs from NASH mouse livers, whereas these protein complexes could not be formed in NLRP3-/- mice. In in vitro experiments, palmitic acid (PA) decreased the mitochondrial membrane potential and subsequently induced mtDNA release from the mitochondria to the cytoplasm. NLRP3 inflammasome expression was substantially increased, and mtDNA-NLRP3 inflammasome complexes formed upon PA stimulation. Our data suggest that mtDNA released from mitochondria during PA stimulation causes NLRP3 inflammasome activation, providing a missing link between NLRP3 inflammasome activation and NASH development, via binding of cytosolic mtDNA to the NLRP3 inflammasome.

The endoplasmic reticulum co-chaperone ERdj3/DNAJB11 promotes hepatocellular carcinoma progression through suppressing AATZ degradation.

AIM: The co-chaperone ERdj3/DNAJB11 is involved in the endoplasmic reticulum stress response observed in cancer cells. We hypothesized that ERdj3 functions as a hepatocellular carcinoma (HCC) oncogene by inhibiting AATZ degradation. MATERIALS & METHODS: ERdj3 and AATZ expressions were analyzed in 84 HCC patients. Cell proliferation, epithelial-mesenchymal transition marker expression, migration and invasiveness were assessed in HepG2 and Huh-7 cells. A murine xenograft tumor model was constructed. RESULTS: ERdj3 is upregulated in HCC tumors and cell lines. Tumor ERdj3 levels are positively associated with cirrhosis, enhanced HCC status, inferior survival outcomes and AATZ levels. ERdj3 suppresses AATZ degradation. ERdj3 overexpression enhances proliferation, epithelial-mesenchymal transition marker expression, migration, invasiveness and xenograft tumor growth in an AATZ-dependent manner. CONCLUSION: ERdj3 enhances HCC progression through suppressing AATZ degradation.

Suberoylanilide hydroxamic acid alleviates orthotopic liver transplantation­induced hepatic ischemia­reperfusion injury by regulating the AKT/GSK3ß/NF­κB and AKT/mTOR pathways in rat Kupffer cells.

Multiple mechanisms are involved in regulating hepatic ischemia­reperfusion injury (IRI), in which Kupffer cells (KCs), which are liver­resident macrophages, play critical roles by regulating inflammation and the immune response. Suberoylanilide hydroxamic acid (SAHA), a pan­histone deacetylase inhibitor, has anti­inflammatory effects and induces autophagy. To investigate whether SAHA ameliorates IRI and the mechanisms by which SAHA exerts its effects, an orthotopic liver transplantation (OLT) rat model was established after treatment with SAHA. The results showed that SAHA effectively ameliorated OLT­induced IRI by reducing M1 polarization of KCs through inhibition of the AKT/glycogen synthase kinase (GSK)3ß/NF­κB signaling pathway. Furthermore, the present study found that SAHA upregulates autophagy 5 protein (ATG5)/LC3B in KCs through the AKT/mTOR signaling pathway and inhibition of autophagy by knockdown of ATG5 in KCs partly impaired the protective effect of SAHA on IR­injured liver. Therefore, the current study demonstrated that SAHA reduces M1 polarization of KCs by inhibiting the AKT/GSK3ß/NF­κB pathway and upregulates autophagy in KCs through the AKT/mTOR signaling pathway, which both alleviate OLT­induced IRI. The present study revealed that SAHA may be a novel treatment for the amelioration of OLT­induced IRI.