ObjectiveTo investigate the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on acute liver failure (ALF) induced by D-galactosamine (D-GalN) in rats. MethodsA total of 105 male Sprague-Dawley rats were randomly divided into healthy control group, liver failure model group, and rhG-CSF group, with 35 rats in each group. A rat model of ALF was established by intraperitoneal injection of D-GalN (1400 mg/kg). Alanine aminotransferase (ALT) level in the liver, total bilirubin (TBil), peripheral blood leukocyte count, and liver pathological changes were observed at 12, 24, 48, 72, and 120 hours after modeling, and survival rate was observed at 120 hours after modeling. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the LST-t test was used for further comparison between two groups. ResultsCompared with the liver failure model group, the rhG-CSF group had a significantly higher degree of hepatocyte degeneration and necrosis at all time points except 120 hours after modeling, and compared with the liver failure model group at 120 hours after modeling, the rhG-CSF group had better recovery of lobular structure on HE staining. Compared with the liver failure model group, the rhG-CSF group had a tendency of increase in the percentage of cells with positive tumor necrosis factor-α at the five time points after modeling. Compared with the liver failure model group, the rhG-CSF group had significantly higher levels of ALT and TBil at all five time points. Both groups had a significant change in ALT level at 24 hours after modeling (P＜0.05), as well as a significant change in TBil at 24, 48, and 120 hours after modeling (P＜0.05). The rhG-CSF group had a significantly higher peripheral blood leukocyte count than the liver failure model group at all five time points (all P＜005). There was no significant difference in survival rate at 120 hours after modeling between the two groups (P＞0.05). ConclusionApplication of rhG-CSF during the stage of acute inflammatory reaction of ALF may aggravate liver inflammatory response.

At present, there is still a lack of uniform treatment strategies for hepatocellular carcinoma (HCC). Immunotherapy, especially PD-1/PD-L1 checkpoint inhibitors, is a novel therapy for HCC and can bring survival benefits to patients with advanced HCC. However, research data show that only a small number of HCC patients can benefit from this treatment regimen. To date, few biomarkers have been reported to predict the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC patients. This article reviews the biomarkers studied for HCC and other tumors and explores the possible predictive factors for the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC, in order to optimize the selection of treatment population and improve the clinical effect of PD-1/PD-L1 checkpoint inhibitors in the treatment of HCC.

In recent years, immune checkpoint inhibitors (ICIs) have made great progress in the treatment of tumor patients, prolonging their survival. However, the expansion of immunity against tumors with ICIs may also cause an imbalance in immune tolerance, leading to immune-related adverse events (irAEs). Immune-mediated liver injury caused by ICIs (ILICI) is one of the more common types of irAEs. In this review paper, the definition, epidemiology, risk factors, pathogenesis, pathology, clinical manifestations, treatment, recurrence, and re-treatment of ILICI were summarized to provide a basis for clinical diagnosis and treatment.

‍ ObjectiveTo investigate the value of preoperative fibrosis 4 score （FIB-4） combined with prognostic nutritional index （PNI） in predicting recurrence after radiofrequency ablation （RFA） for early-stage hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for the clinical data of 365 patients with the initial diagnosis of early-stage HCC who underwent RFA at Tianjin Third Central Hospital from January 2013 to December 2017， and a statistical analysis was performed for recurrence and survival. The receiver operating characteristic （ROC） curve was plotted for FIB-4 and PNI with postoperative tumor recurrence as the positive event， and their optimal cut-off values were selected. FIB-4 and PNI were graded and combined as FIB-4-PNI score， based on which the patients were divided into 0-point group with 207 patients， 1-point group with 93 patients， and 2-point group with 65 patients. The chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier survival analysis and the log-rank test were used to compare the recurrence-free survival （RFS） and overall survival （OS） between groups， and the Cox regression model was used to investigate the influencing factors for RFS and OS. ResultsThe 1-， 3-， and 5-year RFS rates of all patients were 79.2%， 49.8%， and 34.3%， respectively， with a median RFS of 35 months， while the 1-， 3-， and 5-year OS rates of all patients were 98.9%， 86.9%， and 77.3%， respectively. There were significant differences in cumulative RFS and OS rates between the patients with different levels of FIB-4， PNI， and FIB-4-PNI （RFS rate： χ²=17.890， 29.826， and 32.397， all P<0.001； OS rate： χ²=16.896， 21.070， and 26.121， all P<0.001）. The multivariate Cox regression analysis showed that history of diabetes （hazard ratio ［HR］=1.418， 95% confidence interval ［CI］： 1.046‍ ‍—‍ ‍1.922， P=0.024）， two tumors （HR=1.516， 95%CI： 1.094‍ ‍—‍ ‍2.101， P=0.012）， three tumors （HR=2.146， 95%CI： 1.278‍ ‍—‍ ‍3.604， P=0.004）， FIB-4-PNI 1 point （HR=1.875， 95%CI： 1.385‍ ‍—‍ ‍2.539， P<0.001）， and FIB-4-PNI 2 points （HR=2.35， 95%CI： 1.706‍ ‍—‍ ‍3.236， P<0.001） were independent risk factors for RFS， while two tumors （HR=1.732， 95%CI： 1.005‍ ‍—‍ ‍2.983， P=0.048）， three tumors （HR=3.511， 95%CI： 1.658‍ ‍—‍ ‍7.433， P=0.001）， FIB-4-PNI 1 point （HR=2.094， 95%CI： 1.230‍ ‍—‍ ‍3.565， P=0.006）， and FIB-4-PNI 2 points （HR=3.908， 95%CI： 2.306‍ ‍—‍ ‍6.624， P<0.001） were independent risk factors for OS. ConclusionFIB-4-PNI score can be used as an independent predictive factor for recurrence and overall survival time after RFA for early-stage HCC， and it can be combined with tumor features to predict postoperative recurrence and survival.