BACKGROUND:Prolonged therapy with lamivudine has been associated with tyrosine-methionine-aspartate-aspartate mutation, which results in hepatitis B recurrence. Recently, antiviral agents, such as entecavir, have high efficacy and low resistance rate in hepatitis B-related liver disease. However, the researches on the effect of entecavir in preventing hepatitis B recurrence after liver transplantation are rare. OBJECTIVE:To investigate the effect of entecavir combined with low-dose hepatitis B immunoglobulin in preventing hepatitis B recurrence after liver transplantation. METHODS:The fol ow-up data of 253 patients who had liver transplantation for hepatitis B virus related liver disease were retrospectively analyzed. Al patients received nucleoside analogues therapy formal y before liver transplantation. The effects of entecavir+hepatitis B immunoglobulin and lamivudine+hepatitis B immunoglobulin were compared in al the patients and the patents with hepatitis B recurrence risk factors (positive preoperative HBeAg, DNA-positive hepatitis B virus, hepatoma and tyrosine-methionine-aspartate-aspartate mutation). RESULTS AND CONCLUSION:A total of 253 patients received hepatitis B virus-related liver transplantation, and 29 patients died. There were 202 patients in lamivudine group in which 26 patients were dead and 16 patients had hepatitis B virus recurrence, and the recurrence rate was 7.92%(16/202). However, entecavir group had 51 patients without hepatitis B virus recurrence in which three patients were dead. There were significant differences in the mortality rate and recurrence rate between two groups. Compared with the lamivudine+hepatitis B immunoglobulin, entecavir+hepatitis B immunoglobulin could effectively reduce the recurrence rate of the patients with hepatitis B virus-related risk factors. Hepatitis B immunoglobulin was terminated and nucleoside analogues were modulated when recurrence appeared. Al patients hepatitis B virus DNA were control ed less than 500 IU/mL and liver function returned to normal level. Log-rank test showed that there was no significant difference in the long-term survival rate after timely treatment of hepatitis B virus recurrence. With the prevention of nucleoside analogues combined with hepatitis B immunoglobulin therapy, timely treatment of hepatitis B recurrence has little influence on the prognosis. Entecavir combined with hepatitis B immunoglobulin can effectively prevent the hepatitis B recurrence. For the patients with hepatitis B virus-related risk factors, entecavir combined with hepatitis B immunoglobulin can better reduce the recurrence rate of hepatitis B than lamivudine+hepatitis B immunoglobulin after liver transplantation.

Objective:To investigate the antiviral efficacy of direct-acting antiviral agents (DAAs) in the treatment of liver transplantation (LT) recipients with hepatitis C virus (HCV) infection.Methods:Twenty-two HCV-infected LT recipients treated with DAAs at Fifth Medical Center of Chinese PLA General Hospital from December 2014 to June 2018 were retrospectively analyzed, Twenty cases of HCV RNA gene type 1b were treated with sofosbuvir (400 mg/d) + ledipasvir (90 mg/d) or sofosbuvir (400 mg/d) + daclatasvir (60 mg/d) for 12 weeks or 24 weeks; 2 cases of gene type 2a were treated with sofosbuvir (400 mg/d) for 12 weeks. The effect of antiviral treatment, adverse reactions during treatment, and laboratory indicators such as HCVRNA quantification, blood routine, liver and kidney function during treatment and follow-up were studied.Results:The LT recipients of HCV infection included 16 males and 6 females, with a median age of 61.5 (36-71) years old, and the median time of antiviral treatment was 48 (2-117) months after transplantation. Among the 22 patients, 16 received a 12-week course of treatment. Except for 2 patients who did not get HCVRNA negative conversion at 4-week, all achieved a negative HCV RNA at 4-week and the end of the treatment. Six LT recipients received a 24-week course of treatment (gene type 1b), and HCVRNA was negative at 4-week and the end of treatment. All patients achieved end of treatment virological response and a sustained virological response (SVR) rate of 100% at 12 weeks and 24 weeks after the end of treatment. The serum levels of alanine aminotransferase (ALT) and creatinine were 71.5 (30, 110) U/L and (89.4±25.7) mmol/L before treatment, respectively. ALT decreased to 22 (17.8, 28.5) U/L after 4 weeks of treatment, and serum creatinine decreased to (77.4±11.5) mmol/L at 24 weeks after the end of treatment. The differences before and after treatment were statistically significant (all P<0.05). No serious adverse events occurred during the treatment. Conclusions:DAAs have a definite antiviral effect in the treatment of LT recipients with HCV infection, and long-term SVR can be obtained.

ObjectiveTo investigate the risk factors for tumor recurrence and death after liver transplantation in patients with hepatocellular carcinoma (HCC) and their survival. MethodsThe patients with HCC who underwent liver transplantation in The Fifth Medical Center of Chinese PLA General Hospital from January 2005 to February 2019 were enrolled, and according to the presence or absence of HCC recurrence after liver transplantation, they were divided into recurrence group and non-recurrence group. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to determine the risk factors for HCC recurrence and death after liver transplantation. The Kaplan-Meier method was used for survival analysis, and the receiver operating characteristic (ROC) curve was used to investigate the predictive value of death-related risk factors after liver transplantation. ResultsA total of 391 HCC patients who underwent liver transplantation were enrolled, with a median follow-up time of 2 years, among whom 78(19.95%) experienced HCC recurrence. Preoperative alpha-fetoprotein (AFP) level＞200 ng/ml (recurrence: hazard ratio ［HR］=252, 95% confidence interval ［CI］: 1.58-4.03, P＜0.001; death: HR=2.99, 95%CI: 1.59-5.62, P＜0.001］, total tumor diameter (recurrence: HR=1.20, 95%CI: 1.12-1.28, P＜0.001; death: HR=1.10, 95%CI: 1.02-1.17, P=0.002), and vascular invasion (recurrence: HR=1.15, 95%CI: 1.04-1.26, P=0.016; death: HR=1.10, 95%CI: 1.03-1.18, P=0.004) were independent risk factors for tumor recurrence and death after liver transplantation. The 1-, 5-, and 10-year overall survival rates after liver transplantation were 94.8%, 84.2%, and 83.5%, respectively, and the 1-, 5-, and 10-year disease-free survival rates were 840%, 75.1%, and 75.1%, respectively. AFP, involvement of major blood vessels, body mass index, and total tumor diameter had a certain value in predicting the death of HCC patients with recurrence, with an area under the ROC curve of 0.789 (95% CI: 0.719-0858). ConclusionTumor biological features before transplantation are the key factors for tumor recurrence after transplantation.

Objective: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). Materials and Methods: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. Results: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87–13.40]), IVHG (3.64 [2.15–6.24]), and RHE (7.90 [4.93–12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52–0.66]), IVHG (0.72 [0.64–0.81]), and RHE (0.61 [0.54– 0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36–15.30] and 10.10 [7.10–14.60], respectively, for the blend sign and 2.75 [1.64–4.67] and 2.62 [1.60–4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. Conclusion Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.

Objective:To investigate the changes of microRNA-153 (miR-153) expression and the mechanism of regulating histone H3 lysine 4 (H3K4) methyltransferase (SET7/9) and histone H3K4 methylation (H3K4me1) in the process of arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis.Methods:Human normal hepatocytes (L-02 cells) were cultured in vitro and divided into control, arsenic treatment, arsenic + negative transfection, arsenic + miR-153 up-regulation and arsenic+ miR-153 down-regulation groups according to different treatment methods. Arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were transfected with transfection plasmid and transfection reagent according to a certain proportion (3 μg: 8 μl). After 24 h, arsenic treatment, arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were all treated with 100 μmol/L sodium arsenite (NaAsO 2) as the final concentration for 24 h. The control group was treated with phosphate buffer solution (PBS) of the same volume as NaAsO 2 for 24 h. The expression of miR-153 was detected by real-time quantitative polymerase chain reaction (RT-qPCR); cell apoptosis and cell cycle were detected by flow cytometry; real-time cell dynamic analyzer (RTCA) was used to detect cell proliferation; Western blotting was used to detect the expression of endoplasmic reticulum marker proteins glucose regulatory protein 78 (GRP78), SET7/9 and H3K4me1. Results:The expression levels of miR-153 in each group were significantly different ( F = 10.73, P < 0.05). Compared with the control group [(41.10 ± 6.08)%], the expression level of miR-153 in arsenic treatment group [(4.35 ± 0.20)%] was significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group [(10.00 ± 2.40)%], the expression level of miR-153 in arsenic+ miR-153 up-regulation group [(157.70 ± 42.70)%] was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group [(4.20 ± 0.28)%] was significantly decreased ( P < 0.05). There were significant differences in the total cell apoptosis rate and G1 phase cell proportion among the five groups ( F = 29.69, 104.32, P < 0.05). Compared with the control group, the total cell apoptosis rates and G1 phase cell proportions in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the total cell apoptosis rate and G1 phase cell proportion in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic+ miR-153 down-regulation group were significantly increased ( P < 0.05). The difference of cell proliferation rate in each group was statistically significant ( F = 799.35, P < 0.05). Compared with the control group, the cell proliferation rates in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group, the cell proliferation rate in arsenic+ miR-153 up-regulation group was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group was significantly decreased ( P < 0.05). The protein expression levels of SET7/9, GRP78 and H3K4me1 in each group were significantly different ( F = 78.52, 52.13, 54.32, P < 0.05). Compared with the control group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic treatment group were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic + miR-153 down-regulation group were significantly increased ( P < 0.05). Conclusion:miR-153 plays an important role in arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis, the expression and regulation are related to the changes of SET7/9 and H3K4me1 levels.