Objective To investigate the prognostic value of serum gamma-glutamyltransferase-to-lymphocyte ratio (GLR) in patients with chronic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after radical resection. Methods The clinical data of HBV-HCC patients diagnosed and treated with radical hepatectomy in the Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital) from January 2012 to December 2022 were retrospectively collected and analyzed. Log-rank and multivariate Cox proportional hazard model were performed to analyze the risk factors affecting overall postoperative survival (OS) and relapse-free survival (RFS) of HBV-HCC patients, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of GLR for OS and RFS of HBV-HCC patients. Results A total of 196 eligible HBV-HCC patients underwent radical hepatectomy were included. The optimal cutoff value of GLR was 182.31 through ROC curve, and 144 cases were in low GLR group and 52 cases in high GLR group. Compared with the low GLR group, ratios of preoperative portal vein tumor thrombus, China liver cancer staging (CNLC) stage Ⅲ, preoperative AFP level ≥400 ng/mL and low tumor differentiation were higher in the high GLR group (χ2=10.071, P=0.002; χ2=32.552, P<0.001). Cox proportional hazard model showed that higher maximum tumor diameter (HR=1.099, P=0.009), GLR>182.31 (≤182.31 vs. >182.31, HR=0.211, P<0.001) and low tumor differentiation grade (high+moderate vs. low, HR=0.182, P<0.001) were risk factors for postoperative OS of HBV-HCC patients, and the area under curve (AUC) of these risk factor for predicting OS of HBV-HCC patients was 0.930 [95%CI (0.884, 0.977)]. Preoperative portal vein tumor thrombus (No vs. Yes, HR=0.404, P=0.002) and GLR>182.31 (≤182.31 vs. >182.31, HR=0.435, P=0.001) were risk factors for postoperative RFS of HBV-HCC patients, and the AUC of these risk factor for predicting RFS was 0.729 [95%CI (0.654, 0.805)]. Conclusion This study preliminarily indicates that GLR is associated with postoperative prognosis of HBV-HCC patients, and GLR combined with maximum tumor diameter and tumor differentiation degree has a certain value in predicting OS.
【Abstract】ObjectiveTo investigate the prophylactic effect of lamivudine monotherapy on the recurrence of hepatitis B after liver transplantation. MethodsThirtyone patients with hepatitis B related benign decompensated cirrhosis who underwent liver transplantation between February 1999 to June 2002 and survived more than 3 months were analyzed retrospectively. Lamivudine was administered to each patient after operation and some patients before operation for the prophylaxis of HBV recurrence. The HBV markers and HBV DNA in serum and bioptic liver tissues in all patients were evaluated before and after operation. ResultsTotal HBV recurrence rate was 19.4％（6/31） during average 38.2 months (3.2-70.2 months) follow up. HBV recurrence rate was 7.1％(2/28), 16.0％(4/25), 26.1％(6/23) and survival rate was 87.1％(27/31), 80.6％(25/31), 66.1％(20.5/31) after 1-, 3-and 5-year, respectively. One hundred milligram lamivudine administration peroral daily for 2 weeks prior to transplantation enable HBeAg 54.5％(6/11) and HBV DNA 50.0％(5/10) positive patients convert to negative respectively. ConclusionPreoperative administration of lamivudine monotherapy can effectively prevent allograft from HBV re-infection after liver transplantation. Lamivudine should be used to convert HBV DNA and HBeAg to negative.
ObjectiveTo systematically review the efficacy of different nucleosides (acids) in preventing hepatitis B virus reactivation after chemotherapy in cancer patients. MethodsThe Cochrane Library, PubMed, EMbase, Web of Science, CNKI, WanFang Data, and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of different nucleosides (acids) to prevent HBV reactivation after chemotherapy in cancer patients from inception to June 7th, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Network meta-analysis was then performed by using Stata 16.0 software. ResultsA total of 43 RCTs involving 3 269 patients were included. There were 7 interventions, namely entecavir (ETV), lamivudine (LAM), adefovir dipivoxil (ADV), telbivudine (LdT), tenofovir dipivoxil (TDF), lamivudine combined with entecavir (LAM+ETV), and lamivudine combined with adefovir dipivoxil (LAM+ADV). The results of network meta-analysis showed that the efficacy of reducing the reactivation rate of ETV, LAM, ADV, LdT, TDF, LAM+ETV, LAM+ADV were superior than the control group. The ETV, LAM and ADV were not as effective as LAM+ETV. The leading drug combinations were LAM+ETV (94.8%), LdT (81.5%) and LA+ADV (58.0%). ConclusionsCurrent evidence shows that LAM+ETV, LdT, and LA+ADV are more effective in preventing hepatitis B virus reactivation after chemotherapy in cancer patients. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.
ObjectiveTo observe intervention effect of Shenlingcao oral liquid on asymptomatic chronic hepatitis B virus carriers (AsC).
MethodsA self control before-after trial was conducted in the First Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine and the Ninth People's Hospital of Nanchang City from November 2011 to May 2012. A total of 64 AsCs were treated by Shenlingcao oral liquid (1 bottle/d, 200 mL, once daily for 6 months). Serum HBV viral load, six specific serum markers of HBV and 11 liver function index were tested and recorded before and at the 1th, 3th, 6th months of the treatment. Analysis of variance of repeated data was conducted.
ResultsAfter one month of the treatment, 35/57 (61.40%) AsCs' serum HBV-DNA loads decreased, 1 log decrease was observed in 15 cases, 2 log decrease was observed in 4 cases, and decrease under the detection limit was observed in 12 cases. 41/57 (71.93%) AsCs' serum HBV-DNA loads decreased after 3 months of treatment, 1 log decrease was observed in 21 cases, 2 log decrease was observed in 5 cases, and decrease under the detection limit was observed in 15 cases. 31/49 (63.26%) AsCs' serum HBV-DNA loads decreased after 6 months of the treatment, 1 log decrease was observed in 19 cases, decrease more than 2 log was observed in 7 cases, and decrease under the detection limit was observed in 12 cases. The serum HBV viral loads at different time points of the treatment were significantly different (P<0.001). As medication time went, AsCs' serum HBV viral loads presented a decrease trend after taking Shenlingcao oral liquid, especially obvious at the 3th month.
ConclusionShenlingcao oral liquid could help promote AsCs' ability of clearing virus and controlling serum HBVDNA loads.
This study sought to investigate the in vivo antiviral effect of amantadine (AM) and biphenyl dimethyl dicarboxylate (DDB) on hepatitis B virus (HBV) in HBV replication mice. HBV replication-competent plasmid was transferred into male BALB/c mice by using hydrodynamics-based in vivo transfection procedure to develop HBV replication mouse model. The model mice were matched by body weigh, age and serum levels of hepatitis B e antigen (HBeAg) and were divided into four groups:AM group, DDB group, AM+DDB group and NS group, with the last one as control, and the mice of each group were administered corresponding agent orally twice a day, in a medication course lasting 3 d. On the third day, the mice were sacrificed 4-6 h after the last oral intake. HBV DNA replication intermediates in liver were analyzed by Southern blot hybridization. The serum hepatitis B surface antigen (HBsAg) and HBeAg were detected by enzyme linked immunosorbent assay (ELISA). Compared to the animals in the control group, HBV DNA replication intermediates in liver and HBsAg and HBeAg in serum from the AM and AM plus DDB group of mice decreased, and there was no difference between these two groups of mice. The levels of HBV DNA intermediate from liver and the serum HBsAg and HBeAg between the control and DDB group, however, were not obviously different. In conclusion, the inhibition effect of AM on HBV was detected, but treatment with DDB for 3 days did not influence the viral replication and expression of HBV in the HBV replication mice.
【摘要】 目的 了解乙型肝炎病毒（HBV）X基因在HBV相關肝病肝移植受體術后外周單個核細胞（PBMC）和骨髓CD34+細胞內的整合情況及其對乙肝疫苗接種的影響。 方法 采集1999年6月-2005年11月25例HBV相關肝病肝移植受體的外周靜脈血及其中23例的骨髓血，以密度梯度離心結合單克隆免疫磁珠分離法獲取外周血單個核細胞及骨髓CD34+細胞后，提取細胞DNA。因HBV X基因的整合頻率最高，設計HBV X基因的特異引物，進行HBV-Alu-PCR，終產物進行電泳并回收、連接載體、篩選擴增后測序，檢測有無X基因整合。 結果 經PCR后電泳及測序分析，25例HBV相關肝病肝移植受體術后的PBMC內未檢測出HBV X基因的整合，其中采集到骨髓標本的23例CD34+細胞中亦未檢測到HBV X基因的整合。 結論 肝移植術后受體體內HBV微生態的劇烈改變，使HBV整合的基本條件喪失，在此情況下，外周免疫細胞及骨髓造血干/祖細胞不是發生HBV整合的適宜場所，乙肝疫苗接種效果與HBV X基因整合關系不明確。【Abstract】 Objective To investigate whether hepatitis B virus HBV X gene integrates in peripheral blood mononuclear cell (PBMC) and bone marrow CD34+ cells from HBV related liver disease recipients after liver transplantation. Methods Between June 1999 and November 2005, PBMC were obtained from 25 HBV related liver disease recipients after liver transplantation and bone marrow CD34+ cells obtained from 23 cases among them. The cellular DNA was extracted by DNA isolation and purification kit following the manufacture’s instructions. Specific primers to HBV X gene and to human Alu repeats were used to amplify the virus integration through a 3-round hemi-nest PCR. The PCR final product was judged by 1.2% agarose electrophoresis, ligated to T vector, proliferated in E. coil 5α and sequenced. Results According to agarose electrophoresis and sequencing analysis, there were no HBV X gene integration in PBMC and bone marrow CD34+ cells from HBV related liver transplant recipients after surgery. Conclusions Because of the radical change of HBV microecological environment in HBV related liver transplant recipients after operation, the fundamental condition of HBV integration has been lost, which led PBMC and bone marrow CD34+ cells not suit to HBV X gene integrate to human genome. And the impact of HBV X gene integration on HBV vaccination is still undefined.
ObjectiveTo explore the relationship between liver transplantation procedure with or without preservation of retrohepatic vena cava and postoperative reinfection of hepatitis B virus.MethodsHepatitis B virus makers of 15 retrohepatic vena cava samples from hepatitis B virus active replicating recipients was detected using immunohistochemistry stain LSAB and HBV DNA hybridization in situ. Hepatitis B virus reinfection rate and survival rate after transplantation in classic group (20 cases) and piggyback group (7 cases) was analyzed retrospectively. ResultsHepatitis B virus makers including HBsAg and HBcAg and HBV DNA of all 15 retrohepatic vena cava samples, 10 from classic group and 5 from piggyback group, was negative. In classic group, 20 recipients were followedup 6-30 months, mean 18 months, only one case of hepatitis B recurrence was confirmed 22 months after operation; In piggyback group,7 recipients were followedup 5-12 months, mean 8 months, none of hepatitis B virus reinfection was encountered. Recurrence rate in classic group and piggyback group was 5.0%(1/20) and 0(0/7), respectively.ConclusionThis preliminary study indicated that the retrohepatic vena cava of hepatitis B virus active replicating recipients don’t have the residence and replication of hepatitis B virus particle. Orthotopic liver transplantation procedure with preservation of retrohepatic vena cava appears not to increase the hepatitis B virus reinfection rate in hepatitis B virus active replicating recipients after transplantation.
