ObjectiveTo detect the expression of indoleamine2, 3-dioxygenase (IDO) and HBV preS mRNA in HepG2 cells and its inhibitory effect on the proliferation of human peripheral blood lymphocyte. MethodsThe AdIDOEGFPpreS was transfected to human hepatocarcinoma cell line HepG2 and the specific fragment of IDO mRNA and HBV preS mRNA in these HepG2 cells were detected by RT-PCR. Then the transfected HepG2 cells were cocultured with human peripheral blood lymphocyte and the inhibitory effect of IDO on the proliferation of human peripheral blood lymphocyte was observed. ResultsThe IDO and HBV preS mRNA were successfully transferred to HepG2 cells, so the specific fragment of IDO and HBV preS mRNA could be found in the transfected HepG2 cells but not in the control group HepG2 cells by RT-PCR. Furthermore, the relative expression intensity of IDO and HBV preS were 1.27 and 1.18, respectively. When co-cultured with human peripheral blood lymphocyte, the counts per minute in the transfected HepG2 cells 〔(7 471±1 375) beats/min〕 was significantly less than that in the control group 〔(13 821±1 997) beats/min〕, Plt;0.001. ConclusionThe target gene IDO and HBV preS can be transferred and expressed in HepG2 cells successfully, which can obviously suppress the proliferation of human peripheral blood lymphocyte.
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 investigate the correlation of spontaneous YMDD mutation in different hepatitis B virus (HBV) genotypes with HBV-related hepatocellular carcinoma (HCC). MethodFrom May 2010 to May 2012, 110 HBV-related hepatocellular cancer patients not treated by anti-virus drugs and 1 079 chronic HBV infectors (including asymptomatic HBV carriers, chronic hepatitis B patients, and HBV-related liver cirrhosis patients) were included in our study. HBV YMDD mutation was detected by fluorescence hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using Diagnosis Kit for HBV YMDD Mutation (Qiagen Biotechnology). Serum HBV genotype was detected by real time PCR using genotype specific TaqMan probe. According to data type, t-test, χ2-test and unconditional logistic regression were used for statistical analysis. ResultsIn the HCC group, genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 39 patients (35.5%), 16 patients (14.5%) and 14 patients (12.7%), respectively. In the chronic HBV infection group, HBV genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 153 patients (14.2%), 46 patients (4.3%) and 17 patients (1.6%), respectively. The difference between the two groups were statistically significant (χ2=33.368, P<0.001; χ2=21.353, P<0.001; χ2=48.889, P<0.001). Unconditional logistic regression analysis suggested that infection of genotype C virus and genotype C virus with spontaneous YMDD mutation might be important risk factors for the development of HCC[OR=2.943, 95%CI (1.778, 4.872), P<0.001; OR=5.989, 95%CI (2.394, 14.980), P<0.001]. ConclusionsInfection of genotype C virus with spontaneous YMDD mutation is tightly related with the occurrence of HCC and has important value for earlier warning of HCC.
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.
Objective To evaluate the efficacy and safety of antiviral drugs for hepatitis B with YMDD motif variant. Methods We electronically searched MEDLINE (1989-April, 2004), EMBASE (1989-April, 2004), CBMdisc (expand) (1989-April, 2004), and handsearched unpublished Chinese conference proceedings. Randomized and quasi-randomized trials in patients with chronic hepatitis B with YMDD motif variant correlative to lamivudine were collected. Two reviewers extracted the data and assessed the quality of literature independently. The data were then analyzed by RevMan 4.2 software. Results Five studies involving 6 trials and 284 patients were included. According to the results of meta-analysis, antiviral therapy with adefovir plus lamivudine showed significantly better effects on the clearance of serum HBV-DNA and HBeAg and normalization of ALT than that of lamivudine alone (RR 16.61, 95%CI 2.29 to 120.71; RR 6.66, 95%CI 1.23 to 35.88 and RR 6.26, 95%CI 2.29 to 17.12 respectively); also, oxymatrine plus thymothin showed obviously better effects on the clearance of serum HBV-DNA and HBeAg (RR 2.96, 95%CI 1.26 to 6.93 and RR 2.51, 95%CI 1.05 to 5.98 respectively).But adefovir alone showed no better effects on clearance of serum HBV-DNA and HBeAg than that of lamivudine alone (RR 11.00, 95%CI 0.65 to 186.02 and RR 7.00, 95%CI 0.39 to 126.92 respectively); interferon plus lamivudine showed no better effects on the clearance of serum HBV-DNA, HBeAg and the normalization of ALT (RR 3.50, 95%CI 0.90 to 13.58; RR 4.90, 95%CI 0.70 to 35.10 and RR 2.80, 95%CI 0.91 to 8.12 respectively). Chinese herbs plus lamivudine showed no better effects on the clearance of serum HBV-DNA (RR 1.16, 95%CI 0.89 to 1.51). There were no significant side effects in the groups, except flu like symptom in the interferon group, slight kidney impairment in the adefovir group, and aggravation of rare cases in lamivudine group. Conclusions Antiviral therapy with adefovir plus lamivudine, or oxymatrine plus thymothin, shows better effects than with lamivudine alone in terms of antiviral therapy and clinical outcome improvement. However, the evidence is too weak to draw a definite conclusion in this systematic review. Larger sample size and rigorously designed randomized, double blind, placebo control trials are required for future study.
Objective To systematically review the efficacy and safety of interferon based antiviral therapy for children with hepatitis B. Methods PubMed, EMbase, The Cochrane Library, WanFang Data and CNKI databases were searched to collect randomized controlled trials (RCTs) of interferon based antiviral therapy for children with hepatitis B from inception to December 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 12 studies involving 723 patients were included. The results of meta-analysis showed that: follow-up <12 months, the virological response rate (RR=2.82, 95%CI 1.98 to 4.02, P<0.000 01), serum HBeAg clearance rate (RR=3.02, 95%CI 1.95 to 4.67,P<0.000 01) and ALT normalization rate (RR=1.42, 95%CI 1.19 to 1.70,P=0.000 1) were significantly higher in the interferon group than the control group. Follow-up >12 months, the virological response rate (RR=1.75, 95%CI 1.18 to 2.60, P=0.006) and serum HBeAg clearance rate (RR=2.17, 95%CI 1.28 to 3.65, P=0.004) were also significantly higher in the interferon group. Severe adverse effects were not reported in included studies. Conclusion Current evidence shows that higher virological response is found in HBV infected children with interferon treatment. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
ObjectiveTo analyze hepatitis B virus (HBV) genotype distribution and drug-resistant mutations in West China Hospital of Sichuan University, providing basis for hepatitis B individualized treatment.MethodsA total of 786 chronic hepatitis B patients admitted to West China Hospital of Sichuan University from January 2016 to December 2018 were enrolled in the study. Genotype and drug-resistant mutations were analyzed by Sanger sequencing, and statistical analysis was conducted by χ2 test.ResultsThree genotypes (B, C and D) were identified in 786 samples, 489 (62.2%) in genotype B, 291 (37.0%) in genotype C , and 6 (0.8%) in genotype D. The distribution differences of B and C genotypes in age and ethnic groups were statistically significant (P<0.05). Among them, 627 cases had drug-resistant mutations, with a drug-resistant mutation rate of 79.8%. A total of 262 cases (33.3%) were resistant to lamivudine and tibivudine, 102 cases (13.0%) were resistant to lamivudine, tibivudine and entecavir; 83 cases (10.6%) were resistant to adefovir dipivoxil. No tenofovir resistant strains were detected in 786 samples. There were statistically significant differences in drug resistance between B and C genotypes (χ2=14.356, P<0.01). The most common single mutation was M204I [179 cases (22.8%)], followed by 46 cases (5.9%) of A181V/T associated with adefovir dipivoxil resistance. The most common mixed mutation was L180M+M204V/I in 83 cases (10.6%), and another 102 cases (13.0%) showed M250V and/or V173L and/or T184A/G/S/I and/or S202G/I with L180M+M204V/I.ConclusionsHBV genotypes in West China Hospital of Sichuan University are mainly B and C, and the situation of drug resistance is severe and the mutation pattern is complex. Therefore, detecting HBV genotype and drug resistance mutation is necessary, which may develop better clinical treatments.
ObjectiveTo investigate the influence of strengthening intervention on antiviral treatment compliance for cirrhosis patients following chronic hepatitis B. MethodsOne hundred patients with cirrhosis following chronic hepatitis B undergoing antiviral treatment between January 2007 and January 2009 were randomly divided into intervention group and control group with 50 patients in each group.Patients in the control group received routine care.For patients in the intervention group,besides routine care,strengthening education on the disease,medication guide,and weekly telephone follow-up after discharge were also added.On the time points of 6,12,18,24,30,36 months after patients were discharged,we followed them up with self-designed questionnaire,and compared the two groups of patients on the rates of fully complying with doctors,not fully complying with doctors and completely not complying with doctors.And the reasons were also analyzed. ResultsEighteen months after being discharged,the two groups had no significant difference in the rate of complying with doctors (P>0.05),while the difference was significant 24,30,36 months after leaving the hospital (P<0.05).The reasons were not following the doctors were mainly high cost and unsatisfying treatment effect.In the control group,the reasons also included lack of knowledge about the disease and lack of guidance and supervision. ConclusionThrough strengthening nursing intervention,patients'treatment compliance can be improved significantly.
ObjectiveTo explore the influence of paternal serum HBV-DNA load levels and pregnant women's HBsAb on vertical transmission of hepatitis B virus (HBV) from HBsAg positive fathers to infants in order to provide effective methods for paternal-fetal ventrical transmission of HBV prevention. MethodsUsing HBsAg and HBV-DNA as indicators to screen pregnant women and their husbands after gained consent, 121 families with HBVM negative or only HBsAb positive and HBV-DNA negative pregnant women, HBsAg positive husbands and their newborns were selected. In this case-control study, according to neonatal cord blood HBV-DNA detection, 23 newborns with cord blood HBV-DNA positive were selected as cases, 98 newborns as controls. ResultsThe positive rate of neonatal cord blood HBV-DNA was 19.0% (23/121); and there was dose-response relationship between paternal serum HBV-DNA load levels and neonatal cord blood HBV-DNA positive (trend χ2=60.108, P=0.000). The analysis of ROC curve showed that paternal serum HBV-DNA load level (106 copies/mL) is a better demarcation point to forecast the occurrence of vertical transmission of HBV from HBsAg positive fathers to infants, because there was a better sensitivity and specificity during forecast; and HBsAb negative pregnant women's were statistically significant (χ2=12.399, P=0.000). There was no significant difference at the positive rate of neonatal cord blood HBV-DNA between the case group and control group when paternal serum HBV-DNA load levels exceed 107 copies/mL (P > 0.05). ConclusionPaternal serum HBV-DNA load levels and HBsAb negative pregnant women are the risk factors of vertical transmission of HBV from HBsAg positive father to infants. Paternal serum HBV-DNA load level (106 copies/mL) is an appropriate index of the occurrence of vertical transmission.
Objective By means of evidence-based clinical practice, to find more effective treatment for a hepatitis B related nephritis patient with renal failure. Methods The following databases as Up to Date (May 2011), The Cochrane Library (Issue 5, 2011), PubMed (1978 to 2011) and CNKI (1978 to 2011) were searched to identify systematic reviews and randomized controlled trials (RCTs) of treating hepatitis B related nephritis with glucocorticoid, immunosuppressor or antiviral therapies, and the quality of collected clinical evidence was evaluated by using GRADEpro software. Results The glucocorticoid or combined immunosuppressors was not recommended for existing adverse effects and not acting on the remission of hepatitis B related nephritis and reduction of proteinuria. However, the antiviral therapy used alone was recommended for acting on the remission of hepatitis B related nephritis and the reduction of proteinuria. In view of adverse effects and expensive price of interferon, the nucleoside analogue antiviral agent was suggested. Considering the renal toxicity of adefovir and tenofovir, and possible drug-resistance of lamivudine, the entecavir (0.5 mg qd) was finally selected with patient’s agreement, and the supporting therapies such as lowering blood pressure, and protecting the kidney and liver were adopted continually. After one month treatment, 24-hour urinary protein got reduced, serum albumin got increased, kidney function got stable, and hepatitis B virus DNA quantity got reduced. Conclusion For treating hepatitis B related nephritis with kidney failure, entacavir can reduce 24-hour urinary protein, raise serum albumin, stabilize kidney function and reduce hepatitis B virus DNA in a short term, but its long-term efficacy still requires further studies.