ObjectivesTo systematically review the risk factors of hepatocellular carcinoma (HCC) in patients with hepatic B surface antigen (HBsAg).MethodsScopus, EMbase, PubMed, and The Cochrane Library databases were systematically searched for relevant studies on HCC after HBsAg seroclearance from inception to October 31st, 2017. Two reviewers independently screened literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was then conducted using R 3.5.3 software.ResultsA total of 28 studies involving 105 411 patients were included. Among 105 411 patients with chronic hepatitis B (CHB), 7 656 patients occurred spontaneously HBsAg seroclearance, while 1 248 patients had HBsAg seroclearance after interferon or nucleoside analogue therapy. The rate of HBsAg seroclearance was 6.77%. Meta-analysis showed that risk factors for HCC after serum HBsAg conversion included cirrhosis (OR=6.43, 95%CI 3.56 to 11.60, P<0.001), male (OR=2.72, 95%CI 1.66 to 4.46,P<0.001), and age ≥50 years at HBsAg seroclearance (OR=3.71, 95%CI 2.17 to 6.35,P<0.001).ConclusionsPatients with CHB after HBsAg seroclearance are still at risk of developing HCC. Therefore, periodic surveillance is recommended, especially for male patients, patients with cirrhosis, and patients who experience HBsAg seroclearance when over 50.
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 explore expressions of the metaherin (MTDH) mRNA and its protein in hepatitis B related hepatocellular carcinoma tissues and its clinical significance.
MethodsSeventy two tissues of patients with hepa-titis B related hepatocellular carcinoma who were treated in Affiliated Taihe Hospital of Hubei Medical University from Jul. 2012 to Oct. 2013 were collected retrospectively. Quantitative PCR (Q-PCR) and Western blot methods were used to detect the expression levels of MTDH mRNA and its protein in 10 cases of hepatitis B related hepatocellular carcinoma tissues and pericarcinoma tissues. Besides, immunohistochemistry was used to determine the expression of MTDH protein in 72 cases of hepatocellular carcinoma tissues, then the relationship of expression of MTDH protein and clinico-pathological features was explored.
ResultsThe expression levels of MTDH mRNA and its protein in hepatocellular carcinoma tissues were both higher than those of pericarcinoma tissues (8.50±0.84 vs. 4.55±0.81, t=10.797, P=0.000; 0.65± 0.24 vs. 0.25±0.16,t=6.375, P=0.013). The MTDH protein was positively expressed in 42 cases (58.3%) and negatively expressed in 30 cases (41.7%) of hepatocellular carcinoma tissues. The results of logistic regression showed that,MTHD protein was up-regulated in patients with category Ⅲ of Edmondson grade (OR=4.783, 95% CI:2.663-11.918, P=0.020), microvascular invasion (OR=37.790, 95% CI:2.227-99.434, P=0.005), and lymph node metastasis (OR=7.332, 95% CI:3.325-30.669, P=0.023).
ConclusionExpressions of MTDH mRNA and its protein are both higher in hepatitis B related hepatocellular carcinoma tissue, which are correlated with poor prognosis.
【Abstract】Objective To investigate the prevention and treatment for recurrence of hepatitis B after liver transplantation on HBV-related diseases. Methods Making a literature summarization based on published papers review.Results Acute and chronic HBV-related diseases are the main indications of liver transplantation.Recurrence rate of hepatitis B is from 80% to 100% in the untreated patients after liver transplantation,and it affects the survivals of patients seriously.It has become a focus to prevent and treat the recurrence of hepatitis B.After a series of explotation and application,there have been a lot of drugs of preventing and treating HBV reinfection, including hepatitis B immunoglobulin,interferon and nucleotide analog antivirus drugs(lamivudine, famcyclovir, adefovir),etc.The therapeutic characteristics of them are different. Their utilizations of dividing or alliance are developing rapidly.Conclusion Liver transplatation is an effective therapy for HBV-related disease. Anti-HBV treatments perioperation play an important role in the improvement of succeed of liver transplantation.
Objective To investigate the prevention of HBV reinfection in the perioperative period of liver transplantation on HBV-related diseases． Methods Published papers were collected and reviewed． Results HBV-related diseases were the main indications of liver transplantation．The prevention for HBV reinfection affects the survivals remarkably. Nowadays, a lot of medication have been used in the prevention of HBV reinfection， and the therapeutic regimens were different from each other. Conclusion Liver transplantation is an effective treatment for HBV-related disease． Appropriate prevention of HBV reinfection in the perioperative period of liver transplantation is important for the survivals of patients．
Objectives To evaluate the effects of hepatitis B immunoglobulin (HBIG) intrauterine injection before delivery on interrupting mother-to-child transmission of hepatitis B virus (HBV). Methods The randomized controlled trials (RCTs) on HBIG intrauterine injection on interrupting mother-to-child transmission of HBV published between January 1992 and May 2012 were searched in The Cochrane Library, PubMed, CBM, CNKI, VIP, WanFang Data, etc. The studies were screened according to inclusive and exclusive criteria, the data were extracted, the quality was assessed by two reviewers independently, and meta-analysis, publication bias and sensitivity analysis was conducted using Stata software. Results The total 42 studies involving 7 212 infants were included. The randomized methods were asserted in all studies, three of which reported the details of randomization, one study mentioned blinded method, two studies mentioned incomplete outcome data, 13 studies had other potential threats to validity, no allocation concealment and selective outcome reporting was mentioned. Results of meta-analysis indicated that the infant HBV infection rates in the HBIG group and the control group were 8.971% and 25.470% (RR=0.359, 95%CI 0.303 to 0.425) at birth, 5.385% and 13.919% (RR=0.391, 95%CI 0.278 to 0.550) after half a year, 5.318% and 12.457% (RR=0.429, 95%CI 0.335 to 0.551) after one year; the infant anti-HBs rates in the HBIG group and the control group were 61.964% and 14.523% (RR=6.712, 95%CI 1.920 to 23.467) at birth, 77.754% and 66.311% (RR=1.209, 95%CI 0.989 to 1.478) after half a year. Funnel graphs showed that there was publication bias. Sensitivity analysis showed that the results except the infant anti-HBs protection after half-a-year follow-up were stable and consistent with the original results. Conclusion Injection of HBIG during pregnancy for HBV-carrying mothers can effectively reduce the occurrence of HBV whenever at birth, after half a year or after one year, and increase the infant anti-HBs protection rate at birth, but it is ineffective to improve anti-HBV protection rate after half a year. Owing to the low quality of the included studies and existence of biases, this conclusion should be cautiously put into clinical practice.
ObjectiveTo explore the predictive value of serum prothrombin induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ) detection for the biological characteristics of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).MethodsThis retrospective study included 394 patients with HBV-related HCC who were newly diagnosed and treated with surgical resection in West China Hospital of Sichuan University between June 2017 and December 2018. Their clinical information such as tumor size, tumor number, tumor cell differentiation, presence of microvascular invasion (MVI), distant metastasis, and portal vein tumor thrombus was collected from the medical record. The laboratory test results of patients during diagnosis and before surgery were collected, including alpha-fetoprotein (AFP), PIVKA-Ⅱ, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GGT), etc., and the relationships between PIVKA-Ⅱ levels and tumor biological characteristics were analyzed. Non-normal continuous variables were presented as medium (lower quartile, upper quartile).ResultsCompared with the patients with low HCC serum PIVKA-Ⅱ levels (≤40 mAU/mL), patients with high serum PIVKA-Ⅱ levels (>40 mAU/mL) had larger tumor diameters [5.00 (3.00, 9.00) vs. 2.50 (1.63, 4.95) cm, P<0.001], more severe Barcelona Clinic Liver Cancer (BCLC) stage (P<0.001), and higher AFP [186.05 (6.86, 1 210.00) vs. 17.83 (4.33, 231.95) ng/mL, P<0.001], ALT [38.00 (26.00, 66.25) vs. 32.00 (22.00, 51.00) U/L, P=0.018], AST [42.00 (30.00, 76.00) vs. 34.00 (25.50, 48.25) U/L, P<0.001], and γ-GGT [71.00 (39.00, 165.50) vs. 55.50 (25.00, 93.00) U/L, P=0.005], and were more likely to form portal vein tumor thrombi (16.61% vs. 3.75%, P=0.003) and MVI (43.67% vs. 11.11%, P<0.001). In BCLC stage 0 HCC patients, the positive rate of PIVKA-Ⅱ was only 51.35%. Multivariate logistic regression analysis showed that PIVKA-Ⅱ>40 mAU/mL was an independent predictor of MVI [odds ratio=6.588, 95% confidence interval (CI) (1.645, 26.383), P=0.008]. The area under receiver operating characteristic curve of PIVKA-Ⅱ level predicting MVI was 0.761 [95%CI (0.693, 0.830)], with a sensitivity of 66.22% and a specificity of 79.06%.ConclusionIn HBV-related HCC patients, high PIVKA-Ⅱ is associated with the poor biological characteristics of tumor, and is an independent risk factor for tumor MVI.
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.
Objective To systematically review the diagnostic value of anti-HCV in serum tested by the third-generation enzyme-linked immunosorbent assay (ELISA 3) in patients with hepatitis C. Methods Such databases as PubMed, MEDLINE, EMbase, The Cochrane Library (Issue 1, 2013), EBSCO, CBM, CNKI, VIP and WanFang Data were electronically and comprehensively searched for relevant studies on the diagnostic value of anti-HCV in serum tested by ELISA 3 in patients with hepatitis C from inception to January 1st, 2013. Relevant journals were also manually retrieved. QUADAS items were used to evaluate the quality of the included studies. Then meta-analysis was performed using Meta-Disc 1.4 software to calculate pooled effect size in sensitivity (SEN), specificity (SPE), likelihood ratio (±LR), diagnostic odds ratio (DOR) and summary receiver operating characteristic curve (SROC curve), and area under the curve (AUC) as well. Results Finally, nine studies were included, involving 1 182 patients with hepatitis C diagnosed by the gold standard and 4 764 patients with non-hepatitis C diseases. The results of meta-analysis using random model showed (SEN=0.96, 95%CI 0.95 to 0.97; SPE=0.96, 95%CI 0.96 to 0.97; +LR=42.21, 95%CI 10.23 to 174.23; –LR=0.02, 95%CI 0.01 to 0.09; DOR=1 635.89, 95%CI 372.37 to 7 186.83; AUC=0.996 5). Conclusion Anti-HCV in serum tested by ELISA 3 has fairly high value in the diagnosis of patients with hepatitis C.
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.
