Fuzheng Xiaoliu granules reduce the 2-year recurrence rate of early-stage hepatitis B virus-related hepatocellular carcinoma after comprehensive minimally invasive surgery: a study protocol for a prospective, multicenter, central randomized, double-blind, placebo-controlled clinical trial

Abstract Background: Hepatitis B virus (HBV) infection is one of the most common risk factors for hepatocellular carcinoma (HCC). With the continuous improvement of minimally invasive treatment techniques such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), comprehensive minimally invasive treatment (TACE & RFA) has been widely used in the treatment of early-stage (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A) HCC and has good safety and clinical efficacy. However, recurrence and metastasis after comprehensive minimally invasive treatment are still key factors affecting the survival rate of patients. In recent years, Chinese medicine has highlighted its unique advantages in the adjuvant treatment of liver cancer surgery and minimally invasive treatment. Thus, this study aimed to evaluate the efficacy and safety of Fuzheng Xiaoliu granules (FZXLG) for treating early-stage HBV-related HCC after comprehensive minimally invasive treatment and to explore whether FZXLG can delay the progression of HBV-related HCC. Methods: This is a prospective, multicenter, central randomized, double-blind, placebo-controlled clinical trial. A total of 312 patients with early HBV-related HCC who underwent comprehensive minimally invasive treatment within 2 months were randomized in a 1:1 ratio into two groups: the experimental group and the control group. The experimental group will receive basic FZXLG plus Western medicine treatment, and the control group will receive basic FZXLG simulator plus Western medicine treatment. Each group will be treated for 1 year and followed-up for 1 year. The primary outcome measure is the 2-year recurrence rate of patients with early-stage HBV-related HCC after minimally invasive treatment. The secondary outcomes include (1) measurable active lesions, (2) alpha-fetoprotein (AFP), (3) immunological indicators, such as comparison of CD3+, CD4+, CD8+ absolute values, CD4+/CD8+ before and after the test, (4) hepatitis B virus quantity, and (5) Karnofsky functional status score. Discussion: These results will provide research data on the efficacy and safety of FZXLG for the treatment of early-stage HBV-related HCC after comprehensive minimally invasive treatment. These findings will also be based on laboratory indicators and adverse events for safety assessment to determine whether FZXLG can reduce the 2-year recurrence rate of HCC after minimally invasive surgery, which will provide reliable evidence for the clinical treatment of HCC.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900022999. Registered on 5 May 2019.

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Cytokine profile during occult hepatitis B virus infection in chronic hepatitis C patients

Virology Journal ◽

10.1186/s12985-021-01487-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Camilla Rodrigues de Almeida Ribeiro ◽

Nathalia Alves Araújo de Almeida ◽

Katrini Guidolini Martinelli ◽

Marcia Amendola Pires ◽

Carlos Eduardo Brandao Mello ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Hepatitis C ◽

Control Group ◽

Occult Hepatitis ◽

Tnf Α ◽

B Virus ◽

Occult Hepatitis B

Abstract Background The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection. Methods 114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected. Results Among 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients. Conclusion These cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.

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Clinical Application of Minimally Invasive Surgery in Pain and Complications after Spinal Trauma

Journal of Clinical and Nursing Research ◽

10.26689/jcnr.v5i1.1774 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Tianhui Liu ◽

Xiaoying Gao ◽

Jianmin Cui

Keyword(s):

Minimally Invasive Surgery ◽

Minimally Invasive ◽

Invasive Surgery ◽

Postoperative Recovery ◽

Spinal Trauma ◽

Minimally Invasive Treatment ◽

Control Group ◽

Study Group ◽

Invasive Treatment ◽

Treatment Scheme

Objective: To study and evaluate the incidence of pain and complications in patients with spinal trauma after minimally invasive treatment. Methods: The research period was selected from January 2018 to December 2020, and 40 patients with spinal trauma were selected. According to the random number table scheme, they were divided into the study group and the control group. The treatment scheme of the control group was traditional surgery, and the treatment scheme of the study group was minimally invasive surgery. The indicators of the two groups were compared and analyzed. Results: Compared with the two groups of surgery and postoperative recovery related indicators, the study group had more advantages (P<0.05); Compared two groups of postoperative NRS score, VAS score and the incidence of complications, the study group had more advantages(P<0.05). Conclusion: Minimally invasive treatment of spinal trauma has significant clinical effect, which can effectively relieve postoperative pain and reduce the incidence of various complications.

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Randomized Controlled Trial of Entecavir Prophylaxis for Rituximab-Associated Hepatitis B Virus Reactivation in Patients With Lymphoma and Resolved Hepatitis B

Journal of Clinical Oncology ◽

10.1200/jco.2012.48.5938 ◽

2013 ◽

Vol 31 (22) ◽

pp. 2765-2772 ◽

Cited By ~ 202

Author(s):

Yi-Hsiang Huang ◽

Liang-Tsai Hsiao ◽

Ying-Chung Hong ◽

Tzeon-Jye Chiou ◽

Yuan-Bin Yu ◽

...

Keyword(s):

Viral Load ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Controlled Trial ◽

Control Group ◽

Hbv Reactivation ◽

Antiviral Prophylaxis ◽

B Virus ◽

To Receive

Purpose The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear. Patients and Methods Eighty patients with CD20+ lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39). Results Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion. Conclusion Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.

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The possible role of S gene mutations of hepatitis B virus in intrauterine transmission

10.21203/rs.2.21142/v1 ◽

2020 ◽

Author(s):

Jiaxin Wu ◽

Yongliang Feng ◽

Zhiqing Yang ◽

Ruijun Zhang ◽

Dandan Wang ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Gene Mutations ◽

Hbv Dna ◽

Mutation Rates ◽

Control Group ◽

Intrauterine Transmission ◽

S Gene ◽

B Virus

Abstract Background: Many hepatitis B virus (HBV) substances could inevitably enter fetuses and occurred neonatal intrauterine transmission. HBV often occurs mutation, especially S gene, and may lead to different outcomes on intrauterine transmission. We explored the associations between HBV S gene mutations of hepatitis B surface antigen positive (HBsAg-positive) mothers and intrauterine transmission. Methods: A total of 399 HBsAg-positive mothers and neonates were recruited and their general demographic information was collected between June 2011 and July 2013. The mothers with HBV DNA levels ≥ 106 IU/ml were selected, 22 mothers whose neonates occurred HBV intrauterine transmission were in the HBV intrauterine transmission group (GT) and 22 mothers were randomly selected from the remaining controls were in the control group (GC). Maternal whole-genome HBV DNA was extracted, amplified, cloned, and sequenced. Obtained sequences were adjusted, genotyped, and analyzed for mutation rates. A case-control study was designed to analyze the relationship between mutations in the S gene of HBV and intrauterine transmission. Results: Fifty-five neonates were found to have experienced intrauterine transmission (13.78%). Genotype B (4.55%), genotype C (88.64%) and inter-genotype B/C (6.81%) were found in the 44 HBsAg-positive mothers. The mutation rates of the S gene, in both genotypes B (0.58% vs 1.41%, P = 0.040) and C (7.56% vs 14.71%, P＜0.001), were lower in group T than in group C. Missense substitutions such as L84I, P47S, K10Q, A41P, M133L, A60V, and I42T only existed in group C. The mutation rates of G73S, I126T, and I126S in group C were higher (P < 0.001, P < 0.001, P = 0.010). Deletions occurred in the S gene. The occurrence of intrauterine transmission with maternal mutation A90V was higher (P < 0.001). This may have increased the risk of neonatal HBsAg expression (P = 0.022). Conclusions: The HBV S gene mutations of HBsAg-positive mothers may reduce the occurrence of HBV intrauterine transmission. It is possible for HBsAg-positive mothers infected with A90V to develop HBV chronic infection and transmit it to the fetus during pregnancy, resulting in neonatal HBV infection.

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The efficacy and safety of methylprednisolone in hepatitis B virus-related acute-on-chronic liver failure: a prospective multi-center clinical trial

BMC Medicine ◽

10.1186/s12916-020-01814-4 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Lin Jia ◽

Ran Xue ◽

Yueke Zhu ◽

Juan Zhao ◽

Juan Li ◽

...

Keyword(s):

Hepatitis B Virus ◽

Dna Replication ◽

Hepatitis B ◽

Liver Failure ◽

Standard Treatment ◽

Hbv Dna ◽

Control Group ◽

Efficacy And Safety ◽

Chronic Liver Failure ◽

B Virus

Abstract Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe condition with high mortality due to lack of efficient therapy. Until now, the use of methylprednisolone (MP) in HBV-ACLF is still controversial. We aimed to evaluate the efficacy and safety of MP in HBV-ACLF. Methods Totally 171 HBV-ACLF patients from three medical centers were randomly allocated into MP group (83 patients treated with MP intravenously guttae for 7 days plus standard treatment: 1.5 mg/kg/day [day 1–3], 1 mg/kg/day [day 4–5], and 0.5 mg/kg/day [day 6–7]) and control group (88 patients treated with standard treatment). The primary endpoints were 6-month mortality and prognostic factors for 6-month survival. The survival time, cause of death, adverse events, liver function, and HBV DNA replication were analyzed. Results The 6-month mortality was significantly lower in MP group than control group [32.4% vs. 42.5%, P = 0.0037]. MP treatment was an independent prognostic factor for 6-month survival [HR (95% CI) 0.547(0.308–0.973); P = 0.040]. Factors associated with reduced 6-month mortality in MP group included HBV DNA and lymphocyte/monocyte ratio (LMR) (P < 0.05). Based on ROC curve, LMR+MELD had a better predictive value for prognosis of HBV-ACLF under MP treatment. No significant difference in HBV DNA replication was observed between groups (P > 0.05). Conclusions MP therapy is an effective and safe clinical strategy in HBV-ACLF, increasing the 6-month survival rate. Clinical trials registered at http://www.chictr.org.cn as ChiCTR-TRC-13003113 registered on 16 March 2013.

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Entecavir Plus Pegylated Interferon and Sequential Hepatitis B Virus Vaccination Increases Hepatitis B Surface Antigen Seroclearance: A Randomized Controlled Proof-of-Concept Study

Clinical Infectious Diseases ◽

10.1093/cid/ciaa807 ◽

2020 ◽

Author(s):

Jeong-Hoon Lee ◽

Yun Bin Lee ◽

Eun Ju Cho ◽

Su Jong Yu ◽

Jung-Hwan Yoon ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Pegylated Interferon ◽

Control Group ◽

Proof Of Concept ◽

Randomized Controlled ◽

Hbv Vaccination ◽

Hbsag Seroclearance ◽

B Virus

Abstract Background Hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure for patients with chronic hepatitis B, but is rarely achievable with oral nucleos(t)ide analogues alone. We conducted a randomized controlled proof-of-concept trial to evaluate the impact of adding pegylated interferon (peg-IFN) alfa-2a plus sequential or concomitant hepatitis B virus (HBV) vaccination. Methods A total of 111 patients who achieved serum HBV DNA <20 IU/mL and quantitative HBsAg <3000 IU/mL with entecavir were randomly assigned (1:1:1) to the E + sVIP group (entecavir + peg-IFN alfa-2a [180 µg every week over 48 weeks] plus sequential HBV vaccination [20 µg of HBsAg on weeks 52, 56, 60, and 76]), the E + cVIP group (entecavir + peg-IFN alfa-2a + concomitant HBV vaccination [weeks 4, 8, 12, and 28]), or the control group (entecavir only). The primary endpoint was HBsAg seroclearance at week 100, and secondary endpoints included safety. Results No differences in baseline quantitative HBsAg were observed among the groups. The E + sVIP group in the intention-to-treat analysis showed a significantly higher chance of HBsAg seroclearance during week 100 than the control group (16.2% vs 0%; P = .025), but the E + cVIP group (5.4%) failed to reach a significant difference (P = .54). Adverse events were significantly more frequent in the E + sVIP (81.1%) and E + cVIP group (70.3%) than the control group (2.7%) (both P < .0001). However, the frequency of serious adverse events did not differ significantly among the 3 groups (2.7%, 5.4%, and 2.7%, respectively; P = 1.00). Conclusions Entecavir plus an additional peg-IFN alfa-2a treatment followed by sequential HBV vaccination under an intensified schedule significantly increases the chance of HBsAg seroclearance compared to entecavir alone. Clinical Trials Registration NCT02097004.

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Genotype-Specific Genomic Markers Associated with Primary Hepatomas, Based on Complete Genomic Sequencing of Hepatitis B Virus

Journal of Virology ◽

10.1128/jvi.01197-07 ◽

2008 ◽

Vol 82 (7) ◽

pp. 3604-3611 ◽

Cited By ~ 39

Author(s):

Joseph J. Y. Sung ◽

Stephen K. W. Tsui ◽

Chi-Hang Tse ◽

Eddie Y. T. Ng ◽

Kwong-Sak Leung ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Rule Learning ◽

Hbv Infection ◽

Control Group ◽

Hbv Genotype ◽

B Virus ◽

Genomic Markers ◽

Genotype C ◽

Complete Genomic

ABSTRACT We aimed to identify genomic markers in hepatitis B virus (HBV) that are associated with hepatocellular carcinoma (HCC) development by comparing the complete genomic sequences of HBVs among patients with HCC and those without. One hundred patients with HBV-related HCC and 100 age-matched HBV-infected non-HCC patients (controls) were studied. HBV DNA from serum was directly sequenced to study the whole viral genome. Data mining and rule learning were employed to develop diagnostic algorithms. An independent cohort of 132 cases (43 HCC and 89 non-HCC) was used to validate the accuracy of these algorithms. Among the 100 cases of HCC, 37 had genotype B (all subgenotype Ba) and 63 had genotype C (16 subgenotype Ce and 47 subgenotype Cs) HBV infection. In the control group, 51 had genotype B and 49 had genotype C (10 subgenotype Ce and 39 subgenotype Cs) HBV infection. Genomic algorithms associated with HCC were derived based on genotype/subgenotype-specific mutations. In genotype B HBV, mutations C1165T, A1762T and G1764A, T2712C/A/G, and A/T2525C were associated with HCC. HCC-related mutations T31C, T53C, and A1499G were associated with HBV subgenotype Ce, and mutations G1613A, G1899A, T2170C/G, and T2441C were associated with HBV subgenotype Cs. Amino acid changes caused by these mutations were found in the X, envelope, and precore/core regions in association with HBV genotype B, Ce, and Cs, respectively. In conclusion, infections with different genotypes of HBV (B, Ce, and Cs) carry different genomic markers for HCC at different parts of the HBV genome. Different HBV genotypes may have different virologic mechanisms of hepatocarcinogenesis.

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Whole-Exome Sequencing-Based Mutational Profiling of Hepatitis B Virus-Related Early-Stage Hepatocellular Carcinoma

Gastroenterology Research and Practice ◽

10.1155/2017/2029315 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Hao Zhan ◽

Jiahao Jiang ◽

Qiman Sun ◽

Aiwu Ke ◽

Jinwu Hu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Axon Guidance ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Early Stage ◽

Genetic Characteristics ◽

Whole Exome ◽

B Virus

Background. Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related mortality in China with increasing incidence. This study is designed to explore early genetic changes implicated in HCC tumorigenesis and progression by whole-exome sequencing. Methods. We firstly sequenced the whole exomes of 5 paired hepatitis B virus-related early-stage HCC and peripheral blood samples, followed by gene ontological analysis and pathway analysis of the single-nucleotide variants discovered. Then, the mutations of high frequency were further confirmed by Sanger sequencing. Results. We identified a mutational signature of dominant T:A>A:T transversion in early HCC and significantly enriched pathways including ECM-receptor interaction, axon guidance, and focal adhesion and enriched biological processes containing cell adhesion, axon guidance, and regulation of pH. Eight genes, including MUC16, UNC79, USH2A, DNAH17, PTPN13, TENM4, PCLO, and PDE1C, were frequently mutated. Conclusions. This study reveals a mutational profile and a distinct mutation signature of T:A>A:T transversion in early-stage HCC with HBV infection, which will enrich our understanding of genetic characteristics of the early-stage HCC.

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