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Objective:To investigate the efficacy of peginterferon alfa-2a (Peg-IFNα-2a) combined with entecavir in sequential treatment of chronic hepatitis B.Methods:A total of 106 patients with chronic hepatitis B who received treatment in Affiliated Hangzhou Xixi Hospital of Zhejiang University School of Medicine from January 2020 to February 2022 were included in this study. They were divided into a control group (entecavir treatment, n = 53) and a study group (sequential therapy with Peg-IFNα-2a followed by entecavir, n = 53). Liver function indicators, liver fibrosis indicators, clinical treatment efficacy, and incidence of adverse reactions were compared between the two groups before and after treatment. Results:After treatment, total bilirubin, alanine aminotransferase and aspartate transaminase in the control and study groups were (94.79 ± 8.71) μmol/L and (67.67 ± 9.19) μmol/L, (256.93 ± 44.07) U/L and (186.56 ± 48.37) U/L, (256.47 ± 43.73) U/L and (200.69 ± 41.34) U/L, and they were (140.05 ± 26.15) μmol/L and (141.32 ± 25.35) μmol/L, (433.66 ± 77.16) U/L and (429.77 ± 73.73) U/L, (352.34 ± 65.19) U/L and (354.05 ± 66.13) U/L before the treatment. After treatment, these indexes in each group were decreased compared with before treatment ( t = 19.19, -12.13, -28.85, -20.96, -19.27, -12.03, all P < 0.05). After treatment, these indexes in the study group were significantly lower than those in the control group ( t = -6.49, -7.30, -6.74, all P < 0.001). After treatment, the levels of hyaluronic acid, laminin, type III procollagen peptide, and type IV collagen in the control and study groups were (124.91 ± 22.99) μg/L and (101.29 ± 22.67) μg/L, (132.71 ± 25.37) μg/L and (110.56 ± 25.49) μg/L, (116.93 ± 20.29) μg/L and (93.14 ± 20.39) μg/L, (63.14 ± 12.19) μg/L and (50.81 ± 11.63) μg/L, and they were (175.73 ± 48.56) μg/L and (177.61 ± 48.51) μg/L, (163.43 ± 41.52) μg/L and (165.57 ± 41.59) μg/L, (139.71 ± 31.75) μg/L and (141.72 ± 31.78) μg/L, (106.97 ± 32.24) μg/L and (104.02 ± 34.12) μg/L before treatment. After treatment, the levels of these indexes in each group were significantly decreased compared with before treatment ( t = -13.04, -8.68, -10.43, -5.82, -13.35, -6.26, -13.02, -10.72, all P < 0.05). After treatment, the levels of these indexes in the study group were significantly lower than those in the control group ( t = -5.32, -4.48, -6.02, -5.32, all P < 0.001). The total response rate in the study group was 88.68% (47/53), which was significantly higher than 62.26% (33/53) in the control group ( χ2 = 9.98, P < 0.05). The HBsAg conversion rate in the study group was 33.96% (18/53), which was significantly higher than 1.32% (6/53) in the control group ( χ2 = 7.75, P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the study and control groups [26.42% (14/53) vs. 30.19% (16/53), χ2 = 0.81, P > 0.05]. Conclusion:Sequential therapy with Peg-IFNα-2a followed by entecavir can effectively improve liver function,reduce liver fibrosis , improve clinical treatment efficacy, and will not increase adverse reactions.
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Objective To investigate the possible influence of long-term antiviral therapy with entecavir on renal function in patients with chronic hepatitis B (CHB) and the sensitive indicators for early identification of renal injury. Methods A cross-sectional real-world study was conducted for the clinical data of 125 CHB patients treated with entecavir for more than 1 year (treatment group) and 44 patients with chronic HBV infection who did not receive antiviral therapy (control group), including the changes in serum creatinine (SCr), estimated glomerular filtration rate (eGFR), and the levels of urinary α1 microglobulin (α1-MG), β2 microglobulin (β2-MG), and N-acetyl-β-D-glucosaminidase (NAG). The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The Logistic regression analysis was used to investigate independent influencing factors for abnormal urinary α1-MG, β2-MG, and NAG in the treatment group. Results There were no significant differences in SCr and eGFR between the treatment group and the control group ( t =0.999 and -1.259, P > 0.05), and both indices were within the normal range in these two groups. The treatment group had significantly higher abnormal rates of urinary α1-MG and β2-MG than the control group (47.2%/42.4% vs 13.6%/13.6%, χ 2 =15.693 and 12.567, both P 2×upper limit of normal (18.4%/21.6% vs 2.3%/4.5%, both P 0.05) and the proportion of patients with urinary NAG > 2×upper limit of normal (8.8% vs 6.8%, P > 0.05). Compared with the control group, the treatment group had a significantly higher proportion of patients with abnormalities in two or more indicators for renal tubular injury (33.6% vs 11.4%, χ 2 =8.519, P 0.05). Conclusion Long-term treatment of CHB with entecavir may be associated with the risk of renal tubular dysfunction, and abnormalities in more than two indicators for renal injury may help to identify renal tubular dysfunction in patients, so as to adjust related treatment in time.
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Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.
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Humanos , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Estudos Prospectivos , Resultado do TratamentoRESUMO
Objective:To investigate the efficacy and safety of camrelizumab in the treatment of advanced hepatocellular carcinoma complicated with hepatitis B virus infection.Methods:One hundred cases of patients with advanced primary hepatocellular carcinoma complicated with hepatitis B virus infection admitted to the Fuyang Cancer Hospital from July 2020 to July 2021 were selected and divided into the observation group (48 cases) and the control group (52 cases) by the random number table method. The control group was treated with transhepatic arterial chemoembolization (TACE) and entecavir, and the observation group was treated with camrelizumab on the basis of the control group. After 3 months of treatment, the efficacy was evaluated, serum Alpha-fetoprotein (AFP) was determined, and the incidence of adverse reactions was counted. Progression-free survival (PFS) and overall survival (OS) were compared in follow-up visits.Results:After 3 months of treatment, the objective remission rates of the observation group and the control group were 47.92% (23/48) and 23.08% (12/52), respectively, and the disease control rates were 85.42% (41/48) and 65.38% (34/52), respectively, with statistically significant differences ( P<0.05); the AFP level in the observation group was significantly lower than that in the control group: (55.41 ± 10.22) μg/L vs. (78.52 ± 9.63) μg/L, with statistically significant differences ( P<0.05); the incidence of reactive skin capillary hyperplasia in the observation group was significantly higher than that in the control group: 83.33% (40/48) vs. 0, with statistically significant differences ( P<0.05); the median PFS and OS in the observation group were significantly longer than those in the control group: 8.00 (6.27, 9.73) months vs. 5.90 (4.70, 7.10) months and 15.50 (13.47, 17.00) months vs. 12.80 (10.21, 15.39) months, with statistically significant differences ( P<0.05). Conclusions:Camrelizumab combined with entecavir and TACE is effective in the treatment of patients with advanced hepatocellular carcinoma complicated with hepatitis B virus infection. Compared with the short-term efficacy and long-term survival of entecavir alone combined with TACE, camrelizumab combined with TACE is more advantageous, and the degree of adverse reactions is less. Therefore, this regimen may have better benefits when considering the efficacy and tolerability.
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Objective: To investigate the efficacy and possible mechanism of action of warm needling moxibustion combined with entecavir in the treatment of compensated cirrhosis due to chronic hepatitis B (CHB).Methods: Ninety patients were randomly divided into a control group and an observation group, with 45 patients in each group. The control group was given oral entecavir, and the observation group was given additional warm needling moxibustion. The serum alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB) levels, portal vein internal diameter, splenic vein internal diameter, spleen thickness, and liver hardness were compared before and after treatment. The serum hyaluronic acid (HA), laminin (LN), procollagen type Ⅲ (PCⅢ), type Ⅳ collagen (Ⅳ-C), interleukin (IL)-21, and platelet-derived growth factor (PDGF) levels were also measured. Results: After treatment, the serum ALT and AST levels decreased (P<0.05), and the serum ALB levels increased (P<0.05) in both groups. The serum ALT and AST levels were lower in the observation group than in the control group (P<0.05), and the ALB level was higher in the observation group (P<0.05). The portal vein internal diameter, splenic vein internal diameter, spleen thickness, and liver hardness values were reduced in both groups after treatment (P<0.05), and were lower in the observation group than in the control group (P<0.05). The serum HA, LN, PCⅢ, and Ⅳ-C levels were reduced in both groups (P<0.05), and were lower in the observation group than in the control group (P<0.05). In the control group, the serum IL-21 level decreased (P<0.05), but the serum PDGF level did not change significantly (P>0.05); in the observation group, the serum IL-21 and PDGF levels decreased significantly (P<0.05) and were lower than those in the control group (P<0.05). Conclusion: Warm needling moxibustion combined with entecavir treatment can improve liver function, reduce the inner diameters of the portal vein and splenic vein, spleen thickness, and liver hardness, and improve liver fibrosis indicators in patients with CHB cirrhosis, which may be related to the reduction of serum IL-21 and PDGF levels.
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Objective To investigate the effect of Ganshuang granule combined with entecavir on portal vein thrombosis (PVT) in patients with hepatitis B cirrhosis. Methods A total of 356 patients with hepatitis B cirrhosis who attended and were hospitalized in The Third People's Hospital of Kunming from January 1, 2018 to December 31, 2020 were enrolled and randomly divided into combination group with 191 patients and control group with 165 patients. The patients in the combination group received Ganshuang granule combined with entecavir, and those in the control group received entecavir alone. The course of treatment was at least 24 weeks. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze the cumulative incidence rate of PVT in both groups, and the log-rank test was used for comparison between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for PVT in patients with hepatitis B cirrhosis. Results The 191 patients in the combination group were followed up for 296.25 person-years in total, with a mean follow-up time of 1.55±0.65 years, and there were 8 patients with PVT, with an incidence rate of 4.19% and an incidence density of 1.41 per ten-thousand person-years. The 165 patients in the control group were followed up for 253.25 person-years in total, with a mean follow-up time of 1.53±0.67 years, and there were 20 patients with PVT, with an incidence rate of 12.12% and an incidence density of 4.79 per ten-thousand person-years. There was a significant difference in the incidence rate of PVT between the two groups ( χ 2 =7.687, P =0.006). The cumulative incidence rate of PVT plotted by the Kaplan-Meier method showed that the combination group had a significantly lower cumulative incidence rate of PVT than the control group ( χ 2 =7.226, P =0.007), with a relative risk of 3.155 (95% confidence interval [ CI ]: 1.351-7.370). The univariate Cox analysis showed that hypertension, alanine aminotransferase, aspartate aminotransferase (AST), albumin (Alb), cholinesterase, estimated glomerular filtration rate, alpha-fetoprotein, D-dimer (D-D), Child-Pugh class, and Ganshuang granule combined with entecavir were influencing factors for PVT (all P < 0.05); the multivariate Cox analysis showed that AST (hazard ratio [ HR ]=1.002, 95% CI : 1.000-1.004, P =0.025), and D-D ( HR =1.907, 95% CI : 1.554-2.338, P < 0.001) were independent risk factors for PVT in patients with hepatitis B cirrhosis, while Alb ( HR =0.844, 95% CI : 0.755-0.944, P =0.003) and Ganshuang granule combined with entecavir ( HR =0.350, 95% CI : 0.144-0.851, P =0.021) were independent protective factors against PVT in patients with hepatitis B cirrhosis. Conclusion Ganshuang granule combined with entecavir can significantly reduce the incidence rate of PVT in patients with hepatitis B cirrhosis, thereby exerting a certain preventive effect against PVT.
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Objective To investigate the clinical effect of tenofovir alafenamide fumarate (TAF) on chronic hepatitis B (CHB) patients with low-level viremia (LLV) after entecavir (ETV) treatment. Methods A total of 160 CHB patients who received ETV antiviral therapy in Wuhan Jinyintan Hospital from March 2019 to October 2020 were enrolled and divided into experimental group and control group by propensity score matching, with 80 patients in each group. The patients in the experimental group were given TAF antiviral therapy, and those in the control group were given ETV treatment; the course of treatment was 24 weeks for both groups. The two groups were compared in terms of HBV-DNA clearance rate, HBeAg clearance rate, alanine aminotransferase (ALT) level, estimated glomerular filtration rate (eGFR), FIB-4 value, liver stiffness measurement, and adverse drug reactions after treatment. The t -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. Results After 24 weeks of treatment, compared with the control group, the experimental group had significantly higher HBV DNA clearance rate (96.25% vs 16.25%, χ 2 =104.03, P 0.05). Conclusion For CHB patients with LLV after ETV treatment, the change to TAF antiviral therapy can effectively increase their HBV DNA clearance rate and HBeAg clearance rate, improve liver and renal function, and reduce the degree of liver fibrosis, with good safety.
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Acute-on-chronic liver failure (ACLF) is a specific category of liver failure, which is mainly characterized by rapid progression and multiple organ failure. At present, patients with ACLF are mainly given with systematic and comprehensive medical therapy to promote liver regeneration. However, liver transplantation is the only potentially curative treatment for patients who failed to respond to medical treatment and rapidly progress into multiple organ failure. Considering the differences of disease progression and clinical prognosis, and the shortage of donor liver in China, it is necessary to actively prevent the triggering factors of ACLF in patients with chronic liver diseases, screen out the recipients who are most likely to benefit from liver transplantation and deliver precision management during perioperative period of liver transplantation. In this article, the application of liver transplantation in ACLF was illustrated from the perspectives of accurate evaluation of ACLF, proper control of liver transplantation indications and meticulous perioperative management, aiming to optimize the therapeutic strategy of liver transplantation in patients with ACLF.
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OBJECTIVES@#Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF.@*METHODS@#The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis..@*RESULTS@#After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group.@*CONCLUSIONS@#TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.
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Humanos , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Alanina/uso terapêutico , Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Tenofovir/análogos & derivados , Resultado do TratamentoRESUMO
ObjectiveTo investigate the efficacy and safety of Fuzheng Huayu tablets (FZHY) combined with entecavir (ETV) in the treatment of chronic hepatitis B (CHB) liver fibrosis. MethodsA total of 52 patients with CHB liver fibrosis with an Ishak stage of ≥F3 who were treated in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from April 2011 to January 2013 were enrolled and divided into FZHY combined with ETV group (combination group) and placebo combined with ETV group (control group), with 26 patients in each group, and the course of treatment was 48 weeks for both groups. Liver biopsy was performed before and after these treatment; clinical outcome was determined based on the reversal rate of Ishak stage for liver fibrosis and the improvement rate of histological activity index (HAI) for inflammation grade, and safety was evaluated based on electrocardiographic findings. Three datasets (full analysis set, per-protocol set, and safety dataset) were identified for analysis; the t-test or the Wilcoxon test was used for comparison of continuous data between two groups, and the CMH chi-square test, the chi-square test, or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsOf all 52 patients, 46 underwent the two liver biopsies before and after treatment, with 22 in the combination group and 24 in the control group. At week 48 of treatment, there was a significant difference in the proportion of patients with Ishak stage reduced by ≥1 stage between the combination group and the control group (81.8% vs 54.2%, χ2=5.297, P=0.021). There was also a significant difference in the improvement rate of HAI grade between the combination group and the control group were (59.1% vs 25.0%, χ2=6.822, P=0.009). There were no significant differences between the two groups in the incidence rates of adverse events and serious adverse events, the safety analysis of vital signs, and laboratory safety indicators (all P>0.05). ConclusionFZHY combined with ETV has significant advantages over ETV alone in improving liver fibrosis and inflammation, and antiviral therapy combined with anti-fibrosis therapy can bring better hepatic histological improvement for CHB patients. FZHY combined with ETV has good safety in the treatment of patients with CHB liver fibrosis.
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ObjectiveTo investigate the influencing factors for persistent low-level viremia (LLV) in chronic hepatitis B(CHB) patients receiving long-term entecavir antiviral therapy. MethodsThe CHB patients who received entecavir antiviral therapy for at least one year in The Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were enrolled as subjects, and according to HBV DNA load at the end of the observation period, the patients were divided into LLV group and sustained virological response (SVR) group. Demographic features and laboratory markers were observed for all patients. The independent samples 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. A multivariate logistic regression analysis was used to investigate the influencing factors for LLV in patients receiving long-term entecavir treatment. ResultsA total of 560 CHB patients were enrolled, with 204 in the LLV group and 356 in the SVR group. There were significant differences between the two groups in age (Z=-3.530, P<0.001), sex (χ2=4.270, P=0.039), presence or absence of liver cirrhosis (χ2=53.879, P<0.001), medication compliance (χ2=5.326, P=0.021), HBeAg positive rate (χ2=90.681, P<0.001), baseline HBV DNA load before treatment (Z=-8.337, P<0.001), baseline HBsAg quantification (Z=-10.472, P<0.001), and medication type (χ2=7.558, P=0.006). The multivariate logistic regression analysis showed that baseline HBeAg status before treatment (odds ratio [OR]=3.381, 95% confidence interval [CI]: 1.985-5.756, P<0.001), HBV DNA load before treatment (OR=1.223, 95%CI: 1.050-1.424, P=0.010), and HBsAg quantification before treatment (OR=2.448, 95%CI: 1.743-3.438, P<0.001) were risk factors for LLV in long-term entecavir antiviral therapy. ConclusionIn clinical practice, CHB patients with high HBV DNA load, high HBsAg quantification, and positive HBeAg tend to have a high risk of LLV even after long-term entecavir antiviral therapy. Therefore, such population should be taken seriously with the dynamic monitoring of HBsAg quantification, HBV DNA load, and HBeAg status.
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ObjectiveTo investigate the effect of entecavir (ETV) antiviral therapy on the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) receiving transcatheter arterial chemoembolization (TACE). MethodsA total of 170 HCC patients who received TACE for the first time in Liver Cancer Center of Nanfang Hospital from January 2011 to March 2018 were enrolled, among whom 114 patients were treated with ETV (ETV treatment group) and 56 patients did not receive antiviral therapy (control group). Baseline demographic data, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), albumin (Alb), platelet count (PLT), Child-Pugh class, HBeAg and HBV DNA levels, alpha-fetoprotein, and BCLC stage were recorded before treatment, and the changes in HBV DNA level, ALT, AST, TBil, Alb, and Child-Pugh class were observed at weeks 4-8 after treatment; long-term survival was also observed after treatment. Short- and long-term clinical benefits (overall survival) were observed for all patients. The t-test or the Wilcoxon signed-rank 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. Multivariate logistic regression analyses were performed for related clinical indices before treatment to identify the risk factors for HBV reactivation. The Kaplan-Meier method was used to analyze the survival curves of overall survival, and the log-rank test was used for comparison of survival curves. ResultsThere was no significant difference in the incidence rate of HBV reactivation between the ETV treatment group and the control group (15.79% vs 16.07%, χ2=0.002,P=0.962). The univariate analysis showed that PLT was a risk factor for HBV reactivation (Z=-2.183,P=0.029), and the multivariate analysis showed that HBV DNA level was an independent risk factor for HBV reactivation (hazard ratio =1.000, 95% confidence interval: 1.000-1.000, P=0.015). The 1-, 3-, and 5-year survival rates were 56.20%, 30.30%, and 13.20%, respectively, in the ETV treatment group and 60.60%, 27.20%, and 16.30%, respectively, in the control group. There was no significant difference in overall survival rate between the two groups (χ2=0.049,P=0.755). ConclusionAntiviral therapy can reduce the incidence rate of HBV reactivation after TACE in patients with HBV-related HCC.
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Objective To explore the therapeutic effect of Gansu tablets combined with entecavir on patients with severe hepatitis B and the effect on patients’ immune function. Methods A total of 108 cases of severe hepatitis B patients who were treated in our hospital from January 2018 to January 2019 were randomly divided into two groups: entecavir group and combination treatment group, 54 cases each. Entecavir group was treated with entecavir, and combination treatment group was treated with Gansu tablets and entecavir. The levels of AST, GGT, alt, FIB, APTT, Pt, GSH Px, LPO and MDA in serum were measured by enzyme-linked immunosorbent assay. T-lymphocyte subsets were measured by cell analyzer. The therapeutic effect and adverse reactions were compared between the two groups. Results The levels of AST, GGT and ALT in the combined treatment group were significantly lower than those in the entecavir group (P 0.05). Conclusion The use of Gansu tablets combined with entecavir in the treatment of severe hepatitis B patients was able to improve liver function, improve coagulation function, reduce oxidative stress injury, and improve the immune function of patients, demonstrating a potential clinical application value.
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ObjectiveTo investigate the dynamic changes of serum HBsAg and hepatitis B virus (HBV) DNA in chronic hepatitis B patients (CHB) with entecavir (ETV) monotherapy for 5 years. MethodsA retrospective analysis was performed for the clinical data of 918 CHB patients who attended the Second Affiliated Hospital of Xi’an Jiaotong University from January 2012 to August 2020 and received ETV monotherapy for ≥5 years, among whom 556 had positive HBeAg and 362 had negative HBeAg at initial treatment. Serum HBsAg level and HBV DNA load at baseline and at 1, 2, 3, 4, and 5 years of treatment were collected to analyze their dynamic changes. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; log10 logarithmic transformation was performed for non-normally distributed repeated measurement data, and then a repeated-measures analysis of variance was used for comparison between groups or within each group; the chi-square test was used for comparison of categorical data between two groups. ResultsBoth HBeAg-positive and HBeAg-negative patients had a significant reduction in HBsAg level over the time of ETV treatment (F=174.168 and 49.845, both P<0.001). The HBeAg-positive patients had a baseline HBsAg level of 18 043.1 (7868.9-26 342.4) IU/ml, which significantly decreased to 13976 (626.4-3419.4) IU/ml after 5 years of ETV treatment (P<0.001); the HBeAg-positive patients had a baseline HBV DNA load of (67±1.7) log10 IU/ml and achieved an HBV DNA clearance rate of 100% after 5 years of ETV treatment. The HBeAg-negative patients had a baseline HBsAg level of 2420.0 (662.6-5621.2) IU/ml, which significantly decreased to 407.2 (56.7-1104.7) IU/ml after 5 years of ETV treatment (P<0.001); the HBeAg-negative patients had a baseline HBV DNA load of 4.9±1.4 log10 IU/ml and achieved an HBV DNA clearance rate of 100% after 5 years of ETV treatment. The HBeAg-positive patients had a significantly higher median HBsAg level than the HBeAg-negative patients at each time point (all P<0.001). Both HBeAg-positive and HBeAg-negative patients showed a changing trend of rapid reduction followed by slow reduction in HBsAg, and the mean annual rate of reduction in HBsAg in the first 2 years of ETV treatment was significantly higher than that in the last 3 years of ETV treatment (HBeAg-positive: Z=-13.605, P<0001; HBeAg-negative: Z=-5.950, P<0.001). The HBeAg-positive patients had a significantly lower HBV DNA clearance rate than the HBeAg-negative patients at 1 year of ETV treatment (χ2=71.013, P<0.001), and both HBeAg-positive and HBeAg-negative patients achieved an HBV DNA clearance rate of 100% at 2, 3, 4, and 5 years of treatment. After 5 years of ETV treatment, the cumulative proportions of patients with HBsAg clearance, HBsAg <200 IU/ml, HBsAg <1000 IU/ml, and HBsAg<1500 IU/ml were 3.6%, 23.9%, 57.0%, and 67.3%, respectively. ConclusionDuring the EVT treatment of CHB, the levels of HBsAg and HBV DNA gradually decrease, and the level of HBsAg shows a trend of rapid reduction followed by slow reduction. After 5 years of ETV monotherapy, 67.3% of the patients can achieve an HBsAg level of <1500 IU/ml.
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ObjectiveTo investigate the clinical effect of entecavir (ETV) rescue treatment in chronic hepatitis B (CHB) patients at the onset of rtA181V/T mutation. MethodsA total of 174 CHB patients who were treated in the outpatient and inpatient departments of The Affiliated Hospital of Xuzhou Medical University from January 2012 to January 2017 and underwent the detection of drug-resistance mutations of the genes in the reverse transcription (RT) polymerase region were enrolled, among whom there were 72 previously untreated patients and 102 treatment-experienced patients with virological breakthrough or poor response. The association between the previous medication history of nucleos(t)ide analogues and the mutation pattern (including rtA181V/T) was evaluated in the treatment-experienced CHB patients. A total of 155 patients were enrolled, among whom 72 patients had no drug-resistance mutations, 45 had rtA181V/T mutation, and 38 had rtA181V/T+rtN236T mutation. The three groups were compared in terms of virologic response and biochemical parameters at baseline and at weeks 24 and 48 of ETV rescue treatment. The t-test was used for comparison of normally distributed continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups; the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between two groups. A logistic regression analysis was used to screen out the influencing factors for poor prognosis. ResultsA analysis of the previous medication history of NAs and the mutation patterns for all patients suggested that the patients with the medication history of multiple NAs tended to have multisite mutations and multi-drug resistance (χ2=4295, P<0.05). The level of HBV DNA at the time of virological breakthrough was lower than that at the time of initial administration of NAs in the rtA181V/T mutation group [(6.22±1.48) log10 IU/ml vs (7.08±1.59) log10 IU/ml, t=3.098, P=0.002] and the rtA181V/T+rtN236T mutation group [(5.94±1.45) log10 IU/ml vs (6.94±1.61) log10 IU/ml,t=2.850, P=0.004]. At week 48 of ETV rescue treatment, there were no significant differences between the three groups in HBV DNA negative conversion rate (83.3% vs 82.2% vs 81.6%, P>0.05) and HBeAg negative conversion rate (22.2% vs 17.8% vs 21.1%, P>0.05), and there were also no significant differences in alanine aminotransferase normalization rate (77.1% vs 85.2% vs 83.3%, P>0.05), aspartate aminotransferase normalization rate (80.4% vs 75.9% vs 76.0%, P>0.05), and total bilirubin normalization rate (80.8% vs 79.3% vs 78.1%, P>0.05). HBV DNA level at the beginning of ETV treatment was the risk factor for the treatment outcome of 48-week antiviral therapy (odds ratio = 1.655, 95% confidence interval: 1.128-2.428, P=0.01). ConclusionETV has a good antiviral effect in treatment-experienced CHB patients with rtA181 drug-resistance mutation, and HBV DNA level at the initiation of ETV treatment can predict the outcome of 48-week ETV rescue treatment.
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Objective:To observe the clinical efficacy of compound Huanggen granules combined with Entecavir tablets for patients with chronic hepatitis B with syndrome of collateral retardation due to blood stasis. Method:The 130 patients with chronic hepatitis B with syndrome of collateral retardation due to blood stasis were randomly divided into observation group and control group by using random number table method. The 65 patients in observation group were treated with compound Huanggen granules combined with Entecavir tablets, and 65 patients in control group were treated with Entecavir tablets orally. The changes of liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin(TBIL), albumin(Alb)] , coagulation function [prothrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), fibrinogen(FIB)], serum Hepatitis B Virus DNA(HBV DNA) levels, hepatitis B e antigen quantification(HBeAg), stiffness of the liver, liver imaging (portal vein width, spleen thickness), liver histopathology knodell HAI classification for chronic hepatitis, and changes in ishak fibrosis score at 24,48 weeks were observed in both groups. Result:After 48 weeks, the indexes of the two groups were improved to different degrees (P<0.05,P<0.01), serum HBV DNA negative conversion rate, liver function, coagulation index, liver stiffness, portal vein diameter, Knodell HAI grade portal inflammation, interface activity, hepatic lobular activity, and Ishak fibrosis score in observation group were better than those in the control group (P<0.05). Patients in the control group had no significant improvement in liver lobular activity after treatment in the Knodell HAI classification of chronic hepatitis. Conclusion:Compound Huanggen granules combined with Entecavir tablets are more effective in treating patients with chronic hepatitis B with syndrome of collateral retardation due to blood stasis than Entecavir tablets alone. The combination of two drugs helps to improve the rapid response rate of HBV DNA, and has a better effect on improving liver function, controlling the development of liver fibrosis and preventing related complications.
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ObjectiveTo investigate the effect of entecavir (ETV) alone or combined with interferon (IFN) on the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for 409 patients with CHB who were admitted to Beijing Ditan Hospital from January 2008 to December 2014, and according to their antiviral therapy, they were divided into ETV+IFN group with 169 patients (IFN treatment for ≥6 months) and ETV group with 240 patients (ETV treatment for ≥12 months). The patients were followed up to June 2019, and the development of HCC was the outcome event. The Mann-Whitney U test was used for comparison of continuous variables between two groups, and the chi-square test was used for comparison of categorical variables between two groups. The propensity score matching (PSM) method was used to eliminate baseline differences between groups, the Kaplan-Meier method and the log-rank test were used to compare the incidence rate of HCC between groups, and the Cox proportional-hazards regression model analysis was used to investigate the risk factors for the development of HCC. ResultsThe median follow-up time in this study was 5.4 years (IQR: 4.9-7.9). There was no significant difference in the cumulative incidence rate of HCC between the two groups before and after PSM (before PSM: 1.2% vs 2.8%, χ2=1.423, P=0.233; after PSM: 1.7% vs 4.1%, χ2=1.676, P=0.195), and the subgroup analysis also showed no significant difference in the cumulative incidence rate of HCC between the two groups in the non-high risk population (1.3% vs 1.5%, χ2=0.335, P=0.563). The Cox proportional-hazards regression model showed that age was an independent risk factor for HCC (hazard ratio=1.107, 95% confidence interval: 1.005-1.219, P=0.038). ConclusionFor CHB patients without a high risk of cancer, compared with ETV monotherapy, ETV combined with IFN for at least 6 months does not significantly reduce the risk of HCC.
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Objective To investigate the clinical effect of traditional Chinese medicine syndrome differentiation-based treatment combined with entecavir in the treatment of chronic hepatitis B. Methods A total of 80 outpatients with chronic hepatitis B were randomly divided into the observation group (n=40) and control group (n=40).The patients in the control group were treated with entecavir tablets. The patients in the observation group were given TCM syndrome differentiation-based treatment in addition to the treatment received by the control group. Clinical symptoms relief, improvement of liver function indexes, serological conversion and HBV-DNA negative rate were compared between the two groups after 48 weeks of treatment. Results The clinical symptoms of abdominal distension, fatigue, pain and anorexia were relieved better in observation group than in control groups. The difference was significant between the two groups (P<0.05). The observation group had significant therapeutic advantages over the ALT recurrence rate compared to the control group, especially 24 weeks ago (P<0.05). There was no statistically significant difference between the combined group and the control group after 12, 24, 48 weeks after treatment, and the HBV-DNA (both greater than 0.05) were clinically modified. Conclusion TCM syndrome differentiation-based treatment combined with entecavir had significant therapeutic advantages in the treatment of chronic hepatitis B, which could relieve clinical symptoms, improve liver function indexes, and converse serological changes and be worthy of clinical popularization.
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Objective To identify whether rtL180M+A186T+M204V mutation is a novel entecavir (ETV)-resistant mutation. Methods A total of 12 708 patients in the Fifth Medical Center of Chinese PLA General Hospital from July 2011 to July 2016 were enrolled in this study. Drug resistance mutation in reverse transcriptase region (RT) were analyzed by direct sequencing and verified by clonal sequencing if rtL180M+A186T+M204V has been detected (≥20 clones/sample); 1.1-mer HBV replicons harboring wild-type or mutant RT gene were constructed respectively and transfected into HepG2 cells for phenotypic analysis. Results ETV experienced patients were detected in 4047 of total patients. Among these patients, classical ETV-resistant mutation of HBV and rtL180M+A186T+M204V mutation were detected in 795(19.64%) and 7(0.17%), respectively. The rtL180M+A186T+M204V mutant was consistent with the features of ETV-resistant mutation: all the rtA186T-positive patients had a history of lamivudine exposure prior to ETV treatment; the emergence of the mutations was associated with virological breakthrough or inadequate virological response to ETV; phenotypic analysis showed that patient-derived rtL180M+A186T+M204V mutant exhibited 13.3% replication capacity and 210.2-fold decreased susceptibility to ETV compared to the wild-type strain, while the mutant remained sensitive to tenofovir (TDF). Conclusions rtL180M+A186T+M204V as a novel ETV-resistance mutation has a low clinical detection rate, which is related to the markedly reduced replication capacity of the mutant. TDF-based rescue therapy should be considered for patients harboring rtL180M+A186T+M204V mutation in clinical practice.
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OBJECTIVE@#To evaluate the therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels.@*METHODS@#We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)].@*RESULTS@#In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( < 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( < 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( < 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- group, the rates were also similar between subgroups 1 and 2 (30.6% 33.3%, > 0.05); but the rates differed significantly between the same subgroups with different treatments ( < 0.05).@*CONCLUSIONS@#In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (> 5 × ULN) show better responses to both ETV and IFN- treatment than those with ALT level below 5×ULN. We thus recommend IFN- for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.