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BACKGROUND: The timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years. METHODS: A retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system. RESULTS: The liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels. CONCLUSIONS: A considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.
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Hepatitis B Crónica , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Alanina Transaminasa , Antígenos e de la Hepatitis B , Estudios Retrospectivos , Fibrosis , Cirrosis Hepática/tratamiento farmacológico , Antivirales/uso terapéutico , Inflamación/tratamiento farmacológico , Virus de la Hepatitis B/genética , ADN ViralRESUMEN
INTRODUCTION: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.
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Antivirales , Hepatitis B Crónica , Humanos , Antivirales/uso terapéutico , LDL-Colesterol , Hepatitis B Crónica/tratamiento farmacológico , Metaanálisis en Red , Tenofovir/uso terapéutico , Resultado del TratamientoRESUMEN
This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.
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Hepatitis B Crónica , Antivirales/efectos adversos , China , ADN Viral , Genotipo , Guanina/análogos & derivados , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Humanos , Maleatos , Resultado del TratamientoRESUMEN
With the wide use of potent and safe nucloes(t-)ide analogues (NAs) treatment, patient-centered care is getting important. Intensive care for comorbidity has gain utmost importance in care of aging chronic hepatitis B (CHB) patients with life-long antiviral treatment. Linkage to care of patients with CHB is essential for the goal of hepatitis B virus (HBV) eradication. As long-term suppression of HBV DNA replication does not prevent hepatocellular carcinoma (HCC), prevention of HCC is another challenge for NAs treatment. There is a possibility of hepatocarcinogenesis in the immune-tolerant phase and risk of loss of patients during active monitoring seeking the time point for antiviral treatment initiation. Initiation of NAs treatment from the immune-tolerant phase would improve the linkage to care. However, universal recommendation is premature and evidence for cost-effectiveness needs to be accumulated. Early initiation of NAs in the evidence of significant disease progression, either HBV associated or comorbidity associated, would be a better strategy to reduce the risk of HCC in patients located in the gray zone.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/prevención & control , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , Medicina de PrecisiónRESUMEN
BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.
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Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Ácido Orótico/uso terapéutico , Tenofovir/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Resultado del TratamientoRESUMEN
The discovery of hepatitis B virus (HBV) has provided a scientific basis for the diagnosis, prevention and treatment of chronic hepatitis B (CHB). The universalization of neonatal hepatitis B vaccine has greatly reduced the HBsAg positive load rate of the Chinese population. Antiviral therapy based on interferon and / or nucleos(t)ide analogues had effectively inhibited HBV replication, improved liver inflammation, liver fibrosis, and reduced the incidence of liver cirrhosis and hepatocellular carcinoma. However, the existing treatment methods can achieve the clinical cure goal of negative HBsAg. In recent years, direct antiviral drugs for HBV life cycle and immunomodulatory drugs for antiviral response have entered an active stage of research and development. Clinical trials that are well-designed, standardized, analyzed, and interpreted are the key to the success of the research and development of a clinical cure for hepatitis B. It is hoped that the experts in hepatology, clinical pharmacology and methodology will work together to promote the research and development process of new drugs for clinical cure of hepatitis B by adopting new clinical trial design, new endpoint indicators, new data management and quality control technology.
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Antivirales , Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Ensayos Clínicos como Asunto , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines of chronic hepatitis B (CHB) suggest the clinical cure as the ideal thearapeutic goal. Although the optimization of the existing antiviral treatment can make some patients achieve clinical cure, but for most patients with chronic hepatitis B, it is difficult to achieve clinical cure according to the existing antiviral treatment plan. The medical community has begun to work together to seek new treatment strategies, especially the immune intervention measures aimed at restoring the immune response in the liver microenvironment. Notably, immune antiviral response plays a crucial role in HBV clearance, and the clinical cure of chronic hepatitis B is finally achieved through the optimized combination of antiviral and immunomodulatory drugs.
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Antivirales , Hepatitis B Crónica , Hepatitis B , Inmunomodulación , Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , HumanosRESUMEN
Liver fibrosis, liver cirrhosis and hepatocellular carcinoma caused by chronic hepatitis B are still the main diseases that seriously affect the health of Chinese population. Notably, even if serum HBV-DNA cannot be detected after treatment, many patients will still develop liver disease. Therefore, in addition to the quantitative analysis of HBV-DNA and HBsAg, other new serological markers should be sought to facilitate the selection of CHB antiviral drugs and methods, monitoring efficacy and follow-up, efficacy prediction, and the risks of viral rebound after drug withdrawal. This article focuses on three new serological markers, namely HBcrAg, HBV-RNA and anti-HBc, with a view to applying them in clinical practice.
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Hepatitis B Crónica , Hepatitis B , Biomarcadores , ADN Viral , Antígenos del Núcleo de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , HumanosRESUMEN
Objective: To summarize the clinical diagnosis and therapeutic method in chronic hepatitis B (CHB) combined with autoimmune hepatitis (AIH). Methods: Clinical manifestations, laboratory examination, imaging, histopathological characteristics, treatment and prognosis of 19 cases diagnosed with CHB combined with AIH followed at the outpatient Department of Gastroenterology of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine during December 2013 to June 2018 were retrospectively analyzed. Paired sample t-test was used before and after treatment for the measurement of normal distribution data. Measurement data of non-normal distribution were expressed as a median (quartile spacing) and Wilcoxon matched-pairs signed rank test was used before and after treatment. Results: Among the 19 cases, 5 were male and 14 were female. The age of onset was 35 to 63 years, and the average age was 47.10 ± 8.76 years. There were 12 cases diagnosed with CHB before AIH, 5 cases diagnosed with AIH before CHB, and 2 cases diagnosed with AIH and CHB at the same time. After the definite diagnosis of CHB combined with AIH, nucleoside (acid) analogues (antiviral against hepatitis B virus) combined glucocorticoid therapy were given, and azathioprine or mycophenolate mofetil (immunosuppressant) was added according to the intrahepatic inflammation (inflammation graded at G3 and above) and leukocyte conditions. The duration of treatment varied between 2 weeks to 16 (median treatment duration of 6 weeks), except for one case who was just diagnosed and followed up. Biochemical indicators and immunoglobulin of the remaining 18 cases before and after treatment was significantly decreased, and the differences were statistically significant (P < 0.05), with HBV DNA < 20 copies/ml. Conclusion: CHB combined with AIH diagnosis can be easily missed. Therefore, it requires comprehensive diagnosis combined with clinical characteristics, autoantibodies, and immunoglobulin levels with special emphasis on pathological characteristics of liver tissue. Anti-HBc-positive patients using immunosuppressant should be carefully monitored for HBV DNA and anti-HBV treatment should be given if necessary.
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Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/terapia , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/terapia , Adulto , China , Femenino , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis Autoinmune/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Objective: To explore the effect of HBV preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B. Methods: Thirty-five cases with chronic hepatitis B without antiviral therapy were enrolled in this cross-sectional study. Nested PCR-TA cloning-sequencing method was used to screen HBV preC/C and S gene mutation sites related to HBeAg serological status. Then, in the longitudinal study (60 cases), the independent correlation between HBV preC/C and S gene antigen epitopes mutations and HBeAg status was explored by using multiple regression models to correct the correlated confounding factors. Results: In this cross-sectional study, 64.4% of preC/C and 68.2% of S mutations had occurred in the epitope region. There were ten mutation sites (PreC/C50, 55, 79, 84, 103, 126, 145, 184 and s110, s213) correlated with HBeAg negative status (P < 0.05). After adjusting for confounding factors such as age, gender, HBV genotype, serum alanine aminotransferase level and precw28 * mutations in the longitudinal studies, the results showed that TC cell epitope (prec47-56, prec117-125, s208-216) and Th cell epitope (prec176-185) were the main independent risk factors affecting the host HBeAg serological status. Conclusion: HBV preC/C region (PreC47-56, PreC117-125 and PreC176-185) and S region (s208-216) epitope mutations are the main independent factors affecting the host HBeAg status, suggesting that these epitope mutations may be involved in the HBeAg seroconversion.
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Antígenos del Núcleo de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/genética , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B , Hepatitis B Crónica/sangre , Estudios Transversales , ADN Viral , Epítopos/genética , Genotipo , Virus de la Hepatitis B/genética , Humanos , Estudios Longitudinales , MutaciónRESUMEN
Objective: To describe the current status of registration and design characteristics of clinical trials of new drugs for curing hepatitis B through domestic and foreign websites, so as to provide references for the follow-up clinical trials of new hepatitis B drugs. Methods: A search was conducted on the US Clinical Trials Database and the Chinese Clinical Trial Registry Center. The search date was from the establishment of the database to May 26, 2020, and the registration trials of new drugs for curing hepatitis B at home and abroad were included. Two researchers independently searched and screened the literature and extracted the data. Results: A total of 106 registered clinical trials of new drugs for curing hepatitis B were included (94 English registration websites and 12 Chinese registration websites), and the number of registrations had increased year by year. Among them, the proportion of therapeutic vaccines and core protein inhibitors were the highest, accounting for 27.4% (n = 29) and 22.6% (n = 24), respectively. The vast majority of clinical trials (n = 96, 90.6%) were in the early stages (Phase I and II). The subjects in phase I clinical trial were mainly healthy people and treated CHB patients, while the subjects in phase II clinical trial were mainly CHB patients who had achieved viral suppression after initial or post-treatment. The main evaluation indicators of Phase I clinical trials were the safety and tolerability of new drugs. The main evaluation indicators in about half of Phase II clinical trials were HBsAg negative conversion/quantitative decline. Overall, the number of clinical trials with the new design was small, accounting for 3.8% (4 / 106). There were relatively few trials of new drugs for curing hepatitis B on domestic registration websites, and the information provided was incomplete. Conclusion: The number of clinical trials of new hepatitis B drugs at home and abroad is increasing year by year, but most of them are in phase I and II, with few adopting new designs. In addition, the information integrity of the domestic website registration center needs to be improved.
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Ensayos Clínicos como Asunto , Hepatitis B Crónica , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Proyectos de InvestigaciónRESUMEN
Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.
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Antivirales , Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , China/epidemiología , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Hepatitis B virus (HBV) infection is one of the common causes of chronic hepatitis in China. Active antiviral therapy can effectively reduce the occurrence risk of end-stage liver diseases, such as decompensated cirrhosis, liver failure and hepatocellular carcinoma. The existing international and domestic guidelines for the prevention and treatment of chronic hepatitis B recommends regular follow-up for patients with normal alanine aminotransferase (ALT). Studies have shown that a high percentage (25.4%-88.9%) of patients with chronic HBV infection have normal ALT levels; however, hepatic histopathology revels obvious inflammation, fibrosis (G≥2 and/or S≥2), cirrhosis and liver cancer. In this paper, we reviewed the relatively insidious risk factors associated with the progression of chronic HBV infection in patients with normal ALT.
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Enfermedad Hepática en Estado Terminal , Hepatitis B Crónica , Virus de la Hepatitis B , Hepatitis B Crónica/epidemiología , Humanos , Cirrosis Hepática , Factores de RiesgoRESUMEN
Objective: To study the virological and serological indicators before treatment and 24 weeks after treatment to predict the partial virological response (PVR) of 48-week entecavir (ETV) treatment, and formulate early clinical adjustment treatment plans for HBeAg-positive CHB patients. Methods: HBeAg-positive CHB-naïve patients diagnosed in the Department of Infectious Diseases, Shengjing Hospital, China Medical University, who were treated with oral ETV monotherapy from January 2018 were enrolled. The groups were divided according to the test results of HBV DNA at 48 weeks. Among them, HBV DNA < 20 IU/ml was the complete viral response (CVR) group, and HBV DNA ≥ 20 IU/ml was the PVR group. The virological and serological indexes of the two groups before treatment and 24 weeks after treatment were compared. ROC curve univariate analysis and multivariate logistic regression were performed to find out the early predictors of PVR in HBeAg-positive CHB patients receiving ETV therapy for 48 weeks. Results: As of July 2020, a total of 90 cases had completed 48 weeks of treatment, including 50 cases of CVR (55.56%) and 40 cases of PVR (44.44%). Before treatment and at 24 weeks of treatment, HBsAg, HBeAg and HBV DNA in the PVR group were significantly higher than those in the CVR group (P < 0.001). Univariate analysis showed that HBV DNA quantification (AUC = 0.961, P < 0.001, PPV = 97.06%, NPV = 87.50%) and HBeAg quantification (AUC = 0.883, P < 0.001, PPV = 90.63%, NPV = 81.03%) had higher predictive value at 24 weeks of treatment. Multivariate analysis showed that HBeAg > 1.952 log(10) S/CO (OR = 3.177, 95% CI: 1.261 ~ 8.267, P = 0.018) and HBV DNA > 2.205 log(10) IU / ml (OR = 43.197, 95% CI: 6.858 ~ 272.069, P < 0.001) were independent predictors of PVR at 24 weeks of treatment, and their combination had the best predictive effect. Conclusion: In HBeAg-positive CHB patients receiving ETV treatment for 48 weeks, HBV DNA combined with HBeAg quantification can be an early predictor of PVR at 24 weeks. Additionally, patients with both HBV DNA and HBeAg > 2 log(10) at 24 weeks of treatment must wait 48 weeks to obtain CVR, so it is recommended that treatment strategies should be adjusted at this time.
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Antígenos e de la Hepatitis B , Hepatitis B Crónica , Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Resultado del TratamientoRESUMEN
Small interfering RNA (siRNA) is mainly involved in RNA interference for stopping gene translation by targeting and degrading HBV-transcribed mRNA. Targeting and stability in siRNA can be enhanced via chemical modification, combination use and improved delivery system. Clinical studies have identified JNJ-3989 (ARO-HBV) and ARB-1740 as well-tolerated siRNA drugs, which significantly reduce HBsAg levels. This article expounds the main mechanisms of siRNA in inhibiting HBsAg expression, improving target and stability as well as relevant preclinical and clinical studies.
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Virus de la Hepatitis B/efectos de los fármacos , ARN Interferente Pequeño/farmacología , Replicación Viral/efectos de los fármacos , ADN Viral/análisis , Antígenos de Superficie de la Hepatitis B/análisis , Virus de la Hepatitis B/genética , Hepatitis B Crónica , Humanos , Interferencia de ARNRESUMEN
Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People's Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion: GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.
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Biomarcadores/metabolismo , Cirrosis Hepática/diagnóstico , Hígado/metabolismo , Proteínas de la Membrana/metabolismo , Aspartato Aminotransferasas/metabolismo , Biopsia , Fibrosis , Hepatitis B , Humanos , Hígado/patología , Proteínas de la Membrana/sangre , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Adulto , ADN Viral , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Carga ViralRESUMEN
BACKGROUND: Previous studies have investigated the vitamin D status in patients with chronic hepatitis B virus (HBV) infection and its relationship with HBV replication, the results however were inconsistent. The present meta-analysis was carried out to compare the vitamin D levels between patients with chronic hepatitis B (CHB) and healthy controls, and to determine whether vitamin D levels were correlated with HBV viral loads significantly. METHODS: A systematic search was conducted via PubMed, Web of Science, EMBASE and the Cochrane Library to identify eligible studies until September 28, 2017. We calculated pooled mean difference (MD) and 95% confidence intervals (CI) to quantitatively estimate the difference of vitamin D levels between CHB patients and controls. In addition, correlation between serum vitamin D levels and HBV viral loads was defined by summary correlation coefficient (r value) and the corresponding 95% CI. RESULTS: A total of 7 studies involving 814 CHB patients and 696 healthy controls were included. A significantly decreased vitamin D levels was found in CHB patients compared with healthy controls: pooled MD (95% CI) was - 2.03 ng/mL (- 2.60, - 1.46). Latitude-stratified subgroup analysis indicated this difference was more obvious in low latitude areas, with a bigger pooled MD (95% CI) of - 2.72 ng/mL (- 4.57, - 0.87). In addition, we observed an inverse correlation between serum vitamin D levels and HBV viral loads: pooled r (95% CI) was - 0.41(- 0.54, - 0.27). CONCLUSIONS: Our results showed that vitamin D levels were lower in CHB patients than that of healthy controls and inversely correlated with HBV viral loads, although future comprehensive studies are needed to clarify the underlying mechanisms.
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Virus de la Hepatitis B , Hepatitis B Crónica/sangre , Carga Viral/estadística & datos numéricos , Vitamina D/sangre , Adulto , Femenino , Hepatitis B Crónica/virología , Humanos , MasculinoRESUMEN
BACKGROUND: Hepatitis B virus (HBV) reactivation is one of the most common precipitating events associated with acute decompensation (AD) or acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB)-related cirrhotic patients. However, whether their serum HBV deoxyribonucleic acid (DNA) levels are associated with ACLF incidence and short-term mortality rate is still ambiguous. METHODS: The ACLF incidences, 28-day and 90-day liver transplantation (LT)-free mortality rates, previous nucleoside/nucleotide analogues (NUCs) treatments and serum HBV DNA levels at admission (ad-levels) of 111 hospitalized patients with AD of CHB-related cirrhosis were analyzed. RESULTS: 43 (38.7%) patients developed ACLF. The 28-day and 90-day LT-free mortality rates of the ACLF cases were 15.4 and 40.9%, respectively. Though NUCs inhibited HBV replication effectively, there were no differences in the ACLF incidence between antiviral treatment-naïve patients and NUCs treatment-experienced patients with or without interruptions (37.5, 41.7 and 45.5%, respectively, P>0.05). The serum HBV DNA ad-level was similar between the patients with and without ACLF development (logarithms: 4.50 ± 1.96 vs 4.32 ± 1.99; ≥2000 IU/ml: 67.4% vs 67.6%; both P>0.05), so was between the ACLF patients died or survived in 28 or 90 days (logarithms: 4.31 ± 1.91 vs 5.54 ± 2.53, 4.81 ± 1.76 vs 4.84 ± 2.40, respectively, both P>0.05). CONCLUSION: Serum HBV DNA ad-level and previous NUCs treatment are not associated with incidence of ACLF and short-term mortality rate in the hospitalized patients with AD of CHB-related cirrhosis.
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Insuficiencia Hepática Crónica Agudizada/diagnóstico , Virus de la Hepatitis B/fisiología , Cirrosis Hepática/diagnóstico , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/patología , Insuficiencia Hepática Crónica Agudizada/terapia , Adulto , Antivirales/uso terapéutico , ADN Viral/sangre , Femenino , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Humanos , Cirrosis Hepática/etiología , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Prevalencia , Índice de Severidad de la Enfermedad , Carga ViralRESUMEN
Based on the progression of clinical and basic research in hepatitis B virus (HBV), we updated the previous HBV guidelines from 2015. The guidelines included the prevention, diagnosis, and antiviral therapy of chronic hepatitis B, which accelerates ro achieve the goal of "the elimination of viral hepatitis as a public health threat by 2030" proposed by the World Health Organization.