ABSTRACT
Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.
Subject(s)
Humans , Adult , Hepatitis B, Chronic/complications , Retrospective Studies , Cross-Sectional Studies , Hepatitis B e Antigens , DNA, Viral , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , DemographyABSTRACT
The main transmission route of chronic hepatitis B virus infection is mother-to-child transmission of hepatitis B virus and the main cause of combined immune prophylaxis failure in neonates at the end of pregnancy is high viral load. Moreover, oral administration of nucleos(t)ide analogues (NAs) during the second and third trimesters of pregnancy can significantly reduce or even completely block mother-to-child transmission of HBV. This article focuses on the necessity and feasibility of oral NAs antiviral therapy for HBV carrier pregnant woman with high viral load, and the issues commences at the time of medication and viral load thresholds.
ABSTRACT
Hepatitis B virus (HBV) infection is the most important risk factor for cirrhosis and hepatocellular carcinoma (HCC) in Chinese patients. Interferon (IFN) and nucleos(t)ide analogues (NAs) are two major regimens for chronic hepatitis B (CHB). A large number of clinical studies have previously confirmed that the risk of HCC in CHB patients can be significantly reduced by NAs treatment. There are also some prospective studies confirming the benefit of IFN treatment. However, only a few clinical studies with limited sample size have directly compared the differences in the incidence of HCC between these two classes of drugs. Although these results suggested that the risk of HCC in IFN group was lower than patients in NA group, the conclusion need to be taken with caution. In the future, a multi-center, large sample size, well-designed, prospective study will be needed to answer this question.
ABSTRACT
Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC) in China. The occurrence of HCC can significantly be reduced with effective long-term antiviral treatment. Since the widespread clinical use of nucleos(t)ide analogues, such as entecavir and tenofovir that has a strong potency and high genetic barrier to resistance; the detection rate of HBV DNA in serum of patients with chronic hepatitis B is no more than 85% ~ 95%, but HCC can still occur in a small number of patients. This article will review whether the timing and selection of NAs treatment differ to prevent and reduce the incidence of HCC.
ABSTRACT
Oral nucleos(t)ide analogues (NAs) is one of the main and efficient way for the treatment of chronic hepatitis B (CHB). Considering the antiviral potency and drug resistance of domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. "An Expert Consensus for the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos(t)ide Analogues," is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition, how to standardize the adjustment to first-line NAs drugs of choice, which can strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy, and improve patient compliance, coinciding with the avoidance of occurrence of serious drug adverse reactions in patients with CHB is presented.
ABSTRACT
Oral nucleos(t)ide analogues (NAs) is one of the main and efficient way for the treatment of chronic hepatitis B (CHB). Considering the antiviral potency and drug resistance of domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. "An Expert Consensus for the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos(t)ide Analogues," is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition, how to standardize the adjustment to first-line NAs drugs of choice, which can strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy, and improve patient compliance, coinciding with the avoidance of occurrence of serious drug adverse reactions in patients with CHB is presented.
Subject(s)
Humans , Antiviral Agents , Therapeutic Uses , Consensus , Guidelines as Topic , Reference Standards , Hepatitis B virus , Hepatitis B, Chronic , Drug Therapy , Nucleosides , Therapeutic Uses , Outcome Assessment, Health Care , Methods , Practice Guidelines as Topic , Treatment OutcomeABSTRACT
Oral nucleos(t)ide analogues(NAs) is one of the main and efficient way for the treatment of chronic hepatitis B(CHB).Considering the antiviral potency of drugs and drug resistance, in the domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. “An Expert Consensus on the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos(t)ide Analogues” is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition,the folliwing is presented: how to standardize the adjustment to first-line NAs drugs of choice, how to strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy and improve patient compliance, and at the same time avoid occurrence of serious drug adverse reactions in patients with CHB.
ABSTRACT
Oral nucleos(t)ide analogues (NAs) is one of the main and efficient way for the treatment of chronic hepatitis B (CHB). Considering the antiviral potency and drug resistance of domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. "An Expert Consensus for the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos(t)ide Analogues," is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition, how to standardize the adjustment to first-line NAs drugs of choice, which can strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy, and improve patient compliance, coinciding with the avoidance of occurrence of serious drug adverse reactions in patients with CHB is presented.
Subject(s)
Humans , Antiviral Agents/therapeutic use , Consensus , Guidelines as Topic/standards , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Nucleosides/therapeutic use , Outcome Assessment, Health Care/methods , Practice Guidelines as Topic , Treatment OutcomeABSTRACT
Objective To analyze the heterogeneities of hepatitis B virus ( HBV ) reverse transcriptase domain (RT) gene mutations related to nucleos (t)ide analogues (NAs) resistance.Methods Blood samples from 2765 chronic hepatitis B patients with virological breakthrough or poor drug response treated in Ningbo No .2 Hospital and Ningbo Fourth Hospital from April 2011 to March 2018 were collected . According to the medication status , it was divided into LAM monotherapy group ( n =603 ) , LdT monotherapy group (n=147), ADV monotherapy group (n=68), ETV monotherapy group (n=10) and the sequential or combined drug resistance of NAs group (n=365).The resistance mutation sites and drug resistance patterns (pathways) of each group were analyzed .The SPSS 19.0 software was used to analyze the data.Results Among 2765 serum samples, the NAs-related HBV-RT resistance mutations were detected in 1193 cases with an overall mutation rate of 43.15％.The mutation rate of LAM monoclonal resistance group was 62.62％ (603/963) with 19 mutation types, the most common single point mutation was rtM204I/V (40.30％, 243/603).The mutation rate of LdT monoclonal resistance group was 45.51％(147/323), and there were 3 mutation types, with the single point mutation rtM204I/V being the most common (59.86％, 88/147).The mutation rate of the ADV monoclonal resistance group was 17.80％(68/382), mainly rtA181T single point mutation (64.71％, 44/68).The mutation rate of the ETV monoclonal resistance group was 4.06％(10/246), and the single point mutation of rtT184A/G/S/I/L/F was the most common one (80.00％, 8/10).The mutation rate of the sequential or combination therapy group was 41.91％ (365/871), among which the mutation rate of the LAM/LdT poor response or the resistance with the sequential ADV group was 63.39％(142/224), and the most single mutation point was rtA181V/T ( 35.21％, 50/142 );the mutation rate of LAM/LdT poor response or drug-resistant with combined ADV group was 42.19％ (54/128), and the most common mutation point was rtA181V/T (46.30％, 25/54);the mutation rate of LAM/LdT with poor response or resistance after sequential ETV 1.0 mg was 44.66％(117/262), and the most common mutation point was rtL180M+M204I/V+S202G/I (31.62％, 37/117);the LAM/LdT poor response or the drug-resistant ETV combined with ADV group had a mutation rate of 7.14％(5/70), all of which were multi-site mutations;the mutation rate of poor response to ADV or resistant with sequential ETV 0.5 mg group was 28.14％(47/167), all of which were multi-site mutations.Secondary ( compensation ) sites such as rtV173L, rtL180M, and rtV214A, and single-point mutations such as rtV207I/L/G, rtS213Tand rtN238T, which were not fully defined , were detected.The resistance patterns ( pathways ) of NAs monotherapy were relatively simple , and the resistance patterns ( pathways ) of NAs experienced patients ( sequential or combined treatment group ) were complex and diverse, and multiple resistance patterns (pathways) existed, along with NAs increasing in species.Non-first-line NAs-related resistance patterns ( pathways ) showed an overall downward trend sand ETV-related drug-resistant mutation showed an overall upward trend .Conclusion The NAs-related HBV resistance mutation sites ( patterns ) are complex and diverse , especially multi-site mutations , refractory drug resistance mutations, multidrug resistance mutations and cross-resistance mutations.Therefore, the optimization of antiviral treatment strategies and drug resistance management concepts need to be continuously updated .
ABSTRACT
Objective@#In this study, the mRNA of interferon (IFN)-α, IFN-γ, Mov10 and TRIM22, which are innate immune factors, was detected in chronic hepatitis B patients with nucleoside analogues multidrug resistance to investigate host innate immune status and explore the host immune molecular mechanism under the nucleos(t)ide analogues multiresistant HBV infection.@*Methods@#Twenty eight nucleos(t)ide analogue resistant patients and 20 healthy individuals in the control group were collected from infection medical clinic department of Heilongjiang provincial hospital. There were 18 cases of multiple drug resistance and 10 cases of cross resistance.Their peripheral blood specimens were collected. The mRNA of IFN-α, IFN-γ, Mov10 and TRIM22, that are the innate immunity factors in peripheral blood, were detected in 28 nucleos(t)ide analogue resistant patients and 20 healthy individuals using RT-PCR and the data were analyzed by statistical mthods.@*Results@#The mRNA levels of Mov10 and TRIM22 mRNA that are innate immune factors in peripheral blood mononuclear cells of multidrug resistant chronic hepatitis B patients were higher than those of control groups with statistically significant differences (P<0.01). TRIM22 mRNA in chronic hepatitis B patients with multidrug resistance showed positive correlation with IFN-α, IFN-γ and Mov10 mRNA; Mov10 mRNA showed positive correlation with TRIM22 and IFN-α mRNA; IFN-α mRNA showed positive correlation with IFN-γ, Mov10 and TRIM22 mRNA. There were no statistically significant differences in the innate immunity factors IFN-α, IFN-γ, Mov10 and TRIM22 mRNA between multidrug resistant group and cross-resistant group.@*Conclusions@#The mRNA levels of Mov10 and TRIM22, that are innate immune factors, were higher in chronic hepatitis B patients with nucleos(t)ide analogues resistance than those of healthy control group. The correlation analysis of mRNA levels between IFN-α, IFN-γ, Mov10 and TRIM22 expression demonstrated that the correlations among them were different under the nucleoside analogues resistant HBV infection.
ABSTRACT
Objective To evaluate the efficacy and safety of long-term nucleos (t) ide analogue treatment in patients with chronic hepatitis B (CHB).Methods Two hundred and two initially treated patients with CHB admitted in Zhejiang Provincial People's Hospital during March 2013 and August 2016 were enrolled in the study.Patients were divided into six groups according to the different antiviral therapy:adefovir group (ADV,n =43),entecavir group (ETV,n =44),lamivudine group (LAM,n =25),telbivudine group (LDT,n =23),LDT + ADV group (n =22),and LAM + ADV group (n =45).HBV DNA negative conversion rate,HBeAg serological conversion rate and estimated glomerular filtration rate (eGFR) at baseline and at 48th,96th,144th wk of treatment were measured.Chi-square test and repeated measure of ANOVA were used to analyze the data.Multivariate Logistic regression analysis was applied to detect the relevant risk factors of renal dysfunction in CHB patients.Results After treatment for 144 wks,the HBV DNA negative conversion rates in ETV and LDT group were higher than that in ADV group (both P ＜ 0.01),the levels of eGFR in ADV,ETV,LAM and LAM + ADV group were declined with time,while the eGFR levels in LDT and LDT + ADV group were increased with time (Ftime =3.939,Fgroup =3.983,P ＜0.01 or ＜0.05).After treatment for 96 wks and 144 wks,the levels of eGFR were higher in LDT and LDT + ADV group than those in other groups,respectively (all P ＜ 0.05).Multivariate Logistic regression analysis showed that age ≥40 (x2 =16.145,OR =4.452,95 ％ CI 2.149-9.223,P ＜ 0.05),mild abnormality of eGFR at baseline (x2 =16.449,OR =4.336,95％ CI 2.144-8.891,P ＜ 0.05),and ADV treatment (x2 =5.837,OR =5.280,95％ CI 1.369-20.365,P ＜ 0.05) were independent risk factors of renal dysfunction in CHB patients.Conclusion LDT long-term monotherapy or combination with ADV may improve renal function for patients with CHB,which provides a reference for long-term treatment of CHB patients with nucleos(t) ide analogues.
ABSTRACT
Recurrence rate after cessation of nucleos(t)ide analogues remains high in clinical practice. According to current evidences, age, HBsAg level, HB VRNA level, time of consolidation therapy and HBV DNA load were considered to be associated with off-treatment responses after cessation of nucleos(t)ide analogues. Combinative factors of several predictors might perform better in future accompanying with further studies of HBV related markers.
ABSTRACT
Objective To summarize and analyze the dynamic change of HBsAg levels in patients with chronic Hepatitis B (CHB) after receiving nucleos(t)ide analogues (NAs) as antiviral treatment.Methods Patients who were performed quantitative Hepatitis B surface antigen(qHBsAg) from July 30, 2012 to December 30,2016 in Peking Union Medical College Hospital were retrospectively enrolled.qHBsAg, HBV DNA, HBeAg were collected and analyzed at baseline and at 192-week follow-up every 24 weeks.qHBsAg and HBeAg were assessed with chemiluminesent microparticle immuno assay(CMIA).HBV DNA was assessed with PCR and COBAS Amplicor.Results 60 patients were included.Patients in HBeAg-positive group had higher HBV DNA than that in HBeAg-negative group (P<0.05)at baseline and the two groups both were under detection limit after 48 weeks.BaselineqHBsAg in HBeAg positive-group and negative-group were (3.43±0.73) log10 IU/mL, (3.08±0.47) log10 IU/mL respectively.qHBsAg in HBeAg-positive group was higher than that in HBeAg negative-group on all follow-ups(P<0.05) except 48weeks.However on 168 weeks and 192 weeks, difference between the two groups was statistically significant(P<0.05).In HBeAg-positive group,quantitative HBeAg dropped significantly during antiviral treatment.Conclusions HBV replication can be suppressed in the process of long-term NAs treatment in CHB patients.However qHBsAg decline is not so obvious, which indicates that HBsAg cleavence is difficult,and long-term NAs therapy is still necessary.
ABSTRACT
The antiviral treatment for children with chronic hepatitis B virus(HBV) infection should be started in the immune active phase.Interferon (IFN) is the drug of first choice in most cases,however,the individual treatment and management of adverse effects need to be considered.Currently,Nucleos (t)ide analogues (NAs) can be used as the first choice only for those special children who can't use IFN.Efficacy will be seriously affected once the emergence of viral resistance mutants to NAs.However,there is high risk of relapse after the NAs are discontinued.Compared with the mono therapy,the therapeutic strategy of interferon combined with NAs have obtained better effect and safety in children with chronic HBV infection.
ABSTRACT
There are about 350 million hepatitis B virus (HBV) carriers worldwide and chronic HBV is considered a major public health problem. The objective of the present study was to assess the effectiveness of the nucleos(t)ide analogues tenofovir (TDF) and entecavir (ETV) in the treatment of chronic HBV. A cross-sectional study was carried out from March-December 2013, including all patients with chronic HBV, over 18 years of age, undergoing therapy through the public health system in southern Brazil. Only the data relating to the first treatments performed with TDF or ETV were considered. Retreatment, co-infection, transplanted or immunosuppressed patients were excluded. Six hundred and forty patients were evaluated, of which 336 (52.5%) received TDF and 165 (25.8%) ETV. The other 139 (21.7%) used various combinations of nucleos(t)ide analogues and were excluded. The negativation of viral load was observed in 87.3% and 78.8% and the negativation of hepatitis B e antigen was achieved in 79% and 72% of those treated with ETV or TDF, respectively. Negativation of hepatitis B surface antigen was not observed. There was no occurrence of adverse effects. This is a real-life study demonstrating that long-term treatment with ETV and TDF is both safe and effective.
Subject(s)
Humans , Male , Female , Middle Aged , Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Tenofovir/therapeutic use , Cross-Sectional Studies , DNA, Viral , Guanine/therapeutic use , Hepatitis B e Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B virus/immunology , Public Health , Treatment Outcome , Viral LoadABSTRACT
Positive serum hepatitis B surface antigen (HBsAg) is an indication of hepatitis B virus (HBV) infection,and the clearance of HBsAg usually stands for clinical cure of chronic hepatitis B (CHB).The clearance of HBsAg is influenced by the host,virus,antiviral drugs and other factors.This paper reviews the recent research progress on the related factors of HBsAg clearance in patients with CHB.
ABSTRACT
Objective To survey the incidence of hepatocellular carcinoma (HCC) in patients with HBV-related cirrhosis receiving nucleos(t)ide analogues treatment and to assess its risk factors.Methods A total of 141 patients with HBV-related liver cirrhosis receiving nucleos(t) ide therapy from April 2008 to June 2011 were enrolled.The clinical data including virological and biochemical tests were retrospectively analyzed.Univariate and multivariate Cox proportional hazards regression model was used to identify the risk factors of HCC occurrence.Results Patients were followed up for 6.4 to 87.6 months with a median followup time of 32.5 months.During the follow-up period,15 out of 141 patients developed HCC with an average annual incidence rate of 3.8％.HCC incidence was higher in HBeAg positive cirrhosis and in those with family history of liver cancer ( RR =4.524 and 3.858,P ＜ 0.05 ).Conclusions Patients with HBV-related cirrhosis have a high incidence rate of HCC even they recieve nucleos (t) ide analogues treatment.HBeAg positive cirrhosis and family history of liver cancer are independent risk factors for HCC.
ABSTRACT
Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.
ABSTRACT
Even though substantial advances have been made in the treatment of chronic hepatitis B in the past decade with the use of oral nucleos(t)ide analogues (NAs), emergence of anti-viral resistance is the most important factor in treatment failure for chronic hepatitis B. Therefore, prevention and management of antiviral resistant HBV is major challenge in the era of oral NAs therapy. Recently, several guidelines for the management of antiviral resistant HBV have been published. Herein, I will discuss how to prevent and manage antiviral resistance.