Clinical characteristics of hepatic flare and efficacy of antiviral therapy in pregnant women with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective@#To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection.@*Methods@#A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve.@*Results@#Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2–5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log10 IU/ml and (3.95 + 0.40) log10 IU/ml; t = 8.465, P < 0.001).@*Conclusion@#Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.

Clinical effect and safety of pegylated interferon-α-2b injection (Y shape, 40 kD) in treatment of HBeAg-positive chronic hepatitis B patients / 中华肝脏病杂志

Objective@#To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control.@*Methods@#This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data.@*Results@#A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events.@*Conclusion@#In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Establishment of a prognostic model for clinical relapse after drug withdrawal in chronic hepatitis B patients with hepatitis B e antigen seroconversion / 中华传染病杂志

Objective To investigate the prognostic factors for clinical relapse in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) seroconversion after drug withdrawal and to establish a prognostic model.Methods Totally 201 CHB patients with HBeAg seroconversion after the antiviral therapy were enrolled.The epidemiological variables including age, gender and family history of hepatitis B were collected.Liver function and hepatitis B virus (HBV) DNA level one week before initiation of antiviral therapy, hepatitis B surface antigen (HBsAg) level at the time of drug withdrawal and the duration of antiviral therapy after HBeAg seroconversion were analyzed.The clinical relapse after 48 weeks of drug withdrawal was followed up.The patients were divided into relapse group and non-relapse group according to clinical variables at 48 weeks after drug withdrawal.The counting data were analyzed by chi-square test and the measurement data were analyzed by t test.The Logistic regression model was used to determine the prognostic factors for clinical relapse.The receiver operating charactenstic (ROC) curve was constructed to assess the performance of the prediction model.Results The clinical relapse rate was 16.42% (33/201) after 48 weeks of drug withdrawal.By multivariate analysis, age, the duration of antiviral therapy after HBeAg seroconversion and HBsAg level at the time of drug withdrawal were independent predictors (χ2=14.546, t=3.202, t=3.286, respectively;all P<0.05).The regression model Logit (P)=1.220×age-0.040×the duration of antiviral therapy after HBeAg seroconversion +0.004×HBsAg level at the time of drug withdrawal-5.426.The sensitivity and specificity with the cut-off value of-0.860 were 73.10% and 90.40%, respectively.Conclusions Age, the duration of antiviral therapy after HBeAg seroconversion and HBsAg level at the time of drug withdrawal are independent predictors for clinical relapse 48 weeks after drug withdrawal in CHB patients with HBeAg seroconversion after antiviral therapy.

Expression levels of IL-37 and HBeAg seroconversion in chronic HBV patients / 中国免疫学杂志

Objective:Detecting serum IL-37 concentrations and HBeAg seroconversion in chronic hepatitis B virus(HBV) patients during the treatment of telbivudine( LDT).Methods:Fifty patients with chronic hepatitis B were included in the study;and 20 healthy people were selected as the control group.The expression levels of interleukin ( IL)-37, IL-6 and CRP were measured by enzyme-linked immunosorbent assay.As the same time,the relationship between serum IL-37 concentrations and HBeAg seroconversion was dynamically observed at 0 w,12 w,24 w,36 w,48 w after treatment.Results:The serum levels of IL-37 in chronic HBV patients were higher than the control group at baseline(q=22.716,P0.05).Conclusion:IL-37 may be involved in the process of HBV infection in CHB patients,and can reflect the degree of liver’ s inflammatory damage.IL-37 may play a significant role in the immune response of CHB patients with HBeAg seroconversion.In future,IL-37 may be an effective therapeutic measure to HBV infection.

Pretreatment ALT Level and Histologic Activity as Predictors of HBeAg Loss in Lamivudine Treatment for Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: Lamivudine is a potent inhibitor of hepatitis B virus replication, but an increased incidence of YMDD mutation may be associated with its long term use. Thus, the decision to initiate therapy should be based on variables that are predictive of lamivudine-induced HBeAg loss. The objective of this analysis was to determine patient-dependent or laboratory variables that predict HBeAg loss. METHODS: We retrospectively analyzed 99 HBeAg-positive patients with chronic hepatitis B who were treated with lamivudine and followed up for more than 52 weeks. All patients had a liver biopsy before starting lamivudine therapy. HBeAg loss and HBeAg seroconversion after 52 weeks of treatment were defined as endpoints. RESULTS: The overall rates of HBeAg loss and HBeAg seroconversion were 41.4% (41/99) and 37.4% (37/99), respectively. The rates of HBeAg loss increased as pretreatment ALT levels increased (P=0.013) and were highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal, occurring in 56.8% of those patients. The rate of HBeAg loss was higher in patients with more active histologic disease on pretreatment liver biopsy (Grade 1 and 2 vs. Grade 3 and 4, 28.3% vs 56.5%, P=0.004). Similar results were seen with HBeAg seroconversion, though seroconversion occurred less frequently than HBeAg loss. Multivariate analysis showed that elevated baseline ALT levels (P<0.05) and histologic activity (P<0.05) were the best independent predictors of HBeAg loss and seroconversion in response to lamivudine. CONCLUSIONS: Pretreatment ALT levels and histologic activity were the most important predictors for response to lamivudine.

Long-term Efficacy and Durability of Lamivudine Therapy in Patients with Chronic Hepatitis B / 대한간학회지

BACKGROUND/AIMS: It has been reported in patients with chronic hepatitis B, that the response rate of lamivudine therapy increases in proportion to the duration of the therapy. What was not well known was the durability of the therapeutic response after the cessation of lamivudine therapy. The aim of this study was to evaluate the long-term efficacy and durability of lamivudine therapy in patients with chronic hepatitis B. Patients and METHODS: We retrospectively analyzed 73 patients with chronic hepatitis B who were treated with lamivudine 100 mg orally once daily and followed up for more than 12 months between April 1997 and March 1999. Sixty-three patients were initially hepatitis B e antigen (HBeAg) positive and Hepatitis B virus (HBV) DNA positive (group I). Ten patients were HBeAg negative and HBV DNA positive (group II). The responders were those who had negative conversion of HBV DNA and normalization of alanine aminotransferase (ALT). Treatment was stopped after HBeAg seroconversion in group I and after thaerapeutic response in group II. RESULTS: The response rates of group I and group II were 68.3% and 70.0% at 12 months, respectively (P = NS). In group I, cumulative HBeAg seroconversion rates at 1 year, 2 years, and 3 years were 30.2%, 38.8%, and 42.4%, respectively. The cumulative durability of response was higher in group I than in group II (64.6% vs. 33.3% at 1 year; 35.4% vs. 22.2% at 2 years; P = .079). The cumulative durability of response was significantly higher in patients who received additional lamivudine therapy for more than 6 months after HBeAg seroconversion than for less than 6 months (90.0% vs. 40.0% at 1 year; 90.0% vs. 20.0% at 2 years; P = .013). CONCLUSIONS: The long-term response to lamivudine therapy showed no difference between HBeAg-negative/HBV DNA-positive and HBeAg-positive patients. The HBeAg seroconversion rate increased in proportion to the duration of lamivudine therapy. The Continuation of treatment for more than 6 months after HBeAg seroconversion might increase the durability of response.

The Effect of Long-erm Lamivudine Therapy for Chronic Liver Disease due to Hepatitis B Virus / 대한간학회지

BACKGROUND/AIMS: We studied to evaluate the virological and biochemical responses to lamivudine and to detect YMDD mutants in patients who received long-erm lamivudine therapy. METHODS: We conducted a one-ear trial of lamivudine in 45 Korean patients with chronic liver disease due to hepatitis B virus. The patients were treated with a single oral average dose of 100 mg of lamivudine every day for 12 months. RESULTS: The suppression of serum HBV DNA was sustained in 77.8% of the patients and the normalization of serum ALT in 80%. The proportions of patients with HBeAg seroconversion were 25%. YMDD mutants were detected in 4 of 8 patients who showed sustained HBV DNA and serum ALT response (n=31) and in 3 of 8 patients who showed HBV DNA or serum ALT breakthrough (n=9). The response to lamivudine therapy in HBeAg-egative patients was excellent. CONCLUSION: Lamivudine therapy resulted in a significant virological and biochemical improvements and were well tolerated. But, YMDD mutants were detected during lamivudine therapy.