Baseline HBV DNA Level Research Articles

The impact of HBV or HCV infection in a cohort of HIV-infected pregnant women receiving a nevirapine-based antiretroviral regimen in Malawi

BackgroundCoinfection with the hepatitis viruses is common in the HIV population in sub-Saharan Africa. The aim of this study was to assess, in a cohort of HIV-infected pregnant women receiving antiretroviral drugs (ARVs), the prevalence of HBV and HCV infections and to determine the impact of these infections on the occurrence of liver toxicity and on the viro-immunological response.MethodsWomen were screened for HBsAg and HCV-RNA before starting, at week 25 of gestational age, an antiretroviral regimen consisting of lamivudine and nevirapine plus either stavudine or zidovudine. Women with CD4+ < 350/mm3 continued ARVs indefinitely, while the other women interrupted treatment 6 months postpartum (end of breastfeeding period). Both groups were followed for 2 years after delivery. Liver function was monitored by alanine aminotransferase (ALT) measurement. The Cox proportional hazards model was used to identify factors associated with the emergence of liver toxicity.ResultsA total of 28 women out of the 309 enrolled in the study (9.1%) were coinfected with HBV (n. 27), or HCV (n. 1). During follow-up 125 women (40.4%) developed a grade ≥ 1 ALT elevation, 28 (9.1%) a grade ≥ 2 and 6 (1.9%) an elevation defining grade 3 toxicity. In a multivariate model including age, baseline CD4+ count and hemoglobin level, the presence of either HBV or HCV infection was significantly associated with the development of an ALT increase of any grade (P = 0.035). Moderate or severe liver laboratory toxicity (grade ≥ 2) was more frequent among women with baseline CD4+ > 250/mm3 (P = 0.030). In HBV-infected women a baseline HBV-DNA level above 10,000 IU/ml was significantly associated to the development of liver toxicity of grade ≥ 1 (P = 0.040). Coinfections had no impact on the immunological and virological response to antiretroviral drugs up to 2 years after delivery.ConclusionsIn this cohort of nevirapine-treated women the presence of HBV or HCV was associated only to the development of mild liver toxicity, while the occurrence of moderate or severe hepatoxicity was correlated to a baseline CD4+ count > 250/mm3. No statistically significant effect of the coinfections was observed on the efficacy of antiretroviral therapy.

Correlation between the suppressor of cytokine signaling-1 and 3 and hepatitis B virus: possible roles in the resistance to interferon treatment

BackgroundThe suppressor of cytokine signaling family (SOCS) is an important negative regulator in the JAK-STAT signaling pathway. This study was designed to explore the correlation between SOCS-1, 2 and 3, Hepatitis B Virus (HBV) and interferon (IFN), and the relationship between SOCS and IFN therapeutic efficacy.MethodsFour types of mouse models were established. Mice were administered with HBV replicative plasmid pHBV4.1 and IFN inducer Poly IC (Group A), pHBV4.1 (Group B), Poly IC (Group C) and saline (Group D), respectively. Liver tissues were harvested from the mice and SOCS expression was determined. Meanwhile, patients with chronic hepatitis B (CHB) were treated with pegylated interferon α-2b for 24-48 weeks. Liver biopsy was collected and the baseline SOCS expression was determined. Serum assay was performed for efficacy evaluation and correlation analysis.ResultsIn animal studies, the expression level of SOCS-1 and 3 was found in the descending order of B, A, C and D. The difference between Group B and D suggested that HBV could induce SOCS. The difference between Group A and C suggested that HBV could still induce SOCS with up-regulated endogenous IFN. The difference between Group C and D suggested that ploy IC could induce SOCS, while the difference between Group B and A suggested that Poly IC might have a stronger inhibition effect for SOCS. There was no difference in SOCS-2 expression. In clinical studies, eight of twenty-four enrolled patients achieved either complete or partial therapeutic response. The expression of both SOCS-1 and 3 was higher in CHB patients than in normal controls. The baseline HBV-DNA level was positively correlated with SOCS-1 and 3. The age, viral genotype, HBVDNA, SOCS-1 and SOCS-3 were found to be related to IFN efficacy.ConclusionHBV could induce both SOCS-1 and 3 expression regardless of endogenous IFN level. Elevated IFN could directly up-regulate SOCS-1 and 3 expression, but it could also indirectly down-regulate SOCS-1 and 3 expression by inhibiting HBV replication. HBV might play a more important role in the SOCS up-regulation than IFN, a possible reason why patients with high HBV viral load encounter poor efficacy of IFN treatment.

Hepatitis B viral load to predict survival of HCC patients treated with sorafenib.

188 Background: Sorafenib demonstrated survival prolongation in patients with advanced hepatocellular carcinoma (HCC). Until now, the effect of HBV DNA titer on prognosis of HCC patients treated with sorafenib has not been determined. Methods: From 2008 to 2012, 78 HBV-related HCC patients who received sorafenib at Severance hospital were included in our analysis. The prognostic effect of pretreatment HBV DNA level was examined by univariate and multivariate analysis. Results: The median overall survival was 5.2 months (95% confidence interval [CI]: 4.0-6.4) and median progression free survival was 3.5 months (95% CI: 2.3–4.7). Multivariate analysis revealed that a high baseline HBV DNA level (&gt;2,000 IU/L) was an independent risk factor for worse overall survival (p=0.005; hazard ratio [HR], 2.85), and rapid disease progression in a subgroup who did not receive antiviral prophylaxis with sorafenib (p=0.008; HR, 87.4). Moreover, viral reactivation occurred more frequently in patients who did not receive prophylactic antiviral therapy with sorafenib compared to those who did (4/38 vs. 0/40; p=0.025). Conclusions: A higher HBV DNA level before sorafenib was associated with poorer prognosis and increased viral reactivation. This result suggests the role of prophylactic antiviral therapy in patients who received sorafenib. [Table: see text]

HBV-DNA level at 6 months of entecavir treatment predicts HBeAg loss in HBeAg-positive chronic hepatitis B patients

To evaluate whether on-treatment HBV-DNA level could predict the treatment response to entecavir in hepatitis B e antigen (HBe)-positive chronic hepatitis B (CHB) patients. A total of 68 treatment-naïve HBeAg-positive patients (75% male, mean age at 46.6 ± 11.9 years) receiving at least 2 years of entecavir therapy were enrolled. The primary therapeutic endpoint was HBeAg loss. On-treatment complete virological response was defined as serum HBV-DNA < 63 IU/mL. The median baseline alanine aminotransferase (ALT) and HBV-DNA levels were 199.5 (27-1622) U/L and 7.7 (3.8-13.2) log10 IU/mL, respectively. The median treatment duration was 31.7 (24.3-69.6) months. The rate of HBeAg loss at 2 years was 30.9%. By univariate analysis, on-treatment complete virological response at Month 6 was associated with HBeAg loss at 2 years (p = 0.019). After adjustment for age, sex, cirrhosis, baseline ALT, and HBV-DNA levels, this factor remained significant in multivariate analysis (odds ratio: 4.35; 95% confidence interval: 1.24-15.24, p = 0.021). On-treatment complete virological response at Month 6 is a favorable factor predictive of HBeAg loss at 2 years of entecavir therapy. Therefore, measurement of serum HBV-DNA level at 6 months of entecavir therapy is optimal to predict HBeAg loss at 2 years of therapy in HBeAg-positive CHB patients.

Relationship between serum HBV DNA level and follicular helper T lymphocyte in patients with chronic hepatitis B and its significance

To explore relationship between HBV DNA level and peripheral blood follicular helper T lymphocyte (Tfh) in patients with chronic hepatitis B (CHB) and its significance. HBV DNA levels of 179 cases of CHB patients with positive HBV DNA, positive HBeAg and positive human leukocyte antigen(HLA)-A2 were tested with real time fluorescent quantitative PCR. Tfh and HBV specific CTL were tested with flow cytometry. IL-21 was also tested. 179 cases of CHB patients were divided into group A and group B based on HBV DNA levels, 86 cases in group A, HBV DNA levels were 10(4)-10(5) copies/ml, 93 cases in group B, HBV DNA levels were 10(6)-10(7) copies/ml. Above testing indexes of the two groups were compared. HBV DNA levels of group A were (4.85 +/- 0.37) log10 copies/ml, HBV DNA levels of group B were (6.83 +/- 0.31 ) log10 copies/ml, t = 27.31, P < 0. 001; Tfh of group A was (5.96 +/- 1.59)%, higher than that of group B (3.71 +/- 2.15)%, t = 4.92, P < 0.01; IL-21 of group A was (42.61 +/- 15.11)ng/L, higher than that of group B (14.91 +/- 3.15) ng/L, t = 8.62, P < 0.01; HBV specific CTL of group A was (0.36 +/- 0.08)%, higher than that of group B (0.18 +/- 0.06)%, t = 19.99, P < 0.001. Serum HBV DNA level of CHB patients is related to the level of peripheral blood Tfh level: patients with low HBV DNA level have high Tfh level, high IL-21 level and high HBV specific CTL level. Patients with high HBV DNA level have low Tfh level, low IL-21 level and low HBV specific CTL level. The mechanism of baseline HBV DNA level affecting anti-viral therapy may be related to Tfh level.

Entecavir versus lamivudine for hepatitis B prophylaxis in patients with haematological disease

Hepatitis B reactivation in patients receiving immunosuppressive therapy or chemotherapy may be associated with acute hepatitis, liver failure and/or death. To audit the efficacy of entecavir as compared to lamivudine for the prophylaxis of HBV reactivation in patients with haematological disease receiving immunosuppression or chemotherapy. Patients treated for haematological disease with pretreatment serological evidence of chronic hepatitis B (CHB) (HBV surface antigen, HBsAg positive) or resolved HBV infection (HBsAg negative but HBV core antibody positive) are included in this study. Patients received lamivudine 100 mg or entecavir 0.5 mg daily. Hepatitis B serology, HBV DNA and ALT were audited at baseline, 6 months, year 1, 2 and 3. HBV reactivation was defined as a 1 log increase in HBV DNA from baseline or reversion to sAg positivity. The occurrence of jaundice, symptomatic hepatitis, liver failure or death were audited. Of the 40 patients included in the study, 65% (4 CHB and 22 resolved HBV) received entecavir and 35% (11 CHB and 3 resolved HBV) received lamivudine. One patient with resolved HBV experienced HBV seroreversion related to premature cessation of entecavir. Eight patients with CHB (two from entecavir group and six from lamivudine group) had detectable HBVDNA levels at baseline; one case of HBV reactivation related to probable lamivudine resistance was identified. No HBV related deaths occurred. Lamivudine and entecavir are both efficacious in the prophylaxis of hepatitis B reactivation. Entecavir should be used in preference to lamivudine in patients CHB with detectable baseline HBV DNA levels.

Efficacy of Tenofovir in Patients with Lamivudine Failure Is Not Different from That in Nucleoside/Nucleotide Analogue-Naïve Patients with Chronic Hepatitis B

We evaluated the efficacy of tenofovir disoproxil fumarate (TDF) in patients with lamivudine failure (LAM-F) in comparison with that in nucleoside/nucleotide analogue (NA)-naïve patients with chronic hepatitis B (CHB). The criteria for inclusion were being NA naïve or having previous LAM-F and receiving TDF therapy for at least 6 months. Biochemical and virological tests were performed at the baseline, at 3-month intervals in the first year, and every 6 months thereafter. The primary outcome measure for efficacy was a complete virological response (CVR), defined as an HBV DNA level of <20 IU/ml. CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional-hazard model was generated in order to find predictive factors independently associated with the time to a CVR. We included 197 patients in the study (136 males; mean age, 43 ± 12 years; 105 patients were NA naïve). Sixty-five patients had hepatitis B e antigen (HBeAg)-positive CHB. The median duration of TDF treatment was 29 (range, 6 to 52) months. Seventy-one patients (77%) in the LAM-F group were treated with TDF add-on therapy. The CVR rates of the NA-naïve and LAM-F groups were comparable in HBeAg-negative (94% versus 96% at month 36, P = 0.10) and HBeAg-positive patients (67% versus 83% at month 36, P = 0.48). According to the multivariate Cox regression model, only HBeAg positivity (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26 to 0.59; P < 0.001) and a high baseline HBV DNA level (HR, 0.44; 95% CI, 0.29 to 0.67; P < 0.001) had a significant influence on the time to a CVR. The similar cumulative CVR rates during the follow-up show that TDF has comparable efficacy in lamivudine-experienced and NA-naïve patients, and the presence of resistance mutations did not alter the response rates.

IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen–negative patients with chronic hepatitis B

Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)-induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult-to-cure hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is unknown. One hundred and one HBeAg-negative patients (92% genotype D) with compensated CHB (84% males, 46 years; hepatitis B virus [HBV] DNA: 6.0 log cp/mL; alanine aminotransferase [ALT]: 136 IU/L; 42% with cirrhosis) were followed up for a median of 11 years (range, 1-17) after a median of 23 months (range, 10-48) of either standard or pegylated (Peg)-IFN-alpha therapy. A post-treatment response was defined as hepatitis B surface antigen (HBsAg) clearance with or without antibody to hepatitis B surface antigen (anti-HBs) seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was assessed in serum samples by using Custom TaqMan SNP Genotyping Assays (Applied Biosystems, Carlsbad, CA). During a median of 11 years of post-treatment follow-up, 21 patients (21%) cleared serum HBsAg, including 15 who developed>10 IU/mL of anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) had CT, and 11 (11%) had TT, with the allelic frequency being 68% for C allele and 32% for T allele. The rate of serum HBsAg clearance was 29% (n=14) in CC compared to 13% (n=7) in non-CC, genotype carriers (P=0.039). Baseline HBV DNA levels<6 log cp/mL (odds ratio [OR], 11.9; 95% confidence interval [CI]: 2.8-50.6; P=0.001), ALT levels>136 IU/L (OR, 6.5; 95% CI: 1.8-22.5; P=0.003), duration of IFN (OR, 1.16; 95% CI: 1.02-1.31; P=0.021), and genotype CC (OR, 3.9; 95% CI: 1.1-13.2; P=0.025) independently predicted HBsAg clearance. IL28B polymorphism is an additional predictor of off-therapy IFN-related HBsAg seroclearance to be used in the pretreatment stratification of HBeAg-negative patients chronically infected by genotype D of HBV.

Viral load and alanine aminotransferase correlate with serologic response in chronic hepatitis B patients treated with entecavir

Although entecavir has been shown to have good efficacy and low resistance for the treatment of chronic hepatitis B (CHB), factors associated with a favorable response remain unknown. This was a retrospective, multicenter study of 248 treatment-naïve hepatitis B e antigen (HBeAg)-positive patients (69.4% male; median age, 39.4 years) treated with entecavir for more than 1 year, and 15.7% of them had cirrhosis at baseline. The primary endpoints were HBeAg loss and/or seroconversion. The median baseline levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA were 201 U/L (range, 27-2415 U/L) and 7.6 log(10) IU/mL (range, 2.2-13.18), respectively. The median treatment period was 25.3 months (range, 12-69.6). The rates of ALT normalization at years 1, 2, and 3 were 83.1%, 87.9%, and 94.9%, respectively. The cumulative rates of HBeAg loss at years 1, 2, and 3 were 20.3%, 38.0%, and 48.9%, respectively. The rates of undetectable HBV-DNA at years 1, 2, and 3 were 52.1%, 78.9%, and 82.5%, respectively. Using Cox proportional hazards model, multivariate analysis showed that baseline ALT greater than five times the upper limit of normal, and viral load were independent factors associated with HBeAg loss (hazard ratio: 1.81, and 0.812; 95% confidence interval: 1.062-3.085; 0.7-0.942, respectively). Entecavir treatment for 3 years can achieve good biochemical and virologic responses in HBeAg-positive CHB patients, but has a modest effect on HBeAg loss and/or seroconversion. In addition, baseline serum ALT and HBV-DNA levels are independent factors associated with favorable treatment responses.

A 96-Week Randomized Trial of Switching to Entecavir in Chronic Hepatitis B Patients with a Partial Virological Response to Lamivudine

Growing numbers of chronic hepatitis B (CHB) patients in the Asia-Pacific region have failed first-line therapy with low genetic barrier drugs. This prospective, 96-week study investigated the antiviral efficacy, safety and tolerability of switching to entecavir versus maintaining lamivudine in CHB patients with a partial virological response to lamivudine. A total of 72 hepatitis B e antigen (HBeAg)-positive patients, with serum HBV DNA≥60 IU/ml after ≥6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day. Mean duration of prior lamivudine treatment was 15.1 months in the lamivudine-maintained patients and 16.1 months in the entecavir-switch patients, with mean baseline HBV DNA levels of 4.66 and 4.55 log(10) IU/ml, respectively. A greater proportion of entecavir-switch than lamivudine-maintained patients achieved undetectable HBV DNA at all time points (67.6% versus 11.4% at week 96; P<0.001). Entecavir-switch patients achieved a greater mean decrease in HBV DNA level by week 4, maintained through week 96. Entecavir-switch patients with baseline HBV DNA<5 log(10) IU/ml were more likely to achieve a virological response at week 96. A total of 6 (17.6%) entecavir-switch and 2 (5.7%) lamivudine-maintained patients achieved HBeAg loss, and 3 (8.8%) entecavir and 1 (2.9%) lamivudine patients achieved HBeAg seroconversion. Genotypic resistance to the assigned intervention emerged in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir-switch patients after 96 weeks. Switching to entecavir in patients with a partial virological response to lamivudine resulted in increased virological efficacy and lower rates of antiviral resistance than maintaining lamivudine.

Pre-S Mutation Is a Significant Risk Factor for Hepatocellular Carcinoma Development: A Long-Term Retrospective Cohort Study

Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC). We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way. A total of 195 patients with chronic HBV infection [age: 43.7±10.8years, males: 141 (72.3%), genotype C: 195 (100%), hepatitis B e antigen (HBeAg) positive: 109 (55.9%), cirrhosis: 79 (40.5%), and pre-S mutation positive: 44 (22.6%)] were followed up for a median of 7.2years (range 1.0-7.8years). HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4%, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7%, p<0.001) and showed higher hazard ratio for HCC [3.04 (95% CI 1.24-7.42), p=0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged ≥50years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3%), compared to those without (16.1%, p<0.001). Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development.

Emergence of lamivudine resistance hepatitis B virus mutations in pregnant women infected with HBV and HIV receiving antiretroviral prophylaxis for the prevention of mother‐to‐infant transmission in Malawi

HIV/HBV co-infection is highly prevalent in sub-Saharan Africa. The aim of this study was to determine if the use of triple combination lamivudine-containing prophylaxis for the prevention of mother-to-infant HIV transmission was associated with the emergence of lamivudine HBV mutations. The study included 21 pregnant co-infected women in Malawi who received either zidovudine or stavudine plus lamivudine and nevirapine from week 25 of gestation until 6 months after delivery or indefinitely if they met the criteria for treatment (CD4+ <350/mm(3)). HBV-DNA was determined using the Roche COBAS assay. Resistance mutations were assessed by the Trugene assay (Siemens Diagnostics). At baseline 33% of the women were HBeAg positive and had HBV-DNA > 10(4) IU/ml. Median CD4 count was 237 cells/mm(3) and median HIV-RNA was 3.8 log(10) copies/ml. After a median of 259 days of treatment, HBV-DNA was detectable in 9 out of 21 patients (42.8%). In three cases the HBV-DNA level was >10(4) IU/ml. Resistance mutations (M204I in five cases and L180M + M204I/V in one case) were present in 6 (28.6%) patients. Women with a resistant virus had significantly higher baseline HBV-DNA levels than those not developing resistance (1.1 × 10(7) IU/ml vs. 20.8 IU/ml, P = 0.022). Levels of ALT and AST were higher in women with resistant viruses compared to those retaining a wild-type virus. A high rate of lamivudine resistance was seen in this cohort of pregnant women. Follow-up of these patients will clarify if the presence of resistance has a significant impact on liver disease.

Lamivudine plus adefovir vs. entecavir in HBeAg‐positive hepatitis B with sequential treatment failure of lamivudine and adefovir

Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12. In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months. Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17-0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83-0.95; P = 0.044). Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.

Five‐year on‐treatment efficacy of lamivudine‐, tenofovir‐ and tenofovir + emtricitabine‐based HAART in HBV–HIV‐coinfected patients

Data on the efficacy of lamivudine (LAM)-, tenofovir (TDF)- and emtricitabine (FTC)-based antiretroviral therapy (HAART) in HBV-HIV coinfection are limited. We completed a retrospective analysis of HBV-HIV-coinfected patients treated at the Medical University of Vienna. One-hundred and ten coinfected patients were included, with 57% being initially HBV e-Antigen (HBeAg) positive. Baseline HBV load was significantly higher in HBeAg+ than in HBeAg- patients (5962 ± 3663 vs 20 ± 19 × 10(6) IU/mL; P < 0.0001). Over a median observation period of 83 month (range: 26-183), 87% received HAART and 91% showed a suppression of HBV replication. After 5 years of continuous treatment, HBeAg seroconversion was achieved in 21% of LAM-, 50% of TDF- (P = 0.042 vs LAM) and in 57% of TDF + FTC (P = 0.008 vs LAM)-treated patients, respectively. HBsAg loss after 5 years was found in 8% (LAM), 25% (TDF; P = 0.085 vs LAM) and 29% (TDF + FTC; P = 0.037 vs LAM) of HBeAg+ patients. In HBeAg- patients, HBsAg loss was achieved in 11% (LAM), 27% (TDF; P = 0.263 vs LAM) and 36% (TDF + FTC; P = 0.05 vs LAM), respectively. Pretreatment CD4+ counts did not influence rates of HBeAg seroconversion and of HBsAg loss. Patients with HBsAg loss had lower baseline HBV-DNA levels and higher AST/ALT levels than patients without HBsAg loss. Transient HAART-related hepatotoxicity was found in 32% (Grade I: 21%; II:7%; III:2%; IV:0%). Most HBV-HIV-coinfected patients achieve complete suppression of HBV replication despite high baseline viremia. TDF-based HAART leads to high rates of HBeAg seroconversion and HBsAg loss after 5 years of continuous exposure. One-third of HBV-HIV-coinfected patients may experience transient HAART-related hepatotoxicity.

Effect and Predictive Elements for 52 Weeks’ Telbivudine Treatment on Naïve HBeAg Positive Chronic Hepatitis B

: Background: Antiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing novartis pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses. Objectives: To reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment. Patients and Methods: A total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24. Results: The reduction in hepatitis virus B (HBV) DnA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, oR = 1.008), and baseline ALT and baseline HBV DnA levels were independent compact factors of SR (P = 0.012, oR = 1.007; P = 0.001, oR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DnA > 107 copies/mL compared with patients with HBV DnA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DnA lower than 300 copies/mL at Week 24 and patients with HBV DnA higher than 300 copies/mL (P = 0.000, P = 0.0016, and P = 0.000, respectively). Conclusions: There were more responders among naïve HBeAg-positive chronic hepatitis B patients with lower HBV DnA levels (especially lower than 107 copies/mL) and higher ALT values (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for treatment strategy should be considered if HBV DnA > 300 copies/mL at Week 24 is observed.

Effect and Predictive Elements for 52 Weeks’ Telbivudine Treatment on Naïve HBeAg positive Chronic Hepatitis B

Antiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). Each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing Novartis Pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses. To reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment. A total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24. The reduction in hepatitis virus B (HBV) DNA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, OR = 1.008), and baseline ALT and baseline HBV DNA levels were independent compact factors of SR (P = 0.012, OR = 1.007; P = 0.001, OR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DNA > 107 copies/mL compared with patients with HBV DNA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DNA lower than 300 copies/mL at Week 24 and patients with HBV DNA higher than 300 copies/mL (P = 0.000, P = 0.0016, and P = 0.000, respectively). There were more responders among naïve HBeAg-positive chronic hepatitis B patients with lower HBV DNA levels (especially lower than 107 copies/mL) and higher ALT values (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for treatment strategy should be considered if HBV DNA > 300 copies/mL at Week 24 is observed.

Factors Predicting the Effi cacy of Adefovir Dipivoxil on Treatment-Naïve Chronic Hepatitis B Patients at 48 Weeks

Background/AimsTo reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV.MethodsIn total, 168 treatment-naïve CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values.ResultsMultiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p<0.05), baseline ALT levels were an independent predictor of serological response (SR) (p<0.05) and the body mass index (BMI) may affect the biochemical response (BR) (p<0.05). There was a statistically significant difference in the VR and SR between patients with a primary nonresponse (PNR) at week 12 and those with a VR at week 12 (p<0.01). Additionally, the VR was significantly different between patients with HBV DNA lower than 103 copies/mL at week 24 and those with greater than 103 copies/mL (p<0.01).ConclusionsPatients with negative HBeAg, lower HBV DNA levels and higher ALT values at baseline are more suitable for ADV treatment, whereas patients with lower BMIs may be more amenable to ALT normalization. Adjustments for treatment strategy should be considered if PNR at week 12 or HBV DNA ≥103 copies/mL at week 24 is observed.

Recent advances in the treatment of chronic hepatitis B

Introduction: At present, two strategies exist for the treatment of chronic hepatitis B (CHB): i) standard or pegylated interferon alpha (IFN) with mainly immune modulatory effects; and ii) nucleos(t)ide analogues (NA) with direct antiviral effects. The optimal treatment for an individual patient remains controversial.Areas covered: The treatment efficacy and prediction of response to antiviral agents for chronic hepatitis B are reviewed and discussed.Expert opinion: The rates of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) loss or seroconversion are continuously increasing in CHB patients after stopping a finite course of IFN, whereas long-term NA therapy is usually required to improve the adverse outcomes of CHB. Lower baseline HBV DNA level is a strong predictor for both sustained viral suppression and HBeAg seroconversion in patients receiving IFN-based as well as NAs therapy. In addition, HBeAg-positive patients with genotype A or B infection have better responses to IFN-based therapy than those with genotypes C or D infection. Furthermore, on-treatment predictors such as declines of serum HBV DNA, HBsAg and HBeAg levels may be helpful in making decisions of subsequent therapy. Regarding the association of host genetic factors with responses to antiviral therapy, current evidence is limited.

HBV lamivudine resistance among hepatitis B and HIV coinfected patients starting lamivudine, stavudine and nevirapine in Kenya

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels.

Three Years of Continuous Entecavir Therapy in Treatment-Naïve Chronic Hepatitis B Patients: VIRAL Suppression, Viral Resistance, and Clinical Safety

We aimed to determine the antiviral potency, viral resistance rate, and clinical safety of 3-year continuous entecavir treatment. We determined the cumulative rates of undetectable hepatitis B virus DNA (HBV DNA) levels (< 12 IU/ml), hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and entecavir signature mutations (using the sensitive line probe assay) and monitored any side effects for 222 treatment-naïve chronic hepatitis B (CHB) patients (40.5% HBeAg positive) on continuous entecavir treatment for 3 years. The median age and follow-up duration were 45 years and 25.1 months, respectively. In all, 222, 188, and 101 patients had been followed up for at least 1, 2, and 3 years, respectively. There were incremental increases in the rates of HBV DNA undetectability, HBeAg seroconversion, and ALT normalization reaching to 92.1, 43.9, and 90.4% at year 3, respectively. In all, 100 and 76.5% of patients with baseline HBV DNA levels < and ≥ 8 logs copies/ml, respectively, had undetectable HBV DNA at year 3. The cumulative rate of entecavir-resistant mutations was 1.2% at year 3. Three patients experienced virologic breakthrough, one with resistance development, one with subsequent HBeAg seroconversion, and one with subsequent decline in HBV DNA. Two patients with baseline rt204I mutations responded to entecavir treatment. There were no serious adverse events. Using very sensitive HBV DNA and viral resistance assays, continuous entecavir treatment for treatment-naïve CHB patients for 3 years was associated with >90% chance of undetectable HBV DNA and only 1.2% chance of emergence of entecavir-resistant mutations.