Low Hepatitis B Virus DNA Research Articles

The hepatitis B virus reactivation after transarterial chemoembolization in Chinese hepatocellular carcinoma patients with low serum hepatitis B virus DNA level.

ObjectiveTo investigate the reactivation of the hepatitis B virus (HBV) following transarterial chemoembolization (TACE) in Chinese hepatocellular carcinoma (HCC) patients with low serum HBV DNA level, and to analyze the factors related to HBV reactivation in HCC patients with low serum HBV DNA level.MethodsFrom November 2011 to January 2014, 109 patients newly diagnosed with HCC with an HBV DNA level less than 2,000 IU/mL were enrolled in the study. These patients underwent at least two TACE procedures and were followed-up for at least 3 months to assess the reactivation of HBV DNA. Ten variables were compared in patients with and without HBV reactivation to evaluate the factors related to HBV reactivation in HCC patients with low serum HBV DNA level.ResultsOf 109 HCC patients with low level HBV DNA, nine patients were HBeAg-positive, the other 100 patients were HBeAg-negative. Twenty-three of 109 (21.1%) patients developed HBV reactivation after TACE. Of nine HBeAg-positive patients, 55.6% (5/9) developed HBV reactivation, while in 100 HBeAg-negative patients, the rate of HBV reactivation was 18% (18/100) (P=0.019). Of ten variables of patients with low level HBV DNA, the levels of AFP and HBeAg status were found to be significantly correlated with HBV reactivation. Nevertheless, on binary logistic regression analysis, only HBeAg-positive status was the independent predictor of HBV reactivation in HCC patients with low serum HBV DNA level (odds ratio, 7.41; P=0.013).ConclusionHCC patients with low serum HBV DNA level still remain associated with risk of viral reactivation after TACE, and HBeAg-positive HCC patients have a higher risk than patients with HBeAg-negative status.

Low serum hyaluronic acid levels associated with spontaneous HBsAg clearance.

PurposeThe pathophysiological underlying mechanism of spontaneous HBsAg clearance in hepatitis B virus (HBV) infected patients is largely unknown. However, serum hyaluronic acid (sHA) plays a role in liver fibrosis progression and reversely could serve as a potential biomarker for HBsAg clearance. This study investigates whether low sHA is associated with HBsAg loss in non-Asian HBV patients.MethodsNon-Asian women living in Amsterdam with known chronic HBV infection between 1990–2003 were invited for a single follow-up visit at the Municipal Health Service Amsterdam between September 2011 to May 2012. Serum hyaluronic acid and liver stiffness measurement together with clinical evaluation, biochemical and virologic blood tests were performed.ResultsOf the 160 women, HBsAg loss occurred in 38 (23 %) patients between diagnosis and follow-up. sHA levels were lower in HBsAg negative patients compared to HBsAg positive patients (14.5 [9.4–27.2] ng/mL vs 25.0 [12.3–42.5] ng/mL, p <0.01). A similar distinction in sHA between low and high HBV DNA was noted. sHA had a significant discriminatory ability to differentiate between HBsAg positive and HBsAg negative patients, (AUC 0.65 [95 % CI 0.55–0.75], p < 0.01). In multivariable analysis only sHA level was associated with HBsAg loss (OR 0.4 [0.2–0.9]). Finally, F3-F4 fibrosis (cut-off >8.1 kPa) was diagnosed in 3 % in HBsAg negative patients compared to 10 % in HBsAg positive patients (p = 0.15).ConclusionSerum HA levels are lower in patients who experience spontaneous HBsAg loss compared to HBsAg positive patients.

Ten-year follow-up of hepatitis B relapse after cessation of lamivudine or telbivudine treatment in chronic hepatitis B patients

The high rate of relapse after cessation of nucleos(t)ide analogues (NUCs) treatment in chronic hepatitis B (CHB) patients leads us to reassess the feasibility for off-therapy, but long-term follow-up data are scarce. We assessed the feasibility for off-therapy by a long-term observation of relapse in response to lamivudine (LAM) and telbivudine (LdT). Eighty-six NUC-naive CHB patients, treated with LAM (n = 46) or LdT (n = 40) who reached the guidelines recommended for off-therapy, were followed for up to 10 years. Hepatitis B virus (HBV), viral serology and biochemistries were periodically determined. COX model was used to predict the risk of relapse. A total of 52.3% of patients experienced relapse within a median of 115 months (range, 61–122 months). A total of 93.3% of relapses occurred within 48 months. Relapse rates in hepatitis B e antigen (HBeAg)-positive (n = 56) and HBeAg-negative (n = 30) patients were 39.3% and 76.7%, respectively (p < 0.01). HBeAg-positive patients who achieved an early viral response (EVR), defined as undetectable HBV DNA within 6 months, had a lower relapse rate compared to non-EVR patients (21.4% vs. 59.2%, p < 0.01). EVR patients who had both lower HBV DNA (<106 copies/mL) at baseline and lower hepatitis B surface antigen (HBsAg) at end of treatment had a relapse rate of 10.7%. The high relapse rates in CHB patients over this 10-year follow-up make LAM or LdT off therapy infeasible in most of the cases, except in the case of HBsAg loss and/or seroconversion. HBeAg-positive patients with EVR, lower HBV DNA and HBsAg had lower relapse rates and could be good candidates for off-therapy. Long-term monitoring, especially during the first 4 years, is critical for patients off-therapy.

Stopping Preemptive Antiviral Therapy for Hepatitis B Virus Can Be Considered for Patients with Favorable Predictors.

Preemptive antiviral therapy is recommended for chronic hepatitis B virus (HBV)-infected patients receiving cytotoxic chemotherapy. However, little data are available for the stopping therapy. We evaluated clinical outcome and predictors of off-treatment virological response of patients who discontinued therapy. Ninety-five adult patients who discontinued therapy were enrolled. They were analyzed for sustained off-treatment virological response, defined as HBV DNA levels below 2000 IU/ml for at least 12 months after the end of therapy. Sustained off-treatment virological response was seen in 52 patients (54.7%). The baseline HBV DNA level was an independent factor associated with sustained off-treatment virological response, and the rate was 72.1 and 23.5% for those with HBV DNA < 2000 IU/ml and ≥ 2000 IU/ml, respectively (P < 0.001). The duration of consolidation treatment showed marginal association with sustained off-treatment virological response [odd ratio (95% confidence interval) 1.20 (0.98-1.47), P = 0.069] for those with baseline HBV DNA < 2000 IU/ml, but not for those with ≥ 2000 IU/ml. The sustained off-treatment virological response rate was 54.5, 71.4, 73.9, and 100% for consolidation treatment duration of <3, 3-6, 6-12, and ≥ 12 months, respectively, among those with baseline HBV DNA < 2000 IU/ml. The baseline HBV DNA level was indicator for sustained off-treatment virological response after stopping preemptive antiviral therapy. Consolidation treatment duration showed association with sustained off-treatment virological response only for those with low baseline HBV DNA levels.

HBeAg-negative chronic hepatitis patients should be monitored more strictly: a cross-sectional retrospective study on antiviral treatment-naïve patients.

To investigate the prevalence and characteristics of hepatitis B e antigen (HBeAg) negative/treatment naïve subjects with low hepatitis B virus (HBV) DNA levels (<10(4) copies/ml) and low alanine aminotransferase (ALT) levels (<2 × upper limit of normal) in patients with HBV-related hepatocellular carcinoma (HCC). A total of 226 treatment naïve patients diagnosed with HBV-related HCC, divided into five Barcelona Clinic Liver Cancer (BCLC) stages, were enrolled and retrospectively analyzed. Virological parameters including hepatitis B surface antigen (HBsAg), HBeAg, HBV DNA levels, and laboratory parameters including ALT and aspartame aminotransferase were accessed at the time of HCC was diagnosed. Comparison between HBeAg positive patients and HBeAg negative patients was performed using a χ(2) test. While laboratory parameters correlated with BCLC stages, virological parameters did not. HBeAg negative patients were more prevalent than HBeAg positive patients (160, 70.8% vs. 66, 29.2%). HBsAg and HBV DNA levels in HBeAg negative patients were significantly lower than that in HBeAg positive patients (all P < 0.001). Of the 160 HBeAg negative patients, 74 (46.25%) had low HBsAg, 76 (47.5%) had low DNA levels, and 35 (21.9%) patients had low DNA and normal ALT levels. In treatment naïve patients with HBV-related HCC, the majority (70.8%) were HBeAg negative patients. More than one fifth of HBeAg negative patients had low HBV DNA levels and normal ALT levels, indicating more strict monitoring for HBeAg negative patients is needed.

Rapid fluorescent lateral-flow immunoassay for hepatitis B virus genotyping.

Hepatitis B virus (HBV) genotyping plays an important role in the clinical management of chronic hepatitis B (CHB) patients. However, the current nucleic acid based techniques are expensive, time-consuming, and inconvenient. Here, we developed a novel DNA-independent HBV genotyping tool based on a one-step fluorescent lateral flow immunoassay (LFIA). Epitope-targeting immunization and screening techniques were used to develop HBV genotype specific monoclonal antibodies (mAbs). These mAbs were used to develop a multitest LFIA with a matched scanning luminoscope for HBV genotyping (named the GT-LFIA). The performance of this novel assay was carefully evaluated in well-characterized clinical cohorts. The GT-LFIA, which can specifically differentiate HBV genotypes A, B, C, and D in a pretreatment-free single test, was successfully developed using four genotype specific mAbs. The detection limits of the GT-LFIA for HBV genotypes A, B, C, and D were 2.5-10.0 IU HBV surface antigen/mL, respectively. Among the sera from 456 CHB patients, 439 (96.3%; 95% confidence interval (CI), 94.1-97.8%) were genotype-differentiable by the GT-LFIA and 437 (99.5%; 95% CI, 98.4-99.9%) were consistent with viral genome sequencing. In the 21 patients receiving nucleos(t)ide analogue therapy, for end-of-treatment specimens that were HBV DNA undetectable and were not applicable for DNA-dependent genotyping, the GT-LFIA presented genotyping results that were consistent with those obtained in pretreatment specimens by viral genome sequencing and the GT-LFIA. In conclusion, the novel GT-LFIA is a convenient, fast, and reliable tool for differential HBV genotyping, especially in patients with low or undetectable HBV DNA levels.

Efficacy of tenofovir switch therapy for nucleos(t)ide-experienced patients with chronic hepatitis B.

Tenofovir disoproxil fumarate has been used in chronic hepatitis B patients with suboptimal virologic response to nucleos(t)ide analogues. The efficacy of tenofovir switch therapy has not been well studied in Asian patients. To evaluate the efficacy of tenofovir switch therapy in nucleos(t)ide-experienced patients, and identify the factors associated with treatment response of tenofovir switch therapy. Nucleos(t)ide-experienced hepatitis B e antigen-positive and -negative patients prescribed with tenofovir were retrospectively identified and recruited for prospective analysis. Hepatitis B virus (HBV) DNA and other biochemical parameters were monitored in regular 3-6monthly follow-up visits. Primary efficacy endpoint was maintained-virologic response with tenofovir switch therapy, defined as undetectable HBV DNA (<20IU/mL) until the last follow-up visit. An overall of 214/252 (84.9%) patients achieved maintained-virologic response after 22 (7-55) months of tenofovir switch therapy. On multivariate analysis, a lower HBV DNA level at the time of switching to tenofovir was an independent factor associated with treatment efficacy. Maintained-virologic response after switching to tenofovir was achieved in 177/190 (93.2%) patients with HBV DNA <20000IU/mL vs. 37/62 (59.7%) patients with HBV DNA ≥20000IU/mL (P<0.001). Absence of genotypic resistance to lamivudine or adefovir dipivoxil was not associated with improved treatment outcome. Tenofovir switch therapy is an effective treatment strategy in nucleos(t)ide-experienced chronic hepatitis B patients. However, in patients with HBV DNA ≥20000IU/mL at the time of switching to tenofovir, the chance of achieving maintained undetectable HBV DNA is significantly reduced.

Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies.

To evaluate the long-term efficacy adefovir (ADV)-based combination therapies in entecavir (ETV)-resistant chronic hepatitis B (CHB) patients. Fifty CHB patients with genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV (ADV/ETV, n = 23) or ADV plus lamivudine (LMV) (ADV/LMV, n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by real-time PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA < 20 IU/mL) were calculated using the Kaplan-Meier method, and the difference was determined by a log-rank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR, respectively. Baseline median HBV DNA levels were 5.53 (2.81-7.63) log10 IU/mL. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27 (12-45) mo. Overall, cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates (35%, 43%, 65%, and 76%, respectively) than those with the ADV/LAM combination (18%, 30%, 30%, and 62%, respectively; P = 0.048). In the multivariate analysis, low baseline HBV DNA levels (< 5.2 log10 IU/mL) and initial virologic response at 3 mo (IVR-3; HBV DNA < 3.3 log10 IU/mL after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors. If tenofovir is not available, ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may be continued if IVR-3 is achieved.

Clinical Significance of Hepatitis B Virus Precore and Core Promoter Variants in Korean Patients With Chronic Hepatitis B

We aimed to clarify the clinical significance of precore (preC)/core promoter (CP) variants of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. We assessed serum HBeAg, HBV DNA levels, alanine transferase (ALT) levels, and progression of liver fibrosis in 226 Korean CHB patients, presumed to be infected with genotype C HBV, to analyze HBV variants in the preC region (G1896A) and CP regions (A1762T, G1764A). CP and preC variants were more frequently found in HBeAg-negative patients than in HBeAg-positive patients (P<0.05). HBeAg-positive patients with CP variants had higher ALT levels and more advanced fibrosis scores (all P<0.01) than those without variants; those with preC variant had lower HBV DNA levels (P=0.009), with no significant difference in ALT levels and fibrosis scores. However, no significant correlation was found between HBV variants and clinicopathologic findings in HBeAg-negative patients. Furthermore, multivariate analysis revealed that (1) progression of liver fibrosis (≥F2) was associated with older age in both HBeAg-positive and HBeAg-negative patients (P<0.05) and with CP variants in the HBeAg-positive group (P=0.007), and (2) HBV DNA levels were positively correlated with ALT levels, irrespective of HBeAg (P<0.05), whereas they were negatively correlated with the presence of preC variant in the HBeAg-positive group (P=0.004). In HBeAg-positive CHB patients infected with genotype C HBV, preC variant was associated with enhanced host immune response with lower HBV DNA levels, whereas CP variants were associated with severe liver damage and liver fibrosis progression.

Clinical performance of a new hepatitis B surface antigen quantitative assay with automatic dilution

Hepatitis B virus surface antigen (HBsAg) levels reflect disease status and can predict the clinical response to antiviral treatment; however, the emergence of HBsAg mutant strains has become a challenge. The Abbott HBsAg quantification assay provides enhanced detection of HBsAg and HBsAg mutants. We aimed to evaluate the performance of the Abbott HBsAg quantification assay with automatic sample dilutions (shortened as automatic Architect assay), compared with the Abbott HBsAg quantification assay with manual sample dilutions (shortened as manual Architect assay) and the Roche HBsAg quantification assay with automatic sample dilutions (shortened as Elecsys). A total of 130 sera samples obtained from 87 hepatitis B virus (HBV)-infected patients were collected to assess the correlation between the automatic and manual Architect assays. Among the 87 patients, 41 provided 42 sera samples to confirm the linearity and reproducibility of the automatic Architect assay, and find out the correlation among the Elecsys and two Architect assays. The coefficients of variation (0.44–9.53%) and R2 = 0.996–1, which were both determined using values obtained from the automatic Architect assay, showed good reproducibility and linearity. Results of the two Architect assays demonstrated a feasible correlation (n = 130 samples; R = 0.898, p < 0.01). With regard to subgroups, correlations between the two Architect assays were better in the hepatitis B e antigen (HBeAg)-negative group (HBeAg-negative group vs. HBeAg-positive group: R = 0.885 vs. R = 0.865, both p < 0.01) and low HBV DNA group (low DNA group vs. high DNA group: R = 0.886 vs. R = 0.844, both p < 0.01). Significant correlations were also found between the results of the Elecsys and Architect assays (R > 0.93 in all cases). In conclusion, the correlation between the automatic and manual dilution Architect assays was feasible, particularly in the HBeAg-negative and low DNA groups. With lower labor costs and less human error than the manual version, the Abbott automatic dilution Architect assay provided a good clinical performance with regard to the HBsAg levels.

Changing serum levels of quantitative hepatitis B surface antigen and hepatitis B virus DNA in hepatitis B virus surface antigen carriers: A follow-up study of an elderly cohort

This study was to elucidate longitudinally quantitative changes of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA in elder HBsAg carriers in a community. Among 1002 residents screened for HBsAg in 2005, 405 responded to this follow-up study in 2010. Fifty-nine (14.6%) were HBsAg carriers in 2005; HBsAg quantification and HBV DNA were measured. HBsAg quantification (cutoff 1600 IU/mL) and HBV DNA (cutoff 2000 IU/mL) were combined to stratify the participants between two screens. A total of 30 men and 29 women with a mean age of 63.9 ± 7.9 years were enrolled. Quantitative levels of HBsAg and HBV DNA were significantly correlated in 2005 (r = 0.509, p < 0.001) and 2010 (r = 0.777, p < 0.001). Concentrations of HBsAg (IU/mL) significantly decreased from 2.2 ± 1.0 log in 2005 to 1.7 ± 1.5 log in 2010 (p < 0.001). The level of HBsAg was decreased in 48 (81.4%) individuals and HBsAg was undetectable in eight (13.6%). The annual incidence of HBsAg clearance was 2.7%. These 59 HBsAg carriers in 2005 were divided into four groups: low HBsAg low HBV DNA (n = 32), high HBsAg low HBV DNA (n = 5), low HBsAg high HBV DNA (n = 12) and high HBsAg high HBV DNA (n = 10). All 32 individuals in the low HBsAg low HBV DNA group were still in that group in 2010, whereas only two of the high HBsAg high HBV DNA group became inactive. As with a younger cohort in hospital, HBsAg quantification was still well correlated with HBV DNA in elderly HBsAg carriers in the community. Lower levels of both HBsAg and HBV DNA might represent an inactive HBV infection.

Occult hepatitis B virus infection with positive hepatitis B e antigen

BackgroundHepatitis B e antigen (HBeAg) is a marker to indicate active replication of hepatitis B virus (HBV). Occult HBV infection (OBI), referred to persistence of HBV DNA in serum and/or liver without detectable serum hepatitis B surface (HBsAg), usually has low HBV DNA levels. The presence of HBeAg in OBI is unusual. MethodsWe report 2 patients who presented negative for HBsAg but positive for HBeAg and HBV DNA. HBV markers were quantified in the longitudinal sera in a period of 1–2years. The HBV DNA sequences were analyzed in 2 patients' sera and 1 patient's liver. ResultsBoth patients were also positive for total anti-HBs and anti-HBc but negative for anti-HBe and anti-HBc IgM. HBV DNA levels were 234–567IU/ml in case 1 and 42–1130IU/ml in case 2. The alignment analysis of the S gene showed that HBV in both patients was genotype C, serotype adr. Cloning analysis of the a determinant of HBsAg showed that the immune escape mutants were predominant in both patients over the follow-up period. The HBV had double mutations (A1762T and G1764A) in the basal core promoter but had no mutation in the pre C/C gene in both patients. ConclusionsThe patients with negative HBsAg but positive HBeAg may represent a unique type of OBI. Test for HBeAg would be critical to identifying such type of OBI.

Decreasing hepatitis B viral load is associated with a risk of significant liver fibrosis in hepatitis B e antigen positive chronic hepatitis B.

Alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA levels and age are used commonly to assess liver histology in chronic hepatitis B. Increasing levels of HBV DNA are associated with the increasing prevalence of significant fibrosis in HBeAg-negative patients. It is unclear whether these data can be applied to HBeAg-positive patients. In present study, liver biopsies were performed and clinical parameters were measured in 234 treatment-naive chronic HBeAg-positive patients. The proportion of significant fibrosis in patients with ALT 1-2 × ULN was similar to in patients with ALT more than 2 × ULN (48.4% vs. 51.8%). Patients over 30 years of age (>30 years) had a higher prevalence of significant fibrosis than patients 30 years of age and younger (61.0% vs. 33.6%). Negative correlation between HBV DNA levels and significant fibrosis was observed in patients >30 years. The optimal level of serum HBV DNA to evaluate low risk of significant fibrosis was ≥6.7 log10 IU/ml. Patients with serum HBV DNA levels ≥8.5 log10 IU/ml all had no significant fibrosis, however, patients with HBV DNA levels <4.7 log10 IU/ml all had significant fibrosis. Logistic regressions showed that age, aspartate aminotransferase, platelet count, and HBV DNA levels were independent predictors of significant fibrosis. In summary, older age, elevated ALT, and lower HBV DNA levels are associated with significant fibrosis. Decreasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis in patients >30 years. The threshold of HBV DNA levels for treatment of HBeAg-positive patients needs to be combined with age.

乙型肝炎相关性肝衰竭患者HBV DNA低水平复制及特异性抗体表达的临床意义

Objective To investigate the influential factors and clinical significance of low- level hepatitis B virus ( HBV) DNA replication and specific antibody expression in patients with HBV- related liver failure. Methods A retrospective analysis was performed on the medical records of 391 patients with HBV- related liver failure and 394 patients with chronic hepatitis B ( CHB) hospitalized in the Tianjin Second People's Hospital from June 2008 to December 2013. The HBV DNA level was compared between patients with HBV- related liver failure and those with CHB, and the influential factors were analyzed. According to the expression of HBV serum markers ( HBV- Ms) , patients with liver failure were divided into specific antibody- positive group ( positive for anti- HBs, anti- HBe or anti- HBc) and specific antibody- negative group ( negative for anti- HBs, anti- HBe or anti- HBc) . The changes in HBV DNA level and survival were compared between the two groups. Between- group comparison was made by independent- samples t test or Mann- Whitney rank sum test, and comparison of enumeration data was made by chi- square test. Results The patients with HBV- related liver failure had a significantly lower HBV DNA level than the CHB patients ( Z =- 16. 469, P < 0. 05) . The levels of HBV DNA in HBeAg- positive and- negative patients with liver failure were significantly lower than those in patients with CHB ( Z1=- 11. 665, P < 0. 05; Z2=- 12. 853, P < 0. 05) . Of the391 patients with HBV- related liver failure, 29 ( 7. 42%) were specific antibody- positive, and 25 ( 86. 21%) of them died; 362 ( 92. 58%) were specific antibody-negative, and 157 ( 43.37%) of them died. There was a significant difference in mortality between the specific antibody- positive and specific antibody- negative groups ( P < 0. 05) . The specific antibody- positive group had a significantly lower HBV DNA level than the specific antibody- negative group ( Z =- 3. 594, P < 0. 05) . For either group, the HBV DNA level was significantly lower in HBeAg- negative patients than in HBeAg- positive patients ( Z = 7. 427 or 7. 513, P < 0. 05) . Conclusion HBV M expression and the body's immune status play a role in the progression of HBV- related liver failure. HBV DNA replication is at a low level in the immune clearance phase. Being positive for anti- HBs, anti- HBe, and anti- HBc suggest a super immune response to HBV, leading to rapid progression of disease and high mortality.

Comparison of telbivudine versus lamivudine in interrupting perinatal transmission of hepatitis B virus

BackgroundInfection with hepatitis B virus (HBV) during pregnancy may lead to perinatal transmission. ObjectivesTo compare the efficacy and safety of telbivudine versus lamivudine in interrupting perinatal transmission of hepatitis B virus. Study designAll pregnant women enrolled in this study were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Test patients underwent antiviral therapy with telbivudine or lamivudine while control patients received hepatitis B immune globulin (HBIG) injection. ResultsPatients in the telbivudine group had significantly lower HBV DNA and HBeAg levels and higher HBV DNA negative conversion rates compared to those in the lamivudine group before delivery. HBV DNA negative conversion rates in patients with abnormal alanine aminotransferase (ALT) levels were significantly higher than those in patients with normal ALT levels in the telbivudine and lamivudine groups before delivery. The intrauterine HBV infection rate and the percentage of immunization failure were both 0% in the telbivudine and lamivudine groups (χ2=0, 0; P=1, 1 respectively), compared to both 5% in the HBIG group (χ2=11.83, 7.86; P=0.002, 0.009 respectively). The side effects of three groups in mother and child were all unobvious. ConclusionsTelbivudine and lamivudine can reduce HBV DNA levels in pregnant women, interrupt the vertical transmission of HBV and be used safely in mothers and children.

Prediction of Hepatocellular Carcinoma Recurrence in Patients With Low Hepatitis B Virus DNA Levels and High Preoperative Hepatitis B Surface Antigen Levels

In patients with low viral loads, high levels of hepatitis B surface antigen (HBsAg) have been shown to predict development of hepatocellular carcinoma (HCC). Whether high levels of HBsAg increase the risk for HCC recurrence after hepatic resection remains unknown. To investigate the association between levels of HBsAg and the risk for tumor recurrence after curative resection in HCC patients with low levels of hepatitis B virus (HBV) DNA. We performed a retrospective analysis of the clinical data of 1062 patients with low HBV DNA levels (<200 IU/mL) who underwent partial hepatectomy for HCC. In particular, we investigated the association between levels of HBsAg and recurrence of HCC. Partial hepatectomy for HCC. The risk for first tumor recurrence between patients with high and low HBsAg levels. We calculated cumulative incidences and hazard ratios after adjusting for competing mortality. The risk for tumor recurrence increased with HBsAg levels of 1000 IU/mL or greater. When we compared the groups with low (<1000 IU/mL) and high (≥1000 IU/mL) HBsAg levels, the 5-year disease-free survival rate (46.1% vs 34.1% [P = .002]) and the overall survival rate (57.5% vs 48.8% [P = .004]) were better in the group with low HBsAg levels. On multivariate analysis, hepatitis B e antigen seropositivity, HBsAg level of 1000 IU/mL or greater, tumor size of greater than 5 cm, blood transfusion, surgical margin of less than 1.0 cm, the presence of satellite nodules, and the presence of portal vein tumor thrombus were independent risk factors for HCC recurrence. When compared with hepatitis B e antigen status, HBsAg level better predicted recurrence of HCC. A preoperative HBsAg level of 1000 IU/mL or greater is an independent risk factor for HCC recurrence in patients with low HBV DNA levels.

Amino acid polymorphism in the reverse transcriptase region of hepatitis B virus and the relationship with nucleos(t)ide analogues treatment for preventing mother-to-infant transmission.

A high maternal serum hepatitis B virus (HBV) DNA level is associated with vaccine failure. The administration of nucleos(t)ide analogues (NAs) in pregnancy for decreasing serum HBV is regarded as an effective and safe method to reduce HBV perinatal transmission. However, the effect of NAs treatment is closely related to amino acid polymorphisms in the HBV reverse transcriptase (RT) region. The full-length RT coding region of 334 HBV isolates from untreated Chinese women of childbearing age with persistent HBV infection were sequenced and amino acid polymorphic analysis was performed to evaluate its impact on NAs treatment for decreasing HBV perinatal transmission. Of the 334 isolates, 36 (10.8%) harbored NAs resistance (NAr) mutations which were mainly putative drug mutations related to lamivudine. The primary drug mutation rtA181T/V was detected in three HBeAg-negative women with an HBV DNA level of <4 log IU/ml. These NAr mutations were rarely detected in women with an HBV DNA level of ≥7 log IU/ml (P = 0.014) or in women younger than 35 years (P = 0.001). The NAr mutation rate among young women (<35 years) who had a high HBV DNA level (≥7 log IU/ml) was significantly lower than in women who had lower HBV DNA levels (<7 log IU/ml) or who were older (≥35 years; P = 0.017). These results suggest that younger women with a high HBV DNA level harbor fewer NAr mutations and that this population may respond to NAs treatment for the prevention of mother-to-infant transmission.

Hepatitis C viremia interferes with serum hepatitis B virus surface antigen and DNA levels in hepatitis B uremics.

Hepatitis B virus (HBV) and HCV might cause reciprocal interference. We aimed to elucidate the influence of HCV and interleukin-28B (IL-28B) genetic variants in the HBV DNA and HBsAg levels in uremic HBV carriers. Assessment of HCV and HBV viral loads, HBsAg levels and IL-28B genotype were performed in 229 HBsAg-positive patients from a cohort of 1,681 uremics. Patients with HCV viremia had significantly lower HBV DNA (2.58±0.80 vs. 3.16±1.48 log IU/mL, p=0.005) and HBsAg levels (1.33±1.35 vs. 2.23±1.31 log IU/mL, p=0.002) compared with those without. IL-28B rs8099917 genotype had no impact on HBsAg and HBV DNA levels. In multivariate regression analysis, HCV RNA levels had a more significant negative correlation with HBsAg levels [β -0.905; 95% confidence interval (CI) -1.477, -0.334; p=0.002] than with HBV DNA levels (β -0.586; 95% CI -1.206, 0.034; p=0.06). The serum HBV DNA and HBsAg levels had a positive correlation (r=0.43, p<0.001) among the 215 HBeAg-negative patients. However, the correlation was not observed in patients with HCV viremia (r=0.23, p=0.29). Linear regression analysis revealed that age (β -0.286; 95% CI -0.043, -0.014; p<0.001) and the HBV DNA level (β 0.373; 95% CI 0.239, 0.549; p<0.001) correlated independently with the HBsAg level among HBeAg-negative patients without HCV viremia, but not among those with concomitant HCV viremia. HCV viremia suppressed both HBsAg and HBV DNA levels. The HBsAg levels correlated with the HBV DNA levels only in patients without concomitant HCV viremia.

Performance of two real-time PCR assays for hepatitis B virus DNA detection and quantitation

In-house developed real-time PCR (qPCR) techniques could be useful conjunctives to the management of hepatitis B virus (HBV) infection in resource-limited settings with high prevalence. Two qPCR assays (qPCR1 and qPCR2), based on primers/probes targeting conserved regions of the X and S genes of HBV respectively, were evaluated using clinical samples of varying HBV genotypes, and compared to the commercial Roche Cobas AmpliPrep/Cobas TaqMan HBV Test v2.0. The lower detection limit (LDL) was established at 104 IU/ml for qPCR1, and 91 IU/ml for qPCR2. Good agreement and correlation were obtained between the Roche assay and both qPCR assays (r = 0.834 for qPCR1; and r = 0.870 for qPCR2). Differences in HBV DNA load of > 0.5 Log10 IU/ml between the Roche and the qPCR assays were found in 49/122 samples of qPCR1, and 35/122 samples of qPCR2. qPCR1 tended to underestimate HBV DNA quantity in samples with a low viral load and overestimate HBV DNA concentration in samples with a high viral load when compared to the Roche test.Both molecular tools that were developed, used on an open real-time PCR system, were reliable for HBV DNA detection and quantitation. The qPCR2 performed better than the qPCR1 and had the additional advantage of various HBV genotype detection and quantitation. This low cost quantitative HBV DNA PCR assay may be an alternative solution when implementing national programmes to diagnose, monitor and treat HBV infection in low- to middle-income countries where testing for HBV DNA is not available in governmental health programmes.

Low Prevalence of Liver Disease but Regional Differences in HBV Treatment Characteristics Mark HIV/HBV Co-Infection in a South African HIV Clinical Trial

BackgroundHepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA ‘Safeguard the household study’ in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation.Methods812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline.ResultsForty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3–4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007).ConclusionOne third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations.