Negative HBcAg in immunohistochemistry assay of liver biopsy is a predictive factor for the treatment of patients with nucleos(t)ide analogue therapy.

The hepatitis B core antigen (HBcAg) is an important target for antiviral response in chronic hepatitis B (CHB) patients. However, the correlation between HBcAg in the hepatocyte nucleus and nucleos(t)ide analogue (NA) therapeutic response is unclear. We sought to evaluate the role of HBcAg by analysing liver biopsies for viral response in NA-naïve hepatitis B e antigen (HBeAg) positive (+) CHB patients via immunohistochemistry (IHC). A total of 48 HBcAg-negative (-) patients and 48 HBcAg (+) patients with matching baseline characteristics were retrospectively analysed for up to 288 weeks. Virological response (VR) rates of patients in the HBcAg (-) group were significantly higher at week 48 and 96 than the HBcAg (+) group (77.1% versus 45.8% at week 48, respectively, P = 0.002 and 95.3% versus 83.3% at week 96, respectively, P = 0.045). The serological negative conversion rate of HBeAg was significantly higher in the HBcAg (-) than in the HBcAg (+) group from week 96 to 288 (35.4 % versus 14.6% at week 96, respectively, P = 0.018; 60.4% versus 14.6%, respectively, P < 0.001 at week 144; 72.9% versus 35.4%, respectively, P < 0.001 at week 288). The cumulative frequencies of VR and lack of HBeAg were higher in the HBcAg (-) group (both P < 0.05). Binary logistic regression analysis showed that HBcAg (-) was the predictor for the lack of HBeAg (OR 4.482, 95% CI: 1.58-12.68). In summary, the absence of HBcAg in the hepatocyte nucleus could be an independent predictor for HBeAg seroconversion rates during NA-naïve treatment in HBeAg (+) CHB patients.

Comparing Efficacy of Lamivudine, Adefovir Dipivoxil, Telbivudine, and Entecavir in Treating Nucleoside Analogues Naïve for HBeAg-Negative Hepatitis B with Medium Hepatitis B Virus (HBV) DNA Levels.

BACKGROUND The antiviral effect of HBV in different nucleos (t) ide analogues is still not well known. This study was conducted to compare the effectiveness of lamivudine (LMV), adefovir dipivoxil (ADV), telbivudine (LdT), and entecavir (ETV) monotherapy in chronic HBeAg-negative hepatitis B patients with medium load of HBV DNA. MATERIAL AND METHODS The effective data of 207 patients treated by LMV (n=43), ADV (n=57), LdT (n=54) or ETV (n=53) were collected and analyzed during 144-week follow-up by retrospective analysis. RESULTS Serum HBV DNA levels were significantly lower in the ETV group 1.91±0.45 log10 IU/ml) than in the LdT group (2.09±0.62 log10 IU/ml), ADV group (2.26±0.73 log10 IU/ml), and LMV group (2.08±0.75 log10 IU/ml) at 12 weeks (P=0.0464). HBV DNA levels were maintained at lower levels in the ETV group compared to other 3 groups during follow-up (48 weeks, P<0.001; 96 weeks, P<0.001). Multivariate Cox regression analysis showed that LMV (P=0.001), ADV, (P<0.001), and LdT (P<0.001) were all negative predictors of HBV DNA-negative time, but ETV was not. Viral breakthrough occurred in 34.8% (15/43) of patients in the LMV group; 5.26% (3/57) in the ADV group, 7.4.0% (4/54) in the LdT group, and 0% (0/53) in the ETV group at the end of follow-up. No significant differences were found in mean ALT levels (all P>0.05) or in cumulative normalization rates (P=0.473). CONCLUSIONS ETV was more potent and faster for viral response and lower viral breakthrough in medium load of HBV DNA when compared to LMV, ADV, or LdT monotherapy in HBeAg-negative CHB.

Association between Nonalcoholic Fatty Liver Disease and Bone Mineral Density in HIV-Infected Patients Receiving Long-term TDF-Based Antiretroviral Therapy.

BACKGROUND: Tenofovir (TDF) has a detrimental effect on bone mineral density (BMD), while nonalcoholic fatty liver disease (NAFLD) is associated with a lower BMD. OBJECTIVE: To help understand the mutual effects of NAFLD and TDF on BMD, this study was designed to explore the potential association between NAFLD and BMD in HIV-infected patients receiving long-term TDF-based antiretroviral therapy (ART). METHODS: A total of 89 HIV-infected patients who received TDF-based ART for more than three years were enrolled in this cross-sectional study. We measured BMD using an ultrasonic bone density apparatus, and liver ultrasonography was performed to determine the severity of the fatty liver. The association of NAFLD with BMD was examined using multiple logistic regression analyses. RESULTS: Patients with NAFLD showed a worse BMD status than those without NAFLD. The incidence rates of osteopenia (42.86% versus 25.93%) and osteoporosis (17.14% versus 3.70%) were significantly higher in HIV-infected patients with NAFLD than in those without NAFLD. After multivariate adjustment, the odds ratio (OR) for patients with NAFLD exhibiting a worse BMD status compared with those without NAFLD was 4.49 (95% confidence interval [CI] 1.42, 14.15). CONCLUSION: Based on our results, NAFLD was significantly associated with a worse BMD status, including osteopenia and osteoporosis, in HIV patients after receiving long-term TDF-based ART. Furthermore, we may want to avoid using TDF for ART in HIV-infected patients with NAFLD.

Comparison of transcriptional profiles between CD4+ and CD8+ T cells in HIV type 1-infected patients.

The CD4+/CD8+ T cell ratio is altered when HIV-1 infects the human immune system. However, the exact mechanisms of how CD4+ and CD8+T cells participate in HIV infection are still unknown. This study used bioinformatics methods to compare the transcriptional profiles between CD4+ and CD8+ T cells in HIV-1-infected patients in order to explore the potential molecular mechanisms of CD4+ and CD8+ T cells in HIV-1 infection. We found that expression patterns of differentially expressed genes (DEG) in CD4+T cells were dramatically different from those in CD8+ T cells. We also constructed protein-protein interaction (PPI) networks to extract functional modules at each stage, and found that some of the important genes such as BRCA1 were central hubs of the modules. Finally, we applied functional annotation to the modules and found that CD4+/CD8+ T cells played critical roles in regulating the cell cycle and other cellular pathways. Thus, this study would greatly further our understanding of the roles of T cells in HIV infection, and provide potential clues for developing AIDS vaccines in the future.