Expression and prognostic significance of the PD-1/PD-L1 pathway in AIDS-related non-Hodgkin lymphoma.

OBJECTIVE: Immune tolerance and evasion play a critical role in virus-driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, in aggressive acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) remain poorly understood, particularly in the Epstein-Barr virus (EBV)-positive subset. METHODS: We used in situ hybridization with EBV-encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD-1/PD-L1/L2 pathway in a multi-institutional cohort of 58 patients with AR-NHL and compared EBV-positive and EBV-negative cases. RESULTS: The prevalence of EBV+ in AR-NHL was 56.9% and was associated with a marked increase in the expression of PD-1/PD-L1/PD-L2 in malignant cells. Patients with AR-NHLs who tested positive for both EBER and PD-1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD-L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD-1 tissue-expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD-1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD-L1 (r = 0.354, p = 0.014) expression. CONCLUSIONS: These data emphasize the importance of PD-1-mediated immune evasion in the complex landscape of immune oncology in AR-NHL co-infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup.

Prospective observational study of baloxavir marboxil in adults and adolescents with uncomplicated influenza from China.

Introduction: There are limited data on the efficacy of baloxavir marboxil (baloxavir) versus oseltamivir in Chinese patients with influenza A. Methods: This study is an observational real-world investigation encompassing 246 patients (baloxavir, n = 147; oseltamivir, n = 99) confirmed positive for influenza A. The choice between baloxavir and oseltamivir antiviral treatments was determined collaboratively by the clinician and the patient. A thorough comparative analysis was undertaken between the two groups, examining parameters such as the duration of fever and symptoms, viral load dynamics, lymphocyte changes, and enhancements in health-related quality of life (QoL). Results: No significant differences were observed in demographic data between the two groups. The duration of fever was significantly shorter in the baloxavir group (P < 0.001). However, the duration of symptoms was not significant different (P = 0.167). Multivariable Cox analysis showed the independent factors affecting duration of fever were baloxavir treatment (HR = 2.033, P < 0.001), fever on day 1 (HR = 0.741, P = 0.010) and CRP level (HR = 1.009, P = 0.039). Moreover, sex (HR= 0.660, P = 0.019) and monocyte count (HR = 1.355, P = 0.018) were independent factors affecting the duration of symptoms. No significant difference in change of health-related quality of life (P > 0.05), positive rate of viral antigen on day 3 (P = 0.477) between the two groups. Remarkably, a mutation was observed in one case on the third-day after baloxavir treatment compared with first-day, from cysteine to serine at position 384 of the PA subunit. Conclusion: In the clinical setting, baloxavir demonstrated comparable clinical benefits to oseltamivir, establishing its efficacy as an effective antiviral therapy for Chinese patients with influenza.

Bcl-2 Antagonist Obatoclax Reactivates Latent HIV-1 via the NF-κB Pathway and Induces Latent Reservoir Cell Apoptosis in Latently Infected Cells.

The implementation of combined antiretroviral therapy (cART) has rendered HIV-1 infection clinically manageable and efficiently improves the quality of life for patients with AIDS. However, the persistence of a latent HIV-1 reservoir is a major obstacle to achieving a cure for AIDS. A "shock and kill" strategy aims to reactivate latent HIV and then kill it by the immune system or cART drugs. To date, none of the LRA candidates has yet demonstrated effectiveness in achieving a promising functional cure. Interestingly, the phosphorylation and activation of antiapoptotic Bcl-2 protein induce resistance to apoptosis during HIV-1 infection and the reactivation of HIV-1 latency in central memory CD4+ T cells from HIV-1-positive patients. Therefore, a Bcl-2 antagonist might be an effective LRA candidate for HIV-1 cure. In this study, we reported that a pan-Bcl-2 antagonist obatoclax induces HIV-1 reactivation in latently infected cell lines in vitro and in PBMCs/CD4+ T cells of HIV-infected individuals ex vivo. Obatoclax promotes HIV-1 transcriptional initiation and elongation by regulating the NF-κB pathway. Obatoclax activates caspase 8 and does not induce the phosphorylation of the antiapoptotic protein Bcl-2 in latent HIV-1 infected cell lines. More importantly, it preferentially induces apoptosis in latently infected cells. In addition, obatoclax exhibited potent anti-HIV-1 activity on target cells. The abilities to reactivate latent HIV-1 reservoirs, inhibit HIV-1 infection, and induce HIV-1 latent cell apoptosis make obatoclax worth investigating for development as an ideal LRA for use in the "shock and kill" approach.

Effective Analysis of Antiviral Treatment in Patients with HBeAg-Seropositive Chronic Hepatitis B with ALT < 2 Upper Limits of Normal: A Multi-center Retrospective Cohort Study.

INTRODUCTION: Although the indications for antiviral therapy for patients with chronic hepatitis B have been gradually expanded in different guidelines, antiviral treatment efficacy remains unclear among HBeAg-seropositive patients with alanine aminotransferase (ALT) < 2 upper limits of normal (ULN). This study aimed to evaluate the efficacy of antiviral therapy for these patients. METHODS: In total, 102 treatment-naive patients who were HBeAg seropositive with ALT < 2 ULN and had received nucleotide analogs were included, and their clinical data were retrospectively analyzed. RESULTS: After 96-week treatment, 84.3% (n = 86), 26.5% (n = 27) and 20.6% (n = 21) patients achieved virological response, HBeAg seroclearance and HBeAg seroconversion, respectively. Logistic regression analysis revealed that baseline AST (odds ratio [OR] = 1.069, 95% confidence interval [CI] 1.014-1.127, p = 0.014), serum HBV DNA (OR = 0.540, 95% CI 0.309-0.946, p = 0.031) and quantitative HBsAg levels (OR = 0.147, 95% CI 0.036-0.597, p = 0.007) were independent factors for virological response. At baseline, HBsAg < 4.63 log10 IU/ml was identified as a strong predictor for the 96-week virological response, with a concordance rate of 0.902. Moreover, the levels of liver stiffness values (8.30 ± 3.86 vs. 6.17 ± 1.91, p < 0.001) at week 96 had significantly declined compared to baseline. CONCLUSION: Nucleotide analog treatment effectively suppressed HBV DNA in patients with HBeAg-seropositive chronic hepatitis B with ALT < 2 × ULN and greatly improved liver fibrosis. The study also found that HBsAg < 4.63 log10 IU/ml was a strong predictor of the virological response.

Soluble Programmed Cell Death-1 is a Novel Predictor of HBsAg Loss in Chronic Hepatitis B Patients When Long-Term Nucleos(t)ide Analog Treatment is Discontinued.

Purpose: The immunoinhibitory receptor, programmed death 1 (PD-1), plays a critical role in immune suppression during chronic viral infection. The significance of circulating soluble PD-1 (sPD-1) in patients with chronic hepatitis B who have discontinued long-term nucleos(t)ide analog (NA) treatment remains unknown. Patients and Methods: A prospective cohort study was conducted using serial blood samples from chronic hepatitis B patients who discontinued long-term NA treatment. The current analysis included 115 non-cirrhotic patients with HBV DNA negative and HBsAg positive at the moment of NA discontinuation. Levels of sPD-1 were measured in all available samples using sandwich enzyme-linked immunoassay. Results: Sixty-two patients experienced a clinical relapse and 14 occurred HBsAg loss, with 8-year cumulative rates of 56.6% and 23.4%, respectively. Time-dependent receiver operating characteristic curve analysis for sPD-1 derived 156 pg/mL, which is equivalent to the detectable threshold, as an optimal cut-off value for predicting 8-year clinical relapse. Patients with detectable sPD-1 at end of treatment (EOT) had a significant lower incidence of clinical relapse (48% vs 67%, hazard ratio [HR] 0.454, p = 0.006), but a remarkable higher probability of HBsAg loss (33.7% vs 2.4%, HR 9.17, p = 0.038), compared to those who with undetectable sPD-1, respectively. Conclusion: EOT sPD-1 levels predicted clinical relapse and HBsAg loss after treatment discontinuation and may help to guide a finite NA treatment plan for patients with chronic hepatitis B virus infection.

aMAP Score as a Predictor for Long-Term Outcomes in Patients with HBV-Related Acute-on-Chronic Liver Failure.

BACKGROUND AND AIM: The long-term outcomes of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remain not well known. This study aimed to investigate whether aMAP score can predict re-hospitalization, hepatocellular carcinoma (HCC) occurrence and long-term mortality in patients with HBV-ACLF. METHODS: A total of 82 patients diagnosed with HBV-ACLF and survived over 6 months were enrolled. The median follow-up period was 105 (75.9, 134.1) months. The Cox proportional hazards or logistic regression analysis was used to determine independent risk factors. Cumulative incidence of HCC and survival rate were evaluated using Kaplan-Meier analysis. RESULTS: Multivariate analysis identified that the aMAP risk score was an independent predictor of re-hospitalization (odds ratio [OR] = 1.112, 95% confidence interval [CI]: 1.021-1.211, p = 0.015), hepatocellular carcinoma occurrence (hazards ratio [HR] = 2.277, 95% CI: 1.014-5.114, p = 0.046) and mortality (HR = 1.366, 95% CI: 1.040-1.794, p = 0.025). High-risk aMAP scores were associated with higher risk of HCC occurrence and mortality. CONCLUSION: A higher aMAP score was an independent risk predictor of re-hospitalization, HCC occurrence and mortality, respectively, in HBV-ACLF patients who survived over 6 months, which can be applicable for early risk stratification and clinical decision.

Hepatitis B Core-Related Antigen is a Biomarker for off-Treatment Relapse After Long-Term Nucleos(t)ide Analog Therapy in Patients with Chronic Hepatitis B.

OBJECTIVE: It remains unknown how to stratify the risk of clinical relapse of chronic hepatitis B (CHB) patients after stopping nucleos(t)ide analogs (NAs) antiviral therapy. METHODS: The current post hoc analysis included 122 non-cirrhotic patients with chronic hepatitis B virus infection who were positive for hepatitis B envelope antigen (HBeAg) and discontinued long-term NA therapy after achieving HBeAg seroconversion for a median of 2.5 years. Post hoc analysis of end-of-treatment (EOT) hepatitis B core-related antigen (HBcrAg) levels was performed using a chemiluminescent enzyme immunoassay. RESULTS: A total of 78/122 (63.9%) patients experienced sustained response after NAs cessation, and 44/122 (36.1%) patients experienced clinical relapse. In multivariate analysis, EOT HBcrAg (hazard ratio [HR] = 2.105 95% CI: 1.440-3.077, p < 0.001), hepatitis B surface antigen (HBsAg) ≥100 IU/mL (HR = 4.406, 95% CI 1.567-12.389, p = 0.005) and age (HR = 1.051, 95% CI: 1.010-1.093, p = 0.049) were independently associated with clinical relapse. A cut-off value of 4.0 log10 U/mL of HBcrAg was defined by maximized Youden's index. An EOT HBcrAg level of ≥4.0 log10 U/mL was associated with higher risks of clinical relapse (65.8% vs 23.2%, p<0.001) and HBeAg reversion (27.5% vs 1.6%, p < 0.001). In majority of patients (n = 91) who had a high EOT HBsAg level (≥100 IU/mL), serum HBcrAg level could further discriminate patients at low risk of clinical relapse. Patients with an HBcrAg level ≥4.0 log10 U/mL had significantly higher cumulative incidence rates of clinical relapse (78.1% vs 29.4%, p < 0.001) and HBeAg reversion (29.4% vs 0%, p < 0.001). CONCLUSION: Serum EOT HBcrAg level can be a predictor of off-treatment relapse in patients with CHB. An HBcrAg level of 4.0 log10 U/mL may identify patients at high risk of clinical relapse after treatment cessation.

Serum hepatitis B virus RNA level is associated with biochemical relapse in patients with chronic hepatitis B infection who discontinue nucleos(t)ide analogue treatment.

BACKGROUND: Nucleos(t)ide analogue (NA) discontinuation may be attempted in carefully selected patients with chronic hepatitis B (CHB) infection. AIM: To investigate whether a novel serum marker of quantitative hepatitis B virus (HBV) RNA levels could predict biochemical relapse after NA discontinuation. METHODS: We prospepctively followed non-cirrhotic Asian patients with CHB who stopped NA according to pre-specified stopping criteria. The primary endpoint was biochemical relapse (HBV DNA >2000 IU/mL and alanine transaminase >2x upper limit of normal), which were also the re-treatment criteria. RESULTS: Biochemical relapse occurred in 50 patients (48.3% at year 6). Multivariable analysis showed that higher HBV RNA levels (HR 1.34; P < 0.001) at the time of NA discontinuation were associated with increased biochemical relapse risk. The area under the curve of HBV RNA at the time of NA discontinuation for the incidence of biochemical relapse was 0.760 at 6 years. Six years after treatment discontinuation, all patients with HBV RNA levels ≥20 000 copies/mL at the end of treatment developed a biochemical relapse compared with 23.8% of patients with HBV RNA levels<1000 copies/mL (P < 0.001). More patients with HBV RNA levels <1000 copies/mL at end of treatment achieved loss of hepatitis B surface antigen than patients with higher levels (30.9% vs 1.6%; P = 0.027). CONCLUSIONS: The HBV RNA level at end of treatment predicted biochemical relapse after treatment discontinuation and may be used to guide decisions on treatment discontinuation.

Hepatitis B surface antigen kinetics after discontinuation of and retreatment with oral antivirals in non-cirrhotic HBeAg-positive chronic hepatitis B.

The outcome of nucleos(t)ide analogues (NAs) discontinuation and retreatment is still uncertain. We evaluated hepatitis B surface antigen (HBsAg) kinetics after NAs discontinuation and during retreatment due to off-treatment clinical relapse among non-cirrhotic HBeAg-positive CHB patients. Four groups were studied: 129 HBeAg-positive patients from a prospective cohort who stopped NAs therapy after achieving sustained response (Group A), 39 patients who received retreatment after off-treatment clinical relapse in the discontinuation group (Group B), 214 patients who maintained treatment after achieving sustained response (Group C) and 291 patients who firstly initiated antiviral treatment (Group D). During a 5-year follow-up, the cumulative incidence of HBsAg loss was significantly higher in Group A than Group C (22.3% vs. 1.6%, p < .001). The quantitative HBsAg (qHBsAg) level at enrolment and NAs discontinuation were independently associated with HBsAg loss. Additionally, patients in Group B showed significantly greater HBsAg loss than those in the Groups C and D, with 5-year cumulative incidences of 9.0%, 1.6% (p = .040) and 0.6% (p < .001), respectively. Moreover, patients in the Group B exhibited better virologic response (100% vs. 98.8%, p < .001) and HBeAg seroconversion (92.6% vs. 69.8%, p < .001) than those in Group D at year 5. Propensity score-matched analysis also showed the similar trend of HBsAg decline. NAs discontinuation with or without subsequent retreatment resulted in a more profound reduction of HBsAg in non-cirrhotic HBeAg-positive patients, suggesting that discontinuation may be a potential cure strategy for those with sustained virological suppression.

Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog.

BACKGROUND AND AIM: Hepatitis B virus (HBV) RNA has attracted increasing attention as a novel serum marker for intrahepatic HBV replication. However, the predictive value of the serum level of HBV RNA for hepatitis B e-antigen (HBeAg) seroconversion and viral response among patients with a high viral load (HVL) is unclear. We evaluated the role of the serum level of HBV RNA as a predictor of treatment response in chronic HBV (CHB) patients with an HVL. PATIENTS AND METHODS: The study cohort was 66 HBeAg-positive CHB patients with an HVL (serum HBV DNA >1.9×106 IU/mL) at baseline from our previous prospective cohort study treated with lamivudine (LAM) and adefovir dipivoxil(ADV) (N=31) or entecavir alone (N=35) for ≤96 weeks. The serum HBV RNA level was quantified by TaqMan® probe-based reverse transcription real-time quantitative polymerase chain reaction at four time points. RESULTS: The baseline serum HBV RNA level (in log10 copies/mL) in patients treated with LAM+ADV and ETV monotherapy was 8.97±1.22 and 9.15±0.92, respectively. After nucleos(t)ide analog (NA) therapy, the serum HBV RNA level decreased steadily in all patients (week 0 vs week 12, p<0.001; week 12 vs week 24, p=0.010; week 24 vs week 48, p<0.001). Fifty-three (80.3%) patients achieved a virologic response (VR), and 12 (18.2%) achieved HBeAg seroconversion after 96 weeks. Multivariate analyses revealed that the serum HBV RNA level at week 12 could predict HBeAg seroconversion (OR 3.560, 95% CI: 1.39-9.110, p=0.008) and VR (1.908, 1.115-3.265, 0.018) at 96 weeks. Analyses of receiver operating characteristic curves indicated that the serum HBV RNA level 12 weeks after NA treatment had predictive value for HBeAg seroconversion (AUC=0.847, p<0.001) and VR (AUC=0.736, p=0.011). CONCLUSION: The serum level of HBV RNA at 12 weeks could predict HBeAg seroconversion and a VR during NA treatment in CHB patients with an HVL.

Genetic variations in the CXCR5 gene decrease the risk of clinical relapse after discontinuation of nucleos(t)ide analogue therapy in patients with chronic hepatitis B.

Discontinuation of nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) remains a global but controversial problem. Clinical outcomes of NA cessation depend on the interplay between viral factors and host immunity. Recent studies have shown that genetic polymorphisms might influence the immune response in chronic HBV infection. A total of 33 single-nucleotide polymorphisms (SNPs) from 16 genes (BCL6, CD40, CD40L, CTLA-4, CXCL13, CXCR5, ICOS, IL-21, HLA-C, NTCP, UBE2L3, STAT4, IFN-λ3, CYP27B1, INST10, and IPS1) were selected and analyzed in 106 CHB patients enrolled in an off-treatment cohort. Significantly unbalanced distributions between patients who experienced clinical relapse and those who did not were found regarding two SNPs, rs676925 in CXCR5 and rs733618 in CTLA-4. Furthermore, the genotype 'GC' of rs676925 were associated with decreased risk of clinical relapse, implicating that rs676925 may serve as a protective factor for HBV control and facilitate a virus-specific immune response. We also compared the expression of CXCR5 in lymphocytes and its ligand CXCL13 in plasma between different genotypes of rs676925. However, no significant differences were observed. In conclusion, this study suggested that the rs676925 'GC' genotype of the CXCR5 gene were associated with decreased risk of clinical relapse after discontinuation of long-term NA therapy in CHB patients.

Elevated expression of serum soluble ST2 in clinical relapse after stopping long-term Nucleos(t)ide analogue therapy for chronic hepatitis B.

BACKGROUND: The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown. METHODS: A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups. RESULTS: Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy. CONCLUSIONS: In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment. TRIAL REGISTRATION: The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970 . Registration date: December 15, 2017.

Circulating miR-122 Is a Predictor for Virological Response in CHB Patients With High Viral Load Treated With Nucleos(t)ide Analogs.

Chronic hepatitis B (CHB) infection remains worldwide health problem. Antiviral treatment options for CHB patients include nucleos(t)ide analogs (NAs) and interferon. Most of the current biomarkers for predicting treatment response are virus-dependent. MicroRNA-122 is the most abundant liver-specific miRNA and has been identified involved in multiple liver physiology and pathology including hepatotropic virus infection. To identify the role of miR-122 in NA therapy, 80 CHB patients with high viral load (HVL) were enrolled and serum miR-122 levels at baseline, week 12 and week 24 were measured. Serum miR-122 levels were significantly lower in patients who developed virological response (VR), compared with non-VR group. Levels of miR-122 at week 12 and week 24 were determined to be independent prognostic indicators for a VR with satisfactory AUROC values at 0.812 and 0.800, respectively. During NA therapy, serum miR-122 level deceased steadily and an earlier reduction was observed in VR group, indicating early reduction of miR-122 level might increase the possibility of developing virological response. In conclusion, we identified the dynamic change of serum miR-122 level and miR-122 levels at week 12 and week 24 as independent predictors for VR in CHB patients with HVL treated with NAs.

Plasma CXCL13 is a predictive factor for HBsAg loss and clinical relapse after discontinuation of nucleos(t)ide analogue treatment.

In this study, we investigated whether plasma cytokine/chemokine levels could predict HBsAg loss or clinical relapse (CR) after stopping nucleos(t)ides analogue (NA) treatment. Theplasma cytokines/chemokines levels were measured at 0, 4, 8, 12, 24 and 48 weeks after NA discontinuation by using the enzyme-linked immunoassay (ELISA) kit. Cox regression analysis revealed that CXCL13 level at the end of treatment (EOT) was an independent predictor for CR (HR 0.26, p < 0.001) and HBsAg loss (HR 3.01, p = 0.008) after treatment cessation. Among the patients with EOT CXCL13 level < 80 pg/ml, the cumulative incidences of CR and HBsAg loss were 65% and 0% at 4 years, respectively. As for the patients with EOT CXCL13 level ≥ 1000 pg/ml, 47.5% cases had HBsAg loss. Our study showed that EOT CXCL13 level was associated with off-treatment response, which may be used to guide cessation of NA treatment in clinical practice.

Serum hepatitis B core antibody levels predict HBeAg seroconversion in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analogs.

BACKGROUND: Patients with chronic hepatitis B virus (HBV) infection who are hepatitis B virus e antigen (HBeAg) positive are increasingly being treated with nucleos(t)ide analogs (NUCs). However, the predictive value of serum hepatitis B virus core antibody (HBcAb) levels for HBeAg seroconversion among patients with high viral load remains unclear. METHODS: This study consisted of 74 patients with high viral load (HBV DNA >1 × 107 copies/mL) enrolled in a multicenter, randomized, controlled trial, treated with lamivudine and adefovir (N = 32) or entecavir (N = 42) for up to 96 weeks. Serum HBV DNA, quantitative hepatitis B virus surface antigen (HBsAg), HBeAg, and HBeAb was tested at each visit. Quantitative HBcAb evaluation was conducted for all the available samples in the trial, by using a newly developed double-sandwich anti-HBc immunoassay. RESULTS: Serum HBcAb levels were significantly higher in patients with a serum alanine aminotransferase (ALT) level more than five times the upper limit of normal (ULN) compared with patients with ALT levels within 5 × ULN (4.25 ± 0.61 vs. 3.94 ± 0.47 log10 IU/mL, P = 0.0345). Patients with HBeAg seroconversion were associated with a higher level of HBcAb at baseline, compared with those without HBeAg seroconversion (4.38 ± 0.54 vs. 4.02 ± 0.58 log10 IU/mL, P = 0.029). The area under receiver operating characteristic curve of baseline HBcAb for HBeAg seroconversion was 0.71 (95% CI: 0.55-0.86, P = 0.013). When the baseline HBcAb level was >4.375 log10 IU/mL, the sensitivity and specificity to predict HBeAg seroconversion at week 96 were 62.5% and 74.2%, and the positive likelihood ratio (LR) and negative LR were 2.42 and 0.51, respectively. The multivariate analysis result indicated that baseline serum HBcAb level was the only independent predictor for HBeAg seroconversion at week 96, with an odds ratio of 4.78. CONCLUSION: Baseline serum HBcAb level >4.375 log10 IU/mL could satisfactorily predict HBeAg seroconversion among patients with high viral load treated with NUC.

Effectiveness of entecavir or telbivudine therapy in patients with chronic hepatitis B virus infection pre-treated with interferon compared with de novo therapy with entecavir and telbivudine.

Little is known about the optimal treatment following the initial failure of interferon therapy and the potential different efficacy with de novo therapy with entecavir (ETV) or telbivudine (LDT) and following the interferon therapy failure.ETV or LDT therapy following the interferon therapy failure was compared with that of de novo therapy with ETV or LDT in patients with chronic hepatitis B virus (HBV) infection. Treatment parameters included virological response, hepatitis B e antigen (HBeAg) seroconversion, and alanine aminotransferase (ALT) normalization.Of 180 patients studied, 56 received de novo telbivudine monotherapy (LDT group); 45 received entecavir monotherapy (ETV group); 40 received LDT following interferon (interferon-telbivudine [IFN-LDT] group); and 39 received ETV following interferon (interferon-entecavir [IFN-ETV] group). At week 52, virological response occurred in significantly more patients in the IFN-ETV group than the ETV group (87.2% vs 57.8%, P = .003). At week 104, HBeAg seroconversion occurred in significantly more patients in the IFN-ETV group than the ETV group (44.4% vs 22.2%, P = .03). At week 52, virological response was achieved by significantly more patients in the IFN-LDT group than the LDT group (85.0% vs 64.3%, P = .02).This study showed that switch to rescue therapy with ETV or LDT therapy after failure of interferon therapy resulted in more rapid virologic response than with de novo treatment with either ETV or LDT; rescue therapy with ETV resulted in a greater HBeAg seroconversion rate.

A noninvasive diagnostic model to assess nonalcoholic hepatic steatosis in patients with chronic hepatitis B.

OBJECTIVE: The objective of this study was to develop a noninvasive diagnostic test for nonalcoholic hepatic steatosis in patients with chronic hepatitis B (CHB) by using routinely available clinical markers. METHODS: A retrospective study of patients with CHB, with or without hepatic steatosis (fatty change) who were diagnosed with controlled attenuation parameter (CAP) measured by transient elastography were included. Patient information was analyzed on lifestyle; laboratory tests, including serum lipid levels; blood pressure; blood uric acid; and medical history of type 2 diabetes mellitus (T2DM). RESULTS: A total of 1312 patients were included in the study; 618 patients had confirmed hepatic steatosis. The CAP levels were significantly correlated with patient height (p < 0.001), weight (p < 0.001), waistline measurement (p < 0.001), hipline measurement (p < 0.001), and diastolic blood pressure (DBP) (p < 0.001). Multivariate logistic regression analysis resulted in the development of an equation for the diagnostic of simple steatosis: the fatty liver (FL) test. The area under the receiver operating characteristic (AUROC) curve of the FL test was 0.79 (p < 0.001) in the training group and 0.82 in the validation group. When the FL test was >-0.425, the sensitivity, specificity, positive likelihood ratio (LR) and negative LR were 74.72%, 72.12%, 2.68, and 0.35 respectively. The average FL test result was -0.54 ± 1.26 in patients with CHB without hypertension, and 0.42 ± 1.35, 1.12 ± 1.65, and 1.98 ± 1.22 in patients with hypertension grade 1, 2, and 3, respectively (p < 0.001). CONCLUSION: This study has demonstrated a noninvasive test for hepatic steatosis in patients with CHB.