Serum HBV RNA Research Articles

Kinetics of Hepatitis B Virus replication in anti-HBc positive/HBsAg-negative people with HIV switching to Tenofovir sparing therapy

Objectives: To unravel the still unexplored HBV-replicative kinetics in antiHBc-positive/HBsAg-negative people-with-HIV (PWH) suspending TDF/TAF. Methods: 101 antiHBc-positive/HBsAg-negative PWH switching to TDF/TAF-sparing therapy were included. Serum HBV-DNA and HBV-RNA were quantified by droplet-digital-PCR at switching (T0), within 12-months (T1) and 12-24 months post-switch (T2). Results: At T0, 33.7% had cryptic HBV-DNA (undetected by commercial assays, median[IQR]:2[1-5]IU/ml) and 22% were positive to HBV-RNA alone (median[IQR]:4[3-4]IU/ml), indicating an active HBV-reservoir despite HBsAg-negativity and TDF/TAF-pressure. Notably, antiHBs-titer<100mIU/ml independently correlated with cryptic HBV-DNA at T0 (OR[95%CI]:2.6[1.02-6.5], P=0.04). After TDF/TAF-withdrawal, the rate of PWH achieving HBV-DNA>10IU/ml increased from 12.9% at T1 to 42.6% at T2 (P<0.0001). Likewise, a rise from 2% to 11% was observed for HBV-DNA>100IU/ml (P=0.02); median(IQR) HBV-DNA: 579(425-770)IU/ml. Notably, HBV-DNA>10IU/ml at T2 occurred in 70% of PWH with cryptic HBV-DNA, in 38.5% with HBV-RNA alone and in 25% negative to both HBV-markers at T0 (P=0.01). Cryptic HBV-DNA at T0 and lower nadir CD4+T-cell-count independently predicted HBV-DNA>10IU/ml at T2 (OR[95%CI]:8.2[1.7-40.6], P=0.01; OR[95%CI]:8.1[1.3-52.1], P=0.03). Lastly, persistent HBV-DNA positivity was independently associated with a reduced CD4+T-cell recovery at T2 (OR[95%CI]:0.07[0.01-0.77], P=0.03). Conclusions: This study underlines the importance to regularly monitor antiHBc-positive/HBsAg-negative PWH undergoing TDF/TAF-sparing regimen and the role of highly-sensitive HBV markers in optimizing their management.

High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy.

Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core-related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation. Patients with HBeAg-negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation. End of treatment (EOT) and off-treatment levels of serum HBcrAg, HBsAg, HBV RNA and HBV DNA were used to predict key clinical outcomes including hepatitis flare (ALT ≥5 × ULN and HBV DNA > 2000 IU/mL). The SCALE-B score was calculated for the purposes of model validation. HBcrAg was tested amongst 65 participants. The median age was 54 years, 54% were male and 83% were Asian. HBcrAg was detectable in 86% patients. HBcrAg level ≥4 log U/mL at EOT was predictive of hepatitis flare [8/10 (80%) vs. 17/55 (31%), p = .001]. The presence of either HBcrAg ≥4 log U/mL or detectable HBV RNA at EOT predicted for both biochemical relapse and hepatitis flare. The SCALE-B model at EOT predicted for virological relapse, biochemical relapse, hepatitis flare and HBsAg loss in this cohort. An increase in the serum HBcrAg level off-treatment was also associated with hepatitis flare. No participant with EOT HBcrAg level ≥4 log U/mL achieved HBsAg loss. High levels of serum HBcrAg predict for hepatitis flare after stopping NA therapy and low likelihood of HBsAg loss at week 96. People with high levels of serum HBcrAg are not suitable candidates for NA discontinuation.

Relationship Between Serum HBV-RNA Levels, Sero-biochemical Indices, and Clinicopathological Parameters in Patients with Hepatitis B Virus

Background: Studies have indicated that HBV RNA exhibits a distinct profile, and the plasma amino acid profile significantly correlates with the different stages of HBV infection. Objectives: This study investigates the relationship between HBV RNA and the plasma amino acid profile and the levels of HBeAg, HBsAg, HBV DNA levels, and other clinical indexes in diagnosing chronic HBV infection diseases. Methods: In this observational study, a total of 155 patients were included. They were categorized as Hepatitis B virus carriers, chronic Hepatitis B (CHB), Hepatitis B-related cirrhosis, and hepatocellular carcinoma patients. Following routine laboratory techniques, the DNA, RNA, serological indexes (HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb), biochemical indexes (ALT, AST), and the concentration of amino acids were determined from the serum. Results: Any relationship between different parameters considered was determined with the chi-square test, correlation, and multivariate logistic regression analysis. We observed that the HBV DNA and RNA levels were significantly higher in patients with chronic Hepatitis B compared to other groups (P &lt; 0.01). The HBV RNA levels significantly correlated with methionine levels (P &lt; 0.05) and not with other amino acids considered in this study. Further, the HBV DNA levels emerged as an independent risk factor for HBV RNA levels, and the area under the ROC curve was 0.840 (P &lt; 0.01) when the levels of HBV RNA, HBV DNA, and methionine were combined to diagnose chronic Hepatitis B. Conclusions: Our study shows that the levels of HBV RNA are correlated with methionine metabolism levels, and this relationship can be used to diagnose and predict the efficacy of treatment for different stages of HepatitisHepatitis B virus infectious diseases.

Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B.

This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.

Steady Decline of HBV DNA Load under NAs in Lymphoma Patients and a Higher Level of qAnti-HBc Predict HBV Reactivation.

Background: Patients with lymphoma and chronic hepatitis B virus infection need to be treated with both chemotherapy and nucleotide analogue (NA) therapy. However, dynamic changes in HBV DNA loads with increasing chemotherapy cycles are lacking. It is unknown whether HBV replication markers, namely, the quantitative hepatitis B core antibody (qAnti-HBc), HBV RNA, and the hepatitis B virus core-related antigen (HBcrAg), are also markers for predicting HBV reactivation (HBVr). Methods: From 29 June 2010 to 6 December 2021, the data of patients with single-site diffuse large B-cell lymphoma and HBV infection (HBsAg+ and HBsAg-/anti-HBc+) were collected from a hospital medical record system, retrospectively. Serum HBV DNA loads (using real-time fluorescent quantitative PCR tests), qAnti-HBc levels (using a newly developed chemiluminescent particle immunoassay), HBV RNA levels (using the simultaneous amplification testing method based on real-time fluorescence detection), and HBcrAg levels (using a Lumipulse G HBcrAg assay) were tested, and factors related to HBVr were analyzed. Results: Under NAs, the HBV DNA loads of 69 HBsAg+ lymphoma patients declined from 3.15 (2.13-4.73) lg IU/mL to 1.00 (1.00-1.75) lg IU/mL, and further declined to 1.00 (1.00-1.04) lg IU/mL at the end of a 24-month follow-up. The qAnti-HBc levels decreased gradually during chemotherapy in HBsAg+ lymphoma patients (F = 7.090, p = 0.009). The HBV RNA and HBcrAg levels remained stable. A multivariate analysis revealed that higher qAnti-HBc levels (1.97 ± 1.20 vs. 1.12 ± 0.84 lg IU/mL, OR = 6.369, [95% CI: 1.523-26.641], p = 0.011) and higher HBV RNA levels (1.00 ± 1.13 vs. 0.37 ± 0.80 lg copies/mL, OR = 3.299, [95% CI: 1.229-8.854], p = 0.018) were related to HBVr in HBsAg-/anti-HBc+ lymphoma patients. Conclusions: HBV DNA loads declined under NAs during chemotherapy in lymphoma patients. In HBsAg-/anti-HBc+ lymphoma patients, a higher level of baseline serum qAnti-HBc and HBV RNA levels can predict the likelihood of HBVr during chemotherapy.

Study of the predictive role of serum HBV RNA on HBeAg serological conversion in children with chronic hepatitis B

Objective: To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B. Methods: 175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC). Results: The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion: HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

Interpreting Serogical Markers in Hepatitis B Virus Infection

Abstract Hepatitis B virus (HBV) is considered a global health-related problem. The World Health Organization estimates an incidence of approximately 1.5 million new cases annually despite an available effective vaccine, and approximately 296 million people worldwide are living with chronic hepatitis B. This large number of patients require continuous monitoring of the treatment efficacy, disease progression, and screening for the HBV-related liver complications. Recently, it has become more evident that we need better predictive markers to allow treatment cessation when there is a reduced risk of viral reactivation, in addition to the present need to predict disease outcome and improve the management of people living with chronic hepatitis B. Novel HBV biomarkers are focused on in this minireview. These new markers include quantification of serum HBV RNA, hepatitis B core–related antigen, quantitative hepatitis B surface antigen, quantitative anti–hepatitis B core antigen, and detection of HBV nucleic acid–related antigen. The target of finding new markers for HBV replication is to provide crucial clinical data in a noninvasive way for detecting the replicative and transcriptional activity of the virus. This may support better management of patients compared with the criterion-standard invasive marker for detecting the intrahepatic replication and transcription of HBV, which is the quantification of covalently closed circular DNA.

Serum HBV RNA levels among untreated adults with chronic hepatitis B in distinct immune phases and liver histopathology statuses.

HBV RNA is a novel serum biomarker that reflects intrahepatic HBV covalently closed circular DNA (cccDNA) transcription activity. Serum HBV RNA levels among treatment-naïve adults during the natural history of chronic hepatitis B (CHB) and distinct liver histopathology statuses remain elusive. In our study, we include a total of 411 treatment-naïve CHB patients, among which 43 patients were HBeAg-positive immune-tolerant [IT(e+)], 84 patients were HBeAg-positive immune active [IA(e+)], 65 patients in HBeAg-negative immune active phases [IA(e-)], 149 patients were HBeAg-negative inactive phases [IC(e-)], and 70 patients were in Gray Zone (GZ). HBV RNA was measured in this cohort and its potential correlation with traditional serological markers and liver histopathology were analyzed. Our data showed that HBV RNA was strongly correlated with HBV DNA, HBeAg, HBsAg and ALT. Further subgroup analysis revealed a close correlation between HBV RNA and HBV DNA in patients in the IA (e+) and IA (e-) phases, but neither in IT(e+) nor IC(e-) phase. HBV RNA levels were consistently increased with the advanced degrees of hepatic inflammation, but not hepatic fibrosis. Of note, HBV RNA from HBeAg-positive patients negatively correlated with liver fibrosis, whereas HBV RNA from HBeAg-negative patients was weakly associated with liver inflammation. To sum up, serum HBV RNA shows a distinct profile among CHB patients in different immune statuses and hepatic histopathology stages/grades. Simultaneous testing of HBV RNA and traditional indicators might provide a comprehensive clinical assessment of CHB patients.

Serum HBV RNA: a promising biomarker for blood product safety screening and enhanced diagnostic efficiency in chronic hepatitis B virus infection.

Serum HBV RNA: a promising biomarker for blood product safety screening and enhanced diagnostic efficiency in chronic hepatitis B virus infection.

STUDY ON CHANGES IN SERUM HBV RNA LEVELS IN PATIENTS WITH CHRONIC HEPATITIS B TREATED WITH TENOFOVIR DISOPROXIL FUMARATE

Objectives: To determine the changes in serum HBV RNA levels in treatment-naïve chronic hepatitis B (CHB) patients who were treated with Tenofovir Disoproxil Fumarate (TDF). Methods: 77 treatment-naïve CHB patients were treated with long-term TDF monotherapy at the Department of Infectious Diseases, Military Hospital 103, Vietnam Military Medical University from 2017 to 2020. Samples were collected at several time points: At the baseline, after 3, 6, 9, and 12 months of TDF treatment. Serum HBV DNA and HBV RNA levels were quantified by the Real Time RT-PCR method. Statistical analyses were performed with Medcalc 20.019. Results: Serum HBV RNA levels tended to decrease during the TDF treatment in a biphasic pattern. In the first phase, from baseline to 3 months of treatment, HBV RNA levels decreased rapidly (the median slope of the decrease was 0.38 log copies/mL/month). In the second phase, from 3 - 12 months of treatment, serum HBV RNA levels decreased more slowly than in the first phase (the median slope of the decrease was 0.09 log copies/mL/month; p &lt; 0.05). Serum HBV RNA levels decreased more slowly than serum HBV DNA levels in the first phase, but there was no significant difference in the second phase (p &gt; 0.05). Conclusion: Serum HBV RNA levels decreased in a biphasic pattern with a different slope during TDF treatment. Serum HBV RNA levels decreased more slowly than HBV DNA and may complement this marker in the assessment of treatment outcomes and prognosis for chronic hepatitis B.

Serum HBsAg and HBcrAg is associated with inflammation in HBeAg-positive chronic hepatitis B patients.

Liver inflammation is the main risk factor for developing liver fibrosis, cirrhosis, and even hepatocellular carcinoma in chronic hepatitis B (CHB) patients. To replace biopsy, additional non-invasive biomarkers to diagnose and grade liver necroinflammation are urgently required in clinical practice. Ninety-four CHB patients, including 74 HBeAg-positive and 20 HBeAg-negative patients, were enrolled and started entecavir or adefovir therapy. Serum HBV RNA, HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), ALT and AST levels, as well as intrahepatic HBV DNA and cccDNA were measured at baseline and during treatment. Liver inflammation was assessed at baseline and month 60 by liver biopsy. Inflammation regression was defined as a ≥1-grade decrease according to the Scheuer scoring system. In HBeAg-positive CHB patients, at baseline, serum HBsAg and HBcrAg levels negatively correlated with inflammation grade, while ALT and AST levels positively correlated with inflammation grade. AST plus HBsAg exhibited excellent diagnostic ability for significant inflammation with an AUROC of 0.896. After 60 months of antiviral treatment, almost all the patients' liver inflammation ameliorated to G1, and no patients had inflammation progression. Besides ALT and AST, serum HBsAg and HBcrAg correlated with inflammation grade in HBeAg-positive CHB patients before NAs treatment. Moreover, the combination of HBsAg and AST exhibited excellent diagnostic ability for significant inflammation.

Serum HBV RNA is associated with liver fibrosis regression in HBeAg-positive chronic hepatitis B patients treated with nucleos(t)ide analogues.

Noninvasive methods for assessing hepatic fibrosis are clinically necessary. This study aims to explore HBV markers correlated with liver fibrosis and capable of diagnosing significant fibrosis and predicting fibrosis regression. Seventy-four HBeAg-positive chronic hepatitis B (CHB) patients were enrolled and started on entecavir or adefovir therapy. Serum HBV RNA, HBV DNA, HBsAg and hepatitis B core-related antigen (HBcrAg) levels were measured at baseline and during treatment. Liver fibrosis was assessed at baseline and month 60 by liver biopsy. Fibrosis regression was defined as Ishak fibrosis score decreased ≥1-point. At baseline, HBsAg, HBcrAg and HBV RNA levels had a stronger correlation with Ishak fibrosis score (r=-.441, p=.002; r=-.469, p=.001; r=-.398, p=.001) than APRI and FIB-4 (r=.321 p=.006; r=.371, p=.001). HBsAg >4 log10 IU/ml plus HBcrAg >7 log10 IU/ml or HBsAg >4 log10 IU/ml plus HBV RNA >5 log10 copies/ml exhibited the same excellent diagnostic ability for significant fibrosis with the AUROC of 0.857. After 60 months of antiviral treatment, 66.7% of patients who suffered significant fibrosis at baseline achieved fibrosis regression, and an HBV RNA decline from baseline to month 6 greater than 0.63 log10 copies/ml could predict the fibrosis regression at month 60. In conclusion, serum HBsAg, HBcrAg and HBV RNA are potential markers for predicting significant liver fibrosis. HBV RNA measurement would be particularly useful for monitoring hepatic fibrosis changes in HBeAg-positive CHB patients.

The predictive effect of serum HBV-RNA and HBcrAg on the disease changes in patients with chronic hepatitis B

The predictive effect of serum HBV-RNA and HBcrAg on the disease changes in patients with chronic hepatitis B

Evidence of Residual Ongoing Viral Replication in Chronic Hepatitis B Patients Successfully Treated With Nucleos(t)ide Analogues.

Chronic hepatitis B is usually treated with nucleos(t)ide analogues (NAs). However, a cure is rarely achieved, even with years of treatment. Here, we investigated whether viral replication is completely halted and how long covalently closed circular DNA (cccDNA) persists in patients successfully treated with NAs. A series of longitudinal serum samples and a collection of cross-sectional liver biopsies were obtained from patients successfully treated with NAs. Viral variants in serum HBV RNA were enumerated by deep sequencing. Viral replication intermediates in hepatocytes were directly visualized by in situ hybridization. The apparent half-life of each cccDNA was estimated. Three of 6 successfully treated patients demonstrated clear evidence of a small proportion of virus evolution, although the overwhelming proportion of variants were identical or possessed a similar degree of divergence through time. The apparent half-life of variants was estimated to be from approximately 7.42 weeks to infinite. Hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA in 4 of 7 liver needle biopsies. We conclude that even after prolonged treatment, a small proportion of the cccDNA reservoir is constantly replenished by continued low-level HBV replication, whereas a large proportion of the cccDNA reservoir persists over time.

Levels of HBV RNA in chronic HBV infected patients during first-line nucleos(t)ide analogues therapy

BackgroundSerum HBV RNA has been considered a potential biomarker in monitoring the prognosis of chronic hepatitis B (CHB). However, Real-life cohort studies on the profile of HBV RNA in chronic HBV infected patients during first-line nucleos(t)ide analogues (NAs) are lacking. We aimed to investigate HBV RNA dynamic pattern and clinical value chronic HBV infected patients under NA therapy.MethodsHBV RNA and clinical assessments were measured in 82 treatment-naïve chronic HBV infected patients. These enrolled patients were categorized into HBeAg-positive chronic HBV infected (n = 53) and HBeAg-negative chronic HBV infected (n = 29). Of these, there were 59, 46, and 30 chronic HBV infected patients completed the follow-up clinical assessments at 12, 24, and 48 weeks of NAs therapy, respectively.ResultsIn treatment-naïve patients, there was a positive correlation between HBV RNA and HBV DNA, HBsAg (r = 0.602 and 0.502. P < 0.05). The median level of HBV DNA was higher than HBV RNA by 1.64 log10 copies/mL. The mean level of serum HBV RNA was 4.62 (IQR: 3.05–5.82) log10 copies/mL at baseline, and the median level of HBV RNA was 2.88 (IQR: 0–4.67), 2.71 (IQR: 0–4.22), and 2.96 (IQR: 0–4.32) log10 copies/mL at week 12, 24, and 48, respectively. HBV RNA showed a positive linear correlation with HBV DNA at 12, 24, and 48 weeks of NA treatment (r = 0.640, 0.715, and 0.656 respectively, P < 0.05). In patients who were treated 48 weeks NAs, 67% had quantifiable HBV RNA while only 37% had quantifiable HBV DNA.ConclusionHBV RNA has signature profiles in different stages of chronic HBV infected patients receiving first-line NAs. During antiviral treatment, HBV RNA can still monitor the virus activity in patients whose serum HBV DNA cannot be detected.

Serum HBV RNA as a predictor of virological response in treatment-naive chronic HBeAg-positive HBV-infected patients with normal alanine aminotransferase.

Serum HBV RNA as a predictor of virological response in treatment-naive chronic HBeAg-positive HBV-infected patients with normal alanine aminotransferase.

The Prognostic Value of Serum HBV-RNA during Hepatitis B Virus Infection is Related to Acute-on-Chronic Liver Failure.

Background Serum HBV-RNA levels can predict antiviral response in chronic hepatitis B (CHB) patients; however, its role in HBV-related ACLF (HBV-ACLF) remains unclear. Here, we determined its implications for HBV-ACLF. Methods Baseline serum HBV-RNA levels were retrospectively detected in HBV-ACLF and CHB patients. The association of serum HBV-RNA level with clinical outcomes was evaluated by performing multiple logistic regression. A nomogram was developed to formulate an algorithm incorporating serum HBV-RNA for predicting the survival of HBV-ACLF patients. After being discharged from the hospital, the HBV-ACLF patients were followed up for 36 weeks. Results In this study, 82 HBV-ACLF patients and 33 CHB patients were included. Serum HBV-RNA levels were significantly higher in CHB patients than in HBV-ACLF patients (4.15 ± 2.63 log10 copies/mL VS 5.37 ± 2.02 log10 copies/mL) (P < 0.05). Among the HBV-ACLF cases, patients with poor outcomes had lower serum HBV-RNA levels, but the difference was not significant. The area under the receiver operating characteristic curve of the serum HBV-RNA inclusive model was 0.745, superior to 0.66 from MELD scores (P < 0.05). During the follow-up for four weeks, the serum HBV-RNA levels, especially in the survival group, were found to be lower than the baseline levels. Conclusions Serum HBV-RNA levels were associated with disease severity and might predict the long-term clinical outcome of HBV-ACLF patients.

Significance of serum HBV RNA in non-cirrhotic HBeAg-negative chronic hepatitis B patients who discontinue effective antiviral therapy.

HBV RNA is considered as a promising predictor in patients who discontinue nucleos(t)ide analogues (NAs). We determined HBV RNA levels in non-cirrhotic HBeAg-negative patients who discontinued NAs and assessed their predictability for 12-month outcomes. Fifty-seven patients of DARING-B study were included. HBV RNA levels were determined in stored monthly serum samples drawn at 0-3months after end of therapy (EOT). Other markers previously determined in the same cohort including hepatitis B core-related antigen (HBcrAg) were also assessed. HBV RNA at EOT was detectable in 7% of patients, who developed virological/clinical relapse and required retreatment at month 2; in patients with undetectable EOT HBV RNA, 12-month cumulative rates of virological relapse, clinical relapse and retreatment were 68%, 28% and 21%, respectively (p ≤ 0.008). HBV RNA at month-1 after EOT was detectable in 19% of patients being associated with higher probability only of virological relapse (p=0.001). HBV RNA levels correlated significantly to HBV DNA, HBcrAg, ALT and interferon-induced protein-10, but not HBsAg levels. Combined EOT HBV RNA and HBcrAg detection and/or HBsAg >1000 IU/ml was associated only with higher probability of retreatment having higher sensitivity and lower specificity than HBV RNA alone. In conclusion, serum HBV RNA is detectable in a minority of non-cirrhotic HBeAg-negative patients under effective long-term NAs therapy offering low sensitivity but 100% specificity for early retreatment due to severe clinical relapses after NA discontinuation. The combinations of EOT HBV RNA with HBcrAg and/or high HBsAg levels increase sensitivity but decrease specificity for prediction of retreatment after NAs withdrawal.

Predictive value of serum HBV RNA for therapeutic effect of entecavir in patients with chronic hepatitis B

To investigate the value of HBV RNA for predicting the therapeutic effect of long-term entecavir (ETV) antiviral therapy in patients with chronic hepatitis B (CHB). Serum samples were collected from 59 CHB patients treated with ETV for 96 or 108 months. HBV RNA levels, HBV DNA levels, and serological marker (HBeAg) levels were measured at baseline and 3, 6, 9, 12, 36, 72, and 96 (or 108) months during the therapy. Although HBV RNA level decreased after 12 and 36 months of ETV antiviral therapy, no significance changes occurred in HBV RNA negative conversion rate (P>0.05). After 72 months of treatment or longer, 33 patients had HBV RNA levels lower than 100 copies/mL, and among them 29 patients had HBV RNA levels lower than the detection limit, and HBV RNA negative conversion rate was statistically significant (P < 0.05). A lower HBV RNA level was associated with a higher HBeAg negative conversion rate (P < 0.05). Age and HBV RNA level were positively correlated with HBeAg negative conversion rate (P < 0.05). Prolonged ETV antiviral therapy results in better clearance of HBV RNA and a higher negative conversion rate in CHB patients. The length of antiviral therapy and age are positively correlated with the negative conversion rate of HBV RNA, and earlier administration of the antiviral treatment achieves better therapeutic effect. Serum HBV RNA level can be used as an indicator for predicting conversion to negative HBeAg in CHB patients receiving ETV therapy.

HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy.

Liver injury may persist in patients with HBV receiving antiviral therapy who have ongoing transcription and translation. We sought to assess ongoing HBV transcription by serum HBV RNA, translation by serum hepatitis B core related antigen (HBcrAg), and their associations with hepatic HBsAg and HBcAg staining in patients coinfected with HBV and HIV. This is a cross-sectional study of 110 adults coinfected with HBV and HIV who underwent clinical assessment and liver biopsy. Immunohistochemistry (IHC) was performed for HBsAg and HBcAg. Viral biomarkers included quantitative HBsAg, HBV RNA, and HBcrAg. Participants' median age was 49 years (male, 93%; Black, 51%; HBeAg+, 65%), with suppressed HBV DNA (79%) and undetectable HIV RNA (77%) on dually active antiretroviral therapy. Overall, HBV RNA and HBcrAg were quantifiable in 81% and 83%, respectively (96% and 100% in HBeAg+, respectively). HBcAg staining was detected in 60% and HBsAg in 79%. Higher HBV RNA was associated with higher HBcAg and HBsAg IHC grades (both p < 0.0001). The HBsAg membranous staining pattern was significantly associated with higher HBV-RNA and HBcrAg levels. HBcAg and HBsAg IHC staining persisted despite viral suppression, and IHC grades and staining patterns correlated with markers of transcription (HBV RNA) and translation (HBcrAg). These data indicate that apparent HBV suppression is associated with residual transcription and translation that could contribute to liver pathology. Additional antiviral strategies directed to HBV protein expression may be useful to ameliorate liver injury.