Serum HBV RNA Dynamic and Drug Withdrawal Predictor Value in Patients With Chronic HBV Infection on Long-term Nucleos(t)ide Analogue (NA) Therapy.

AIMS: This study aimed to investigate the dynamic pattern of serum hepatitis B virus (HBV) RNA in chronic hepatitis B (CHB) patients on long-term nucleos(t)ide analogue (NA) therapy and evaluate predictor value of end-of-treatment (EOT) serum HBV RNA status on drug-withdrawal durability. METHODS: We carried out a real-life cohort study of 326 CHB patients on NA treatment between February 12, 2016 and February 21, 2018. Thirty of these patients discontinued NA treatment after enrollment, and were included in 2-year off-therapy follow-up. Serum HBV RNA levels were determined using the RNA simultaneous amplification testing method. RESULTS: Both serum HBV RNA and DNA levels declined significantly in long-term antiviral progress. When the treatment duration was longer than 3 years, the undetectable rates of HBV RNA and DNA were 55.10% and 97.0%, respectively. The serum HBV RNA-negative rate was 39.5%. The cumulative 2-year off-therapy viral and clinical relapse rate was 40.56%; 95% confidence interval (95% CI), 21.51-59.61 and 31.31%; 95% CI, 11.32-51.29 in all patients, respectively. Patients with EOT hepatitis B surface antigen (HBsAg)≤1000 IU/mL plus HBV RNA negativity had a relatively lower cumulative 2-year off-therapy viral relapse rate (23.01%; 95% CI, 0.17-45.99). EOT HBsAg≤1000 IU/mL plus HBV RNA negativity showed obvious superiority for the EOT HBsAg≤1000 IU/mL single in drug withdrawal durability prediction, with better specificity (18.18% vs. 72.73%, P=0.03), and the positive predictive value and negative predictive value were 76.92% and 47.06%, respectively. CONCLUSIONS: In the long-term antiviral process, both serum HBV RNA and DNA levels declined significantly. EOT serum HBV RNA negativity was not an independent drug withdrawal marker, but can complement the HBsAg titer to monitor drug withdrawal in CHB patients on long-term NA therapy.

Hepatocellular carcinoma with worsened hypoglycemia after transarterial chemoembolization: a case report and systematic review.

Non-islet cell tumor hypoglycemia (NICTH) is an extremely uncommon and serious complication of hepatocellular carcinoma (HCC). Here, we reported a case of a 47-year-old male patient with moderate to poorly differentiated HCC complicated by hypoglycemia that worsened after transarterial chemoembolization (TACE). The patient was admitted into The First Affiliated Hospital of Naval Medical University due to fatigue, nausea, dizziness and passage of tea colored urine. He was diagnosed with NICTH induced by HCC according to CT scanning and laboratory tests. TACE was used as the primary therapy but the hypoglycemia worsened afterward. Then the patient received a liver transplantation as a possible radical cure and hypoglycemia was resolved. We systematically review the management of hypoglycemia caused by HCC and the results show that patients undergoing treatment that mainly alleviate tumor burdens obtained a significantly higher response rate than patients undergoing therapies mainly regulating biologic functions (50.0% vs 27.3%). Cytoreductive surgery, TACE and radiotherapy which aimed to alleviate tumor burdens are effective therapies have great potential, but the risk of hypoglycemic deterioration requires particular attention when using these treatments, especially with TACE.

Correction to: Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection.

Following publication of the original article [1].

Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection.

BACKGROUND: As an alternative biomarker of intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B virus (HBV) RNA may evolve during long-lasting virus-host interactions during chronic hepatitis B viral infection. The distribution pattern of serum HBV RNA levels in the natural course of chronic HBV infection remains unclear. The aim of this study was to evaluate the levels of HBV RNA during the natural course of CHB and the role in distinguishing the natural history of HBV infection. METHODS: A total of 291 treatment-naïve chronic HBV carriers were enrolled. Based on the clinical, biochemical, serological, and histological data as well as HBV DNA levels, patients were classified into the following four categories: the immune-tolerant phase (IT,n = 35), HBeAg-positive immune-active phase (EPIA,n = 121), inactive chronic hepatitis B(ICH,n = 77) and HBeAg-negative immune reactive hepatitis (ENH,n = 58) [corrected]. The parameters and distribution patterns of serum HBV RNA were evaluated in relation to viral replication status, immune phase, disease category and Child-Pugh class. The relationships between serum HBV RNA and other serum hepatitis B viral markers were also analyzed. RESULTS: Serum HBV RNA levels were significantly lower in the HBeAg-negative patients compared to those in the HBeAg-positive patients, with the lowest levels seen in inactive carriers. In HBeAg-negative patients, serum HBV RNA levels increased if there is reactivation to active hepatitis and showed obvious superiority for the combination of serum HBV DNA (cutoff>3.39 Log copies/mL) and HBsAg (cutoff>2.74 Log IU/mL) in discriminating between 'HBeAg-negative immune reactive' phase and inactive chronic hepatitis B phases of HBeAg-negative chronic HBV infection. Serum HBV RNA levels were positively correlated with serum HBV DNA and HBsAg levels in all chronic HBV-infected patients. A stratified analysis revealed that a correlation between serum HBV RNA and HBV DNA or HBsAg was present in HBeAg-positive patients; however, in HBeAg-negative patients, serum HBV RNA was positively correlated with HBV DNA only. CONCLUSION: During the natural course of chronic HBV infection, serum HBV RNA levels vary. Serum HBV RNA can act as a biomarker to predict the natural history of disease in chronic hepatitis B patients. In treatment-naïve HBeAg-negative chronic HBV-infected individuals, serum HBV RNA shows superiority in differentiating the 'HBeAg-negative reactive' phase.

Viral infection parameters not nucleoside analogue itself correlates with host immunity in nucleoside analogue therapy for chronic hepatitis B.

AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy. METHODS: Fifty-two hepatitis B envelope antigen (HBeAg) positive CHB patients were enrolled and divided equally into two groups. One group received telbivudine (LDT, 600 mg/d), and the other group received lamivudine (LAM, 100 mg/d). Clinical, virological and immunological parameters were assessed at the baseline and at 4, 12, 24, 36 and 48 wk. RESULTS: Both groups achieved significant hepatitis B virus (HBV) replication inhibition and alanine aminotransferase normalization at 48 wk. At the baseline, compared to healthy controls, CHB patients had a lower circulating CD8 T cell frequency (29.44% ± 11.55% vs 37.17% ± 7.30%, P = 0.03) and higher frequencies of programmed death 1 positive CD8 T cells (PD-1+ CD8 T) (16.48% ± 10.82% vs 7.02% ± 3.62%, P = 0.0001) and CD4+ CD25+ FoxP3+ T regulatory cells (Tregs) (23.64% ± 9.38% vs 13.60% ± 6.06%, P = 0.001). On therapy, at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid (HBV DNA) and HBeAg declining, the frequencies of PD-1+ CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups. At treatment week 4, patients treated with LDT had a lower frequency of PD-1+ CD8 T cells compared to patients treated with LAM (10.08% ± 6.83% vs 20.51% ± 20.96%, P = 0.02). The frequency of PD-1+ CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level (r = 0.45, P = 0.01) and HBeAg level (r = 0.47, P = 0.01) at treatment week 24, but the frequency of Treg cells was only significantly correlated with the HBeAg level (r = 0.44,P = 0.02). Furthermore, the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy. CONCLUSION: NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines. This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.