Aim
We retrospectively investigated patients with administration of nucleos(t)ide analogs (NAs) for prevention of or against hepatitis B virus (HBV) reactivation, and their clinical outcomes after ...cessation of the NA.
Methods
We enrolled 180 patients who were positive for HBsAg when they started immunosuppressive therapy or chemotherapy and an NA was administered to prevent HBV reactivation (HBV carrier group), and 82 patients with resolved HBV infection who started administration of an NA after HBV reactivation (de novo HBV group). Cessation of the NA depended on each physician's judgment without definite criteria.
Results
A total of 27 patients in the HBV carrier group and 22 in the de novo HBV group stopped NA therapy. In the HBV carrier group, 16 patients experienced virological relapse, which was defined as HBV DNA levels ≥20 IU/ml, and one with hematological disease had an alanine aminotransferase flare after cessation of NA. Of the 16 patients, the NA was reintroduced in three, whereas, the remaining 13 had low levels of HBV DNA and no alanine aminotransferase flare. In the de novo HBV group, virological relapse occurred in six patients, and one with hematological disease had an alanine aminotransferase flare after cessation of the NA. The NA was reintroduced in four of the six patients.
Conclusions
We may be able to consider to cease NA therapy proactively in HBV carriers and resolved patients with non‐hematological disease, if their primary diseases are under remission after completion of immunosuppressive therapy or chemotherapy. However, careful follow up is necessary after stopping NA therapy.
The aim of this study was to assess the effects of anti-tumour necrosis factor (TNF) agents on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative and anti-hepatitis ...B core (HBc)-positive patients (HBV occult carriers) with rheumatic diseases.
Evidence of HBV reactivation after anti-TNF therapy in HBV occult carriers with a rheumatic disease was studied by summarising results and by performing meta-analysis analysis.
A total of 468 HBsAg-negative and anti-HBc-positive patients with a rheumatic disease undergoing treatment with an anti-TNF agent were identified in nine studies. The anti-TNF agents used were etanercept in 269 cases, adalimumab in 95, and infliximab in 100 cases, and these were administered for rheumatoid arthritis (RA) in 327 patients, ankylosing spondylitis in 49, and psoriatic arthritis (PsA) in 73 patients. Follow-up periods ranged from 6 to 60 months. HBV reactivation in patients on an anti-TNF agent was reported in 8 cases (8/468 = 1.7%). Seven of these patients had RA and 1 had PsA. Seven patients received etanercept and one adalimumab. HBV-DNA was detectable in 7 of these 8 cases. Antiviral treatment was administered in 6 of the 8 (lamivudine in 2, entecavir in 4) and clinical outcomes were satisfactory in all 8 patients.
HBV reactivation was found in 8 (1.7%) patients among 468 HBsAg-negative and anti-HBc-positive patients with rheumatic diseases treated with anti-TNF agents. Our data suggest that HBsAg-negative and anti-HBc-positive patients undergoing anti-TNF therapy need to be carefully monitored during anti-TNF therapy.
Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) has become a popular regimen for adults with acute lymphoblastic leukemia (ALL). We assessed the efficacy ...and tolerability of hyper-CVAD in the treatment of adult ALL.
We retrospectively reviewed ALL patients aged 18 or above receiving the hyper-CVAD regimen. We assessed complete remission rate and overall survival, as well as hepatitis B carrier rate and hepatitis flare due to hepatitis B virus (HBV) reactivation.
Fifty-two patients were treated with the hyper-CVAD regimen. The median age at diagnosis was 42 years; 27% of patients were Philadelphia (Ph) chromosome positive. The complete remission (CR) rate was 90.4% after the first cycle of chemotherapy. The induction mortality rate was 1.9%. Three patients required two cycles of hyper-CVAD to achieve CR. The median overall survival was 39.6 months and the 5-year overall survival was 50%. Age over 30 years and white blood cell count of more than 30 × 10
/l were found to be prognostic for poor overall survival in multivariate analysis. The hepatitis B carrier rate was 17% in our cohort, and the rate of hepatitis flare due to HBV reactivation was 11% in patients with current infection.
Hyper-CVAD is feasible and tolerable with a good CR rate in the treatment of adult ALL patients. It is an option for the treatment of ALL. Antiviral prophylaxis should be considered in ALL patients with HBV infection to reduce the risk of HBV reactivation.
Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody ...(HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90–3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.
Cyprinid herpesvirus 2 (CyHV-2) is a highly contagious pathogen of goldfish (Carassius auratus) and Prussian carp (Carassius auratus gibelio) causing herpesviral hematopoietic necrosis. Our previous ...study revealed that CyHV-2 can persistently infect the kidney and spleen of goldfish that recovered from a primary infection. In this study, we tried to identify the cells persistently infected with the virus in surviving fish and investigated virus reactivation in the survivors injected with immunosuppressants, namely dexamethasone (Dex) and cyclosporine A (CsA). Virus DNA was detected from the monocytes that were isolated from the trunk kidney of the asymptomatic survivors, suggesting that monocytes/macrophages are major cells that may be persistently infected with CyHV-2. A significant increase of virus DNA levels was detected in the group injected with Dex at 10 and 21 days post-injection (dpi). In the fish group injected with CsA, the virus DNA level was the same as that in the control group at 10 dpi but increased in some organs at 21 dpi. Compared with Dex-injected fish at 10 dpi, the group injected with both Dex and CsA showed a greater increase in virus DNA levels. The gene expression of phagocytosis-associated genes, major histocompatibility complex (MHC) class II and p47phox, and anti-virus antibody levels increased in the CsA group due to virus reactivation in the infected cells but not in the Dex and Dex & CsA groups, indicating that Dex effectively suppressed monocyte/macrophage function and antibody production. In addition, recombinant interferon γ (IFNγ) supplementation in the kidney leukocyte culture that was isolated from survivors showed a reduction of virus DNA. CsA may inhibit T-helper 1 (Th1) cells and consequently IFNγ production, causing a synergetic effect with Dex on virus reactivation. The results suggest that the activity of monocytes/macrophages stimulated by IFNγ can relate to virus latency and reactivation in asymptomatic virus carriers.
•Monocytes/macrophages can be major cells persistently infected with CyHV-2 in survivors.•Dexamethasone (Dex) injection induced CyHV-2 reactivation in survivors.•The combination of Dex and cyclosporine A (CsA) injection greatly induced virus reactivation.•The activity of monocytes/macrophages can relate to virus latency and reactivation in survivors.
Chronic hepatitis B virus (HBV) infection remains a serious global health concern. Cisplatin is a chemotherapeutic agent commonly used to treat various cancers. However, HBV-infected patients ...receiving chemotherapy are at risk of HBV reactivation via unknown mechanisms, which we aimed to elucidate in this study. We found that autophagy plays a central role in cisplatin-induced HBV replication. Cisplatin treatment induced autophagy in both HBV-replicating cells and an HBV-transgenic mouse model as evident from marked upregulation of microtubule-associated protein 1 light chain 3 (LC3)-II and the accumulation of red fluorescent protein (RFP)-LC3 puncta. Cisplatin induced complete autophagic flux, which was detected via monitoring of p62 degradation and RFP-GFP-LC3 expression. Inhibition of autophagy by chloroquine, 3-methyladenine, or Atg5 knockdown significantly attenuated cisplatin-induced HBV replication. Additionally, cisplatin-induced autophagy could be significantly attenuated by using the ROS scavenger N-acetyl-l-cysteine. Mechanically, cisplatin promoted HBV replication and autophagy through ROS/JNK and AKT/mTOR signaling. Inhibition of JNK or activation of Akt/mTOR signaling reversed cisplatin-mediated autophagy and HBV replication promotion. In contrast, suppression of Akt/mTOR signaling further promoted cisplatin-induced HBV replication. Finally, pharmacotherapeutic inhibition of autophagy or ROS production impaired HBV production induced by cisplatin in vivo. Together, our results indicate that ROS/JNK and mTOR/AKT-mediated autophagy plays an important role in cisplatin-induced HBV reactivation.
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•Cisplatin stimulates HBV replication in vitro and in vivo.•Cisplatin induces autophagy to enhance hepatitis B virus replication.•Inhibition of autophagy or ROS/JNK axis rendered cisplatin-induced HBV biosynthesis.•Cisplatin promotes HBV replication and autophagy by ROS/JNK and AKT/mTOR pathway.
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