Nasopharyngeal carcinoma (NPC) is caused by infection with Epstein–Barr virus (EBV) and endemic in certain geographic regions. EBV lytic gene, BALF2, closely associates with viral reactivation and ...BALF2 gene variation, the H‐H‐H strain, causes NPC in endemic region, southern China. Here, we investigate whether such EBV variations also affect NPC in a non‐endemic region, Japan. Viral genome sequencing with 47 EBV isolates of Japanese NPC were performed and compared with those of other EBV‐associated diseases from Japan or NPC in Southern China. EBV genomes of Japanese NPC are different from those of other diseases in Japan or endemic NPC; Japanese NPC was not affected by the endemic strain (the BALF2 H‐H‐H) but frequently carried the type 2 EBV or the strain with intermediate risk of endemic NPC (the BALF2 H‐H‐L). Seven single nucleotide variations were specifically associated with Japanese NPC, of which six were present in both type 1 and 2 EBV genomes, suggesting the contribution of the type 2 EBV‐derived haplotype. This observation was supported by a higher viral titer and stronger viral reactivation in NPC with either type 2 or H‐H‐L strains. Our results highlight the importance of viral strains and viral reactivation in the pathogenesis of non‐endemic NPC.
Epstein–Barr virus (EBV) genome variation such as BALF2 that is associated with viral reactivation is a risk factor of nasopharyngeal carcinoma (NPC) in endemic regions such as southern China. We found unique BALF2 genome variation in EBV isolates of NPC in Japan, an non‐endemic region, different from endemic NPC. We revealed the importance of viral strains and their reactivation in the pathogenesis of non‐endemic NPC.
To assess the incidence of hepatitis B virus (HBV) reactivation in patients receiving direct-acting antiviral agent (DAA)-based therapy or interferon (IFN)-based therapy for hepatitis C and the ...effectiveness of preemptive anti-HBV therapy for preventing HBV reactivation.
The PubMed, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAA-based therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model.
The rate of HBV reactivation was 21.1% in hepatitis B surface antigen (HBsAg)-positive patients receiving DAA-based therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBsAg-positive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy (RR = 0.20, 95%CI: 0.06-0.64,
= 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBsAg-positive patients undergoing DAA-based therapy (RR = 0.31, 95%CI: 0.1-0.96,
= 0.042).
The rate of HBV reactivation and hepatitis flare occurrence is higher in HBsAg-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.
Background and Aims
Hepatitis B virus (HBV) reactivation is a serious condition and has been extensively described in chemotherapeutic immunosuppressive population. However, little is known about HBV ...reactivation in immunocompetent patients with chronic hepatitis B (CHB). In this study, we evaluated the prevalence and the clinical significance of HBV reactivation in CHB patients with acute exacerbations.
Method
Patients were screened from two prospective multicenter observational cohorts (CATCH-LIFE cohort). A total of 1,020 CHB patients with previous antiviral treatment history were included to assess the prevalence, risk factors, clinical characteristics of HBV reactivation, and its influence on the progression of chronic liver disease.
Results
The prevalence of HBV reactivation was 51.9% in CHB patients with acute exacerbations who had antiviral treatment history in our study. Among the 529 patients with HBV reactivation, 70.9% of them were triggered by discontinued antiviral treatment and 5.9% by nucleos(t)ide analogs (NUCs) resistance. The prevalence of antiviral treatment disruption and NUCs resistance in patients with HBV reactivation is much higher than that in the patients without (70.9% vs. 0.2%, and 5.9% vs. 0, respectively, both
p
< 0.001). Stratified and interaction analysis showed that HBV reactivation was correlated with high short-term mortality in cirrhosis subgroup (HR = 2.1,
p
< 0.001). Cirrhotic patients with HBV reactivation had a significantly higher proportion of developing hepatic failure (45.0% vs. 20.3%,
p
< 0.001), acute-on-chronic liver failure (ACLF; 31.4% vs. 21.8%,
p
= 0.005), and short-term death (14.0% vs. 5.9% for 28-day, and 23.3% vs. 12.4% for 90-day, both
p
< 0.001) than those without. HBV reactivation is an independent risk factor of 90-day mortality for cirrhosis patients (OR = 1.70,
p
= 0.005), as well as hepatic encephalopathy, ascites, and bacterial infection.
Conclusion
This study clearly demonstrated that there was a high prevalence of HBV reactivation in CHB patients, which was mainly triggered by discontinued antiviral treatment. The HBV reactivation strongly increased the risk of developing hepatic failure, ACLF and short-term death in HBV-related cirrhotic patients, which may suggest that HBV reactivation would be a new challenge in achieving the WHO target of 65% reduction in mortality from hepatitis B by 2030.
Herpes Simplex Virus (HSV) establishes a latent infection in neurons, in which viral transcription is restricted and viral promoters are associated with heterochromatin. In response to certain ...stimuli, the virus reactivates to permit transmission. The exact physiological triggers of reactivation, the cell signaling pathways involved, and how signals act on heterochromatin-associated lytic promoters, are not understood. Previously, we identified a role for a neural stress pathway involving DLK and JNK activity in HSV reactivation, triggered by nerve growth factor (NGF) deprivation. Reactivation was associated with a JNK-dependent histone phospho/methyl switch on lytic gene promoters. Because the same histone phospho/methyl switch occurs in cortical neurons following hyperexcitability (triggered by forskolin), we examined whether HSV reactivation was linked to hyperexcitability, and the contribution of JNK activity and histone phosphorylation. Using our primary neuronal model of HSV reactivation, we found that forskolin triggered DLK/JNK-dependent reactivation via a pathway that was distinct from NGF deprivation. The initial burst of HSV lytic gene expression in response to forskolin occurred independently of histone demethylase activity, and was accompanied by a histone phospho/methyl switch. To determine whether forskolin-mediated reactivation was linked to neuronal activity, we investigated the contribution of ion channel activity. Inhibition of voltage-gated potassium and sodium channels, or hyperpolarization-activated cyclic nucleotide-gated channels, prevented forskolin-mediated reactivation. In addition, hyperexcitability, resulting from the removal of a tetrodotoxin block, triggered HSV reactivation in a DLK/JNK-dependent manner. We next investigated whether physiological triggers induce HSV reactivation via hyperexcitability. IL-1 induced DNA damage associated with hyperexcitability in adult neurons. IL-1 also triggered DLK/JNK-dependent HSV reactivation, which was dependent on ion channel activity. Therefore, these data indicate that neuronal hyperexcitability in response to physiological stimuli, such as inflammation, trigger HSV reactivation, and mark out the activation of DLK/JNK and a histone phospho/methyl switch as key events in the hyperexcitability-mediated reactivation.
In this article, we discuss a recently published article that demonstrated a novel way of identifying viral pathogens reactivating in human cells to be used as cellular therapy, in this instance ...chimeric antigen receptor (CAR) T cells. The authors used search engines and databases to identify viruses able to reactivate in T cells and then tested this initially in T-cell cultures, specifically human herpesvirus 6. This virus was then shown to reactivate infrequently in vitro and in vivo in CAR T cells as a consequence of T-cell activation. The methodology may be most clinically useful for more frequently reactivating viruses in other types of cellular therapy such as allogenic CAR T cells or induced pluripotent stem cells.
A 54-year-old woman underwent chemotherapy including rituximab and autologous peripheral blood stem cell transplantation (auto-PBSCT) for diffuse large B-cell lymphoma. Before the treatment, she ...exhibited a resolved hepatitis B virus (HBV) infection. She was diagnosed with HBV reactivation based on positive serum HBV-DNA test results, 55 months after her last treatment. Subsequently, he was treated with tenofovir alafenamide fumarate (TAF) therapy and her liver function improved. Patients undergoing chemotherapy including rituximab and auto-PBSCT are at a high risk of HBV reactivation. In such cases, careful and long-term observations may be required to detect HBV reactivation.
A 79-year-old man with lymphoma who tested negative for anti-hepatitis C virus (HCV) antibody received rituximab-containing chemotherapy. Liver dysfunction of unknown cause had persisted since the ...second cycle of chemotherapy. Ten months after treatment, he rapidly developed massive ascites and atrophy of the liver, and we detected HCV RNA in his serum using real time polymerase chain reaction. Furthermore, medical interviews showed that the patient had no episodes for acute HCV infection, but he did have a history of unspecified liver dysfunction. These findings support the possibility of the reactivation of seronegative occult HCV infection due to chemotherapy in a cancer patient.
•Detection of VZV DNA in blood from patients with localized HZ is common.•The detection of VZV DNA in blood during HZ prodromal phase remains controversial.•Patients with stored blood samples ...available the week preceding HZ were selected.•VZV DNA was detected in blood of 77 % of patients during the week preceding HZ onset.•Early blood VZV DNA detection might improve HZ prognosis of immunosuppressed patients.
To assess whether varicella zoster virus (VZV) DNA can be detected in blood before herpes zoster (HZ) rash onset.
Monocentric retrospective study from January 2019 to March 2023 including patients with HZ and stored blood samples performed during the week preceding the onset of HZ rash. Blood samples were retrospectively analyzed for VZV DNA by quantitative PCR.
Among the 138 patients with HZ during the study period, stored blood samples performed during the week preceding the onset of HZ rash were available for 13 of them. Twelve (92 %) patients were immunosuppressed, mostly due to solid organ transplantation (38 %), solid malignancy (31 %) or autoimmune disease (23 %). During the week preceding HZ onset, VZV DNA was detected in blood from 10 (77 %) patients, with a median value of 3.6 log (copies/mL) (IQR 3.3–3.9). At the time of HZ onset, all VZV PCR performed in available blood samples were positive.
Our findings demonstrates that VZV DNA can be commonly detected in blood from immunocompromised patients during the prodromal phase of HZ. Early screening of VZV DNA in blood from high-risk immunocompromised patients might improve HZ therapeutic management.
This study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with ...primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients.
We enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups.
A total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35-33.33, p<0.001). Patients in antiviral group received more cycles of HAIC compared with non-antiviral group (3.11 ± 1.69 vs 1.75 ± 1.18, p<0.05) at the time of HBV reactivated. Seven of the 25 HBV reactivation patients developed hepatitis. OS in antiviral group was significantly longer than that of non-antiviral group (median 16.46 vs 10.68 months; HR=0.57; 95% CI, 0.36-0.91; p<0.05).
HBV reactivation is more prone to occur in the HBsAg-positive HCC patients undergoing HAIC without antiviral prophylaxis. Regular monitoring of HBV DNA and antiviral prophylaxis are suggested to prevent HBV reactivation as well as prolong the OS of these patients.
HAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC.
https://www.clinicaltrials.gov/, identifier NCT02436044.
BACKGROUND: Heavy training schedules or endurance competitions in marathon are forms of extreme physical stress and lead to immunodepression in runners which could be associated with increased ...susceptibility to viral reactivation by ubiquitous viral infection such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Lately, it was confirmed presence of elevated CMV and EBV loads and the lower antibody titers in competitive athletes. The most common clinical features are fatigue and adynamia accompanied with liver damage, varying from mild and transient elevation of aminotransferases to serious acute hepatitis and liver failure.
CASE REPORT: Bearing in mind that a professional practice of marathon running is hazardous for the liver, therapeutic action is necessary as soon as possible to avoid serious complications and even cessation of professional competition. In our case report of professional female marathon runner, we need to treat CMV and EBV reactivation which caused liver damage, prevented regular trainings, and upcoming competitions. We opted for four sessions of nanomembrane based apheresis performed every other day for removal pathological products resulting from virus reactivation to break through the course of the disease and to prevent complications. After completing the whole procedure control laboratory tests and abdominal ultrasound were in physiological ranges.
CONCLUSION: Hence, nanomembrane based apheresis can be effective and safe treatment of liver damages for elite marathon runners as well as for athletes.
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