OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

OBJECTIVE: To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival. METHODS: A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed. RESULTS: For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×10⁴ copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×10⁹/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×10⁴ copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005). CONCLUSION The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×10⁴ copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.
Humans ; Viremia/complications* ; Retrospective Studies ; Cytomegalovirus Infections/complications* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Cytomegalovirus ; Graft vs Host Disease/complications*

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.
Humans ; Epstein-Barr Virus Infections/diagnosis* ; Herpesvirus 4, Human/genetics* ; Retrospective Studies ; Viremia ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Lymphoproliferative Disorders/etiology* ; DNA, Viral ; Viral Load

OBJECTIVE: To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients. METHODS: The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed. RESULTS: Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively. CONCLUSION The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.
Child ; Cytomegalovirus Infections ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Parents ; Retrospective Studies ; Thalassemia/therapy* ; Transplantation Conditioning/methods* ; Treatment Outcome ; Viremia

Low-level viremia (LLV) was defined as persistent or intermittent episodes of detectable hepatitis B virus (HBV) DNA (<2000 IU/mL, detection limit of 10 IU/mL) after 48 weeks of antiviral treatment. Effective antiviral therapies for chronic hepatitis B (CHB) patients, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), have been shown to inhibit the replication of HBV DNA and prevent liver-related complications. However, even with long-term antiviral therapy, there are still a number of patients with persistent or intermittent LLV. At present, the research on LLV to address whether adversely affect the clinical outcome is limited, and the follow-up treatment for these patients is open to question. At the same time, the mechanism of LLV is not clear. In this review, we summarize the incidence of LLV, the association between LLV and long-term outcomes, possible mechanisms, and management strategies in these patient populations.
Antiviral Agents/therapeutic use* ; DNA, Viral ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Humans ; Nucleosides/therapeutic use* ; Tenofovir/therapeutic use* ; Treatment Outcome ; Viremia/drug therapy*

BACKGROUND: BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN. METHODS: We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up. RESULTS: After a mean follow-up period of 14.4 (range, 0.3-109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow-up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min·1.73 m, t = 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min·1.73 m, t = 3.034, P = 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min·1.73 m), urine viral loads (median, 1.3 × 10vs. 1.4 × 10 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ = 6.341, P = 0.042). CONCLUSION Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.
Adolescent ; Adult ; Aged ; BK Virus ; Child ; Female ; Glomerular Filtration Rate ; Graft Rejection ; Graft Survival ; Humans ; Kidney Diseases ; complications ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Polyomavirus Infections ; complications ; Retrospective Studies ; Viral Load ; Viremia ; complications ; Young Adult

Foot-and-mouth disease (FMD) is an acute epidemic that spreads rapidly among cattle and pigs. In 2014, in Korea, despite enforced vaccination, the type O Southeast Asia (SEA) topotype viruses (Mya-98 lineage) infected mainly cattle and pigs simultaneously, thereby causing enormous damage. If a vaccine that is completely protective against this FMD virus is developed and used, it can become a very important preventive measure in Asia, which is where this type of virus mainly circulates. The SEA topotype has been steadily evolving and transforming into new variations since it became epidemic in Asia. Therefore, it became necessary to develop a new vaccine that could provide protection against the FMD virus strain that was responsible for the 2014–2015 outbreak in Korea. This study aimed to develop a vaccine that would provide complete protection against the SEA topotype FMD virus to control sporadic FMD outbreaks, which occur despite the enforcement of vaccination, and to completely prevent virus shedding, thereby preventing the virus from spreading. The vaccine candidate virus developed in this study showed low pathogenicity and can be distinguished from the wild-type FMD virus strain. The developed vaccine was able to protect mice from SEA and Middle East–South Asia topotype virus strains and induced high titers of antibodies against both virus strains in pigs, thereby confirming the sufficiency of its protective function. In particular, the results of the SEA topotype virus challenge test in pigs revealed that perfect immunity was created in the vaccinated pigs, without virus shedding and viremia.
Animals ; Antibodies ; Asia ; Asia, Southeastern ; Cattle ; Disease Outbreaks ; Foot-and-Mouth Disease ; Korea ; Mice ; Swine ; Vaccination ; Viremia ; Virulence ; Virus Shedding

The Schmallenberg virus (SBV) is an orthobunyavirus that causes abortions, stillbirths, and congenital defects in pregnant sheep and cattle. Inactivated or live attenuated vaccines have been developed in endemic countries, but there is still interest in the development of SBV vaccines that would allow Differentiating Infected from Vaccinated Animals (DIVA). Therefore, an attempt was made to develop novel DIVA-compatible SBV vaccines using SBV glycoproteins expressed in baculovirus. All vaccines and phosphate buffered saline (PBS) controls were prepared with adjuvant and administered subcutaneously to cattle at 6 month of age. The first trial included 2 groups of animals vaccinated with either carboxyl-terminus glycoprotein (Gc) or PBS and boosted after 2 weeks. In the second trial, 3 groups of cattle were administered either Gc, Gc and amino-terminus glycoprotein (Gn), or PBS with a booster vaccination after 3 weeks. The animals were challenged with SBV 9 days after the booster vaccination in the first study, and 3 weeks after the booster vaccination in the second study. Using a SBV Gc-specific enzyme-linked immunosorbent assay, antibodies were first detected in serum samples 14 days after the first vaccination in both trials, and peaked on days 7 and 9 after the booster in the first and second trials, respectively. Low titers of neutralizing antibodies were detected in serum from only 3/6 and 2/4 animals in the first and second trial, respectively, at 14 days after the first vaccination. The titers increased 2 to 3-fold after the booster vaccination. SBV-specific RNA was detected in the serum and selective tissues in all animals after SBV challenge independent of vaccination status. The SBV candidate vaccines neither prevented viremia nor conferred protection against SBV infection.
Animals ; Antibodies ; Antibodies, Neutralizing ; Baculoviridae ; Cattle ; Congenital Abnormalities ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins ; Orthobunyavirus ; RNA ; Sheep ; Stillbirth ; Vaccination ; Vaccines ; Vaccines, Attenuated ; Vaccines, Subunit ; Viremia

Tacrolimus is widely used with other immunosuppressive agents to prevent rejection of a kidney transplant (KT). However, tacrolimus-induced fever is very rarely diagnosed. We report a case of tacrolimus-induced fever after KT. A 53-year-old female was diagnosed with cytomegalovirus (CMV) viremia. She had received a KT 2 months previously. Ganciclovir was started immediately at that time. A fever developed on day 12 of admission. Because of dysuria and a residual urine sensation with pyuria, we started intravenous antibiotics to treat urinary tract infection. Although other infectious reasons were ruled out and CMV viremia and the urinary tract infection improved, the fever spike did not improve. Thus, we suspected drug-induced fever. First, the ganciclovir and antibiotics were discontinued. However, the fever continued. To exclude tacrolimus-induced fever, tacrolimus was discontinued and cyclosporine was used with other immunosuppressive agents. Tacrolimus was discontinued after 1 day and the fever was no longer confirmed.
Anti-Bacterial Agents ; Cyclosporine ; Cytomegalovirus ; Dysuria ; Female ; Fever ; Ganciclovir ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Kidney ; Middle Aged ; Pyuria ; Sensation ; Tacrolimus ; Urinary Tract Infections ; Viremia

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4–47.8) months and 8.2 (range, 2.8–98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.
Allografts ; Child ; Diagnosis ; Follow-Up Studies ; Herpesvirus 4, Human ; Humans ; Incidence ; Kidney Transplantation ; Kidney ; Neutropenia ; Organ Transplantation ; Retrospective Studies ; Risk Factors ; Rituximab ; Tacrolimus ; Tissue Donors ; Transplants ; Viral Load ; Viremia