Background: Despite the obvious advantages of metagenomic next-generation sequencing (mNGS) in etiological diagnosis of various infectious diseases, there are few reports on etiological diagnosis of suspected thoracic and abdominal infections in patients with end-stage liver disease (ESLD).Methods: Seventy-three ESLD patients were enrolled from January 2019 to May 2021 due to suspected complicated thoracic and abdominal infections with poor response to empirical anti-infective treatment. Pleural effusion and ascites samples of these patients were collected for mNGS detection and conventional pathogen culture. The application value of mNGS in etiological diagnosis of thoracic and abdominal infections in ESLD patients was finally evaluated.Results: A total of 96 pathogens were detected using mNGS method, including 47 bacteria, 32 viruses, 14 fungi, 2 Mycobacterium tuberculosis, and 1 parasite. The positive rate of mNGS reached 42.5%, which was significantly higher than that of conventional culture method (21.9%) (p = 0.008). Considering neutrophil counts, the overall positive rate of bacteria detection of both methods in Polymorphonuclear Neutrophils (PMN) ≥250/mm³ group was 64.3% and in PMN <250/mm³ group was 23.7%. Compared with the final clinical diagnosis, the agreement rate of mNGS in patients with positive bacteria detection and with suspected positive bacteria detection was 78.6% (11/14) and 44.4% (8/18), respectively. In addition, the agreement rate of mNGS was 66.7% (4/6, respectively) in patients with positive and suspected fungal detection. Interestingly, of the 11 patients with fungal detection, 5 had alcoholic liver disease, accounting for 45.5% of all patients with alcoholic liver disease. We also detected 32 strains of viruses using mNGS, mainly cytomegalovirus (62.5%).Conclusions: The mNGS method is a useful supplement to conventional culture methods, which performs a higher positive rate, higher sensitivity, and broader pathogen spectrum, especially for rare pathogens and those difficult to culture. For ESLD patients, mNGS has great prospects in early etiological diagnosis of thoracic and abdominal infections. In addition, the cutoff values for the diagnosis of bacterial infection (PMN ≥250/mm³) in the thoracic and abdominal cavities may need to be redefined.

Introduction: Mother‐to‐child transmission (MTCT) of the hepatitis B virus (HBV) is a serious public health challenge. Estimating HBV MTCT incidence by region under different prophylaxis regimens is critical to understanding the regional disease burden and prioritizing interventions. This study aimed to calculate HBV MTCT incidence under different prophylaxis regimens globally and regionally and identify the HBV DNA threshold for maternal peripartum antiviral prophylaxis.Material and methods: This review was registered in advance in PROSPERO (CRD 42019120567). We searched PubMed, Embase, China National Knowledge Infrastructure, ClinicalTrials.gov, and Cochrane Library databases for studies on MTCT in pregnant women with chronic HBV infection from their inception until June 13, 2022. MTCT was defined as hepatitis B surface antigen (HBsAg) or HBV DNA seropositivity in infants aged 6–12 months. We calculated the pooled HBV MTCT incidence using the DerSimonian‐Laird random‐effects model.Results: Among 300 studies, 3402 of 63 293 infants had HBV due to MTCT. Without prophylaxis regimens, the pooled HBV MTCT incidence was 31.3%, ranging from 0.0% (95% confidence interval [CI] 0.0%–6.0%; European Region) to 46.1% (95% CI 29.7%–63.0%; Western Pacific Region). Following the introduction of the hepatitis B vaccine, the HBV MTCT incidence decreased from 82.9% to 15.9% in HBeAg‐positive women and from 10.3% to 2.3% in HBeAg‐negative women. Maternal peripartum antiviral treatment alongside infant immunoprophylaxis further decreased MTCT incidence to 0.3% (95% CI 0.1%–0.5%). Despite infant immunoprophylaxis, the incidences of MTCT at maternal HBV DNA levels of <2.30, 2.00–3.29, 3.00–4.29, 4.00–5.29, 5.00–6.29, 6.00–7.29 and ≥7.00 log₁₀ IU/ml were 0.0% (95% CI 0.0%–0.0%), 0.0% (95% CI 0.0%–0.0%), 0.0% (95% CI 0.0%–0.5%), 0.6% (95% CI 0.0%–2.6%), 1.0% (95% CI 0.0%–3.1%), 4.3% (95% CI 1.8%–7.5%), and 9.6% (95% CI 7.0%–12.5%), respectively.Conclusions: HBV MTCT incidence varies across regions. The Western Pacific Region bears the heaviest burden. Peripartum antiviral prophylaxis plus infant immunoprophylaxis is promising for interrupting HBV MTCT. Regarding the HBV DNA threshold for peripartum antiviral prophylaxis, maternal HBV DNA of 4.00 log₁₀ IU/ml or greater seems justified.

Background: Metagenomic next-generation sequencing (mNGS) is a novel nucleic acid method for the detection of unknown and difficult pathogenic microorganisms, and its application in the etiological diagnosis of fever of unknown origin (FUO) is less reported. We aimed to comprehensively assess the value of mNGS in the etiologic diagnosis of FUO by the pathogen spectrum and diagnostic performance, and to investigate whether it is different in the time to diagnosis, length of hospitalization, antibiotic consumption and cost between FUO patients with and without early application of mNGS. Methods: A total of 149 FUO inpatients underwent both mNGS and routine pathogen detection was retrospectively analyzed. The diagnostic performance of mNGS, culture and CMTs for the final clinical diagnosis was evaluated by using sensitivity, specificity, positive predictive value, negative predictive value and total conforming rate. Patients were furtherly divided into two groups: the earlier mNGS detection group (sampling time: 0 to 3 days of the admission) and the later mNGS detection group (sampling time: after 3 days of the admission). The length of hospital stay, time spent on diagnosis, cost and consumption of antibiotics were compared between the two groups. Results: Compared with the conventional microbiological methods, mNGS detected much more species and had the higher negative predictive (67.6%) and total conforming rate (65.1%). Patients with mNGS sampled earlier had a significantly shorter time to diagnosis (6.05+/-6.23 vs. 10.5+/-6.4 days, P < 0.001) and days of hospital stay (13.7+/-20.0 vs. 30.3 +/-26.9, P < 0.001), as well as a significantly less consumption (13.3+/-7.8 vs. 19.5+/-8.0, P < 0.001) and cost (4543+/-7326 vs. 9873 +/- 9958 China Yuan [CNY], P = 0.001) of antibiotics compared with the patients sampled later. Conclusions: mNGS could significantly improve the detected pathogen spectrum, clinical conforming rate of pathogens while having good negative predictive value for ruling out infections. Early mNGS detection may shorten the diagnosis time and hospitalization days and reduce unnecessary consumption of antibiotics.

Objectives: This study aimed to evaluate the efficacy and safety of long-term postpartum tenofovir disoproxil fumarate (TDF) therapy in hepatitis B virus (HBV)-infected mothers with high viral load. Methods: In this retrospective cohort study, HBV-infected mothers with HBV DNA>2 × 10⁵ IU/mL who initiated TDF prophylaxis treatment during pregnancy were divided into TDF continuation and discontinuation groups according to whether they stopped TDF treatment within 3 months after birth or not. Virological and biochemical markers were collected before TDF treatment, antepartum and postpartum. Results: In 131 women followed for a median of 18 months postpartum, alanine aminotransferase (ALT) abnormality rate was significantly lower in TDF continuation group vs. discontinuation group (39.4% vs. 56.9%, P = 0.045), and continuous TDF therapy in postpartum was independently associated with lower risk of ALT flares [OR = 0.308, 95% confidence interval (CI), 0.128–0.742; P = 0.009]. Long-term postpartum TDF treatment can promote the decline of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels, but the HBeAg seroconversion rate in two groups was not significant (15.5% vs. 11.7%, P = 0.541). There were no statistical differences in bone metabolism markers between two groups (P > 0.05). Compared with the TDF discontinuation group, TDF continuation group had a significantly lower estimated glomerular filtration rate level and higher creatinine level in postpartum but within normal ranges (P < 0.05). Conclusions: For pregnant women who received prophylactic TDF treatment, long-term TDF therapy continued in postpartum can reduce the risk of ALT flares and promote the rapid decline of HBeAg and HBsAg levels.