Aims/Background: Tuberculosis (TB) is a highly prevalent opportunistic infection and a leading cause of mortality worldwide, particularly among those living with human immunodeficiency virus (HIV). Among these patients, the diagnostic accuracy of conventional TB testing is generally limited by atypical clinical manifestations, the frequent occurrence of extrapulmonary TB, challenges in obtaining sputum samples, and consistently low bacterial loads in clinical specimens. Therefore, this study assesses the diagnostic performance of a novel chemiluminescence immunoassay (CLIA) for detecting urinary lipoarabinomannan (LAM) in individuals coinfected with HIV and TB. Methods: A prospective cohort study was conducted involving 297 people living with HIV (PLWH) recruited from Beijing Youan Hospital, Capital Medical University, China, between May 2021 and December 2024. By September 2025, when this analysis was finalized, all patients had received at least 6 months of follow-up. Of these, 76 patients had TB (34 definite cases and 42 probable cases), while 221 non-TB patients with confirmed alternative diagnoses were included as a control group. A novel double-antibody sandwich CLIA was specifically designed to detect the Mycobacterium tuberculosis LAM antigen in urine specimens. For comparative evaluation, all samples were concurrently analyzed using the commercially available Determine™ TB LAM Ag test (AlereLAM, Abbott Laboratories, USA). Investigators were blinded to the laboratory test results until the completion of enrollment, and laboratory technicians were blinded to patients’ diagnoses throughout the study duration. Results: Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.925 at the optimal cutoff of 1.46. Median CLIA values increased in a graded manner across groups: 0.98 in the non-TB group, 1.96 in the probable TB group, and 4.46 in the definite-TB group (p < 0.001). Compared with AlereLAM, CLIA demonstrated significantly higher sensitivity (85.3% vs. 58.8%) but lower specificity (89.6% vs. 98.2%). Neither LAM-CLIA nor AlereLAM exhibited a significant association with patient cluster of differentiation (CD) 4+ T cell counts (p > 0.05). Conclusion: CLIA-based urinary LAM detection demonstrates superior sensitivity compared with conventional lateral flow assays, providing a rapid and quantitative approach for detecting HIV-associated TB. This method has significant potential to improve early TB detection in high-risk populations, particularly where culture-based methods are unavailable.

Background:Carbapenem resistant klebsiella pneumoniae infection increased the mortality rate of liver transplant recipients. This study aims to provide more evidence for the clinical diagnosis and treatment of carbapenem resistant klebsiella pneumonia infection in liver transplant recipients. Methods:This study included liver transplant recipients who developed CRKP infections during the perioperative period from January 2019 to December 2024 at Beijing You'an Hospital. Statistical analysis was performed on their clinical and outcomes characteristics. Results:Among the 48 liver transplant recipients with CRKP infections, the 30 days mortality rate and the 90 days mortality rate after infection was 25%(12/48) and 31.25%(15/48). The mortality rates of patients with abdominal cavity infections were significantly higher than those of other patients (p < 0.05). The mortality rate of patients with mechanical ventilation and with septic shock during infection was higher (p < 0.05). Among the initial laboratory indicators after patient infection, there were significant differences in platelet (PLT), procalcitonin (PCT), total bilirubin (TBIL), creatinine (CR), and urea (UR) between the survival group and the death group (p < 0.05). Intra-abdominal infection (OR = 7.413, 95% CI: 1.218-45.136, p = 0.030) and septic shock (OR = 25.015, 95% CI: 4.128-151.594, p < 0.001) were both independent risk factors for 90-days mortality. The drug sensitivity results of CRKP strains from liver transplant recipients showed that the three drugs with the lowest resistance rates were ceftazidime-avibactam, polymyxin, and tigecycline. Different drugs and drug combinations did not cause differences in the all-cause mortality rates of patients after infection (p > 0.05). The risk of death in patients who received effective antibiotics within 48 hours was reduced by 54.3% (HR = 0.457, 95% CI: 0.163-1.285, p = 0.135), but due to the limited sample size, this result did not reach statistical significance. Conclusion:Clinicians should remain vigilant for abdominal infections, promptly control the infection source, and recognize early signs of septic shock to initiate timely treatment-key measures to reduce mortality for liver transplant recipients with CRKP infection. Additionally, effective antibiotic therapy within 48 hours after sampling may confer a survival benefit.

Objectives:Liver abscess is a severe complication that can occur following thermal ablation of liver cancer, with an incidence rate ranging from 0.2% to 2.4%. This study aimed to identify risk factors associated with the development of post-ablation liver abscesses and to characterize the microbiological features of the isolated pathogens. Methods:A matched case-control study was conducted at Beijing Youan Hospital from January 2018 to December 2023. Cases were defined as patients who developed liver abscesses within three months following ablation therapy, while controls comprised patients who did not develop such abscesses. Clinical and microbiological data were collected and analyzed. The relevant independent risk factors for the occurrence of liver abscesses were identified and assessed using multivariate logistic regression analysis. Results:Post-ablation liver abscesses predominantly occurred in male patients aged 60 years or older, typically manifesting around six days after the procedure. Common symptoms included fever, chills, abdominal distension, and abdominal pain. Multivariate analysis identified diabetes mellitus (OR=3.215; 95% CI 1.330-7.771), history of abdominal surgery (OR=2.810; 95% CI 1.074-7.353), biliary disease (OR=18.832; 95% CI 2.291-154.795), and elevated ALP levels (OR=1.010; 95% CI 1.002-1.019) as independent risk factors for post-ablation liver abscesses. Among the 61 patients with liver abscesses, a total of 78 bacterial strains were isolated from the abscess fluid, with Gram-negative bacteria accounting for 75.6% of the isolates. Escherichia coli (30.8%) and Klebsiella pneumoniae (20.5%) were the most frequently identified pathogens. Drug sensitivity testing revealed that both Escherichia coli and Klebsiella pneumoniae exhibited high susceptibility to Amikacin, Cefoxitin, Ceftazidime, Imipenem, Meropenem, and Piperacillin-tazobactam. Conclusions:Post-ablation liver abscesses are primarily caused by Gram-negative bacteria. A history of diabetes, prior abdominal surgery, biliary disease, and elevated ALP levels are significant risk factors influencing the development of post-ablation liver abscesses.

Objective: This study aimed to investigate the diagnostic value of stress-induced phosphoprotein 1 (STIP1) in serum for hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP)-negative HCC (ANHC). Methods: In this study, serum samples were collected from 158 HCC patients and 63 non-HCC patients. Logistic regression analysis was performed to identify independent risk factors associated with HCC and ANHC. The diagnostic values of each index for HCC and ANHC were analyzed using receiver operating characteristic (ROC) curve analysis. Results: The STIP1, des-gamma-carboxy prothrombin (DCP), and AFP levels were higher in the HCC groups than in the non-HCC groups (P < .05). Age, DCP, STIP1, and hepatitis B virus infection were independent predictors of HCC (P < .05). The diagnostic value of STIP1 for HCC was higher than that of DCP. Additionally, age, STIP1, and hepatitis B virus infection were independent predictors for ANHC patients. The ROC curve exhibited an area under the curve value of 0.919 for STIP1, with a diagnostic cutoff value of 68.5 U/mL. Moreover, 36 ANHC patients and 19 AFP-negative non-HCC patients were included to validate the diagnostic model. A total of 20 patients had STIP1 levels greater than 68.5 U/mL, resulting in diagnostic accuracy of 67.3%, sensitivity of 55.6%, and specificity of 89.5%. Conclusion: STIP1 demonstrates excellent diagnostic value for HCC and ANHC.

Background Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI.Methods Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism.Results Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C,sK122R,sI126T,sT131P,and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A,sG10D,sF20S,and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure.Conclusions HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.

In this article, we report a male patient infected with HIV presenting with cryptococcal meningitis, pneumonia, and bloodstream infection, along with intestinal obstruction and gastrointestinal bleeding. Cerebrospinal fluid and bloodstream analyses revealed the presence of Cryptococcus neoformans complex. The isolated strain was sequenced and was found to belong to Cryptococcus neoformans var. grubii with a new sequence type (ST). The strain led to fatal multisystemic cryptococcosis in a short time, and the patient died due to hemorrhagic shock because of gastrointestinal bleeding despite emergency rescue efforts. There are few reports about cryptococcosis in HIV-infected patients caused by new ST isolates. We report a new Cryptococcus neoformans ST (ST702) isolate causing infection in an HIV-infected patient, which merits further study and clinical attention.

BackgroundCryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes.MethodsWe reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed.ResultsA total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately.ConclusionsAlthough cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient’s clinical condition.

Background: Evaluating the clinical performance of Elecsys HIV Duo assay for primary human immunodeficiency virus (HIV) screening and acute HIV infection detection. Methods: This study was conducted from April 2022 to April 2023 and involved two distinct populations. For the HIV screening population, three HIV Duo results [HIV Duo, HIV antigen (Ag), and HIV antibody (Ab)] in primary screening were obtained (January 2021 to June 2021). In the diagnosed HIV population, retrospective samples from November 2016 to March 2023 were measured. Results: The HIV screening population included 111,383 samples from a real-world screening program. The assay demonstrated a specificity of 99.91 % (95 % CI: 99.89 %, 99.93 %) and a PPV of 0.8516 (95 % CI: 0.8225, 0.8776). Regarding the diagnosed HIV population, 836 HIV patients were enrolled, including 14 acute HIV infectious patients with only HIV Ag + and a Western Blot (WB) confirmation rate of 0 %. The median (IQR) of the numeric cut-off index (COI) ratios of HIV Duo Ab and Ag significantly differed among the Ag + Ab-, Ag-Ab+, and Ag + Ab + subgroups. Conclusion: The Elecsys HIV Duo assay is suitable for primary HIV screening and can be integrated into a novel laboratory HIV testing algorithm to improve acute HIV detection in Chinese clinical practice.

BackgroundA variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions.MethodsWe retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used.ResultsFive clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis.ConclusionClustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.

Abstract Background In this study, the serological characteristics, sequencing analysis and cytokine levels of HBsAg negative and HBV DNA positive patients were analyzed to preliminarily determine whether being HBsAg clearance was related to immune function. Methods Evaluate the basic medical records and laboratory data of 279 HBsAg negative and HBV DNA positive patients. Serum samples from 30 HBsAg negative and HBV DNA positive patients, 20 matched HBsAg persistently positive patients and 16 healthy people were tested for 48 cytokines, chemokines and growth factors. Sanger sequencing was used to analyze the HBV S region sequences of HBsAg negative and HBV DNA positive patients samples. Results Of the 76428 HBV-infected patients enrolled, 358 (0.47%) were defined as HBsAg negative and HBV DNA positive patients. The main serological patterns of HBsAg negative and HBV DNA positive patients were anti-HBe and anti-HBc positive, accounting for 47.67%. HBV DNA load<200IU/ml was found in 94.98%. Serum sCD40L, G-CSF, IFN-γ, MIP-1α, RANTES and Eotaxin levels were significantly higher in the HBsAg negative group than in the HBsAg positive group(P＜0.05), but IL-4, IL-6, IL-8, IL-13, IL-17A, PDGF-AA, TGF-α and TNF-β levels were lower in the HBsAg negative group(P<0.05). Between the HBsAg negative group and the healthy control group, there were also differences in the levels of several serum cytokines, chemokines, and growth factors. The levels of AST/ALT were positively correlated with IL-15(P=0.040/0.009) and IL-18(P=0.031/P=0.003). Nine HBsAg negative samples were sequenced, revealing amino acid substitutions in the HBV S protein, including immune escape mutations(Y100C, S114T, C124Y, P127L, G130R, T131N, M133T) and affecting HBsAg secretion mutations(E2R/K/D). Conclusions The levels of HBV DNA replication and transcription are low in most HBsAg negative and HBV DNA positive patients. Since there were fewer HBsAg negative and HBV DNA positive patients in this study with significant and meaningful HBV mutations, viral factors might not be the primary causes. Therefore, it is more valuable to proceed from the host factor. By inducing a slightly stronger host immune response and controlling liver inflammation, several cytokines and chemokines, including G-CSF, IFN-γ, MIP-1α, RANTES and Eotaxin, may promote in the clearance of HBsAg.

目的 总结25730例乙型肝炎病毒感染患者血清学标志物模式.方法 回顾性分析2018～2021年乙型肝炎病毒(hepatitis B virus,HBV)感染患者中血清学模式、比例及合并感染情况.收集北京佑安医院2018～2021年HBV感染患者的乙肝五项(HBsAg、Anti-HBs、HBeAg、Anti-HBe、Anti-HBc)、肝功能、HBV DNA载量、AFP和PT检测结果及基本临床信息,采用SPSS 26.0统计学软件分析HBV感染患者的疾病诊断、乙肝五项血清学标志物阳性模式和临床特征情况.结果 2018～2021年就诊患者HBsAg阳性率依次为63.80％、61.37％、58.44％和53.16％,呈逐年下降趋势,组间两两比较差异均有统计学意义(P<0.001).25730例患者按照年龄分为1～30岁组、31～60岁组和>60岁组,3个年龄组急性乙型肝炎、慢性乙型肝炎、HBV相关性肝硬化、HBV相关性肝癌及肝癌术后、肝移植术后临床诊断差异均有统计学意义(均P<0.05).随着年龄增长,慢乙肝的患者比例呈下降趋势(x2=2390.617,P<0.001);而HBV相关性肝硬化、HBV相关性肝癌及肝癌术后和肝移植术后的HBV感染患者随着年龄增长,患者比例呈上升趋势(x2=1390.946,P<0.001;x2=586.225,P<0.001;x2=22.647,P<0.001).乙肝五项血清模式有20种,其中常见模式有9种(比例最高为145阳)、少见模式5种(比例最高为5阳),罕见模式6种(比例最高为235阳).HBV感染中丙肝抗体阳性率为2.658％(312/11740),HIV确证阳性率为0.158％(16/10113),抗核抗体阳性率为68.483％(4663/6809).结论 2018～2021年,全院就诊患者HBsAg阳性检出率逐年下降.HBV感染患者疾病进展与患者年龄相关.HBV感染者乙肝五项血清学指标模式呈现多样性,结合HBV DNA结果和合并感染有助于对特殊模式的理解.

This study aimed to isolate and characterize phages as an alternative treatment of multidrug- or pan-drug-resistant Pseudomonas aeruginosa. Phage titers and bacterial densities correlated, with the phages disappearing after bacteria were eliminated. We isolated phages in filtered sewage water by a double-layered agar spot test. Fifty-eight P. aeruginosa strains were used to screen the host spectrum of the 14 phages isolated. Random amplification of polymorphic DNA-typing polymerase chain reaction was used to analyze the genomic homologies of the 58 host bacteria strains and four phages with a broad host spectrum. Transmission electron microscopy was used to observe the morphology of the four phages with a broad host spectrum. Mice with intraabdominal P. aeruginosa infection were used as an in vivo animal model to investigate the therapeutic effect of the selected phage. Four virulent phages with a broad host spectrum specific to P. aeruginosa strains were isolated. They were all double-stranded DNA viruses and belonged to four different genotypes. The test curve showed that phage I had the highest adsorption rate, the shortest latent period, and the largest burst size. The infected mouse model indicated that small doses of phage I could prevent the death of infected mice. Phage titers and bacterial densities correlated, with phages disappearing after bacteria were eliminated. Phage I was the most effective and promising treatment of drug-resistant P. aeruginosa.

目的 探讨血浆蛋白C(protein C,PC)、血浆蛋白S(protein S,PS)、血浆抗凝血酶(antithrombin,AT)、血浆凝血因子Ⅷ(coagulation factor Ⅷ,F Ⅷ)在不同Child-Pugh肝功能分级的慢性肝硬化患者中的应用意义.方法 选取2020年12月至2021年12月首都医科大学附属北京佑安医院进行诊治的96例慢性肝硬化患者作为研究对象,另选择同期体检正常的15例正常人作为对照组,分别采用发色底物法和凝固法测定不同Child-Pugh肝功能分级患者的PC、PS、AT、FⅧ等水平并进行比较,并分析相关性.结果 蛋白C、蛋白S、AT、FⅧ在不同Child-Pugh肝功能分级的分组间有显著差异.随着Child-Pugh肝功能分级变差,患者的蛋白C、蛋白S和AT的活性明显降低,FⅧ活性增加.结论 慢性肝硬化有高凝风险,建议检测和评估血栓形成的可能.

Background: Spontaneous fungal peritonitis (SFP) and fungiascites is less well-recognized and described in patients with liver cirrhosis. The aims of this study were to determine the clinical characteristics, prognosis, and risk factors of cirrhotic patients with SFP/fungiascites and to improve early differential diagnosis with spontaneous bacterial peritonitis (SBP). Methods: This was a retrospective case–control study of 54 cases of spontaneous peritonitis in cirrhotic patients (52 SFP and 2 fungiascites) with fungus-positive ascitic culture. Fifty-four SBP cirrhotic patients with bacteria-positive ascitic culture were randomly enrolled as a control group. A nomogram was developed for the early differential diagnosis of SFP and fungiascites. Results: Hospital-acquired infection was the main cause of SFP/fungiascites. Of the 54 SFP/fungiascites patients, 31 (57.41%) patients carried on with the antifungal treatment, which seemed to improve short-term (30-days) mortality but not long-term mortality. Septic shock and HCC were independent predictors of high 30-day mortality in SFP/fungiascites patients. We constructed a predictive nomogram model that included AKI/HRS, fever, (1,3)-β-D-glucan, and hospital-acquired infection markers for early differential diagnosis of SFP/fungiascites in cirrhotic patients with ascites from SBP, and the diagnostic performance was favorable, with an AUC of 0.930 (95% CI: 0.874–0.985). Conclusions: SFP/fungiascites was associated with high mortality. The nomogram established in this article is a useful tool for identifying SFP/fungiascites in SBP patients early. For patients with strongly suspected or confirmed SFP/fungiascites, timely antifungal therapy should be administered.

目的 比较PCT、IL-6、NLR和PLR在自发性细菌性腹膜炎患者中的诊断效能,对比筛选自发性细菌性腹膜炎患者更合理的感染学指标辅助诊断方案.方法 收集本院176例临床肝硬化合并腹水患者血液及腹水标本,其中合并自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)患者85例,未合并SBP患者91例.检测患者全血常规、血清和腹水PCT及IL-6,进行统计分析.结果 肝硬化合并SBP患者血清及腹水PCT、IL-6、NLR和PLR水平明显高于未合并SBP患者,差异有统计学意义.在培养结果阳性和培养结果阴性的SBP患者标本中,所有指标差异均无统计学意义,同时,腹水培养出革兰阴性菌和培养出革兰阳性菌的患者的标本中,血清IL-6及NLR差异有统计学意义,其他指标差异无统计学意义.血清PCT、腹水PCT、血清IL-6、腹水IL-6、NLR和PLR诊断SBP的ROC曲线下面积分别为0.750、0.677、0.800、0.837、0.776、0.624,其中腹水IL-6诊断价值最大,约登指数最大时,其灵敏度为67.1％,特异性为86.8％.患者有效治疗前后腹水PCT水平差异无统计学意义,血清PCT、血清IL-6和腹水IL-6在治疗后水平下降,差异有统计学意义.其中,血清IL-6和腹水IL-6治疗前后差异明显.结论 在自发性细菌性腹膜炎的辅助诊断中,IL-6相比PCT、NLR和PLR更具优势.结合诊断效益和经济效益,推荐使用IL-6对SBP患者进行辅助诊断.

Background:Clinically, some patients whose HBsAg becomes negative owing to antiviral therapy or spontaneously still show a low level of HBV DNA persistence in serum. T-lymphocyte subsets, cytokine levels and HBV S gene sequences were analyzed in this study.Methods:A total of 52 HBsAg-negative and HBV DNA-positive patients(HBsAg-/HBV DNA+ patients), 52 persistently HBsAg-positive patients(HBsAg+/HBV DNA+ patients) and 16 healthy people were evaluated. T-lymphocyte subsets of these patients were detected by flow cytometry, serum cytokines and chemokines were detected by the Luminex technique, and the HBV S region was evaluated by Sanger sequencing. T%, T-lymphocyte, CD8+ and CD4+T lymphocyte were lower in the HBsAg-negative group than in the HC group. Compared with the HBsAg-positive group, the HBsAg-negative group had lower levels in T lymphocyte %, CD8+T lymphocyte %, CD8+T lymphocyte and CD4/CD8. These difference were statistically significant (P<0.05). Serum IFN-γ, IFN-α and FLT-3L levels were significantly higher in the HBsAg-negative group than in the HBsAg-positive group (P<0.05). However, levels of many cytokines related to inflammation (i.e., IL-6, IL-8, IL10, IL-12, IL-17A) were lower in the HBsAg-negative group. Fifty-two HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., Y100C, S114T, C124Y, P127L, G130R, T131N, M133T, C137S, G145A) and TMD region substitutions (i.e., E2K/R/D, G7D/R, G10D, A17R, F20L/S, L21V, L22V).Conclusions:According to the results of T-lymphocyte subsets and serum cytokines, it can be deduced that the cellular immune function of HBsAg-negative patients is superior to that of HBsAg-positive patients, with attenuation of liver inflammation. HBsAg-negative patients may show a variety of mutations and amino acid replacement sites at high frequency in the HBV S region, and these mutations may lead to undetectable HBsAg, HBsAg antigenic changes or secretion inhibition.

目的 分析失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与乙型肝炎病毒标志物、生化及凝血等指标的相关性.方法 回顾性分析2018年1月至2020年12月我院收治的645例失代偿期乙型肝炎肝硬化患者的临床资料,根据HBV-DNA水平分为4组:阴性组、低病毒载量组(<2.0×103 IU/mL)、中病毒载量组(2.0×103～2.0×105 IU/mL)和高病毒载量组(>105 IU/mL),测定所有患者乙型肝炎病毒血清学标志物(HBV-M)、肝功能相关生化指标(ALT、AST、TBIL、DBIL、ALB)、凝血相关指标(PT、INR、APTT、TT、D-D、PLT),比较4组患者各项指标的差异,并分析各项指标与HBV-DNA水平的相关性.结果 在失代偿期乙型肝炎肝硬化患者中,HBsAg和HBeAg的定量数值随着HBV-DNA水平的升高而增高,HBsAg的明显升高主要体现在HBV-DNA阴性组和低病毒载量组之间(779.40 vs 5773.00IU/mL),而HBeAg的表达在中病毒载量组(0.19 COI)和高病毒载量组(7.96 COI)中才出现显著升高,低病毒载量组的HBeAg阳性表达率较低.随着病毒载量的升高,患者的ALT、AST、TBIL、DBIL、D/T、AFP指标均有所升高,而ALB的水平降低;除TT存在显著性差异外,PT、APTT、INR、Fib、D-D、PLT这6个指标差异均无统计学意义.经Pearson相关性分析检验,失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与ALT、AST、TBIL、DBIL、AFP、PT、APTT、TT、D-D、HBsAg、HBeAg水平呈正相关(r>0,P均<0.05),与ALB、Fib水平呈负相关(r<0,P均<0.05),与PLT、HBeAb水平不存在相关性.结论 在失代偿期乙型肝炎肝硬化患者中,血清HBV-DNA载量与HBsAg、HBeAg表达水平密切相关,与ALT、AST、TBIL、DBIL、D/T、ALB等肝功能相关生化指标相关,与凝血相关指标存在关联,但在不同HBV-DNA载量组中无差异.HBV-DNA载量可作为HBeAg阴性患者肝脏损害程度的有效预测指标.

Objective:We conducted a real-world multi-center clinical study with a large sample size to comprehensively evaluate the performance of three commercial hepatitis C virus (HCV) core antigen assays. The study aimed to evaluate the performance for their use in HCV infection screening, and to provide clues for further improving the sensitivity and specificity of the assays.Methods:Key performance indicators including the lower limit of detection (LOD), diagnostic sensitivity, and specificity of three HCV antigen assays (the Architect, Laibo, and ChemClin HCV core antigen assays) were evaluated using commercial seroconversion panels reflecting early HCV infection and clinical routine serum samples of outpatients and inpatients from 3 tertiary hospitals from January 2018 to April 2022. Factors that affect the performance indicators were further investigated.Results:The window period for detecting HCV infection with the three antigen assays was equal to or slightly longer than that of the RNA assay, but all are shorter than that of the anti-HCV assay. There was a good linear positive correlation between HCV core antigen and HCV RNA levels in treatment naive patients with hepatitis C ( r=0.90, P<0.01). For the most common genotype 1b strain in China, the LOD of the three HCV assays were equivalent to 531 IU/ml (Architect), 3,698 IU/mL (Laibo), and 4,624 IU/mL (ChemClin) HCV RNA, respectively. Due to the skewed distribution of HCV RNA levels in treatment-naive hepatitis C patients, more than 95% of the patients had viral loads higher than 6 166 IU/ml. Therefore, the three HCV antigens assays still maintained a satisfactory diagnostic sensitivity (94.33%-99.40%). Among 54 immunodeficient patients (leukemia patients) with HCV infection, 9% (5/54) had negative anti-HCV results, while the HCV antigen assays found all these infectors. Through further experiments, we revealed the amino acid polymorphism in the core region of genotype 3 strain impaired the sensitivity of all three HCV antigen assays. In addition, the sensitivity of the two domestic assays was impaired by anti-HCV antibodies in the serum. The specificity of HCV antigen assays for diagnosing hepatitis C is 99.94% to 99.98%. The rheumatoid factors, autoantibodies, and other unknown interference substances can lead to a small number of low level, "false positive" antigen results. Conclusions:HCV core antigen assay may be used as a satisfactory approach of infection screening, especially for the immunodeficient patents. However, the sensitivity and specificity of the assays are influenced by multiple factors, which should be further improved.

OBJECTIVE:Acute-on-chronic liver failure (ACLF) is a type of liver failure commonly found in China, and currently the mechanism of the disease remains unknown. This study aimed to investigate the epidemiology, clinical features and prognostic factors in ACLF.METHODS:This study retrospectively included 170 patients with ACLF admitted to Beijing Friendship Hospital in Beijing, China from November 2017 to May 2019. Patients were divided into 2 groups: the improved group and the deteriorated group, according to the severity of their disease. Patients' demographic data; clinical manifestations; complications; laboratory indicators including platelets (PLT), alanine aminotransferase (ALT), aspartate amino transferase (AST), total bilirubin (TBIL), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), and alkaline phosphatase (ALP) were collected. The relationship between these factors and the patients' prognosis were analyzed by logistic multivariate regression analysis.RESULTS:The highest morbidity rate was in the age group 40 to 49 years (29.41%). The age group with the second highest morbidity was between 50 and 59 years (25.29%), followed by >60 (21.18%), 30 to 39 (20.59%), 20 to 29 (2.94%) and <20 years (0.59%). A total of 53 patients (31.18%) had a family history of hepatitis B virus infection. The patients' main clinical manifestations were ascites (77.65%) and weakness (68.23%). The most common complications were hypoalbuminemia (80%), infection (67.65%) and electrolyte imbalance (44.12%). In addition, the PTA (P = .009), hepatorenal syndrome (P = .005) and hepatic encephalopathy (level IV) (P = .005) were independently related to the prognosis of ACLF. There is a significant relationship between complications and prognosis (χ2 = 8.502; P = .004).CONCLUSION:This study showed that prothrombin activity, hepatorenal syndrome and hepatic encephalopathy were independently related to the prognosis of ACLF. This outcome provided more options for reducing patient mortality in clinic.