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Background and aimsCurrent guidelines are controversial regarding the continuation of nucleos(t)ide analogues (NAs) therapy after delivery in Hepatitis B virus (HBV)-infected pregnant women. The postpartum period may be an opportune moment for achieving hepatitis B e antigen (HBeAg) seroconversion earlier with constant NAs therapy due to the restoration of immune function after delivery. We investigated prenatal and pregnant factors associated with HBeAg seroconversion after pregnancy and developed a nomogram to predict HBeAg seroconversion rates, aiding decision-making for optimal management in women.MethodsWe retrospectively included 489 HBeAg-positive mothers as the training cohort from January 2014 to December 2018 and prospectively enrolled 94 patients as the external validation cohort from January 2019 to December 2021 at the First Affiliated Hospital of Xi’an Jiaotong University. In the training cohort, independent predictors were identified using the least absolute shrinkage and selection operator (LASSO) regression algorithm. Subsequently, multivariate logistic regression was employed to establish the nomogram. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). Both discrimination and calibration were evaluated through bootstrapping with 1,000 resamples. The external validation cohort was subsequently used to validate the nomogram.ResultsFactors such as pregnancy hepatitis flare (OR: 5.122, 95% CI: 2.725–9.928, p

ABSTRACTApproximately two-thirds of hepatocellular carcinoma (HCC) is considered a “cold tumor” characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvβ3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure implies that integrin αvβ3 may play an important role in immune cells. However, the expression and potential role of integrin αvβ3 in T cells of HCC patients remain unknown. Here, we established two HCC models and found that cilengitide had a dual effect on the HCC microenvironment by exerting both antitumor effect and immunosuppressive effect on T cells. This may partly explain the failure of cilengitide in clinical trials. In clinical specimens, HCC-infiltrating T cells exhibited deficient expression and activation of integrin β3, which was associated with poor T-cell infiltration into tumors. Additionally, integrin β3 functioned as a positive immunomodulatory molecule to facilitate T-cell infiltration and T helper 1-type immune response in vitro. Furthermore, T cells and platelet-derived microparticles (PMPs) co-culture assay revealed that PMPs adoptively transferred integrin β3 to T cells and positively regulated T cell immune response. This process was mediated by clathrin-dependent endocytosis and macropinocytosis. Our data demonstrate that integrin β3 deficiency on HCC-infiltrating T cells may be involved in shaping the immunosuppressive tumor microenvironment. PMPs transfer integrin β3 to T cells and positively regulate T cell immune response, which may provide a new insight into immune therapy of HCC.

Background & Aims: The function of cholinergic anti-inflammatory pathway (CAP) in acute liver failure (ALF) with inflammatory storm remains indefinite. The liver-gut axis has been proved to be crucial for liver homeostasis. Investigation about CAP regulation on liver-gut axis would enrich our understanding over cholinergic anti-inflammatory mechanism. Methods: Co-injection of lipopolysaccharide and D-galactosamine was used to establish the model of ALF. PNU-282987 was used to activate the CAP. Histological staining, real-time polymerase chain reaction, Western blotting, RNA sequencing, and flow cytometry were conducted. Liver biopsy specimens and patients’ serum from patients with liver failure were also analyzed. Results: We confirmed that activating the CAP alleviated hepatocyte destruction, accompanied by a significant decrease in hepatocyte apoptosis, pro-inflammatory cytokines, and NLRP3 inflammasome activation. Moreover, hepatic MAdCAM1 and serum MAdCAM1 levels were induced in ALF, and MAdCAM1 levels were positively correlated with the extent of liver damage and the expression of pro-inflammatory markers. Furthermore, activating the CAP mainly downregulated ectopic expression of MAdCAM1 on endothelial cells, and inhibition of NF-κB p65 nuclear translocation was partly attributed to the decreased MAdCAM1. Notably, in ALF, the aberrant hepatic expression of MAdCAM1 subsequently recruited gut-derived α4β7+ CD4+T cells to the liver, which exhibited an augmented IFN-γ-secreting and IL-17-producing phenotype. Finally, we revealed that the levels of serum and hepatic MAdCAM1 were elevated in patients with liver failure and closely correlated with clinical course. Increasing hepatic infiltration of β7+ cells were also confirmed in patients. Conclusions: Activating the CAP attenuated liver injury by inhibiting MAdCAM1/α4β7 -mediated gut-derived proinflammatory lymphocytes infiltration, which provides a potential therapeutic target for ALF.

Objectives: The liver has an excellent ability to regenerate, and disrupted liver regeneration after various injuries leads to an unfavorable prognosis for patients. In this study, we sought to identify novel therapeutic hallmarks that are associated with yes-associated protein 1 (YAP1)-mediated hepatocyte proliferation during the process of liver regeneration. Methods: Partial hepatectomy was conducted to induce liver regeneration in rats. Primary hepatocytes were isolated and cultured. Hepatocyte proliferation was assessed using immunohistochemistry staining, and expression of YAP1 was detected. RNA sequencing and bioinformatics analysis were used to search for potential regulators of YAP1. The association between ubiquitin-specific peptidase 1 (USP1) and YAP1 was validated using in vivo and in vitro experiments. Results: YAP1 was significantly elevated in regenerative hepatocytes, especially in the nucleus. Knockdown of YAP1 using small interfering RNA or pharmacological inhibition using verteporfin significantly attenuated the proliferation of hepatocytes. The bioinformatics analysis results revealed that USP1 was associated with YAP1-mediated hepatocyte proliferation during liver regeneration. ML-323, a specific inhibitor of USP1-USP1 associated factor 1 (UAF1), significantly decreased the expression of YAP1, Cyclin D1, and proliferating cell nuclear antigen, while these decreased expressions could be rescued by YAP1 overexpression. Furthermore, ML-323 treatment significantly inhibited liver regeneration following partial hepatectomy. Conclusions: In conclusion, we identified USP1 as a novel biomarker that is associated with YAP1-mediated hepatocyte proliferation in liver regeneration. Pharmacological inhibition of USP1 by ML-323 substantially impairs hepatocyte proliferation during liver regeneration.

Abstract Introduction A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p

Abstract 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

Abstract. Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonosis with a global distribution. China is one of the countries with a high incidence of HFRS, which has long endangered the lives and health of the Chinese people. The Infectious Disease Branch of the Chinese Preventive Medicine Association and the Infectious Diseases Branch of the Chinese Medical Association organized national multidisciplinary experts, based on domestic and international research results combined with experts’ practical experiences, to reach this consensus after thorough discussion. This consensus contains 17 recommendations aimed at prevention and identification of important clinical issues to further standardize the prevention, diagnosis, and treatment of HFRS.

Background and aimSepsis is a syndromic response to infection and is associated with high mortality, thus imposing a significant global burden of disease. Although low-molecular-weight heparin (LMWH) has been recommended to prevent venous thromboembolism, its anticoagulant and anti-inflammatory effects in sepsis remain controversial. Owing to the modification of the Sepsis-3 definition and diagnostic criteria, further evaluation of the efficacy and benefit population of LMWH is required.MethodsWe performed a retrospective cohort study to assess whether LMWH improved the inflammation, coagulopathy, and clinical outcomes against Sepsis-3 and to identify the target patients. All patients diagnosed with sepsis at the First Affiliated Hospital of Xi'an Jiaotong University (the largest general hospital in northwest China) from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria.ResultsAfter 1:1 propensity score matching, 88 pairs of patients were categorized into the treatment and control groups based on subcutaneous LMWH administration. Compared with the control group, a significantly lower 28-day mortality was observed in the LMWH group (26.1 vs. 42.0%, p = 0.026) with a comparable incidence of major bleeding events (6.8 vs. 8.0%, p = 0.773). Cox regression analysis showed that LMWH administration was the independent protective factor for septic patients (aHR, 0.48; 95% CI, 0.29–0.81; p = 0.006). Correspondingly, the LMWH treatment group showed a significant improvement in inflammation and coagulopathy. Further subgroup analysis showed that LMWH therapy was associated with favorable outcomes in patients younger than 60 years and diagnosed with sepsis-induced coagulopathy (SIC), ISTH overt DIC, non-septic shock, or non-diabetics and in patients included in the moderate-risk group (APACHE II score 20–35 or SOFA score 8–12).ConclusionOur study results showed that LMWH improves 28-day mortality by improving inflammatory response and coagulopathy in patients meeting Sepsis-3 criteria. The SIC and ISTH overt DIC scoring systems can better identify septic patients who are likely to benefit more from LMWH administration.

Abstract. End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.

Abstract Background Hemorrhagic fever with renal syndrome (HFRS) is a disease with increased systemic inflammation and a high fatality rate. Oxidative stress is crucial for inflammation in the pathogeneses of various diseases. We aimed to identify biomarkers of oxidative stress that may assess the severity and disease outcomes of patients with HFRS. Methods Between January 2015 and September 2018, we analyzed a retrospective cohort of 149 HFRS patients and 30 healthy individuals. Serum levels of SOD were measured using an ELISA commercial kit, and survival analysis was carried out using the Kaplan–Meier method. Results Patients with HFRS had significantly lower serum SOD levels compared with healthy controls (108.40 ± 2.47 U/mL vs 164.23 ± 3.82 U/mL, P

Abstract Background Fewer than 50% of patients with acute-on-chronic liver failure (ACLF) recover spontaneously, and ACLF has high mortality without liver transplantation. Oxidative stress has been shown to mediate hepatic inflammation during acute liver failure (ALF). We wanted to see if a biomarker for oxidative stress might be used to measure the severity and prognosis of ACLF patients. Methods A retrospective cohort of 124 ACLF patients, as well as healthy individuals, liver cirrhosis and ALF patients, was studied between January 2015 and September 2018. The levels of plasma superoxide dismutase (SOD) were detected using an ELISA commercial kit, and the Kaplan–Meier method was used for survival analysis. Results Patients with ACLF had statistically higher plasma SOD levels than the controls did (healthy controls and liver cirrhosis patients); however, the levels did not differ from those in patients with ALF. The plasma SOD level may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 1.201, 95% CI 1.001–1.403, P 428 U/mL was linked to a statistically significant increase in the likelihood of death or liver transplantation in ACLF patients. Combination of plasma SOD levels and MELD scores improved performance in measuring the severity and prognosis of ACLF patients. Conclusion Patients with ACLF can be classified into high-risk and low-risk groups based on their plasma SOD levels at the time of admission to the hospital. The patient outcome is more closely connected with the combination of SOD level and MELD score than either value alone. This approach might be used to predict patient prognoses and prioritize liver transplant candidates.

Abstract Background Viral hepatitis E clinically ranges from self-limiting hepatitis to lethal liver failure. Oxidative stress has been shown to mediate hepatic inflammation during HBV-induced liver failure. We investigated whether a biomarker of oxidative stress may be helpful in assessing severity and disease outcomes of patients with HEV-induced liver failure. Methods Clinical data were obtained from patients with HEV-induced acute viral hepatitis (AVH, n = 30), acute liver failure (ALF, n = 17), and acute-on-chronic liver failure (ACLF, n = 36), as well as from healthy controls (HC, n = 30). The SOD and HMGB1 levels were measured in serum by ELISA. HL-7702 cells were cultured and stimulated by serum from HEV-infected patients or by HMGB1; oxidative status was investigated by CellROX and apoptosis was investigated by flow cytometry. Results Patients with HEV-induced liver failure (including ALF and ACLF) showed increased SOD levels compared with HEV-AVH patients and healthy controls. SOD levels > 400 U/mL were associated with a significantly higher risk of mortality in HEV-ALF and HEV-ACLF patients. Serum from HEV-infected patients led to ROS accumulation, HMGB1 secretion, and apoptosis in HL-7702 cells. Antioxidant treatment successfully inhibited HEV-induced HMGB1 secretion, and HMGB1 promoted apoptosis in HL-7702 cells. Conclusion HEV increased oxidative stress in the pathogenesis of HEV-induced hepatic diseases. Early testing of serum SOD may serve as a predictor of both HEV-ALF and HEV-ACLF outcomes. Moreover, development of strategies for modulating oxidative stress might be a potential target for treating HEV-induced liver failure patients.

Abstract Background & Aims There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. Methods Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. Results Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. Conclusions TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. Trial registration This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019).

Abstract Background A series of evidence revealed that body mass index was an important confounding factor in the research of uric acid and ischemic heart disease/hypertension. The objective of this study was to investigate whether obesity status can modify the association between serum uric acid and the severity of liver damage in NAFLD, and the possible interactive effect of hyperuricemia and obesity. Methods We conducted a cross-sectional study in a total of 557 ultrasound diagnosed-NAFLD. The hepatic steatosis and liver fibrosis were quantitatively evaluated by transient elastography. Hyperuricemia was defined as serum uric acid > 420 μmol/L in men, > 360 μmol/L in women and obesity was defined as body mass index ≥ 25 kg/m2. The adjusted OR values of hyperuricemia and obesity were analyzed by multivariate logistic regression analysis, and the additive model was used to investigate the possible interactive effect. Results Multivariate regression analysis showed that hyperuricemia was associated with serious hepatic steatosis (1.74[1.09–2.79]) and elevated ALT (2.17[1.38–3.41]), but not with advanced fibrosis (1.61[0.91–2.85]). The association was further investigated in different BMI group. Hyperuricemia was associated with higher odds of serious hepatic steatosis (2.02[1.14–3.57]) and elevated ALT (2.27[1.37–3.76]) only in obese NAFLD, not in non-obese subjects. Similarly, patients with hyperuricemia had higher odds of advanced fibrosis in obese subjects (2.17[1.13–4.18]), not in non-obese subjects (0.60[0.14–2.70]). Furthermore, there was an additive interaction between hyperuricemia and obesity on the odds of serious hepatic steatosis (AP: 0.39[0.01–0.77]) and advanced fibrosis. (AP: 0.60[0.26–0.95]). Conclusions Hyperuricemia and obesity had a significantly synergistic effect on the hepatic steatosis and fibrosis. Thus, management of uric acid may need to be targeted in obese NAFLD.

Abstract Objectives A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. Results 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

Objective(s): To investigate the protective effect of glycyrrhizin (GL) on hepatic ischemia-reperfusion injury (HIRI).Materials and Methods: Forty SD rats were randomly divided into sham group, HIRI group, GL 100 mg/kg group, and GL 200 mg/kg group. The pathological alterations of liver tissue in each group were observed. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), endothelin-1 (ET-l), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detected. Western blot was used to detect the expression levels of cytoplasmic protein caspase-3, Bax, Bcl-2, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear protein Nrf2.Results: Compared with the HIRI group, the levels of AST, ALT, ET-1, TNF-α, IL-1β, and IL-6 in GL groups were lower, serum NO content was higher, MDA content was lower, SOD and GSH-Px activities were significantly increased, apoptosis index was lower (PConclusion: GL has a protective effect on the liver of HIRI rats, and its mechanism may be related to activation of the Nrf2/HO-1 signaling pathway, inhibition of oxidative stress, inflammation, autophagy, and apoptosis.

Pregnant women with hemorrhagic fever with renal syndrome (HFRS) are a significant challenge for clinicians. The clinical characteristics of HFRS in pregnant women and its influence on both the pregnant women and fetus have yet to be clarified clearly. To highlight the specific clinical features of HFRS in pregnant women and the outcomes of pregnant women with HFRS and their fetuses, we screened pregnant women with HFRS from inception to May 1st 2021. We also conducted a comparison with non-pregnant women complicated with HFRS. Twenty-seven pregnant women and 87 non-pregnant women with complete electronic medical records were enrolled for final analyses; 55.6% (15/27) and 21.8% (19/87) were diagnosed as critical type in pregnant women and non-pregnant women, respectively. Compared with non-pregnant patients, there was a significantly higher likelihood of critical status in pregnant patients; the risk was significantly higher in late trimester (p

Background. Inflammation plays a critical role in the progression of acute-on-chronic liver failure (ACLF). Atg13 is a vital regulatory component of the ULK1 complex, which plays an essential role in the initiation of autophagy. Previously, hepatic stellate cells (HSCs) were considered to be noninflammatory cells that contribute only to hepatic fibrosis. Recently, it has been found that HSCs can secrete inflammatory cytokines and participate in hepatic inflammation. Autophagy and proteasome-mediated degradation constitute two major means of protein turnover in cells. Autophagy has been shown to regulate inflammation, but it is unclear whether ubiquitin (Ub)-proteasome system (UPS) is involved in inflammatory responses in HSCs during ACLF. Methods. Clinical data were collected from ACLF patients, and surgically resected paraffin-embedded human ACLF liver tissue specimens were collected. The expression of Atg13 was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Secretion of IL-1β was assessed by ELISA. Atg13 was knocked down by siRNA in LX2 cells. Coimmunoprecipitation assay was used to detect protein binding and polyubiquitination of Atg13. In vitro tests with LX2 cells were performed to explore the effects and regulation of p38 MAPK, Atg13, UPS, autophagy, and inflammation. Results. Serum lipopolysaccharide (LPS) was positively associated with disease severity in ACLF patients, and p38 MAPK was overexpressed in ACLF liver tissue. We evaluated the role of Atg13 in HSC inflammation and explored the possible underlying mechanisms. Inflammatory factors were upregulated via activation of p38 MAPK and inhibition of autophagy in LX-2 cells. Expression of Atg13 was decreased in LPS-incubated LX2 cells. Atg13 knockdown markedly inhibited autophagy and promoted LPS-induced inflammation in LX2 cells. Our in vitro experiments also showed that LPS induced depletion of Atg13 via UPS, and this process was dependent on p38 MAPK. Conclusions. LPS induces proteasomal degradation of Atg13 via p38 MAPK, thereby participating in the aggravation of LPS-induced autophagy inhibition and inflammatory responses in LX2 cells. Atg13 serves as a mediator between autophagy and proteasome. Modulation of Atg13 or proteasome activity might be a novel strategy for treating HSC inflammation.

BackgroundDespite 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).MethodsSeventy-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.ResultsA 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

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests.Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient's clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged.Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients.

Interferon (IFN) treatment is widely applied in viral hepatitis and multiple myeloproliferative diseases. However, there is considerable controversy on how to deal with unintended pregnancy during IFN treatment, even selective termination is suggested by hepatologists. To settle this clinical dilemma, we conducted a systematic review to retrieve all published articles involving IFN exposure during pregnancy up until March 31, 2021. Only 8 case reports that were relevant with outcomes of pregnant women with viral hepatitis exposed to IFN-α were retrieved, and 17 studies reporting pregnancy outcomes after exposure to type I IFNs involving 3,543 pregnancies were eligible for meta-analysis. No birth defect was reported in the case reports of pregnant women with viral hepatitis. The meta-analysis showed that risks of pregnancy outcomes and birth defects were not increased after exposure to IFN-α. Further comprehensive meta-analysis concerning the IFN-α and IFN-β exposure demonstrated that the risks of live birth (OR 0.89, 95% CI: 0.62–1.27), spontaneous abortion (OR 1.09, 95% CI: 0.73–1.63), stillbirth (OR 1.38, 95% CI: 0.51–3.72), preterm delivery (OR 1.24, 95% CI: 0.85–1.81), and maternal complications (OR 0.72, 95% CI: 0.38–1.38) were not increased in patients exposed to IFNs. The pooled estimates of live birth, spontaneous abortion, stillbirth, preterm delivery, and maternal complications were 85.2, 9.4, 0, 7.5, and 6.5%, respectively. Importantly, the risk of birth defects was not increased (OR 0.68, 95% CI: 0.39–1.20) after IFN exposure, with a pooled rate of 0.51%. Therefore, IFN exposure does not increase the prevalence of spontaneous abortion, stillbirth, preterm delivery, and birth defects. Clinical decision should be made after weighing up all the evidence.

Abstract Background Sofosbuvir is the keystone of direct antiviral agents for the chronic hepatitis C (CHC). The safety of sofosbuvir in patients with stage 4–5 chronic kidney disease (CKD) needs further observation in real world. Case presentation Thirty-three patients with stage 5 CKD and hepatitis C virus (HCV) infection from 2 hemodialysis centers accepted sofosbuvir based treatment as we reported previously. Serum potassium concentrations were tested every 4 weeks or on demand. Ten of 33 patients showed recurrence of hyperkalemia. We summarized the characteristics of hyperkalemia occurrence in these 10 patients. Overall, 24 episodes of hyperkalemia were observed in these 10 patients, 21 were under treatment and 3 were after treatment. Patients with or without hyperkalemia before sofosbuvir treatment didn’t show significantly differences in the median frequencies of hyperkalemia episodes during the observation period (3.5 vs. 2, p = 0.264). Conclusions Patients with stage 5 CKD and HCV infection treated with sofosbuvir based regimens, even halved sofosbuvir, should be taken caution and closely monitoring serum potassium and renal function is necessary.

The optimal timing of initiating antiviral treatment for immune-tolerant (IT) patients remains unknown. We conducted this study in liver biopsy-proven IT patients to compare the long-term outcomes of untreated and treated patients suffering non-cirrhotic chronic hepatitis B (CHB). This retrospective cohort study recruited 171 consecutive treatment-naïve CHB patients who completed liver biopsy test. Patients were stratified into IT (n = 60), mildly-active (MA; n = 31), immune-active (IA; n = 80), according to alanine aminotransferase (ALT) and liver biopsy data. One hundred and nine patients receiving antiviral treatment constituted the treated set, and 62 patients under close follow-up comprised the untreated set. Primary outcomes were virological response, HBeAg seroconversion, HBsAg loss, ALT normalization, and liver stiffness measurement normalization (NCT03740789). The study population was predominantly male (62.6%) with a mean age of 31 years. The proportion of virological response in treated patients in the MA phase was 57.1%, and the proportion of HBeAg seroconversion was 28.6%, which showed no difference with the 43.8% virological response and 31.5% HBeAg seroconversion in IA patients. The proportions of virological response and seroconversion were 18.2 and 9.1%, respectively, in the IT phase, which were lower than the rates in the MA and IA phases. However, 95.5% of IT patients persisted normal ALT, and 100% of IT patients persisted normal liver stiffness measurement in the treated group. Therefore, antiviral treatment should be considered for CHB patients with high viral load regardless of phase to minimize further damage to hepatocytes.

Background. HBV-resistant mutants in treatment-naïve patients may lead to antiviral treatment failure. It is not clear if HBV mutants are present in pregnant women and about the influence of the preexisting mutants on the short-term antiviral therapy during pregnancy. Method. We enrolled 73 pregnant women with high HBV DNA load and telbivudine (TBV) treatment during pregnancy in this retrospective study. The UDPS was used to detect the HBV mutations before and after the TBV treatment. Results. Before TBV treatment, the complexity of HBV quasispecies of all subjects was 0.40 ± 0.09; 41.1% (30/73) and 53.4% (39/73) subjects had rtM204I/V and rtN236 T/A detected, respectively; and 9.6% (7/73) patients had more than 20% frequency mutation of rtM204I/V, which was also similar with high frequency of rtN236 T/A mutation (41.1% vs. 53.4%, P=0.136; frequencies >20%: 9.6% vs. 5.5%, P=0.347). After TBV treatment, 71.2% (52/73) subjects had HBV DNA load ≥ 103 IU/mL at delivery. Among them, 75.0% of patients with rtM204I positive had HBV DNA load ≥103 IU/mL at delivery, which was comparable with the subjects without rtM204I (75.0% vs. 70.8%, P=0.710). No changes were found in the frequencies and the complexity of HBV quasispecies of rtM204I mutation after the TVB treatment. Conclusion. The prevalence of preexisting drug-resistant mutations among pregnant women was high using UPDS. However, the preexisting HBV mutation had limited influence on the efficacy of short-term TBV treatment, and TBV treatment during late pregnancy seemed not to increase the risk of emerging HBV-resistant mutants.

BACKGROUND: Psychological and physical stress has been demonstrated to have an impact on health through modulation of immune function. Despite high prevalence of stress among patients with hepatitis B virus (HBV) infection, little is known about whether and how stress exerts an effect on the course of hepatitis B. METHODS: Eighty patients with chronic hepatitis B(CHB) completed the Perceived Stress Scale-10(PSS-10) and State-Trait Anxiety Inventory(STAI). Fresh whole blood was subject to flow cytometry for lymphocytes count. Plasma samples frozen at -80 °C were thawed for cytokines, alanine aminotransferase (ALT), and virus load. These patients were grouped into high or low perceived stress, state anxiety and trait anxiety groups according to the scale score. Sociodemographic, disease-specific characteristics, lymphocytes count and cytokines were compared. RESULTS: Firstly, a negative association between ALT and stress (t = -4.308; p = .000), state anxiety (t = -3.085; p = .003) and trait anxiety (t = -4.925; p = .000) were found. As ALT is a surrogate marker of hepatocytes injury, and liver injury is a consequence of immune responses. Next, we tested the relationship between stress/anxiety and lymphocytes. No statistical significance were found with respect to counts of total T cells, CD4+ T cell, CD8+ T cell, NK cell, and B cell count between high and low stress group. Type-2 cytokine interleukin-10 (IL-10) level was significantly higher in high stress group relative to lower counterpart (t = 6.538; p = 0.000), and type-1 cytokine interferon-gamma (IFN-γ) level shown a decreased tendency in high stress group (t = -1.702; p = 0.093). Finally, INF-γ:IL-10 ratio displayed significant decrease in high perceived stress(t = -4.606; p = 0.000), state anxiety(t = -5.126; p = 0.000) and trait anxiety(t = -4.670; p = 0.000) groups relative to low counterparts. CONCLUSION: Our data show stress is not related to the lymphocyte cells count in CHB patients, however, stress induces a shift in the type-1/type-2 cytokine balance towards a type-2 response, which implicated a role of psychological stress in the course of HBV related immune-pathogenesis.

Background: Lymphopenia and high CT score is associated with COVID-19 severity. Herein we describe the change pattern in lymphocyte count and CT score during hospitalization and explore a possible association with the severity of COVID-19. Methods: In this retrospective study, 13 non-severe COVID-19 patients diagnosed at admission were enrolled. One patient progressed to severe disease. Change patterns in lymphocyte counts and CT scores of all patients were analyzed. Results: Lymphocyte count increased gradually from day 5 post-illness onset (day 5 vs. day 15, p = 0.001). Lymphocyte count of the severe patient fluctuated at low levels throughout the 15-day period. Chest CT scores of non-severe patients increased significantly during the first 5 days of illness onset, but decreased gradually beginning day 9 (illness onset vs. day 5, p = 0.002, day 9 vs. day 15, p = 0.015). In the severe patient, CT score continued to increase over the 11 days post-illness onset period. Conclusions: Non-severe COVID-19 patients had significantly increased lymphocyte counts and decreased CT scores beginning day 5 and day 9 of illness onset, respectively. The patients without increased lymphocyte counts and decreased CT scores during the early 2nd week of illness onset may develop to severe COVID-19. [ABSTRACT FROM AUTHOR]