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1.
BMJ Open ; 11(1): e037793, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419900

RESUMO

PURPOSE: Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality, unclear mechanism and controversial diagnosis criteria. The Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study has been conducted in China to fill the gaps. In the first phase (the CATCH-LIFE investigation cohort), 2600 patients were continuously recruited from 14 national nationwide liver centres from 12 different provinces of China in 2015-2016, and a series of important results were obtained. To validate the preliminary results, we designed and conducted this multicentre prospective observational cohort (the CATCH-LIFE validation cohort). PARTICIPANTS: Patients diagnosed with chronic liver disease and hospitalised for acute decompensation (AD) or acute liver injure were enrolled, received standard medical therapy. We collected the participants' demographics, medical history, laboratory data, and blood and urine samples during their hospitalisation. FINDINGS TO DATE: From September 2018 to March 2019, 1370 patients (73.4% men) aged from 15 to 79 years old were enrolled from 13 nationwide liver centres across China. Of these patients, 952 (69.5%) had chronic hepatitis B, 973 (71.1%) had cirrhosis and 1083 (79.1%) complicated with AD at admission. The numbers and proportions of enrolled patients from each participating centre and the patients' baseline characteristics are presented. FUTURE PLANS: A total of 12 months is required for each participant to complete follow-up. Outcome information (survival, death or receiving liver transplantation) collection and data cleansing will be done before June 2020. The data in the CATCH-LIFE validation cohort will be used for comparison between the new ACLF diagnostic criteria derivated from the CATCH-LIFE investigation cohort with existing ones. Moreover, future proteomic and metabolic omics analyses will provide valuable insights into the mechanics of ACLF, which will promote the development of specific therapy that leads to decrease patients' mortality. REGISTRATION: NCT03641872.

2.
Dis Markers ; 2020: 8814841, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381244

RESUMO

Background: Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function and high short-term mortality. Clusterin, with biological functions similar to small heat shock proteins, can protect cells from apoptosis induced by various stressors. The aim of this study was to detect the level of serum clusterin in hepatitis B virus- (HBV-) related ACLF and to assess the predictive value of clusterin for the short-term prognosis of HBV-ACLF. Methods: We detected serum clusterin by ELISA in 108 HBV-ACLF patients, 63 HBV-non-ACLF patients, and 44 normal controls. Results: Serum clusterin was markedly lower in HBV-ACLF patients (median, 51.09 µg/mL) than in HBV-non-ACLF patients (median, 188.56 µg/mL) and normal controls (median, 213.45 µg/mL; all P < 0.05). Nonsurviving HBV-ACLF patients who died within 90 days had much lower clusterin levels than did surviving patients, especially those who died within 28 days (nonsurvival group vs. survival group: 39.82 ± 19.34 vs. 72.26 ± 43.52, P < 0.001; survival time ≤ 28 vs. survival time > 28: median 28.39 vs. 43.22, P = 0.013). The results showed that for identifying HBV-ACLF, the sensitivity of clusterin (93.7%) was similar to the sensitivities of the international normalized ratio (INR; 94.4%) and total bilirubin (TBIL; 94.8%), but its specificity (90.7%) was higher than that of prothrombin activity (PTA; 65.8%) and TBIL (69.8%) and was similar to INR (88.9%). As the concentration of clusterin increased, the mortality of HBV-ACLF patients decreased significantly from 59.3% to 7.0%. Clusterin had better ability for predicting the prognosis of HBV-ACLF patients than did the model for end-stage liver disease (MELD) score and the chronic liver failure consortium (CLIF-C) ACLF score (MELD vs. clusterin: P = 0.012; CLIF-C ACLF vs. clusterin: P = 0.031). Conclusion: Serum clusterin is a potential biomarker for HBV-ACLF which can be used to assess clinical severity and the short-term prognosis of patients with this disease and may help clinicians identify HBV-ACLF with greater specificity and improved prognostic accuracy than existing prognostic markers.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33178324

RESUMO

Aim: Fuzhenghuayu (FZHY) capsule can inhibit the progression of cirrhosis. This study explored whether FZHY can reduce the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B-caused cirrhosis (HBC) undergoing antiviral therapy. Methods: A retrospective review of 842 patients with HBC between 2011 and 2015 was performed, including 270 treated with FZHY combined with nucleos (t) ide analogues (NAs) and 572 with NAs alone. The incidence of HCC was compared between the FZHY (n = 259) and control (n = 259) groups using 1 : 1 propensity score (PS) matching. The incidence of HCC in patients with HBC with different Child-Turcotte-Pugh (CTP) classifications and Toronto HCC risk index (THRI) scores was analyzed using Kaplan-Meier curves. Results: The 5-year cumulative incidence of HCC before and after PS matching was 151 (17.9%) and 86 (16.6%), respectively. In PS-matched samples, the multivariate Cox proportional-hazards model indicated that the FZHY group demonstrated a significantly lower risk for HCC than the control group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.19-0.53 P < 0.001). The risk of HCC diminished with increased duration of FZHY use. The stratified analysis revealed that the FZHY group, regardless of CTP classification, benefited significantly from FZHY therapy. Patients in the medium- and high-THRI risk groups were the dominant population for FZHY. Conclusions: FZHY combined with NAs was associated with a significantly lower risk of HCC than NAs alone in patients with HBC, which supports the integration of FZHY with antiviral treatment into clinical practice.

4.
Onco Targets Ther ; 13: 11421-11431, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192075

RESUMO

Background: Individuals with hepatocellular carcinoma (HCC) are at risk of tumor recurrence after surgical resection, which affects their survival. The aim of the present study was to establish a model for predicting tumor progression in patients with HCC. Methods: To develop and validate the efficacy of a novel prognostic model, a retrospective cohort with HCC (n = 1005) at Beijing Ditan Hospital was enrolled from January 2008 and June 2017. Furthermore, a prospective cohort (n = 77) was recruited to validate the association between thyroid-stimulating hormone (TSH) levels and tumor progression in patients with HCC. Results: The model used in predicting the progression of HCC included four variables (namely, Barcelona Clinic Liver Cancer [BCLC] stage, presence of portal vein tumor thrombus, alpha-fetoprotein level, and TSH level). The AUROC of the 1-year progression-free survival (PFS) model was 0.755 and 0.753 in the deriving cohort and validation cohort, respectively, and these values were significantly higher than those of the Child-Pugh score, Model for End-stage Liver Disease (MELD), tumor-lymph node-metastasis (TNM) staging system, Okuda classification, and CLIP score. A simple assessment using a nomogram showed the 1-year PFS rate of patients with HCC. In the prospective cohort, the KM curve showed that the high TSH level group had a shorter PFS than the low TSH level (p = 0.001). Conclusion: The prognostic model of HCC progression was superior to other well-known classical tumor scoring systems. A high TSH level was correlated to poor outcome, particularly those with advanced HCC.

5.
Infect Dis Ther ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146854

RESUMO

INTRODUCTION: Sepsis is a complication in acute-on-chronic liver failure (ACLF) patients associated with high rates of mortality and morbidity. Early diagnosis of sepsis in ACLF patients can improve prognosis. This study aimed to explore potential effective biomarkers for the early diagnosis of sepsis in ACLF patients. METHODS: Ninety-four ACLF patients with sepsis were enrolled from 10 hospitals across China from January 2015 to June 2016 as well as 49 ACLF patients without infection from Xiangya Hospital. The first-day admission data and SOFA score and CLIF-SOFA score were collected. The differences of indicators between groups were compared with Kruskal-Wallis test. The receiver-operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency of the selected factors. RESULTS: Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and presepsin were significantly higher in ACLF-sepsis patients compared with ACLF patients with no infection (P < 0.001). sTREM-1 and presepsin presented higher diagnostic value in sepsis for ACLF patients compared with other biomarkers [white blood cells (WBC), procalcitonin (PCT) and C-reactive protein (CRP)]. Combining sTREM-1 or presepsin with the CLIF-SOFA score increased the diagnostic efficiency (AUC = 0.876 or AUC = 0.913, respectively). CONCLUSIONS: sTREM-1 and presepsin are potential biomarkers for the early diagnosis of sepsis in ACLF patients. The combination of presepsin and the CLIF-SOFA score is a promising method for diagnosing sepsis in ACLF patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02457637.

6.
Hepatol Int ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128206

RESUMO

BACKGROUND AND AIM: Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. METHODS: 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. RESULTS: The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9-43.2%) in the experiment group and 27.21% (95% CI 22.0-32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4-12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. CONCLUSION: Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. CLINICAL TRIAL NUMBER: ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

7.
J Oncol ; 2020: 1341863, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884569

RESUMO

Background: To compare the efficacies of transcatheter arterial chemoembolization (TACE) with radiofrequency ablation (RFA) (TACE + RFA) and TACE alone in patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI). Methods: In total, 664 patients having HCC with MVI were included. Of these patients, 141 were treated with TACE + RFA, 254 with TACE alone, and 269 with supportive therapy (control group). The overall survival (OS) was compared among these groups. Propensity score matching (PSM) was performed for balancing the characteristics of the three groups. Results: After one-to-one PSM, the 12-month OS rates were higher in the TACE and TACE + RFA groups than in the control group (p=0.0009 and p=0.0017, respectively). Furthermore, higher 12-month OS rates were observed in the TACE + RFA group than in the TACE group (p=0.0192). The 12-month OS rates of patients were remarkably higher in α-fetoprotein (AFP) < 400 ng/ml, tumor < 3, tumor diameter < 5 cm, or portal vein tumor thrombosis (PVTT) group who were treated with TACE + RFA than in those who were treated with TACE (p=0.0122, p=0.0090, p=0112, and p=0.0071, respectively). Conclusions: TACE + RFA provides a superior survival outcome than TACE alone in HCC patients, especially in AFP <400 ng/ml, tumor <3, tumor diameter <5 cm, or PVTT group.

8.
Chin J Integr Med ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32876859

RESUMO

OBJECTIVE: To assess whether adjuvant Chinese patent medicines (CPMs) to standard treatment could reduce recurrent bleeding after variceal bleeding in cirrhotic patients. METHODS: This study retrospectively collected 555 consecutive patients who recovered from variceal bleeding. A population-based cohort study was established depending on if adjuvant CPMs were administered to prevent rebleeding. A total of 139 patients who had taken ⩾28 cumulative defined daily doses (cDDDs) of CPMs were included in the CPMs cohort, and 416 patients who used <28 cDDDs of CPMs were enrolled in the non-CPMs cohort. On evaluation of rebleeding incidence, 1:2 propensity score matched was used to estimate for reducing bias. Patients were followed for at least 12 months. The end-point of this study was clinically significant esophagogastric variceal rebleeding. RESULTS: Following multivariate analysis, CPMs therapy was an independent factor for variceal rebleeding [adjusted hazard ratio (AHR)=0.657; 95% confidence interval=0.497-0.868; P=0.003]. After the 1:2 propensity score matching, a significant reduction (23.5%) in the incidence of variceal rebleeding in patients was observed, from 58.3% in the non-CPMs cohort to 44.6% in the CPMs cohort (modified log-rank test, P=0.002) within a year. The AHRs for rebleeding were 0.928, 0.553, and 0.105, for 28-90 cDDDs, 91-180 cDDDs, and >180 cDDDs of CPMs, respectively. The median rebleeding interval in the CPMs cohort was significantly larger compared with the non-CPMs cohort (113.5 vs. 93.0 days; P=0.008). CONCLUSION: Adjuvant CPMs to standard therapy can significantly reduce the incidence of variceal rebleeding and delay the time to rebleeding.

9.
Front Oncol ; 10: 1189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850343

RESUMO

In clinical practice, the cancer-immunity cycle of an individual patient with hepatocellular carcinoma (HCC) must be described to support the clinical management of cancer. The present study explored the immunograms of patients with liver cancer based on liver RNA sequencing data to visually display the individualized cancer-immunity cycles. Two independent HCC cohorts [The Cancer Genome Atlas (TCGA) and Liver Cancer-RIKEN, Japan (LIRI-JP) HCC cohorts] with whole exome sequencing (WES) data, RNA sequencing data, and clinical data from TCGA and International Cancer Genome Consortium (ICGC) were enrolled in this study. This study constructed HCC immunograms of cancer immune cells to visually explore the anticancer immune responses of patients with HCC. The patterns of the HCC immunograms were categorized into two clusters: hot and cold HCC immunograms. Favorable overall survival (OS) and disease-free survival (DFS) were observed in the hot immunogram cluster in the TCGA cohort. The results for LIRI-JP cohort were similar to the TCGA cohort. The OS of patients with HCC presenting the hot immunogram was longer than patients with the cold immunogram in the LIRI-JP HCC cohort. Compared with cold immunograms, hot immunograms were characterized by higher levels of immune cell infiltration and stronger immune signatures, including cytolytic activity, IFN-γ signature, immunocostimulator, immunoinhibitor, chemokine, adhesion molecule, MHC I, MHC II, and non-class MHC levels. The main difference in molecular features between hot and cold immunograms was reflected in WNT-CTNNB1 alterations and copy number variant (CNV) and loss of heterozygosity (LOH) scores, which are the molecular features associated with resistance to immunotherapy and tumor escape. The immunogram patterns were distinct in terms of the different molecular features of HCC tumors. The HCC immunogram for the cancer-immune cycle was able to visualize the personalized antitumor immune response of patients with HCC, and the patterns of the HCC immunograms contributed to the clinical outcomes of patients, which may facilitate an individualized assessment of the antitumor immune response for optimal personalized immunotherapy.

10.
Med Sci Monit ; 26: e924040, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32769964

RESUMO

BACKGROUND Probiotic therapy has been shown to be beneficial against some liver diseases. However, there is still uncertainty regarding the clinical efficacy of probiotics for the treatment of variceal rebleeding. This research explored the efficacy of probiotics in variceal rebleeding. MATERIAL AND METHODS This was a retrospective study of 704 consecutive patients with liver cirrhosis who recovered from esophagogastric variceal bleeding after endoscopic treatment. Patients were subdivided into a probiotics cohort (n=214) and a non-probiotics cohort (n=490) based on the cumulative defined daily dose (cDDD) of probiotics received during follow-up. Propensity score matching was utilized to obtain a relatively balanced cohort of 200 patients per group for the analysis. Patients were monitored for rebleeding during the one-year follow-up. RESULTS Multivariate Cox regression analysis revealed that probiotic therapy (≥28cDDD) was an independent protector against rebleeding (AHR=0.623; 95% CI=0.488-0.795; P<0.001). After propensity score matching, Kaplan-Meier analysis revealed that the rebleeding rate was higher in the non-probiotics cohort (n=200) than in the probiotics cohort (n=200) (56.0% vs. 44.0%, P=0.002). The incidence of rebleeding decreased with increased probiotic dosage (56.0%, 48.5%, 43.3%, and 38.1% in <28 cDDD, 28-60 cDDD, 61-90 cDDD, and >90 cDDD groups, respectively; P=0.011). The median rebleeding interval in the probiotics cohort (n=95) was significantly longer than that in the non-probiotics cohort (n=261) (147.0 vs. 91.0 days; P<0.001). CONCLUSIONS Adjuvant probiotic therapy significantly reduced the incidence of variceal rebleeding and delayed rebleeding after endotherapy in patients with cirrhosis.

11.
Front Pharmacol ; 11: 867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655395

RESUMO

Background: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the adult liver, exhibiting rapid progression and poor prognosis. Chlorogenic acid (CGA), a polyphenol, has several biological activities, including the suppression of liver cancer cell invasion and metastasis. Increased levels or alterations in the function of DNMT1 are associated with the inactivation of tumor suppressor genes. However, the CGA-affected DNMT1 expression mediated mechanism is still unclear. Methods: The human hepatocellular carcinoma (HCC) HepG2 cells were treated with a positive control drug (5-AZA) or varying doses of CGA. DNA methyltransferase 1 (DNMT1) protein levels and other relevant proteins were evaluated using Western blotting and immunocytochemistry. Cell-cycle analysis was performed by flow cytometry-based PI staining, and cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transwell invasion and wound healing assays were used to evaluate cell migration and invasion. In vivo proliferation of the HCC cells was detected. We investigated the expression of DNMT1, p53, p21, p-ERK, MMP-2, and MMP-9 in tumors using immunohistochemical analysis. Results: Our results showed that CGA inhibited the proliferation, colony formation, invasion, and metastasis of HepG2 cells both in vitro and in vivo by down-regulating DNMT1 protein expression, which enhanced p53 and p21 activity, and resulting in a significant reduction in cell proliferation and metastasis. Moreover, CGA inactivated ERK1/2 and reduced MMP-2 and MMP-9 expression in HepG2 cells. Conclusions: CGA can suppress liver cancer cell proliferation, invasion, and metastasis through several pathways. CGA could serve as a candidate chemopreventive agent for HCC.

12.
J Altern Complement Med ; 26(10): 956-965, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32614605

RESUMO

Objectives: Fufang Banmao (FFBM) capsule, a type of Chinese medicinal formulation, has decades of history in treating hepatocellular carcinoma (HCC). This retrospective study aimed to observe the effect of FFBM capsules on the 6-month survival of patients with advanced HCC and Vp3-4 portal vein tumor thrombosis (PVTT) who received supportive therapy alone. Design: In total, 320 HCC/Vp3-4 PVTT patients underwent treatment with supportive therapy, of whom 95 took FFBM capsules and were treated with supportive therapy (FFBM group) and 225 received supportive therapy alone (control group). Comparisons of the 6-month overall survival (OS) rate of the two groups were performed. Propensity score matching (PSM) was used to match the characteristics between individuals in the two groups. A nomogram was built based on independent predictive factors for OS. Results: Cox multivariate analysis revealed that hepatic encephalopathy, aspartate transaminase (AST) and γ-glutamyl transpeptidase levels, Child-Pugh class, prothrombin time, α-fetoprotein level, largest tumor diameter, and use of FFBM capsules were independent predictive factors of OS. Variceal bleeding, alanine transaminase, AST, total bilirubin, and Barcelona Clinic for Liver Cancer stage were different at baseline in the FFBM and control groups. Analysis revealed no significant adverse effects or toxicities relevant to the medications. After PSM (1:1), 95 patient pairs were analyzed as FFBM versus control. The OS probability was remarkably higher for patients in the FFBM group than in those in the control group at 6 months (p < 0.0001). The median survival time was 4 months in the FFBM group and 2.2 months in the control group. Kaplan-Meier analysis showed significant statistical differences in the 6-month OS rates in the patients with total nomogram scores ≥84 (p < 0.0001). Conclusions: Given the satisfying survival outcomes, the results suggested that FFBM capsules should be administered to patients with HCC/Vp3-4 PVTT in the high-risk group (score ≥84). FFBM capsules have the potential for improving patient survival time in those with advanced HCC and Vp3-4 PVTT who receive supportive therapy alone, especially those in the high-risk group (score ≥84).

13.
Front Oncol ; 10: 813, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670867

RESUMO

Background: Transarterial chemoembolization (TACE) represents a widely accepted treatment procedure for intermediate stage or unresectable hepatocellular carcinoma (HCC). However, few studies have evaluated serologic prognosis factors in patients with HCC before TACE. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein affecting tumorigenesis and metastasis, and leading to poor prognosis in HCC. Therefore, to further explore the potential prognosis value of SPARC, the expression levels in the plasma of patients and its potential molecular mechanisms underlying the regulation of HCC were investigated in this study. Materials and Methods: The study population included 43 patients with HCC who underwent TACE. To evaluate the expression of SPARC in different grades of pathological tissues, the immunohistochemistry was performed on tissues from 89 patients with HCC. Lentiviral vectors carrying interference sequences, as well as vectors harboring the complete open reading frame of SPARC for the knockdown or overexpression of SPARC in HuH-7 or HepG2 cells, respectively, allowed us to determine the biological functions of SPARC in vitro and in vivo. We also evaluated the levels of phosphorylated extracellular signal-regulated kinases 1/2 (p-ERK1/2) and matrix metalloproteinases 2/9 (MMP2/9) activation. Results: The association between serum levels of SPARC and the survival at different TNM and Barcelona-Clinic Liver Cancer (BCLC) stages in patients with HCC undergoing TACE were evaluated. We observed a significant upregulation of SPARC in high grade HCC tissues, predicting unfavorable prognosis, and suggesting an important tumor-promoting effect of SPARC. Functional studies indicated that downregulation of SPARC contributed to the inhibition of proliferation and metastasis of HuH-7 cells in vitro, whereas its overexpression led to opposite phenotypes. Mechanistically, decreased expression of SPARC resulted in dephosphorylation of ERK1/2 and deactivation of MMP2/9, thereby inhibiting growth and metastasis of HCC. Importantly, low expression levels of SPARC inhibited the formation of subcutaneous tumors in nude mice. Conclusions: SPARC was found to facilitate proliferation and metastasis of HCC via modulation of the ERK1/2-MMP2/9 signaling pathways. Our research has provided a glimpse on the biological mechanism of SPARC and might contribute to the eventual treatment of liver cancer.

14.
Open Forum Infect Dis ; 7(5): ofaa169, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32490031

RESUMO

Background: There is currently a lack of nonspecific laboratory indicators as a quantitative standard to distinguish between the 2019 coronavirus disease (COVID-19) and an influenza A or B virus infection. Thus, the aim of this study was to establish a nomogram to detect COVID-19. Methods: A nomogram was established using data collected from 457 patients (181 with COVID-19 and 276 with influenza A or B infection) in China. The nomogram used age, lymphocyte percentage, and monocyte count to differentiate COVID-19 from influenza. Results: Our nomogram predicted probabilities of COVID-19 with an area under the receiver operating characteristic curve of 0.913 (95% confidence interval [CI], 0.883-0.937), greater than that of the lymphocyte:monocyte ratio (0.849; 95% CI, 0.812-0.880; P = .0007), lymphocyte percentage (0.808; 95% CI, 0.768-0.843; P < .0001), monocyte count (0.780; 95% CI, 0.739-0.817; P < .0001), or age (0.656; 95% CI, 0.610-0.699; P < .0001). The predicted probability conformed to the real observation outcomes of COVID-19, according to the calibration curves. Conclusions: We found that age, lymphocyte percentage, and monocyte count are risk factors for the early-stage prediction of patients infected with the 2019 novel coronavirus. As such, our research provides a useful test for doctors to differentiate COVID-19 from influenza.

15.
Hepatol Int ; 14(4): 567-576, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32556865

RESUMO

OBJECT: Disease progression is an important factor affecting the long-term survival in hepatocellular carcinoma (HCC). The progression-free survival (PFS) has been used as a surrogate endpoint for overall survival (OS) in many solid tumors. However, there were few models to predict the PFS in HCC patients. This study aimed to explore the prognostic factors that affect the PFS in HCC and establish an individualized prediction model. METHODS: We included 2890 patients with hepatitis B-related HCC hospitalized at Beijing Ditan Hospital, Capital Medical University and randomly divided into training and validation cohort. Cox multivariate regression was used to analyze independent risk factors affecting the 1-year PFS of HCC, and an artificial neural networks (ANNs) model was constructed. C-index, calibration curve, and decision curve analysis were used to evaluate the performance of the model. RESULTS: The median survival time was 26.2 m (95% CI: 24.08-28.32) and the 1-year PFS rate was 52.3% in whole study population. Cox multivariate regression showed smoking history, tumor number ≥ 2, tumor size ≥ 5 cm, portal vein tumor thrombus, WBC, NLR, γ-GGT, ALP, and AFP ≥ 400 ng/mL were risk factors for 1-year progression-free survival, while albumin and CD4 T cell counts were protective factors in HCC patients. A prediction model for 1-year PFS was constructed ( https://lixuan.me/annmodel/myg-v3/ ). The ANNs model's ability to predict 1-year PFS had an area under the receiver operating characteristic curve (AUROC) of 0.866 (95% CI 0.848-0.884) in HCC patients, which was higher than predicted by TNM, BCLC, Okuda, CLIP, CUPI, JIS, and ALBI scores (p < 0.0001). In addition, the ANNs model could also estimate the probability of 1-year OS and presented a higher AUROC value, 0.877 (95% CI 0.858-0.895), than those other models. All patients were divided into high-, medium-, and low-risk groups, according to the ANNs model scores. Compared with the hazard ratios (HRs) of PFS and OS in low-risk group, those in the high-risk group were 26.42 (95% CI 18.74-37.25; p < 0.0001) and 11.26 (95% CI 9.11-13.93; p < 0.0001), respectively. CONCLUSION: The ANNs model has good individualized prediction performance and may be helpful to evaluate the probability of progression-free survival in HCC during clinical practice.

16.
J Transl Med ; 18(1): 206, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434518

RESUMO

BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.


Assuntos
Infecções por Coronavirus/diagnóstico , Estado Terminal , Linfócitos/patologia , Neutrófilos/patologia , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Progressão da Doença , Feminino , História do Século XXI , Humanos , Lactente , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
17.
BMC Gastroenterol ; 20(1): 75, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32188419

RESUMO

BACKGROUND: This study aimed to develop prognostic models for predicting 28- and 90-day mortality rates of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) through artificial neural network (ANN) systems. METHODS: Six hundred and eight-four cases of consecutive HBV-ACLF patients were retrospectively reviewed. Four hundred and twenty-three cases were used for training and constructing ANN models, and the remaining 261 cases were for validating the established models. Predictors associated with mortality were determined by univariate analysis and were then included in ANN models for predicting prognosis of mortality. The receiver operating characteristic curve analysis was used to evaluate the predictive performance of the ANN models in comparison with various current prognostic models. RESULTS: Variables with statistically significant difference or important clinical characteristics were input in the ANN training process, and eight independent risk factors, including age, hepatic encephalopathy, serum sodium, prothrombin activity, γ-glutamyltransferase, hepatitis B e antigen, alkaline phosphatase and total bilirubin, were eventually used to establish ANN models. For 28-day mortality in the training cohort, the model's predictive accuracy (AUR 0.948, 95% CI 0.925-0.970) was significantly higher than that of the Model for End-stage Liver Disease (MELD), MELD-sodium (MELD-Na), Chronic Liver Failure-ACLF (CLIF-ACLF), and Child-Turcotte-Pugh (CTP) (all p < 0.001). In the validation cohorts the predictive accuracy of ANN model (AUR 0.748, 95% CI: 0.673-0.822) was significantly higher than that of MELD (p = 0.0099) and insignificantly higher than that of MELD-Na, CTP and CLIF-ACLF (p > 0.05). For 90-day mortality in the training cohort, the model's predictive accuracy (AUR 0.913, 95% CI 0.887-0.938) was significantly higher than that of MELD, MELD-Na, CTP and CLIF-ACLF (all p < 0.001). In the validation cohorts, the prediction accuracy of the ANN model (AUR 0.754, 95% CI: 0.697-0.812 was significantly higher than that of MELD (p = 0.019) and insignificantly higher than MELD-Na, CTP and CLIF-ACLF (p > 0.05). CONCLUSIONS: The established ANN models can more accurately predict short-term mortality risk in patients with HBV- ACLF. The main content has been postered as an abstract at the AASLD Hepatology Conference (https://doi.org/10.1002/hep.30257).

18.
Biomed Res Int ; 2020: 1473718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149077

RESUMO

Background: Portal vein tumor thrombosis (PVTT) is one of the major predictive factors for patients with hepatocellular carcinoma (HCC). The objective of this study was to establish a prognostic nomogram for identifying individual survival outcomes in patients with HCC and PVTT on conservative treatment based on specific factors. Methods: Two hundred and ten patients with HCC and PVTT on conservative treatment in Beijing Ditan Hospital between June 2008 and May 2017 were studied retrospectively as a derivation cohort. We built a nomogram based on independent risk factors for survival prediction. The concordance index (c-index) and a calibration curve were used to evaluate the predictive accuracy. During the study, 102 patients were included at the Putuo Hospital and Third People's Hospital of Changzhou as a validation cohort. Results: In the derivation cohort, the independent factors for overall survival were identified by multivariate analysis, namely, aspartate aminotransferase ≥119 IU/L, gamma-glutamyl transferase ≥115 IU/L, Child-Pugh class C liver function, creatinine ≥91 µmoI/L, α-fetoprotein ≥400 ng/ml, and largest tumor diameter ≥5 cm. The nomogram had a c-index of 0.737 (95% confidence interval, 0.692-0.782) and the calibration curves fitted well. The median survival time was 4.2 months in the derivation cohort, with an MST of 5 months for BCLC C stage and 1.8 months for BCLC D stage patients. Kaplan-Meier analysis showed significant statistical differences in the 6-month overall survival rates of the primary and validation cohorts after the total scores were divided into three quartiles (low risk: 0-85; intermediate risk: 86-210; high risk: ≥211; p < 0.0001 in both cohorts). Conclusions: The nomogram can be a more accurate and individualized prediction for 6-month overall survival of patients with HCC and PVTT on conservative treatment, and it is possible to consider further active interventions for patients in the low-risk group (0-85 scores) to achieve the aim of prolonging survival.

19.
PLoS One ; 15(3): e0230154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32150567

RESUMO

To gain better insight into the regulatory networks of anthocyanin biosynthesis, an integrated analysis of the metabolome and transcriptome in purple and green leaves of Tetrastigma hemsleyanum was conducted. Transcript and metabolite profiles were archived by RNA-sequencing data analysis and LC-ESI-MS/MS, respectively. There were 209 metabolites and 4211 transcripts that were differentially expressed between purple and green leaves. Correlation tests of anthocyanin contents and transcriptional changes showed 141 significant correlations (Pearson correlation coefficient >0.8) between 16 compounds and 14 transcripts involved in the anthocyanin biosynthesis pathway. Some novel genes and metabolites were discovered as potential candidate targets for the improvement of anthocyanin content and superior cultivars.


Assuntos
Antocianinas/metabolismo , Metaboloma/genética , Folhas de Planta/metabolismo , Transcriptoma/genética , Vitaceae/genética , Antocianinas/genética , Cor , Biologia Computacional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Proteínas de Plantas/genética , Espectrometria de Massas em Tandem , Vitaceae/química , Vitaceae/metabolismo
20.
Liver Int ; 40(6): 1447-1456, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32128975

RESUMO

BACKGROUND & AIMS: Current guidelines on the management of bacterascites are limited. This multicentre, retrospective study investigated the clinical features and outcomes of cirrhosis patients with bacterascites. METHODS: Two series of cirrhosis patients were evaluated. The first included 418 patients with ascites-positive cultures at 11 hospitals during 2012-2018. Clinical characteristics and outcomes were recorded. The second included 208 patients with sterile ascites from a prospective cohort (NCT02457637). Clinical features and outcomes of cirrhotic patients with or without bacterascites were investigated. RESULTS: In the first series, bacterascites was diagnosed in 254/418 (60.8%) patients, and culture-positive spontaneous bacterial peritonitis (SBP) in 164/418 (39.2%) patients. Gram-positive bacteria were more prevalent in bacterascites patients than in culture-positive SBP patients (59.1% vs 22.0%; P < .001). For patients with acute-on-chronic liver failure (ACLF) in bacterascites and culture-positive SBP groups, the 28-day transplant-free mortality (41.3% vs 65.5%; P = .015) and the prevalence of in-hospital acute kidney injury (AKI) (84.8% vs 75%; P = .224). For patients without ACLF in the bacterascites (n = 208) and culture-positive SBP groups (n = 108), the 28-day transplant-free mortalities were 13% vs 13.9% (P = .822), the probabilities of progression to ACLF within 28 days were 10.1% vs 14.8% (P = .216) and the prevalences of in-hospital AKI were 14.4% vs 30.6% (P = .001). Bacterascites patients had higher 28-day mortality than those patients with sterile ascites, after propensity score matching (18.4% vs 8.6%; P = .010). CONCLUSION: Bacterascites patients had non-negligible poor clinical outcomes, including in-hospital AKI, progression to ACLF and 28-day mortality. Future studies are warranted to expedite the diagnosis of bacterascites and optimize antibiotic treatment.

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