1.Influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis
Danqing XU ; Huan MU ; Yingyuan ZHANG ; Lixian CHANG ; Yuanzhen WANG ; Weikun LI ; Zhijian DONG ; Lihua ZHANG ; Yijing CHENG ; Li LIU
Journal of Clinical Hepatology 2025;41(2):269-276
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January, 2019 to December, 2022 were enrolled, among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group, and 154 patients without recompensation were enrolled as control group. Related clinical data were collected, and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and the receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis, 63 (29.03%) had recompensation. There were significant differences between the recompensation group and the control group in HIV history (χ2=4.566, P=0.034), history of partial splenic embolism (χ2=6.687, P=0.014), Child-Pugh classification (χ2=11.978, P=0.003), grade of ascites (χ2=14.229, P<0.001), albumin (t=4.063, P<0.001), prealbumin (Z=-3.077, P=0.002), high-density lipoprotein (t=2.854, P=0.011), high-sensitivity C-reactive protein (Z=-2.447, P=0.014), prothrombin time (Z=-2.441, P=0.015), carcinoembryonic antigen (Z=-2.113, P=0.035), alpha-fetoprotein (AFP) (Z=-2.063, P=0.039), CA125 (Z=-2.270, P=0.023), TT3 (Z=-3.304, P<0.001), TT4 (Z=-2.221, P=0.026), CD45+ (Z=-2.278, P=0.023), interleukin-5 (Z=-2.845, P=0.004), tumor necrosis factor-α (Z=-2.176, P=0.030), and portal vein width (Z=-5.283, P=0.005). The multivariate analysis showed that history of partial splenic embolism (odds ratio [OR]=3.064, P=0.049), HIV history (OR=0.195, P=0.027), a small amount of ascites (OR=3.390, P=0.017), AFP (OR=1.003, P=0.004), and portal vein width (OR=0.600, P<0.001) were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history, grade of ascites, history of partial splenic embolism, AFP, portal vein width, and the combined predictive model of these indices had an area under the ROC curve of 0.556, 0.641, 0.560, 0.589, 0.745, and 0.817, respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis, those with a history of partial splenic embolism, a small amount of ascites, and an increase in AFP level are more likely to experience recompensation, while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.
2.Efficacy and safety of coblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets in treatment of patients with chronic hepatitis C virus infection
Chunyan MOU ; Danqing XU ; Huan MU ; Jiangyan ZHANG ; Lixian CHANG ; Yuanqiang HE ; Yingyuan ZHANG ; Weikun LI ; Xiuling ZHANG ; Xiliang HE ; Qin PENG ; Li LIU
Journal of Clinical Hepatology 2025;41(9):1779-1787
ObjectiveTo investigate the therapeutic efficacy, influencing factors, and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus (HCV) infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1, 2021 to May 31, 2024 were enrolled, among whom there were 86 patients with compensated liver cirrhosis (CLC group) and 167 patients with chronic hepatitis C (CHC group). The patients were treated with coblopasvir hydrochloride capsules (60 mg)/sofosbuvir tablets (400 mg) with or without ribavirin tablets for 12 weeks, and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment (SVR12) and safety, and the secondary outcome measures were the changes in liver function, renal function, blood routine, and liver stiffness measurements (LSM) after 4 weeks of treatment, after 12 weeks of treatment, and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups, and the Friedman test was used for comparison between multiple groups, while the Bonferroni method was used for paired comparison within each group; the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years, and there were 151 male patients (59.7%). Of all patients, 33.99% (86/253) had liver cirrhosis, 25.69% (65/253) had hypertension, 10.67% (27/253) had HIV infection, 8.70% (22/253) had diabetes, 3.95% (10/253) had liver cancer, 1.98% (5/253) had chronic hepatitis B, and 7.91% (20/253) were treatment-experienced patients. As for genotype distribution, 2.77% (7/253) had genotype 1, 12.65% (32/253) had genotype 2, 66.01% (167/253) had genotype 3, 16.60% (42/253) had genotype 6, and 1.98% (5/253) had unknown genotype. The patients had an overall SVR12 rate of 92.09%, with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age (odds ratio [OR]=1.086, 95% confidence interval [CI]: 1.007 — 1.170, P=0.032) and HCC (OR=9.178, 95%CI: 1.722 — 48.912, P=0.009) were independent influencing factors for sustained virologic response. Compared with baseline data, the CLC group had significant reductions in alanine aminotransferase (ALT) (χ2=107.103, P0.05), aspartate aminotransferase (AST) (χ2=90.602, P0.05), and LSM (χ2=42.235, P0.05) after 12 weeks of treatment, while the CHC group had significant reductions in total bilirubin (χ2=15.113, P0.05), ALT (χ2=202.237, P0.05), AST (χ2=161.193, P0.05), and LSM (χ2=37.606, P0.05). The incidence rate of serious adverse events was 1.58%, and none of the patients withdrew from drug therapy; the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%, among which fatigue (17.39%) and nausea (2.37%) were the most common adverse events, and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.
3.Value of FibroScan, gamma-glutamyl transpeptidase-to-platelet ratio, S index, interleukin-6, and tumor necrosis factor-α in the diagnosis of HBeAg-positive chronic hepatitis B liver fibrosis
Yingyuan ZHANG ; Danqing XU ; Huan MU ; Chunyan MOU ; Lixian CHANG ; Yuanzhen WANG ; Hongyan WEI ; Li LIU ; Weikun LI ; Chunyun LIU
Journal of Clinical Hepatology 2025;41(4):670-676
ObjectiveTo investigate the value of noninvasive imaging detection (FibroScan), two serological models of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) score and S index, and two inflammatory factors of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B (CHB), as well as the consistency of liver biopsy in pathological staging, and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients, and related examinations were performed before liver biopsy, including total bilirubin, alanine aminotransferase, platelet count, gamma-glutamyl transpeptidase, albumin, IL-6, TNF-α, liver stiffness measurement (LSM), and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy, and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic (ROC) curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsIn the consistency check, inflammation degree based on liver biopsy had a Kappa value of 0.807 (P<0.001), and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 (P<0.001), suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM, GPR score, S index, IL-6, and TNF-α (all P<0.05), and GPR score, S index, IL-6, and TNF-α were positively correlated with LSM (all P<0.05). GPR score, S index, IL-6, and TNF-α were all independent risk factors for diagnosing significant liver fibrosis (≥S2) and progressive liver fibrosis (≥S3) (all P<0.05). As for each indicator alone, GPR score had the highest value in the diagnosis of significant liver fibrosis (≥S2), followed by S index, IL-6, and TNF-α, while S index had the highest value in the diagnosis of progressive liver fibrosis (≥S3), followed by GPR score, TNF-α, and IL-6. The joint model had a higher predictive value than each indicator alone (all P<0.05). ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score, S index, IL-6, and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB, and the combined prediction model established by them can better diagnose liver fibrosis.
4.Influencing factors for recompensation in patients with decompensated hepatitis B cirrhosis
Danqing XU ; Yingyuan ZHANG ; Huan MU ; Caifen SA ; Chunyan MOU ; Yuanzhen WANG ; Weikun LI ; Li LIU
Journal of Clinical Hepatology 2025;41(7):1364-1370
Objective To investigate the influencing factors for recompensation in patients with decompensated hepatitis B cirrhosis,and to establish a predictive model.Methods A total of 517 patients who attended The Third People's Hospital of Kunming and were diagnosed with decompensated hepatitis B cirrhosis from January 1,2016 to December 31,2022 were enrolled.The clinical data of the patients were reviewed,and the 207 patients with no portal hypertension-related complications within at least 1 year were enrolled as recompensation group,while the 310 patients without recompensation were enrolled as persistent decompensation group.Related clinical data were collected,and the univariate and multivariate Cox regression analyses were performed for the factors that might affect the occurrence of recompensation.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.The"rms"package was used to establish a nomogram;the receiver operating characteristic(ROC)curve was plotted,and the area under the ROC curve(AUC)was calculated;the Hosmer-Lemeshow test was used to evaluate the degree of fitting of the model;the"Calibration Curves"package was used to plot the calibration curve for model assessment.Results Among the patients with decompensated hepatitis B cirrhosis,207(40.03%)had recompensation.The univariate Cox regression analysis showed that there were significant differences between the recompensation group and the persistent decompensation group in TIPS history,genotyping,portal vein thrombosis,complicated infection,Child-Pugh class,age,hemoglobin(Hb),platelet count,total protein,albumin(Alb),alanine aminotransferase,triglyceride,cholesterol,creatinine,Na,interleukin-6,high-sensitivity C-reactive protein,portal vein width,and portal vein velocity(all P<0.05).The multivariate regression analysis showed that TIPS history(hazard ratio[HR]=2.491,95%confidence interval[CI]:1.325-4.681,P=0.005),portal vein thrombosis(HR=0.345,95%CI:0.152-0.783,P=0.001),Hb(HR=1.007,95%CI:1.000-1.013,P=0.028),Alb(HR=1.048,95%CI:1.017-1.080,P=0.002),and portal vein width(HR=0.899,95%CI:0.835-0.967,P=0.004)were independent influencing factors for recompensation in patients with decompensated hepatitis B cirrhosis.A nomogram model was established based on the above five influencing factors,and the Hosmers-Lemeshow test showed that this model had a good degree of fitting(χ2=3.202,P=0.921).The nomogram model had an AUC of 0.728,a sensitivity of 50.3%,and a specificity of 85.0%,and the calibration curve showed good consistency between the actual value of this model in predicting the occurrence of recompensation and the predicted value in patients with decompensated hepatitis B cirrhosis.Conclusion Patients with decompensated hepatitis B cirrhosis who have a history of TIPS and high levels of Alb and Hb are more likely to have recompensation,and it is relatively difficult for patients with portal vein thrombosis and an increase in portal vein width to achieve recompensation.
5.Circular RNA_005987 mediates contrast-associated acute kidney injury through activating autophagy signaling by sponging miRNA-129-5p
Yeshen ZHANG ; Siyu KONG ; Haobin LIU ; Weikun CHEN ; Guangjun HUANG ; Yining DAI ; Ning TAN ; Yuanhui LIU
Chinese Journal of Nephrology 2025;41(2):114-124
Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.
6.Efficacy and safety of coblopasvir hydrochloride combined with sofosbuvir in treatment of patients with genotype 3 hepatitis C virus infection
Yingyuan ZHANG ; Huan MU ; Danqing XU ; Chunyan MOU ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Li LIU
Journal of Clinical Hepatology 2025;41(6):1075-1082
ObjectiveTo investigate the efficacy and safety of the direct-acting antiviral agents coblopasvir hydrochloride/sofosbuvir (CLP/SOF) regimen used alone or in combination with ribavirin (RBV) in the treatment of patients with genotype 3 hepatitis C virus (HCV) infection in terms of virologic response rate, liver function recovery, improvement in liver stiffness measurement (LSM), and adverse drug reactions, and to provide a reference for clinical medication. MethodsA total of 98 patients with genotype 3 HCV infection who attended The Third People’s Hospital of Kunming from January 2022 to December 2023 were enrolled, and according to the treatment method, the patients were divided into CLP/SOF+RBV treatment group with 55 patients and CLP/SOF treatment group with 43 patients. The patients were observed in terms of rapid virologic response at week 4 (RVR4), sustained virologic response (SVR), previous treatment experience, underlying diseases, laboratory and imaging indicators, and adverse reactions during treatment. The course of treatment was 12 weeks, and the patients were followed up for 12 weeks after drug withdrawal. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Friedman test was used for comparison within each group at different time points, and the Bonferroni method was used for further comparison and correction of P value; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for SVR12. ResultsBefore treatment, there were significant differences between the CLP/SOF+RBV treatment group and the CLP/SOF treatment group in terms of LSM, total bilirubin (TBil), gamma-glutamyl transpeptidase (GGT), HCV genotype, and the presence or absence of liver cirrhosis and compensation (all P<0.05). The 98 patients with genotype 3 HCV infection had an RVR4 rate of 81.6% and an SVR12 rate of 93.9%. The patients with genotype 3a HCV infection had an RVR4 rate of 84.44% and an SVR12 rate of 97.78%, while the patients with genotype 3b HCV infection had an RVR4 rate of 79.25% and an SVR12 rate of 90.57%. There were significant differences in RVR4 and SVR12 rates between the patients without hepatocellular carcinoma and those with hepatocellular carcinoma, there was a significant difference in RVR4 rate between the patients without HIV infection and those with HIV infection, and there was a significant difference in SVR12 rate between the previously untreated patients and the treatment-experienced patients (all P<0.05). The univariate Logistic regression analysis showed that treatment history, hypertension, hepatocellular carcinoma, ascites, albumin (Alb), and platelet count were influencing factors for SVR12 (all P<0.05), and the multivariate Logistic regression analysis showed that hepatocellular carcinoma (odds ratio=0.034, 95% confidence interval: 0.002 — 0.666, P=0.026) was an independent influencing factor for SVR12. After treatment with CLP/SOF combined with RBV or CLP/SOF alone, the patients with genotype 3 HCV infection showed gradual reductions in the liver function parameters of TBil, GGT, and alanine aminotransferase (all P<0.05) and a gradual increase in the level of Alb (P<0.05). As for renal function, there were no significant changes in blood urea nitrogen and creatinine after treatment (P>0.05). For the patients with or without liver cirrhosis, there was a significant reduction in LSM from baseline after treatment for 12 weeks (P<0.05). Among the 98 patients with genotype 3 HCV infection, 9 tested positive for HCV-RNA at 12 weeks after treatment, 2 showed no response during treatment, 4 showed virologic breakthrough, and 3 experienced recurrence. The overall incidence rate of adverse events during treatment was 17.35% for all patients. ConclusionCLP/SOF alone or in combination with RBV has a relatively high SVR rate in the treatment of genotype 3 HCV infection, with good tolerability and safety in patients during treatment, and therefore, it holds promise for clinical application.
7.Analysis of influencing factors and construction of predictive model for HBsAg clearance in patients with HBeAg-negative chronic hepatitis B treated with PEG-IFN-α-2b
Yingyuan ZHANG ; Danqing XU ; Huan MU ; Yuanqiang HE ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Chunyan MOU ; Li LIU
Journal of Clinical Hepatology 2025;41(8):1525-1532
Objective To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B(CHB)receiving peginterferon alfa-2b(PEG-IFN-α-2b)treatment,analyze the effects of various indicators on the HBsAg clearance rate under different characteristics,and construct and evaluate a combined predictive model.Methods We included 125 patients with HBeAg-negative CHB at Kunming Third People's Hospital from May 2021 to May 2023.After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks,they were divided into HBsAg clearance group and HBsAg non-clearance group.Their general information and serological,biochemical,and virological indicators at different time points during treatment were recorded.Continuous data in normal distribution were compared using the t test.Continuous data in non-normal distribution were compared using the Mann-Whitney U test,and comparisons across different time points were performed using the multiple paired-sample Friedman test.Categorical data were compared using the χ2 test.A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.Results Before treatment,there were significant differences in baseline HBsAg level(Z=-3.997,P<0.05)and treatment history(χ2=8.221,P<0.05)between the two groups.During treatment,gradually decreasing trends were observed in white blood cell count(χ2=104.944),neutrophil count(χ2=132.036),platelet count(χ2=162.881),and thyroid-stimulating hormone level(TSH,χ2=83.304,all P<0.05),while alanine aminotransferase(ALT,χ2=157.618)and alpha fetoprotein(χ2=159.472)showed gradually increasing trends(both P<0.05).At 48 weeks of treatment,treatment history(odds ratio[OR]=0.232,95%confidence interval[CI]:0.071-0.753),baseline HBsAg level(OR=13.423,95%CI:3.276-54.997),the extent of decrease in HBsAg from baseline after 12 weeks of treatment(OR=0.143,95%CI:0.040-0.515),the maximum ALT level during treatment(OR=0.986,95%CI:0.980-0.993),and the minimum TSH level during treatment(OR=3.281,95%CI:1.413-7.619)were independent factors affecting HBsAg clearance(all P<0.05).A combined predictive model for HBsAg clearance was built:Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment.The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following:the maximum ALT value during treatment(AUC=0.824),baseline HBsAg value(AUC=0.727),the minimum TSH value during treatment(AUC=0.707),the extent of HBsAg reduction from baseline after 12 weeks of treatment(AUC=0.641),and treatment history(AUC=0.636).The combined model showed better predictive performance than the individual indicators,with the AUC being 0.921(all P<0.05).Conclusion The combined model,constructed with baseline HBsAg value,the extent of HBsAg reduction from baseline after 12 weeks of treatment,the maximum ALT value during treatment,and the minimum TSH value during treatment,has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b,which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.
8.Influencing factors for recompensation in patients with decompensated hepatitis B cirrhosis
Danqing XU ; Yingyuan ZHANG ; Huan MU ; Caifen SA ; Chunyan MOU ; Yuanzhen WANG ; Weikun LI ; Li LIU
Journal of Clinical Hepatology 2025;41(7):1364-1370
Objective To investigate the influencing factors for recompensation in patients with decompensated hepatitis B cirrhosis,and to establish a predictive model.Methods A total of 517 patients who attended The Third People's Hospital of Kunming and were diagnosed with decompensated hepatitis B cirrhosis from January 1,2016 to December 31,2022 were enrolled.The clinical data of the patients were reviewed,and the 207 patients with no portal hypertension-related complications within at least 1 year were enrolled as recompensation group,while the 310 patients without recompensation were enrolled as persistent decompensation group.Related clinical data were collected,and the univariate and multivariate Cox regression analyses were performed for the factors that might affect the occurrence of recompensation.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.The"rms"package was used to establish a nomogram;the receiver operating characteristic(ROC)curve was plotted,and the area under the ROC curve(AUC)was calculated;the Hosmer-Lemeshow test was used to evaluate the degree of fitting of the model;the"Calibration Curves"package was used to plot the calibration curve for model assessment.Results Among the patients with decompensated hepatitis B cirrhosis,207(40.03%)had recompensation.The univariate Cox regression analysis showed that there were significant differences between the recompensation group and the persistent decompensation group in TIPS history,genotyping,portal vein thrombosis,complicated infection,Child-Pugh class,age,hemoglobin(Hb),platelet count,total protein,albumin(Alb),alanine aminotransferase,triglyceride,cholesterol,creatinine,Na,interleukin-6,high-sensitivity C-reactive protein,portal vein width,and portal vein velocity(all P<0.05).The multivariate regression analysis showed that TIPS history(hazard ratio[HR]=2.491,95%confidence interval[CI]:1.325-4.681,P=0.005),portal vein thrombosis(HR=0.345,95%CI:0.152-0.783,P=0.001),Hb(HR=1.007,95%CI:1.000-1.013,P=0.028),Alb(HR=1.048,95%CI:1.017-1.080,P=0.002),and portal vein width(HR=0.899,95%CI:0.835-0.967,P=0.004)were independent influencing factors for recompensation in patients with decompensated hepatitis B cirrhosis.A nomogram model was established based on the above five influencing factors,and the Hosmers-Lemeshow test showed that this model had a good degree of fitting(χ2=3.202,P=0.921).The nomogram model had an AUC of 0.728,a sensitivity of 50.3%,and a specificity of 85.0%,and the calibration curve showed good consistency between the actual value of this model in predicting the occurrence of recompensation and the predicted value in patients with decompensated hepatitis B cirrhosis.Conclusion Patients with decompensated hepatitis B cirrhosis who have a history of TIPS and high levels of Alb and Hb are more likely to have recompensation,and it is relatively difficult for patients with portal vein thrombosis and an increase in portal vein width to achieve recompensation.
9.Analysis of influencing factors and construction of predictive model for HBsAg clearance in patients with HBeAg-negative chronic hepatitis B treated with PEG-IFN-α-2b
Yingyuan ZHANG ; Danqing XU ; Huan MU ; Yuanqiang HE ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Chunyan MOU ; Li LIU
Journal of Clinical Hepatology 2025;41(8):1525-1532
Objective To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B(CHB)receiving peginterferon alfa-2b(PEG-IFN-α-2b)treatment,analyze the effects of various indicators on the HBsAg clearance rate under different characteristics,and construct and evaluate a combined predictive model.Methods We included 125 patients with HBeAg-negative CHB at Kunming Third People's Hospital from May 2021 to May 2023.After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks,they were divided into HBsAg clearance group and HBsAg non-clearance group.Their general information and serological,biochemical,and virological indicators at different time points during treatment were recorded.Continuous data in normal distribution were compared using the t test.Continuous data in non-normal distribution were compared using the Mann-Whitney U test,and comparisons across different time points were performed using the multiple paired-sample Friedman test.Categorical data were compared using the χ2 test.A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.Results Before treatment,there were significant differences in baseline HBsAg level(Z=-3.997,P<0.05)and treatment history(χ2=8.221,P<0.05)between the two groups.During treatment,gradually decreasing trends were observed in white blood cell count(χ2=104.944),neutrophil count(χ2=132.036),platelet count(χ2=162.881),and thyroid-stimulating hormone level(TSH,χ2=83.304,all P<0.05),while alanine aminotransferase(ALT,χ2=157.618)and alpha fetoprotein(χ2=159.472)showed gradually increasing trends(both P<0.05).At 48 weeks of treatment,treatment history(odds ratio[OR]=0.232,95%confidence interval[CI]:0.071-0.753),baseline HBsAg level(OR=13.423,95%CI:3.276-54.997),the extent of decrease in HBsAg from baseline after 12 weeks of treatment(OR=0.143,95%CI:0.040-0.515),the maximum ALT level during treatment(OR=0.986,95%CI:0.980-0.993),and the minimum TSH level during treatment(OR=3.281,95%CI:1.413-7.619)were independent factors affecting HBsAg clearance(all P<0.05).A combined predictive model for HBsAg clearance was built:Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment.The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following:the maximum ALT value during treatment(AUC=0.824),baseline HBsAg value(AUC=0.727),the minimum TSH value during treatment(AUC=0.707),the extent of HBsAg reduction from baseline after 12 weeks of treatment(AUC=0.641),and treatment history(AUC=0.636).The combined model showed better predictive performance than the individual indicators,with the AUC being 0.921(all P<0.05).Conclusion The combined model,constructed with baseline HBsAg value,the extent of HBsAg reduction from baseline after 12 weeks of treatment,the maximum ALT value during treatment,and the minimum TSH value during treatment,has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b,which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.
10.Circular RNA_005987 mediates contrast-associated acute kidney injury through activating autophagy signaling by sponging miRNA-129-5p
Yeshen ZHANG ; Siyu KONG ; Haobin LIU ; Weikun CHEN ; Guangjun HUANG ; Yining DAI ; Ning TAN ; Yuanhui LIU
Chinese Journal of Nephrology 2025;41(2):114-124
Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

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