1.Construction of a nomogram model for clinical cure of chronic hepatitis B with a low level of hepatitis B surface antigen treated with pegylated interferon α-2b
Yingyuan ZHANG ; Huan MU ; Lixian CHANG ; Danqing XU ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Huangchenghao ZHANG ; Chunyan MOU ; Li LIU
Journal of Clinical Hepatology 2026;42(5):1038-1047
ObjectiveTo investigate the predictive factors for HBsAg clearance in chronic hepatitis B (CHB) patients with a low level of hepatitis B surface antigen (HBsAg) treated with pegylated interferon α-2b (PEG-IFN-α-2b), to establish a combined predictive model and a nomogram based on multiple factors, and to provide a reference for formulating individualized treatment regimens and predicting treatment outcome in clinical practice. MethodsA retrospective analysis was performed for 167 CHB patients with HBsAg <1 500 IU/mL who attended The Third People’s Hospital of Kunming from January 2022 to January 2024 and were treated with PEG-IFN-α-2b. According to whether clinical cure was achieved, the patients were divided into HBsAg clearance group and HBsAg non-clearance group. Related data were collected, including general information and serological/biochemical/virological indicators at different time points during treatment. The independent samples t-test was used for comparison of normally distributed continuous data, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data; the chi-square test was used for comparison of categorical data. The multivariate logistic regression analysis was used to identify independent influencing factors. The receiver operating characteristic (ROC) curve was used to assess the value of indicators used alone or in combination in predicting clinical cure, and calibration curves were plotted to assess the risk prediction model. ResultsThe univariate analysis showed that there were significant differences between the two groups in age (t=-6.839, P<0.05), history of nucleos(t)ide analogue treatment for over 1 year (χ2=59.339, P<0.05), genotype (χ2=4.610, P<0.05), nonalcoholic fatty liver disease (χ2=5.319, P<0.05), hepatitis B virus DNA status before treatment (χ2=60.861, P <0.05), compensated liver cirrhosis (χ2=10.960, P<0.05), HBeAg status before treatment (χ2=19.060, P<0.05), a history of interferon treatment (χ2=8.162, P<0.05), presence of interferon antibodies after treatment (χ2=12.858, P<0.05), HBsAg level before treatment (Z=-7.412, P<0.05), alanine aminotransaminase (ALT) level at baseline (Z=-6.117, P<0.05), ALT level at 12 weeks of treatment (Z=-7.171, P<0.05), platelet count (PLT) at 24 weeks of treatment (Z=-3.622, P<0.05), and thyroid stimulating hormone (TSH) level at 24 weeks of treatment (Z=-2.830, P<0.05). The multivariate logistic regression analysis showed that age (odds ratio [OR]=1.230, P=0.007), history of nucleos(t)ide analogue treatment for over 1 year (OR=0.008, P=0.011), HBeAg status before treatment (OR=0.003, P=0.012), HBsAg level before treatment (OR=1.005, P=0.014), ALT level at baseline (OR=0.949, P=0.014), ALT level at 12 weeks of treatment (OR=0.969, P=0.016), PLT at 24 weeks of treatment (OR=0.969, P=0.022), and TSH level at 24 weeks of treatment (OR=3.608, P=0.045) were independent influencing factors for HBsAg clearance at 48 weeks of treatment in CHB patients with HBsAg <1 500 IU/mL. The Hosmer-Lemeshow goodness-of-fit test yielded χ2=1.398, P=0.994, indicating that the model had good fitting. The Bootstrap method was used to perform internal validation of the nomogram model, and there was a good degree of fitting between the calibration curve and the ideal curve, with a mean absolute error of 0.029. The ROC curve analysis showed that the combination of predictive factors had an area under the ROC curve of 0.982 (95% confidence interval: 0.961 — 0.999), with a sensitivity of 94.10% and a specificity of 93.10%, suggesting that the nomogram model had a good discriminatory ability. For the CHB patients with HBsAg <1 500 IU/mL and different features, further analysis of HBsAg clearance rate at 48 weeks of treatment showed an HBsAg clearance rate of 69.60% for those with HBsAg ≤67.65 IU/mL before treatment, 58.30% for those with a baseline ALT level of ≥62.50 U/L, 68.30% for those with an ALT level of ≥92.50 U/L at 12 weeks of treatment, 42.40% for those with PLT ≥104×109/L at 24 weeks of treatment, and 48.30% for those with a TSH level of ≤1.38 μIU/mL at 24 weeks of treatment, with significant differences between the two groups (all P<0.001). ConclusionAge, history of nucleos(t)ide analogue treatment for over 1 year, HBeAg status before treatment, HBsAg level before treatment, baseline ALT level, ALT level at 12 weeks of treatment, PLT level at 24 weeks, and TSH level at 24 weeks of treatment are independent predictive factors. The combined prediction nomogram model constructed in this study has a relatively high value in predicting clinical cure at 48 weeks of PEG-IFN-α-2b treatment in CHB patients with HBsAg<1 500 IU/mL, thereby providing a reference for selecting suitable treatment population and predicting clinical cure.
2.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.
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.Risk factors for concurrent hepatic hydrothorax before intervention in primary liver cancer and construction of a nomogram prediction model
Yuanzhen WANG ; Renhai TIAN ; Yingyuan ZHANG ; Danqing XU ; Lixian CHANG ; Chunyun LIU ; Li LIU
Journal of Clinical Hepatology 2025;41(1):75-83
ObjectiveTo investigate the influencing factors for hepatic hydrothorax (HH) before intervention for primary hepatic carcinoma (PHC), and to construct and assess the nomogram risk prediction model. MethodsA retrospective analysis was performed for the clinical data of 353 hospitalized patients who attended the Third People’s Hospital of Kunming for the first time from October 2012 to October 2021 and there diagnosed with PHC, and according to the presence or absence of HH, they were divided into HH group with 153 patients and non-HH group with 200 patients. General data and the data of initial clinical testing after admission were collected from all PHC patients. 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 groups. After the multicollinearity test was performed for the variables with statistical significance determined by the univariate analysis, the multivariate Logistic regression analysis was used to identify independent influencing factors. The “rms” software package was used to construct a nomogram risk prediction model, and the Hosmer-Lemeshow test and the receiver operating characteristic (ROC) curve were used to assess the risk prediction model; the “Calibration Curves” software package was used to plot the calibration curve, and the “rmda” software package was used to plot the clinical decision curve and the clinical impact curve. ResultsAmong the 353 patients with PHC, there were 153 patients with HH, with a prevalence rate of 43.34%. Child-Pugh class B (odds ratio [OR]=2.652, 95% confidence interval [CI]: 1.050 — 6.698, P=0.039), Child-Pugh class C (OR=7.963, 95%CI: 1.046 — 60.632, P=0.045), total protein (OR=0.947, 95%CI: 0.914 — 0.981, P=0.003), high-sensitivity C-reactive protein (OR=1.007, 95%CI: 1.001 — 1.014, P=0.025), and interleukin-2 (OR=0.801, 95%CI: 0.653 — 0.981, P=0.032) were independent influencing factors for HH before PHC intervention, and a nomogram risk prediction model was established based on these factors. The Hosmer-Lemeshow test showed that the model had a good degree of fitting (χ2=5.006, P=0.757), with an area under the ROC curve of 0.752 (95%CI: 0.701 — 0.803), a sensitivity of 78.40%, and a specificity of 63.50%. The calibration curve showed that the model had good consistency in predicting HH before PHC intervention, and the clinical decision curve and the clinical impact curve showed that the model had good clinical practicability within a certain threshold range. ConclusionChild-Pugh class, total protein, interleukin-2, and high-sensitivity C-reactive protein are independent influencing factors for developing HH before PHC intervention, and the nomogram model established based on these factors can effectively predict the risk of developing HH.
5.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.
6.Mechanism study on human antigen R inhibitor MS-444 attenuating fat absorption and obesity by inhibiting intestinal triglyceride synthesis
Yuanzhen SHAO ; Cihang LIU ; Ying WANG ; Zhiying ZHENG ; Wengong WANG
Chinese Journal of Geriatrics 2025;44(11):1562-1569
Objective:To investigate the effects of the small molecule inhibitor of human antigen R (HuR)protein, MS-444 on intestinal fat absorption and triglyceride synthesis.Methods:MS-444 was administered by enema to normal chow diet(NCD)and high-fat diet(HFD)mouse models.Key indicators including body weight, serum triglycerides(TAG), serum free fatty acids(FFA), hepatic lipid deposition, and adipose tissue weights were measured.Additionally, the impact of MS-444 on intestinal lipid absorption and the triglyceride synthesis enzymes diacylglycerol acyltransferase 2 (DGAT2)and monoacylglycerol acyltransferase 2(MGAT2)were also assessed.Results:The study demonstrated that MS-444 enema markedly reduced serum TAG and FFA levels in both NCD-and HFD-fed mice [NCD mice TAG: (0.854±0.145)mmol vs.(0.608±0.120)mmol, P=0.032, NCD mice FFA: (0.650±0.119)mmol vs.(0.432±0.106)mmol, P=0.032; HFD mice TAG: (1.410±0.254)mmol vs.(0.704±0.132)mmol, P=0.008, HFD mice FFA: (1.202±0.195)mmol vs.(0.772±0.102)mmol, P=0.008], as well as hepatic lipid deposition [(14.300±0.704)μmol/g vs.(7.640±1.584)μmol/g, P=0.008] in HFD-fed mice.MS-444 modulated intestinal fat absorption by lowering TAG levels[(10.350±2.046)μmol/g vs.(6.802±2.037)μmol/g, P=0.031], while elevating intestinal FFA levels[(5.746±1.433)μmol/g vs.(8.050±1.121)μmol/g, P=0.032]. Mechanistically, MS-444 significantly inhibited the interaction between HuR and the enzymes DGAT2 and MGAT2 in the proximal small intestine, leading to downregulation of their mRNA and protein expression, thereby inhibiting intestinal triglyceride synthesis. Conclusions:MS-444 can alleviate HFD-induced non-alcoholic fatty liver disease(NAFLD)and obesity by reducing intestinal fat absorption.The functional interaction between HuR and the enzymes DGAT2 and MGAT2 may play a key regulatory role, indicating the therapeutic potential application value of MS-444 in metabolic disorders.
7.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.
8.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.
9.Establishment and validation of a nomogram model for patients with decompensated HBV/HCV cirrhosis comorbid with portal vein thrombosis
Renhai TIAN ; Yuanzhen WANG ; Hongyan WEI ; Lixian CHANG ; Chunyun LIU ; Li LIU
Journal of Clinical Hepatology 2025;41(8):1579-1588
Objective To investigate the independent risk factors for portal vein thrombosis(PVT)in patients with viral hepatitis-related decompensated cirrhosis,and to establish and validate a nomogram risk prediction model.Methods A retrospective analysis was performed for the clinical data of 1 116 patients with decompensated HBV/HCV cirrhosis who attended The Third People's Hospital of Kunming for the first time from January 2022 to December 2023,and according to the presence or absence of PVT,they were divided into PVT group and control group.The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.Univariate analysis and least absolute shrinkage and selection operator(LASSO)regression analysis were used to identify variables,and a binary logistic regression analysis was used to obtain independent influencing factors and establish a predictive model,which was visualized using a nomogram.The model was validated based on the receiver operating characteristic(ROC)curve,the area under the ROC curve(AUC),the Hosmer-Lemeshow test,Bootstrap sampling(1 000 iterations),the calibration curve,the decision curve analysis(DCA),and the clinical impact curve(CIC).Results There were 178 patients in the PVT group and 938 patients in the control group,and the prevalence rate of PVT was 15.9%(178/1 116).Male patients accounted for 68.5%(764/1 116),and the patients with drinking,Child-Pugh class B liver function,and ascites accounted for 51.0%(569/1 116),78.8%(879/1 116),and 67.1%(749/1 116),respectively.Compared with the control group,the PVT group had significantly higher age(Z=-2.362,P<0.05),prothrombin time(Z=-2.403,P<0.05),international normalized ratio(Z=-2.470,P<0.05),free thyroxine(Z=-5.910,P<0.05),D-dimer(Z=-5.764,P<0.05),interleukin-6(Z=-6.581,P<0.05),interleukin-10(IL-10)(Z=-3.915,P<0.05),interleukin-8(Z=-3.705,P<0.05),diameter of the portal vein(Z=-9.690,P<0.05),and spleen thickness(Z=-7.183,P<0.05),as well as significantly lower levels of white blood cell count(Z=-2.115,P<0.05),platelet count(Z=-3.026,P<0.05),fibrinogen(Z=-2.169,P<0.05),alanine aminotransferase(Z=-3.151,P<0.05),prealbumin(Z=-3.509,P<0.05),cholinesterase(Z=-3.415,P<0.05),alpha-fetoprotein(Z=-3.513,P<0.05),triglycerides(Z=-2.679,P<0.05),CD3 cell count(Z=-6.059,P<0.05),CD4 cell count(Z=-7.257,P<0.05),CD8 cell count(Z=-2.340,P<0.05),CD4+/CD8+cell ratio(Z=-4.479,P<0.05),triiodothyronine(Z=-3.338,P<0.05),free triiodothyronine(FT3)(Z=-9.560,P<0.05),and portal blood flow velocity(Z=-4.568,P<0.05).The multivariate logistic regression analysis was performed for the variables with statistical significance identified by the LASSO regression analysis,and the results showed that age(odds ratio[OR]=1.046,95%confidence interval[CI]:1.026-1.066),CD4+/CD8+cell ratio(OR=0.568,95%CI:0.410-0.787),FT3(OR=0.956,95%CI:0.944-0.968),IL-10(OR=1.021,95%CI:1.001-1.042),diameter of the portal vein(OR=1.446,95%CI:1.329-1.574),and spleen thickness(OR=1.035,95%CI:1.014-1.055)were independent influencing factors.A model was established as Logit(P)=-8.784+0.045×age-0.566×CD4+/CD8+-0.046×FT3+0.021×IL-10+0.369×diameter of the portal vein+0.034×spleen thickness,and a nomogram model was established and validated based on this model,with an AUC of 0.859(95%CI:0.833-0.887).The Hosmer-Lemeshow test showed that the model had a high goodness of fit(χ2=11.349,P=0.183).Bootstrap internal validation showed a mean absolute error of 0.006 and a C-index of 0.855.The decision curve analysis showed that the model had a high net clinical benefit within a wide range of thresholds.Conclusion Age,CD4+/CD8+ratio,FT3,IL-10,diameter of the portal vein,and spleen thickness may be independent influencing factors for PVT in patients with decompensated HBV/HCV cirrhosis.The predictive model established based on these six variables can help to predict the risk of PVT in patients with hepatitis-related decompensated cirrhosis in the early stage in clinical practice.
10.Establishment and Evaluation of a Risk Prediction Model for Chronic Liver Failure Complicated by Primary Hepatocellular Carcinoma Before Intervention
Yuanzhen WANG ; Hongyan WEI ; Renhai TIAN ; Yongzhen CHEN ; Danqing XU ; Yingyuan ZHANG ; Lixian CHANG ; Chunyun LIU ; Li LIU
Journal of Kunming Medical University 2025;46(3):139-147
Objective To analyze the influencing factors of chronic liver failure in patients with primary hepatic carcinoma(PHC)before intervention,and to establish and evaluate a nomogram risk prediction model.Methods A retrospective analysis was conducted by collecting general data and clinical test data within 24 hours of admission for PHC patients.Univariate analysis and Lasso regression were used for variable selection,followed by multivariate logistic regression analysis to identify independent influencing factors for CLF before PHC intervention,leading to the establishment of a nomogram risk prediction model.The model was evaluated using the Hosmer-Lemeshow test,receiver operating characteristic(ROC)curve,calibration curve,clinical decision curve,and clinical impact curve.Result A total of 353 cases of PHC patients were collected,including 153 cases in the liver failure group and 200 cases in the non-liver failure group,with a prevalence rate of 43.3%.Variables selected by Lasso regression included gastrointestinal bleeding,prothrombin time(PT),albumin(ALB),total bilirubin(TBIL),and gamma glutamyl transferase(GGT).Multivariate logistic regression analysis showed that gastrointestinal bleeding(OR=13.549,95%CI:2.899~63.322,P=0.001),PT(OR=1.599,95%CI:1.282~1.995,P<0.001),TBIL(OR=1.016,95%CI:1.006~1.025,P=0.002),and GGT(OR=1.002,95%CI:1.000~1.003,P=0.028)were independent risk factors for chronic liver failure prior to PHC intervention,leading to the establishment of a nomogram risk prediction model.The Hosmer Lemeshow test showed that the model had a good fit(x2=6.152,P>0.05);the area under ROC was 0.902(0.869-0.934),with a sensitivity of 80.4%and a specificity of 87.5%.The calibration curve indicated that the model predicts chronic liver failure prior to PHC intervention with good consistency.Clinical decision curve analysis and clinical impact curve analysis showed that the model has good clinical utility within a certain threshold range.Conclusion Gastrointestinal bleeding,PT ≥16.05s,TBIL≥37.80 mmol/L,and GGT≥ 99.00 U/L are independent risk factors for the occurrence of chronic liver failure before PHC intervention.The established nomogram risk prediction model has certain clinical application value in predicting the risk of chronic liver failure before PHC intervention.

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