BACKGROUND The portal vein thrombosis(PVT)can exacerbate portal hypertension and lead to complications,increasing the risk of mortality.AIM To evaluate the predictive capacity of artificial neural networks(ANNs)in qua...BACKGROUND The portal vein thrombosis(PVT)can exacerbate portal hypertension and lead to complications,increasing the risk of mortality.AIM To evaluate the predictive capacity of artificial neural networks(ANNs)in quan-tifying the likelihood of developing PVT in individuals afflicted with hepatitis B-induced cirrhosis.METHODS A retrospective study was conducted at Beijing Ditan Hospital,affiliated with Capital Medical University,including 986 hospitalized patients.Patients admitted between January 2011 and December 2014 were assigned to the training set(685 cases),while those hospitalized from January 2015 to December 2016 were divided into the validation cohort(301 cases).Independent risk factors for PVT were identified using COX univariate analysis and used to construct an ANN model.Model performance was evaluated through metrics such as the area under the receiver operating characteristic curve(AUC)and concordance index.RESULTS In the training set,PVT occurred in 19.0%of patients within three years and 23.7%within five years.In the validation cohort,PVT developed in 16.7%of patients within three years and 24.0%within five years.The ANN model incorporated nine independent risk factors:Age,ascites,hepatic encephalopathy,gastrointestinal varices with bleeding,Child-Pugh classification,alanine aminotransferase levels,albumin levels,neutrophil-to-lymphocyte ratio,and platelet.The model achieved an AUC of 0.967(95%CI:0.960–0.974)at three years and 0.975(95%CI:0.955–0.992)at five years,significantly outperforming existing models such as model for end-stage liver disease and Child-Pugh-Turcotte(all P<0.001).CONCLUSION The ANN model demonstrated effective stratification of patients into high-and low-risk groups for PVT deve-lopment over three and five years.Validation in an independent cohort confirmed the model's predictive accuracy.展开更多
Objective:To study the levels of serum cystatin C(Cys-C),total bile acid(TBA),and other routine blood parameters on patients with decompensated hepatitis B cirrhosis.Methods:Study group 1 consisted of 30 patients with...Objective:To study the levels of serum cystatin C(Cys-C),total bile acid(TBA),and other routine blood parameters on patients with decompensated hepatitis B cirrhosis.Methods:Study group 1 consisted of 30 patients with hepatitis B-related decompensated cirrhosis,and study group 2 consisted of 30 patients with hepatitis B;while the control group consisted of 30 healthy people who underwent physical examination.The blood parameters were used to evaluate the clinical treatment effect of patients.Results:The TBA,Cys-C,alanine transaminase(ALT),total bilirubin(TBIL),aspartate aminotransferase(AST),and international normalized ratio(INR)in study group 1 were significantly higher than those of study group 2 and the control group;while the platelet count(PLT),hemoglobin(Hb),albumin(ALB),and estimated glomerular filtration rate(eGFR)were significantly lower in the study group 1 compared to the control group and study group 2(P<0.05).The Cys-C,PLT,TBA,AST,TBIL,and INR of patients in study group 1 who were successfully treated were significantly lower than the patients who were not successfully treated(P<0.05).Conclusion:Serum Cys-C,TBA,and routine blood parameters are useful in predicting the condition and the prognosis of patients of hepatitis B-related decompensated cirrhosis.展开更多
Background The World Health Organization(WHO)targets a 65%reduction in hepatitis B-related deaths by 2030 compared to 2015 to eliminate viral hepatitis as a major public health threat.It is unknown whether and how Chi...Background The World Health Organization(WHO)targets a 65%reduction in hepatitis B-related deaths by 2030 compared to 2015 to eliminate viral hepatitis as a major public health threat.It is unknown whether and how China can achieve this target despite significant intervention achievements.We aimed to predict the hepatitis B-related deaths in China and identify key developments needed to achieve the target.Methods An age-and time-dependent dynamic hepatitis B virus(HBV)transmission compartmental model was developed to predict the trend of hepatitis B-related deaths under base-case and subsequent scenarios from 2015 to 2040.In base-case scenario,we assumed the diagnosis and treatment(D&T)rate would reach 72%in 2030,as proposed by WHO.Subsequent scenarios were set based on the results of base-case and one-way sensitivity analysis.Results Compared with 2015,hepatitis B-related deaths would be reduced by 23.89%in 2030 and 51.79%in 2040,respectively,and the WHO's impact target of 65%reduction would not be achieved until 2038 at the earliest under base-case scenario.HBV clearance rate and current treatment effectiveness were the most sensitive parameters that significantly influenced the decline of hepatitis B-related deaths from 2015 to 2040.In the subsequent scenario,when D&T rate improving to 90%by 2030,with the current treatment effectiveness and HBV clearance rate being optimized from 2016,the WHO's impact target would be achieved in 2038.Increasing the clearance rate further from 2%to 2.8%during 2016–2030 linearly,the impact target would be achieved on time.Conclusions It is difficult for China to achieve the WHO's impact target of 65%reduction in hepatitis B-related deaths by 2030 even we assumed the D&T rate would reach 72%in 2030 and beyond.A comprehensive scale-up of available strategies,especially innovative drugs and technologies will ensure that China achieves the target on schedule.展开更多
Background Hepatitis B virus infection is closely related to hepatocellular carcinoma （HCC）. Cyclooxygenase-2 （COX-2） is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study,...Background Hepatitis B virus infection is closely related to hepatocellular carcinoma （HCC）. Cyclooxygenase-2 （COX-2） is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B （CHB） patients, liver cirrhosis patients, and hepatocellular carcinoma （HCC） patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province. Methods Patients were divided into four groups： 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0. Results The COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups （0R=2.835, 95%C/： 1.751-4.589）; HCC and CHB groups （OR=1.933, 95%C/： 1.248-2.994）; and HCC and liver cirrhosis groups （OR=1. 175, 95%C/： 1.119-2.628）. Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC. Conclusion COX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.展开更多
BACKGROUND Hepatitis B-associated cirrhosis is an important disease burden in China.However,there is a lack of effective predictors in clinical practice to drive delivery and enable early treatment to delay disease pr...BACKGROUND Hepatitis B-associated cirrhosis is an important disease burden in China.However,there is a lack of effective predictors in clinical practice to drive delivery and enable early treatment to delay disease progression.AIM To analyzing the clinical characteristics of patients with hepatitis and cirrhosis,the nomogram model was established and validated.METHODS The clinical data of 1070 patients with hepatitis B who were treated in our hospital from October 2015 to July 2022 were collected.In a 7:3 ratio,749 cases were divided into training cohorts and 321 cases were divided into validation cohorts.In addition,the training cohort and validation cohort were further divided into hepatitis group and hepatitis B-related cirrhosis group based on whether the patient progressed to cirrhosis.Binary logistic regression was used to analyze the influencing factors of hepatitis progression to cirrhosis.A roadmap prediction model was established,and the predictive effect of the model was evaluated by patientsubject receiver operating characteristic curve(ROC),and the effectiveness of the model was evaluated by decision curve analysis.RESULTS Binary logistic regression analysis was performed using hepatitis B-related cirrhosis=1 and hepatitis=0 as dependent variables,and univariate analysis of serological indicators was used as covariates.The results showed that glutamic oxaloacetate aminotransferase/glutamate acetone aminotransferase levels,prothrombin time activity,and hepatitis B e antigen levels were all contributing factors to the progression of hepatitis to cirrhosis.The area under the ROC curve was 0.693[95%confidence interval(CI):0.631 to 0.756]for the training cohort and 0.675(95%CI:0.561 to 0.790)for the validation cohort.In addition,the decision analysis curves of the prediction models of both the training cohort and the validation cohort confirmed the effectiveness of the nomogram prediction model.CONCLUSION Three independent factors influencing the progression to cirrhosis in patients with hepatitis B were identified.The construction of a nomogram prediction model from hepatitis to cirrhosis has high application value as a tool for predicting the occurrence of liver cirrhosis in hepatitis B patients.展开更多
Objective Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)generally have small sample sizes and a class imbalance.However,most machine learning models are desig...Objective Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)generally have small sample sizes and a class imbalance.However,most machine learning models are designed based on balanced data and lack interpretability.This study aimed to propose a traditional Chinese medicine(TCM)diagnostic model for HBV-ACLF based on the TCM syndrome differentiation and treatment theory,which is clinically interpretable and highly accurate.Methods We collected medical records from 261 patients diagnosed with HBV-ACLF,including three syndromes:Yang jaundice(214 cases),Yang-Yin jaundice(41 cases),and Yin jaundice(6 cases).To avoid overfitting of the machine learning model,we excluded the cases of Yin jaundice.After data standardization and cleaning,we obtained 255 relevant medical records of Yang jaundice and Yang-Yin jaundice.To address the class imbalance issue,we employed the oversampling method and five machine learning methods,including logistic regression(LR),support vector machine(SVM),decision tree(DT),random forest(RF),and extreme gradient boosting(XGBoost)to construct the syndrome diagnosis models.This study used precision,F1 score,the area under the receiver operating characteristic(ROC)curve(AUC),and accuracy as model evaluation metrics.The model with the best classification performance was selected to extract the diagnostic rule,and its clinical significance was thoroughly analyzed.Furthermore,we proposed a novel multiple-round stable rule extraction(MRSRE)method to obtain a stable rule set of features that can exhibit the model’s clinical interpretability.Results The precision of the five machine learning models built using oversampled balanced data exceeded 0.90.Among these models,the accuracy of RF classification of syndrome types was 0.92,and the mean F1 scores of the two categories of Yang jaundice and Yang-Yin jaundice were 0.93 and 0.94,respectively.Additionally,the AUC was 0.98.The extraction rules of the RF syndrome differentiation model based on the MRSRE method revealed that the common features of Yang jaundice and Yang-Yin jaundice were wiry pulse,yellowing of the urine,skin,and eyes,normal tongue body,healthy sublingual vessel,nausea,oil loathing,and poor appetite.The main features of Yang jaundice were a red tongue body and thickened sublingual vessels,whereas those of Yang-Yin jaundice were a dark tongue body,pale white tongue body,white tongue coating,lack of strength,slippery pulse,light red tongue body,slimy tongue coating,and abdominal distension.This is aligned with the classifications made by TCM experts based on TCM syndrome differentiation and treatment theory.Conclusion Our model can be utilized for differentiating HBV-ACLF syndromes,which has the potential to be applied to generate other clinically interpretable models with high accuracy on clinical data characterized by small sample sizes and a class imbalance.展开更多
Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previ...Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was.to characterize the TLR4 expression in peripheral blood mononuclear cells （PBMCs） of ACLF pa- tients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected （CHB） patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 ex- pression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was ana- lyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expres- sion of TLR4 on CD4＋ and CD8＋ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4＋ and CD8＋T cells were positively correlated with serum total bilirubin （TBIL）, direct bilirubin （DBIL）, international normalized ratio （INR） levels and white blood cells （WBCs）, and negatively correlated with serum albumin （ALB） levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4＋ T cells, which was also posi- tively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.展开更多
BACKGROUND As a country with a high burden of hepatitis B,China has about 86 million cases of hepatitis B virus infection,ranking the first in the world.Currently,there are about 390000 deaths due to hepatitis B-relat...BACKGROUND As a country with a high burden of hepatitis B,China has about 86 million cases of hepatitis B virus infection,ranking the first in the world.Currently,there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year.Consequently,how to control portal hypertension,improve liver functional reserve,and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention.Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt(TIPS),the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcoholinduced and immune cirrhosis,which may be related to the effective etiological treatment.AIM To investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China(2019)in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODS The clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively.According to different anti-viral drugs,the patients were divided into entecavir(ETV)(n=70),tenofovir alafenamide fumarate(TAF)(n=32),and tenofovir disoproxil fumarate(TDF)(n=35)groups.The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma,survival,and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTS At 24 mo after surgery,the Child-Pugh score in the TAF group(6.97±0.86)was lower than that in the TDF(7.49±0.82;t=-2.52,P=0.014)and ETV groups(7.64±1.17;t=-2.92,P=0.004).The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72±1.5,which was lower than that in the TDF(10.74±2.33;t=-2.09,P=0.040)and ETV groups(10.97±2.17;t=-2.93,P=0.004).At 24 mo after surgery,the estimated glomerular filtration rate(eGFR)in the TAF group(104.41±12.54)was higher than that in the TDF(93.54±8.97)and ETV groups(89.96±9.86)(F=21.57,P<0.001).CONCLUSION At 24 mo after surgery,compared with TDF and ETV,TAF has significant advantages in the improvement of liver functional reserve and eGFR.展开更多
Background The heme oxygenase/carbon monoxide （HO/CO） system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin （COH...Background The heme oxygenase/carbon monoxide （HO/CO） system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin （COHb） level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis （HBC） complicated by hepatic encephalopathy （HE）, and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC. Methods According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group （group N） consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen （PaO2） and oxygen saturation （SaO2） were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome （HRS）, upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis （SBP） in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades （I, II, III, and IV）, PaO2, SaO2 and hypoxemia were analyzed. Results The COHb level in group P-H （（1.672＋0.761）%） was significantly higher than that in group N （（0.983±0.231）%） （P 〈0.01 ）, and the level in group H （（2.102±1.021）%） was significantly higher than groups P-H and N （P 〈0.01 ）. A positive correlation was observed between the COHb concentration and the grade of HE （rs=0.357, P=-0.004）. There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices （（2.302±1.072）% vs. （1.802±1.041）%, P 〉0.05） or the occurrence of SBP （（2.960±0.561）% vs. （2.030±1.021）%, P 〉0.05）. Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS （（2.502±1.073）% vs. （1.981＋1.020）%, P=0.029）. The COHb level had a negative correlation with PaO2 （r=-0.335, P=0.007） while no statistically significant relationship was found with SaO2 （r=-0.071, P 〉0.05）. However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased （（2.621±0.880）% vs. （1.910±0.931）%, P=0.011 ）. Conclusions COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.展开更多
基金Supported by The Beijing Hospitals Authority Youth Programme,No.QMl220201802.
文摘BACKGROUND The portal vein thrombosis(PVT)can exacerbate portal hypertension and lead to complications,increasing the risk of mortality.AIM To evaluate the predictive capacity of artificial neural networks(ANNs)in quan-tifying the likelihood of developing PVT in individuals afflicted with hepatitis B-induced cirrhosis.METHODS A retrospective study was conducted at Beijing Ditan Hospital,affiliated with Capital Medical University,including 986 hospitalized patients.Patients admitted between January 2011 and December 2014 were assigned to the training set(685 cases),while those hospitalized from January 2015 to December 2016 were divided into the validation cohort(301 cases).Independent risk factors for PVT were identified using COX univariate analysis and used to construct an ANN model.Model performance was evaluated through metrics such as the area under the receiver operating characteristic curve(AUC)and concordance index.RESULTS In the training set,PVT occurred in 19.0%of patients within three years and 23.7%within five years.In the validation cohort,PVT developed in 16.7%of patients within three years and 24.0%within five years.The ANN model incorporated nine independent risk factors:Age,ascites,hepatic encephalopathy,gastrointestinal varices with bleeding,Child-Pugh classification,alanine aminotransferase levels,albumin levels,neutrophil-to-lymphocyte ratio,and platelet.The model achieved an AUC of 0.967(95%CI:0.960–0.974)at three years and 0.975(95%CI:0.955–0.992)at five years,significantly outperforming existing models such as model for end-stage liver disease and Child-Pugh-Turcotte(all P<0.001).CONCLUSION The ANN model demonstrated effective stratification of patients into high-and low-risk groups for PVT deve-lopment over three and five years.Validation in an independent cohort confirmed the model's predictive accuracy.
基金SPPH Incubator Fund for Development of Science and Technology(2021YJY-19)SPPH Foundation for Development of Science and Technology(2021BJ-26)International Science and Technology Cooperation Projects of Shaanxi Province(2022KW-14).
文摘Objective:To study the levels of serum cystatin C(Cys-C),total bile acid(TBA),and other routine blood parameters on patients with decompensated hepatitis B cirrhosis.Methods:Study group 1 consisted of 30 patients with hepatitis B-related decompensated cirrhosis,and study group 2 consisted of 30 patients with hepatitis B;while the control group consisted of 30 healthy people who underwent physical examination.The blood parameters were used to evaluate the clinical treatment effect of patients.Results:The TBA,Cys-C,alanine transaminase(ALT),total bilirubin(TBIL),aspartate aminotransferase(AST),and international normalized ratio(INR)in study group 1 were significantly higher than those of study group 2 and the control group;while the platelet count(PLT),hemoglobin(Hb),albumin(ALB),and estimated glomerular filtration rate(eGFR)were significantly lower in the study group 1 compared to the control group and study group 2(P<0.05).The Cys-C,PLT,TBA,AST,TBIL,and INR of patients in study group 1 who were successfully treated were significantly lower than the patients who were not successfully treated(P<0.05).Conclusion:Serum Cys-C,TBA,and routine blood parameters are useful in predicting the condition and the prognosis of patients of hepatitis B-related decompensated cirrhosis.
基金supported by the National Science and Technology Key Project of the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX10721202).
文摘Background The World Health Organization(WHO)targets a 65%reduction in hepatitis B-related deaths by 2030 compared to 2015 to eliminate viral hepatitis as a major public health threat.It is unknown whether and how China can achieve this target despite significant intervention achievements.We aimed to predict the hepatitis B-related deaths in China and identify key developments needed to achieve the target.Methods An age-and time-dependent dynamic hepatitis B virus(HBV)transmission compartmental model was developed to predict the trend of hepatitis B-related deaths under base-case and subsequent scenarios from 2015 to 2040.In base-case scenario,we assumed the diagnosis and treatment(D&T)rate would reach 72%in 2030,as proposed by WHO.Subsequent scenarios were set based on the results of base-case and one-way sensitivity analysis.Results Compared with 2015,hepatitis B-related deaths would be reduced by 23.89%in 2030 and 51.79%in 2040,respectively,and the WHO's impact target of 65%reduction would not be achieved until 2038 at the earliest under base-case scenario.HBV clearance rate and current treatment effectiveness were the most sensitive parameters that significantly influenced the decline of hepatitis B-related deaths from 2015 to 2040.In the subsequent scenario,when D&T rate improving to 90%by 2030,with the current treatment effectiveness and HBV clearance rate being optimized from 2016,the WHO's impact target would be achieved in 2038.Increasing the clearance rate further from 2%to 2.8%during 2016–2030 linearly,the impact target would be achieved on time.Conclusions It is difficult for China to achieve the WHO's impact target of 65%reduction in hepatitis B-related deaths by 2030 even we assumed the D&T rate would reach 72%in 2030 and beyond.A comprehensive scale-up of available strategies,especially innovative drugs and technologies will ensure that China achieves the target on schedule.
文摘Background Hepatitis B virus infection is closely related to hepatocellular carcinoma （HCC）. Cyclooxygenase-2 （COX-2） is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B （CHB） patients, liver cirrhosis patients, and hepatocellular carcinoma （HCC） patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province. Methods Patients were divided into four groups： 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0. Results The COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups （0R=2.835, 95%C/： 1.751-4.589）; HCC and CHB groups （OR=1.933, 95%C/： 1.248-2.994）; and HCC and liver cirrhosis groups （OR=1. 175, 95%C/： 1.119-2.628）. Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC. Conclusion COX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.
基金Supported by the“Climbing Program”Construction Project“High Peak Project”Department of Major Infectious Disease Prevention and Control.
文摘BACKGROUND Hepatitis B-associated cirrhosis is an important disease burden in China.However,there is a lack of effective predictors in clinical practice to drive delivery and enable early treatment to delay disease progression.AIM To analyzing the clinical characteristics of patients with hepatitis and cirrhosis,the nomogram model was established and validated.METHODS The clinical data of 1070 patients with hepatitis B who were treated in our hospital from October 2015 to July 2022 were collected.In a 7:3 ratio,749 cases were divided into training cohorts and 321 cases were divided into validation cohorts.In addition,the training cohort and validation cohort were further divided into hepatitis group and hepatitis B-related cirrhosis group based on whether the patient progressed to cirrhosis.Binary logistic regression was used to analyze the influencing factors of hepatitis progression to cirrhosis.A roadmap prediction model was established,and the predictive effect of the model was evaluated by patientsubject receiver operating characteristic curve(ROC),and the effectiveness of the model was evaluated by decision curve analysis.RESULTS Binary logistic regression analysis was performed using hepatitis B-related cirrhosis=1 and hepatitis=0 as dependent variables,and univariate analysis of serological indicators was used as covariates.The results showed that glutamic oxaloacetate aminotransferase/glutamate acetone aminotransferase levels,prothrombin time activity,and hepatitis B e antigen levels were all contributing factors to the progression of hepatitis to cirrhosis.The area under the ROC curve was 0.693[95%confidence interval(CI):0.631 to 0.756]for the training cohort and 0.675(95%CI:0.561 to 0.790)for the validation cohort.In addition,the decision analysis curves of the prediction models of both the training cohort and the validation cohort confirmed the effectiveness of the nomogram prediction model.CONCLUSION Three independent factors influencing the progression to cirrhosis in patients with hepatitis B were identified.The construction of a nomogram prediction model from hepatitis to cirrhosis has high application value as a tool for predicting the occurrence of liver cirrhosis in hepatitis B patients.
基金Key research project of Hunan Provincial Administration of Traditional Chinese Medicine(A2023048)Key Research Foundation of Education Bureau of Hunan Province,China(23A0273).
文摘Objective Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)generally have small sample sizes and a class imbalance.However,most machine learning models are designed based on balanced data and lack interpretability.This study aimed to propose a traditional Chinese medicine(TCM)diagnostic model for HBV-ACLF based on the TCM syndrome differentiation and treatment theory,which is clinically interpretable and highly accurate.Methods We collected medical records from 261 patients diagnosed with HBV-ACLF,including three syndromes:Yang jaundice(214 cases),Yang-Yin jaundice(41 cases),and Yin jaundice(6 cases).To avoid overfitting of the machine learning model,we excluded the cases of Yin jaundice.After data standardization and cleaning,we obtained 255 relevant medical records of Yang jaundice and Yang-Yin jaundice.To address the class imbalance issue,we employed the oversampling method and five machine learning methods,including logistic regression(LR),support vector machine(SVM),decision tree(DT),random forest(RF),and extreme gradient boosting(XGBoost)to construct the syndrome diagnosis models.This study used precision,F1 score,the area under the receiver operating characteristic(ROC)curve(AUC),and accuracy as model evaluation metrics.The model with the best classification performance was selected to extract the diagnostic rule,and its clinical significance was thoroughly analyzed.Furthermore,we proposed a novel multiple-round stable rule extraction(MRSRE)method to obtain a stable rule set of features that can exhibit the model’s clinical interpretability.Results The precision of the five machine learning models built using oversampled balanced data exceeded 0.90.Among these models,the accuracy of RF classification of syndrome types was 0.92,and the mean F1 scores of the two categories of Yang jaundice and Yang-Yin jaundice were 0.93 and 0.94,respectively.Additionally,the AUC was 0.98.The extraction rules of the RF syndrome differentiation model based on the MRSRE method revealed that the common features of Yang jaundice and Yang-Yin jaundice were wiry pulse,yellowing of the urine,skin,and eyes,normal tongue body,healthy sublingual vessel,nausea,oil loathing,and poor appetite.The main features of Yang jaundice were a red tongue body and thickened sublingual vessels,whereas those of Yang-Yin jaundice were a dark tongue body,pale white tongue body,white tongue coating,lack of strength,slippery pulse,light red tongue body,slimy tongue coating,and abdominal distension.This is aligned with the classifications made by TCM experts based on TCM syndrome differentiation and treatment theory.Conclusion Our model can be utilized for differentiating HBV-ACLF syndromes,which has the potential to be applied to generate other clinically interpretable models with high accuracy on clinical data characterized by small sample sizes and a class imbalance.
基金supported by the National Science and Technology Major Project for Infectious Diseases of China(No.2012ZX10004503)
文摘Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was.to characterize the TLR4 expression in peripheral blood mononuclear cells （PBMCs） of ACLF pa- tients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected （CHB） patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 ex- pression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was ana- lyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expres- sion of TLR4 on CD4＋ and CD8＋ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4＋ and CD8＋T cells were positively correlated with serum total bilirubin （TBIL）, direct bilirubin （DBIL）, international normalized ratio （INR） levels and white blood cells （WBCs）, and negatively correlated with serum albumin （ALB） levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4＋ T cells, which was also posi- tively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.
文摘BACKGROUND As a country with a high burden of hepatitis B,China has about 86 million cases of hepatitis B virus infection,ranking the first in the world.Currently,there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year.Consequently,how to control portal hypertension,improve liver functional reserve,and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention.Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt(TIPS),the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcoholinduced and immune cirrhosis,which may be related to the effective etiological treatment.AIM To investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China(2019)in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODS The clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively.According to different anti-viral drugs,the patients were divided into entecavir(ETV)(n=70),tenofovir alafenamide fumarate(TAF)(n=32),and tenofovir disoproxil fumarate(TDF)(n=35)groups.The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma,survival,and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTS At 24 mo after surgery,the Child-Pugh score in the TAF group(6.97±0.86)was lower than that in the TDF(7.49±0.82;t=-2.52,P=0.014)and ETV groups(7.64±1.17;t=-2.92,P=0.004).The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72±1.5,which was lower than that in the TDF(10.74±2.33;t=-2.09,P=0.040)and ETV groups(10.97±2.17;t=-2.93,P=0.004).At 24 mo after surgery,the estimated glomerular filtration rate(eGFR)in the TAF group(104.41±12.54)was higher than that in the TDF(93.54±8.97)and ETV groups(89.96±9.86)(F=21.57,P<0.001).CONCLUSION At 24 mo after surgery,compared with TDF and ETV,TAF has significant advantages in the improvement of liver functional reserve and eGFR.
基金This study was supported by grants from the National Natural Science Foundation of China，Science and Technology Project of Dalian City
文摘Background The heme oxygenase/carbon monoxide （HO/CO） system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin （COHb） level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis （HBC） complicated by hepatic encephalopathy （HE）, and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC. Methods According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group （group N） consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen （PaO2） and oxygen saturation （SaO2） were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome （HRS）, upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis （SBP） in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades （I, II, III, and IV）, PaO2, SaO2 and hypoxemia were analyzed. Results The COHb level in group P-H （（1.672＋0.761）%） was significantly higher than that in group N （（0.983±0.231）%） （P 〈0.01 ）, and the level in group H （（2.102±1.021）%） was significantly higher than groups P-H and N （P 〈0.01 ）. A positive correlation was observed between the COHb concentration and the grade of HE （rs=0.357, P=-0.004）. There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices （（2.302±1.072）% vs. （1.802±1.041）%, P 〉0.05） or the occurrence of SBP （（2.960±0.561）% vs. （2.030±1.021）%, P 〉0.05）. Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS （（2.502±1.073）% vs. （1.981＋1.020）%, P=0.029）. The COHb level had a negative correlation with PaO2 （r=-0.335, P=0.007） while no statistically significant relationship was found with SaO2 （r=-0.071, P 〉0.05）. However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased （（2.621±0.880）% vs. （1.910±0.931）%, P=0.011 ）. Conclusions COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.
