Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Value of total bilirubin rebound rate and total bilirubin clearance rate in evaluating the prognosis of severe drug-induced liver injury after artificial liver support therapy / 临床肝胆病杂志

Objective To investigate the value of total bilirubin rebound rate (TBRR), total bilirubin clearance rate (TBCR), and TBCR after 1 week of treatment (ΔTBCR) in evaluating the short-term prognosis of patients with severe drug-induced liver injury (DILI) after artificial liver support therapy. Methods A retrospective analysis was performed for 203 patients with severe DILI who received artificial liver support therapy in Tianjin Third Central Hospital from September 2013 to December 2021, and general information, biochemical parameters, and clinical classification were collected. The patients were divided into improved group and unhealed group according to the prognosis at discharge, and Model for End-Stage Liver Disease (MELD) score, TBRR, TBCR, and ΔTBCR were calculated. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U 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. The receiver operating characteristic (ROC) curve was plotted to investigate the value of assessment indices in predicting the prognosis of patients, and the Kaplan-Meier method was used to investigate the difference in the length of hospital stay in the context of different assessment indices. Results Compared with the unhealed group, the improved group had significantly lower age ( t =-2.762, P < 0.05), white blood cell count ( Z =-3.184, P < 0.05), total bilirubin ( t =-2.809, P < 0.05), conjugated bilirubin ( t =-2.739, P < 0.05), international normalized ratio ( Z =-2.357, P < 0.05), MELD score ( t =-3.090, P < 0.05), and TBRR ( t =-4.749, P < 0.05), as well as significantly higher albumin ( t =2.198, P < 0.05), prothrombin time activity ( t =2.018, P < 0.05), TBCR ( t =2.166, P < 0.05), and ΔTBCR ( t =9.549, P < 0.05). MELD score, TBRR, TBCR, and ΔTBCR had an area under the ROC curve (AUC) of 0.656, 0.727, 0.611, and 0.879, respectively, and ΔTBCR had a better predictive value than TBRR ( Z =3.169, P =0.001 5). The optimal cut-off value was 22.5% for TBRR (with a sensitivity of 94.6% and a specificity of 45.2%) and 27.4% for ΔTBCR (with a sensitivity of 77.7% and a specificity of 86.5%). ΔTBCR showed a good predictive value in different clinicopathological types, with extremely high sensitivity (91.4%) and specificity (100.0%) in evaluating the treatment outcome of patients with mixed-type DILI after artificial liver support therapy. Conclusion TBRR and ΔTBCR have a higher value than MELD score in evaluating the short-term prognosis of patients with severe DILI after artificial liver support therapy, among which ΔTBCR has a higher predictive value.

Clinical effect of direct-acting antiviral agents in treatment of chronic hepatitis C patients with thrombocytopenia / 临床肝胆病杂志

Objective To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT). Methods A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT 100×10 9 /L at baseline had a greater increase in PLT( P < 0.05). Conclusion CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.

Research advances in coronavirus disease 2019-related liver injury / 临床肝胆病杂志

The coronavirus disease 2019 (COVID-19) pandemic has brought great threats and challenges to global public health and has changed the priorities of medical resource allocation. A considerable proportion of patients with liver injury is observed during the clinical diagnosis and treatment of COVID-19, especially in those with a severe or critical illness. This article summarizes the epidemiology, mechanism, clinical features, and treatment of liver injury caused by COVID-19, in order to help clinicians with decision making and treatment optimization.

Mechanism of intestinal flora imbalance in the development and progression of liver cancer and the role of probiotics in preventing liver cancer / 临床肝胆病杂志

Intestinal flora imbalance plays a certain role in the development and progression of liver cancer, while probiotics have a certain impact on liver cancer, both of which are the focus of clinical research. This article introduces the mechanism of action of intestinal flora imbalance in the pathogenesis of liver cancer and the preventive effect of probiotics against liver cancer. Intestinal flora imbalance can participate in the pathological process of liver cancer by activating Toll-like receptor 4, regulating the level of metabolites, producing endotoxin, and inducing bacterial translocation and intestinal bacterial overgrowth, while probiotics can effectively prevent liver cancer by maintaining enterohepatic circulation, enhancing immune function, promoting the reproduction of intestinal probiotics, and reducing the toxicity of carcinogens, which can be further studied as the focus of subsequent liver cancer prevention in clinical practice.

Measurement of glycosylated albumin and its application value in liver cirrhosis patients with different Child-Pugh classes / 临床肝胆病杂志

Objective To investigate the level of glycosylated albumin (GA) in liver cirrhosis patients with different Child-Pugh classes and its application value in predicting liver function. Methods A total of 486 patients with liver cirrhosis who were hospitalized in Tianjin Third Central Hospital from January 1 to December 31, 2019, were enrolled, among whom 227 patients had liver cirrhosis without diabetes and 259 patients had liver cirrhosis with diabetes. The patients were divided into groups according to Child-Turcotte-Pugh (CTP) score, and fasting blood glucose, glycosylated hemoglobin, and percentage of GA (GA%) were measured. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the Dwass-Steel-Critchlow-Fligner test was used for further comparison between two groups. Scatter plots and fitting curves were plotted for CTP score and GA% to evaluate the association between them and calculate the cut-off value. Results For the cirrhosis patients without diabetes, there were significant differences between the patients with different Child-Pugh classes in GA% ( χ 2 =24.809, P < 0.001), fasting blood glucose ( χ 2 =11.899, P =0.003), and glycosylated hemoglobin ( χ 2 =13.607, P =0.001); further pairwise comparison showed that there was a significant difference in GA% between Child-Pugh class A/B liver cirrhosis patients without diabetes and Child-Pugh class C liver cirrhosis patients ( P < 0.05), Child-Pugh class A patients had a significantly higher level of fasting blood glucose than Child-Pugh class B patients ( P < 0.05), and Child-Pugh class A patients had a significantly higher level of glycosylated hemoglobin than Child-Pugh class B/C patients ( P < 0.05). For the patients with liver cirrhosis and diabetes, there were significant differences between the patients with different Child-Pugh classes in GA% ( χ 2 =10.734, P =0.005) and fasting blood glucose ( χ 2 =16.295, P < 0.001); further pairwise comparison showed that Child-Pugh class C liver cirrhosis patients with diabetes had a significantly lower GA% than Child-Pugh class A/B patients ( P < 0.05) and Child-Pugh class A patients had a significantly lower fasting blood glucose level than Child-Pugh class B patients ( P < 0.05). The fitting curve showed that GA% increased with the increase in CTP score in the liver cirrhosis patients without diabetes, reached the highest value at the CTP score of 6.5, and then started to decrease, with the lower value at the CTP score of 11.5, which showed a curvilinear relationship; in the liver cirrhosis patients with diabetes, GA% first increased and then decreased with the increase in CTP score, with a cut-off value of 8. Conclusion GA% first increases and then decreases along with the progression of liver cirrhosis. There is a significant difference in GA between liver cirrhosis patients with different Child-Pugh classes, suggesting that the reduction in GA is closely associated with liver function decompensation in end-stage liver cirrhosis.

A prospective multicenter and real-world study on the diagnostic value of combination of number connection test-B and line tracing test in mild hepatic encephalopathy / 中华消化杂志

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Influencing factors of rebleeding after gastroscopy in patients with liver cirrhosis and esophagogastric variceal bleeding / 临床肝胆病杂志

Objective To investigate the influencing factors for rebleeding after gastroscopy in patients with liver cirrhosis and esophagogastric variceal bleeding. Methods A retrospective analysis was performed for the clinical data of the patients with liver cirrhosis and esophagogastric variceal bleeding who were hospitalized in Tianjin Third Central Hospital from January 1, 2017 to December 31, 2018, and according to the presence or absence of rebleeding and bleeding time, the patients were divided into non-bleeding group ( n =148) and bleeding group ( n =119). The risk factors for rebleeding after gastroscopy were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Cox regression model was used for univariate and multivariate analyses. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of Child-Turcotte-Pugh (CTP), fibrosis-4 (FIB-4), and albumin-bilirubin (ALBI) scores in predicting rebleeding after gastroscopy, and MedCalc was used to compare the area under the ROC curve (AUC). Results A total of 267 patients with liver cirrhosis and esophagogastric variceal bleeding were enrolled, among whom 53 (19.9%) had liver cancer. A total of 119 patients suffered from rebleeding, with an overall rebleeding rate of 44.6% and a median time to rebleeding of 11.0 (0-39.0) months. The univariate Cox regression analysis showed that liver cancer (hazard ratio [ HR ]=0.377, P 0.05). Conclusion Liver cancer, AST, PT, CTP score, FIB-4 score, and ALBI score are associated with rebleeding after gastroscopy in patients with liver cirrhosis and esophagogastric variceal bleeding, among which CTP, FIB-4, and ALBI scores have a good value in predicting rebleeding outcome, while there is no significant difference in predictive ability between them.

Rebleeding and prognosis of patients with liver cirrhosis and severe esophagogastric variceal bleeding / 临床肝胆病杂志

ObjectiveTo investigate the risk factors for rebleeding within 5 years and the influencing factors for 5-year survival in patients with liver cirrhosis and severe esophagogastric variceal bleeding (EVB). MethodsA retrospective analysis was performed for 129 patients with liver cirrhosis who attended Tianjin Third Central Hospital from May 2012 to May 2014 due to severe EVB for the first time, with a follow-up time of 5 years. Related clinical data were analyzed, including age, sex, cause of liver cirrhosis, presence or absence of infection at the first time of bleeding, liver stiffness measurement (LSM), splenic stiffness measurement (SSM), portal vein diameter, biochemical parameters, rebleeding time, and prognosis. Esophagogastric variceal rebleeding was defined as the primary endpoint and death was defined as the secondary endpoint. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the independent risk factors for rebleeding, and a Cox regression analysis was used to analyze the predictive indicators for 5-year survival in EVB patients; the Kaplan-Meier curve was used to analyze the cumulative non-rebleeding rate. ResultsAmong the 129 patients, 87(67.4%) experienced rebleeding during follow-up. There were significant differences between the rebleeding group and the non-rebleeding group in the proportion of patients with alcoholic cirrhosis (χ2=4.896, P=0.027), portal vein diameter (t=2.203, P=0.030), LSM(Z=-2.771, P=0.006), and SSM(t=2.678, P=0.010). The patients with alcoholic cirrhosis had a significantly higher mean number of times of bleeding than those with non-alcoholic cirrhosis (all P＜0.05). The multivariate logistic regression analysis showed that alcoholic cirrhosis (odds ratio ［OR］=5.687, 95% confidence interval ［CI］: 1.230-26.129, P=0.025), LSM(OR=1.039, 95% CI: 1.010-1.070, P=0007), and SSM(OR=1.078, 95% CI: 1.028-1.129, P=0.001) were independent risk factors for rebleeding within 5 years after treatment in EVB patients. Among the 129 patients, 45 (34.9%) died. The univariate Cox regression analysis showed that there were significant differences between the death group and the survival group in age, times of bleeding, mean arterial pressure, portal vein diameter, aspartate aminotransferase, lymphocyte percentage, and presence or absence of infection at the first time of bleeding (all P＜005). Further multivariate analysis showed that 5-year survival rate was associated with portal vein diameter (OR=1.459, 95% CI: 1056-2.014, P=0.022), age (OR=1.053, 95% CI: 1.006-1.103, P=0.026), times of bleeding (OR=1.286, 95% CI: 1.040-1.591, P=0.020), and presence or absence of infection at the first time of bleeding (OR=5.239, 95% CI: 1.750-15.641, P=0.003). ConclusionAlcoholic cirrhosis, LSM, and SSM are independent risk factors for rebleeding within 5 years in EVB patients, and age, times of bleeding, portal vein diameter, and presence or absence of infection at the first time of bleeding are associated with 5-year survival.

Advances in the models for predicting the risk of liver cancer during antiviral therapy in patients with chronic hepatitis B / 临床肝胆病杂志

Hepatitis B virus infection is one of the primary causes of liver cirrhosis and liver cancer. The use of antiviral drugs significantly reduces the risk of liver cancer in patients with chronic hepatitis B (CHB), but some of the patients who receive antiviral drugs for a long time still develop liver cancer. Therefore, it is necessary to early identify and predict the risk of liver cancer in such patients. Currently, several models for predicting the risk of liver cancer during antiviral therapy in CHB patients have been developed based on the risk factors such as liver cirrhosis, age, sex, liver stiffness, virology, serological markers, alcohol consumption, and history of diabetes, including REACH-B, PAGE-B, mPAGE-B, APA-B, CAMD, AASL, and REAL-B. This article reviews the research advances in the models for predicting the risk of liver cancer during antiviral therapy in CHB patients.

Evaluation and influencing factors of the short-term prognosis of severe alcoholic hepatitis with different underlying liver diseases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of patients with severe alcoholic hepatitis (AH) with different underlying liver diseases and the influencing factors for short-term prognosis. MethodsA retrospective analysis was performed for the clinical data of 170 patients with severe AH who were admitted to Tianjin Third Central Hospital from August 2004 to August 2018, and according to the underlying liver disease, they were divided into group A (27 patients without liver cirrhosis), group B (52 patients with compensated liver cirrhosis), and group C (91 patients with decompensated liver cirrhosis). Related scores were calculated, including Maddrey’s discriminant function (MDF) score, Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score, Model for End-Stage Liver Disease (MELD) score, age-bilirubin-international normalized ratio-creatinine (ABIC) score, and Glasgow alcoholic hepatitis score (GAHS). An analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. Univariate and multivariate Cox regression analyses were used to screen out the independent influencing factors for the short-term prognosis of patients with severe AH. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rate between groups. The receiver operating characteristic (ROC) curve was used to calculate the area under the ROC curve (AUC) and 95% confidence interval (CI), sensitivity, and specificity for each predictive model, and the DeLong method was used for comparison. ResultsThe 28-day survival rates of patients in groups A, B, and C were 88.9%, 80.8%, and 51.6%, respectively, with a significant difference between the three groups (χ2=1983, P＜0.001). The AUCs (95% CIs) of MELD score, MDF score, GAHS score, ABIC score, and CLIF-SOFA score were 0.584 (0.493-0.676), 0.696 (0.605-0.786), 0.644 (0.554-0.735), 0.745 (0.662-0.827), and 0.795 (0.726-0.863), respectively, in predicting 28-day mortality rate, and there were significant differences between CLIF-SOFA score and MDF, MELD, and GAHS scores (all P＜0.05); CLIF-SOFA score had a sensitivity of 79.0% and a specificity of 67.9% at the optimal cut-off value of 850 points in predicting 28-day mortality rate. Different underlying liver diseases (hazard ratio ［HR］=2.296, 95% CI: 1.356-3887, P=0.002) and hepatic encephalopathy (HR=1.911, 95% CI: 1.059-3.449, P=0.031) at disease onset were risk factors for 28-day prognosis. ConclusionPatients with severe AH with different underlying liver diseases have different clinical features and short-term prognoses. Different underlying liver diseases and hepatic encephalopathy at disease onset are closely associated with the 28-day prognosis of patients with severe AH. CLIF-SOFA score can predict the 28-day prognosis of patients with severe AH.

Automated Breast Ultrasound: Interobserver Agreement,Diagnostic Value, and Associated Clinical Factors ofCoronal-Plane Image Features

Objective@#To evaluate the interobserver agreement, diagnostic value, and associated clinical factors of automated breastultrasound (ABUS) coronal features in differentiating breast lesions. @*Materials and Methods@#This study enrolled 457 pathologically confirmed lesions in 387 female (age, 46.4 ± 10.3 years),including 377 masses and 80 non-mass lesions (NMLs). The unique coronal features, including retraction phenomenon,hyper- or hypoechoic rim (continuous or discontinuous), skipping sign, and white wall sign, were defined and recorded. Theinterobserver agreement on image type and coronal features was evaluated. Furthermore, clinical factors, including the lesionsize, distance to the nipple or skin, palpability, and the histological grade were analyzed. @*Results@#Among the 457 lesions, 296 were malignant and 161 were benign. The overall interobserver agreement for imagetype and all coronal features was moderate to good. For masses, the retraction phenomenon was significantly associated withmalignancies (p < 0.001) and more frequently presented in small and superficial invasive carcinomas with a low histologicalgrade (p = 0.027, 0.002, and < 0.001, respectively). Furthermore, continuous hyper- or hypoechoic rims were predictive ofbenign masses (p < 0.001), whereas discontinuous rims were predictive of malignancies (p < 0.001). A hyperechoic rim wasmore commonly detected in masses more distant from the nipple (p = 0.027), and a hypoechoic rim was more frequently foundin large superficial masses (p < 0.001 for both). For NMLs, the skipping sign was a predictor of malignancies (p = 0.040). @*Conclusion@#The coronal plane of ABUS may provide useful diagnostic value for breast lesions.

A randomized controlled trial on 240-week monotherapy with entecavir or adefovir in patients with chronic hepatitis B and cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the efficacies ofentecavir and adefovir in patients with chronic hepatitis B (CHB) and cirrhosis when administered as monotherapies using a 240-week course.</p><p><b>METHODS</b>Ninety patients diagnosed with CHB and cirrhosis (compensated or decompensated) were randomly divided into two treatment groups for administration of either entecavir (0.5 mg/day, oral; n =38) or adefovir (10 mg/day, oral; n =52) for 240 weeks. All participants underwent B-ultrasound and were tested for levels of HBV-DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, creatinine, alpha-fetoprotein (AFP) and various serological markers of the hepatitis B virus at baseline and at treatment weeks 24, 48, 96, 144, 192, and 240. Instances of drug-related complications and adverse reactions were recorded. Patients who did not achieve complete virological response by treatment week 48 or who experienced virological breakthrough at any time during the study course were recorded and started on an appropriate combination therapy regimen. Statistical analyses were carried out using the t-test, chi-square test, and Cox regression modeling.</p><p><b>RESULTS</b>The dropout rate in the entecavir group was 2.6% and in the adefovir group was 13.5%. At treatment week 240, significantly more patients in the entecavir group had undetectable serum HBV-DNA (91.9% vs. adefovir group: 57.8%; x2=10.362, P=0.001), a negative conversion rate of hepatitis B e antigen (HBeAg) (46.2% vs. adefovir group: 24%; x2=5.055, P=0.025), and rate of HBeAg seroconversion (23.1% vs. adefovir group: 8%, P=0.047).The entecavir group and the adefovir group showed no significant differences upon per-protocol analysis and intention-to-treat analysis, nor in the rates of hepatocellular carcinoma development (entecavir group: 8.1% vs. adefovir group: 6.7%; x2=0.000, P=1.000) or mortality (entecavir group: 8.1% vs. adefovir group: 4.4%; x2=0.051, P=0.821). The possibility of achieving undetectable serum HBV-DNA was 2.761 times higher in the entecavir group than in the adefovir group (95.0% CI: 1.630 to 4.679). The possibility of HBeAg seroconversion was 0.192 times higher for males than for females (95.0% CI: 0.046 to 0.806).</p><p><b>CONCLUSION</b>Compared to adefovir, entecavir provides high efficiency and rapid viral suppression as a monotherapy for CHB patients when administered in a 240-week course.</p>

Assessment of the presence of esophageal varices bleeding in patients with hepatitis B virus-related cirrhosis by a noninvasive score system / 中华传染病杂志

Objective To retrospectively analyze the diagnostic value of a noninvasive score system based on transient elastography (TE),serological test and imaging examination on esophageal variceal bleeding (EVB) in patients with hepatitis B virus (HBV)-related cirrhosis.Methods Between April 2011 and December 2012,172 patients with HBV-related cirrhosis including 120 males and 52 females who visited clinic or hospitalized at the Department of Hepatology,Tianjin Third Central Hospital,were retrospectively enrolled.The mean age was (52.9 ± 10.6) years.Patients underwent upper gastrointestinal endoscopy to evaluate esophageal varices (EV) and were further categorized into three stages of mild,moderate and severe according to the morphology of EV and the risk of bleeding.Liver stiffness and spleen stiffness measurement were performed using Fibroscan.Portal vein width,splenic width and spleen thickness were measured using color Doppler ultrasound.All the patients were tested for white blood cell counts and platelet counts.With endoscopy as the gold standard,receiver operating characteristic (ROC) curves and the areas under curves (AUC) were used to assess the performance of the noninvasive score system in predicting EV by liver stiffness,spleen stiffness,portal vein width,spleen thickness and platelet counts.Student's t-test was performed to determine differences between continuous variables.Pearson's correlation was used to evaluate the association between EVB and these parameters.Results All these 172 patients underwent endoscopy.Among them,41 were EVB patients and 131 with no bleeding of EV.Among 172 EV patients,39 without EV,30 were mild EV,47 were moderate EV and 56 were severe EV.EVB was all positively correlated with liver and spleen stiffness,portal vein width,spleen thickness,splenic vein width (r=0.224,0.771,0.214,0.425 and 0.364,respectively; all P＜0.05).EVB was negatively correlated with platelet counts (r=-0.408,P=0.000).Liver stiffness,spleen stiffness,portal vein width,spleen thickness and splenic vein width in EVB patients were significantly higher than those in EV patients (P＜0.05).In contrast,platelet counts level was lower in EVB patients with difference of statistical significance (P＜0.05).AUC of non-invasive score system for EV and EVB were 0.953 and 0.882,respectively (P＜0.05).The optimal cut-off level of noninvasive score system for prediction of EV and EBV were 7 (sensitivity:96 ％,specificity:85 ％) in EV patients and 10 (sensitivity:78％,specificity:89 ％) in EVB patients.Conclusion Non-invasive score system based on liver stiffness,spleen stiffness,spleen thickness,width of splenic and portal vein and platelet counts is of clinical importance in assessing the presence of EV in patients with HBV-related cirrhosis,which is higher clinically valuable in the diagnosis for EV.

The Effects of Preemptive Antiviral Therapy on HBV DNA Negative HBV-Related Hepatocellular Carcinoma Patients Receiving Transcatheter Arterial Chemoembolization / 天津医药

Objective To investigate the effects of prophylactic antiviral therapy for HBV DNA negative HBV-relat-ed hepatocellular carcinoma (HCC) patients undergoing hepatic arterial chemoembolization (TACE). Methods Fifty-four consecutive patients with HBV-related HCC and received TACE were enrolled in this study. Thirty patients received pre-emptive antiviral drugs before TACE were defined as the treatment group. Twenty-four patients, who did not use antiviral drugs until HBV reactivation after TACE, were included in control group. The incidence of HBV reactivation, duration from HBV DNA positive point to the last time of TACE, the occurrence of abnormal alanine aminotransferase (ALT) caused by HBV reactivation, the peak of aspartate aminotransferase (AST) and the number of liver failure caused by HBV reactivation were observed after TACE in two groups. Results The incidence of HBV reactivation, the occurrence of abnormal ALT, the occurrence of abnormal ALT caused by HBV reactivation, the peak ALT and peak AST were significantly lower in treatment group than those of control group (P ＜ 0.05). No liver failure caused by HBV reactivation was found in treatment group. There were four patients with liver failure caused by HBV reactivation in control group. There was no significant difference in cumulative survival rate between two groups (P=0.071). Conclusion It is suggested that preemptive antiviral therapy can prevent the reactivation of hepatitis B virus, prevent the deterioration of liver function,and decrease the occurrence of liv-er failure caused by HBV reactivation in patients receiving TACE.

Noninvasive assessment of esophageal-gastric varices by spleen stiffness in liver cirrhosis patients / 中华传染病杂志

Objective To investigate the value of spleen stiffness measured by transient elastography (FibroScan,FS) for diagnosing esophageal-gastric varices in liver cirrhosis patients.Methods A total of 259 cirrhotic patients in Tianjin Third Central Hospital from Apr 2011 to Apr 2012,and 30 healthy controls were enrolled.All the patients and controls were evaluated for spleen and liver stiffness by FS and 201 cirrhotic patients also underwent gastroscopy for the diagnosis of esophageal-gastric varices.By using gastroscopy as the gold standard,the receiver operating characteristic (ROC) curves of three parameters including spleen stiffness,liver stiffness and platelet/thickness of spleen were delineated for different disease stage.The areas under curves (AUC) were used to evaluate the value of these parameters in the diagnosis of esophageal-gastric varices.Results The spleen and liver stiffness values in cirrhotic patients were (44.64 ± 22.27) kPa and (24.27 ±18.89) kPa,respectively,while those in healthy controls were (20.94± 14.78) kPa and (6.12±5.77) kPa,respectively,which were both lower than cirrhotic patients (P＜0.05).The stiffness values of liver and spleen both increased with higher Child-Pugh scores.And the liver stiffness values were different among groups (F=0.068,P =0.000),while the spleen stiffness values in patients with Child-Pugh A and B were different from that in patients with Child-Pugh C (P＜0.05).In patients with moderate or serious esophageal-gastric varices,the spleen and liver stiffness values were significantly higher.The ROC curve analysis showed that the AUC of spleen stiffness,liver stiffness and platelet/thickness of spleen in the patients with moderate to serious esophageal-gastric varices were 0.918,0.749 and 0.743,respectively.The corresponding optimal cut-off values were 50.7 kPa,20.1 kPa and 1.65.The AUC,sensitivity and specificity of spleen stiffness were all higher than liver stiffness and platelet/thickness of spleen.Conclusion Spleen stiffness measured by transient elastography is a valuable parameter for non-invasive diagnosis of esophageal-gastric varices in cirrhotic patients.