Regression of Liver Fibrosis in Patients on Hepatitis B Therapy Is Associated With Decreased Liver-Related Events.

BACKGROUND & AIMS: Liver fibrosis in patients with chronic hepatitis B can regress with successful antiviral therapy. However, the long-term clinical benefits of fibrosis regression have not been fully elucidated. This study investigated the association between biopsy-proven fibrosis regression by predominantly progressive, indeterminate, and predominantly regressive (P-I-R) score and liver-related events (LREs) in chronic hepatitis B patients. METHODS: Patients with on-treatment liver biopsy and significant fibrosis/cirrhosis (Ishak stage ≥3) were included in this analysis. Fibrosis regression was evaluated according to the P-I-R score of the Beijing Classification. LREs were defined as decompensations, hepatocellular carcinoma, liver transplantation, or death. The Cox proportional hazards model was used to determine associations of fibrosis regression with LREs. RESULTS: A total of 733 patients with Ishak stages 3/4 (n = 456; 62.2%) and cirrhosis (Ishak stages 5/6; n = 277; 37.8%) by on-treatment liver biopsy were enrolled. According to the P-I-R score, fibrosis regression, indeterminate, and progression were observed in 314 (42.8%), 230 (31.4%), and 189 (25.8%) patients, respectively. The 7-year cumulative incidence of LREs was 4.1%, 8.7%, and 18.1% in regression, indeterminate, and progression, respectively (log-rank, P < .001). Compared with patients with fibrosis progression, those with fibrosis regression had a lower risk of LREs (adjusted hazard ratio, 0.40; 95% CI, 0.16-0.99; P = .047), followed by the indeterminate group (adjusted hazard ratio, 0.86; 95% CI, 0.40-1.85; P = .691). Notably, this favorable association also was observed in patients with cirrhosis or low platelet counts (<150 × 109/L). CONCLUSIONS: Antiviral therapy-induced liver fibrosis regression assessed by P-I-R score is associated with reduced LREs. This shows the utility of histologic fibrosis regression assessed by on-treatment P-I-R score as a surrogate endpoint for clinical events in patients with hepatitis B virus-related fibrosis or early cirrhosis.

Machine-learning model comprising five clinical indices and liver stiffness measurement can accurately identify MASLD-related liver fibrosis.

BACKGROUND & AIMS: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B-related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD)-related fibrosis diagnosis and establish a machine-learning (ML) model to improve the diagnostic performance. METHODS: A total of 946 biopsy-proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). RESULTS: The AUROCs of aMAP versus fibrosis-4 index (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut-off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB-4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM-plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM-plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM-plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). CONCLUSIONS: The aMAP score is capable of diagnosing MASLD-related fibrosis. The LSM-plus model could accurately identify MASLD-related cirrhosis and advanced fibrosis.

Exploring the spatiotemporal pattern evolution of carbon emissions and air pollution in Chinese cities.

Based on data from 335 cities in China, this study employs the standard deviation ellipse method to portray unbalanced and differential spatiotemporal evolution patterns of environmental emissions and socioeconomic elements. A logarithmic mean Divisia index analysis and in-depth discussion are carried out to disclose the main driving factors and underlying reasons for the differences. Decoupling trends exist among carbon emissions, gross domestic product (GDP) and population in terms of their gravity center migrations. The standard deviation ellipse direction of carbon emissions gradually changed from 'northeast‒southwest' to 'northwest‒southeast', and the standard deviation ellipse areas of carbon emissions and air pollution continuously expanded over time; at the same time, that of GDP contracted. Economic growth has always been the main driver of carbon emissions and air pollution nationally, but its role has weakened. Moreover, decreases in the energy intensity and carbon and pollution intensities are the main factors contributing to emissions reductions. Differentiated spatiotemporal economic structure evolution, regional heterogeneities in the energy intensity and efficiency, and cross-region power energy transmissions are identified as the underlying reasons for the unbalanced spatiotemporal patterns of the environmental emissions and socioeconomic elements. Based on these findings, policy suggestions can be made to address the imbalances and promote carbon mitigation, air quality improvement and high-quality social-economic development at the city level.

Efficacy and safety analysis of midazolam combined with dezocine sedation and analgesia colonoscopy in patients with inflammatory bowel disease: a prospective single-center open study.

Objective: Colonoscopy plays an important role in the diagnosis, prognosis prediction, assessment of disease activity and severity, and treatment of inflammatory bowel disease (IBD)-related complications. However, some patients refuse to undergo colonoscopy due to perceived pain and other discomfort, their diagnosis and treatment are affected. Therefore, we conducted a prospective study to explore the efficacy and safety of midazolam combined with dezocine for sedation in IBD patients undergoing colonoscopy. Methods: 224 patients were divided into sedative-colonoscopy-group (SCG, n = 93), anesthesia-colonoscopy-group (ACG, n = 90) and ordinary-colonoscopy-group (OCG, n = 41). The vital signs (blood pressure, pulse, respiration and blood oxygen saturation), pain degree during colonoscopy, satisfaction and complication rates of the three groups were compared. Results: Before colonoscopy, there was no significant difference among the vital signs of the three groups. The vital signs of the ACG were significantly lower than those of the SEG and the OCG (p < 0.05), and the difference was not significant between the SCG and OCG during colonoscopy. The colonoscopy pain score in the SCG was lower than that in the OCG (0.79 ± 1.09 vs. 2.98 ± 1.27, p < 0.001). The satisfaction score of the SCG (9.26 ± 1.16) was not significantly different from that of the ACG (9.42 ± 1.41) but was higher than that of the OCG (6.63 ± 1.13) (p < 0.001). The total complication rate of the ACG was 45.56% (41/90), which was significantly higher than that of the SCG [20.43% (19/93)] and the OCG [19.51% (8/41)]. Colon perforation, abnormal blood pressure fluctuation and hypoxemia were significantly more common in the ACG than in the SCG and the OCG (p < 0.05). However, there was no significant difference in the incidence of complications between the SCG and OCG. Conclusion: Compared with ordinary-colonoscopy, colonoscopy performed under midazolam and dezocine sedation is more comfortable for patients, thereby increasing satisfaction and compliance. Colonoscopy that is performed under midazolam and dezocine is similar to colonoscopy that is anesthesia with propofol in terms of comfort, satisfaction and compliance and similar to ordinary-colonoscopy in terms of safety. Considering the shortage of anesthesiologists, the application of midazolam combined with dezocine for digestive endoscopy is worthy of clinical promotion.

The In Situ Preparation of Ni-Zn Ferrite Intercalated Expanded Graphite via Thermal Treatment for Improved Radar Attenuation Property.

The composites of expanded graphite (EG) and magnetic particles have good electromagnetic wave attenuation properties in the centimeter band, which is valuable in the field of radar wave interference. In this paper, a novel preparation method of Ni-Zn ferrite intercalated EG (NZF/EG) is provided in order to promote the insertion of Ni-Zn ferrite particles (NZF) into the interlayers of EG. The NZF/EG composite is in situ prepared via thermal treatment of Ni-Zn ferrite precursor intercalated graphite (NZFP/GICs) at 900 °C, where NZFP/GICs is obtained through chemical coprecipitation. The morphology and phase characterization demonstrate the successful cation intercalation and NZF generation in the interlayers of EG. Furthermore, the molecular dynamics simulation shows that the magnetic particles in the EG layers tend to disperse on the EG layers rather than aggregate into larger clusters under the synergy of van der Waals forces, repulsive force, and dragging force. The radar wave attenuation mechanism and performance of NZF/EG with different NZF ratios are analyzed and discussed in the range of 2-18 GHz. The NZF/EG with the NZF ratio at 0.5 shows the best radar wave attenuation ability due to the fact that the dielectric property of the graphite layers is well retained while the area of the heterogeneous interface is increased. Therefore, the as-prepared NZF/EG composites have potential application value in attenuating radar centimeter waves.

An Innovative model of magnetically intercalated expanded graphite for calculating radar attenuation performance at 2-18 GHz.

With the emergence of various filtering technologies, the radar jamming efficiency of the technology based on radar cross section is ever lower, therefore cannot meet military requirements. In this context, the jamming technology based on attenuation mechanism has been developed and plays an increasingly important role in disturbing radar detecting. Magnetically expanded graphite (MEG) has excellent attenuation efficiency because it can cause dielectric loss as well as magnetic loss. Moreover, MEG features good impedance matching, which makes more incidence of electromagnetic waves into the material; and its multi-layer structure is conducive for electromagnetic wave reflection and absorption. In this work, the structure model of MEG was established by analyzing the layered structure of expanded graphite (EG) and the dispersion of intercalated magnetic particles. The electromagnetic parameters of thus-modeled MEG were calculated based on the equivalent medium theory; and effects of EG size, magnetic particle type and volume fraction on the attenuation performance were studied by the variational method. It is indicated that MEG with 500-µm diameter has the best attenuation effect and the highest increment of absorption cross section appears at 50% volume fraction of the magnetic particles at 2 GHz. The imaginary part of complex permeability of the magnetic material has the most significant influence on the attenuation effect of MEG. This study provides guidance for the design and application of MEG materials in disturbing radar detecting field.

aMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients.

BACKGROUND & AIMS: The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. METHODS: A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. RESULTS: In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). CONCLUSIONS: The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.

Graphical education and appropriate time before elective colonoscopy make better bowel preparation.

Background: Inadequate bowel preparation leads to lower polyp detection rates, longer procedure times and lower cecal intubation rates. However, there is no consensus about high-quality bowel preparation, so our study evaluated graphical education and appropriate time before elective colonoscopy. Patients and Methods: We performed a secondary analysis of a national colorectal cancer screening programme of 738 patients. The patients were divided into a group given a graphical information manual (n = 242) or a word-only one (n = 496). They were also divided into groups according to the interval between bowel preparation and colonoscopy: 6-8 h (Group 1, n = 106), 9-12 h (Group 2, n = 228) and 13-17 h (Group 3, n = 402). All patients were scored according to the Boston Bowel Preparation Scale (BBPS) during the examination. Results: The bowel preparation of the graphical group was significantly better than the text group (P < 0.001). After adjustment, the bowel preparation score of Group 1 and Group 2 were both significantly higher than that of Group 3 (P = 0.012 and P = 0.032). Maximum BBPS was 6.31 when the interval time was 6.52 h (95% confidence interval: 5.95-6.66), and when the interval was <10 h, the BBPS was ≥6. Conclusion: High-quality bowel preparation was linked to graphical education and appropriate time before colonoscopy. We suggest that the interval between taking the first laxative and colonoscopy should be <10 h, preferably 6.5 h. Prospective multicentre research is needed to give more evidence of high-quality bowel preparation methods.

Baveno VII algorithm outperformed other models in ruling out high-risk varices in individuals with HBV-related cirrhosis.

BACKGROUND & AIMS: The Baveno VII consensus recommends that spleen stiffness measurement (SSM) ≤40 kPa is safe for ruling out high-risk varices (HRVs) and avoiding endoscopic screening in patients who do not meet the Baveno VI criteria. This study aimed to validate the performance of the Baveno VII algorithm in individuals with HBV-related cirrhosis. METHODS: Consecutive individuals with HBV-related cirrhosis who underwent liver stiffness measurement (LSM) and SSM - using a 50 Hz shear wave frequency, spleen diameter measurement, and esophagogastroduodenoscopy (EGD) were prospectively enrolled from June 2020. A 100 Hz probe has been adopted for additional SSM assessment since July 2021. RESULTS: From June 2020 to January 2022, 996 patients were screened and 504 were enrolled for analysis. Among the 504 patients in whom SSM was assessed using a 50 Hz probe, the Baveno VII algorithm avoided more EGDs (56.7% vs. 39.1%, p <0.001) than Baveno VI criteria, with a comparable missed HRV rate (3.8% vs. 2.5%). Missed HRV rates were >5% for all other measures: 11.3% for LSM-longitudinal spleen diameter to platelet ratio score, 20.0% for platelet count/longitudinal spleen diameter ratio, and 8.8% for Rete Sicilia Selezione Terapia-hepatitis. SSM@100 Hz was assessed in 232 patients, and the Baveno VII algorithm with SSM@100 Hz spared more EGDs (75.4% vs. 59.5%, p <0.001) than that with SSM@50 Hz, both with a missed HRV rate of 3.0% (1/33). CONCLUSIONS: We validated the Baveno VII algorithm, demonstrating the excellent performance of SSM@50 Hz and SSM@100 Hz in ruling out HRV in individuals with HBV-related cirrhosis. Furthermore, the Baveno VII algorithm with SSM@100 Hz could safely rule out more EGDs than that with SSM@50 Hz. CLINICAL TRIAL NUMBER: NCT04890730. IMPACT AND IMPLICATIONS: The Baveno VII guideline proposed that for patients who do not meet the Baveno VI criteria, SSM ≤40 kPa could avoid further unnecessary endoscopic screening. The current study validated the Baveno VII algorithm using 50 Hz and 100 Hz probes, which both exhibited excellent performance in ruling out HRVs in individuals with HBV-related cirrhosis. Compared with the Baveno VII algorithm with SSM@50 Hz, SSM@100 Hz had a better capability to safely rule out unnecessary EGDs. Baveno VII algorithm will be a practical tool to triage individuals with cirrhosis in future clinical practice.

Efficacy and safety of midazolam combined with dezocine for sedation and analgesia in digestive endoscopy: A prospective open single-center study.

Objective: Digestive endoscopy is an important means of diagnosing and treating gastrointestinal diseases and a tool for screening and monitoring early gastrointestinal tumors. Digestive endoscopy can be performed using midazolam combined with dezocine for sedation and analgesia. This study explored the efficacy and safety of midazolam combined with dezocine. Methods: A total of 135 patients undergoing digestive endoscopy in the Department of Gastrointestinal Endoscopy of the Sixth Affiliated Hospital, Sun Yat-sen University, from June 2021 to September 2021, were enrolled and non-blindly and non-randomly divided into a sedation-endoscopy-group (SEG, n = 45), anesthesia-endoscopy-group (AEG, n = 44), and ordinary-endoscopy-group (OEG, n = 46). Vital signs, levels of sedation and analgesia, the degree of pain during colonoscopy, satisfaction, and the incidence of complications were compared among the three groups. Results: There were no statistically significant differences in vital signs (blood pressure, pulse, respiration, and blood oxygen saturation) among the three groups before endoscopy (p > 0.05). The AEG reported no pain during colonoscopy, and the pain score during colonoscopy for the SEG was lower than that for the OEG (1.11 ± 1.21 vs. 3.00 ± 1.16, p < 0.001). The scores for satisfaction were 8.84 ± 1.30 points in the SEG, 8.95 ± 1.10 points in the AEG, and 6.37 ± 0.90 points in the OEG; the differences were statistically significant (p < 0.001). The total incidence of complications in the AEG was 38.64% (17/44), which was significantly higher than that in the SEG [13.33% (6/45)] and OEG [13.04% (6/46)] (p < 0.001). In the SEG, the overall incidence of complications in women was significantly higher than that in men (p = 0.027). Conclusion: Digestive endoscopy using midazolam combined with dezocine for sedation makes patients more comfortable, more satisfied and more compliant than the ordinary endoscopy. Additionally, it is comparable to endoscopy under general anesthesia with propofol with regard to comfort, satisfaction, and patient compliance and comparable to the ordinary endoscopy with regard to safety. Considering the shortage of anesthesiologists, the application of midazolam combined with dezocine in digestive endoscopy is worthy of clinical popularization. This study has been registered in the Hospital Ethics Committee of the Sun Yat-sen University Sixth Affiliated Hospital (Ethical Number: 2021ZSLYEC-182).

Real-Time Artificial Intelligence-Based Histologic Classifications of Colorectal Polyps Using Narrow-Band Imaging.

Background and Aims: With the development of artificial intelligence (AI), we have become capable of applying real-time computer-aided detection (CAD) in clinical practice. Our aim is to develop an AI-based CAD-N and optimize its diagnostic performance with narrow-band imaging (NBI) images. Methods: We developed the CAD-N model with ResNeSt using NBI images for real-time assessment of the histopathology of colorectal polyps (type 1, hyperplastic or inflammatory polyps; type 2, adenomatous polyps, intramucosal cancer, or superficial submucosal invasive cancer; type 3, deep submucosal invasive cancer; and type 4, normal mucosa). We also collected 116 consecutive polyp videos to validate the accuracy of the CAD-N. Results: A total of 10,573 images (7,032 images from 650 polyps and 3,541 normal mucous membrane images) from 478 patients were finally chosen for analysis. The sensitivity, specificity, PPV, NPV, and accuracy for each type of the CAD-N in the test set were 89.86%, 97.88%, 93.13%, 96.79%, and 95.93% for type 1; 93.91%, 95.49%, 91.80%, 96.69%, and 94.94% for type 2; 90.21%, 99.29%, 90.21%, 99.29%, and 98.68% for type 3; and 94.86%, 97.28%, 94.73%, 97.35%, and 96.45% for type 4, respectively. The overall accuracy was 93%. We also built models for polyps ≤5 mm, and the sensitivity, specificity, PPV, NPV, and accuracy for them were 96.81%, 94.08%, 95%, 95.97%, and 95.59%, respectively. Video validation results showed that the sensitivity, specificity, and accuracy of the CAD-N were 84.62%, 86.27%, and 85.34%, respectively. Conclusions: We have developed real-time AI-based histologic classifications of colorectal polyps using NBI images with good accuracy, which may help in clinical management and documentation of optical histology results.

Ultrasonic spleen thickness-based indexes surpass Baveno VI criteria in high-risk gastroesophageal varices detection.

AIMS: To evaluate the efficiency of ultrasonic spleen thickness (UST), routine variables and (expanded) Baveno VI criteria for high-risk gastroesophageal varices (HRGOV) detection in cirrhotic patients. METHODS: In total, 305 cirrhotic patients were retrospectively enrolled in the deriving cohort and 328 cirrhotic patients with hepatitis B sustained viral response were prospectively enrolled in the validation cohort. HRGOV was defined as medium and severe gastroesophageal varices (GOV), mild GOV with red signs or Child-Pugh C. The cut-offs for HRGOV were determined by likelihood ratio indicating strong evidences. Algorithms of Spleen thickness-Age-Liver stiffness measurement (LSM, by Fibroscan®)-Albumin (SALA) and Spleen thickness-Platelet-Albumin (SPA) were derived by multivariate analyses. RESULTS: The area under receiver operating characteristics curve of SALA, SPA, UST, platelet, and LSM were 0.849, 0.835, 0.808, 0.746, and 0.655 in the deriving cohort, and improved to 0.901, 0.904, 0.858, 0.876, and 0.811 in the validation cohort, respectively. While SALA, SPA, UST, platelet, Baveno VI criteria (BVI), and expanded BVI spared 46.6%, 38.0%, 29.2%, 21.0%, 12.1%, and 23.6% esophagogastroduodenoscopy in the deriving cohort, these numbers were improved to 68.1%, 66.8%, 27.1%, 37.8%, 36.0%, and 61.0% in the validating cohort, respectively; however, the negative likelihood ratio of expanded BVI was up to 0.16. SPA spared less esophagogastroduodenoscopy than SALA, which can be supplemented by stepwise applying UST and SPA. Sequentially combining UST and SALA, BVI and SALA exempted additional 10-5% endoscopies. CONCLUSIONS: SPA, without LSM, improves HRGOV detection comparing with BVI. UST based algorithms combination can achieve the best efficiency especially in sustained virus response hepatitis B.

Association of Serum Hepatitis B Virus RNA With Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Under Nucleos(t)ide Analogues Therapy.

BACKGROUND: Whether serum hepatitis B virus (HBV) RNA associates with hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients has not been fully elucidated. METHODS: We enrolled 2974 patients receiving nucleos(t)ide analogues (NAs) from a prospective, observational CHB cohort to investigate the effect of serum HBV RNA, measured at study entry (baseline), on HCC development, using Cox regression analyses. RESULTS: During median follow-up of 4.4 years, 90 patients developed HCC. Patients with detectable baseline HBV RNA (n = 2072) exhibited significantly higher HCC risk than those with undetectable level (5-year HCC incidence estimated by Kaplan-Meier method: 4.1% versus 1.8%, P = .009; adjusted hazard ratio [aHR] = 2.21, P = .005). HBV RNA levels of 609-99 999 and ≥100 000 copies/mL were associated with incrementally increasing HCC risk (aHR = 2.15 and 3.05, respectively; P for trend = .003), compared to undetectable level (<609 copies/mL). Moreover, patients with single-detectable either HBV DNA or RNA and double-detectable DNA and RNA had 1.57- and 4.02-fold higher HCC risk, respectively, than those with double-undetectable DNA and RNA (P for trend = .001). CONCLUSIONS: High-level HBV RNA is associated with increased HCC risk in NAs-treated patients. Achieving undetectable HBV RNA may contribute to better clinical outcomes, indicating it could be a valuable endpoint of anti-HBV treatment.

Health-related quality of life improves after entecavir treatment in patients with compensated HBV cirrhosis.

BACKGROUND AND AIM: Antiviral therapy is effective in decreasing disease progression in HBV cirrhosis. However, the long-term effect of antiviral therapy on health-related quality of life (HRQoL) in patients with compensated HBV cirrhosis is unknown. METHODS: The patients with compensated HBV cirrhosis enrolled in a randomized controlled trial of entecavir-based therapy were recruited in the present study, if they had HRQoL score at 5-year follow-up or who developed liver-related events (LRE) during follow-up were included. HRQoL was measured with 36-Item Short-Form Health Survey (SF-36) and EuroQol-5D (EQ-5D) at baseline and yearly during follow-up. LRE was defined as the development of decompensation, HCC, or death. RESULTS: A total of 161 patients were included in the present study, with a median age of 48.0 (41.0, 53.0) years, 77.6% being male and 37.2% being HBeAg-positive. During 5 years, 45 patients developed LRE. All eight dimensions of SF-36 were significantly improved after 5 years of antiviral therapy (all p < 0.001), with all dimensions improved more than five points except for physical functioning. Proportion of patients reporting no problems in all five dimensions in EQ-5D increased from 57.8 to 72.0%; visual analogue scale (VAS) and utility index (UI) increased significantly (VAS 79.8 ± 16.4 to 84.4 ± 13.2, UI 0.91 ± 0.13 to 0.95 ± 0.10, both p < 0.001). HRQoL improved or kept stable in the majority of patients who had LRE during follow-up, even stratified by Baveno VI criteria for clinically significant portal hypertension. CONCLUSION: After 5 years of ETV treatment, HRQoL significantly improved in patients with compensated HBV cirrhosis. (NCT01943617, NCT02849132).

Energetic and magnetic directional aggregation properties of KPA@Fe3O4composite particles prepared via a microcrystalline co-precipitation route.

The development of new electromagnetic interference materials has attracted much attention in the information warfare. Herein, a novel KPA@Fe3O4composite particle was synthesized via a microcrystalline co-precipitation method. X-ray diffractions, scanning electron microscopes and vibrating sample magnetometer measurements were used to characterize the products. The results indicated that the surface of the potassium picrate (KPA) crystals was covered by magneticFe3O4nanoparticles, and composite particles exhibited excellent magnetic properties. Furthermore, the thermal behavior of the composite particles was investigated by differential scanning calorimetry, which showed that the composite particles inherited the energetic property of pure KPA crystals when the mass fraction of magnetic component was 50%, or 65%. As for the composite particles with 75% magnetic component, the thermal stability of was poor. In addition, the magnetic directional aggregation performance of composite particles was analyzed by dynamic simulation, which moved toward the magnetic source. For the composite particles with 50% magnetic component, the maximum concentration was about 63 times of the initial concentration, and the peak velocity was 0.63 m s-1. With the mass fraction of magnetic component increasing to 65%, the concentration and velocity of the composite particles generally increased at the corresponding moment. As the mass fraction of magnetic component increased to 75%, the change of them was not obvious. Therefore, the composite particles withFe3O4/KPA mass ratios of 65/35 had the best comprehensive properties. The excellent energetic and magnetic directional aggregation properties can allow the composites to be used in many potential applications in the information warfare.

Prediction of liver-related events in patients with compensated HBV-induced cirrhosis receiving antiviral therapy.

BACKGROUND AND AIMS: Many models have been developed to predict liver-related events (LRE) in chronic hepatitis B, few focused on compensated HBV-induced cirrhosis. We aimed to describe the incidence of LRE and to determine independent risk predictors of LRE in compensated HBV-induced cirrhosis patients receiving antiviral therapy using routinely available parameters. METHODS: Prospective cohorts of treatment-naïve adults with compensated HBV-induced cirrhosis were enrolled. Patients were treated with entecavir (ETV) or ETV + thymosin-alpha1 (Thy-α1) or lamivudine (LAM) + adefovir (ADV). Data were collected at baseline and every 6 months. LRE was defined as development of decompensation, HCC or death. RESULTS: Totally 937 patients were included, 608 patients treated with ETV, 252 with ETV + Thy-α1, and 77 with LAM + ADV. After a median follow-up of 4.5 years, 88 patients developed LRE including 48 with HCC. The cumulative incidence of LRE at year 1, 3, and 5 was 2.1%, 7.0%, and 12.7%, respectively, and was similar for three treatment groups. All models using variables at month 6 or 12 had better fit than models using baseline values. The best model for prediction of LRE used PLT, GGT, and AFP at month 6 [AUC: 0.762 (0.678-0.814)], for hepatic decompensation-PLT, LSM and GGT at month 12 (AUC: 0.834 (0.675-0.919)), and for HCC-AFP and GGT at month 6 [AUC 0.763 (0.691-0.828)]. All models had negative predictive values of 94.0-98.8%. CONCLUSION: Models using on-treatment variables are more accurate than models using baseline variables in predicting LRE in patient with compensated HBV-induced cirrhosis receiving antiviral therapy. ClincialTrials.gov number NCT01943617, NCT01720238, NCT03366571, NCT02849132.

Glucagon Like Peptide-1 Receptor Agonists Alter Pancreatic and Hepatic Histology and Regulation of Endoplasmic Reticulum Stress in High-fat Diet Mouse Model.

BACKGROUND: Obesity is a major health problem worldwide, and non-alcoholic fatty pancreas disease (NAFPD) and non-alcoholic fatty liver disease (NAFLD) are obesity-associated complications. Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, has been approved for treatment of obesity. We aimed to evaluate the therapeutic effects of liraglutide on the complications through its regulation of endoplasmic reticulum (ER) stress. METHODS: A high-fat diet mouse model was established in C57BL/6J mice. Two groups of mice were fed a high-fat diet with 60% fat for 16 weeks and control mice were fed standard chow. A four-week 0.6 mg/kg/day liraglutide treatment was started in one high-fat diet group after 12 weeks of the high-fat diet. After sacrificing the mice, pancreatic and hepatic tissues were prepared for western blot and immunohistochemistry for ER stress proteins, including activating transcription factor 4 (ATF4), caspase 12, C/EBP homologous protein (CHOP) eukaryotic initiation factor 2 α (eIF2α), glucose regulated protein (GRP) 78 and protein kinase RNA-like endoplasmic reticulum kinase (PERK). RESULTS: Liraglutide significantly decreased body weight gained by mice consuming a high-fat diet (27.6 g vs. 34.5 g, P<0.001), and levels of all ER proteins increased significantly in both the pancreas and liver (all P<0.05). Expression of most ER stress proteins in pancreatic tissue correlated with disease scores of NAFLD (all P<0.05). However, no significant differences were found in pancreatic ATF 4 expression between mice without NAFLD, and those with early non-alcoholic steatohepatitis (NASH) and fibrotic NASH (P=0.122). CONCLUSION: Liraglutide may reduce the severity of NAFPD and NAFLD through regulating the ER stress pathway and downstream apoptosis signaling.

aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. METHODS: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). RESULTS: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%. CONCLUSIONS: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. LAY SUMMARY: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.

Alanine aminotransferase influencing performances of routine available tests detecting hepatitis B-related cirrhosis.

The performances of routine tests such as FIB-4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width-platelet ratio (RPR), γ-glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut-offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB-4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was âˆ for APRI cut-off 2 diagnosing cirrhosis in ALT < 2 upper limit of normal (ULN), 14.6 for APRI cut-off 1.5 determining significant fibrosis in ALT ≤ 5ULN and 20.6 for FIB-4 cut-off 3.2 diagnosing ≥ F3 in the total cohort, respectively. The optimal cut-offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut-offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut-offs may be a preferred alternative. In resource-limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.

Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries.

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.