Non-invasive Assessment of Liver Fibrosis Regression in Patients with Chronic Hepatitis B: A Retrospective Cohort Study.

INTRODUCTION: Non-invasive tests (NITs) have been alternative methods of liver biopsy for the cross-sectional assessment of liver fibrosis in patients with chronic hepatitis B (CHB). However, there are limited data on the longitudinal association between NITs and histological changes of liver fibrosis. This study aimed to evaluate whether NITs can be used to assess liver fibrosis regression (LFR) during anti-HBV treatment. METHODS: This retrospective study included 337 patients with CHB who underwent contemporaneous NITs, such as liver stiffness measurement (LSM), the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and the γ-glutamyl transpeptidase to platelet ratio (GPR), and liver biopsy at baseline and followed by a repeated liver biopsy and NITs assessment. The LFR was defined as fibrosis regression by at least one stage assessed by METAVIR scoring system. RESULTS: The median interval between the two paired liver biopsy assessment was 31 months (IQR 24-45). At the first liver biopsy, the fibrosis stage was F2 in 159 (47.2%), F3 in 68 (20.2%), and F4 in 110 (32.6%) patients. At the second liver biopsy, the number of patients with fibrosis stages F0-1, F2, F3, and F4 was 102 (30.3%), 106 (31.5%), 63 (18.7%), and 66 (19.6%), respectively. At follow-up liver biopsy, 169 patients (50.1%) had LFR, 128 patients (38.0%) had no change in fibrosis stage, and 40 patients (11.9%) had liver fibrosis progression on histology. A decrease in liver stiffness measurement (LSM) by 25% is the optimal cutoff for predicting LFR. Patients with a 25% or larger decrease in LSM value had more LFR than those with a less than 25% decrease in LSM value (78.1% vs 22.9%, p < 0.001). CONCLUSION: LSM might be used to monitor regression of liver fibrosis during antiviral treatment using nucleos(t)ide analogues (NUCs) in patients with CHB.

The mechanism of Renshen-Fuzi herb pair for treating heart failure-Integrating a cardiovascular pharmacological assessment with serum metabolomics.

Background: Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF. Methods: Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF. Results: RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the "Metabolite-Target-Component" interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically. Conclusion: The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF.

The exposure levels and health risk assessment of antibiotics in urine and its association with platelet mitochondrial DNA methylation in adults from Tianjin, China: A preliminary study.

There has been extensive research on antibiotics exposure in adults by biomonitoring, but the biological mechanisms and potential risks to human health remain limited. In this study, 102 adults aged 26-44 years in Tianjin were studied and 23 common antibiotics in urine were analyzed by Liquid chromatography-mass spectrometry (LC-MS). All antibiotics were detected in urine, with an overall detection frequency of 40.4% (the detection frequencies of phenothiazines, quinolones, sulfonamides, tetracyclines, and chloramphenicol were 77%, 54%, 24%, 28%, and 49%, respectively.). Ofloxacin and enrofloxacin had the highest detection frequencies (85% and 81%), with median concentrations of 0.26 (IQR: 0.05-1.36) and 0.09 (IQR: 0.03-0.14) ng/mL, respectively. Based on health risk assessment, the predicted estimated daily exposures (EDEs) ranged from 0 µg/kg/day to 13.98 µg/kg/day. The hazard quotient (HQ) values of all the antibiotics except ofloxacin and ciprofloxacin were bellow one, which are considered safe. For all blood samples, the mitochondrial DNA (mtDNA) methylation levels in the MT-ATP6 (ranging between 3.86% and 34.18%) were slightly higher than MT-ATP8 and MT-ND5 (ranging between 0.57% and 9.32%, 1.08% and 19.62%, respectively). Furthermore, mtDNA methylation from MT-ATP6, MT-ATP8 and MT-ND5 were measured by bisulfite-PCR pyrosequencing. The association (P < 0.05) was found between mtDNA methylation level (MT-ATP8 and MT-ND5) and individual antibiotics including chlorpromazine, ciprofloxacin, enrofloxacin, norfloxacin, pefloxacin, sulfaquinoxaline, sulfachloropyridazine, chloramphenicol, and thiamphenicol, indicating that persistent exposure to low-dose multiple antibiotics may affect the mtDNA methylation level and in turn pose health risks.

Stated acceptance and behavioral responses of drivers towards innovative connected vehicle applications.

This research is aimed at investigating drivers' attitudes towards connected vehicle technology in general and two connected vehicle applications in particular-Lane Speed Monitoring and High Speed Differential Warning-which have been demonstrated via simulation to be effective in enhancing traffic mobility and safety, respectively. An online survey was sent to customers of an automobile manufacturer in the United States. Out of the 1453 survey responses that were received, 650 complete and valid responses were used to analyze the respondents' stated acceptance of and expected behavioral responses to the two connected vehicle applications under a variety of scenarios. Statistical analyses were conducted to examine the influence of demographic and socioeconomic factors. The results reveal that the respondents express high willingness to use connected vehicle technology and the two applications under various circumstances, and the willingness is strongly associated with age, gender, education level, and income. Higher levels of acceptance are observed in older, male, higher-educated, or higher-income respondents, while the patterns of conditional acceptance and expected behavioral responses vary with specific scenarios. These results provide useful information for application developers, traffic operators, and policy makers to steer connected vehicle technology development and deployment in the direction that will benefit both the users and the society.

Evaluation of eLIFT for Non-invasive Assessment of Liver fibrosis and Cirrhosis in Patients with Chronic Hepatitis B Virus Infection.

Recently, the easy Liver Fibrosis Test (eLIFT), a sum of points attributed to age, gender, gamma-glutamyl transpeptidase, aspartate transaminase, platelets, and prothrombin time, was developed for diagnosing advanced fibrosis and cirrhosis in chronic liver disease. We aimed to evaluate the performance of eLIFT to predict liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). Histologic and laboratory data of 747 CHB patients were analyzed. The performance of eLIFT for diagnosing liver fibrosis and cirrhosis was compared with that of aspartate transaminase to platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4). To predict advanced fibrosis, the AUROC of eLIFT was comparable with that of APRI (0.66 vs 0.71, p = 0.095) and FIB-4 (0.66 vs 0.67, p = 0.612). To predict severe fibrosis, the AUROC of eLIFT was lower than that of APRI (0.65 vs 0.83, p < 0.001) and FIB-4 (0.65 vs 0.82, p < 0.001). To predict cirrhosis, the AUROC of eLIFT was also lower than that of APRI (0.64 vs 0.85, p = 0.001) and FIB-4 (0.64 vs 0.76, p = 0.033). The eLIFT is not a good non-invasive test for the diagnosis of liver fibrosis and cirrhosis in CHB patients.

The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty liver disease.

BACKGROUND/AIM: The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a novel serum model, which was reported more accurate than aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) for diagnosing significant fibrosis and cirrhosis in HBV mono-infection in West Africa. We aimed to evaluate the diagnostic performance of GPR for liver fibrosis in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD). RESULTS: Of 131 patients, 41 (31.3%), 20 (15.3%), and 10 (7.6%) were classified as having significant fibrosis, severe fibrosis and cirrhosis, respectively. To predict significant fibrosis, the AUROC of GPR was higher than that of APRI (0.86 vs 0.75, p = 0.001) and FIB-4 (0.86 vs 0.66, p < 0.001). To predict severe fibrosis, the AUROC of GPR was also higher than that of APRI (0.89 vs 0.77, p = 0.002) and FIB-4 (0.89 vs 0.72, p = 0.001). To predict cirrhosis, no difference was found between the AUROC of GPR and that of APRI (0.92 vs 0.86, p = 0.104). MATERIALS AND METHODS: 131 patients with CHB-NAFLD were included, and the diagnostic performances of GPR, APRI and FIB-4 were compared by receiver operating characteristic (ROC) curves and the area under ROC curves (AUROCs). CONCLUSIONS: The GPR could be used as a non-invasive marker to predict liver fibrosis and cirrhosis in CHB-NAFLD individuals.

Evaluation of APRI and FIB-4 for noninvasive assessment of significant fibrosis and cirrhosis in HBeAg-negative CHB patients with ALT ≤ 2 ULN: A retrospective cohort study.

To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN).Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy.In this study, the areas under the receiver operating characteristic curves (AUROCs) of APRI were lower than that of FIB-4 (0.62 vs 0.69; P = 0.019) for diagnosing significant fibrosis; however APRI and FIB-4 were comparable for diagnosing cirrhosis (0.77 vs 0.81; P = 0.374). When the cut-off proposed by WHO HBV guideline for APRI (>2.0) was used, no cirrhotic patients were correctly predicted. For FIB-4, the WHO proposed cut-off of 3.25 correctly identified significant fibrosis 83% of the time; but for APRI, the WHO proposed cut-off of 1.5 identified significant fibrosis 56%. In ruling out significant fibrosis, the WHO proposed APRI cut-off of 0.5 had a predictive value of 39%, and the FIB-4 cut-off of 1.45 correctly identified lack of significant fibrosis in 47% of the patients. In this study, based on ROC analysis, the optimal cut-offs were 0.46 and 0.65 for APRI, and 1.05 and 1.29 for FIB-4, for diagnosing significant fibrosis and cirrhosis, respectively. When the new cut-off of APRI (>0.65) was used, 82% of the cirrhotic patients were correctly predicted. In ruling out significant fibrosis, the new APRI cut-off (<0.46) had a predictive value of 80%, and new FIB-4 cut-off (<1.05) correctly identified lack of significant fibrosis in 84% of the patients.The WHO guidelines proposed cut-offs might be higher for HBeAg-negative CHB patients with ALT ≤2 ULN, and might underestimate the proportion of significant fibrosis and cirrhosis. A new set of cut-offs should be used to predict significant fibrosis and cirrhosis in this specific population.

A survey of the availability, prices and affordability of essential medicines in Jiangsu Province, China.

BACKGROUND: Field surveys conducted in China before the implementation of the essential medicine policy showed that Chinese individuals faced less access to essential medicines. This paper aims to evaluate the availability, prices and affordability of essential medicines in Jiangsu Province, China after the implementation of the policy in 2009. METHODS: A cross-sectional survey was conducted in Jiangsu in 2013 using the World Health Organization/Health Action International (WHO/HAI) methodology. Data on the availability and prices of 50 essential medicines were collected from the public and private healthcare sectors. RESULTS: The mean availabilities of innovator brands and lowest priced generics (LPGs) were 11.5% and 100% in primary healthcare facilities, 36.8% and 32.6% in the secondary and tertiary sectors, and 18.7% and 42.9% in the private sector, respectively. The median price ratios (MPRs) were 1.26 to 2.05 for generics and 3.76 to 27.22 for innovator brands. Treating ten common diseases with LPGs was generally affordable, whereas treatment with IBs was less affordable. CONCLUSIONS: The high availability of LPGs at primary healthcare facilities reflects the success of the essential medicine policy, while the low availability in secondary and tertiary levels and in private pharmacies reflects a failure to implement the policy in these levels. The health policy should be fully developed and enforced at the secondary and tertiary levels and in the private sector to ensure equitable access to health services.