Non-invasive biomarkers for liver inflammation in non-alcoholic fatty liver disease: present andfuture

Inflammation is the key driver of liver fibrosis progression in non-alcoholic fatty liver disease (NAFLD). Unfortunately, it is often challenging to assess inflammation in NAFLD due to its dynamic nature and poor correlation with liver biochemical markers. Liver histology keeps its role as the standard tool, yet it is well-known for substantial sampling, intraobserver, and interobserver variability. Serum proinflammatory cytokines and apoptotic markers, namely cytokeratin-18, are well-studied with reasonable accuracy, whereas serum metabolomics and lipidomics have been adopted in some commercially available diagnostic models. Ultrasound and computed tomography imaging techniques are attractive due to their wide availability; yet their accuracies may not be comparable with magnetic resonance imaging-based tools. Machine learning and deep learning models, be they supervised or unsupervised learning, are promising tools to identify various subtypes of NAFLD, including those with dominating liver inflammation, contributing to sustainable care pathways for NAFLD.

U-shaped relationship between urea level and hepatic decompensation in chronic liver diseases

Background/Aims@#We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. @*Methods@#The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. @*Results@#Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). @*Conclusions@#We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

Non-invasive tests of non-alcoholic fatty liver disease / 中华医学杂志(英文版)

For the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.

Inhibitory effect of iNOS inhibitor on the apoptosis of rat abdominal aortic aneurysm smooth muscle cells / 中国现代普通外科进展

Objective:To explore the establishment of an animal model of abdominal aortic aneurysm(AAA),and elaborate the role of iNOS inhibitor in the smooth muscle apoptosis of abdominal aortio aneurysm in rats,to find a new theoretical basis for the clinical treatment of small drugs AAA.Methods:SD rats underwent intra-aortic elastase (25U/mL) perfusion to induce AAAs,the positive control group (30) and experiment group (30) use elastase perfusion while the negative control group(30) gives the saline perfusion.After operation the positive and negative control groups were treated with intraperitoneal injections of saline,experimental group injects the iNOS inhibitor Aminoguanidi hydrochloride;Postoperative second,7,and 14 days,The NO content in the serum and specimen of abdominal aortic aneurysm was detected by iNOS Immuno histochemistry and Terminal Transferase-mediated dUTP Nick End-Labeling (TUNEL) to evaluate distribution of smooth muscle apoptosis in abdominal aortic aneurysm.Results:Underwent intra-aortic elastase perfusion to induce AAAs have a high-success-rate.Rate of AAA formation in positive control group 10％,60％,80％,respectively.The treatment group was 0％,10％,20％,and the negative control group was not formed.The treatment group and the negative control group were lower than the positive control group,there were significant differences.In the positive control group,NO content increased gradually from second days,7 days to reach the peak and maintained at a higher level,the treatment group serum NO content was lower than the other two groups,there was significant difference (P＜0.05),iNOS was strong expression in the positive control group,in the other two groups of mild expression.TUNEL results showed that a lot of apoptotic cells in the positive control group,after 7 days showed a significant increase trend,to observe the end (2 weeks) gradually increased.,The positive control group was higher than the negative control group and the negative control group,there was significant difference(P＜0.05).Conclusion:iNOS inhibitors significantly decreased the content of NO in serum,reduced the apoptosis of smooth muscle cells,and inhibited the formation of abdominal aortic aneurysm.To provide theoretical basis for clinical application of iNOS inhibitors in the treatment and control of AAA.