Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF), characterized by an acute deterioration of liver function in the patients with chronic hepatitis B (CHB), is lack of predicting biomarkers for prognosis. Plasma is an ideal sample for biomarker discovery due to inexpensive and minimally invasive sampling and good reproducibility. In this study, immuno-depletion of high-abundance plasma proteins followed by iTRAQ-based quantitative proteomic approach was employed to analyze plasma samples from 20 healthy control people, 20 CHB patients and 20 HBV-ACLF patients, respectively. As a result, a total of 427 proteins were identified from these samples, and 42 proteins were differentially expressed in HBV-ACLF patients as compared to both CHB patients and healthy controls. According to bioinformatics analysis results, 6 proteins related to immune response (MMR), inflammatory response (OPN, HPX), blood coagulation (ATIII) and lipid metabolism (APO-CII, GP73) were selected as biomarker candidates. Further ELISA analysis confirmed the significant up-regulation of GP73, MMR, OPN and down-regulation of ATIII, HPX, APO-CII in HBV-ACLF plasma samples (p < 0.01). Moreover, receiver operating characteristic (ROC) curve analysis revealed high diagnostic value of these candidates in assessing HBV-ACLF. In conclusion, present quantitative proteomic study identified 6 novel HBV-ACLF biomarker candidates and might provide fundamental information for development of HBV-ACLF biomarker.
Background: Portal vein thrombosis (PVT) is a relatively common complication of cirrhosis. However, the effect of PVT on the prognosis might not be unequivocal. A systematic review and meta-analysis were performed to investigate the effect of PVT on the prognosis of patients with cirrhosis who have not received a liver transplant. Methods: Three databases, including PubMed, EMBASE, and Cochrane Library, were searched for studies published up to March 2020. The survival or mortality rate of patients with PVT served as the main index to evaluate the prognosis of these patients. Hepatic decompensation served as the index of disease progression. Meta-analyses were conducted using Review Manager software 5.2. Results: Sixteen clinical studies were included and analyzed. PVT was associated with an increased risk of mortality in patients with decompensated cirrhosis. According to the meta-analysis, patients with cirrhosis presenting with PVT had a lower 1-year survival rate than patients without PVT (odds ratio (OR), 0.32; 95% confidence interval (CI), 0.14–0.75; P = .008). The cumulative survival rates were similar between the 2 groups at 3 years (OR, 1.04; 95% CI, 1.00–1.08; P = .06), 5 years (OR, 1.33; 95% CI, 0.71–2.48; P = .38) and 10 years (OR, 1.24; 95% CI, 0.79–1.93; P = .35). PVT was associated with a higher mortality rate in patients with Child-Pugh class B and C disease. A significantly increased risk of death was observed in patients with complete PVT. Patients with both PVT and cirrhosis had a higher rate of decompensation than patients without PVT. Conclusions: The presence of PVT might exert a slight effect on the overall prognosis of patients with cirrhosis. PVT might mainly affect the short-term prognosis by increasing hepatic decompensation events in patients with cirrhosis. However, PVT might not influence the long-term prognosis of patients with cirrhosis.
Hepatic fibrosis is overly exuberant wound healing in which excessive connective tissue builds up in the liver. The treatment of hepatic fibrosis is still difficult and remains a challenge to the clinician. In recent years, the TGF-β signaling pathway regulator tyrosine kinase Abl has been raised as a new and promising target of hepatic fibrosis therapy. Here, considering that there are numerous drugs and drug-like compounds being approved or under clinical development and experimental investigation, it is expected that some of the existing drugs can be re-exploited as new agents to target Abl with the capability of suppressing hepatic fibrosis. To achieve this, a synthetic protocol that integrated molecular docking, affinity scoring dynamics simulation and free energy analysis was described to systematically profile the inhibitory potency of various drugs and drug-like compounds against the kinase domain of Abl. Consequently, 4 out of 13 tested drug candidates were successfully identified to have high-Abl inhibitory activities. By visually examining the dynamics behavior, structural basis and energetic property of few typical Abl-drug complex cases, a significantly different pattern of non-bonded interactions between the binding of active and inactive drug ligands to Abl receptor was revealed; the former is defined by strong, specific chemical forces, while the latter can only form non-specific hydrophobic contacts with slight atomic collisions.
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