Prediction of serum M30 and M65 levels for the short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure during artificial liver support system therapy / 中华传染病杂志

Objective@#To analyze the dynamic changes of serum M30 and M65 levels in patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) during artificial liver support system(ALSS) therapy, and to explore their predictive efficiency and clinical values for short-term prognosis of HBV-ACLF.@*Methods@#Seventy-six patients with HBV-ACLF who underwent ALSS therapy for the first time from May 2016 to May 2019 in the First Hospital of Jiaxing were selected.The patients were divided into improvement group (38 cases) and non-recovered group (38 cases)according to their prognosis, and 38 healthy persons were selected as control group during the same period.The serum levels of M30 and M65 were detected by enzyme-linked immunosorbent assay(ELISA). The predictive values of M30 and M65 levels for short-term prognosis in patients receiving ALSS were calculated by receiver operating characteristic analysis curve (ROC). M30 and M65 levels before and after ALSS were compared by two-way repeated measures analysis of variance.@*Results@#The levels of M30 and M65 in the improvement group, non-recovered group and control group were significantly different before the first ALSS therapy (F=109.36 and 90.42, respectively, both P<0.01). The levels of M30 and M65 were not significantly different between improvement group and non-recovered group before treatment (t=0.836 and 0.286, respectively, both P>0.05). However, after twice ALSS therapy, the levels of M30 and M65 in non-recovered group were significantly higher than those in improvement group (t=30.699 and 64.777, respectively, both P<0.01). Moreover, after the second ALSS therapy, the levels of M30 and M65 were both significantly lower compared to those after the first-time therapy in the improvement group (t=3.350 and 5.932, respectively, both P<0.01). The areas under curve (AUC) of M30, M65 and the combination of M30 and M65 for prognosis prediction were 0.796, 0.844 and 0.906, respectively. The AUC of combination of M30 and M65 was significantly higher than M30 or M65 alone (Z=2.163 and 2.141, respectively, P=0.031 and 0.032, respectively). The cut-off values of M30 and M65 were 591.91 and 924.50 U/L, respectively. The sensitivity and specificity of combined M30 and M65 were 94.7% and 82.5%, respectively.@*Conclusions@#Serum M30 and M65 levels can predict the short-term prognosis of HBV-ACLF patients after ALSS therapy.The combination of M30 and M65 is of better diagnostic value.

Prediction of serum M30 and M65 levels for the short-term prognosis of patients with hepatith B virus related acute-on-chronic liver failure during artificial liver support system therapy / 中华传染病杂志

The levels of M30 and M65 in the improvement group,non-recovered group and control group were significantly different before the first ALSS therapy(F=109.36 and 90.42,respectively,both P＜0.01).The levels of M30 and M65 were not significantly different between improvement group and non-recovered group before treatment(t=0.836 and 0.286,respectively,both P＞0.05).However,after twice ALSS therapy,the levels of M30 and M65 in non-recovered group were significantly higher than those in improvement group(t=30.699 and 64.777,respectively,both P＜0.01).Moreover,after the second ALSS therapy,the levels of M30 and M65 were both significantly lower compared to those after the first-time therapy in the improvement group(t=3.350 and 5.932,respectively,both P＜0.01).The areas under Curve(AUC)of M30,M65 and the combination of M30 and M65 for prognosis prediction were 0.796,0.844 and 0.906,respectively.The AUC of combination of M30 and M65 was significantly higher than M30 or M65 alone(Z=2.163 and 2.141,respectively,P=0.031 and 0.032,respectively).The cut-off values of M30 and M65 were 591.91 and 924.50 U/L,respectively.The sensitivity and specificity of combined M30 and M65 were 94.7％and 82.5％,respectively.Conclusions Serum M30 and M65 levels can predict the short-term prognosis of HBV-ACLF patients after ALSS therapy.The combination of M30 and M65 is of better diagnostic value.

Clinical value of serum markers M30 and M65 for primary biliary cholangitis / 临床检验杂志

Objective@#To quantify the serum levels of apoptosis-related molecules M30 and M65 in the patients with primary biliary cholangitis (PBC) and analyze their clinical significance for PBC. @*Methods@#A total of 79 patients with PBC and 40 healthy individuals were involved in this study from January 2017 to April 2019. The levels of serum M30 and M65 were measured by enzyme-linked immunosorbent assay (ELISA) and the ratio of M30/M65 was calculated. The parameters of liver function were tested by automatic biochemical analyzer. ALT, AST and GGT were determined by rate method, ALP was assayed by the method of NPP substrate-AMP buffer and T-Bil was determined by oxidation method. Autoantibodies including AMA-M2, anti-GP210 and anti-SP100 were detected by automated multiplexed bead-based and immunoblotting assays. The correlation of M30, M65 and M30/M65 ratio with liver function items were analyzed by spearman assay. The levels of M30, M65 and M30/M65 ratio were analyzed by ROC curve to evaluate their values in PBC screening. @*Results@#M65 level in PBC group was significantly higher than that in control group (P＜0.001) with statistically significant difference and M30/M65 ratio was significantly lower than that in control group with statistically significant difference (P＜0.001). There was no significant difference for the level of M30 between the two groups (P=0.641). Among the PBC patients, 18 were anti-GP210-positive and 17 were anti-SP100-positive. In anti-GP210 positive group the levels of M30 and M65 were significantly higher than those in the negative group (P values were 0.002 and 0.001 respectively). In anti-SP100 positive group the level of M65 was significantly higher than that in the negative group (P=0.027) and M30/M65 ratio was significantly lower than that in negative group with statistically significant difference (P=0.005). Spearman correlation analysis showed that the levels of M30 and M65 were positively correlated with ALT, AST and T-Bil (P＜0.05). The cut off values of M30 and M65 were 63.62 U/L and 155.37 U/L and M30/M65 was 0.32, respectively. The screening sensitivities were 63.30%, 89.10% and 93.30%, and the specificities were 51.60%, 90.00% and 75.00%, respectively. @*Conclusion@#The level of M65 in the serum of PBC patients significantly increased and M30/M65 ratio significantly decreased, which could be used as a promising serum marker of laboratory for PBC screening.

Expression of M30 and M65 in celiac disease. Analytical cross-sectional study

ABSTRACT BACKGROUND: The role of villous atrophy in apoptosis, a distinctive feature of celiac disease, is a matter of controversy. The aim of this study was to determine the apoptosis rate through immunohistochemical staining for M30 and M65 in celiac disease cases. DESIGN AND SETTING: Analytical cross-sectional study in a tertiary-level center. METHODS: Duodenal biopsies from 28 treatment-naive patients with celiac disease, 16 patients with potential celiac disease, 10 patients with a gluten-free diet and 8 controls were subjected to immunohistochemical staining for the end-apoptotic marker M30 and the total cell death marker M65. H-scores were compared. Several laboratory parameters were recorded concomitantly, and at the one-year follow-up for celiac disease and potential celiac disease patients. RESULTS: There was a significant difference in H-score for M30 expression between the celiac disease, potential celiac disease and gluten-free diet groups (P = 0.009). There was no significant difference in H-score for M65 expression. There was a positive correlation between the H-score for M30 expression and the anti-tissue transglutaminase immunoglobulin A (anti-tTgIgA) and anti-tissue transglutaminase immunoglobulin G (anti-tTgIgG) levels (R = 0.285, P = 0.036; and R = 0.307, P = 0.024, respectively); and between the H-score for M65 expression and the anti-tTgIgA and anti-tTgIgG levels (R = 0.265, P = 0.053; and R=0.314, P = 0.021, respectively). There was no difference between celiac disease and potential celiac disease patients regarding the laboratory parameters selected. CONCLUSION: The rates of apoptosis and nutritional deficiencies in patients with potential celiac disease were similar to those in patients with celiac disease.

Propofol or sevoflurane anaesthesia does not affect hepatic integrity as assessed by the M30 & M65 cell death markers & liver enzymes.

Background & objectives: General anaesthetics may induce apoptosis. The pro-apoptotic/necrotic markers M30 (caspase-cleaved cytokeratin-18) and M65 (intact cytokeratin-18) have been used to identify early apoptosis in liver disease. The aim of this study was to detect the effect of propofol and sevoflurane anaesthesia on these markers and blood transaminase levels in female patients undergoing elective surgery. Methods: Sixty-seven women undergoing mastectomy or thyroidectomy under general anaesthesia were randomly allocated to the propofol or sevoflurane groups. Venous blood samples for measuring the apoptotic and necrotic markers M30 and M65 as well as for measuring the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST) liver enzymes were collected before induction of anaesthesia, immediately after completion of surgery, and 24 and 48 h postoperatively. Results. The M30 values preoperatively and 0, 24 and 48 h postoperatively were 280±229, 300±244, 267±198 and 254±189 U/l in the propofol group and 237±95, 242±109, 231±94 and 234±127 U/l in the sevoflurane group, respectively. The M30 values did not differ within or between the groups. The M65 levels at the same time intervals were 470±262, 478±271, 456±339 and 485±273 in the propofol group and 427±226, 481±227, 389±158 and 404±144 U/l in the sevoflurane group, respectively. No significant changes were found in the M65 either within or between the propofol and the sevoflurane groups. The ALT and AST levels did not change at these time intervals. Interpretation & conclusions: Under the present study design propofol or sevoflurane anaesthesia did not induce apoptosis or affected the liver function as assessed by the M30, M65 markers and liver enzymes in patients undergoing mastectomy or thyroidectomy under general anaesthesia.

Significance of Cytokeratin Fragment M65 and Cytokines IL6, IL8 and IL17A in Bone Marrow Aspirates of Colorectal Cancer Patients.

Aims: Soluble cytokeratin (CK) fragments and inflammatory interleukins (ILs) in bone marrow (BM) aspirates of colorectal cancer (CRC) patients are expected to indicate presence of disseminated tumor cells (DTCs) and anticancer response of the host, respectively. The present study investigated the relations of CK18 fragment M65, IL6, IL8, and IL17A in BM samples to the presence of DTCs and prognosis. Place and Duration of Study: Department of Medicine (Medical Unit II) and Department of Surgery, Donauspital Vienna, between 2002 and July 2005. Methodology: BM aspirates were obtained immediately prior to and one and two years after tumor surgery, respectively, and M65 and cytokines were quantified by ELISA assays. Results: 16/66 patients revealed tumor-positive BM aspirates, and 10/46 evaluable patients relapsed within five years. M65 levels exhibited no relation to either positive biopsies, relapses or methylation status of O6-methyl guanine methyl transferase (MGMT). In contrast, IL17A concentrations of BM aspirates were elevated in nonrelapsed versus relapsed, as well as MGMT-wildtype versus MGMT-methylated patients. Due to large individual variations, IL6 and IL8 levels of BM showed no significant differences for non-relapsed versus relapsed patients. Conclusion: M65 levels of BM samples of CRC patients exhibited no correlation with micrometastases or disease recurrence, respectively; however, patients who achieved disease-free survival revealed increases of IL17A in BM aspirates, possibly indicating immune response to tumor cells.