Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure

AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC >= 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Case Control Study of Post-endoscopic Variceal Ligation Bleeding Ulcers in Severe Liver Disease: Outcomes and Management

Background and Aims:The management of post-endoscopic variceal ligation(EVL)bleeding ulcers(PEBUs)is currently based on local expertise and patients liver disease status.The present retrospective study investigated associations between the endoscopic morphology of PEBUs and patient outcomes.Methods:Patients underwent EVL(primary or secondary),from January 2015 to January 2018,in two tertiary care hospitals in India(ILBS New Delhi and Dharamshila Narayana New Delhi).Mortality rates were determined at post-EVL day five and week six.PEBUs were typified based on Jamwal&Sarin classification system as follows:A,ulcer with active spurting;B,ulcer with ooze;C,ulcer base with visible vessel or clot;and D,clean or pigmented base.Results:Of 3854 EVL procedures,141(3.6%)patients developed PEBU,and 46/141(32.6%)suffered mortality.Among the former,the PEBU types A,B,C,and D accounted for 17.7,26.2,36.3,and 19.8%,respectively.Of those who died,39.1,30.4,21.7,and 8.8%had PEBU types A,B,C,and D.Treatments included transjugular intrahepatic portosystemic shunts(TIPS),esophageal self-expandable metal stent(SEMS),glue and sclerosant injection,Sengstaken-Blakemore tube placement and liver transplant.On univariate analysis,no correlation with hepatic venous pressure gradient,TIPS placement,size of varices,or number of bands was found.The Model for EndStage Liver Disease(MELD)-sodium score correlated positively with outcome.After adjusting for MELD-sodium score,mortality was best predicted by type-A ulcer(p=0.024;OR 8.95,CI 1.34-59.72).Conclusions:PEBU occurred in 3.6%of a large EVL cohort.Stratifying patients based on PEBU type can help predict outcomes,independent of the MELD-sodium score.Classifying PEBUs by endoscopic morphology may inform treatment strategies,and warrants further validation.