Predictive factors of failure to control bleeding and 6-week mortality after variceal hemorrhage in liver cirrhosis - a tertiary referral center experience.

INTRODUCTION: Mortality from variceal bleeding remains high despite the therapeutic progress in severe cirrhosis. Understanding the predictive factors of failure to control bleeding (FTB) and mortality will lead to better future therapies. Comorbidities are thought to be important prognostic factors for variceal bleeding. The aim of the study was to assess the factors associated with FTB and with 42-day mortality and to evaluate the influence of comorbidities on these patients' prognosis. MATERIAL AND METHODS: We prospectively included in the study all consecutive patients with cirrhosis and variceal bleeding presenting to the emergency room and we followed them up over 6 weeks. CirCom score and Charlson index were used for the assessment of comorbidities. RESULTS: Of the 138 patients included in the study, 27 (19.5%) were considered to have FTB. Child C class (74.07% vs. 32.43%, p < 0.001), Meld score (20.5 vs. 16.00, p = 0.004) and creatinine level (1.04 vs. 0.81, p = 0.01) were associated with FTB, but only Child class was independently associated with FTB in multivariate analysis (OR = 2.94, p = 0.006). Mortality at 42 days (21.7%) was influenced by the severity of the disease assessed through Child class (76.66% vs. 30.55% - Child C, p < 0.001) and MELD score (21.00 vs. 16.00, p < 0.001). Creatinine level (1.00 vs. 0.7, p = 0.02) and acute kidney injury (26.66% vs. 7.40%, p = 0.009) were also prognostic factors for the 6-week mortality. Comorbidities did not influence the mortality (CirCom > 1 (16.7% vs. 21.3%, p = 0.76) or Charlson index > 4 (36% vs. 47.2%, p = 0.41). CONCLUSIONS: The severity of cirrhosis is an important prognostic factor for FTB and 42-day mortality. Identifying the factors associated with early mortality may help selecting patients needing more than conventional therapy.

Hepatocyte microvesicle levels improve prediction of mortality in patients with cirrhosis.

Microvesicles (MVs) are extracellular vesicles released by cells following activation or apoptosis. Some MV subpopulations augment with cirrhosis severity and contribute to portal hypertension. This study aimed at determining if plasma MV levels can estimate the presence of hepatic venous pressure gradient (HVPG) ≥10 mm Hg and predict mortality in patients with advanced chronic liver disease. All patients with severe fibrosis or cirrhosis undergoing liver catheterization between 2013 and 2015 at two centers were prospectively included. We measured circulating levels of annexin V+ , platelet, leukocyte, endothelial, and hepatocyte MVs. The test cohort included 139 patients. Hepatocyte MV levels were 4.0-fold and 2.2-fold higher in patients with Child-Pugh C than in those with Child-Pugh A or B liver disease, respectively. Levels of other MV subpopulations were not influenced by liver disease severity. Hepatocyte MV levels correlated with HVPG but could not identify patients with HVPG ≥10 mm Hg. Hepatocyte MV level >65 U/L predicted 6-month mortality independently of Child-Pugh score and of Model for End-Stage Liver Disease (MELD). Patients with hepatocyte MV levels >65 U/L and MELD >15 had a higher 6-month mortality than other patients (23% versus 3%; P = 0.001). These findings were confirmed in a validation cohort including 103 patients. CONCLUSION: Circulating MV levels cannot identify patients with HVPG ≥10 mm Hg; by contrast, hepatocyte MV levels strongly improve prediction of 6-month mortality in patients with advanced chronic liver disease; therapies associated with decreased levels of circulating hepatocyte MV might be attractive strategies in patients with severe cirrhosis. (Hepatology 2018).

Predictors of variceal or nonvariceal source of upper gastrointestinal bleeding. An etiology predictive score established and validated in a tertiary referral center.

BACKGROUND & AIMS. For upper gastrointestinal bleeding (UGIB), guidelines recommend pharmacological treatment before endoscopy. Therefore, it is important to establish an early diagnosis of the variceal or non-variceal source of bleeding. This study aims to analyze the clinical and laboratory parameters which are predictors of the UGIB etiology, and to develop a score for predicting variceal or non-variceal bleeding. METHODS. This study comprised patients presenting to the emergency department of a tertiary care center with UGIB, throughout a 1-year period. Clinical, ultrasound data and laboratory parameters were noted. RESULTS. Of the 517 patients with UGIB, 29.8% had variceal and 70.2% non-variceal bleeding. Six factors were associated with variceal hemorrhage: cirrhosis (OR=10.74, 95% CI: 3.50-32.94, p<0.001), history of variceal hemorrhage (OR=13.11, 95%CI: 3.09-55.57, p<0.001), ascites (OR=4.41, 95% CI: 1.74-11.16, p=0.002), thrombocytopenia (OR=2.77, 95% CI: 1.18-6.50, p=0.01), elevated INR (OR=4.77, 95% CI:1.47-15.42, p=0.009) and elevated bilirubin levels (OR=2.43, 95% CI:1.01-5.84, p=0.04). Two factors were associated with non-variceal bleeding: the use of NSAIDs (OR=0.32, 95%CI: 0.13-0.83, p=0.01) and of anticoagulants (OR=0.04, 95%CI: 0.00-0.89, p=0.04). A prediction score for UGIB etiology was designed based on this model. We calculated a cutoff value of 0.968, higher values being predictive of variceal bleeding. Positive predictive value (PPV) and negative predictive value (NPV) were: 82.7% and 97%, respectively. The score was validated prospectively in another group of 162 patients: PPV and NPV were 72.7% and 95.3%, respectively. CONCLUSIONS. Several factors were identified as predictors for the etiology of UGIB. Due to its high PPV and NPV, our UGIB etiology score might be useful in predicting variceal bleeding and could assist in the selection of pharmacological therapy before endoscopy.