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.

VKORC1-1639 G>A Polymorphism and the Risk of Non-Variceal Upper Gastrointestinal Bleeding.

BACKGROUND AND AIMS: The mutations in the gene that encodes vitamin K epoxide reductase (VKOR) enzyme are responsible for low levels of vitamin K. The purpose of this study was to evaluate whether the presence of the VKORC1 -1639 G> A polymorphism is a risk factor for non-variceal upper gastrointestinal bleeding (UGIB) in patients without concomitant therapy with vitamin K antagonists. METHODS: This case-control study comprised 163 consecutive patients diagnosed with UGIB and 178 controls, in whom the diagnosis of UGIB was excluded. The following data were recorded: age, gender, alcohol consumption, smoking, history of UGIB, nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin consumption. Genetic analysis included genotyping for the VKORC1 -1639 G>A polymorphism. RESULTS: History of UGIB (OR 3.463, CI95% 1.463-8.198, p=0.005), smoking (OR 2.498, CI95% 1.358-4.597, p=0.003), alcohol consumption (OR 3.283, CI95% 1.796-6.000, p<0.001), use of NSAIDs (OR 4.542, CI95% 2.502-8.247, p<0.001) or of low-dose aspirin (OR 2.390, CI95% 1.326-4.310), and the VKORC1 -1639 G> A AA genotype (OR 1.364, CI95% 0.998-1.863, p=0.05) were associated with an increased risk of UGIB. The risk of UGIB was analyzed in patients with genotype AA who used aspirin or NSAIDs. The genotype AA has not kept its status of independent risk factor (p=0.3). In subjects with NSAIDs/aspirin therapy and genotype AA there was a two times higher chance of UGIB compared to those under NSAIDs/aspirin therapy alone (OR 7.6 vs. 3.6, p<0.001). CONCLUSION: Patients with non-variceal UGIB caused by the use of NSAIDs or low-dose aspirin are more frequent carriers of the VKORC1 -1639 G>A AA genotype, as compared to those without UGIB.

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.

Treatment of hepatocellular carcinoma in a tertiary Romanian center. Deviations from BCLC recommendations and influence on survival rate.

BACKGROUND & AIM: The Barcelona-Clinic Liver Cancer (BCLC) staging system is based on the results obtained in the setting of several cohort studies and randomized clinical trials. We have evaluated the applicability of the BCLC staging system and the effect of treatment allocation according to BCLC on the survival rate and prognosis in patients with hepatocellular carcinoma (HCC) in a tertiary center. METHODS: Treatment indications for 473 patients referred to our center with the diagnosis of HCC were retrospectively analyzed. Patients were split in three groups: a group treated according to BCLC recommendation, an overtreated group and an undertreated group. The survival rate was calculated using the Kaplan Meier method and compared using the log-rank test. RESULTS: Patients distribution according to BCLC staging system was: 17 patients (3.6%) in very early stage (O), 161 (34.0 %) in early (A), 140 (29.6%) in intermediate (B), 82 (17.3%) in advanced (C) and 73 patients (15.4%) in terminal stage (D). Only 275 patients (58.1%) from stage 0, A-D were treated according to BCLC. The mean survival rate in stage 0 and A was higher for patients receiving curative treatment in comparison with undertreated patients (41 vs 28 months, p< 0.05). Overtreated patients in stage B or C had a better survival than patients treated according to BCLC (25 months vs 21 months, p=0.973, and 28 months vs 4 months, p=0.308, respectively), without statistical significance. Patients in stage B and C treated according to BCLC recommendations had a better survival than those undertreated (21 months vs 13 months, p=0.002, and 4 vs 3 months, p=0.036, respectively). CONCLUSIONS: Deviations from BCLC recommendations occur in 40% of patients with HCC. Undertreatment results in a decreased survival of patients diagnosed with HCC. Overtreated BCLC-B and C patients have an increased survival in comparison with those treated with standard therapy.