Functional Capacity, Respiratory Muscle Strength, and Oxygen Consumption Predict Mortality in Patients with Cirrhosis.

Introduction. Liver diseases influence musculoskeletal functions and may negatively affect the exercise capacity of patients with cirrhosis. Aim. To test the relationship between the six-minute walk test (6MWT), maximal inspiratory pressure (MIP), and exercise capacity (VO2peak) measures and the survival rate of patients with cirrhosis. Methods. This prospective cohort study consisted of 86 patients diagnosed with cirrhosis with the following aetiology: hepatitis C virus (HCV), hepatitis B virus (HBV), and/or alcoholic cirrhosis (AC). All patients were followed up for three years and submitted to the 6MWT, pressure measurements with a compound gauge, and an exercise test (VO2peak). Results. The survival analysis showed that the individuals who covered a distance shorter than 410 m during the 6MWT had a survival rate of 55% compared with a rate of 97% for the individuals who walked more than 410 m (p = 0.0001). Individuals with MIPs below -70 cmH2O had a survival rate of 62% compared with a rate of 93% for those with MIPs above -70 cmH2O (p = 0.0001). The patients with values below 17 mL/kg had a survival rate of 55% compared with a rate of 94% for those with values above 17 mL/kg (p = 0.0001). Conclusion. The 6MWT distance, MIP, and oxygen consumption are predictors of mortality in patients with cirrhosis.

Exercise capacity of cirrhotic patients with hepatopulmonary syndrome.

INTRODUCTION: Hepatopulmonary syndrome (HPS) is characterized by a clinical triad of liver disease and/or portal hypertension, intrapulmonary vascular dilatation and abnormal arterial oxygenation. These conditions can worsen muscle strength, exercise capacity and functionality in the affected population. OBJECTIVE: The objective of this study was to compare exercise capacity, functional condition and respiratory muscle strength in cirrhotic patients diagnosed with HPS and cirrhotic patients without this diagnosis. MATERIAL AND METHODS: This cross-sectional study used a convenience sample consisting of 178 patients (92 patients with HPS and 86 patients without HPS) with a diagnosis of liver cirrhosis caused by either alcohol consumption or the hepatitis C virus (HCV). Peak oxygen consumption (VO2 peak) was used to verify exercise capacity, the six-minute walk test (6MWT) was used to test functionality, and manovacuometry was used to evaluate the strength of the respiratory muscles. The Kolmogorov-Smirnov test and Student's t-test were used for the statistical analysis. The data were analyzed using SPSS 16.00, and p < 0.05 was considered significant. RESULTS: The group of patients with the diagnosis of HPS exhibited a lower VO2 peak (14.2 ± 2.3 vs. 17.6 ± 2.6, p < 0.001), shorter distance walked in the 6MWT (340.8 ± 50.9 vs. 416.5 ± 91.4, p < 0.001), lower maximal inspiratory pressure (-49.1 ± 9.8 vs. -74.2 ± 13.9, p = 0.001) and lower maximum expiratory pressure (60.1 ± 12.2 vs. 76.8 ± 14.7, p = 0.001). CONCLUSION: The group of cirrhotic patients diagnosed with HPS exhibited lower values for VO2 peak, distance walked in the 6MWT and respiratory muscle strength than the cirrhotic patients not diagnosed with HPS.

Impact of MELD score implementation on liver allocation: experience at a Brazilian center.

Introduction. Model for end-stage liver disease (MELD) is an accurate predictor of mortality in patients with cirrhosis, and has been used on liver allocation in Brazil since 2006. However, its impact on organ allocation, waiting list and post-transplant mortality is still poorly characterized. This study aimed to assess the impact of implementation of the MELD system on liver allocation and mortality after liver transplantation (LT) in Southern Brazil. Material and methods. Adult patients with chronic liver disease on the waiting list for primary deceased-donor LT were divided into two cohorts (pre- and post-MELD implementation) according to the date of waiting list placement. Disease severity, as assessed by MELD score at placement, was similar in both cohorts. Patients were followed for at least 18 months to assess the outcomes of interest (death/LT). Results. Higher MELD scores correlated with waiting list mortality, which increased 20% with each additional point (HR 1.2; 95%CI 1.14-2.26; p < 0.001). Waiting list mortality was 30.9% before and 21.7% after MELD implementation (nonsignificant). Transplant rate increased after MELD implementation (52 vs. 40%, p = 0.002). After excluding patients with hepatocellular carcinoma, mean MELD scores at LT were significantly higher in the MELD era (p < 0.01). There was no significant correlation between MELD scores at LT and post-LT survival. During 18-month follow-up, post-LT mortality rate was 25.4% before and 20% after MELD implementation (nonsignificant). Conclusion. MELD implementation was associated with a reduction in waiting list mortality. Although sicker patients received LT in the MELD era, post-transplant survival was similar in both periods.

Evaluation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma.

INTRODUCTION: Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients. OBJECTIVE: To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp. MATERIAL AND METHODS: A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry. RESULTS: Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%, respectively, and was significantly higher when in the presence of allele T (p = 0.002). CONCLUSION: The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.

Prognostic factors associated with in-hospital mortality in patients with spontaneous bacterial peritonitis.

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is associated with a high in-hospital mortality rate ranging from 20-40%. The model for end-stage liver disease (MELD) has been suggested as a predictor of in-hospital mortality in patients with SBP. However, the accuracy of the MELD has been questioned, and the integrated MELD (iMELD) score, which incorporates age and serum sodium to the previous model, has been proposed to improve prognostic accuracy. The iMELD has not yet been evaluated in patients with SBP. AIM: To evaluate the accuracy of iMELD and MELD scores in predicting in-hospital mortality in patients with SBP and to identify other prognostic factors of mortality in this group of patients. RESULTS: Of 40 patients analyzed, 65% were male, 50% had hepatitis C, and 27.5% had hepatocellular carcinoma. Mean age was 55.6 years; 25.7% were classified as Child-Pugh class B, and 74.3% as class C. Mean scores were 46.0 and 19.9 for iMELD and MELD, respectively. In-hospital mortality was 40%. Univariate analysis showed that total bilirubin, creatinine, MELD and iMELD scores were significantly associated with in-hospital mortality. The prognostic accuracy was 80% and 77% for iMELD and MELD scores, respectively. CONCLUSION: In conclusion, bilirubin, creatinine, MELD and iMELD were predictors of in-hospital mortality in cirrhotic patients with SPB. iMELD was slightly more accurate than MELD in this group of patients.

MELD scores with incorporation of serum sodium and death prediction in cirrhotic patients on the waiting list for liver transplantation: a single center experience in southern Brazil.

To compare the accuracy of standard model for end-stage liver disease (MELD) score with that of four MELD-based scores incorporating serum sodium (SNa) to predict three- and six-month mortality in cirrhotic patients after their placement on the waiting list for liver transplantation (LT). A cohort study was performed. Receiver operating characteristic (ROC) curves were generated for MELD, MELD incorporating SNa (MELD-Na, MELD-Na2), integrated MELD (iMELD), and MELD to SNa ratio (MESO) index to assess the predictive accuracy of these scores to determine three- and six-month mortality. The c-statistic (area under the ROC curve [AUC]) was used to determine predictive power and the Cox proportional-hazard ratio to estimate death risk. We studied 558 patients. There was a statistically significant difference in the predictive accuracy of scores at three months (AUCs: MELD = 0.79 [95% CI = 0.72-0.87]; MELD-Na = 0.84 [95% CI = 0.78-0.90]; MELD-Na2 = 0.85 [95% CI = 0.80-0.91]; iMELD = 0.85 [95% CI = 0.80-0.90]; MESO = 0.81 [95% CI = 0.80-0.91]) and at six months (MELD = 0.73 [95% CI = 0.67-0.80]; MELD-Na = 0.79 [95% CI = 0.73-0.84]; MELD-Na2 = 0.80 [95% CI = 0.74-0.85]; iMELD = 0.80 [95% CI = 0.75-0.85]; MESO = 0.75 [95% CI = 0.69-0.81]) (p < 0.001). Death risk was independent of age and sex. Sodium-modified MELD scores are able to more accurately predict three- and six-month mortality among cirrhotic patients awaiting LT.