摘要
AIM: To elucidate the efficacies of tolvaptan(TLV) as a treatment for refractory ascites compared with conventional treatment. METHODS: We retrospectively enrolled 120 refractory ascites patients between January 1, 2009 and September 31, 2014. Sixty patients were treated with oral TLV at a starting dose of 3.75 mg/d in addition to sodium restriction(> 7 g/d), albumin infusion(10-20 g/wk), and standard diuretic therapy(20-60 mg/d furosemide and 25-50 mg/d spironolactone) and 60 patients with large volume paracentesis in addition to sodium restriction(less than 7 g/d), albumin infusion(10-20 g/wk), and standard diuretic therapy(20-120 mg/d furosemide and 25-150 mg/d spironolactone). Patient demographics and laboratory data, including liver function, were not matched due to the small number of patients. Continuous variables were analyzed by unpaired t-test or paired t-test. Fisher's exact test was applied in cases comparing two nominal variables. We analyzed factors affecting clinical outcomes using receiver operating characteristic curves and multivariate regression analysis. We also used multivariate Cox's proportional hazard regression analysis to elucidate the risk factors that contributed to the increased incidence of ascites.RESULTS: TLV was effective in 38(63.3%) patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. Multivariate regression analysis indicated that > 25% reduced urine osmolality [odds ratio(OR) = 20.7; P < 0.01] and positive hepatitis C viral antibodies(OR = 5.93; P = 0.05) were positively correlated with an improvement of refractory ascites, while the total bilirubin level per 1.0 mg/dL(OR = 0.57;P = 0.02) was negatively correlated with improvement. In comparing the TLV group and controls, only the serum sodium level was significantly lower in the TLV group(133 mE q/L vs 136 mE q/L; P = 0.02). However, there were no significant differences in the other parameters between the two groups. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group(P = 0.01). Cox hazard proportional multivariate analysis indicated that the use of TLV(OR = 0.58; P < 0.01), uncontrolled liver neoplasms(OR = 1.92; P < 0.01), total bilirubin level per 1.0 mg/dL(OR = 1.10; P < 0.01), and higher sodium level per 1.0 m Eq/L(OR = 0.94; P < 0.01) were independent factors that contributed to incidence. CONCLUSION: Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments.
AIM To elucidate the efficacies of tolvaptan （TLV）as a treatment for refractory ascites compared withconventional treatment.METHODS： We retrospectively enrolled 120 refractoryascites patients between January 1, 2009 and September31, 2014. Sixty patients were treated with oral TLVat a starting dose of 3.75 mg/d in addition to sodiumrestriction （〉 7 g/d）, albumin infusion （10-20 g/wk）, andstandard diuretic therapy （20-60 mg/d furosemide and25-50 mg/d spironolactone） and 60 patients with largevolume paracentesis in addition to sodium restriction（less than 7 g/d）, albumin infusion （10-20 g/wk）, andstandard diuretic therapy （20-120 mg/d furosemide and25-150 mg/d spironolactone）. Patient demographicsand laboratory data, including liver function, werenot matched due to the small number of patients.Continuous variables were analyzed by unpaired t -testor paired t -test. Fisher＇s exact test was applied in casescomparing two nominal variables. We analyzed factorsaffecting clinical outcomes using receiver operatingcharacteristic curves and multivariate regressionanalysis. We also used multivariate Cox＇s proportionalhazard regression analysis to elucidate the risk factorsthat contributed to the increased incidence of ascites.RESULTS： TLV was effective in 38 （63.3%） patients.The best cut-off values for urine output and reducedurine osmolality as measures of refractory ascitesimprovement were 〉 1800 mL within the first 24 h and〉 30%, respectively. Multivariate regression analysisindicated that 〉 25% reduced urine osmolality [oddsratio （OR） = 20.7; P 〈 0.01] and positive hepatitis Cviral antibodies （OR = 5.93; P = 0.05） were positivelycorrelated with an improvement of refractory ascites,while the total bilirubin level per 1.0 mg/dL （OR = 0.57;P = 0.02） was negatively correlated with improvement.In comparing the TLV group and controls, only theserum sodium level was significantly lower in the TLVgroup （133 mEq/L vs 136 mEq/L; P = 0.02）. However,there were no significant differences in the otherparameters between the two groups. The cumulativeincidence rate was significantly higher in the controlgroup with a median incidence time of 30 d in the TLVgroup and 20 d in the control group （P = 0.01）. Coxhazard proportional multivariate analysis indicated thatthe use of TLV （OR = 0.58; P 〈 0.01）, uncontrolledliver neoplasms （OR = 1.92; P 〈 0.01）, total bilirubinlevel per 1.0 mg/dL （OR = 1.10; P 〈 0.01）, and highersodium level per 1.0 mEq/L （OR = 0.94; P 〈 0.01）were independent factors that contributed to incidence.CONCLUSION： Administration of TLV results in bettercontrol of refractory ascites and reduced the incidenceof additional invasive procedures or hospitalizationcompared with conventional ascites treatments.
