BACKGROUND Holoprosencephaly(HPE)is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain.Although HPE with diabetes insi...BACKGROUND Holoprosencephaly(HPE)is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain.Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported,HPE with the syndrome of inappropriate antidiuretic hormone secretion(SIADH)is very rare.Tolvaptan,a vasopressin V2 receptor antagonist,is effective in adults with SIADH.However,there is no report of its efficacy in infants with SIADH.The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration.CASE SUMMARY A 2414-g female infant was born at 38 wk by normal vaginal delivery.Facial anomalies and head magnetic resonance imaging indicated semilobar HPE.After birth,she had hyponatremia due to SIADH and was treated using water and sodium restriction.However,she developed an exaggerated response to the fluid restrictions,resulting in large fluctuations in serum sodium levels.Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration.Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life.There were no side effects,such as hypernatremia or liver dysfunction,during the administration of tolvaptan.CONCLUSION This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.展开更多
AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular car...AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma.METHODS: Thirty-nine patients(mean age 55 years, males: 32) with decompensated liver cirrhosis and refractory ascites were enrolled. All patients received a combination of tolvaptan(15 mg/d for 5-14 d) and diuretics(40-80 mg/d of furosemide and 80-160 mg/d of spironolactone). The etiology of cirrhosis included hepatitis B(69.2%), hepatitis C(7.7%) and alcohol-in-duced(23.1%). Changes in the urine excretion volume, abdominal circumference and edema were assessed. The serum sodium levels were also measured, and adverse events were recorded. A follow-up assessment was conducted 1 mo after treatment with tolvaptan.RESULTS: Tolvaptan increased the mean urine excretion volume(1969.2 ± 355.55 mL vs 3410.3 ± 974.1 mL, P < 0.001), and 89.7% of patients showed improvements in their ascites, 46.2% of whom showed significant improvements. The overall efficacy of tolvaptan in all patients was 89.7%; the efficacies in patients with hepatocellular carcinoma and hepatorenal syndrome were 84.2% and 77.8%, respectively. The incidence of hyponatremia was 53.8%. In patients with hyponatremia, the serum sodium levels increased after tolvaptan treatment(from 128.1 ± 4.22 mEq/L vs 133.1 ± 3.8 mEq/L, P < 0.001). Only mild drug-related adverse events, including thirst and dry mouth, were observed. CONCLUSION: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis.展开更多
AIM: To investigate the role of tolvaptan in regulating aquaporin(AQP)-2 expression and fecal water content in cirrhotic rats with ascites.METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injec...AIM: To investigate the role of tolvaptan in regulating aquaporin(AQP)-2 expression and fecal water content in cirrhotic rats with ascites.METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups(vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups(days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin(HE) staining and feces were collected for determination of fecal water content. CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group(100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content inthe distal colon was increased by 5 mg/kg tolvaptan on day 1(66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan.CONCLUSION: Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea.展开更多
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, 20...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.展开更多
AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors in 40 patients wit...AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient(HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.RESULTS: Subjects comprised patients with a median age of 65(range, 40-82) years. According to the ChildPugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were-1.0 kg(P = 2.04 × 10^(-6)) and-1.3 kg(P = 1.83 × 10^(-5)), respectively. The median HVPG value was 240(range, 105-580) mm H2 O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mm H_2 O in predicting treatment response. The response rate was 87.5%(7/8) in patients with HVPG of 190 mm H2 O or less, whereas it was only 12.5%(2/16) in those with HVPG of greater than 190 mm H2O(P = 7.46 × 10^(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG(P = 0.045) and serum hyaluronic acid(P = 0.017) were detected as useful factors.CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.展开更多
AIM To investigate the factors influenced the efficacy of tolvaptan(TLV) in liver cirrhosis.METHODS We retrospectively enrolled 61 consecutive patients with refractory hepatic ascites. All of them had been treated wit...AIM To investigate the factors influenced the efficacy of tolvaptan(TLV) in liver cirrhosis.METHODS We retrospectively enrolled 61 consecutive patients with refractory hepatic ascites. All of them had been treated with furosemide and spironolactone before admission, and treated with TLV for 7 d in our hospital. The effect of TLV was defined by the rate of body weight loss, and the factors that influenced TLV efficacy were analyzed using multiple regression.RESULTS Coexistent hepatocellular carcinoma(HCC) was the only significant predictive variable that attenuated the efficacy of TLV. In stratified analysis, high doses of furosemide decreased the efficacy of TLV in patients with HCC, and increased efficacy in those without HCC. In the latter, a high Child-Pugh-Turcotte score had a positive influence and a high concentration of lactate dehydrogenase had a negative influence on the effectiveness of TLV.CONCLUSION Development of ascites may differ between patients with liver failure and those with HCC progression. A sufficient preceding dose of furosemide decreases diuretic effect of TLV.展开更多
We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese v...We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese version of the Support Team Assessment Schedule. The psoas muscle index (PMI) was used to define sarcopenia. A statistically significant difference was observed in the PMI between patients receiving low-dose (3.6 ± 1.2 cm2/m2) and high-dose furosemide (3.1 ± 1.2 cm2/m2) before tolvaptan treatment (P = 0.048). The PMI increased from 3.2 ± 1.1 cm2/m2 to 3.5 ± 1.3 cm2/m2 (P = 0.002) in responders, but decreased from 3.4 ± 1.2 cm2/m2 to 3.0 ± 1.0 cm2/m2 (P = 0.106) in non-responders before and after tolvaptan treatment, respectively. The long-term prognosis improved in responders compared with non-responders (mean survival time: 646 days vs. 228 days, P < 0.001). Early introduction of tolvaptan treatment is necessary to prevent the progression of sarcopenia.展开更多
We investigated Tolvaptan efficacy and long-term prognosis with focus on nutrition in 20 patients with refractory hepatic ascites in hepatocellular carcinoma (HCC). Bloating improved in 55% of patients, as determined ...We investigated Tolvaptan efficacy and long-term prognosis with focus on nutrition in 20 patients with refractory hepatic ascites in hepatocellular carcinoma (HCC). Bloating improved in 55% of patients, as determined using a Japanese version of the Support Team Assessment Schedule. Nutritional status improved with Tolvaptan treatment, based on the Controlling Nutritional Status score and Onodera’s prognostic nutritional index. Long-term prognosis was better in responders than in non-responders (mean survival time: 308 days vs. 97 days, p = 0.031). Tolvaptan was even effective in many patients with HCC, with additional improvement in long-term prognosis expected with improvement in the nutritional status.展开更多
BACKGROUND Polycystic kidney disease(PKD)is a genetic disorder characterized by the growth of numerous cysts within the kidneys.Disease progress of some patients often occurs at the early stage.Thus,managing and contr...BACKGROUND Polycystic kidney disease(PKD)is a genetic disorder characterized by the growth of numerous cysts within the kidneys.Disease progress of some patients often occurs at the early stage.Thus,managing and controlling disease progress is important to slow the kidney function decline especially for the patient with other disorders.CASE SUMMARY One 80-year-old male autosomal dominant polycystic kidney disease(ADPKD)patient with chronic kidney disease and other clinical disorders was treated with tolvaptan and edoxaban.Estimated glomerular filtration rate,creatinine and uric acid were monitored during the treatment.In addition,the whole exome sequencing was performed to screen ADPKD genetic variants.The kidney function decline was prevented after using tolvaptan and edoxaban treatment and in the meantime,a venous thromboembolism was removed and leg and pedal edema were alleviated.One mutation c.10102G>A/p.D3368N in the PKD1 gene was identified.CONCLUSION Tolvaptan combined with edoxaban administration could delay kidney function decline and eliminate the edema caused by the thromboembolism.展开更多
Aims:No solid evidence-based opinion was raised regarding predictors of the degree of ascites reduction with tolvaptan.This retrospective cohort study aimed to examine whether serum copeptin concentration is a useful ...Aims:No solid evidence-based opinion was raised regarding predictors of the degree of ascites reduction with tolvaptan.This retrospective cohort study aimed to examine whether serum copeptin concentration is a useful predictor of this.Methods:The study population consisted of 80 patients with liver cirrhosis treated with tolvaptan for hepatic ascites effusions at Nara Medical University Hospital from May 2014 to December 2018.Forty-three patients who lost>1.5 kg of body weight in the first week after starting tolvaptan were classified as good responders and the remaining 37 as poor responders.Various laboratory parameters were measured immediately before the start of tolvaptan therapy to examine factors associated with predicting its efficacy.Results:In the univariate analysis,no significant differences with respect to age(67.6 vs.69.8 years,p>0.05),sex,body mass index(24.8 vs.23.7 kg/m^(2),p>0.05),Child-Pugh score(9.4 vs.9.7,p>0.05),and Model for End-stage Liver Disease score(11 vs.12,p>0.05)were found between the two groups.Conversely,aspartate transferase and alanine transaminase(ALT)levels were significantly lower in the good response group(52.9±56.3 vs.68.8±50.7 U/L,p<0.05;26.2±30.6 vs.40.5±33.5 U/L,p<0.01),whereas serum copeptin and serum sodium concentrations were significantly higher(57.1±15.0 vs.45.8±16.0 pg/mL,p<0.01;136.3±3.4 vs.133.8±5.8 mEq/L,p<0.05).In the multivariate analysis,serum copeptin concentration and ALT were statistically significant factors(p<0.01,p<0.05).Regression analysis of the association between the tolvaptan efficacy for refractory ascites and pretreatment serum copeptin concentration showed that a copeptin concentration cutoff of 45.9 pg/mL could predict treatment efficacy with a sensitivity,specificity,and area under the curve of 76.7%,59.5%,and 0.71%,respectively.Conclusion:Serum copeptin concentration may be a predictor of tolvaptan efficacy for refractory ascites effusion in Japanese patients with liver cirrhosis.展开更多
Objective:The aim of this study was to investigate the efficacy and safety of tolvaptan,as well as the impact of its treatment dose and duration in heart failure patients with congestive signs.Methods:The PubMed,Embas...Objective:The aim of this study was to investigate the efficacy and safety of tolvaptan,as well as the impact of its treatment dose and duration in heart failure patients with congestive signs.Methods:The PubMed,Embase,Cochrane Library,and ClinicalTrials.gov databases were searched to collect data from all randomized controlled trials(RCT)examining the efficacy and safety of tolvaptan in heart failure patients with congestive signs compared with placebo or blank control until March 4,2021.Urine volume,change in body weight,improvement in dyspnea,and reduction of edema were evaluated as efficacy indicators.All-cause mortality,worsening heart failure,and adverse events were considered safety indicators.The quality of eligible publications was assessed using the Cochrane risk of bias for RCTs.Results:Ten RCTs with 5,980 patients were included in this analysis.Compared with control,tolvaptan significantly reduced weight in the short term(day 1,7 RCTs,weighted mean difference(WMD):-1.09,95%confidence interval(CI):-1.27 to-0.91;day 2,2 RCTs,WMD:-1.67,95%CI:-3.00 to-0.33;day 7,4 RCTs,WMD:-0.95,95%CI:-1.25 to-0.66),increased urine volume(WMD:1,825.72,95%CI:1,438.38-2,213.07),and relieved dyspnea(risk ratio(RR):1.12,95%CI:1.05-1.19)without increasing the mortality rate(RR:0.96,95%CI:0.87-1.06).Furthermore,the weight loss and increase in urine volume were not dose-dependent effects,and prolonged medication did not lead to sustained weight loss.In addition,there seemed to be more adverse events(RR:1.17,95%CI:1.03-1.32)after treatment with tolvaptan.Further analysis revealed that patients treated with tolvaptan were more likely to report thirst(RR:6.09,95%CI:3.37-11.00)and dry mouth(RR:6.36,95%CI:4.09-9.90),as well as develop hypernatremia(RR:12.76,95%CI:3.52-46.32).Conclusions:The meta-analysis shows that tolvaptan can improve congestion with no increase in mortality rate,but should be used to guard against adverse events.Deserve to be mentioned,the number of RCTs included was limited,suggesting that the observed results should be interpreted with caution.Additional robust clinical studies are warranted to validate the present findings.展开更多
文摘BACKGROUND Holoprosencephaly(HPE)is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain.Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported,HPE with the syndrome of inappropriate antidiuretic hormone secretion(SIADH)is very rare.Tolvaptan,a vasopressin V2 receptor antagonist,is effective in adults with SIADH.However,there is no report of its efficacy in infants with SIADH.The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration.CASE SUMMARY A 2414-g female infant was born at 38 wk by normal vaginal delivery.Facial anomalies and head magnetic resonance imaging indicated semilobar HPE.After birth,she had hyponatremia due to SIADH and was treated using water and sodium restriction.However,she developed an exaggerated response to the fluid restrictions,resulting in large fluctuations in serum sodium levels.Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration.Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life.There were no side effects,such as hypernatremia or liver dysfunction,during the administration of tolvaptan.CONCLUSION This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.
基金Supported by The Program of Beijing Science and Technology Commission,No.D131100005313004the Beijing HighLevel Talent Academic Leader/Personnel Training Programs awarded to Ding HG,2011-2-19+1 种基金Li B,2013-3-072and Li L,2013-3-073
文摘AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma.METHODS: Thirty-nine patients(mean age 55 years, males: 32) with decompensated liver cirrhosis and refractory ascites were enrolled. All patients received a combination of tolvaptan(15 mg/d for 5-14 d) and diuretics(40-80 mg/d of furosemide and 80-160 mg/d of spironolactone). The etiology of cirrhosis included hepatitis B(69.2%), hepatitis C(7.7%) and alcohol-in-duced(23.1%). Changes in the urine excretion volume, abdominal circumference and edema were assessed. The serum sodium levels were also measured, and adverse events were recorded. A follow-up assessment was conducted 1 mo after treatment with tolvaptan.RESULTS: Tolvaptan increased the mean urine excretion volume(1969.2 ± 355.55 mL vs 3410.3 ± 974.1 mL, P < 0.001), and 89.7% of patients showed improvements in their ascites, 46.2% of whom showed significant improvements. The overall efficacy of tolvaptan in all patients was 89.7%; the efficacies in patients with hepatocellular carcinoma and hepatorenal syndrome were 84.2% and 77.8%, respectively. The incidence of hyponatremia was 53.8%. In patients with hyponatremia, the serum sodium levels increased after tolvaptan treatment(from 128.1 ± 4.22 mEq/L vs 133.1 ± 3.8 mEq/L, P < 0.001). Only mild drug-related adverse events, including thirst and dry mouth, were observed. CONCLUSION: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis.
文摘AIM: To investigate the role of tolvaptan in regulating aquaporin(AQP)-2 expression and fecal water content in cirrhotic rats with ascites.METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups(vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups(days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin(HE) staining and feces were collected for determination of fecal water content. CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group(100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content inthe distal colon was increased by 5 mg/kg tolvaptan on day 1(66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan.CONCLUSION: Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea.
文摘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.
文摘AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient(HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.RESULTS: Subjects comprised patients with a median age of 65(range, 40-82) years. According to the ChildPugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were-1.0 kg(P = 2.04 × 10^(-6)) and-1.3 kg(P = 1.83 × 10^(-5)), respectively. The median HVPG value was 240(range, 105-580) mm H2 O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mm H_2 O in predicting treatment response. The response rate was 87.5%(7/8) in patients with HVPG of 190 mm H2 O or less, whereas it was only 12.5%(2/16) in those with HVPG of greater than 190 mm H2O(P = 7.46 × 10^(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG(P = 0.045) and serum hyaluronic acid(P = 0.017) were detected as useful factors.CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.
文摘AIM To investigate the factors influenced the efficacy of tolvaptan(TLV) in liver cirrhosis.METHODS We retrospectively enrolled 61 consecutive patients with refractory hepatic ascites. All of them had been treated with furosemide and spironolactone before admission, and treated with TLV for 7 d in our hospital. The effect of TLV was defined by the rate of body weight loss, and the factors that influenced TLV efficacy were analyzed using multiple regression.RESULTS Coexistent hepatocellular carcinoma(HCC) was the only significant predictive variable that attenuated the efficacy of TLV. In stratified analysis, high doses of furosemide decreased the efficacy of TLV in patients with HCC, and increased efficacy in those without HCC. In the latter, a high Child-Pugh-Turcotte score had a positive influence and a high concentration of lactate dehydrogenase had a negative influence on the effectiveness of TLV.CONCLUSION Development of ascites may differ between patients with liver failure and those with HCC progression. A sufficient preceding dose of furosemide decreases diuretic effect of TLV.
文摘We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese version of the Support Team Assessment Schedule. The psoas muscle index (PMI) was used to define sarcopenia. A statistically significant difference was observed in the PMI between patients receiving low-dose (3.6 ± 1.2 cm2/m2) and high-dose furosemide (3.1 ± 1.2 cm2/m2) before tolvaptan treatment (P = 0.048). The PMI increased from 3.2 ± 1.1 cm2/m2 to 3.5 ± 1.3 cm2/m2 (P = 0.002) in responders, but decreased from 3.4 ± 1.2 cm2/m2 to 3.0 ± 1.0 cm2/m2 (P = 0.106) in non-responders before and after tolvaptan treatment, respectively. The long-term prognosis improved in responders compared with non-responders (mean survival time: 646 days vs. 228 days, P < 0.001). Early introduction of tolvaptan treatment is necessary to prevent the progression of sarcopenia.
文摘We investigated Tolvaptan efficacy and long-term prognosis with focus on nutrition in 20 patients with refractory hepatic ascites in hepatocellular carcinoma (HCC). Bloating improved in 55% of patients, as determined using a Japanese version of the Support Team Assessment Schedule. Nutritional status improved with Tolvaptan treatment, based on the Controlling Nutritional Status score and Onodera’s prognostic nutritional index. Long-term prognosis was better in responders than in non-responders (mean survival time: 308 days vs. 97 days, p = 0.031). Tolvaptan was even effective in many patients with HCC, with additional improvement in long-term prognosis expected with improvement in the nutritional status.
文摘BACKGROUND Polycystic kidney disease(PKD)is a genetic disorder characterized by the growth of numerous cysts within the kidneys.Disease progress of some patients often occurs at the early stage.Thus,managing and controlling disease progress is important to slow the kidney function decline especially for the patient with other disorders.CASE SUMMARY One 80-year-old male autosomal dominant polycystic kidney disease(ADPKD)patient with chronic kidney disease and other clinical disorders was treated with tolvaptan and edoxaban.Estimated glomerular filtration rate,creatinine and uric acid were monitored during the treatment.In addition,the whole exome sequencing was performed to screen ADPKD genetic variants.The kidney function decline was prevented after using tolvaptan and edoxaban treatment and in the meantime,a venous thromboembolism was removed and leg and pedal edema were alleviated.One mutation c.10102G>A/p.D3368N in the PKD1 gene was identified.CONCLUSION Tolvaptan combined with edoxaban administration could delay kidney function decline and eliminate the edema caused by the thromboembolism.
文摘Aims:No solid evidence-based opinion was raised regarding predictors of the degree of ascites reduction with tolvaptan.This retrospective cohort study aimed to examine whether serum copeptin concentration is a useful predictor of this.Methods:The study population consisted of 80 patients with liver cirrhosis treated with tolvaptan for hepatic ascites effusions at Nara Medical University Hospital from May 2014 to December 2018.Forty-three patients who lost>1.5 kg of body weight in the first week after starting tolvaptan were classified as good responders and the remaining 37 as poor responders.Various laboratory parameters were measured immediately before the start of tolvaptan therapy to examine factors associated with predicting its efficacy.Results:In the univariate analysis,no significant differences with respect to age(67.6 vs.69.8 years,p>0.05),sex,body mass index(24.8 vs.23.7 kg/m^(2),p>0.05),Child-Pugh score(9.4 vs.9.7,p>0.05),and Model for End-stage Liver Disease score(11 vs.12,p>0.05)were found between the two groups.Conversely,aspartate transferase and alanine transaminase(ALT)levels were significantly lower in the good response group(52.9±56.3 vs.68.8±50.7 U/L,p<0.05;26.2±30.6 vs.40.5±33.5 U/L,p<0.01),whereas serum copeptin and serum sodium concentrations were significantly higher(57.1±15.0 vs.45.8±16.0 pg/mL,p<0.01;136.3±3.4 vs.133.8±5.8 mEq/L,p<0.05).In the multivariate analysis,serum copeptin concentration and ALT were statistically significant factors(p<0.01,p<0.05).Regression analysis of the association between the tolvaptan efficacy for refractory ascites and pretreatment serum copeptin concentration showed that a copeptin concentration cutoff of 45.9 pg/mL could predict treatment efficacy with a sensitivity,specificity,and area under the curve of 76.7%,59.5%,and 0.71%,respectively.Conclusion:Serum copeptin concentration may be a predictor of tolvaptan efficacy for refractory ascites effusion in Japanese patients with liver cirrhosis.
基金the State Key Program of National Natural Science Foundation of China(81530014)National Key R&D Plan of China(2017YFC1700502)National Natural Science Foundation for Young Scientists of China(81700366).
文摘Objective:The aim of this study was to investigate the efficacy and safety of tolvaptan,as well as the impact of its treatment dose and duration in heart failure patients with congestive signs.Methods:The PubMed,Embase,Cochrane Library,and ClinicalTrials.gov databases were searched to collect data from all randomized controlled trials(RCT)examining the efficacy and safety of tolvaptan in heart failure patients with congestive signs compared with placebo or blank control until March 4,2021.Urine volume,change in body weight,improvement in dyspnea,and reduction of edema were evaluated as efficacy indicators.All-cause mortality,worsening heart failure,and adverse events were considered safety indicators.The quality of eligible publications was assessed using the Cochrane risk of bias for RCTs.Results:Ten RCTs with 5,980 patients were included in this analysis.Compared with control,tolvaptan significantly reduced weight in the short term(day 1,7 RCTs,weighted mean difference(WMD):-1.09,95%confidence interval(CI):-1.27 to-0.91;day 2,2 RCTs,WMD:-1.67,95%CI:-3.00 to-0.33;day 7,4 RCTs,WMD:-0.95,95%CI:-1.25 to-0.66),increased urine volume(WMD:1,825.72,95%CI:1,438.38-2,213.07),and relieved dyspnea(risk ratio(RR):1.12,95%CI:1.05-1.19)without increasing the mortality rate(RR:0.96,95%CI:0.87-1.06).Furthermore,the weight loss and increase in urine volume were not dose-dependent effects,and prolonged medication did not lead to sustained weight loss.In addition,there seemed to be more adverse events(RR:1.17,95%CI:1.03-1.32)after treatment with tolvaptan.Further analysis revealed that patients treated with tolvaptan were more likely to report thirst(RR:6.09,95%CI:3.37-11.00)and dry mouth(RR:6.36,95%CI:4.09-9.90),as well as develop hypernatremia(RR:12.76,95%CI:3.52-46.32).Conclusions:The meta-analysis shows that tolvaptan can improve congestion with no increase in mortality rate,but should be used to guard against adverse events.Deserve to be mentioned,the number of RCTs included was limited,suggesting that the observed results should be interpreted with caution.Additional robust clinical studies are warranted to validate the present findings.
