Predictors of tolvaptan short‐term response in patients with refractory ascites: A meta‐analysis

Abstract

Background and Aim Tolvaptan represents an oral V2‐receptor antagonist, which has been suggested as a promising add‐on diuretic treatment for refractory ascites. The present meta‐analysis aims to accumulate current evidence and identify which clinical and laboratory factors are linked to short‐term response to tolvaptan therapy. Methods Medline, Scopus, Cochrane Central Register of Controlled Trials, http://Clinicaltrials.gov, and Google Scholar databases were searched from inception. All observational studies reporting the correlation of patients' characteristics with tolvaptan response were selected. Results Tolvaptan response was associated with significantly higher baseline body weight (mean difference: 4.59 kg, 95% confidence interval [CI]: [3.58, 5.61]), presence of hepatitis C (odds ratio: 1.59 95% CI: [1.18, 2.14]), lower blood urea nitrogen (BUN) (mean difference: −6.88 mg/dL, 95% CI: [−8.13, −5.63]), lower serum creatinine (mean difference: −0.17 mg/dL, 95% CI: [−0.30, −0.05]), lower C‐reactive protein (mean difference: −1.43 mg/dL, 95% CI: [−2.52, −0.35]), and higher sodium levels (mean difference: 1.00 mEq/L, 95% CI: [0.45, 1.55]). The outcomes of bodyweight, hepatitis C, BUN, and C‐reactive protein remain significant independently of response definition and risk of bias. Conclusions The present findings suggest bodyweight, BUN, C‐reactive protein, and hepatitis C as potential predictive factors of tolvaptan short‐term response in patients with refractory ascites. Future studies are needed to introduce cut‐off values and construct an optimal combined screening model.

The efficacy of serum copeptin and zinc-alpha2-glycoprotein for predictors of tolvaptan treatment in decompensated cirrhotic patients

“…In addition, we indicated that serum BUN, copeptin and ZAG levels were independent predictors of the overall response to tolvaptan therapy. We further showed that serum creatinine and cystatin C levels were not predictive of patient response to tolvaptan, thus con rming the ndings reported by others 14,15 . In LC, arteriolar vasodilation causes under lling of the systemic arterial vascular space, and the decrease in the effective blood volume leads to a decrease in arterial pressure 21 .…”

“…Indeed, in this study, ZAG correlated with body weight, BMI and CRP. Bellos also reported that body weight loss and elevated CRP were the predictors for Non-responders to tolvaptan 15 . We assumed that association of serum ZAG with multiple factors including renal function, cachexia (relating to body weight and BMI) and/or in ammation (relating to CRP) led to the result.…”

“…Tolvaptan is a novel, nonpeptide, orally administered, selective vasopressin V 2 -receptor antagonist that downregulates the expression of aquaporin-2 in the renal collecting duct. Current research has uncovered a promising role for tolvaptan as an add-on treatment in patients with hepatic ascites resistant to furosemide and/or spironolactone, as it is able to decrease body weight and alleviate edema 14,15 . However, the effect of tolvaptan is highly variable among patients with approximately one half of the patient cohort responding to the drug 14 .…”

“…However, the effect of tolvaptan is highly variable among patients with approximately one half of the patient cohort responding to the drug 14 . Blood urea nitrogen (BUN) 14 and C-reactive protein (CRP) 15 are recognized for differentiating diagnoses between Responders and Non-responders for tolvaptan, but these factors are insu cient, thus additional biomarkers are needed. Recently, in addition to the aforementioned studies, several studies have also reported Responders to tolvaptan led to improvement of long-term survival rates in cirrhotic patients with ascites 16,17 .…”

Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis

“…Finally, since hepatotoxicity represents the main concern about the wide use of tolvap- tan in cirrhotic patients [39], it is important to develop accurate screening tests that would identify tolvaptan nonresponders, in order to limit its unnecessary administration. More specifically, it has been shown that tolvaptan response may be associated with body weight, blood urea nitrogen, serum creatinine, C-reactive protein, and serum sodium levels, while no predictive value has been estimat-ed for patients' age, gender, MELD-Na score, or presence of hepatocellular carcinoma [40]. In addition, similarly to prediction of hepatorenal treatment response [41], urinary sodium has been proposed as a promising marker of tolvaptan response [35], although limited evidence is currently available to draw safe conclusions about its exact role.…”