Masanori Atsukawa1, Akihito Tsubota2, Koichi Takaguchi3, Hidenori Toyoda4, Motoh Iwasa5, Tadashi Ikegami6, Makoto Chuma7, Akito Nozaki7, Haruki Uojima8, Atsushi Hiraoka9, Shinya Fukunishi10, Keisuke Yokohama10, Toshifumi Tada4, Keizo Kato11, Hiroshi Abe11, Joji Tani12, Hironao Okubo13, Tsunamasa Watanabe14, Nobuhiro Hattori14, Akemi Tsutsui3, Tomonori Senoh3, Yuji Yoshida15, Tomomi Okubo15, Norio Itokawa15, Ai Nakagawa-Iwashita1, Chisa Kondo1, Taeang Arai1, Kojiro Michitaka9, Etsuko Iio16, Takashi Kumada4, Yasushito Tanaka16, Yoshiyuki Takei5, Katsuhiko Iwakiri1. 1. Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. 2. Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan. 3. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 4. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. 5. Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie, Japan. 6. Tokyo Medical University Ibaraki Medical Center, Inashiki, Ibaraki, Japan. 7. Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan. 8. Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. 9. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 10. Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan. 11. Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan. 12. Department of Internal Medicine, Yashima General Hospital, Takamatsu, Japan. 13. Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan. 14. Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. 15. Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan. 16. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Abstract
BACKGROUND AND AIM: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS: Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.
BACKGROUND AND AIM: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS:Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.