Management of Cirrhosis and Ascites
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《新英格兰医药杂志》
To the Editor: In their review article, Ginès et al. (April 15 issue)1 state that in patients with large-volume ascites, the "serum creatinine concentration is normal or only moderately higher than normal, indicating that the glomerular filtration rate is normal or only moderately reduced." We disagree with this statement because the serum creatinine concentration overestimates the glomerular filtration rate in patients with cirrhosis and has a much lower sensitivity (18.5 percent) than the creatinine clearance (sensitivity, 74.0 percent) or the inulin clearance for the detection of renal failure.2
Over a three-year period at our institution, 8 of 43 patients (19 percent) with large-volume ascites and a normal serum creatinine concentration (up to 120 μmol per liter) who were awaiting liver transplantation had a creatinine clearance of less than 40 ml per minute, whereas 12 of 51 patients (24 percent) with a "moderately higher" serum creatinine concentration (up to 130 μmol per liter) had a creatinine clearance of less than 40 ml per minute. We recommend measurement of creatinine clearance in patients with large-volume ascites, despite a normal serum creatinine concentration, to identify those at high risk for deterioration in renal function due to the complications of cirrhosis and associated interventions.
James P. O'Beirne, M.B., B.S.
Matthew R. Foxton, M.B., B.S.
Michael A. Heneghan, M.D.
King's College Hospital
London SE5 9RS, United Kingdom
drobeirne@aol.com
References
Ginès P, Cárdenas A, Arroyo V, Rodés J. Management of cirrhosis and ascites. N Engl J Med 2004;350:1646-1654.
Caregaro L, Menon F, Angeli P, et al. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med 1994;154:201-205.
To the Editor: Ginès and colleagues recommend propranolol or nadolol for the prevention of bleeding due to gastroesophageal varices. A study of primary prevention of variceal bleeding with a combination of isosorbide mononitrate plus propranolol, as compared with monotherapy with propranolol, has shown that combination therapy has a significant advantage over monotherapy.1 Furthermore, in patients with Child–Pugh class A or B cirrhosis, treatment with isosorbide mononitrate plus nadolol resulted in a 50 percent greater reduction in the incidence of variceal bleeding than that observed with nadolol monotherapy.2
In short, pharmacotherapy with a beta-blocker and isosorbide mononitrate is effective for the primary prevention of variceal bleeding in patients with cirrhosis. Pharmacotherapy for the prevention of recurrent variceal bleeding remains controversial, especially in patients with advanced cirrhosis, in whom nonpharmacologic methods may be preferable.3
M. Emmanuel Bhaskar, M.D.
Meenakshi Medical College and Research Institute
Kancheepuram 631552, India
drmeb1974@yahoo.co.in
References
Garcia-Pagan JC, Feu F, Bosch J, Rodés J. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991;114:869-873.
Merkel C, Marin R, Sacerdoti D, et al. Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000;31:324-329.
Sharara AI, Rockey DC. Gastroesophageal variceal hemorrhage. N Engl J Med 2001;345:669-681.
The authors reply: In our review article, patients with ascites were divided, for practical purposes, into three groups: those with moderate-volume ascites, those with large-volume ascites, and those with refractory ascites. Although patients with refractory ascites usually have large-volume ascites, they were considered a separate group because the management of refractory ascites differs from that of ascites that responds to diuretic therapy. Therefore, our comment on the serum creatinine concentration and the glomerular filtration rate in patients with large-volume ascites, alluded to by Dr. O'Beirne and colleagues, refers only to patients with large-volume ascites who do not have refractory ascites. We agree with Dr. O'Beirne and colleagues that the serum creatinine concentration overestimates the glomerular filtration rate in patients with cirrhosis and ascites. Nevertheless, when the glomerular filtration rate is measured by means of a sensitive technique (i.e., measurement of inulin clearance), most of the patients with cirrhosis and large-volume ascites who do not have refractory ascites have either a normal or a moderately reduced glomerular filtration rate.1 A severe reduction in the glomerular filtration rate in the setting of a completely normal serum creatinine concentration in a patient with cirrhosis and ascites is very uncommon.2 The creatinine clearance may have greater sensitivity than the serum creatinine concentration in the assessment of the glomerular filtration rate, but it relies on a very accurate urine collection, which is not always possible to obtain.
As Dr. Bhaskar states, propranolol in combination with isosorbide mononitrate causes a greater reduction in portal pressure than does propranolol alone in patients with cirrhosis who have portal hypertension.3 However, the results are controversial with respect to the efficacy of this combination therapy as compared with that of beta-blockers alone in the prevention of a first episode of variceal bleeding. Merkel et al. showed that the combination of nadolol and isosorbide mononitrate was more effective than nadolol alone in the prevention of a first episode of variceal bleeding.4 However, a more recent study involving a larger series of patients showed that the efficacy of propranolol plus isosorbide mononitrate was similar to that of propranolol alone in the prevention of a first episode of variceal bleeding.5 Therefore, whether isosorbide mononitrate improves the efficacy of beta-blockers for the prevention of a first episode of variceal bleeding in patients with cirrhosis remains to be proved.
Pere Ginès, M.D.
Hospital Clinic
08036 Barcelona, Spain
gines@medicina.ub.es
Andrés Cárdenas, M.D.
Beth Israel Deaconess Medical Center
Boston, MA 02215
Vicente Arroyo
Hospital Clinic
08036 Barcelona, Spain
References
Ginès P, Fernandez-Esparrach G, Arroyo V, Rodés J. Pathogenesis of ascites in cirrhosis. Semin Liver Dis 1997;17:175-189.
Ginès P, Arroyo V, Rodés J. Disorders of renal function in cirrhosis: pathophysiology and clinical aspects. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease. 3rd ed. Philadelphia: W.B. Saunders, 1996:650-75.
Garcia-Pagan JC, Feu F, Bosch J, Rodés J. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991;114:869-873.
Merkel C, Marin R, Sacerdoti D, et al. Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000;31:324-329.
Garcia-Pagan JC, Morillas R, Banares R, et al. Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT. Hepatology 2003;37:1260-1266.
Over a three-year period at our institution, 8 of 43 patients (19 percent) with large-volume ascites and a normal serum creatinine concentration (up to 120 μmol per liter) who were awaiting liver transplantation had a creatinine clearance of less than 40 ml per minute, whereas 12 of 51 patients (24 percent) with a "moderately higher" serum creatinine concentration (up to 130 μmol per liter) had a creatinine clearance of less than 40 ml per minute. We recommend measurement of creatinine clearance in patients with large-volume ascites, despite a normal serum creatinine concentration, to identify those at high risk for deterioration in renal function due to the complications of cirrhosis and associated interventions.
James P. O'Beirne, M.B., B.S.
Matthew R. Foxton, M.B., B.S.
Michael A. Heneghan, M.D.
King's College Hospital
London SE5 9RS, United Kingdom
drobeirne@aol.com
References
Ginès P, Cárdenas A, Arroyo V, Rodés J. Management of cirrhosis and ascites. N Engl J Med 2004;350:1646-1654.
Caregaro L, Menon F, Angeli P, et al. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med 1994;154:201-205.
To the Editor: Ginès and colleagues recommend propranolol or nadolol for the prevention of bleeding due to gastroesophageal varices. A study of primary prevention of variceal bleeding with a combination of isosorbide mononitrate plus propranolol, as compared with monotherapy with propranolol, has shown that combination therapy has a significant advantage over monotherapy.1 Furthermore, in patients with Child–Pugh class A or B cirrhosis, treatment with isosorbide mononitrate plus nadolol resulted in a 50 percent greater reduction in the incidence of variceal bleeding than that observed with nadolol monotherapy.2
In short, pharmacotherapy with a beta-blocker and isosorbide mononitrate is effective for the primary prevention of variceal bleeding in patients with cirrhosis. Pharmacotherapy for the prevention of recurrent variceal bleeding remains controversial, especially in patients with advanced cirrhosis, in whom nonpharmacologic methods may be preferable.3
M. Emmanuel Bhaskar, M.D.
Meenakshi Medical College and Research Institute
Kancheepuram 631552, India
drmeb1974@yahoo.co.in
References
Garcia-Pagan JC, Feu F, Bosch J, Rodés J. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991;114:869-873.
Merkel C, Marin R, Sacerdoti D, et al. Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000;31:324-329.
Sharara AI, Rockey DC. Gastroesophageal variceal hemorrhage. N Engl J Med 2001;345:669-681.
The authors reply: In our review article, patients with ascites were divided, for practical purposes, into three groups: those with moderate-volume ascites, those with large-volume ascites, and those with refractory ascites. Although patients with refractory ascites usually have large-volume ascites, they were considered a separate group because the management of refractory ascites differs from that of ascites that responds to diuretic therapy. Therefore, our comment on the serum creatinine concentration and the glomerular filtration rate in patients with large-volume ascites, alluded to by Dr. O'Beirne and colleagues, refers only to patients with large-volume ascites who do not have refractory ascites. We agree with Dr. O'Beirne and colleagues that the serum creatinine concentration overestimates the glomerular filtration rate in patients with cirrhosis and ascites. Nevertheless, when the glomerular filtration rate is measured by means of a sensitive technique (i.e., measurement of inulin clearance), most of the patients with cirrhosis and large-volume ascites who do not have refractory ascites have either a normal or a moderately reduced glomerular filtration rate.1 A severe reduction in the glomerular filtration rate in the setting of a completely normal serum creatinine concentration in a patient with cirrhosis and ascites is very uncommon.2 The creatinine clearance may have greater sensitivity than the serum creatinine concentration in the assessment of the glomerular filtration rate, but it relies on a very accurate urine collection, which is not always possible to obtain.
As Dr. Bhaskar states, propranolol in combination with isosorbide mononitrate causes a greater reduction in portal pressure than does propranolol alone in patients with cirrhosis who have portal hypertension.3 However, the results are controversial with respect to the efficacy of this combination therapy as compared with that of beta-blockers alone in the prevention of a first episode of variceal bleeding. Merkel et al. showed that the combination of nadolol and isosorbide mononitrate was more effective than nadolol alone in the prevention of a first episode of variceal bleeding.4 However, a more recent study involving a larger series of patients showed that the efficacy of propranolol plus isosorbide mononitrate was similar to that of propranolol alone in the prevention of a first episode of variceal bleeding.5 Therefore, whether isosorbide mononitrate improves the efficacy of beta-blockers for the prevention of a first episode of variceal bleeding in patients with cirrhosis remains to be proved.
Pere Ginès, M.D.
Hospital Clinic
08036 Barcelona, Spain
gines@medicina.ub.es
Andrés Cárdenas, M.D.
Beth Israel Deaconess Medical Center
Boston, MA 02215
Vicente Arroyo
Hospital Clinic
08036 Barcelona, Spain
References
Ginès P, Fernandez-Esparrach G, Arroyo V, Rodés J. Pathogenesis of ascites in cirrhosis. Semin Liver Dis 1997;17:175-189.
Ginès P, Arroyo V, Rodés J. Disorders of renal function in cirrhosis: pathophysiology and clinical aspects. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease. 3rd ed. Philadelphia: W.B. Saunders, 1996:650-75.
Garcia-Pagan JC, Feu F, Bosch J, Rodés J. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991;114:869-873.
Merkel C, Marin R, Sacerdoti D, et al. Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000;31:324-329.
Garcia-Pagan JC, Morillas R, Banares R, et al. Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT. Hepatology 2003;37:1260-1266.