Method of treating patients with hepatorenal syndrome type 1

Abstract

The principles and embodiments of the present disclosure relate to methods for using terlipressin to treat a patient having impaired renal function associated with liver disease. A patient identified as suffering from HRS-1 is tested to determine if the patient meets at least two out of three criteria, wherein the three criteria include a WBC<4 or >12 cells/4; HR>90 bpm; and any one of HCO3<21 mmol/L or PaCO2<32 mmHg or >20 breaths per minute. If the patient meets at least two of the criteria, he or she is administered terlipressin in an amount effective to produce a reduction in serum creatinine of at least 1.0 mg/dL.

What is claimed is: 
     
         1 . A method for treating HRS-1, the method comprising:
 diagnosing a plurality of patients as having HRS-1;   determining that a first and a second patient of the plurality do not have overt sepsis, septic shock, or uncontrolled infection;   testing the first and second patients to determine whether each meets each of the following three criteria (i)-(iii):
 (i) a white blood cell count either less than 4,000 cells/mm 3  or greater than 12,000 cells/mm 3 , 
 (ii) a heart rate of greater than 90 beats per minute, and 
 (iii) either (a) a partial pressure of carbon dioxide in the blood (PaCO 2 ) of <32 mmHg or (b) a blood bicarbonate (HCO 3 ) level of <23 mmol/L or (c) tachypnea with more than 20 breaths per minute; 
   determining that the first patient meets at least two of the three criteria;   determining that, because the first patient meets at least two of the three criteria, the first patient's renal function is more likely to improve upon treatment with terlipressin than if the first patient exhibited only one or none of the three criteria;   initiating administration of terlipressin to the first patient within two days of the determination that the first patient meets at least two of the three criteria, wherein the terlipressin is administered as an IV in an amount effective to reduce the first patient's serum creatinine level by at least 1.0 mg/dL;   determining that the second patient meets only one or none of the three criteria;   determining that, because the second patient does not meet at least two of the three criteria, the second patient's renal function is less likely to respond to treatment with terlipressin than if the second patient exhibited at least two of the three criteria; and   excluding the second patient from treatment with terlipressin.   
     
     
         2 . The method of  claim 1 , wherein a treatment other than terlipressin is administered to the second patient. 
     
     
         3 . The method of  claim 2 , wherein the second patient is treated with one or more of nor-epinephrine, vasopressin, or a combination of midodrine and octreotide. 
     
     
         4 . The method of  claim 2 , wherein the second patient is given a transjugular intrahepatic portosystemic shunt. 
     
     
         5 . The method of  claim 2 , wherein the second patient is treated with kidney dialysis. 
     
     
         6 . The method of  claim 1 , wherein criterion (iii) is a HCO 3  level<23 mmol/L. 
     
     
         7 . The method of  claim 1 , wherein criterion (iii) is a HCO 3  level<21 mmol/L. 
     
     
         8 . The method of  claim 1 , wherein the first patient is administered terlipressin as an IV every 4 to 6 hours for 4 days. 
     
     
         9 . A method of identifying a subset of HRS-1 patients with an increased likelihood of responding to treatment with terlipressin compared to other HRS-1 patients, the method comprising:
 identifying a plurality of patients who have type 1 hepatorenal syndrome and who do not have overt sepsis, septic shock, or uncontrolled infection;   for each patient of the plurality, measuring at least two of the following three variables (a)-(c):
 variable (a): white blood cell count; 
 variable (b): number of heart beats per minute; 
 variable (c): either blood HCO 3  level or PaCO 2  level or breaths per minute; 
   within the plurality of patients, identifying a subset comprising one or more patients, all of whom meet at least two of the following three criteria (i)-(iii):
 (i) a white blood cell count either less than 4,000 cells/mm 3  or greater than 12,000 cells/mm 3 , 
 (ii) a heart rate of greater than 90 beats per minute, and 
 (iii) either HCO 3 <23 mmol/L or PaCO 2 <32 mmHg or >20 breaths per minute, wherein other patients of the plurality meet only one or none of the three criteria, so are not in the subset; and 
   determining that the one or more patients in the subset have an increased likelihood of responding to treatment with terlipressin compared to the other patients of the plurality who are not in the subset.   
     
     
         10 . The method of  claim 9 , comprising treating at least one patient of the subset with terlipressin; measuring the at least one patient's serum creatinine level after treatment has begun; and observing that the serum creatinine level in the blood of the at least one patient decreased upon treatment with terlipressin. 
     
     
         11 . The method of  claim 10 , comprising excluding from terlipressin treatment the patients of the plurality who meet only one or none of the three criteria, so are not in the subset. 
     
     
         12 . The method of  claim 9 , wherein criterion (iii) is a HCO 3  level<23 mmol/L. 
     
     
         13 . The method of  claim 9 , wherein criterion (iii) is a HCO 3  level<21 mmol/L. 
     
     
         14 . A method of distributing a pharmaceutical product, the method comprising:
 supplying terlipressin to a medical provider responsible for treating a patient suffering from type 1 hepatorenal syndrome;   providing a recommendation to the medical provider to treat a patient who (a) is suffering from type 1 hepatorenal syndrome, (b) does not have overt sepsis, septic shock, or uncontrolled infection, and (c) meets two or more of the following three criteria (i)-(iii):
 (i) a white blood cell count either less than 4,000 cells/mm 3  or greater than 12,000 cells/mm 3 , 
 (ii) a heart rate of greater than 90 beats per minute, and 
 (iii) either HCO 3 <23 mmol/L or PaCO 2 <32 mmHg or >20 breaths per minute, with terlipressin in an amount effective to reduce the patient's serum creatinine level. 
   
     
     
         15 . The method of  claim 14 , wherein criterion (iii) is a HCO 3  level<23 mmol/L. 
     
     
         16 . The method of  claim 14 , wherein criterion (iii) is a HCO 3  level<21 mmol/L.