Hepatorenal Syndrome ; drug therapy ; Humans ; Vasoconstrictor Agents ; therapeutic use

Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis related complications has been recognized during recent years. This paper aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis related complications. Hepatobiliary Study Group of Chinese Society of Gastroenterology of Chinese Medical Association and Hepatology Committee of Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Overall, 10 major statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis related complications.
Electrolytes ; Esophageal and Gastric Varices/drug therapy* ; Gastrointestinal Hemorrhage/etiology* ; Hepatorenal Syndrome/etiology* ; Humans ; Liver Cirrhosis/drug therapy* ; Lypressin/adverse effects* ; Terlipressin/adverse effects* ; Vasoconstrictor Agents/adverse effects*

OBJECTIVETo perform an analysis and comparative study of the clinical data for patients with cirrhosis and type 1 hepatorenal syndrome (HRS) who received treatment with terlipressin using high-or low-dose regimens.

METHODSA total of 56 patients with cirrhosis and type 1 HRS who presented for treatment to the Wuhan Medical Treatment Center and Taizhou Central Hospital between March 2010 and October 2012 were enrolled in the study. The patients were randomly assigned to the terlipressin treatment groups for receipt of the high-dose regimen (1 mg/6-8 h;n =27) or low-dose regimen (1 mg/12 h;n =29). All patients were assessed for 24-hour urine volume, serum blood urea nitrogen (BUN) and creatinine (Cr) levels, therapeutic effect and prognosis, and adverse reactions. Measurements were made before and after the treatment, and on post-treatment days 3, 7 and 14. Inter-group differences were assessed by statistical analyses.

RESULTSThe high-dose group showed an increase in 24-hour urine volumes from post-treatment day 3 (1112 ± 262 ml) to day 7 (1938 ± 312 ml), and the volumes on both days were significantly better than those of the low-dose group (day 3:986 ± 162 ml and day 7:1760 ± 300 ml, t =1.500, 1.830, P=0.038, 0.041). The high-dose group also showed a significantly better decreases in serum BUN levels (35.1 ± 8.6 to 30.2 ± 6.3 mmol/L vs.low-dose group: 43.2 ± 10.9 to 35.1 ± 7.6 mmol/L, t =3.200, 5.901, P =0.043, 0.047) and in serum Cr values (219.0 ± 35.1 to 128.2 ± 41.6 vs.low-dose group: 230.3 ± 82.1 to 151.5 ± 38.7, t =2.997, 5.765, P =0.036, 0.046).On post-treatment day 14 the 24-hour urine volume of patients in the high-dose group decreased (to 720+/-136 ml), but the difference from that of the low-dose group was not significant (vs. 620 ± 164 ml, t =1.855, P =0.069). The serum BUN level increased in the high-dose group (to 54.4 ± 15.0 mmol/L), which was statistically different from that in the low-dose group (vs .57.7 ± 17.3 mmol/L, t=5.166, P =0.022); the same trend was seen for the serum Cr value (397.8 ± 127.4 mumol/L vs. 480.3 ± 179.8 mumol/L, t =5.638, P =0.047). No statistically significant differences were observed for the groups in regard to significant efficiency, efficiency or 2-week survival rate (x2 =2.314, 1.767, 0.678, P =0.128, 0.128, 0.410 respectively), but the total efficiency was significantly different between the two groups (x² =5.793, P =0.016). In addition, no serious adverse reactions (including precordial pain, myocardial infarction or intestinal necrosis) were observed in either group.

CONCLUSIONTerlipressin therapy at both high and low dosages can lead to significant beneficial effects within as little as 3 days after the treatment; however, the high-dose appears to produce a better lasting efficacy (at day 14 after the treatment). The difference in doses does not appear to markedly affect significant efficiency, efficiency, nor the 2-week survival rate.

Adolescent ; Adult ; Aged ; Dose-Response Relationship, Drug ; Female ; Hepatorenal Syndrome ; drug therapy ; etiology ; Humans ; Liver Cirrhosis ; complications ; drug therapy ; Lypressin ; administration & dosage ; analogs & derivatives ; therapeutic use ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Ascites, hepatic encephalopathy and variceal hemorrhage are three major complications of portal hypertension. The diagnostic evaluation of ascites involves an assessment of its etiology by determining the serum-ascites albumin gradient and the exclusion of spontaneous bacterial peritonitis. Ascites is primarily related to an inability to excrete an adequate amount of sodium into urine, leading to a positive sodium balance. Sodium restriction and diuretic therapy are keys of ascites control. But, with the case of refractory ascites, large volume paracentesis and transjugular portosystemic shunts are required. In hepatorenal syndrome, splanchnic vasodilatation with reduction in effective arterial volume causes intense renal vasoconstriction. Splanchnic and/or peripheral vasoconstrictors with albumin infusion, and renal replacement therapy are only bridging therapy. Liver transplantation is the only definitive modality of improving the long term prognosis.
Anti-Bacterial Agents/therapeutic use ; Ascites/complications/*diagnosis/therapy ; Bacterial Infections/*diagnosis ; Hepatic Encephalopathy/complications ; Hepatorenal Syndrome/complications/*diagnosis/therapy ; Humans ; Hypertension, Portal/*complications ; Liver Transplantation ; Peritonitis/*diagnosis/drug therapy/etiology ; Serum Albumin/administration & dosage

No abstract available.
Adult ; Hepatitis C/diagnosis ; Hepatorenal Syndrome/*diagnosis/drug therapy/surgery ; Humans ; Liver Cirrhosis/*diagnosis ; Lypressin/analogs & derivatives/therapeutic use ; Male ; Portasystemic Shunt, Transjugular Intrahepatic ; Stomach Neoplasms/*surgery ; Tomography, X-Ray Computed ; Vasoconstrictor Agents/therapeutic use

Hepatorenal syndrome is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin is a nonselective V1 vasopressin agonist. When comparing with ornipressin, it is known to have a similar vasoconstricting potency, but much less ischemic complication. We report a case of gangrene on toes and necrosis on the infusion site of left hand which developed after the use of terlipressin due to hepatorenal syndrome in a 41-year-old-man with liver cirrhosis. Ischemic complication of terlipressin is rare and there has been no case report in Korea. Although it is rare, we must pay attention to the peripheral ischemic complication of terlipressin.
Adult ; Hand/*blood supply ; Hepatorenal Syndrome/drug therapy ; Humans ; Ischemia/*chemically induced ; Lysine Vasopressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Toes/*blood supply ; Vasoconstrictor Agents/*adverse effects/therapeutic use

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.
Bilirubin/blood ; Creatinine/blood ; Electrocardiography ; Fatal Outcome ; Hepatorenal Syndrome/*drug therapy ; Humans ; Intestinal Mucosa/pathology ; Intestines/surgery ; Liver Cirrhosis/diagnosis/therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Necrosis/*chemically induced/surgery ; Tomography, X-Ray Computed ; Vasoconstrictor Agents/*adverse effects/*therapeutic use