Terlipressin versus noradrenaline in the treatment of hepatorenal syndrome: systematic review with meta-analysis and full economic evaluation.

OBJECTIVE: The aim of this study was to compare the efficacy and costs of terlipressin and noradrenaline for the treatment of hepatorenal syndrome from the perspective of the Brazilian public health system and that of a major private health insurance. METHODS: Comparison of efficacy was performed through a systematic review with a meta-analysis of randomized-controlled trials using a random-effects model. Economic evaluation was carried out through cost minimization. RESULTS: Four studies (154 patients) were included in the meta-analysis. There was no evidence of a difference between treatments with terlipressin or noradrenaline in terms of 30-day survival (risk ratio=1.04, 95% confidence interval=0.84-1.30, P=0.70). From the perspective of the public health system, costs of the treatments with terlipressin or noradrenaline were Int$7437.04 and Int$8406.41, respectively. From the perspective of the private health insurance, costs of treatments with terlipressin and noradrenaline were Int$13,484.57 and Int$15,061.01, respectively. CONCLUSION: There was no evidence of superiority between treatment strategies using terlipressin or noradrenaline in terms of the survival of patients with hepatorenal syndrome, but the strategy using terlipressin was more economical under two different perspectives.

Noradrenaline or terlipressin for hepatorenal syndrome?

Hepatorenal syndrome is a condition associated with very high mortality that may be reverted in some cases with vasoconstrictors. Terlipressin has generally been considered standard treatment, but noradrenaline has been postulated as alternative. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including four pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded noradrenaline and terlipressin probably have similar effects on reverting hepatorrenal syndrome and decreasing mortality, but noradrenaline is associated with less adverse effects, and has lower costs.

El síndrome hepatorrenal es una condición asociada a altísima mortalidad, que puede ser recuperada en ciertos casos con el uso de vasoconstrictores. Generalmente se considera que terlipresina es el tratamiento estándar, pero noradrenalina se ha planteado como una alternativa. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen cuatro estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que noradrenalina y terlipresina son probablemente igual de efectivas en lograr mejoría del síndrome hepatorrenal y disminuir la mortalidad, pero que noradrenalina se asocia a menos efectos adversos, y tiene un menor costo.

Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study.

BACKGROUND/AIMS: Treatment of hepatorenal syndrome (HRS) is based on vasoconstrictors. Terlipressin is the one with the soundest evidence. Noradrenalin has been suggested as an effective alternative. The current study was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in patients with HRS. METHODS: Twenty-two consecutive cirrhotic patients with HRS (9 with HRS type 1; 13 with HRS type 2) were included. Patients were randomly assigned to be treated with noradrenalin (0.1-0.7 microg/kg/min) and albumin (10 patients) or with terlipressin (1-2 mg/4h) and albumin (12 patients). Treatment was administered until HRS reversal or for a maximum of two weeks. Patients were followed-up until liver transplantation or death. RESULTS: Reversal of HRS was observed in 7 of the 10 patients (70%) treated with noradrenalin and in 10 of the 12 patients (83%) treated with terlipressin, p=ns. Treatment led in both groups to a significant improvement in renal and circulatory function. No patient developed signs of myocardial ischemia. CONCLUSIONS: Data from this unblinded, pilot study suggest that noradrenalin is as effective and safe as terlipressin in patients with HRS. These results would support the use of noradrenalin, a cheap and widely available drug, in the management of these patients.

Transjugular intrahepatic portosystemic shunt in the management of ascites and hepatorenal syndrome.

Ascites is the most common complication of liver cirrhosis and when it develops mortality is 50% at 5 years, apart from liver transplantation. Large volume paracentesis has been the only option for ascites refractory to medical treatment. The role of transjugular intrahepatic portosystemic shunt in the management of diuretic-resistant ascites has been evaluated in many cohort studies and five randomized trials up to now, clearly showing improvement in natriuresis and clinical efficacy. It, however, remains unclear how transjugular intrahepatic portosystemic shunt affects survival and quality of life, because hospital admissions owing to worsening encephalopathy may counterbalance the reduced need of paracentesis. What is clear is that the patient selection is critical. About 30% of patients with ascites develop hepatorenal syndrome at 5 years, leading to high mortality in its severe and progressive form. As its main pathogenetic factor is derangement of circulatory function owing to portal hypertension, these patients may benefit from transjugular intrahepatic portosystemic shunt, but this has been shown only in small series, in which mortality remains very high, owing to the underlying poor liver function.

Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost.

BACKGROUND: Intravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis. AIMS: To compare an intravenous-oral step-down schedule with ciprofloxacin (switch therapy) to intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis, and to evaluate the impact of terlipressin and albumin in the treatment of type 1 hepatorenal syndrome on mortality. METHODS: A total of 116 cirrhotic patients with spontaneous bacterial peritonitis, were randomly given switch therapy with ciprofloxacin (61 patients) or intravenous ceftazidime (55 patients). All patients who developed type 1 hepatorenal syndrome were treated with terlipressin (2-12 mg/day) and albumin (20-40 g/day). RESULTS: Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%. CONCLUSIONS: Switch therapy with cephalosporin is more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in cirrhotic patients who are not on prophylaxis with quinolones.

Urinary sodium levels related to jaundice duration in the assessment of postoperative risk of hepatorenal syndrome in elderly patients undergoing surgery for biliary obstruction.

The early diagnosis of hepatorenal syndrome (HRS) is based chiefly on biochemical alterations and in particular, the relationship between urinary sodium levels and duration of jaundice seems to offer the most reliable prognostic index. Urinary sodium levels were determined in 32 elderly patients, who underwent surgery for benign or malignant biliary obstruction, without, major organ resection; in this group 4 patients died of HRS (12.5 per cent). The diagnostic accuracy of the method reached 97 per cent.