Background & Aims-Hepatorenal syndrome (HRS) type 1 is a progressive functional renal failure in subjects with advanced liver disease. The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS.

In comparison with large-volume paracentesis, the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites.

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Background and aims: Diagnosis of moderately impaired renal function is of particular importance in patients with cirrhosis of the liver. Whereas patients with a markedly impaired glomerular filtration rate can be diagnosed easily by elevated serum creatinine concentrations, moderately reduced renal function may be missed by this conventional parameter. Recently, cystatin C has been suggested as a sensitive marker of renal function, independent of sex or muscle mass. Therefore, the aim of this study was to investigate the value of serum cystatin C concentration for the detection of moderately impaired renal function. Methods: Ninety seven inhospital patients with cirrhosis and a 24 hour creatinine clearance of at least 40 ml/min were investigated and divided into group 1 (creatinine clearance >70 ml/min; n=55) and group 2 (creatinine clearance 40-69 ml/min; n=42). Results: Serum cystatin C concentrations (mean (SD): 1.31 (0.51) v 1.04 (0.34) mg/l (p=0.008)) and creatinine concentrations (1.03 (0.52) v 0.86 (0.22) mg/100 ml (p=0.03)) were higher in group 2 than in group 1; there was no significant difference in urea concentrations. Receiver-operator characteristics (ROC) revealed a differential diagnostic advantage of cystatin C over creatinine and urea. At cut off concentrations of 1.0 mg/l, 0.9 mg/100 ml, and 28 mg/100 ml, respectively, cystatin C, creatinine, and urea exhibited 69%, 45%, and 44% sensitivity (p<0.05). As patients with a small muscle mass or reduced physical activity could be particularly prone to overestimation of their renal function, separate analyses were performed for the subgroups of female and Child-Pugh class C patients, respectively. In both groups, discrimination between patients with moderately impaired and normal renal function was best with cystatin C. In female patients, sensitivity of cystatin C (77.8%) was superior (p<0.05) to that of creatinine (38.9%) and urea (41.2%). In Child-Pugh C patients, the ROC curve was significantly better for cystatin C than for creatinine. Conclusions: Serum cystatin C determination could be a valuable tool in patients with cirrhosis, particularly with Child-Pugh class C or in female patients, for early diagnosis of moderately impaired renal function.

Hepatic arterial buffer response (HABR) is considered an important compensatory mechanism to maintain perfusion of the liver by hepatic arterial vasodilation on reduction of portal venous perfusion. HABR has been suggested to be impaired in patients with advanced cirrhosis. In patients with hepatopetal portal flow, placement of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal venous liver perfusion. Accordingly, patients with severe cirrhosis should have impaired HABR after TIPS implantation. Therefore, the aim of this study was to investigate the effect of TIPS on HABR as reflected by changes in resistance index ( H epatic arterial buffer response (HABR) is an intrinsic regulatory mechanism of the liver to maintain total hepatic blood flow when portal perfusion decreases. Increased hepatic arterial blood flow mediated by adenosine washout in the portal triad 1-3 and independent of hepatic oxygen supply or demand compensates for the reduced portal tributary blood flow (for review, see Lautt 4,5 ). This phenomenon has been shown under various experimental conditions such as endotoxinemia 6 or portal vein ligation 7 and in the clinical setting after liver transplantation. 8 Just recently, maintenance of HABR has been shown in an animal model of cirrhosis (namely, CCl 4 -induced cirrhosis in the rat). 9,10 Thus far, it is not clear whether HABR is preserved in patients with cirrhosis and whether it is dependent on the stage of liver disease. Several studies have shown an increased hepatic arterial resistance in patients with cirrhosis. This was related to the degree of portal hypertension, 11,12 portal resistance, 12,13 and Child-Pugh score, 12 respectively. In contrast to these observations, Kleber et al. 14 recently reported an increased hepatic arterial flow volume and decreased pulsatility index of the hepatic artery in Child-Pugh class C patients. In this study, intra-arterial infusion of adenosine induced an increase in hepatic arterial blood flow that was independent of Child-Pugh class, suggesting that HABR may be independent of the stage of liver disease.Hepatofugal portal venous blood flow has been reported in 2% to 15% of patients with cirrhosis. [15][16][17] According to the HABR hypothesis, this condition should be a strong stimulus for hepatic arterial vasodilation. Similarly, the transjugular intrahepatic portosystemic shunt (TIPS) procedure results in a decreased portal perfusion fraction of total liver blood flow. 18 Therefore, assuming an impaired HABR in patients with advanced cirrhosis, hepatic arterial blood flow should increase less and the decrease in resistance of the hepatic artery should be lower after the TIPS procedure than in patients with compensated cirrhosis.To test this hypothesis, we compared the hepatic arterial resistance index (RI) in cirrhotic patients with hepatopetal and hepatofugal portal venous blood flow. Furthermore, the effects of TIPS on RI were examined in both groups of patients using duplex Doppler ultrasonography. Patients and MethodsPatients. A...

Peripheral vasodilation is considered an important factor in the pathophysiology of the hepatorenal syndrome (HRS). Therefore, the aim of this study was to evaluate the therapeutic potential of the vasoconstrictor ornipressin plus dopamine in the treatment of the most severe form of HRS, namely HRS type 1. Seven cirrhotic patients (creatinine clearance 15 ؎ 1 mL/min, UNaV 7 ؎ 2 mmol/24 h) with HRS type 1 were included in the study after normalization of central venous pressure with intravenous albumin and low-dose dopamine had failed to prevent further deterioration of renal function. Ornipressin was given continuously (intravenous 6 IU/h) in combination with dopamine (2-3 g/kg/min) until creatinine clearance had increased to above 40 mL/min or adverse events prevented further treatment. HRS was reverted in 4 of 7 patients after 5 to 27 days (creatinine clearance 51 ؎ 4 mL/min, UNaV 47 ؎ 11 mmol/24 h) of treatment. Withdrawal was necessary in 1 patient after 15 days because of intestinal ischemia. Treatment failure was observed in 2 of 7 patients (creatinine clearance 19 ؎ 10 mL/min, UNaV 8 ؎ 3 mmol/24 h). Two of 4 responders had recidivant HRS 2 and 8 months after initial therapy, respectively. HRS in 1 of these patients was reverted with 18 days of ornipressin retreatment. The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia. Altogether, 3 of 7 patients survived HRS type 1, 1 after successful ornipressin therapy and liver transplantation, 1 with 2 successful courses of ornipressin, and 1 with liver transplantation after ornipressin treatment had failed. Thus, ornipressin plus dopamine can be a useful therapeutic option in patients with HRS type 1, especially as bridge to liver transplantation. (HEPATOLOGY 1999;30:870-875.)The hepatorenal syndrome (HRS) is a serious complication in patients with cirrhosis and ascites and associated with a poor prognosis. 1 It is characterized by a marked reduction of renal blood flow and glomerular filtration rate and a progressive increase in blood urea nitrogen and serum creatinine concentration in patients with markedly reduced liver function and ascites refractory to medical therapy. 2,3 Peripheral arterial vasodilation is thought to play an important role in the pathogenesis of HRS: By reducing the central blood volume peripheral vasodilation activates volume-and sodiumretaining neurohumoral systems, such as the renin-aldosterone system and the sympathetic nervous system. These mediators are responsible for renal vasoconstriction and avid sodium retention in advanced cirrhosis. 4,5 So far, liver transplantation is considered the only causal therapy for HRS. The outcome after transplantation, however, seems to be significantly impaired in patients with HRS compared with patients with normal renal function before liver transplantation. 6 Therefore, pharmacological interventions such as low-dose dopamine infusions have been recommended as a bridge to transplantation. 7 Despite improved renal perfusion in patients with HRS...

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The development of hepatorenal syndrome type 1 (HRS1) is associated with a poor prognosis. Liver transplantation improves this prognosis, but the degree of the improvement is unclear. Most patients receive vasoconstrictors such as terlipressin before transplantation, and this may affect the posttransplant outcomes. We examined a cohort of patients with access to liver transplantation from our previously published study of terlipressin plus albumin versus albumin alone in the treatment of HRS1. The purpose of this analysis was the quantification of the survival benefits of liver transplantation for patients with HRS1. Ninety-nine patients were randomized to terlipressin or placebo. Thirty-five patients (35%) received a liver transplant. Among those receiving terlipressin plus albumin, the 180-day survival rates were 100% for transplant patients and 34% for nontransplant patients; among those receiving only albumin, the rates were 94% for transplant patients and 17% for nontransplant patients. The survival rate was significantly better for those achieving a reversal of hepatorenal syndrome (HRS) versus those not achieving a reversal (47% versus 4%, P < 0.001), but it was significantly lower for the responders versus those undergoing liver transplantation (97%). We conclude that the use of terlipressin plus albumin has no significant impact on posttransplant survival. Liver transplantation offers a clear survival benefit to HRS1 patients regardless of the therapy that they receive or the success or failure of HRS reversal. The most likely benefit of terlipressin in patients undergoing liver transplantation for HRS1 is improved pretransplant renal function, and this should make the posttransplant management of this difficult group of patients easier. For patients not undergoing transplantation, HRS reversal with terlipressin and/or albumin improves survival.