Italian Medicine Agency.

The aim of the study was to verify the effects of the administration of an inhibitor of the release of endogenous vasodilators together with a vasoconstrictor agent in patients with hepatorenal syndrome (HRS). This new medical perspective was compared with a traditional medical approach for HRS, such as the infusion of nonpressor doses of dopamine to produce renal vasodilation. Thirteen patients with type 1 HRS were enrolled in the study. Five of them were treated with the oral administration of midodrine and the parenteral administration of octreotide. In addition, the patients received 50 to 100 mL of 20% human albumin solution daily for 20 days. Midodrine and octreotide were dosed to obtain a stable increase of at least 15 mm Hg of mean arterial pressure. Eight patients were treated with the intravenous administration of nonpressor doses of dopamine (2-4 g/kg/min) and the same daily amount of albumin. After 20 days of treatment with midodrine and octreotide, an impressive improvement in renal plasma flow (RPF), glomerular filtration rate, and urinary sodium excretion was observed in patients. This was accompanied by a significant reduction in plasma renin activity, plasma vasopressin, and plasma glucagon. No side effects were observed. Three patients were discharged from the hospital. One of them successfully underwent liver transplantation. One of the two remaining patients is still alive after 472 days with a preserved renal function, and the other died from terminal liver failure after 76 days. One of the two patients who were not discharged from the hospital successfully underwent liver transplantation, and the other died from pneumonia after 29 days. Seven out of eight patients who were treated with dopamine experienced a progressive deterioration in renal function and died during the first 12 days. Only one patient recovered renal function and underwent liver transplantation. In conclusion, the long-term administration of midodrine and octreotide seems to be an effective and safe treatment of type 1 HRS in patients with cirrhosis. (HEPATOLOGY 1999;29:1690-1697.)Hepatorenal syndrome (HRS) occurs in 18% of cirrhotic patients with ascites. HRS is characterized by intense vasoconstriction, low glomerular filtration rate (GFR), preserved tubular function, and normal renal histology. 1 The diagnostic criteria of HRS have been recently reviewed, and HRS has been classified on a clinical basis into two different types: type 1 characterized by rapidly progressive renal function impairment and type 2 in which renal failure does not have a rapidly progressive course. 2 From a pathophysiological point of view HRS is considered to be the extreme expression of a reduced effective circulating volume because of arteriolar vasodilation, particularly in the splanchnic area. 3 Consequently, the extreme increase in the activity of both renin-angiotensin and sympathetic nervous system as well as the elevated circulating levels of endothelin are the most likely cause of HRS. [4][5][6][7][8][9]

The aim of the study was to investigate the prevalence and clinical course of renal failure that was induced by the various types of bacterial infections in patients with cirrhosis and ascites. Three hundred and nine patients, who were consecutively admitted to the 3 major hospitals of Padova, Italy, during the first 6 months of 2005, were studied prospectively. Of these, 233 patients (75.4%) had evidence of ascites. In 104 patients with cirrhosis and ascites (44.6%) a bacterial infection was diagnosed. A bacterial infection-induced renal failure was observed in 35 of 104 patients (33.6%). The prevalence of renal failure was higher in biliary or gastrointestinal tract infections and in spontaneous bacterial peritonitis (SBP) and in than in other types of infections. In addition, the progressive form of renal failure was only precipitated by biliary or gastrointestinal tract infections, SBP, and urinary tract infections (UTI). In a multivariate analysis only MELD score (P ‫؍‬ 0.001), the peak count of neutrophil leukocyte in blood (P ‫؍‬ 0.04), and the lack of resolution of infection (P ‫؍‬ 0.03) had an independent predictive value on the occurrence of renal failure. Conclusion: The results of the study show that the development of bacterial-induced renal failure in patients with cirrhosis and ascites is related to the MELD score, and to both the severity and the lack of resolution of the infection. A progressive form of renal failure occurs only as a consequence of biliary or gastrointestinal tract infections, SBP, and UTI. (HEPATOLOGY 2007;45:223-229.)

Spontaneous bacterial peritonitis (SBP) is a common, life-threatening complication of liver cirrhosis. Third-generation cephalosporins have been considered the first-line treatment of SBP. In 2014, a panel of experts suggested a broader spectrum antibiotic regimen for nosocomial SBP, according to the high rate of bacteria resistant to third-generation cephalosporins found in these patients. However, a broader-spectrum antibiotic regimen has never been compared to third-generation cephalosporins in the treatment of nosocomial SBP. The aim of our study was to compare meropenem plus daptomycin versus ceftazidime in the treatment of nosocomial SBP. Patients with cirrhosis and nosocomial SBP were randomized to receive meropenem (1 g/8 hours) plus daptomycin (6 mg/kg/day) or ceftazidime (2 g/8 hours). A paracentesis was performed after 48 hours of treatment. A reduction in ascitic fluid neutrophil count <25% of pretreatment value was considered a treatment failure. The primary outcome was the efficacy of treatment defined by the resolution of SBP after 7 days of treatment. Thirty-two patients were randomized and 31 were analyzed. The combination of meropenem plus daptomycin was significantly more effective than ceftazidime in the treatment of nosocomial SBP (86.7 vs. 25%; P < 0.001). Ninety-day transplant-free survival (TFS) was not significantly different between the two groups. In the multivariate analysis, ineffective response to first-line treatment (hazard ratio [HR]: 20.6; P 5 0.01), development of acute kidney injury during hospitalization (HR: 23.2; P 5 0.01), and baseline mean arterial pressure (HR: 0.92; P 5 0.01) were found to be independent predictors of 90-day TFS. Conclusion: The combination of meropenem plus daptomycin is more effective than ceftazidime as empirical antibiotic treatment of nosocomial SBP. Efficacy of the empirical antibiotic treatment is a strong predictor of 90-day survival in patients with nosocomial SBP.

In patients with cirrhosis and hepatorenal syndrome (HRS), terlipressin has been used either as continuous intravenous infusion or as intravenous boluses. To date, these two approaches have never been compared. The goal of this study was to compare the administration of terlipressin as continuous intravenous infusion versus intravenous boluses in the treatment of type 1 HRS. Seventy-eight patients were randomly assigned to receive either continuous intravenous infusion (TERLI-INF group) at the initial dose of 2 mg/day or intravenous boluses of terlipressin (TERLI-BOL group) at the initial dose of 0.5 mg every 4 hours. In case of no response, the dose was progressively increased to a final dose of 12 mg/day in both groups. Albumin was given at the same dose in both groups (1 g/kg of body weight at the first day followed by 20-40 g/day). Complete response was defined by decrease of serum creatinine (sCr) from baseline to a final value £ 133 lmol/L, partial response by a decrease 50% of sCr from baseline to a final value >133 lmol/L. The rate of adverse events was lower in the TERLI-INF group (35.29%) than in the TERLI-BOL group (62.16%, P < 0.025). The rate of response to treatment, including both complete and partial response, was not significantly different between the two groups (76.47% versus 64.85%; P value not significant). The mean daily effective dose of terlipressin was lower in the TERLI-INF group than in the TERLI-BOL group (2.23 6 0.65 versus 3.51 6 1.77 mg/day; P < 0.05). Conclusion: Terlipressin given by continuous intravenous infusion is better tolerated than intravenous boluses in the treatment of type 1 HRS. Moreover, it is effective at doses lower than those required for intravenous bolus administration. (HEPATOLOGY 2016;63:983-992)