Non-selective β Blockers Increase Risk for Hepatorenal Syndrome and Death in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis

M Mandorfer; S Bota; P Schwabl; T Bucsics; N Pfisterer; M Kruzik; M Hagmann; A Blacky; A Ferlitsch; W Sieghart; M Trauner; M Peck-Radosavljevic; T Reiberger

doi:10.1055/s-0034-1376030

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

Non-selective β Blockers Increase Risk for Hepatorenal Syndrome and Death in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis

M Mandorfer ¹^,², S Bota ¹^,², P Schwabl ¹^,², T Bucsics ¹^,², N Pfisterer ¹^,², M Kruzik ¹^,², M Hagmann ³, A Blacky ⁴, A Ferlitsch ¹^,², W Sieghart ¹^,², M Trauner ¹^,², M Peck-Radosavljevic ¹^,², T Reiberger ¹^,²^,⁵

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
²Vienna Hepatic Hemodynamic Lab, Vienna, Austria
³Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
⁴Clinical Institute of Hospital Hygiene, Vienna General Hospital, Vienna, Austria
⁵Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Boston, United States

Abstract

Background & Aims: Non-selective β blockers (NSBBs) reduce the hepatic venous portal pressure gradient and the risk for variceal hemorrhage in patients with cirrhosis. However, development of spontaneous bacterial peritonitis (SBP) in these patients could preclude treatment with NSBBs, due to their effects on the circulatory reserve. We investigated the effects of NSBBs in patients with cirrhosis and ascites, with and without SBP.

Methods: We performed a retrospective analysis of data from 607 consecutive patients with cirrhosis who had their first paracentesis at the Medical University of Vienna from 2006 through 2011. Cox models were calculated to investigate the effects of NSBBs on SBP incidence and transplant-free survival. The model for SBP incidence was adjusted for Child-Pugh stage; models for transplant-free survival were adjusted for Child-Pugh stage and presence of varices.

Results: No effect of NSBB treatment (hazard ratio [HR]: 0.728; 95% confidence interval [95% CI]: 0.422 – 1.198; P= 0.211) on SBP incidence was observed.

NSBBs increased transplant-free survival in patients without SBP (HR: 0.75; 95% CI: 0.581 – 0.968; P= 0.027) and reduced days of non-elective hospitalization (NSBB: 19.4 days/person-year; 95% CI: 18.9 – 19.9 vs. no-NSBB: 23.9 days/person-year; 95% CI: 23.4 – 24.4). NSBBs had only moderate effects on systemic hemodynamics at patients' first paracentesis.

However, at the first diagnosis of SBP, the proportion of hemodynamically compromised patients with systolic blood pressures < 100 mmHg was higher among those who received NSBBs (38% vs. no-NSBB: 18%; P= 0.002), as was the proportion of patients with arterial pressure < 82 mmHg (NSBB: 64% vs. no-NSBB: 44%; P= 0.006). Among patients with SBP, NSBBs reduced transplant-free survival (HR: 1.58; 95% CI: 1.098 – 2.274; P= 0.014) and increased days of non-elective hospitalization (NSBB: 29.6 days/person-year; 95% CI: 28.2 – 31 vs. no-NSBB: 23.7 days/person-year; 95% CI: 22.7 – 24.8). A higher proportion of patients on NSBBs had hepatorenal syndrome (NSBB: 24% (20/83) vs. no-NSBB: 11% (9/82); P= 0.027) and grade C acute kidney injury (NSBB: 20% (17/86) vs. no-NSBB: 8% (7/90); P= 0.021).

Conclusions: Among patients with cirrhosis and SBP, NSBBs increase the proportion who are hemodynamically compromised, time of hospitalization, and risks for hepatorenal syndrome and acute kidney injury. They also reduce transplant-free survival. Thus, our results define SBP as a clinical event that closes the therapeutic window for NSBB treatment.