Editorial

When Should the β-Blocker Window in Cirrhosis Close?

Non-selective betablockers (NSBBs) remain the cornerstone of medical treatment of portal hypertension. The evidence for their efficacy to prevent variceal bleeding is derived from prospective trials, which largely excluded patients with refractory ascites and renal failure. In parallel to the increasing knowledge on portal hypertension-induced changes in systemic hemodynamics, cardiac function, and renal perfusion, emerging studies have raised concerns about harmful effects of NSBBs. Clinicians are facing an ongoing controversy on the use of NSBBs in patients with advanced cirrhosis. On the one hand, NSBBs are effective in preventing variceal bleeding and might also have beneficial non-hemodynamic effects, however, they also potentially induce hypotension and limit the cardiac reserve. An individualized NSBB regimen tailored to the specific pathophysiological stage of cirrhosis might optimize patient management at this point. This article aims to give practical recommendations on the use of NSBBs in patients with decompensated cirrhosis.

Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis.

We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form–36 health survey) were secondary outcome measures.

A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups.

Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.