Liver Transplantation in a Randomized Controlled Trial of Emergency Treatment of Acutely Bleeding Esophageal Varices in Cirrhosis

Abstract

Background Bleeding esophageal varices (BEV) in cirrhosis has been considered an indication for liver transplantation (LT). This issue was examined in a randomized controlled trial (RCT) of unselected, consecutive patients with advanced cirrhosis and BEV that compared endoscopic sclerotherapy (EST) (n=106) to emergency direct portacaval shunt (EPCS) (n=105). Methods Diagnostic workup and treatment were initiated within 8 hours. Patients were evaluated for LT on admission and repeatedly thereafter. 96% underwent over 10 years of regular follow-up. The analysis was supplemented by 1300 unrandomized cirrhotic patients who previously underwent portacaval shunt (PCS) with 100% follow-up. Results In the RCT, long-term bleeding control was 100% following EPCS, only 20% following EST. 3, 5, 10, and 15-year survival rates were 75%, 73%, 46%, and 46% following EPCS, compared to 44%, 21%, 9%, and 9% following EST (p<0.001). Only 13 RCT patients (6%) were ultimately referred for LT mainly because of progressive liver failure; only 7 (3%) were approved for LT and only 4 (2%) underwent LT. 1- and 5-year LT survival rates were 0.68% and 0, compared to 81% and 73% after EPCS. In the 1300 unrandomized PCS patients. 50 (3.8%) were referred and 19 (1.5%) underwent LT. Five-year survival rate was 53% compared to 72% for all 1300 patients. Conclusions If bleeding is permanently controlled, as occurred invariably following EPCS, cirrhotic patients with BEV seldom require LT. PCS is effective first-line and long-term treatment. Should LT be required in patients with PCS, although technically more demanding, numerous studies have shown that PCS does not increase mortality or complications. EST is not effective emergency or long-term therapy.

A randomized controlled trial of emergency treatment of bleeding esophageal varices in cirrhosis for hepatocellular carcinoma

“…We examined the issue of liver transplantation as part of our trial of emergency treatment of BEV, and in addition, we analyzed our results regarding liver transplantation in 1300 nonrandomized patients in whom we previously performed portacaval shunt beginning in 1978. 35 The results of our study indicate that liver transplantation is seldom required following control of bleeding by portacaval shunt. If recurrent BEV is prevented, as was true in 100% of the portacaval shunt patients, both randomized and nonrandomized, prolonged survival occurs, equal to or better than survival following liver transplantation.…”

“…Screening for HCC by ultrasonography every 6 months was done according to the consensus recommendation of the American Association for the Study of Liver disease 21 and the European Association for the Study of the Liver. 35 The screening for HCC by AFP determinations monthly for the first postentry year and every 3 months thereafter was more frequent than that recommended by consensus. Regrettably, there are no reports in the literature that describe a more effective surveillance program for detecting HCC in cirrhotic patients with BEV.…”

Surgical portosystemic shunts in the era of TIPS and liver transplantation are still relevant

“…Despite the fact that only a small fraction of cirrhosis patients with bleeding will ultimately undergo liver transplantation after the TIPS placement (3–10% in most series), an unsubstantiated belief that those patients will be candidates for possible liver transplant has resulted in the adoption of the TIPS as the decompressive shunt of choice and as a bridge to transplant by clinical decision makers. In a randomized controlled trial (RCT) reported by Orloff (MJ) et al ., which compared endoscopic sclerotherapy with emergency PSS in 211 unselected consecutive patients with advanced cirrhosis and bleeding oesophageal varices, only 6% were referred for OLT and only 2% underwent OLT, with worse 1‐ and 5‐year survival rates . In addition, this analysis was supplemented by 1300 non‐randomized cirrhosis patients who previously underwent SSPCS with 100% follow‐up, of whom only 3.8% were referred for and only 1.5% actually underwent OLT, again with a worse 5‐year survival rate …”

Alcoholic Versus Nonalcoholic Cirrhosis in a Randomized Controlled Trial of Emergency Therapy of Bleeding Varices

“…However, there is good reason to propose that these findings are applicable to patients undergoing elective treatment of BEV. In point of fact we examined the issue of alcoholic versus nonalcoholic cirrhosis in an unrandomized study of 1300 patients who underwent direct portacaval shunts for BEV, 700 electively and 600 as an emergency [19]. We found no differences between alcoholics and nonalcoholics in any of the outcome parameters including control of bleeding, survival, PSE and effect on liver function.…”