Comparison of extracorporeal cellular therapy (ELAD®) vs standard of care in a randomized controlled clinical trial in treating Chinese subjects with acute-on-chronic liver failure.

Background: Preliminary evidence of safety and efficacy of an extracorporeal cellular therapy (ELAD^®) has been demonstrated in subjects with acute forms of liver failure. This study compared ELAD with standard of care in Chinese subjects with acute-on-chronic liver failure (ACLF), predominantly secondary to chronic viral hepatitis.

Subjects and methods: Subjects meeting eligibility criteria were randomized to either the ELAD group or the control group. All subjects received plasma exchange and venovenous hemofiltration and either ELAD treatment for 3-5 days, unless terminated early, along with standard of care or standard of care alone (control) and were then followed up for 12 weeks.

Results: Forty-nine subjects (ELAD subjects, 32; controls, 17) were randomized under this protocol. Kaplan-Meier analysis of transplant-free survival (TFS) revealed a significant difference in favor of ELAD vs control (P=0.049, Wilcoxon signed-rank test). There was a significant difference in TFS on day 28 in ELAD vs control (P=0.022). In a multiple regression model, the relationship between group assignment and outcome was significant (P=0.031) when changes in food intake and Model for End-Stage Liver Disease (MELD) scores at screening were included as additional independent variables. The duration of ELAD treatment alone was a significant predictor of TFS (P=0.043). Median time to a 5-point increase in MELD, transplant, or death was longer than 72 days with ELAD vs 26 days for control (P=0.036). Total bilirubin level decreased by 25% during ELAD treatment vs 37% increase in the control group (P<0.001) over an equivalent period. Adverse events attributed to the ELAD system were expected and could be managed conservatively. Intergroup differences in certain vital signs and laboratory parameters were noted during treatment and generally resolved posttreatment.

Conclusion: ELAD treatment was well tolerated by Chinese subjects with ACLF, predominately secondary to chronic viral hepatitis. Results demonstrate a significant improvement in TFS in ELAD vs control groups in association with significant improvements in serum bilirubin levels presumably related to improvement in hepatic function.