Artificial liver device improves outcomes, but with safety concerns

The Molecular Adsorbent Recirculating System (MARS), a nonbiological artificial liver device, leads to better clinical and biological outcomes among patients receiving the intervention, according to a recent study. However, adverse events and safety concerns related to the device are common.

More than half (52.8 percent; n=95) of the 180 device-treated patients saw at least one adverse event. The most common safety concern was MARS-associated thrombocytopaenia, which developed in 30.6 percent of admissions and 12.7 percent of all treatment sessions. Platelet count dropped from a mean of 131×10⁹/L before therapy to 106×10⁹/L after. There were no cases of type 2 heparin-induced thrombocytopaenia. [Crit Care 2022;26:282] 

Of the participants enrolled, 31.1 percent underwent the device intervention for acute-on-chronic liver failure. Other common indications included acute liver failure (17.8 percent), postsurgery liver failure (15.5 percent), refractory pruritus (28.9 percent), and drug intoxication (6.7 percent).

“It is worth noting that patients with platelets levels lower than 50×10⁹/L were excluded from most controlled trials on MARS therapy, whereas they were included in this study after platelets transfusion,” the researchers said. “Therefore, the adverse events recorded in this group may be less influenced by exterior factors.”

“The benefit-risk ratio in these patients makes it particularly important to monitor adverse events as any adverse event in these patients without major organ failure would unbalance the benefit-risk ratio of MARS therapy,” they said.

Clinical, biological improvements

Aside from safety, researchers also assessed the clinical and biological impacts of the MARS device as a secondary endpoint.

Among patients with acute-on-chronic liver failure, total bilirubin levels dropped significantly from 505 to 349 µmol/L (p<0.01) after device use, while prothrombin time increased from 42 percent to 47 percent (p<0.01). Similar significant improvements were found for the Glasgow coma scale score and encephalopathy rate (p=0.01 for both).

Similarly, total bilirubin levels were significantly reduced in patients who received the MARS treatment for acute liver failure and postsurgery liver failure. In both groups, biological markers of liver failure were significantly improved after device intervention: alanine transaminase levels dropped from 440 to 250 IU/L (p<0.01) in the former patient group, and from 153 to 100 IU/L (p=0.02) in the latter.

Aspartate transaminase levels likewise decreased significantly after device treatment in patients with postsurgery (100 to 72 IU/L; p=0.04) and acute (259 to 116 IU/L; p=0.02) liver failure.

Of the 52 patients with refractory pruritus, 43 saw at least a 50-percent drop in pruritus (p<0.01). After three MARS sessions, bile acid levels dropped significantly from 95 µmol/L at baseline to 48 µmol/L (p<0.01). Similar impacts were found for total bilirubin and serum gamma glutamyl transferase (p<0.01 for both).

“Large multicentre randomized controlled trials are needed to confirm these exploratory results,” the researchers said.

More appropriate measures of efficacy need to be established. For patients with refractory pruritus, pruritus symptom burden may be a valuable way to assess the value of the MARS device, while transplantation-free survival could be a useful metric for those with acute liver failure, they explained.

“Overall, short- and long-term mortality “should always be monitored and could define efficacy of MARS therapy,” the researchers said.