Hepatic encephalopathy (HE) is a common problem after insertion of a trans-jugular intrahepatic portosystemic shunt (TIPS), which may be difficult to manage. We present a case of severe post-TIPS HE unresponsive to high doses of L-ornithine-L-aspartate (LOLA) despite reduction of venous ammonia levels in a dose-dependent fashion. Ultimately, high-grade HE was successfully treated by a reduction stent and the patient subsequently underwent successful liver transplantation.