Introduction
Patients with primary biliary cholangitis (PBC) are at an increased risk of developing cirrhosis and eventually experiencing hepatic decompensation. While there is increasing evidence for more prevalent aetiologies of cirrhosis that a successful removal/suppression of the underlying aetiological factor can induce significant improvements in liver function and even enable hepatic recompensation, similar insights in PBC are scarce.
Aims & Methods
In this study, we aimed to explore clinical implications of hepatic recompensation according to the novel Baveno VII criteria in PBC, while considering a biochemical response to ursodeoxycholic acid (UDCA) according to Paris-II criteria as surrogate marker of a successful aetiological treatment. Specifically, we included cirrhotic PBC patients at the time of first hepatic decompensation (ascites, hepatic encephalopathy [HE], variceal bleeding) and analysed their subsequent clinical disease course. In accordance with Baveno VII criteria, we defined hepatic recompensation as (i) resolution of ascites and HE despite discontinuation of diuretics and HE treatment, (ii) absence of variceal bleeding and (iii) sustained improvements in biochemical liver function.
Results
This study enrolled 42 PBC patients with decompensated cirrhosis (age: 63.5 [IQR:51.9-69.2] years; 88.1% female) who were followed-up for a median of 41.9 (IQR:11.0-70.9) months after decompensation. The cause of index decompensation was ascites in 54.8%, variceal bleeding in 35.7% and HE in 9.5% of cases. At time of decompensation, the median MELD-Na was 14 (IQR:11-15). Overall, 33 patients were treated with UDCA for at least 1 year (median dose: 12.5 [IQR:10.7-15.0] mg/kg) and 36% of those (12/33) achieved the Paris-II response criteria.
Over the course of the study, 7 patients (16.7%) achieved recompensation. In a competing risk model, baseline parameters linked to a higher probability of recompensation included a lower MELD-Na (SHR: 0.90; 0.047), a lower Child-Pugh score (SHR: 0.59; p=0.019), lower bilirubin (SHR: 0.44; p=0.005), lower alkaline phosphatase (SHR: 0.96; p=0.001) and variceal bleeding as index decompensation (SHR: 4.37; p=0.069). Interestingly, while 5/12 (42%) UDCA responders recompensated and a response at 1 year was linked to a higher probability of recompensation (SHR: 5.08; p=0.041), 2/21 (10%) patients without UDCA response still eventually achieved recompensation.
Regarding prognostic implications, recompensation was linked to a numerically improved transplant-free survival in a time-dependent Cox regression model (HR: 0.46; p=0.335). Specifically, 3 recompensated patients survived without any further complications or the need for liver transplantation over a follow-up time of 35, 40 and 294 months after recompensation. Nevertheless, the remaining 4 recompensated patients presented with liver-related complications after developing hepatic malignancies and/or portal vein thrombosis (PVT) and two eventually died (18 and 29 months after recompensation). In contrast, of the patients who remained decompensated, 10 underwent liver transplantation (29%) and 17 died (49%).
Conclusion
Patients with decompensated cirrhosis due to PBC may achieve hepatic recompensation under UDCA therapy, particularly if the degree of liver dysfunction at index decompensation is less pronounced. Nonetheless, recompensated patients should be monitored carefully for the development of hepatic malignancy and PVT, as liver transplantation may still be required.
Disclosure
Albert Friedrich Stättermayer: Speaker and/or consultant and/or advisory board member for Boehringer Ingelheim, Gilead, and MSD. Benedikt Simbrunner: Travel support from AbbVie and Gilead. Mattias Mandorfer: Speaker and/or consultant and/or advisory board member for AbbVie, Collective Acumen, Gilead, and W. L. Gore & Associates; Travel support from AbbVie and Gilead. Michael Trauner: Grant support from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and UltraGenyx; Honoraria for consulting from Albireo, Boehringer Ingelheim, BiomX, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, Pliant, Regulus and Shire; Speaker fees from Bristol-Myers Squibb, Falk, Gilead, Intercept and MSD; Travel support from AbbVie, Falk, Gilead and Intercept. Thomas Reiberger: Grant support from Abbvie, Boehringer-Ingelheim, Gilead, Gore, Intercept, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, and Siemens; Speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; Consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; Travel support from Abbvie, Boehringer-Ingelheim, Gilead and Roche.
