Introduction

IgG4-related disease of the liver, pancreas, and bile ducts (IgG4-HPB) can lead to fibrosis and organ damage. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and Enhanced liver fibrosis (ELF) score are validated, non-invasive methods for measuring liver fibrosis in other chronic liver diseases, but little is known about their utility in IgG4-HPB.

Aims & Methods

The aim of this study is to assess LSM using Fibroscan® and ELF in patients with IgG4-HPB. This is a retrospective observational cohort of patients meeting the ACR/EULAR classification criteria for IgG4-Related Disease at Oxford University Hospitals. Clinical data collected included demographics, organ involvement, clinical flares, serum biomarkers and organ damage. LSM was recorded in 55 IgG4-HPB patients, and sequential LSM was recorded in 32 patients. Serum ELF was measured in 23 patients. Wilcoxon rank, Mann-Whitney U, and Fisher’s exact tests were performed.

Results

Ninety-seven patients with IgG4-HPB were included; median age was 68 years ±19, and 79% were male. Among the entire cohort, 69% had established organ dysfunction and/or damage and, when subdivided by organ involvement, damage was present in 72% of those with liver and biliary disease (IgG4-HB) and 65% of those with pancreatic disease only (IgG4-AIP) (Table 1).

	Overall cohort (n = 97)	HPB cohort (n = 57)	AIP cohort (n = 40)	p-value
Median age (IQR)	67.5 (19)	68.5 (19)	65.5 (18)	0.91
Men	77 (79%)	44 (77%)	33 (82%)	0.61
Established organ damage	67 (69%)	41 (72%)	26 (65%)	>0.99
Diabetes	33 (34%)	26 (46%)	12 (29%)	0.14
Cardiometabolic disease	41 (42%)	22 (39%)	20 (49%)	0.11
MASLD	19 (20%)	13 (23%)	6 (15%)	0.59
Mean cumulative steroid dose (SD)	7326 (17468)	9012 (21263)	4260 (3074)	0.32
Median number of flares (IQR)	1 (2)	1 (2)	0 (1)	0.25

LSM was recorded in 55 patients: IgG4-HB (n = 38) had a higher mean LSM compared with IgG4-AIP (n = 17) (6.1 kPa vs 5 kPa, p = 0.04). IgG4-HB were risk-stratified by LSM: 66% had LSM <8kPa, 21% had LSM ≥8 but <12kPa, and 13% had LSM ≥12kPa. There was a higher prevalence of metabolic associated steatotic liver disease (MASLD) and its metabolic factors (diabetes, hypertension, hypercholesterolemia, and ischaemic heart disease) in those with more advanced liver fibrosis (LSM≥12 kPa). Furthermore, survival analysis showed that patients with LSM ≥ 8kPa develop organ damage faster than those with LSM < 8kPa (p=0.0086).

In longitudinal analysis, 32 patients with IgG4-HPB had serial LSMs. Of those with IgG4-HB (n = 22), 23% showed an increase in LSM over a median of 2 years (IQR 1-4). The proportion of patients meeting criteria for MASLD increased from 20% to 25% over a median of two years. In those with paired readings during active disease and remission (n = 8), there was no discernible variation in LSM.

Twenty-three patients with IgG4-HPB had an ELF test and were stratified by the score: 13/23 (56%) <9.8 and 10/23 (43%) ≥9.8. ELF accurately identified patients with more significant liver fibrosis; no patient with LSM ≥ 8kPA was seen in the <9.8 group (p = 0.0021). There was no association of ELF with disease activity or serum biomarkers.

Conclusion

This is the first study assessing the role of LSM by Fibroscan® and of ELF score in patients with IgG4-HPB. An increased LSM over time was associated with the accumulation of cardiometabolic risk factors, evidence of MASLD, and end-organ damage, while ELF score ruled out advanced fibrosis in this cohort concurrently.

Disclosure

EC: Speaking Fees: Horizon Therapeutics, Advanz (Intercept), Albireo, Dr Falk Pharma, Gilead, GSK; Consulting Fees: Advanz (Intercept), Horizon Therapeutics, Ipsen, Mirum, Moderna, Sanofi, Zenus Pharma; Grant Support: Jansen, Innovate UK, PSC Support, Wellcome Trust; Institutional Funding Support: BRC Oxford NIHR (UK), Oxford Charitable Fund, Research Capability Fund.
SK, RM and CM have nothing to declare.

Introduction

The recommended treatment for severe complications of portal hypertension (PH) is transjugular intrahepatic portosystemic shunt (TIPS) implantation. Despite alcohol-related liver disease (ALD) representing the most frequent cause of advanced chronic liver disease (ACLD) and PH, literature on the effects of ongoing alcohol use (AU) after TIPS placement currently remains scarce.

Aims & Methods

The study population consisted of patients with ALD-related ACLD who had undergone TIPS implantation at two Viennese tertiary care centers (pooled cohort from the prospective AUTIPS study, NCT03409263: 01/2017-11/2022; and a retrospective cohort: 09/2000-09/2019). Through the electronic patient management system, individual demographic, laboratory, and clinical data were retrieved. AU after TIPS placement was investigated according to clinical documentation, serum ethanol quantification if available, and patients' reporting.

Results

Overall, the study population consisted of 276 patients (median follow-up 29 [IQR 54] months), 196 (71.0%) of which had received TIPS for refractory ascites while in 80 (29.0%) the indication for TIPS implantation had been variceal hemorrhage. The median age was 56 (IQR 13) years and 215 (77.9%) of the patients were men. At the time of the TIPS insertion, the median MELD was 11 (IQR 9) and 38 (13.8%) individuals were classified as Child-Pugh C. AU after TIPS placement was documented in 85 (30.8%) study participants. Baseline characteristics at TIPS implantation were similar in patients with and without post-TIPS AU, specifically regarding the prevalence of ascites (p=0.51), variceal hemorrhage (p=0.87), and hepatic encephalopathy (p=0.87).
Bacterial infections were more frequently detected among patients with ongoing AU (log-rank p=0.002). Importantly, patients with ongoing AU showed a higher incidence of acute-on-chronic liver failure (ACLF; log-rank p<0.001) and higher overall mortality (log-rank p=0.005; including liver-related death [log-rank p<0.001]).
Furthermore, cumulative incidence of ACLF (p=0.014) and liver-related death (p=0.004) were significantly higher in patients with ongoing AU. Of note, ongoing AU was independently associated with ACLF (asHR: 1.66; 95%CI: 1.13-2.44; p=0.010) and liver-related death (asHR: 2.09; 95%CI: 1.32-3.33; p=0.002) in multivariable competing risks regression analysis adjusted for age, MELD, and portal pressure gradient after TIPS implantation.

Conclusion

AU represents an independent risk factor for outcome deterioration after TIPS placement. These findings emphasize the paramount role of psychiatric care and harm reduction measures in addition to hepatological optimization after TIPS implantation.

Disclosure

C.S. received travel support from Gilead, Abbvie, Galapagos and Gebro; speaking honoraria from Abbvie and Gilead; and payments for consulting from Gilead.
M.S. received travel support from MSD, Sandoz, BMS, Abbvie and Gilead; and speaking honoraria from BMS.
M.J. received speaking honoraria from Abbvie and Gilead.
T.R. received grant support from Abbvie, Boehringer- Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Boehringer-Ingelheim, Gilead, and Roche.
M.M. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Collective Acumen, Gilead, and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb, and Gilead.
B.S. received travel support from AbbVie and Gilead.