PSC Linked to Worse Transplant, Mortality Outcomes Than PBC, Autoimmune Hepatitis

New research is shining light on notable differences in outcomes among patients with primary sclerosing cholangitis (PSC) relative to those with primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH).1

Leveraging data from the Hepascore and Clinical Outcome (HACO) cohort, the study found patients with PSC have worse outcomes for overall death or transplant, liver-related mortality, and liver-related decompensation than those with PBC and AIH. Further analysis identified the Liver Outcome Score (LOS) and Hepascore as significant predictors of certain outcomes.1

PBC, PSC, and AIH constitute the classic autoimmune liver diseases. While AIH target the hepatocytes, the targets of the autoimmune attack in PBC and PSC are the biliary epithelial cells. Historically, the prognosis of each of the 3 autoimmune liver diseases has been poor, often progressing to end-stage liver disease and requiring liver transplantation.2

“Advancements in understanding the natural history and prognostic factors of AIH, PBC, and PSC have been crucial in refining management strategies and improving patient outcomes,” Dujinthan Jayabalan, MD, a clinical lecturer for the faculty of internal medicine at the University of Western Australia Medical School and a physician trainee at Sir Charles Gairdner Hospital, and colleagues wrote.1

To investigate the natural history and assess the predictors of outcomes in patients with autoimmune liver diseases, investigators conducted a retrospective cohort study of patients diagnosed with AIH, PBC, and PSC in the HACO cohort, a state-wide cohort of Australian patients evaluated for chronic liver disease. Patients who had undergone liver transplantation before the study or had a diagnosis of autoimmune liver disease overlap syndrome were excluded from the present analysis.1

Outcomes, including all-cause death, liver-related death, liver-related decompensation, hepatocellular carcinoma (HCC), and liver transplantation, were extracted from the Western Australia Data Linkage Unit. The study’s primary endpoints were overall death or liver transplant; liver-related mortality; and liver-related decompensation, defined as ascites, variceal bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome, or hepatic encephalopathy.1

In total, 561 patients were included in the study. Of these, 237 had AIH, 157 had PBC, and 167 had PSC. The median follow-up time in each group was 4.4 (range, 0.2–9.9) years, 4.0 (range, 0.01–9.5) years, and 3.5 (range 0.1–8.8) years, respectively.1

Among the patients with AIH, 21 deaths occurred, 9 of which were classified as being liver-related. A single patient underwent liver transplant, 1 patient developed HCC, and 16 patients experienced liver-related decompensation. The 5-year transplant-free survival in this group was 88% (95% CI, 81%–92%), 5-year liver-related survival was 95% (95% CI, 91%–98%), and 5-year liver-related decompensation-free rate was 90% (95% CI, 84%–94%).1

Among the patients with PBC, 12 deaths occurred, 8 of which were liver-related. A total of 3 patients underwent liver transplant, 2 patients developed HCC, and 10 patients experienced liver-related decompensation. The 5-year transplant-free survival was 92% (95% CI, 85%–96%), 5-year liver-related survival was 95% (95% CI, 89%–98%), and 5-year liver-related decompensation-free rate was 89% (95% CI, 78%–95%).1

Among the patients with PSC, 57 deaths occurred, 38 of which were liver-related. In total, 19 patients underwent liver transplant, 3 patients developed HCC, and 41 patients experienced liver-related decompensation. The 5-year transplant-free survival was 61% (95% CI, 51%–69%), 5-year liver-related survival was 72% (95% CI, 63%–80%), and 5-year liver-related decompensation-free rate was 60% (95% CI, 48%–71%).1

Investigators noted patients with PSC had significantly worse overall death or transplant, liver-related mortality, and liver-related decompensation compared with those with AIH and PBC (all P <.0001).1

Additionally, investigators identified LOS as a significant independent predictor of overall death or transplant, liver-related mortality, and liver-related decompensation among patients with AIH and PBC. In patients with PSC, LOS was a significant independent predictor of overall death or transplant, and Hepascore was a significant independent predictor of liver-related mortality and liver-related decompensation.1

Investigators acknowledged multiple limitations to these findings, including the retrospective nature of the study; the lack of availability of treatment data upon chart review; inherent inclusion bias associated with the requirement of ≥ 1 Hepascore test for entry into the HACO cohort; and the study’s relatively short follow-up time, with median follow-up time being < 5 years.1

“Patients with PSC have worse outcomes when compared to AIH and PBC. LOS has been demonstrated to be a predictor of overall death or transplant in patients with AIH, PBC, and PSC and of liver-related mortality and liver-related decompensation in PBC and PSC,” investigators concluded.1 “Further, large-volume validation studies using LOS as a prognostic model are crucial to ensure the best outcomes for patients with autoimmune liver diseases.”

References

1. Jayabalan D, Huang Y, Calzadilla-Bertot L, et al. Natural History and Predictors of Clinical Outcomes in Autoimmune Liver Diseases: A Multicenter Study. Journal of Gastroenterology and Hepatology. https://doi.org/10.1111/jgh.16850
2. Liberal R, Grant CR. Cirrhosis and autoimmune liver disease: Current understanding. World J Hepatol. doi:10.4254/wjh.v8.i28.1157