Implications of anaemia and response to anaemia treatment on outcomes in patients with cirrhosis

Jassin Rashidi-Alavijeh; Nargiz Nuruzade; Alexandra Frey; Eva-Maria Huessler; Anne Hörster; Amos Cornelius Zeller; Andreas Schütte; Hartmut Schmidt; Katharina Willuweit; Christian Markus Lange

doi:10.1016/j.jhepr.2023.100688

Implications of anaemia and response to anaemia treatment on outcomes in patients with cirrhosis

JHEP Rep. 2023 Jan 28;5(4):100688. doi: 10.1016/j.jhepr.2023.100688. eCollection 2023 Apr.

Affiliations

¹ Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany.
² Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Duisburg, Germany.

Abstract

Background & aims: Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis.

Methods: Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models.

Results: A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis.

Conclusions: An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients.

Impact and implications: Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin.

Clinical trial registration: UME-ID-10042.

Keywords: ACLF, acute-on-chronic liver failure; AIH, autoimmune hepatitis; ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; CRP, C-reactive protein; Haemoglobin; INR, international normalised ratio; Iron deficiency; Iron supplementation; LT, liver transplantation; Liver transplantation; MELD, model for end-stage liver disease; NASH, non-alcoholic steatohepatitis; NSBBs, non-selective beta blockers; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; Rifaximin; SSC, secondary sclerosing cholangitis; TIPS, transjugular intrahepatic portosystemic shunt; aPTT, activated partial thromboplastin time; ΔHb3, difference of haemoglobin levels after 3 months; ΔHb6, difference of haemoglobin levels after 6 months.