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      Spur cells in liver cirrhosis are predictive of acute-on-chronic liver failure and liver-related mortality regardless of severe anaemia

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          Abstract

          Chronic anaemia in advanced liver disease is a frequent finding. The aim was to explore the clinical impact of spur cell anaemia, a rare entity typically associated with end-stage of the disease. One-hundred and nineteen patients (73.9% males) with liver cirrhosis of any etiology were included. Patients with bone marrow diseases, nutrients deficiencies and hepatocellular carcinoma were excluded. In all patients, a blood sample was collected to check for the presence of spur cells on blood smear. A complete blood biochemical panel was recorded together with Child–Pugh (CP) score and Model for End-Stage Liver Disease (MELD) score. For each patients, clinically relevant events, such as acute-on-chronic liver failure (ACLF) and 1 year liver-related mortality, were registered. Patients were then grouped according to the percentage of spur cells at smear (> 5%, 1–5%, < 1%). Severe anaemia was defined as haemoglobin levels lower than 8 g/dL. 9.2% of subjects had > 5% spur cells, only 2 had evidence of haemolysis. In patients with > 5% spur cells, haemoglobin and albumin were lower compared with the other sub-group, while MELD score, CP score, International Normalized Ratio, ferritin, creatinine and unconjugated bilirubin were higher. Patients with more spur cells were more decompensated and developed more frequently ACLF. ACLF and liver-related mortality were significantly and independently associated with the presence of > 5% spur cells but not with baseline severe anaemia. Cirrhotic patients have a fairly high prevalence of spur cells, not always associated with severe haemolytic anaemia. The presence of spur red cells is per se associated with a worse prognosis and, therefore, should be always evaluated to prioritize patients for intensive management and eventually liver transplantation.

          Lay Summary

          Chronic anaemia is a frequent finding in liver cirrhosis and spur cell anaemia has been shown to be an uncommon non-immune haemolytic disease typically related to advanced-liver disease. In our study, spur cell anaemia (spur cells >5%) was found in almost 10% of outpatient cirrhotics and was significantly related to more decompensated disease, higher incidence of ACLF and 1 year liver-related mortality. More importantly, the vast majority of patients with high percentage of spur cells did not have severe anaemia. Therefore, spur cells should be searched for in patients with advanced liver disease by a simple blood smear evaluation, even in the absence of significant anaemia, because of relevant prognostic impact and in order to prioritize patients to intensive management and possibly liver transplantation.

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          Spectrum of anemia associated with chronic liver disease.

          Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically significant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirin-induced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by deficiency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.
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            Incidence, predictors and outcomes of acute-on-chronic liver failure in outpatients with cirrhosis

            Acute-on-chronic liver failure (ACLF) is the most life-threatening complication of cirrhosis. Prevalence and outcomes of ACLF have recently been described in hospitalized patients with cirrhosis. However, no data is currently available on the prevalence and the risk factors of ACLF in outpatients with cirrhosis. The aim of this study was to evaluate incidence, predictors and outcomes of ACLF in a large cohort of outpatients with cirrhosis.
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              Prevalence of and risk factors for anaemia in patients with advanced chronic liver disease

              Abstract Background Anaemia is common in advanced chronic liver disease (ACLD) as a result of various risk factors. Aims & Methods We evaluated the prevalence and severity of anaemia as well as the impact of anaemia on clinical outcomes in consecutive patients with ACLD and portal hypertension. Results Among 494 patients, 324 (66%) patients had anaemia. Anaemic patients showed higher MELD (12 ± 4 vs 9 ± 3; P < .001), lower albumin (34 ± 6 vs 39 ± 5 g/dL; P < .001) and more often Child‐Pugh B/C stage (56% vs 17%; P < .001). The prevalence of moderate‐severe anaemia (haemoglobin <10 g/dL) increased with the degree of portal hypertension (HVPG: 6‐9 mm Hg: 22% vs HVPG: 10‐19 mm Hg: 24% vs HVPG ≥ 20 mm Hg: 36%; P = .031). The most common aetiologies of anaemia were gastrointestinal bleeding (25%) and iron deficiency (9%), while reason for anaemia remained unclear in 53% of cases. Male gender (odds ratio [OR]: 1.94 [95% CI: 1.09‐3.47]; P = .025), MELD (OR: 1.20 [95% CI: 1.09‐1.32]; P < .001), hepatic decompensation (OR: 4.40 [95% CI: 2.48‐7.82]; P < .001) and HVPG (OR per mm Hg: 1.07 [95% CI: 1.02‐1.13]; P = .004) were independent risk factors for anaemia. Anaemia was associated with hepatic decompensation (1 year: 25.1% vs 8.1%; 5 years: 60.3% vs 32.9%; P < .0001), hospitalization (73% vs 57%; P < .001) and a higher incidence rate of acute‐on‐chronic liver failure (0.05 [95% CI: 0.04‐0.07] vs 0.03 [95% CI: 0.01‐0.04]). Anaemic patients had worse overall survival (1 year: 87.1% vs 93.7%, 5 year survival: 50.5% vs 68.6%; P < .0001) and increased liver‐related mortality (1 year mortality: 9.7% vs 5.7%, 5 year mortality: 38.0% vs 26.9%; P = .003). Conclusion Two‐thirds of patients with ACLD suffer from anaemia. The degree of hepatic dysfunction and of portal hypertension correlate with severity of anaemia. Anaemia is associated with decompensation, ACLF and increased mortality in patients with ACLD.
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                Author and article information

                Contributors
                bevilacqua.michele@yahoo.com
                Journal
                Intern Emerg Med
                Intern Emerg Med
                Internal and Emergency Medicine
                Springer International Publishing (Cham )
                1828-0447
                1970-9366
                22 May 2023
                22 May 2023
                2023
                : 18
                : 5
                : 1397-1404
                Affiliations
                [1 ]Department of Medicine, General Medicine C, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
                [2 ]GRID grid.411475.2, ISNI 0000 0004 1756 948X, Liver Unit, Department of Medicine, , University and Azienda Ospedaliera Universitaria Integrata of Verona, ; Verona, Italy
                [3 ]GRID grid.5611.3, ISNI 0000 0004 1763 1124, Clinical Biochemistry, , University of Verona, ; Verona, Italy
                Author information
                http://orcid.org/0000-0001-7955-0117
                Article
                3303
                10.1007/s11739-023-03303-x
                10412654
                37212944
                1eadd4c9-9559-49cb-9786-72e651de3a17
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 January 2023
                : 8 May 2023
                Funding
                Funded by: Università degli Studi di Verona
                Categories
                Im - Original
                Custom metadata
                © Società Italiana di Medicina Interna (SIMI) 2023

                Emergency medicine & Trauma
                spur cell anaemia,liver cirrhosis,hepatic decompensation,liver-related mortality,aclf,liver transplantation

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