Clinical Interest of Serum Alpha-2 Macroglobulin, Apolipoprotein A1, and Haptoglobin in Patients with Non-Alcoholic Fatty Liver Disease, with and without Type 2 Diabetes, before or during COVID-19
Olivier Deckmyn,
Thierry Poynard,
Pierre Bedossa,
Valérie Paradis,
Valentina Peta,
Raluca Pais,
Vlad Ratziu,
Dominique Thabut,
Angelique Brzustowski,
Jean-François Gautier,
Patrice Cacoub,
Dominique Valla
Affiliations
Olivier Deckmyn
BioPredictive, 75007 Paris, France
Thierry Poynard
Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, 75013 Paris, France
Pierre Bedossa
Department of Pathology, Physiology and Imaging, Beaujon Hospital APHP Diderot University, 75006 Paris, France
Valérie Paradis
Department of Pathology, Physiology and Imaging, Beaujon Hospital APHP Diderot University, 75006 Paris, France
Valentina Peta
BioPredictive, 75007 Paris, France
Raluca Pais
Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, 75013 Paris, France
Vlad Ratziu
Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, 75013 Paris, France
Dominique Thabut
Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, 75013 Paris, France
Angelique Brzustowski
Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepatology, Beaujon Hospital, 92110 Clichy, France
Jean-François Gautier
Inserm U1149, Centre de Recherche sur l’ Inflammation CRI, 92110 Clichy, France
Patrice Cacoub
Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Internal Medicine and Clinical Immunology, Pitié-Salpêtrière Hospital, 75013 Paris, France
Dominique Valla
Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepatology, Beaujon Hospital, 92110 Clichy, France
In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened by T2DM after adjustment by age, sex, obesity, and COVID-19. Three datasets were used: the “Control Population”, which enabled standardization of protein serum levels according to age and sex (N = 27,382); the “NAFLD-Biopsy” cohort for associations with liver features (N = 926); and the USA “NAFLD-Serum” cohort for protein kinetics before and during COVID-19 (N = 421,021). The impact of T2DM was assessed by comparing regression curves adjusted by age, sex, and obesity for the liver features in “NAFLD-Biopsy”, and before and during COVID-19 pandemic peaks in “NAFLD-Serum”. Patients with NAFLD without T2DM, compared with the values of controls, had increased A2M, decreased ApoA1, and increased haptoglobin serum levels. In patients with both NAFLD and T2DM, these significant mean differences were magnified, and even more during the COVID-19 pandemic in comparison with the year 2019 (all p < 0.001), with a maximum ApoA1 decrease of 0.21 g/L in women, and a maximum haptoglobin increase of 0.17 g/L in men. In conclusion, T2DM is associated with abnormal levels of A2M, ApoA1, and haptoglobin independently of NAFLD, age, sex, obesity, and COVID-19.
