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Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity
  1. Pierre Bedossa1,
  2. Joan Tordjman2,3,
  3. Judith Aron-Wisnewsky2,3,
  4. Christine Poitou2,3,
  5. Jean-Michel Oppert2,
  6. Adriana Torcivia4,
  7. Jean-Luc Bouillot5,
  8. Valerie Paradis1,
  9. Vlad Ratziu6,
  10. Karine Clément2,3
  1. 1Department of Pathology, Assistance Publique-Hôpitaux de Paris (AP-HP), Beaujon Hospital, INSERM U1149, University Paris-Diderot, Paris, France
  2. 2Nutrition Department, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, (AP-HP), University Pierre et Marie Curie, Paris, France
  3. 3Université Pierre et Marie Curie, INSERM, UMRS 1166, NutriOmique team F-75015, Paris, France
  4. 4Department of Digestive and Hepato-Pancreato-Biliary Surgery, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France
  5. 5Surgery Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Ambroise Paré Hospital, Boulogne-Billancourt, France
  6. 6Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Liver Center, Université Pierre et Marie Curie, Paris, France
  1. Correspondence to Professor Pierre Bedossa, Department of Pathology, Beaujon Hospital, 100 Boulevard General Leclerc, Clichy 92110, France; pierre.bedossa{at}


Objective Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients.

Design Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics.

Results Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres).

Conclusions These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators.


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  • Contributors PB, JT, KC conceived and designed the study. PB drafted the manuscript. JT, JAW, CP, J-MO collected the patients clinical and laboratory data. PB, JT, KC contributed to the analysis of the data. VP and VR contributed to the writing of the manuscript. AT and J-LB operated the patients. All authors critically revised the manuscript and approved its final version.

  • Funding The study was supported by the Assistance Publique-Hôpitaux de Paris, and the Direction of Clinical Research (CRC) for clinical investigation (PHRC 02076 to KC, CRC P050318 to CP and CRCCRCCRC-FIBROTA to JAW and KC), as well as the Fondation pour la Recherche Médicale, Horizon 2020 EPoS project, grant 634413, and the National Agency of Research (ANR Adipofib, and the national programme ‘Investissements d'Avenir’ with the reference ANR-10-IAHU-05).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The local ethics committee of University Pierre and Marie Curie.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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