Persistence of severe hepatic fibrosis despite substantial weight loss with bariatric surgery
A research team from AP-HP, Inserm and Sorbonne University carried out work, within the IHU ICAN, on the effects of bariatric surgery on the severity of liver damage in patients with NASH (Non-Alcoholic Steatohepatitis or Metabolic Steatohepatitis) and severe fibrosis (bridge fibrosis or compensated cirrhosis).
This study shows that in 50% of patients who underwent bariatric surgery, despite significant weight loss (20% to 30% of initial BMI) and improvement in metabolic risk factors (mainly type 2 diabetes), severe fibrosis persists in the medium term (5 years after surgery). The results of this work were published on January 25, 2022 in the journal Hepatology.
Obesity in France concerns 17% of the adult population and it increasingly affects children and adolescents. It has many consequences on the state of health of people who are affected, including the development of “fatty liver” (liver steatosis). Hepatic steatosis is defined by the accumulation of fat in liver cells favored by the presence of metabolic risk factors (particularly diabetes and obesity).
In France, liver steatosis affects 18% of the population and 25% of the general population worldwide. Ultimately, this pathology, also called NASH, can lead to the appearance of more serious diseases such as cirrhosis or liver cancer. To date, there is no effective drug treatment for NASH, which makes research into other avenues of care for patients all the more important.
Previous work has shown dramatic improvement in NASH liver damage after bariatric surgery in parallel with weight loss. Nevertheless, efficacy data in patients with advanced forms of NASH remain limited.
The study, coordinated by Dr Raluca Pais (AP-HP, IHU ICAN), Dr Judith Aron-Wisnewsky (APHP, Inserm, Sorbonne University, IHU ICAN), Pr Vlad Ratziu (AP-HP, INSERM, Sorbonne University , IHU ICAN) and Prof. Karine Clément (AP-HP, Inserm, Sorbonne University, NutriOmics Unit), made it possible to analyze the effects of bariatric surgery on the evolution of severe histological lesions in NASH. The patients, from the “BARICAN bariatric surgery” cohort coordinated by the nutrition department led by Pr Jean-Michel Oppert at the Pitié-Salpêtrière AP-HP hospital, had an initial liver biopsy at the time of surgery. bariatric and a follow-up biopsy.
This study confirms the excellent results of bariatric surgery: overall, 29% of patients had normal histology at follow-up biopsy; 74% had NASH resolution without fibrosis progression; 70% had fibrosis regression. However, in patients with severe fibrosis before surgery, severe fibrosis persistedin 47% of cases in the medium term after surgery, despite the resolution of NASH in 69% of cases.
Patients who do not respond to bariatric surgery have a lesser improvement in metabolic risk factors (less weight loss, remission of diabetes) even if clinically significant. The factors associated with the persistence of fibrosis after bariatric surgery, in addition to the follow-up interval, were age and type of surgery (less regression of fibrosis after the sleeve regardless of weight loss). The factors associated with the absence of liver lesions after bariatric surgery were greater weight loss, improved insulin resistance and less initial severity of necroinflammatory lesions.
In conclusion, Dr. Raluca Pais specifies that “this study shows that, despite established efficacy for the regression of NASH, bariatric surgery is less effective for the regression of severe fibrosis. Fibrosis regression requires more time and probably additional mechanisms. Weight loss alone may not be enough to reverse severe fibrosis. »
Authors:
Raluca Pais: Public Assistance Paris Hospitals, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne University, Paris, France; Institute of Cardiometabolism and Nutrition, Paris, France; Saint Antoine Research Center, INSERM UMRS_938 Paris, France; Judith Aron Wisnewsky: Public Assistance Paris Hospitals, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne University, Paris, France; CRNH Ile de France, INSERM, UMRS U1269, Nutrition and Obesities Systemic Approaches (NutriOmics), Paris, France; Pierre Bedossa : INSERM UMRS 1138 CRC Paris, France, Paris ; Maharajah Ponnaiah : Institute of Cardiometabolism and Nutrition, Paris, France ; Jean-Michel Oppert:Public Assistance Paris Hospitals, Pitié Salpêtrière Hospital, Paris, France; Sorbonne University, Paris, France; Jean-Michel Siksik: Public Assistance Paris Hospitals, Pitié-Salpêtrière Hospital, Paris, France; Laurent Genser: Assistance Publique Hôpitaux De Paris, Hôpital Pitié-Salpêtrière, Paris, France ; Sorbonne Université, Paris, France ; CRNH Ile de France, INSERM, UMRS U1269, Nutrition and Obesities Systemic Approaches (NutriOmics), Paris, France ; Frederic Charlotte : Assistance Publique Hôpitaux De Paris, Hôpital Pitié Salpêtrière, Paris, France ; Sorbonne Université, Paris, France ; Dominique Thabut: Assistance Publique Hôpitaux De Paris, Hôpital Pitié-Salpêtrière, Paris, France ; Sorbonne Université, Paris, France ; Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France ; Karine Clement: Assistance Publique Hôpitaux De Paris, Hôpital Pitié-Salpêtrière, Paris, France ; Sorbonne Université, Paris, France ; CRNH Ile de Persistance d’une fibrose avancée (fibrose en pont, F3) avant et après la chirurgie bariatrique France, INSERM, UMRS U1269, Nutrition and Obesities Systemic Approaches (NutriOmics), Paris, France ; Vlad Ratziu : Assistance Publique Hôpitaux De Paris, Hôpital Pitié-Salpêtrière, Paris, France ; Sorbonne Université, Paris, France ; Institute of Cardiometabolism and Nutrition, Paris, France ; INSERM UMRS 1138 CRC Paris, France, Paris.