Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients.

BACKGROUND & AIMS The effects of bariatric surgery in patients with nonalcoholic fatty liver disease (NASH) are not well established. We performed a prospective study to determine the biological and clinical effects of bariatric surgery in patients with NASH. METHODS From May 1994 through May 2013, one hundred and nine morbidly obese patients with biopsy-proven NASH underwent bariatric surgery at the University Hospital of Lille, France (the Lille Bariatric Cohort). Clinical, biological, and histologic data were collected before and 1 year after surgery. RESULTS One year after surgery, NASH had disappeared from 85% of the patients (95% confidence interval [CI]: 75.8%-92.2%). Compared with before surgery, patients had significant reductions in mean ± SD body mass index (BMI, from 49.3 ± 8.2 to 37.4 ± 7) and level of alanine aminotransferase (from 52.1 ± 25.7 IU/L to 25.1 ± 20 IU/L); mean levels of γ-glutamyltransferases were reduced from 51 IU/L before surgery (interquartile range [IQR], 34-87 IU/L) to 23 IU/L afterward (IQR, 14-33 IU/L) and mean insulin resistance index values were reduced from 3.6 ± 0.5 to 2.9 ± 0.5 (P < .01 for each comparison). NASH disappeared from a higher proportion of patients with mild NASH before surgery (94%) than severe NASH (70%) (P < .05) according to Brunt score. In histologic analysis, steatosis was detected in 60% of the tissue before surgery (IQR, 40%-80%) but only 10% 1 year after surgery (IQR, 2.5%-21.3%); the mean nonalcoholic fatty liver disease score was reduced from 5 (IQR, 4-5) to 1 (IQR, 1-2) (each P < .001). Hepatocellular ballooning was reduced in 84.2% of samples (n = 69; 95% CI: 74.4-91.3) and lobular inflammation in 67.1% (n = 55; 95% CI: 55.8-77.1). According to Metavir scores, fibrosis was reduced in 33.8% of patients (95% CI: 23.6%-45.2%). Patients whose NASH persisted 1 year after surgery (n = 12) had lost significantly less weight (change in BMI, 9.1 ± 1.5) than those without NASH (change in BMI, 12.3 ± 0.6) (P = .005). Patients who underwent laparoscopic gastric banding lost less weight (change in BMI, 6.4 ± 0.7) than those who underwent gastric bypass (change in BMI, 14.0 ± 0.5) (P < .0001), and a higher proportion had persistent NASH (30.4% vs 7.6% of those with gastric bypass; P = .015). CONCLUSIONS Bariatric surgery induced the disappearance of NASH from nearly 85% of patients and reduced the pathologic features of the disease after 1 year of follow-up. It could be a therapeutic option for appropriate morbidly obese patients with NASH who do not respond to lifestyle modifications. More studies are needed to determine the long-term effects of bariatric surgery in morbidly obese patients with NASH.

[1]  F. Pattou,et al.  Roux-en-Y Gastric Bypass Versus Adjustable Gastric Banding to Reduce Nonalcoholic Fatty Liver Disease: A 5-Year Controlled Longitudinal Study , 2014, Annals of surgery.

[2]  M. Scotté,et al.  Comparison of the Effectiveness of Four Bariatric Surgery Procedures in Obese Patients with Type 2 Diabetes: A Retrospective Study , 2014, Journal of obesity.

[3]  Deepak L. Bhatt,et al.  Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes. , 2014, The New England journal of medicine.

[4]  C. Still,et al.  Risk Factors Associated With Mortality After Roux-en-Y Gastric Bypass Surgery , 2014, Annals of surgery.

[5]  M. Kroh,et al.  Can Diabetes Be Surgically Cured? Long-Term Metabolic Effects of Bariatric Surgery in Obese Patients with Type 2 Diabetes Mellitus , 2013, Annals of surgery.

[6]  F. Pattou,et al.  Bariatric surgery for curing NASH in the morbidly obese? , 2013, Journal of hepatology.

[7]  Joan Tordjman,et al.  Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients , 2012, Hepatology.

[8]  N. Chalasani,et al.  Erratum: The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology (Gastroenterology (2012) 142 (1592-1609)) , 2012 .

[9]  K. Cusi,et al.  Corrigendum:The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association , 2012, The American Journal of Gastroenterology.

[10]  Michael Charlton,et al.  The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. , 2012, Gastroenterology.

[11]  Richard A. Flavell,et al.  Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity , 2012, Nature.

[12]  R. Abramof Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes , 2012 .

[13]  R. Ness-Abramof Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes , 2012 .

[14]  J. Alvarez‐Leite,et al.  Food quality, physical activity, and nutritional follow-up as determinant of weight regain after Roux-en-Y gastric bypass. , 2012, Nutrition.

[15]  Reneé H Moore,et al.  A two-year randomized trial of obesity treatment in primary care practice. , 2011, The New England journal of medicine.

[16]  J. Crowley,et al.  Vitamin E and the Risk of Prostate Cancer The Selenium and Vitamin E Cancer Prevention Trial ( SELECT ) , 2011 .

[17]  W. Bilker,et al.  Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone , 2011, Diabetes Care.

[18]  B. Neuschwander‐Tetri,et al.  Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings , 2011, Hepatology.

[19]  T. Barrientos-Gutiérrez,et al.  Bariatric surgery for non-alcoholic steatohepatitis in obese patients. , 2010, The Cochrane database of systematic reviews.

[20]  D. Houlihan,et al.  Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. , 2010, The New England journal of medicine.

[21]  F. Pattou,et al.  Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. , 2009, Gastroenterology.

[22]  B. Neuschwander‐Tetri,et al.  Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial , 2009, Hepatology.

[23]  G. Aithal,et al.  Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. , 2008, Gastroenterology.

[24]  Alexander Pertsemlidis,et al.  Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease , 2008, Nature Genetics.

[25]  Claude Bouchard,et al.  Effects of bariatric surgery on mortality in Swedish obese subjects. , 2007, The New England journal of medicine.

[26]  L. Sjöström Surgical intervention as a strategy for treatment of obesity , 2000, Endocrine.

[27]  J. Barkin Gastric Bypass Surgery Improves Metabolic and Hepatic Abnormalities Associated With Nonalcoholic Fatty Liver Disease , 2007 .

[28]  F. Pattou,et al.  The evolution of severe steatosis after bariatric surgery is related to insulin resistance. , 2006, Gastroenterology.

[29]  S. Harrison,et al.  Non-Alcoholic Steatohepatitis: Effect of Roux-en-Y Gastric Bypass Surgery , 2006, The American Journal of Gastroenterology.

[30]  S. Sanderson,et al.  The natural history of nonalcoholic fatty liver disease: a population-based cohort study. , 2005, Gastroenterology.

[31]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[32]  Jonathan C. Cohen,et al.  Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity , 2004, Hepatology.

[33]  Henry Buchwald,et al.  Bariatric surgery: a systematic review and meta-analysis. , 2004, JAMA.

[34]  J. Dixon,et al.  Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss , 2004, Hepatology.

[35]  D A Follmann,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans , 2022 .

[36]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions , 1999, American Journal of Gastroenterology.

[37]  Z. Younossi,et al.  Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. , 1999, Gastroenterology.

[38]  P. Bedossa,et al.  An algorithm for the grading of activity in chronic hepatitis C , 1996, Hepatology.

[39]  M. Duerson,et al.  Jejunoileal bypass for morbid obesity. Late follow-up in 100 cases. , 1983, The New England journal of medicine.

[40]  F. Eriksson Biliointestinal bypass. , 1981, International journal of obesity.