Reversal of fibrosis in patients with nonalcoholic steatohepatosis after gastric bypass surgery

Abstract

Background: Roux-en-Y gastric bypass (RYGB) improves the pathophysiology that contributes to obesity-related nonalcoholic steatohepatitis (NASH). Whether obesity-related fibrosis improves is unclear. We hypothesized that RYGB reverses NASH and fibrosis, and indocyanine green (ICG) clearance provides a sensitive measure for detecting asymptomatic fatty liver disease.

Methods: One hundred six obese adults scheduled for RYGB had preoperative liver function assessed using standard tests and ICG clearance and core liver biopsies obtained during RYGB. Once patients lost 60% of their preoperative weight or weight loss plateaued, liver function was reassessed. Repeat liver biopsies were obtained on patients with NASH at the time of RYGB.

Results: RYGB improved steatosis, lobular inflammation, hepatocyte ballooning and fibrosis. Serum albumin, AST, and ALT decreased the most in patients with NASH and NASH plus fibrosis. Twenty seven (26%) patients had normal baseline liver histology and 45 (43%) had NASH or NASH plus fibrosis. Nine of 13 patients with substantial fatty liver had normalized histology after weight loss, while severity of disease in the rest had stabilized or was reduced. Mean ICG clearance in patients with normal/mild fatty liver disease and those with histological fatty livers did not differ significantly.

Conclusions: RYGB surgery reverses NASH and liver fibrosis. Underlying mechanisms that facilitate improvement remain unclear.

Keywords: Anesthesia; Fatty; Fibrosis; Liver; Non-alcoholic steatohepatitis; Roux-en-Y gastric bypass.

Fig. 1

Receiver operating characteristic curves with area under the curve and standard error in parentheses. Displayed are the biochemical liver function tests and non- invasive ICG clearance test at pre-RYGB predicting significant fatty liver disease (nonalcoholic steatohepatitis). ICG = indocyanine green, RYGB = Roux-en-Y gastric bypass

Fig. 2

Receiver operating characteristic curves with area under the curve and standard error n parentheses for a multivariable model using all the preoperative liver function tests (except PTT due to a large proportion of missing values) and the ICG k value at pre-RYGB to predict significant fatty liver disease. Significant fatty liver, including nonalcoholic steatohepatitis (NASH) and NASH plus fibrosis, is defined as steatosis >5% with at least a few balloon cells and lobular inflammation >2 foci/200×. ICG = indocyanine green, PTT = Partial Thromboplastin Time, RYGB = Roux-en-Y gastric bypass