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

Brian M Parker,Jiang Wu,Daniel I Sessler,Jing You,Philip R Schauer,John P Kirwan,David S Barnes,Lisa Yerian

doi:10.1186/s40608-017-0168-y

Abstract

BackgroundRoux-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.MethodsOne 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.ResultsRYGB 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.ConclusionsRYGB surgery reverses NASH and liver fibrosis. Underlying mechanisms that facilitate improvement remain unclear.

Highlights

Roux-en-Y gastric bypass (RYGB) improves the pathophysiology that contributes to obesity-related nonalcoholic steatohepatitis (NASH)
Morbid obesity is strongly associated with nonalcoholic fatty liver disease (NAFLD), which is among the most common worldwide causes of chronic liver disease [2]
We tested the hypotheses that liver disease observed at the Parker et al BMC Obesity (2017) 4:32 time of surgery is reversible with weight loss, as evidenced by improvements in the standard biochemical tests, indocyanine green (ICG) clearance, and especially histology

Summary

Methods

Adults with class II and III obesity, scheduled for RYGB surgery were enrolled in this prospective observational study (NCT00701376). Follow-up biochemical testing was obtained including AST, ALT, ALK, total bilirubin, albumin and PT. Standard preoperative biochemical testing included AST, ALT, ALK, total bilirubin, albumin, and PT. The DDG-2001 Analyzer constructs a dyedensitogram (graphical representation) of serum ICG clearance using a non-invasive optical pulse-spectrometry finger or nasal probe. Data analysis Primary analyses Changes from before to after RYGB for each of the biochemical liver function tests (including AST, ALT, ALK, total bilirubin, albumin, and PT), ICG clearance and histological measures (including NAS steatosis, NAS lobular inflammation, NAS hepatocyte balloon, and fibrosis) were evaluated with paired t and Wilcoxon signed rank tests. We estimated the correlation between changes from baseline in biochemical liver function tests, non-invasive ICG clearance tests, and histological measures using Pearson correlation coefficient or Spearman rank-order correlation, as appropriate. Secondary analyses We grouped patients into one of the following four liver disease categories based on their histological measures prior to surgery. (1) normal liver defined as steatosis 5% without any ballooning cells and lobular inflammation

Results

Background

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Conclusion