Gastroenterology

Gastroenterology

Volume 159, Issue 4, October 2020, Pages 1290-1301.e5
Gastroenterology

Original Research
Full Report: Clinical—Liver
Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis

https://doi.org/10.1053/j.gastro.2020.06.006Get rights and content

Background and Aims

Studies are needed to determine the long-term effects of bariatric surgery for patients with nonalcoholic steatohepatitis (NASH). We evaluated sequential liver samples, collected the time of bariatric surgery and 1 and 5 years later, to assess the long-term effects of bariatric surgery in patients with NASH.

Methods

We performed a prospective study of 180 severely obese patients with biopsy-proven NASH, defined by the NASH clinical research network histologic scores. The patients underwent bariatric surgery at a single center in France and were followed for 5 years. We obtained liver samples from 125 of 169 patients (76%) having reached 1 year and 64 of 94 patients (68%) having reached 5 years after surgery. The primary endpoint was the resolution of NASH without worsening of fibrosis at 5 years. Secondary end points were improvement in fibrosis (reduction of ≥1 stage) at 5 years and regression of fibrosis and NASH at 1 and 5 years.

Results

At 5 years after bariatric surgery, NASH was resolved, without worsening fibrosis, in samples from 84% of patients (n = 64; 95% confidence interval, 73.1%-92.2%). Fibrosis decreased, compared with baseline, in samples from 70.2% of patients (95% CI, 56.6%-81.6%). Fibrosis disappeared from samples from 56% of all patients (95% CI, 42.4%-69.3%) and from samples from 45.5% of patients with baseline bridging fibrosis. Persistence of NASH was associated with no decrease in fibrosis and less weight loss (reduction in body mass index of 6.3 ± 4.1 kg/m2 in patients with persistent NASH vs reduction of 13.4 ± 7.4 kg/m2; P = .017 with resolution of NASH). Resolution of NASH was observed at 1 year after bariatric surgery in biopsies from 84% of patients, with no significant recurrence between 1 and 5 years (P = .17). Fibrosis began to decrease by 1 year after surgery and continued to decrease until 5 years (P < .001).

Conclusions

In a long-term follow-up of patients with NASH who underwent bariatric surgery, we observed resolution of NASH in liver samples from 84% of patients 5 years later. The reduction of fibrosis is progressive, beginning during the first year and continuing through 5 years.

Section snippets

Outcomes

The primary outcome of our study was the resolution of NASH with no worsening of fibrosis 5 years after surgery. The secondary outcomes were (1) improvement in fibrosis (reduction of ≥1 stage) at 5 years, and (2) progression of NASH and fibrosis, compared with baseline, at 1 and 5 years. Fibrosis stage 1a, 1b, and 1c were considered to be stage 1 for the statistical analysis. Other secondary outcomes included changes from baseline to 5 years in serum aminotransferase, γ-glutamyltranspeptidase,

Cohort Patients

Of the patients enrolled in the Lille bariatric cohort at analysis, 180 presented with liver specimen-proven NASH at surgery (Figure 1). This NASH cohort mainly included women, mean age of 46.7 years, with a median fibrosis score of 2 (IQR, 1–3). Patient characteristics are summarized in Table 1. The main surgical procedure was gastric bypass (66.1%) (Supplementary Table 1).

During the 5-year follow-up, 3 patients died of nonliver-related causes, including 2 deaths from surgical complications

Discussion

In this long-term prospective study with consecutive liver biopsies, bariatric surgery induced the resolution of NASH without worsening of fibrosis in 84% of patients at 5 years. Long-term resolution of NASH led to the regression of fibrosis in 70% of patients. The resolution of NASH occurred within the first year and was maintained over the 5-year period, whereas fibrosis began to improve within 1 year and continued throughout the 5-year follow-up.

With an 80% success rate for the resolution of

Conclusion

This prospective 5-year follow-up of obese NASH patients showed that the beneficial effects of bariatric surgery on the resolution of NASH were durable and led to a sustained reduction in fibrosis over 5 years.

Acknowledgments

The authors gratefully acknowledge Shirley Balik, Marie Clement, Aurelie Lobez, and Sarah Surmont, for their daily work on prospective data collection. The authors acknowledge Dr D. Buob and Dr B. Bouchindhomme for their work and implication in the analysis of liver biopsy specimens.

CRediT Authorship Contributions

Guillaume Lassailly, MD (Data curation: Equal; Formal analysis: Equal; Investigation:

Equal; Methodology: Equal; Writing – original draft: Lead; Writing – review & editing:

Equal); Robert Caiazzo, MD, PhD

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Conflicts of interest The authors disclose no conflicts.

Funding This work was supported by grants from the French Ministry of Health (Programme Hospitalier de Recherche Clinique) and from the Conseil Régional Nord-Pas de Calais (ARCIR Obésité et Alcool), Agence National de la Recherche (European Genomic Institute for Diabetes [EGID], ANR-10-LABX-46, PreciNASH, ANR-16-RHUS-0006), and the European commission (FEDER).

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