The Concept of Indeterminable NASH Inducted by Preoperative Diet and Metabolic Surgery: Analyses of Histopathological and Clinical Features

Abstract

Practitioners routinely perform intraoperative liver biopsies during laparoscopic sleeve gastrectomy (LSG) to evaluate nonalcoholic fatty liver disease (NAFLD). In some patients, hepatocyte ballooning, inflammation, and fibrosis without steatosis are observed, even in the absence of other etiologies. We call this finding indeterminable nonalcoholic steatohepatitis (Ind-NASH). In this study, we clarified the prevalence, as well as histopathological and clinical features, of Ind-NASH through intraoperative liver biopsy in Japanese patients presenting with severe obesity. We enrolled 63 patients who had undergone LSG and intraoperative liver biopsy. In patients diagnosed with histopathological NASH, we performed protocol liver biopsies at 6 and 12 months after LSG. We statistically analyzed these histopathological findings and clinical parameters and found the prevalence rate of Ind-NASH discovered through intraoperative biopsy to be 15.9%. Protocol liver biopsy also revealed that Ind-NASH was an intermediate condition between NASH and normal liver. The clinical features of patients with Ind-NASH are a higher body weight compared to NASH (134.9 kg vs. 114.7 kg; p = 0.0245), stronger insulin resistance compared to nonalcoholic fatty liver (homeostasis model assessment–insulin resistance: 7.1 vs. 4.9; p = 0.0188), and mild liver dysfunction compared to NASH. Patients with Ind-NASH observed positive weight-loss effects from a preoperative diet compared to the postoperative course (percentage total weight loss: 32.0% vs. 26.7%; p < 0.0001). Patients with Ind-NASH may also be good candidates for metabolic surgery owing to their good treatment response; therefore, efforts should be made by specialists in the near future to deeply discuss and define Ind-NASH.

Effects of laparoscopic sleeve gastrectomy on nonalcoholic fatty liver disease and TGF-β signaling pathway

“…As we previously reported, LSG dramatically improves not only the clinical parameters related to NAFLD but also liver fibrosis, as assessed using the pericellular fibrosis score (PFS), a central vein fibrosis index [4]. In addition, though time-consuming, we also reported that fibrosis of NASH was improved by MS and resulted in a return to normal liver function [1]. Thus, expanding the indications for MS further is a desirable goal of future research.…”

“…Three groups were compared according to the NAS or PFS using one-way analysis of variance with Tukey's post hoc test. Univariate and multivariate analyses with a linear regression model were conducted to analyze predictive factors associated with NAS and PFS; the variables were selected based on the results of univariate analysis and previous reports [1,4]. All statistical analyses were performed using the EZR software version 1.61 (Jichi Medical University, Saitama Medical Center, Saitama, Japan) [17].…”

“…In response, metabolic surgery (MS), such as laparoscopic sleeve gastrectomy (LSG), which promotes weight loss, can effectually treat NAFLD [1,3]. As we previously reported, LSG dramatically improves not only the clinical parameters related to NAFLD but also liver fibrosis, as assessed using the pericellular fibrosis score (PFS), a central vein fibrosis index [4].…”

“…One of the challenges in diagnosing NAFLD is that the histopathological evaluation of liver tissues obtained via biopsy remains the gold standard [1]. A liver biopsy is required for a liver fibrosis evaluation, and while several non-invasive scoring systems have been introduced [5][6][7], they are somewhat complicated because they combine such indicators such as transaminases and type 4 collagen 7S.…”

Identification of a Fatty Acid for Diagnosing Non-Alcoholic Steatohepatitis in Patients with Severe Obesity Undergoing Metabolic Surgery

“…NAFLD subtypes include nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), with NASH patients who suffer from advanced fibrosis being at increased risk of liver cirrhosis and liver disease-related death [ 2 ]. Metabolic surgery (MS), including laparoscopic sleeve gastrectomy (LSG), dramatically improved histological findings of NASH as well as type 2 diabetes (T2D); therefore, LSG and other MS may be strong alternatives for improving NASH [ 3 , 4 ].…”