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Evaluation of ballooned hepatocytes as a risk factor for future progression of fibrosis in patients with non-alcoholic fatty liver disease

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

A Letter to the Editor to this article was published on 26 March 2019

Abstract

Background

The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased. Non-alcoholic steatohepatitis (NASH) shows progression of liver fibrosis in NAFLD. It remains unclear which patients with NAFLD will show progression of liver fibrosis. Therefore, we aimed to investigate the risk factor associated with the progression of liver fibrosis among patients with NAFLD.

Methods

This observational study enrolled 157 patients with biopsy-proven NAFLD. Thirty-two patients were excluded because of lack of data. The accuracy of the formulae for estimating liver fibrosis, i.e., the FIB-4 index, APRI, and Forns index, was compared. Using serial changes of the best formula for liver fibrosis, we identified factors associated with the progression of liver fibrosis. Histological liver fibrosis was quantified using the Brunt stage.

Results

Sixty-three patients were diagnosed as having NASH. The FIB-4 index provided the best diagnostic accuracy for liver fibrosis [Brunt stage 0 versus 1–4, areas under the curve (AUC) 0.74; 0–1 versus 2–4, AUC 0.77; 0–2 versus 3–4, AUC 0.78; and 1–3 versus 4, AUC 0.87]. The association between body mass index, sex, observation period, and histological findings (liver fat content, bridging fibrosis, and hepatocyte ballooning) with the change in the FIB-4 index was evaluated among patients with NASH, using multivariate analysis. Among these factors, hepatocyte ballooning was associated with an increase in the FIB-4 index.

Conclusion

The FIB-4 index was the best formula for estimating liver fibrosis in patients with biopsy-proven NAFLD, and the presence of ballooned hepatocytes was a risk factor for the progression of liver fibrosis.

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Abbreviations

ALT:

Alanine transaminase

APRI:

Aspartate transaminase to platelet ratio index

AST:

Aspartate transaminase

AUROC:

Area under the receiver operating characteristic

BF:

Bridging fibrosis

BH:

Ballooned hepatocyte

BMI:

Body mass index

FIB-4:

Fibrosis 4

γGT:

Gamma-glutamyl transferase

HOMA-R:

Homeostatic model assessment for insulin resistance

M2BPGi:

Mac-2 binding protein glycan isomer

MR:

Magnetic resonance

NAFL:

Non-alcoholic fatty liver

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

ROC:

Receiver operating characteristic

SHH:

Sonic hedgehog

T4C7s:

Type 4 collagen 7s

TC:

Total cholesterol

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Acknowledgements

This study was supported by KAKENHI Grant no. JP16K21307 and the Keiryokai Research Foundation Grant no. Y117.

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Authors and Affiliations

  1. Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 0208505, Japan

    Keisuke Kakisaka, Yuji Suzuki, Yudai Fujiwara, Tamami Abe, Miki Yonezawa, Hidekatsu Kuroda & Yasuhiro Takikawa

  2. Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan

    Kazuyuki Ishida & Tamotsu Sugai

Authors
  1. Keisuke Kakisaka
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  2. Yuji Suzuki
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Correspondence to Keisuke Kakisaka.

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535_2018_1468_MOESM1_ESM.pptx

Supplemental Fig. 1. Difference of liver fat volume according to ballooned hepatocytes. A and B: Distribution of the liver fat volume among subjects divided by the presence or absence of ballooned hepatocytes (A) or the grading of ballooned hepatocytes (B). (PPTX 73 kb)

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Kakisaka, K., Suzuki, Y., Fujiwara, Y. et al. Evaluation of ballooned hepatocytes as a risk factor for future progression of fibrosis in patients with non-alcoholic fatty liver disease. J Gastroenterol 53, 1285–1291 (2018). https://doi.org/10.1007/s00535-018-1468-9

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  • DOI: https://doi.org/10.1007/s00535-018-1468-9

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