Original Article
Hepatology
Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study

https://doi.org/10.1016/j.cgh.2022.01.002Get rights and content

Background & Aims

There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage.

Methods

This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients.

Results

The median follow-up period was 4.6 years (range, 0.3–21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52–3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02–7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02–5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality.

Conclusions

Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.

Section snippets

Methods

This registry-based multicenter historical cohort study was approved by the institutional review board of Saga University Hospital (approval no. 2020-04-R-02, June 30, 2020), which waived the requirement for informed consent because of the use of pre-existing data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.

Baseline Characteristics

Of 1760 patients, 378 met the exclusion criteria and were initially excluded from this study. However, 16 were reinstated based on positive serology for hepatitis C virus (HCV) but a negative HCV-RNA test and no previous HCV treatment (n = 8) or the presence of burned-out NASH (no increased fat; fibrosis stage 4) (n = 8) (Supplementary Figure 1). Thus, 1398 patients were included in the final analysis. Table 1 describes the baseline characteristics of these patients. The number of patients with

Discussion

Herein, we reported the clinical outcomes of 1398 Asian patients with biopsy-proven NAFLD. Although liver fibrosis was independently associated with liver-related events, it was not associated with overall mortality, after adjusting for confounders, such as histologic features of steatohepatitis.

Liver fibrosis is the most important predictor of mortality in NAFLD.6, 7, 8 In their meta-analysis of fibrosis stage-specific data pooled from five multinational NAFLD cohorts, Dulai et al reported

Conclusion

In conclusion, although fibrosis stage was independently associated with liver-related events before and after adjusting for confounding factors, it was not associated with overall mortality after adjustment. These results are relevant for patient counseling and monitoring, as well as for interpreting and designing future clinical trials in Asian patients with NAFLD.

Acknowledgments

The authors thank Japan Strategic Medical Administration Research Center (J-SMARC) for financial support in this study. The authors thank Ms Keiko Ota and Ms Masayo Kitano (Osaka City University) for their technical assistance in creating this REDCap project. The authors also thank Ms Kozue Tashiro and Ms Maki Miyahara (Saga University Hospital) and Ms Miki Noguchi (Kawasaki Medical School) for their technical assistance in creating virtual slides. The authors also thank BioScienceWriters (//www.biosciencewriters.com/

References (45)

  • B.A. Davison et al.

    Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials

    J Hepatol

    (2020)
  • Z.M. Younossi et al.

    Global epidemiology of nonalcoholic fatty liver disease: meta-analytic assessment of prevalence, incidence, and outcomes

    Hepatology

    (2016)
  • N. Chalasani et al.

    The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases

    Hepatology

    (2018)

  • European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

    J Hepatol

    (2016)
  • V.W. Wong et al.

    Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease Guidelines 2017-Part 1: definition, risk factors and assessment

    J Gastroenterol Hepatol

    (2018)
  • P. Angulo et al.

    Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease

    Gastroenterology

    (2015)
  • T.G. Simon et al.

    Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort

    Gut

    (2021)
  • S. Dam-Larsen et al.

    Final results of a long-term, clinical follow-up in fatty liver patients

    Scand J Gastroenterol

    (2009)
  • G.A. Kim et al.

    Association between non-alcoholic fatty liver disease and cancer incidence rate

    J Hepatol

    (2017)
  • H. Ueshima et al.

    Cardiovascular disease and risk factors in Asia: a selected review

    Circulation

    (2008)
  • A. Sekikawa et al.

    Continuous decline in mortality from coronary heart disease in Japan despite a continuous and marked rise in total cholesterol: Japanese experience after the Seven Countries Study

    Int J Epidemiol

    (2015)
  • J.C. Leung et al.

    Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients

    Hepatology

    (2017)

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    Conflicts of interest The authors disclose no conflicts.

    Funding This research was financially supported by Japan Strategic Medical Administration Research Center (J-SMARC).

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