Original article
The utility of NAFLD fibrosis score for prediction of mortality among patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of cohort study

https://doi.org/10.1016/j.clinre.2017.03.010Get rights and content

Summary

Background

Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder worldwide. Several noninvasive diagnostic scoring systems have been developed to determine the severity of liver fibrosis and to predict long-term outcome of patients with NAFLD in lieu of liver biopsy. We conducted this systematic review and meta-analysis to investigate the role of NAFLD fibrosis score (NFS) for prediction of mortality from NAFLD.

Methods

MEDLINE and EMBASE databases were searched through October 2016 for studies that investigated the association between high NFS and mortality. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effects model, generic inverse variance method. The between-study heterogeneity of effect-size was quantified using the Q statistic and I2.

Results

A total of five cohort studies with 5033 NAFLD patients were identified. High NFS (score of greater than 0.675) was significantly associated with increased mortality with the pooled RR of 4.54 (95%CI: 1.85–11.17). The statistical heterogeneity was high with I2 of 88% (Pheterogeneity < 0.01).

Conclusions

High NFS is associated with increased risk of mortality among patients with NAFLD. This scoring system may be considered as an alternative to liver biopsy for prediction of mortality outcome.

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease worldwide with the estimated global prevalence of 15–25%. It has a strong association with insulin resistance and metabolic syndrome [1]. NAFLD encompasses a wide spectrum of liver pathology, ranging from simple steatosis without fibrosis to nonalcoholic steatohepatitis with varying stages of fibrosis and cirrhosis [2], [3].

Patients with NAFLD have a significantly increased overall and liver-related mortality compared with general population [4], [5]. However, the long-term prognosis for individuals with NAFLD is not the same across the spectrum of disease. Patients with simple steatosis without fibrosis have relatively benign clinical course, with an overall mortality rate similar to general population [6], whereas patients with advanced fibrosis have much worse prognosis [7], [8].

In clinical practice, serial liver biopsy for prognostication of NAFLD is not pragmatic because of the potential complications, possibility of sampling error and cost [9], [10], [11]. Moreover, implementation of this strategy at population level would be challenging due to the high prevalence of the disease.

Several noninvasive diagnostic scoring systems have been developed to help determining the severity of liver fibrosis in lieu of liver biopsy [12]. NAFLD fibrosis score (NFS), a composite score of clinical and laboratory parameters, is one of the most accurate scoring systems to identify advanced fibrosis among patients with NAFLD [13]. Recently, the American Association for the Study of Liver Diseases (AASLD) guideline for management of NAFLD has recommended NFS as a screening tool to identify advanced fibrosis [14].

Several studies have also suggested the potential role of NFS for prediction of long-term outcome of patients with NAFLD. This systematic review and meta-analysis was conducted to summarize all available data to better characterize the association between high NFS and mortality among patients with NAFLD.

Section snippets

Search strategy

Two authors (PU and VJ) independently searched published studies indexed in PubMed/MEDLINE and EMBASE databases from inception to October 2016 using the search strategy that comprised the terms for “NAFLD” and “cohort study” as detailed in Item S1 in supplementary material. No language restriction was applied. References of selected retrieved articles were also manually reviewed.

Eligibility criteria

The eligibility criteria were as follows: (1) The study design must be cohort study. (2) Participants were adult

Results

The initial search yielded 2544 potential relevant articles (1137 articles from MEDLINE and 1407 articles from EMBASE). After the exclusion of 894 duplicated articles, 1650 articles underwent title and abstract review. Of these, 1635 articles were excluded based on title and abstract review as they clearly did not fulfill the eligibility criteria. A total of 15 articles underwent full-length review. Ten articles were excluded at this stage (six articles did not use NFS, two articles were not

Discussion

Identifying subgroup of patients with higher risk of complications and mortality is a challenge for the management of NAFLD. Early identification of those with poor prognosis is important for the initiation of cirrhosis surveillance program and early counseling/referral for liver transplantation. The presence of liver fibrosis from liver biopsy is a well-established predictor for worse long-term outcome and mortality among patients with NAFLD [7], [8]. This higher mortality is a result of

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Role of funding source

None.

Author contributions

V.J. conceived of the study, assessed the quality of the studies, and drafted the manuscript. P.U. searched the literature, assessed the quality of the studies, performed the statistical analysis, and drafted the manuscript. K.W. participated in the statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.

Disclosure of interest

The authors declare that they have no competing interest.

References (26)

  • M. Ekstedt et al.

    Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up

    Hepatology

    (2015)
  • Z.M. Younossi et al.

    Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations

    Modern Pathol

    (1998)
  • M. Mueller et al.

    Percutaneous ultrasonographically guided liver punctures: an analysis of 1961 patients over a period of ten years

    BMC Gastroenterol

    (2012)
  • Cited by (23)

    • Increased serum selenium levels are associated with reduced risk of advanced liver fibrosis and all-cause mortality in NAFLD patients: National Health and Nutrition Examination Survey (NHANES) III

      2020, Annals of Hepatology
      Citation Excerpt :

      A score above 0.676 signifies severe fibrosis or cirrhosis of the liver. A score between −1.455 and 0.675 defines intermediate fibrosis, and a score < -1.455 defines mild fibrosis [20]. These cutoffs were used to determine selenium levels in relation to levels of fibrosis.

    • Higher NAFLD fibrosis score is associated with impaired eGFR

      2020, Journal of the Formosan Medical Association
      Citation Excerpt :

      A high NFS is associated with an increased risk of mortality among patients with NAFLD. The NFS system may be considered an alternative to liver biopsy for the prediction of mortality.40 Previous studies have shown that NAFLD and CKD share many important common cardio-metabolic risk factors, such as IR, chronic inflammation, and obesity, and the NFS has been proven to be the most accurate non-invasive method for scoring of fibrosis in NASH.

    • Blood lead level is associated with advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A nationwide survey (NHANES 2011–2016)

      2020, Annals of Hepatology
      Citation Excerpt :

      A score between −1.455 and 0.675 was deemed intermediate fibrosis, and a score <−1.455 was termed low fibrosis. In this study, we used 0.676 to create a binary variable of high suspicion of liver fibrosis vs. low suspicion of liver fibrosis [17]. Our primary predictor of interest was blood Lead levels.

    View all citing articles on Scopus
    View full text