Simple Noninvasive Systems Predict Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease

doi:10.1053/j.gastro.2013.06.057

Gastroenterology

Volume 145, Issue 4, October 2013, Pages 782-789.e4

https://doi.org/10.1053/j.gastro.2013.06.057 Get rights and content

Background & Aims

Some patients with nonalcoholic fatty liver disease (NAFLD) develop liver-related complications and have higher mortality than other patients with NAFLD. We determined the accuracy of simple, noninvasive scoring systems in identification of patients at increased risk for liver-related complications or death.

Methods

We performed a retrospective, international, multicenter cohort study of 320 patients diagnosed with NAFLD, based on liver biopsy analysis through 2002 and followed through 2011. Patients were assigned to mild-, intermediate-, or high-risk groups based on cutoff values for 2 of the following: NAFLD fibrosis score, aspartate aminotransferase/platelet ratio index, FIB-4 score, and BARD score. Outcomes included liver-related complications and death or liver transplantation. We used multivariate Cox proportional hazard regression analysis to adjust for relevant variables and calculate adjusted hazard ratios (aHRs).

Results

During a median follow-up period of 104.8 months (range, 3−317 months), 14% of patients developed liver-related events and 13% died or underwent liver transplantation. The aHRs for liver-related events in the intermediate-risk and high-risk groups, compared with the low-risk group, were 7.7 (95% confidence interval [CI]: 1.4−42.7) and 34.2 (95% CI: 6.5−180.1), respectively, based on NAFLD fibrosis score; 8.8 (95% CI: 1.1−67.3) and 20.9 (95% CI: 2.6−165.3) based on the aspartate aminotransferase/platelet ratio index; and 6.2 (95% CI: 1.4−27.2) and 6.6 (95% CI: 1.4−31.1) based on the BARD score. The aHRs for death or liver transplantation in the intermediate-risk and high-risk groups compared with the low-risk group were 4.2 (95% CI: 1.3−13.8) and 9.8 (95% CI: 2.7−35.3), respectively, based on the NAFLD fibrosis scores. Based on aspartate aminotransferase/platelet ratio index and FIB-4 score, only the high-risk group had a greater risk of death or liver transplantation (aHR = 3.1; 95% CI: 1.1−8.4 and aHR = 6.6; 95% CI: 2.3−20.4, respectively).

Conclusions

Simple noninvasive scoring systems help identify patients with NAFLD who are at increased risk for liver-related complications or death. NAFLD fibrosis score appears to be the best indicator of patients at risk, based on HRs. The results of this study require external validation.

Section snippets

Patients and Methods

This was a retrospective, international, multicenter cohort study of 320 patients with well-characterized and liver biopsy−confirmed NAFLD. They were untreated, consecutively biopsied patients that met the eligibility criteria as described here, and were recruited before 2002 from the following medical centers: University of Kentucky Medical Center, Lexington, KY; Westmead Hospital, Sydney Australia; Newcastle Hospitals National Health Service Foundation Trust in Newcastle-upon-Tyne, UK;

Baseline Characteristics

Table 1 describes the baseline characteristics of the 320 patients. Median age was 52 years (interquartile range, 43−61 years) with a similar distribution of men and women. There was a predominance of white race and overweight or obese individuals, and about one third to more than a half of patients suffered from diabetes, hypertension, or dyslipidemia. Mean ALT and AST were about twice normal, and there was a uniform distribution of patients across the stages of fibrosis. Mean values of each

Discussion

Our study demonstrates that simple baseline noninvasive scores allow appropriate identification of patients with NAFLD at a higher risk of developing liver-related complications, or the outcome of death/liver transplantation. Given the ready availability of the data and the simplicity of the calculation, along with the relatively high accuracy in separating patients' risks, these scores seems to be valuable and practical tools that can be used clinically for patient counseling and monitoring.

Acknowledgments

Title and abstract edited by Gastroenterology Science Editor, Kristine Novak, PhD.

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Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of liver-related morbidity and mortality worldwide, afflicting approximately a billion individuals. NAFLD is a slowly progressive disease that may evolve in a subset of patients toward cirrhosis, hepatocellular carcinoma, and end-stage liver disease. Liver fibrosis severity is the strongest predictor of clinical outcomes. The emergence of effective therapeutics on the horizon highlights the need to identify among patients with NAFLD, those with severe fibrosis or cirrhosis, who are the most at risk of developing complications and target them for therapy. Liver biopsy has been the reference standard for this purpose. However, it is not suitable for large-scale population evaluation, given its well-known limitations (invasiveness, rare but severe complications, and sampling variability). Thus, there have been major efforts to develop simple noninvasive tools that can be used in routine clinical settings and in drug development. Noninvasive approaches are based on the quantification of biomarkers in serum samples or on the measurement of liver stiffness, using either ultrasound- or magnetic resonance–based elastography techniques. This review provides a roadmap for future development and integration of noninvasive tools in clinical practice and in drug development in NAFLD. We discuss herein the principles for their development and validation, their use in clinical practice, including for diagnosis of NAFLD, risk stratification in primary care and hepatology settings, prediction of long-term liver-related and non–liver-related outcomes, monitoring of fibrosis progression and regression, and response to future treatment.
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: Conflicts of interest The authors disclose no conflicts.

: Funding This study was supported by a National Institute of Health R01 DK82426 grant (to P. Angulo) and The European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F2-2009-241762 for the project FLIP (to E. Bugianesi). J. George is supported by grants from the Sydney Medical Foundation and grants from the National Health and Medical Research Council (632630 and 1049857). These sponsors played no role in the study design or the collection, analysis, and interpretation of data.

^§: Authors share co-senior authorship.

View full text

Original ResearchFull Report: Clinical—LiverSimple Noninvasive Systems Predict Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease

Background & Aims

Methods

Results

Conclusions

Section snippets

Patients and Methods

Baseline Characteristics

Discussion

Acknowledgments

J Hepatol

Gastroenterology

Ann Hepatol

Hepatology

Clin Gastroenterol Hepatol

Clin Liver Dis

Lancet

Am J Gastroenterol

J Am Coll Cardiol

Lancet

Liver Transpl

Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research

Semin Liver Dis

Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease

Hepatology

Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease

Clin Gastroenterol Hepatol

Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States

Liver Transpl

Liver transplantation for nonalcoholic steatohepatitis: the new epidemic

Ann Surg

Original Research
Full Report: Clinical—Liver
Simple Noninvasive Systems Predict Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease