Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)

Danielle Brandman¹, Marie Boyle^{2

3}, Stuart McPherson^{2

3}, Mark L Van Natta⁴, Arun J Sanyal⁵, Kris Kowdley⁶, Brent Neuschwander-Tetri⁷, Naga Chalasani⁸, Manal F Abdelmalek⁹, Norah A Terrault¹⁰, Art McCullough¹¹, Ricki Bettencourt¹², Cyrielle Caussy¹², David E Kleiner¹³, Cynthia Behling¹⁴, James Tonascia⁴, Quentin M Anstee², Rohit Loomba¹²; Members of the Nonalcoholic Steatohepatitis Clinical Research Network

Affiliations

¹ Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
² Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
³ Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.
⁴ John Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵ Department of Internal Medicine, Medical College of Virginia, Richmond, Virginia, USA.
⁶ Swedish Medical Group, Seattle, Washington, USA.
⁷ Division of Gastroenterology and Hepatology, Department of Medicine, Saint Louis University, Saint Louis, Missouri, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
⁹ Division of Gastroenterology, Hepatology, and Nutrition, Duke University, Durham, North Carolina, USA.
¹⁰ Division of Gastroenterology and Liver, Keck Medicine, University of Southern California, Los Angeles, California, USA.
¹¹ Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
¹² NAFLD Research Center, Department of Medicine, University of California San Diego, San Diego, California, USA.
¹³ Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹⁴ Analytic Pathology Medical Group, Sharp Memorial Hospital, San Diego, California, USA.

PMID: 35302256
PMCID: PMC9098681
DOI: 10.1111/apt.16874

Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)

Danielle Brandman et al. Aliment Pharmacol Ther. 2022 Jun.

. 2022 Jun;55(11):1441-1451.

doi: 10.1111/apt.16874. Epub 2022 Mar 17.

Authors

Affiliations

¹ Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
² Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
³ Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.
⁴ John Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵ Department of Internal Medicine, Medical College of Virginia, Richmond, Virginia, USA.
⁶ Swedish Medical Group, Seattle, Washington, USA.
⁷ Division of Gastroenterology and Hepatology, Department of Medicine, Saint Louis University, Saint Louis, Missouri, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
⁹ Division of Gastroenterology, Hepatology, and Nutrition, Duke University, Durham, North Carolina, USA.
¹⁰ Division of Gastroenterology and Liver, Keck Medicine, University of Southern California, Los Angeles, California, USA.
¹¹ Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
¹² NAFLD Research Center, Department of Medicine, University of California San Diego, San Diego, California, USA.
¹³ Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹⁴ Analytic Pathology Medical Group, Sharp Memorial Hospital, San Diego, California, USA.

PMID: 35302256
PMCID: PMC9098681
DOI: 10.1111/apt.16874

Abstract

Background and aims: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD.

Methods: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort.

Results: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89).

Conclusions: This cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher-risk patients maintain access to specialty care.

Keywords: cirrhosis; nonalcoholic fatty liver disease; noninvasive assessment.

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Figures

**FIGURE 1**
Performance of seven clinical prediction rules for diagnosis of cirrhosis in the US cohort (US)

See this image and copyright information in PMC

Comment in

Letter: non-invasive prediction models to exclude cirrhosis in NAFLD-not everyone fits the mould. Authors' reply.
Brandman D, Boyle M, McPherson S, Van Natta ML, Sanyal AJ, Kowdley K, Neuschwander-Tetri B, Chalasani N, Abdelmalek MF, Terrault NA, McCullough A, Bettencourt R, Caussy C, Kleiner DE, Behling C, Tonascia J, Anstee QM, Loomba R. Brandman D, et al. Aliment Pharmacol Ther. 2022 Jul;56(1):182-183. doi: 10.1111/apt.16972. Aliment Pharmacol Ther. 2022. PMID: 35689309 No abstract available.
Letter: non-invasive prediction models to exclude cirrhosis in NAFLD - not everyone fits the mould.
Giri S, Agrawal D, Afzalpurkar S. Giri S, et al. Aliment Pharmacol Ther. 2022 Jul;56(1):180-181. doi: 10.1111/apt.16931. Aliment Pharmacol Ther. 2022. PMID: 35689312 No abstract available.
Letter: comparison of clinical prediction rules for ruling out cirrhosis in non-alcoholic fatty liver disease (NAFLD).
Shiha G, Mikhail N, Soliman R. Shiha G, et al. Aliment Pharmacol Ther. 2022 Sep;56(6):1098-1099. doi: 10.1111/apt.17174. Aliment Pharmacol Ther. 2022. PMID: 35995744 No abstract available.

References

1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. 10.1002/hep.28431 - DOI - PubMed
1. Browning JD, Szczepaniak LS, Dobbins R, Nurember P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387–95. 10.1002/hep.20466 - DOI - PubMed
1. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, et al. Prevalence of nonalcoholic fatty liver disease and non-alcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124–31. 10.1053/j.gastro.2010.09.038 - DOI - PubMed
1. Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643–54 e1– 9; quiz e39–40. doi:10.1016/j.cgh.2014.04.014 - DOI - PMC - PubMed
1. McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015;62(5):1148–55. 10.1016/j.jhep.2014.11.034 - DOI - PubMed

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Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)

Affiliations

Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)

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