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. 2019 Aug 1;14(8):e0220612.
doi: 10.1371/journal.pone.0220612. eCollection 2019.

Increasing metabolic co-morbidities are associated with higher risk of advanced fibrosis in nonalcoholic steatohepatitis

Robert J Wong  1 , Tram Tran  2 , Harvey Kaufman  3 , Justin Niles  3 , Robert Gish  4
Affiliations

Increasing metabolic co-morbidities are associated with higher risk of advanced fibrosis in nonalcoholic steatohepatitis

Robert J Wong et al. PLoS One. .

Abstract

Hepatic fibrosis and advanced fibrosis in particular is the strongest predictor of liver-related outcomes and mortality among nonalcoholic steatohepatitis (NASH) patients. Understanding prevalence and predictors of NASH with advanced fibrosis is critical for healthcare resource planning. Using a large U.S. clinical laboratory database from 10/1/2017-9/30/2018, adults negative for hepatitis B and hepatitis C and after excluding for alcoholic liver disease and pregnancy were evaluated for prevalence of F3 and F4 fibrosis using a systematic algorithm of five fibrosis-4 (FIB-4) criteria: Criteria 1 (≥F3: >2.67), Criteria 2 (2.67<F3≤4.12 and F4>4.12), Criteria 3 (2.67<F3≤3.15, F4>3.15), Criteria 4 (3.25<F3≤3.5, F4>3.5), Criteria 5 (3.25<F3≤4.12, F4>4.12). Metabolic co-morbidities evaluated included decreased high density lipoprotein (<40 mg/dL men, <50 mg/dL women), high triglycerides (≥150 mg/dL), elevated hemoglobin A1C (≥6.5%). Parallel analyses of patients with specific NAFLD/NASH ICD-9/10 codes from 10/1/2013-9/30/2018 were performed. Multivariate logistic regression models evaluated for predictors of ≥F3 fibrosis. Among patients with NAFLD/NASH ICD-9/10 codes, ≥F3 prevalence ranged from 4.35% - 6.90%, and F4 prevalence ranged from 2.52%- 3.67%. Increasing metabolic co-morbidities was associated with higher risk of ≥F3 fibrosis. Compared to NASH patients without metabolic co-morbidities, NASH with four concurrent metabolic co-morbidities had higher risk of ≥F3 (OR 1.56, 95% CI 1.40-1.73, p<0.001). In summary, prevalence of NASH with advanced fibrosis among U.S. adults was as high as 6.90% and prevalence of NASH with cirrhosis was as high as 3.67%, representing 5.18 million and 2.75 million, respectively, when using an estimate of 75 million U.S. adults with NAFLD. Co-morbid metabolic abnormalities were associated with higher risk of advanced fibrosis among NASH patients.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: Robert Wong: research grants, consulting, advisory board, speaker’s bureau – Gilead Sciences; research grants – Abbvie; speaker’s bureau – Salix, Bayer; research grant – AASLD Foundation; Tram Tran: employee and stocks – Gilead Sciences; Harvey Kaufman: None; Justin Niles: None; Robert Gish: consulting, advisor - Abbot, AbbVie, Alexion, Arrowhead, Bayer AG, Biocollections, Bristol-Myers Squibb Company, Contravir, Eiger, Enyo, eStudySite, Genentech, Gilead Sciences, HepaTX, HepQuant, Hoffmann-LaRoche Ltd., Intellia, Intercept, Ionis Pharmaceuticals, Janssen, MedImmune, Merck, Prometheus, Quest, Shionogi, Transgene, Trimaran; Scientific/clinical Advisory Boards -AbbVie, Merck, Arrowhead, Bayer, Contravir, Dova Pharmaceuticals, Eiger, Enyo, Janssen, Medimmune, Janssen/J&J, Intercept, Shionogi, Spring Bank; Clinical trials – eStudySite. Chair Clinical Advisory Board – Arrowhead; Data Safety Monitoring Board – Ionis; Speaker’s bureau – AbbVie, Alexion, Bayer, BMS, Gilead Sciences Inc., Merck; Minor stock shareholder - Athenex, Triact, Synageva, RiboSciences, CoCrystal; Stock options – Arrowhead, Eiger. The above competing interests statement and funding do not alter our adherence to all PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Flowchart to identify the study cohort.
Fig 2
Fig 2. Prevalence of F3 and F4 fibrosis among NAFLD/NASH ICD-9/10 patients with increasing number of metabolic co-morbidities.
See this image and copyright information in PMC

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