Cited by 426Liver Disease Diagnosis and TreatmentLiver Diseases and ImmunityCholesterol and Lipid Metabolism

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The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids

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Puri, Puneet, Daita, Kalyani, Joyce, Andrew, Mirshahi, Faridoddin, Santhekadur, Prasanna K., Cazanave, Sophie, Luketic, Velimir A, Siddiqui, Mohammad S., Boyett, Sherry, Min, Hae‐Ki, Kumar, Divya P., Kohli, Rohit, Zhou, Huiping, Hylemon, Phillip B., Contos, Melissa J., Idowu, Michael, Sanyal, Arun J.·2018·Hepatology

DOI 10.1002/hep.29359PMC PMC5764808

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Abstract

The histologic spectrum of nonalcoholic fatty liver disease (NAFLD) includes fatty liver (NAFL) and steatohepatitis (NASH), which can progress to cirrhosis in up to 20% of NASH patients. Bile acids (BA) are linked to the pathogenesis and therapy of NASH. We (1) characterized the plasma BA profile in biopsy‐proven NAFL and NASH and compared to controls and (2) related the plasma BA profile to liver histologic features, disease activity, and fibrosis. Liquid chromatography/mass spectrometry quantified BAs. Descriptive statistics, paired and multiple group comparisons, and regression analyses were performed. Of 86 patients (24 controls, 25 NAFL, and 37 NASH; mean age 51.8 years and body mass index 31.9 kg/m 2), 66% were women. Increased total primary BAs and decreased secondary BAs (both P < 0.05) characterized NASH. Total conjugated primary BAs were significantly higher in NASH versus NAFL (P = 0.047) and versus controls (P < 0.0001). NASH had higher conjugated to unconjugated chenodeoxycholate (P = 0.04), cholate (P = 0.0004), and total primary BAs (P < 0.0001). The total cholate to chenodeoxycholate ratio was significantly higher in NAFLD without (P = 0.005) and with (P = 0.02) diabetes. Increased key BAs were associated with higher grades of steatosis (taurocholate), lobular (glycocholate) and portal inflammation (taurolithocholate), and hepatocyte ballooning (taurocholate). Conjugated cholate and taurocholate directly and secondary to primary BA ratio inversely correlated to NAFLD activity score. A higher ratio of total secondary to primary BA decreased (odds ratio, 0.57; P = 0.004) and higher conjugated cholate increased the likelihood of significant fibrosis (F≥2) (P = 0.007). Conclusion: NAFLD is associated with significantly altered circulating BA composition, likely unaffected by type 2 diabetes, and correlated with histological features of NASH; these observations provide the foundation for future hypothesis‐driven studies of specific effects of BAs on specific aspects of NASH. (H epatology 2018;67:534‐548).

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Authors: Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., Min, H., Kumar, D. P., Kohli, R., Zhou, H., Hylemon, P. B., Contos, M. J., Idowu, M., & Sanyal, A. J.
Affiliations: Virginia Commonwealth University (US)
Venebio (United States) (US)
University of Southern California (US)
Corresponding author: Puri, Puneet
ORCID: Mirshahi, Faridoddin
Santhekadur, Prasanna K.
Cazanave, Sophie
Luketic, Velimir A
Siddiqui, Mohammad S.
Min, Hae‐Ki
Kumar, Divya P.
Kohli, Rohit
Zhou, Huiping
Hylemon, Phillip B.
Idowu, Michael
Sanyal, Arun J.
Venue: Hepatology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2017-12-23
Volume: 67
Issue: 2
Pages: 534-548
ISSN: 0270-9139 (ISSN-L)
1527-3350
DOI: 10.1002/hep.29359
PMC: PMC5764808
OpenAlex: W2735896722
Cited by: 426
References: 38
Citations by year: 2026: 34 · 2025: 52 · 2024: 59 · 2023: 42 · 2022: 55 · 2021: 69 · 2020: 40 · 2019: 39 · 2018: 31 · 2017: 4
FWCI: 24.41
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
Locations: Hepatology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Bristol-Myers Squibb
GlaxoSmithKline
American Association for the Study of Liver Diseases
Gilead Sciences
National Institutes of Health (R01 DK 10596‐01, UL1TR000058)
National Institute on Alcohol Abuse and Alcoholism (K23AA021179)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK105961, R01DK100314, T32DK007150, R01DK081410, P30DK048522)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords: nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, bile acids, chenodeoxycholic acid, cholic acid, taurocholate, liver fibrosis, steatosis, liver histopathology, NAFLD activity score, type 2 diabetes, hepatocyte ballooning, inflammation, cirrhosis risk, biomarkers
MeSH terms: Receptor, Farnesoid X-Activated, Adult, Aged, Bile Acids and Salts, Cross-Sectional Studies, Female, Humans, Liver Cirrhosis, Male, Middle Aged, Prospective Studies, Severity of Illness Index, Receptors, Cytoplasmic and Nuclear, Non-alcoholic Fatty Liver Disease

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The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids

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