Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Obesity Surgery
Published in: Obesity Surgery 4/2011

01-04-2011 | Clinical Research

A Biomarker Panel for Non-alcoholic Steatohepatitis (NASH) and NASH-Related Fibrosis

Authors: Zobair M. Younossi, Sandra Page, Nila Rafiq, Aybike Birerdinc, Maria Stepanova, Noreen Hossain, Arian Afendy, Zahra Younoszai, Zachary Goodman, Ancha Baranova

Published in: Obesity Surgery | Issue 4/2011

Login to get access

Abstract

Background

Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis.

Aim

This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables.

Methods

Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated.

Results

Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65–M30 (necrosis) [AUC: 0.81, 95% CI, 0.70–0.89, 300 p value <9E 301 −06]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68–0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70–0.89; p value, 0.000062].

Conclusions

This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.
Literature
1.
Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917–23.CrossRefPubMed
2.
Rafiq N, Younossi ZM. Evaluation and management of non-alcoholic fatty liver disease. Clin Liver Dis. 2009;13:249–66.CrossRefPubMed
3.
Younossi ZM, Diehl AM, Ong JP. Nonalcoholic fatty liver disease: an agenda for clinical research. Hepatology. 2002;35:746–52.CrossRefPubMed
4.
Younossi ZM, Gramlich T, Liu Y, et al. Non- alcoholic fatty liver: assessment of variability in the pathologic interpretations. Mod Pathol. 1998;11(6):560–5.PubMed
5.
Matteoni C, Younossi ZM, Gramlich T, et al. A non-alcoholic fatty liver disease: a spectrum of clinical and pathologic severity. Gastroenterology. 1999;116:1413–9.CrossRefPubMed
6.
Rafiq N, Bai CH, Fang Y, et al. Long-term follow-up of patients with non-alcoholic fatty liver. Clini Gastro Hepatol. 2009;7(2):234–8.CrossRef
7.
Ekstedt M et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865.CrossRefPubMed
8.
Rosenberg WM, Voelker M, Thiel R, European Liver Fibrosis Group, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004;127(6):1704–13.CrossRefPubMed
9.
Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54.CrossRefPubMed
10.
Guha IN, Parkes J, Roderick P, et al. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: validating the European liver fibrosis panel and exploring simple markers. Hepatology. 2009;47(2):455–60.CrossRef
11.
Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518–26.CrossRefPubMed
12.
Cales P, Laine F, Boursier J, Deugnier Y, Moal V, Oberti F, et al. Comparison of blood tests for liver fibrosis specific or not to NAFLD J Hepatol. 2009;50:165–73.PubMed
13.
Younossi ZM, Jarrar M, Nugent C, et al. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg. 2008;18(11):1430–7.CrossRefPubMed
14.
Wieckowska A, Zein NN, Yerian LM, et al. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology. 2006;44(1):27–33.CrossRefPubMed
15.
Baranova A, Younossi ZM. The future is around the corner: non-invasive diagnosis of the progressive nonalcoholic steatohepatitis. Hepatology. 2008;47(2):373–5.CrossRefPubMed
16.
Hossain N, Afendy A, Stepanova M, Nader F, Srishord M, Goodman Z, Younossi Z. Independent predictors of fibrosis in patients with non-alcoholic fatty liver disease. Clin Gastro Hepatol 2009;7(11):1224–9.
17.
Bondini S, Kleiner DE, Goodman Z, et al. Pathologic assessment of non-alcoholic fatty liver disease. Clin Liver Dis. 2007;11:17–23.CrossRefPubMed
18.
Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology. 2000;32:477–81.CrossRefPubMed
19.
Ratziu V, Charlotte F, Heurtier A, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–906.CrossRefPubMed
20.
Miele L, Forgione A, Gasbarrini G, et al. Noninvasive assessment of fibrosis in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Transl Res. 2007;149:114–25.CrossRefPubMed
21.
Ratziu V, Giral P, Munteanu M, et al. Screening for liver disease using non-invasive biomarkers (FibroTest, SteatoTest and NashTest) in patients with hyperlipidaemia. Aliment Pharmacol Ther. 2007;25:207–18.CrossRefPubMed
22.
Wieckowska A, Zein NN, Yerian LM, et al. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology. 2006;44:27–33.CrossRefPubMed
23.
Chitturi S, Farell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21(1):27–41.CrossRefPubMed
24.
Edmison J, McCullough AJ. Pathogenesis of non-alcoholic steatohepatitis: human data. Clinics in Liver Disease. 2007;11(1):75–104.CrossRefPubMed
25.
26.
Nugent C, Younossi ZM. Evaluation and management of obesity-related non-alcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol. 2007;14(No. 8):432–41.CrossRef
27.
Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28(4):339–50.CrossRefPubMed
28.
Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–150.CrossRefPubMed
29.
Charatcharoenwitthaya P, Lindor KD. Role of radiologic modalities in the management of NASH. Clin Liver Dis. 2007;11(1):37–54.CrossRefPubMed
30.
Nguyen-Khac E, Capron D. Noninvasive diagnosis of liver fibrosis by ultrasonic transient elastography (Fibroscan). Eur J Gastroenterol Hepatol. 2006;18:1321–5.CrossRefPubMed
31.
Ong J, Elariny H, Collantes R, et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in obese patients. Obesity Surgery. 2005;15(3):310–5.CrossRefPubMed
32.
Baranova A, Gowder SJ, Schlauch K, et al. Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance. Obes Surg. 2006;16:1118–25.CrossRefPubMed
33.
Younossi ZM, Gorreta F, Ong JP, et al. Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis. Liver Int. 2005;25:760–71.CrossRefPubMed
34.
Younossi ZM, Baranova A, Ziegler K, et al. A genomic and proteomic of study of the spectrum of non-alcoholic fatty liver disease. Hepatology. 2005;41(3):665–74.CrossRef
35.
Calvert VS, Collantes R, Elariny H, et al. A systems biology approach to non alcoholic fatty liver disease pathogenesis using multiplexed cell signaling analysis. Hepatology. 2007;46(1):166–72.CrossRefPubMed
36.
Baranova A, Liotta L, Petricoin E, et al. The role of genomics and proteomics technologies in studying non-alcoholic fatty liver disease. Clin Liver Dis. 2007;11:209–20.CrossRefPubMed
37.
Itagaki T, Shimizu I, Cheng X, et al. Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells. Gut. 2005;54:1782–9.CrossRefPubMed
38.
Shimizu I, Kohno N, Tamaki K, et al. Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol. 2007;13:4295–305.PubMed
39.
Shimizu I, Ito S. Protection of estrogens against the progression of chronic liver disease. Hepatol Res. 2007;37:239–47.CrossRefPubMed
Metadata
Title
A Biomarker Panel for Non-alcoholic Steatohepatitis (NASH) and NASH-Related Fibrosis
Authors
Zobair M. Younossi
Sandra Page
Nila Rafiq
Aybike Birerdinc
Maria Stepanova
Noreen Hossain
Arian Afendy
Zahra Younoszai
Zachary Goodman
Ancha Baranova
Publication date
01-04-2011
Publisher
Springer-Verlag
Published in
Obesity Surgery / Issue 4/2011
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-010-0204-1

Other articles of this Issue 4/2011

Obesity Surgery 4/2011 Go to the issue

Clinical Research

The Potential Role of Intragastric Balloon in the Treatment of Obese-Related Infertility: Personal Experience

Clinical Research

Anatomy and Complications Following Laparoscopic Sleeve Gastrectomy: Radiological Evaluation and Imaging Pitfalls

Case Report

Massive Weight Loss Without Surgery in a Super Obese Patient

Clinical Research

The Relationship Between Anthropometric Measures, Blood Gases, and Lung Function in Morbidly Obese White Subjects

Clinical Research

Do Patients Seeking Laparoscopic Adjustable Gastric Banding Surgery Differ from Those Seeking Gastric Bypass Surgery? A Comparison of Psychological Profiles Across Ethnic Groups

Clinical Research

The Four Different Types of Internal Hernia Occurring After Laparascopic Roux-en-Y Gastric Bypass Performed for Morbid Obesity: Are There Any Multidetector Computed Tomography (MDCT) Features Permitting Their Distinction?