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Published in: Journal of General Internal Medicine 5/2020

01-05-2020 | Fatty Liver | Original Research

Predictive Factors and Time to Development of Hepatic Decompensation in Patients with Non-alcoholic Fatty Liver Disease

Authors: Heidi S. Ahmed, MD, Natalie Pedersen, MD, Manju Bengaluru Jayanna, MD, MS, Patrick Ten Eyck, PhD, MS, Antonio Sanchez, MD, Arvind R. Murali, MD

Published in: Journal of General Internal Medicine | Issue 5/2020

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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cirrhosis in the USA.

Objectives

We aimed to determine the time to develop hepatic events in patients with NAFLD and develop a simple model to identify patients at risk for hepatic decompensation.

Design

Retrospective cohort study.

Patients

Seven hundred patients with NAFLD met inclusion criteria for the study. Patients were divided into model construction (n = 450) and validation (n = 250) cohorts.

Main Measures

Demographic, clinical, and laboratory variables were gathered at the time of diagnosis of NAFLD. Kaplan-Meier analysis determined the time to development of hepatic events from initial diagnosis. A time-to-event prediction model was established in the model construction cohort using the multivariate Cox proportional hazards model and was then internally validated.

Key Results

Forty-nine (7%) patients developed hepatic events at a mean duration of 6.2 ± 4.2 years from initial diagnosis. Kaplan-Meier probability of developing a hepatic event at 5-, 10-, and 12-year intervals was 4.8%, 10.6%, and 11.3%, respectively. Age, presence of diabetes, and platelet count were identified as significant variables to predict hepatic events. NAFLD decompensation risk score was developed as “age × 0.06335 + presence of diabetes (yes = 1, no = 0) × 0.92221 − platelet count × 0.01522” to predict the probability of hepatic decompensation. Risk score model had an area under the curve of 0.89 (95% CI = 0.92, 0.86) and it performed well in both the validation (0.91, 0.87–0.94) and the overall cohort (0.89, 0.87–0.91).

Conclusions

A significant proportion of patients with NAFLD developed hepatic decompensation. We have provided a simple, objective model to help identify “at-risk” patients.
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Literature
1.
go back to reference Browning JD, Szczepaniak LS, Dobbins R, Nuremberg 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.PubMedCrossRef Browning JD, Szczepaniak LS, Dobbins R, Nuremberg 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.PubMedCrossRef
2.
go back to reference Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274–85.PubMedCrossRef Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274–85.PubMedCrossRef
3.
go back to reference Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000;132(2):112–7.PubMedCrossRef Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000;132(2):112–7.PubMedCrossRef
4.
go back to reference Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124–31.PubMedCrossRef Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124–31.PubMedCrossRef
5.
go back to reference Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol. 2013;178(1):38–45.PubMedPubMedCentralCrossRef Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol. 2013;178(1):38–45.PubMedPubMedCentralCrossRef
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference Corey KE, Kaplan LM. Obesity and liver disease: the epidemic of the twenty-first century. Clin Liver Dis. 2014;18(1):1–18.PubMedCrossRef Corey KE, Kaplan LM. Obesity and liver disease: the epidemic of the twenty-first century. Clin Liver Dis. 2014;18(1):1–18.PubMedCrossRef
8.
9.
go back to reference Day CP. Natural history of NAFLD: remarkably benign in the absence of cirrhosis. Gastroenterology. 2005;129(1):375–8.PubMedCrossRef Day CP. Natural history of NAFLD: remarkably benign in the absence of cirrhosis. Gastroenterology. 2005;129(1):375–8.PubMedCrossRef
10.
go back to reference Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–2.PubMedCrossRef Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–2.PubMedCrossRef
11.
go back to reference Bhala N, Angulo P, van der Poorten D, Lee E, Hui JM, Saracco G, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology. 2011;54(4):1208–16.PubMedPubMedCentralCrossRef Bhala N, Angulo P, van der Poorten D, Lee E, Hui JM, Saracco G, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology. 2011;54(4):1208–16.PubMedPubMedCentralCrossRef
12.
go back to reference Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J Hepatol. 2009;51(2):371–9.PubMedCrossRef Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J Hepatol. 2009;51(2):371–9.PubMedCrossRef
13.
go back to reference Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2015;149(2):389–97 e10.PubMedPubMedCentralCrossRef Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2015;149(2):389–97 e10.PubMedPubMedCentralCrossRef
14.
go back to reference Al Knawy B, Shiffman M. Percutaneous liver biopsy in clinical practice. Liver Int. 2007;27(9):1166–73.PubMedCrossRef Al Knawy B, Shiffman M. Percutaneous liver biopsy in clinical practice. Liver Int. 2007;27(9):1166–73.PubMedCrossRef
15.
go back to reference Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128(7):1898–906.PubMedCrossRef Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128(7):1898–906.PubMedCrossRef
16.
go back to reference Xiao G, Zhu S, Xiao X, Yan L, Yang J, Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology. 2017;66(5):1486–501.PubMedCrossRef Xiao G, Zhu S, Xiao X, Yan L, Yang J, Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology. 2017;66(5):1486–501.PubMedCrossRef
17.
go back to reference Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54.PubMedCrossRef Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54.PubMedCrossRef
18.
go back to reference Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57(10):1441–7.PubMedCrossRef Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57(10):1441–7.PubMedCrossRef
19.
go back to reference McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265–9.PubMedCrossRef McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265–9.PubMedCrossRef
20.
go back to reference Xun YH, Guo JC, Lou GQ, Jiang YM, Zhuang ZJ, Zhu MF, et al. Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD. Clin Exp Pharmacol Physiol. 2014;41(9):643–9.PubMed Xun YH, Guo JC, Lou GQ, Jiang YM, Zhuang ZJ, Zhu MF, et al. Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD. Clin Exp Pharmacol Physiol. 2014;41(9):643–9.PubMed
21.
go back to reference Alkhouri N, Morris-Stiff G, Campbell C, Lopez R, Tamimi TA, Yerian L, et al. Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2012;32(2):297–302.PubMedCrossRef Alkhouri N, Morris-Stiff G, Campbell C, Lopez R, Tamimi TA, Yerian L, et al. Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2012;32(2):297–302.PubMedCrossRef
22.
go back to reference D'Amico G, Pasta L, Morabito A, D'Amico M, Caltagirone M, Malizia G, et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther. 2014;39(10):1180–93.PubMedCrossRef D'Amico G, Pasta L, Morabito A, D'Amico M, Caltagirone M, Malizia G, et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther. 2014;39(10):1180–93.PubMedCrossRef
23.
go back to reference Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.PubMedCrossRef Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.PubMedCrossRef
24.
go back to reference Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cardenas E, Sanchez-Avila F, Vargas-Vorackova F. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol. 2008;7(4):350–7.PubMedCrossRef Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cardenas E, Sanchez-Avila F, Vargas-Vorackova F. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol. 2008;7(4):350–7.PubMedCrossRef
25.
go back to reference Harrell FE, Jr., Lee KL, Califf RM, Pryor DB, Rosati RA. Regression modelling strategies for improved prognostic prediction. Stat Med. 1984;3(2):143–52.PubMedCrossRef Harrell FE, Jr., Lee KL, Califf RM, Pryor DB, Rosati RA. Regression modelling strategies for improved prognostic prediction. Stat Med. 1984;3(2):143–52.PubMedCrossRef
26.
go back to reference Harrell FE, Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361–87.PubMedCrossRef Harrell FE, Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361–87.PubMedCrossRef
27.
go back to reference Angulo P, Bugianesi E, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Barrera F, et al. Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2013;145(4):782–9 e4.PubMedPubMedCentralCrossRef Angulo P, Bugianesi E, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Barrera F, et al. Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2013;145(4):782–9 e4.PubMedPubMedCentralCrossRef
Metadata
Title
Predictive Factors and Time to Development of Hepatic Decompensation in Patients with Non-alcoholic Fatty Liver Disease
Authors
Heidi S. Ahmed, MD
Natalie Pedersen, MD
Manju Bengaluru Jayanna, MD, MS
Patrick Ten Eyck, PhD, MS
Antonio Sanchez, MD
Arvind R. Murali, MD
Publication date
01-05-2020
Publisher
Springer International Publishing
Keyword
Fatty Liver
Published in
Journal of General Internal Medicine / Issue 5/2020
Print ISSN: 0884-8734
Electronic ISSN: 1525-1497
DOI
https://doi.org/10.1007/s11606-020-05725-1

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