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Clinical Epidemiology of NAFLD

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Clinical Epidemiology of Chronic Liver Diseases

Abstract

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. The ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, but the United States (U.S.) is following closely behind with prevalence increasing from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and hepatocellular carcinoma. The increasing prevalence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA

    Donghee Kim & Aijaz Ahmed

  2. Department of Medicine, Brown University, Providence, RI, USA

    Osama Siddique

  3. Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA

    Brandon J. Perumpail

Authors
  1. Donghee Kim
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  2. Osama Siddique
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  3. Brandon J. Perumpail
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  4. Aijaz Ahmed
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Corresponding author

Correspondence to Aijaz Ahmed .

Editor information

Editors and Affiliations

  1. Division of Gastroenterology and Hepatology, Alameda Health System Highland Hospital, Oakland, CA, USA

    Robert J. Wong

  2. Robert G. Gish Consultants LLC, Hepatitis B Foundation, Stanford Health Care, San Diego, CA, USA

    Robert G. Gish

Summary Table of Landmark Literature

Summary Table of Landmark Literature

Study title and authors

Study design

Summary results

Main limitations

Hamaguchi M, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005;143(10):722–8

A prospective cohort study done over 414 days to investigate the effect of metabolic syndrome on pathogenesis of NAFLD

• Participants with metabolic syndrome had 4–11 times higher risk of future NAFLD

• Abdominal ultrasonography, which is not the gold standard, was used to classify NAFLD

Szczepaniak LS, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005;288(2):E462–8

Randomized controlled clinical trial to measure hepatic triglyceride content (HTGC) using magnetic resonance spectroscopy

• A value of 5.56% or greater of HTGC defined as abnormal in patients with no risk factors.

• Estimated prevalence of NAFLD as 33.6% in the Dallas heart study cohort

• 43% of the study population was obese contributing to the higher prevalence reported in comparison to general population

Younossi ZM, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011;9(6):524–30

A retrospective analysis of national health and nutrition examination surveys used to estimate changes in the prevalence and predictors of chronic liver disease (CLD)

• Prevalence of CLD is increasing: 11.78 ± 0.48% (1988–1994), to 14.78 ± 0.58% (2005–2008) (P < 0.0001)

• Prevalence of NAFLD has increased steadily as well: 5.51 ± 0.31% (1988–1994) to 11.01 ± 0.51% (2005–2008) (P < 0.0001)

• The analysis and results are limited to adults only

• There was no histological definition of NAFLD or NASH used to account for prevalence

Younossi ZM, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84

A systematic review and meta-analytic approach to report the incidence, prevalence, disease progression and burden of NAFLD

• Pooled incidence rate from Asia and Israel were 52 and 28 per 1000 person-year respectively

• Prevalence of NAFLD in US has increased from 15% to 25% between 2005 and 2010

• Prevalence of NASH is between 1.5% and 6.45%

• 9% of NASH patients had advancements in their fibrosis

• High unexplained heterogeneity of included studies

• Under representation of under-developed countries and besides two studies all others were from countries with high human development index

Schwimmer JB, et al. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118(4):1388–93

A retrospective review to determine the prevalence of pediatric fatty liver as diagnosed by histology in a population-based sample

• Prevalence of fatty liver in pediatric age group 2–19 years old was 9.6% (95% CI: 7.4–11.7)

• Prevalence increases with increasing age. Ages 2–4: 0.7 (95% CI: 0–2.0), ages 15–19: 17.3 (95% CI: 13.8–20.8)

• A specific cause of fatty liver disease could not be determined

Wong VW, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut. 2010;59(7):969–74

Prospective longitudinal hospital based cohort study to investigate disease progression over 36 months of different degrees of NAFLD

• 13 patients with simple steatosis at baseline, three (23%) continued to have simple steatosis at month 36, five (39%) developed borderline NASH and three (23%) developed NASH

• Among 17 patients with NASH at baseline, ten (59%) continued to have NASH and six (35%) had borderline NASH at month 36. Only one (6%) patient regressed to simple steatosis

• All patients received lifestyle advice and regular monitoring of metabolic factors. This might have altered the natural history of the disease

• Patients with NAFLD in a hospital clinic may have more advanced disease than those in the community

• Small sample size precluded more detailed analysis of factors associated with disease progression

• Liver biopsy might be limited by sampling bias

Angulo P, et al. Liver fibrosis, but no other histologic features, associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389–97

A retrospective analysis of 619 patients diagnosed with NAFLD from 1975 through 2005 underwent analysis of their laboratory and biopsies results

• Features associated with death or liver transplantation included fibrosis stage 1 (HR, 1.88; 95% CI, 1.28, 2.77), stage 2 (HR, 2.89; 95% CI, 1.93, 4.33), stage 3 (HR, 3.76; 95% CI, 2.40, 5.89), and stage 4 (HR, 10.9; 95% CI, 6.06, 19.62) compared with stage 0

• Survival free of liver transplantation in patients with non-NASH was significantly lower in those with fibrosis as compared to those without fibrosis (p < 0.001)

• Lack of a specific protocol for patient follow-up with regards to endoscopy and imaging procedures in non-cirrhotic patients, and thus it is possible that the number of liver-related events was underestimated

• Over-representation of the white population

Hashimoto E, et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol. 2009;44(Suppl 19):89–95

A large case-control study of NASH patients with and without HCC as well as a prospective cohort study on the natural history of NASH patients with advanced fibrosis who underwent follow-up for HCC at a single tertiary care hospital

• Stage of fibrosis (OR = 4.232; 95% CI, 1.847–9.698; P = 0.001) was an independent predictor of development of HCC

• Older age (OR = 1.108; 95% CI, 1.028–1.195; P = 0.008) and low AST levels (OR = 0.956; 95% CI, 0.919–0.995; P = 0.027), were other factors leading to HCC

• As histological diagnosis is a requirement for diagnosis of NASH, the patients diagnosed with this condition consisted of significantly altered liver function test. Findings might be affected by this selection bias

Rafiq N, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 2009;7(2):234–8

A retrospective analysis of patients with biopsy proven NAFLD and long term follow up (>5 years), to find the long term outcome and specifically liver related mortality in patients with NAFLD

• NASH group had a liver-related mortality of 17.5% in contrast to only 2.7% in the non-NASH group (P = 0.0048)

• NASH on biopsy (P = 0.0250) was an independent predictor of liver related mortality

• A relatively small cohort sample size

• There was no histologic or clinical data to assess the development of cirrhosis or other complications during the follow-up period

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Kim, D., Siddique, O., Perumpail, B.J., Ahmed, A. (2019). Clinical Epidemiology of NAFLD. In: Wong, R., Gish, R. (eds) Clinical Epidemiology of Chronic Liver Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-94355-8_14

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  • DOI: https://doi.org/10.1007/978-3-319-94355-8_14

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-94354-1

  • Online ISBN: 978-3-319-94355-8

  • eBook Packages: MedicineMedicine (R0)

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