Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management.

By S. McPherson, T. Hardy, E. Henderson, A. Burt, C. Day, Q. Anstee. Journal of Hepatology, 2015

1,003 citations recorded by the source corpus.

BACKGROUND AND AIMS There remains uncertainty about the natural history of non-alcoholic fatty liver disease (NAFLD). The spectrum of NAFLD includes non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and steatohepatitis (NASH; steatosis with hepatocyte ballooning degeneration±fibrosis). Our aim was to assess the histological severity of NAFLD in a cohort with serial biopsy data, and determine factors predicting progression. METHODS Patients with two liver biopsies more than a year apart were identified. Clinical and laboratory data were collected from the time of liver biopsy. RESULTS 108 patients had serial biopsies (median interval 6.6years, range 1.3-22.6). 81 (75%) patients had NASH and 27 had NAFL. Overall, 45 (42%) patients had fibrosis progression, 43 (40%) had no change in fibrosis, while 20 (18%) had fibrosis regression. Importantly, no significant difference in the proportion exhibiting fibrosis progression was found between those with NAFL or NASH at index biopsy (37% vs. 43%, p=0.65). Progression to NASH was seen in 44% of patients with baseline NAFL. Of 10 patients with NAFL who had fibrosis progression, 3 progressed by 1 stage, 5 by 2 stages and 2 by 3 stages; all had NASH on follow-up biopsy. Of concern, 6 of 27 (22%) patients with baseline NAFL, reached stage 3 fibrosis at follow-up biopsy. Among the patients with NAFL, 80% of those having fibrosis progression were diabetic at the follow-up liver biopsy compared with 25% of non-progressors (p=0.005). CONCLUSIONS Contrary to current dogma, this study suggests that steatosis can progress to NASH and clinically significant fibrosis.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/3f99519a4a9a4261e3f8be4794053c5b289c3a3e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology, Diabetes and Metabolism

In Epidemiology

In Hepatology

Citations in the corpus

Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease (2018, background): “However, progression to fibrosis also occurs in patients with steatosis alone [7], although rates of progression and overall mortality rates are increased in NASH [1, 8].”
Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update (2017, result): “Contrary to earlier studies, recent data revealed that up to 44% of cases of NAFLD can progress to NASH even in the absence of inflammation at baseline [162] and approximately 23% of cases of NASH progress to cirrhosis over the next 10–15 years [163].”
EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. (2015, background): “Fibrosis progression is possible among patients with simple steatosis or non-alcoholic steatohepatitis; approximately 25% to 37% of patients will have fibrosis progression in 3–5 years [226–228] [229].”
Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence? (2018, background): “Notably, in dual biopsy studies the development of incident T2DM was the strongest predictor of progression to NASH and hepatic fibrosis.(61) Recent studies using magnetic resonance imaging to assess hepatic steatosis and magnetic resonance elastography to estimate liver stiffness have reported high”
Non-alcoholic fatty liver disease - A global public health perspective. (2019, background): “In fact, the more components of metabolic syndrome, the higher the risk of mortality.62–87 Liver-specific mortality among patients with NAFLD was reported to be 0.77 per 1,000 personyears, and among patients with NASH it was reported to be 11.77 per 1,000 person-years.16,20 Journal of Hepatology 201”
Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. (2017, background): “It has been shown that patients with NAFL can develop NASH and progressive fibrosis [7], thus NAFL cannot be entitled a completely benign entity.”