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

McPherson, Stuart; Hardy, Timothy; Henderson, Emily; Burt, Alastair D.; Day, Christopher P.; Anstee, Quentin M.

doi:10.1016/j.jhep.2014.11.034

Cited by 887 publications

(802 citation statements)

References 36 publications

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“…In comparison with previous studies with paired biopsies, the study by Wong et al22 showed fibrosis progression in 28% of patients with nonalcoholic fatty liver (defined as NAFLD activity score <3) over a 3‐year period. The studies by Pais et al23 and McPherson et al24 showed fibrosis progression in 24% and 37% of patients with nonalcoholic fatty liver (defined as isolated steatosis or isolated steatosis and mild inflammation) over a follow‐up time of 3.7 and 8 years, respectively. The latter study also showed a trend for more aggressive disease progression in patients with steatosis and mild inflammation compared to patients with isolated steatosis ( P = 0.07) 24.…”

Section: Discussionmentioning

confidence: 99%

“…The studies by Pais et al23 and McPherson et al24 showed fibrosis progression in 24% and 37% of patients with nonalcoholic fatty liver (defined as isolated steatosis or isolated steatosis and mild inflammation) over a follow‐up time of 3.7 and 8 years, respectively. The latter study also showed a trend for more aggressive disease progression in patients with steatosis and mild inflammation compared to patients with isolated steatosis ( P = 0.07) 24. In our study with a mean follow‐up time of 19.8 years, fibrosis progression ≥1 stage was seen in 61% (22 out of 36) of patients with isolated steatosis at inclusion, of whom 5 patients developed advanced fibrosis or end‐stage liver disease.…”

Section: Discussionmentioning

confidence: 99%

“…There are few paired biopsy studies with approximately 520 patients in total,7, 8, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and all but two studies have a median follow‐up time of less than 7 years (range, 3.0‐7.0 years). Albeit, some studies only include patients with NASH, the rate of fibrosis progression does not seem to be affected by the presence of steatohepatitis.…”

Section: Introductionmentioning

confidence: 99%

“…Albeit, some studies only include patients with NASH, the rate of fibrosis progression does not seem to be affected by the presence of steatohepatitis. Moreover, some studies also show that simple steatosis can progress to steatohepatitis and advanced fibrosis 22, 23, 24…”

Section: Introductionmentioning

confidence: 99%

“…NAFLD is a slowly progressive disease,11 and most follow‐up studies have too short a follow‐up time to assess fibrosis progression 24. Fibrosis progression is seen in 27%‐52% of patients7, 8, 19, 21, 22, 24 over a mean of 3.0‐13.8 years of follow‐up, with the majority of patients with NAFLD having static or regressive fibrosis. Baseline variables predicting fibrosis progression have been hard to determine.…”

Section: Introductionmentioning

confidence: 99%

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Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

Nasr

Ignatova

Kechagias

et al. 2017

Hepatology Communications

112

104

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Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world. The complete natural history of NAFLD is unknown because few high‐quality follow‐up studies have been conducted. Our aim was to find variables predicting disease severity through an extended follow‐up with serial biopsies. In a prospective cohort study, 129 patients who enrolled between 1988 and 1993 were asked to participate in a follow‐up study on two occasions; biochemical, clinical, and histologic data were documented. The mean time between biopsies was 13.7 (±1.7) and 9.3 (±1.0) years, respectively. At the end of the study period, 12 patients (9.3%) had developed end‐stage liver disease and 34% had advanced fibrosis. Out of the 113 patients with baseline low fibrosis (<3), 16% developed advanced fibrosis. Fibrosis progression did not differ among the different stages of baseline fibrosis (P = 0.374). Fifty‐six patients (43%) had isolated steatosis, of whom 9% developed advanced fibrosis (3 patients with biopsy‐proven fibrosis stage F3‐F4 and 2 patients with end‐stage liver disease). Fibrosis stage, ballooning, and diabetes were more common in patients who developed end‐stage liver disease; however, there were no baseline clinical, histologic, or biochemical variables that predicted clinical significant disease progression. Conclusion: NAFLD is a highly heterogeneous disease, and it is surprisingly hard to predict fibrosis progression. Given enough time, NAFLD seems to have a more dismal prognosis then previously reported, with 16% of patients with fibrosis stage <3 developing advanced fibrosis and 9.3% showing signs of end‐stage liver disease. (Hepatology Communications 2018;2:199–210)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

Nasr

Ignatova

Kechagias

et al. 2017

Hepatology Communications

112

104

View full text Add to dashboard Cite

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Association of Histologic Disease Activity With Progression of Nonalcoholic Fatty Liver Disease

et al. 2019

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IMPORTANCE The histologic evolution of the full spectrum of nonalcoholic fatty liver disease (NAFLD) and factors associated with progression or regression remain to be definitively established. OBJECTIVE To evaluate the histologic evolution of NAFLD and the factors associated with changes in disease severity over time. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort substudy from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database study, a noninterventional registry, was performed at 8 university medical research centers. Masked assessment of liver histologic specimens was performed, using a prespecified protocol to score individual biopsies.

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Analysis of a Simulation Model to Estimate Long-term Outcomes in Patients with Nonalcoholic Fatty Liver Disease

et al. 2022

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IMPORTANCEQuantitative assessment of disease progression in patients with nonalcoholic fatty liver disease (NAFLD) has not been systematically examined using competing liver-related and non-liver-related mortality. OBJECTIVE To estimate long-term outcomes in NAFLD, accounting for competing liver-related and non-liver-related mortality associated with the different fibrosis stages of NAFLD using a simulated patient population. DESIGN, SETTING, AND PARTICIPANTS This decision analytical modeling study used individuallevel state-transition simulation analysis and was conducted from September 1, 2017, to September 1, 2021. A publicly available interactive tool, dubbed NAFLD Simulator, was developed that simulates the natural history of NAFLD by age and fibrosis stage at the time of (hypothetical) diagnosis defined by liver biopsy. Model health states were defined by fibrosis states F0 to F4, decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver transplant. Simulated patients could experience nonalcoholic steatohepatitis resolution, and their fibrosis stage could progress or regress. Transition probabilities between states were estimated from the literature as well as calibration, and the model reproduced the outcomes of a large observational study. EXPOSURE Simulated natural history of NAFLD.MAIN OUTCOMES AND MEASURES Main outcomes were life expectancy; all cause, liver-related, and non-liver-related mortality; and cumulative incidence of decompensated cirrhosis and/or HCC. RESULTSThe model included 1 000 000 simulated patients with a mean (range) age of 49 (18-75) years at baseline, including 66% women. The life expectancy of patients aged 49 years was 25.3

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

Abstract: Contrary to current dogma, this study suggests that steatosis can progress to NASH and clinically significant fibrosis.

Cited by 887 publications

References 36 publications

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

Association of Histologic Disease Activity With Progression of Nonalcoholic Fatty Liver Disease

Analysis of a Simulation Model to Estimate Long-term Outcomes in Patients with Nonalcoholic Fatty Liver Disease

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