Liver Fibrosis, but no Other Histologic Features, Associates with Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease
By P. Angulo, D. Kleiner, S. Dam-Larsen, L. Adams, E. Bjornsson, P. Charatcharoenwitthaya, P. Mills, Jill C. Keach, H. Lafferty, Alisha C. Stahler and 2 more. Gastroenterology, 2015
2,665 citations recorded by the source corpus.
Background & Aim Histologic analysis of liver biopsies allows for grading and staging of nonalcoholic fatty liver disease (NAFLD). We performed a longitudinal study to investigate the long-term prognostic relevance of histologic features for patients with NAFLD. Methods We performed a retrospective analysis of 619 patients diagnosed with NAFLD from 1975 through 2005 at medical centers in the United States, Europe, and Thailand. Patients underwent laboratory and biopsy analyses, and were examined every 3–12 months after their diagnosis. Outcomes analyzed were overall mortality, liver transplantation, and liver-related events. Cumulative outcomes were compared by log-rank analysis. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (HR). Time at risk was determined from the date of liver biopsy to the date of outcome or last follow-up examination. Results Over a median follow-up of 12.6 years (range 0.3–35.1), 193 of the patients (33.2%) died or underwent liver transplantation. Features of liver biopsies significantly 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, as well as age (HR, 1.07; 95% CI, 1.05, 1.08), diabetes (HR, 1.61; 95% CI, 1.13, 2.30), current smoking (HR, 2.62; 95% CI, 1.67, 4.10) and statin use (HR, 0.32; 95% CI, 0.14, 0.70). Twenty-six patients (4.2%) developed liver-related events; fibrosis stage 3 (HR 14.2 [95% CI 3.38, 59.68]) and stage 4 (HR 51.5 [95% CI 9.87, 269.2]) compared to stage 0, were significantly associated with the events. Patients with fibrosis, regardless of steatohepatitis or NAFLD activity score, had shorter survival times than patients without fibrosis. Conclusions In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were independently associated with long-term overall mortality, liver transplantation, and liver-related events.
Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Hepatology
View Paper: https://www.semanticscholar.org/paper/387c138b3c9c351af6516ab0dc7cfc46a5bbfa5a
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
- Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. (2016, background): “Instead, the modified definition defines worsening of fibrosis as any one-stage increase based on recent data showing that even early fibrosis is associated with global and liver-related mortality.(7) Importantly, this more stringent definition led to a lower placebo effect.”
- Non-alcoholic fatty liver disease - A global public health perspective. (2019, background): “Therefore, it is the stage of fibrosis and not steatosis that is directly related to overall mortality in patients with NAFLD.(72) Despite these data, the most common cause of death among patients with NAFLD, especially among those with lean NAFLD, is cardiovascular disease.”
- NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice (2017, background): “* Contributed equally to this work and are deemed equal first authors Short title: MCC950 reverses NASH Key words: NAFLD, NLRP3, inflammasome, cholesterol crystals, Kupffer cells, hepatocytes, interleukin-1, fibrosis.”
- Association Between Fibrosis Stage and Outcomes of Patients with Non-Alcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis. (2020, background): “IMPACT It is important to monitor liver fibrosis stage in patients with NAFLD.”
- MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. (2020, neutral): “Journal Pre-proof MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease Mohammed Eslam, Arun J. Sanyal, Jacob George, on behalf of an international consensus panel PII: S0016-5085(20)30171-2 DOI: https://doi.org/10.1053/j.gastro.2019.11.312 Reference: YGAST 631”
- The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). (2016, result): “[5] Angulo P, Kleiner DE, Dam-Larsen S, et al.”
- The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent (2016, positive): “Most importantly the MBOAT7 variant was independently associated with development of fibrosis (Table 2 and Figure 2), which represents the major determinant of the prognosis of patients with NAFLD 39, 40 .”
- Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes (2016, background): “Exclusion criteria for the meta-analysis were as follows: (1) The study was a review article or abstract; (2) the study did not identify patients with NAFLD; (3) The study was in a pediatric population (<18 years old); (4) the study did not exclude other causes of liver disease, such as viral hepati”
- Gut microbiome based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease (2017, positive): “(Angulo et al., 2015; Dulai et al., 2017; Ekstedt et al., 2015; Younossi et al., 2015) Early identification of the presence of advanced fibrosis using non-invasive modalities is a major unmet need in the field.”