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The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study.

ABSTRACT: Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis by prospectively studying 247 such patients from four international centers (in Australia, USA, UK and Italy). Their natural history was then compared with 264 patients with HCV infection who were either naïve or non-responders to treatment. Both cohorts were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at enrollment. In the NAFLD cohort, followed up for a mean of 85.6 months (range, 6-297), there were 48 (19.4%) liver-related complications and 33 (13.4%) deaths or liver transplants. In the HCV cohort, followed up for 74.9 months (mean; range, 6-238), there were 47 (16.7%) liver-related complications and 25 (9.4%) deaths or liver transplants. When adjusting for baseline differences in age and gender, the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort (P = 0.03), including incident hepatocellular cancer (6 versus 18; P = 0.03), but that of cardiovascular events (P = 0.17) and overall mortality (P = 0.6) were similar in both groups. In the NAFLD cohort, platelet count, stage 4 fibrosis, lowered platelet count, and lowered serum cholesterol and alanine aminotransferase (ALT) levels were associated with liver-related complications; an aspartate aminotransferase/ALT ratio >1 and older age were associated with overall mortality, and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality.Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection, but similar overall mortality. Some clinical and laboratory features predict liver-related complications and other outcomes in patients with NAFLD.

SUBMITTER: Bhala N

PROVIDER: S-EPMC3238674 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study.

Bhala Neeraj N Angulo Paul P van der Poorten David D Lee Eric E Hui Jason M JM Saracco Giorgio G Adams Leon A LA Charatcharoenwitthaya Phunchai P Topping Joanne H JH Bugianesi Elisabetta E Day Christopher P CP George Jacob J

Hepatology (Baltimore, Md.) 20110809 4

<h4>Unlabelled</h4>Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis by prospectively studying 247 such patients from four international centers (in Australia, USA, UK and Italy). Their natural history was then compared with 264 patients with HCV infection who were either naïve or non-responders to treatment. Both cohorts were Child-P ...[more]

PMID: 21688282

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Project description:BackgroundThe risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.MethodsThis is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).ResultsThe prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).ConclusionUsing a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.Trial registrationUcsd irb140084.FundingNational Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

Project description:Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.

Project description:ImportanceThe most important surrogate for increased risk of adverse clinical outcomes among patients with nonalcoholic fatty liver disease (NAFLD) is the patient's stage of liver fibrosis. There is a significant barrier to risk-stratifying patients in clinical practice owing to the need for liver biopsy.ObjectiveTo determine the performance of the enhanced liver fibrosis (ELF) test as a noninvasive test for assessment of liver fibrosis among patients with NAFLD.Design, setting, and participantsThis retrospective cross-sectional study was conducted among patients recruited from a large, community-based hospital system's outpatient liver clinic from 2001 to 2020. Patients with NAFLD defined as steatosis greater than 5% without evidence of other liver disease or excessive alcohol use were included. Data were analyzed from August 2020 through February 2021.InterventionEnhanced liver fibrosis score was calculated.Main outcomes and measuresAdvanced fibrosis was identified by liver biopsy or transient elastography.ResultsAmong 829 patients with NAFLD, the mean (SD) age was 53.1 (14.0) years, there were 363 (43.8%) men, 294 patients (35.5%) had type 2 diabetes, and the mean (SD) fibrosis-4 (fib-4) score was 1.34 (0.97). There were 463 patients with liver biopsy, among whom 113 individuals (24.4%) had bridging fibrosis or cirrhosis; among 462 patients with transient elastography data, 79 individuals (17.1%) had liver stiffness results of 9.6 kPa or more (ie, advanced fibrosis). Patients with advanced fibrosis had statistically significantly increased mean (SD) ELF scores compared with patients without advanced fibrosis as determined by biopsy (10.1 [1.3] vs 8.6 [1.0]; P < .001) or transient elastography (10.0 [1.1] vs 9.0 [0.8]; P < .001). Among all patients with NAFLD, the area under the receiver operating characteristic curve (AUROC) for ELF in identifying patients with advanced fibrosis was 0.81 (95% CI, 0.77-0.85) for patients diagnosed by biopsy and 0.79 (95% CI, 0.75-0.82) for those diagnosed by transient elastography. Performance of the ELF score was similar among patients with NAFLD who were aged 65 years or older (AUROC, 0.74; 95% CI, 0.58-0.87) or had type 2 diabetes (AUROC, 0.78; 95% CI, 0.71-0.84). The combination of an ELF score of 7.2 or greater with a fib-4 score of 0.74 or greater was associated with a negative predictive value of 95.1% (95% CI, 91.8%-98.4%) and a sensitivity of 92.5% (95% CI, 87.4%-97.5%), which can reliably rule out advanced fibrosis. An ELF score of 9.8 or greater with a fib-4 score of 2.9 or greater was associated with a positive predictive value of 95.0% (95% CI, 85.5%-100%) and a specificity of 99.7% (95% CI, 99.1%-100%), which can be used to rule in advanced fibrosis.Conclusions and relevanceThese findings suggest that the ELF test performs well in identifying patients with NAFLD who are at increased risk of advanced fibrosis and that this test combined with fib-4 score may be reliably used in clinical practice to assess the presence or absence of advanced fibrosis among patients with NAFLD.

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The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study.

Publications

The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study.

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