Predictors of advanced fibrosis in elderly patients with biopsy-confirmed nonalcoholic fatty liver disease: the GOASIA study.
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SUBMITTER: Pitisuttithum P
PROVIDER: S-EPMC7137333 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
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Predictors of advanced fibrosis in elderly patients with biopsy-confirmed nonalcoholic fatty liver disease: the GOASIA study.
Pitisuttithum Panyavee P Chan Wah Kheong WK Piyachaturawat Panida P Imajo Kento K Nakajima Atsushi A Seki Yosuke Y Kasama Kazunori K Kakizaki Satoru S Fan Jian Gao JG Song Myeong Jun MJ Yoon Seung Kew SK Dan Yock Young YY Lesmana Laurentius L Ho Khek Yu KY Goh Khean Lee KL Wong Vincent Wai Sun VWS Treeprasertsuk Sombat S
BMC gastroenterology 20200406 1
<h4>Background</h4>The Gut and Obesity in Asia (GOASIA) Workgroup was formed to study obesity and gastrointestinal diseases in the Asia Pacific region. We aimed to 1) compare the characteristics of elderly (i.e. age ≥ 60) vs. non-elderly patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD); 2) identify predictors of advanced fibrosis in elderly patients with NAFLD; and 3) assess the performance of non-invasive fibrosis scores in the prediction of advance fibrosis in the elderly p ...[more]
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Project description:ObjectivePopulation-based data are lacking regarding the risk of overall and cause-specific mortality across the complete histological spectrum of non-alcoholic fatty liver disease (NAFLD).DesignThis nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10 568). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, after excluding other etiologies of liver disease, and further categorised as, simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. NAFLD cases were matched to ≤5 general population comparators by age, sex, calendar year and county (n=49 925). Using Cox regression, we estimated multivariable-adjusted HRs (aHRs) and 95% CIs.ResultsOver a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 PY; difference=11.7/1000 PY; aHR=1.93, 95% CI=1.86 to 2.00). Compared with controls, significant excess mortality risk was observed with simple steatosis (8.3/1000 PY, aHR=1.71, 95% CI=1.64 to 1.79), non-fibrotic NASH (13.4/1000 PY, aHR=2.14, 95% CI=1.93 to 2.38), non-cirrhotic fibrosis (18.4/1000 PY, aHR=2.44, 95% CI=2.22 to 2.69) and cirrhosis (53.6/1000 PY, aHR=3.79, 95% CI=3.34 to 4.30)(ptrend <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (ptrend <0.01). The excess mortality associated with NAFLD was primarily from extrahepatic cancer (4.5/1000 PY, aHR=2.16, 95% CI=2.03 to 2.30), followed by cirrhosis (2.7/1000 PY, aHR=18.15, 95% CI=14.78 to 22.30), cardiovascular disease (1.4/1000 PY, aHR=1.35, 95% CI=1.26 to 1.44) and hepatocellular carcinoma (HCC) (1.2/1000 PY, aHR=11.12, 95% CI=8.65 to 14.30).ConclusionAll NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.
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Project description:Background and aimsRecent studies link NAFLD to an increased incidence of HCC and extrahepatic cancers. However, earlier studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity.Approach and resultsWe conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N = 8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to ≤5 general population controls without NAFLD by age, sex, calendar year, and county (N = 39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs. Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8 per 1,000 person-years [PYs]; difference = 2.9 per 1,000 PYs; aHR, 1.27 [95% CI, 1.18-1.36]), driven primarily by HCC (difference = 1.1 per 1,000 PYs; aHR, 17.08 [95% CI, 11.56-25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; Ptrend < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences = 0.2 per 1,000 PYs, 0.1 per 1,000 PYs, and 0.2 per 1,000 PYs, respectively), but no other cancers.ConclusionsCompared with controls, patients with biopsy-proven NAFLD had significantly increased cancer incidence, attributable primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.
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Project description:Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.
| S-EPMC8342487 | biostudies-literature
Project description:PurposeTo evaluate the diagnostic accuracy of magnetic resonance (MR) elastography as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, by using MR elastography as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis.Materials and methodsThis retrospective study was institutional review board approved and HIPAA complaint. Informed consent was waived. This study was conducted in patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MR elastographic examinations. Six laboratory-based models of fibrosis were compared with MR elastographic results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared.ResultsAmong 325 patients with NAFLD with MR elastographic data, there were 142 patients who underwent liver biopsy within 1 year of MR elastography. When comparing MR elastography results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3-F4, 46 [32.4%] of 142) was 4.15 kPa (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899).ConclusionMR elastography is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis.
| S-EPMC3721049 | biostudies-literature
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.
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Project description:The role played by serum folate in the progression of nonalcoholic fatty liver disease (NAFLD) remains controversial. The purpose of this study was to investigate the association of serum folate with NAFLD and advanced liver fibrosis (AHF). We conducted a cross-sectional study with 5417 participants using 2011-2018 NHANES data. Multiple logistic regression analysis and propensity score matching analysis were used to investigate the association of serum folate with NAFLD and AHF. In the completely adjusted model, participants in the high serum folate group had a 27% (OR 0.73, 95% CI 0.62, 0.87, p = 0.0003) and 53% (OR 0.47, 95% CI 0.35, 0.63, p < 0.0001) lower odds of suffering from NAFLD and AHF, respectively, compared to the low serum folate group. The similar results in propensity score matching further validated the above association. Stratified analysis showed that the negative correlation of serum folate with NAFLD and AHF demonstrated a broad consistency across populations. The results of this study indicate that higher serum folate level was associated with lower odds of NAFLD and AHF among US adults. Further prospective studies are necessary due to the limitations of cross-sectional studies.
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Project description:BackgroundThe prognostic factors of morbidity and mortality in patients with lean NAFLD (body mass index < 25.0 kg/m2) are unknown.MethodsIn this retrospective study, 446 Japanese patients with histopathologically-confirmed NAFLD (lean NAFLD, n = 170) were followed for liver events, cardiovascular events, type 2 diabetes mellitus, and non-liver malignancies. The median observation period was 4.6 years. We also investigated the predictors of severe fibrosis (stage 3-4) and mortality in lean NAFLD patients.ResultsGlycolipid metabolic markers, liver function tests, NAFLD fibrosis score (NFS), and histological scoring were significantly lower in lean NAFLD patients than in non-lean NAFLD. The incidence of liver cancer was higher while that of T2DM was lower in lean NAFLD. Kaplan-Meier analysis showed no significant difference in overall survival between the lean and non-lean NAFLD. Multivariate analysis of data of lean NAFLD identified NFS ≥ - 1.455 as significant independent predictor of severe fibrosis, while history of liver cancer and NFS ≥ - 1.455 were predictors of overall survival.ConclusionsAlthough patients with lean NAFLD have better histopathological and biochemical profile compared to patients with non-lean NAFLD, the prognosis is not different between the two groups. Lean NAFLD patients with NFS ≥ - 1.455 or history of liver cancer should be monitored carefully during follow-up.
| S-EPMC7640447 | biostudies-literature
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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Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) affects more than one-third of people living with human immunodeficiency virus (HIV). Nonetheless, its natural history is poorly understood, including which patients are most likely to have a progressive disease course.MethodsWe leveraged a randomized trial of the growth hormone-releasing hormone analogue tesamorelin to treat NAFLD in HIV. Sixty-one participants with HIV-associated NAFLD were randomized to tesamorelin or placebo for 12 months with serial biopsies.ResultsIn all participants with baseline biopsies (n = 58), 43% had hepatic fibrosis. Individuals with fibrosis had higher NAFLD Activity Score (NAS) (mean ± standard deviation [SD], 3.6 ± 2.0 vs 2.0 ± 0.8; P < .0001) and visceral fat content (mean ± SD, 284 ± 91 cm2 vs 212 ± 95 cm2; P = .005), but no difference in hepatic fat or body mass index. Among placebo-treated participants with paired biopsies (n = 24), 38% had hepatic fibrosis progression over 12 months. For each 25 cm2 higher visceral fat at baseline, odds of fibrosis progression increased by 37% (odds ratio, 1.37 [95% confidence interval, 1.03-2.07]). There was no difference in baseline NAS between fibrosis progressors and nonprogressors, though NAS rose over time in the progressor group (mean ± SD, 1.1 ± 0.8 vs -0.5 ± 0.6; P < .0001).ConclusionsIn this longitudinal study of HIV-associated NAFLD, high rates of hepatic fibrosis and progression were observed. Visceral adiposity was identified as a novel predictor of worsening fibrosis. In contrast, baseline histologic characteristics did not relate to fibrosis progression.
| S-EPMC8204775 | biostudies-literature
Project description:AimsThe study aimed to develop a novel noninvasive model to detect advanced fibrosis based on routinely available clinical and laboratory tests.Materials and methodsA total of 309 patients who underwent liver biopsy were randomly divided into the estimation group (n = 201) and validation group (n = 108). The model was developed using multiple regression analysis in the estimation group and further verified in the validation group. Diagnostic accuracy was evaluated using the receiver operating characteristic (ROC) curve.ResultsThe model was named NAFLD Fibrosis Index (NFI): -10.844 + 0.046 × age - 0.01 × platelet count + 0.19 × 2h postprandial plasma glucose (PG) + 0.294 × conjugated bilirubin - 0.015 × ALT + 0.039 × AST + 0.109 × total iron binding capacity -0.033 × parathyroid hormone (PTH). The area under the ROC curve (AUC) of NFI was 0.86 (95% CI: 0.79-0.93, p < 0.001) in the estimation group and 0.80 (95% CI: 0.69-0.91, p < 0.001) in the validation group, higher than NFS, FIB4, APRI, and BARD, and similar to FibroScan (NFI AUC = 0.77, 95% CI: 0.66-0.89, p = 0.001 vs. FibroScan AUC = 0.76, 95% CI: 0.62-0.90, p = 0.002). By applying the low cut-off value (-2.756), advanced fibrosis could be excluded among 49.3% and 48% of patients in the estimation group (sensitivity: 93.1%, NPV: 97.9%, specificity: 55.2%, and PPV: 26.0%) and validation group (sensitivity: 81.3%, NPV: 94.2%, specificity: 53.3%, and PPV: 23.2%), respectively, allowing them to avoid liver biopsy.ConclusionsThe study has established a novel model for advanced fibrosis, the diagnostic accuracy of which is superior to the current clinical scoring systems and is similar to FibroScan.
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