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A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs.

ABSTRACT: A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.

SUBMITTER: Kobayashi T

PROVIDER: S-EPMC9616882 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs.

Kobayashi Takashi T Ogawa Yuji Y Shinoda Satoru S Iwaki Michihiro M Nogami Asako A Honda Yasushi Y Kessoku Takaomi T Imajo Kento K Yoneda Masato M Saito Satoru S Yamamoto Kouji K Oeda Satoshi S Takahashi Hirokazu H Sumida Yoshio Y Nakajima Atsushi A

Scientific reports 20221028 1

A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-s ...[more]

PMID: 36307441

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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:Limited evidence exists on the clinical and economic burden of advanced fibrosis in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) due to the invasiveness of liver biopsies for accurately staging liver disease. The fibrosis-4 (FIB-4) score allows for noninvasive assessment of liver fibrosis by using clinical and laboratory data alone. This study aimed to characterize the comorbidity burden, health care resource use (HCRU), and costs among patients with NAFLD/NASH with FIB-4-defined F3 (bridging fibrosis) and F4 (compensated cirrhosis) fibrosis. Using the Optum Research Database, a retrospective cohort study was conducted among 251,725 commercially insured adult patients with ≥1 NAFLD/NASH diagnosis from January 1, 2008, to August 31, 2016, and laboratory data required to calculate FIB-4 scores. Five criteria using varying FIB-4 score cutoffs were identified based on expert clinical opinion and published literature. Date of the first valid FIB-4 score marked the index date. Mean annual HCRU and costs were calculated during the pre-index and post-index periods. The prevalence of FIB-4-based F3 and F4 fibrosis was 0.40%-2.72% and 1.03%-1.61%, respectively. Almost 50% of patients identified with FIB-4-based F3 or F4 had type 2 diabetes, cardiovascular disease, or renal impairment. Total all-cause health care costs increased significantly from pre-index to post-index for patients with FIB-4-based F3 fibrosis across most criteria (17%-29% increase) and patients with FIB-4-based F4 fibrosis across all criteria (47%-48% increase). Inpatient costs were the primary drivers of this increment. Conclusion: Significant increases in HCRU and costs were observed following FIB-4-based identification of F3 and F4 fibrosis among U.S. adults with NAFLD/NASH. These data suggest the importance of early identification and management of NAFLD/NASH that may halt or reduce the risk of disease progression and limit the underlying burden.

Project description:Dyslipidemia and cardiovascular complications are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis up to hepatocellular carcinoma. Lipoprotein(a) (Lp(a)) has been associated with cardiovascular risk and metabolic abnormalities, but its impact on the severity of liver damage in patients with NAFLD remains to be clarified. Circulating Lp(a) levels were assessed in 600 patients with biopsy-proven NAFLD. The association of Lp(a) with liver damage was explored by categorizing serum Lp(a) into quartiles. The receiver operating characteristic curve was used to analyze the accuracy of serum Lp(a) in hepatic fibrosis prediction. Hepatic expression of lipoprotein A (LPA) and of genes involved in lipid metabolism and fibrogenic processes were evaluated by RNA sequencing in a subset of patients with NAFLD for whom Lp(a) dosage was available (n = 183). In patients with NAFLD, elevated Lp(a) levels were modestly associated with circulating lipids, carotid plaques, and hypertension (P < 0.05). Conversely, patients with low serum Lp(a) displayed insulin resistance (P < 0.05), transaminase elevation (P < 0.05), and increased risk of developing severe fibrosis (P = 0.007) and cirrhosis (P = 0.002). In addition, the diagnostic accuracy of Lp(a) in predicting fibrosis increased by combining it with transaminases (area under the curve fibrosis stage 4, 0.87; P < 0.0001). Hepatic LPA expression reflected serum Lp(a) levels (P = 0.018), and both were reduced with the progression of NAFLD (P < 0.05). Hepatic LPA messenger RNA levels correlated with those of genes involved in lipoprotein release, lipid synthesis, and fibrogenesis (P < 0.05). Finally, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, apolipoprotein E (ApoE) rs445925, and proprotein convertase subtilisin/kexin type 9 (PCSK9) rs7552841, known variants that modulate circulating lipids, may influence serum Lp(a) levels (P < 0.05). Conclusion: Circulating Lp(a) combined with transaminases may represent a novel noninvasive biomarker to predict advanced fibrosis in patients with NAFLD.

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.

Project description:BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk of advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective study included probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 first-degree relative. A total of 396 first-degree relatives - 220 in a derivation cohort and 176 in a validation cohort - were enrolled in the study, and liver fibrosis was evaluated using magnetic resonance elastography and other noninvasive imaging modalities. The primary outcome was prevalence of advanced fibrosis in first-degree relatives.RESULTSPrevalence of advanced fibrosis in first-degree relatives of probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD was 15.6%, 5.9%, and 1.3%, respectively (P = 0.002), in the derivation cohort, and 14.0%, 2.6%, and 1.3%, respectively (P = 0.004), in the validation cohort. In multivariable-adjusted logistic regression models, age of ≥50 years (adjusted OR [aOR]: 2.63, 95% CI 1.0-6.7), male sex (aOR: 3.79, 95% CI 1.6-9.2), diabetes mellitus (aOR: 3.37, 95% CI 1.3-9), and a first-degree relative with NAFLD with advanced fibrosis (aOR: 11.8, 95% CI 2.5-57) were significant predictors of presence of advanced fibrosis (all P < 0.05).CONCLUSIONFirst-degree relatives of probands with NAFLD with advanced fibrosis have significantly increased risk of advanced fibrosis. Routine screening should be done in the first-degree relatives of patients with advanced fibrosis.FUNDINGSupported by NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515, K23DK119460), NHLBI (P01HL147835), and NIAAA (U01AA029019); Academy of Finland grant 309263; the Novo Nordisk, EVO, and Sigrid Jusélius Foundations; and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA.

Dataset Information

A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs.

Publications

A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs.

Similar Datasets

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