Noninvasive Tests (NITs) for Hepatic Fibrosis in Fatty Liver Syndrome.
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ABSTRACT:
SUBMITTER: Han MAT
PROVIDER: S-EPMC7555355 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Noninvasive Tests (NITs) for Hepatic Fibrosis in Fatty Liver Syndrome.
Life (Basel, Switzerland) 20200913 9
Fatty liver syndrome is an emerging health problem in the world, due to the high prevalence of obesity and alcohol use disorder. Given the nature of the disease's advancement to cirrhosis and liver-related complications, it is important to assess the severity of the disease, which is typically done via a liver biopsy. Due to the limitations and risks of liver biopsy, the role of noninvasive tests is essential and evolving to stratify the stage of the liver disease, predict the outcomes, and/or m ...[more]
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Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is highly prevalent in morbidly obese patients, and fibrosis is an independent predictor of mortality. Noninvasive tests (NITs) are being developed for the detection of advanced fibrosis (AF).PurposeTo assess the performance of three NITs (NAFLD fibrosis score, NFS, fibrosis-4 index, FIB-4, and aspartate aminotransferase-to-platelet ratio, APRI), in the identification of AF among morbidly obese patients.Materials and methodsPatients, who underwent bariatric surgery between 2004 and 2009 and had liver biopsy, were included. Fibrosis stages ≥ F2 and ≥ F3 were defined as significant and AF, respectively. Published and optimal thresholds (Youden index) for NFS, FIB-4 and APRI, sensitivity, specificity, positive and negative predictive values (PPV-NPV), and area under the receiver operator curves (AUROC) were evaluated.ResultsAmong 584 patients (mean age 43.3 ± 11.3 years, 21.2% male, 75% white, mean BMI 45.5 ± 8.80), 31.7% had NASH. Stages distributions were F1 = 68.1%, F2 = 16.4%, F3 = 8%, and F4 = 3.2%. At published thresholds, all 3 NITs performed poorly for detection of AF, with AUROC < 0.62. Overall performance at optimal thresholds improved to 0.68, 0.72, and 0.74 for NFS, FIB-4, and APRI, respectively. At optimal thresholds, all tests had good NPV (94.4-95.9%) but low PPV (24.2-32.5%). Combinations of the tests did not improve their performance.ConclusionsNFS, FIB-4, and APRI fall short to detect advanced fibrosis but valuable for excluding advanced fibrosis. More research is needed to develop new NITs with high positive predictive value.
| S-EPMC8041679 | biostudies-literature
Project description:Background and aimsNonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.MethodsA total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis.ResultsMetabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004-5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083-9.725, p<0.001) were significantly associated with advanced fibrosis. Using these two metabolic disorders as a screening tool, a sensitivity, specificity and accuracy of 92%, 81% and 83% was achieved, respectively. With the new algorithms combining metabolic disorders with noninvasive measurements, the number of patients requiring liver biopsy was reduced, especially in combination with the Fibrosis-4 score and metabolic disorders (36% to 17%, p<0.001). In addition, this stepwise algorithm could achieve a high accuracy (85%) and high negative predictive value (93%).ConclusionsMetabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis. With further validation and investigation, new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.
| S-EPMC8516831 | biostudies-literature
Project description:It remains unclear whether screening for advanced fibrosis in the community can identify the subgroup of people with nonalcoholic fatty liver disease (NAFLD) at higher risk for development of liver-related complications. We aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver-related outcomes and mortality in patients with NAFLD from type 2 diabetes (T2D) clinics or primary care. Patients (n = 243) who were screened for NAFLD with advanced fibrosis by using NAFLD fibrosis score (NFS), fibrosis 4 score (FIB-4), enhanced liver fibrosis (ELF) test, and liver stiffness measurements (LSMs) were followed up for clinical outcomes by review of electronic medical records. During a median follow-up of 50 months, decompensated liver disease or primary liver cancer occurred in 6 of 35 (17.1%) patients with baseline LSM > 13 kPa, 1 of 17 (5.9%) patients with LSM 9.5-13 kPa, and in no patients with LSM < 9.5 kPa. No patient with low-risk NFS developed liver decompensation or liver-related mortality. Following repeat NFSs at the end of follow-up, all patients with a liver-related complication were in the high-risk NFS category. Patients who developed liver-related complications were also more likely to have baseline high-risk FIB-4 scores or ELF test ≥9.8 compared to patients who did not develop liver outcomes. Conclusion: Liver fibrosis risk stratification in non-hepatology settings can identify the subset of patients at risk of liver-related complications. Although the rate of development of a decompensation event or hepatocellular carcinoma was low (2.1% per year) in our patients with compensated cirrhosis (LSM > 13 kPa), these events are projected to lead to a substantial increase in NAFLD-related disease burden over the next decade due to the high prevalence of NAFLD in people with obesity and T2D.
| S-EPMC8948588 | biostudies-literature
Project description:ObjectivesEarly identification of children with cystic fibrosis (CF) at risk for severe liver disease (CFLD) would enable targeted study of preventative therapies. There is no gold standard test for CFLD. Ultrasonography (US) is used to identify CFLD, but with concerns for its diagnostic accuracy. We aim to determine if differences in standard blood tests, imaging variables and noninvasive liver fibrosis indices correlate with liver US patterns, and thus provide supportive evidence that a heterogeneous US liver pattern reflects clinically relevant liver disease.MethodsWe studied baseline research abdominal US and bloodwork from 244 children with pancreatic insufficient CF, ages 3 to 12 years, enrolled in a prospective study of the ability of US to predict CF cirrhosis (PUSH study). Children with a heterogeneous (HTG) liver pattern on US (n = 62) were matched 1 : 2 in design with children with normal US (NL, n = 122). Analyses included children with nodular (NOD, n = 22) and homogeneous hyperechoic (HMG, n = 38) livers.ResultsUnivariate analysis showed significant differences between US groups for standard blood tests, spleen size, and noninvasive liver fibrosis indices. Multivariable models discriminated NOD versus NL with excellent accuracy (AUROC 0.96). Models also distinguish HTG versus NL (AUROC 0.76), NOD versus HTG (0.78), and HMG versus NL (0.79).ConclusionsLiver US patterns in children with CF correlate with platelet count, spleen size and indices of liver fibrosis. Multivariable models of these biomarkers have excellent discriminating ability for NL versus NOD, and good ability to distinguish other US patterns, suggesting that US patterns correlate with clinically relevant liver disease.
| S-EPMC6713487 | 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:BackgroundLiver fibrosis predicts liver-related morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Non-invasive scores correlate with the degree of liver fibrosis in these patients.Aims and methodsTo investigate the accuracy of noninvasive scoring systems in predicting long-term outcomes and cancer incidence of patients with NAFLD, we performed a single-center retrospective study of patients with biopsy proven NAFLD. Mean follow up period was 100 months. Outcomes included liver-related complications, hospitalizations, overall mortality and the development of any malignancies.Results32 patients had advanced fibrosis (F3-F4) per biopsy at baseline and 121 patients had mild to moderate fibrosis (F0-F2). Both advanced histologic fibrosis stage as well as higher non-invasive scores predicted repeated hospitalizations and longer hospitalization stays. In a multivariate analysis, liver fibrosis (p = 0.002), FIB-4 score (p<0.001), NFS (p<0.001) but not APRI score (p = 0.07) were predictors of overall mortality, and the occurrence of malignancies was associated with higher APRI (p<0.001), FIB-4 (p<0.001) and NFS (p = 0.008) scores, but not with advanced fibrosis, as determined by liver biopsy (p = 0.105).ConclusionsIn NAFLD patients, noninvasive scoring systems are good predictors of morbidity and mortality and may have an additive value in predicting the development of hepatic and extra-hepatic cancers.
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Project description:UnlabelledThe cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage?F2; testing with liver biopsy and treating patients with ?F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the "treat all" strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER=£9,189).ConclusionsTreating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries.
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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.
| S-EPMC10412549 | biostudies-literature
Project description:Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p < 0.001) with age, regardless of NAFLD status. Therefore, telomere length was corrected for age. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). In multivariate analysis, age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37-0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80-0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.
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Project description:This study aimed to investigate the relationship between serum zinc level and hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). A cross-sectional study was conducted using nationally representative samples from the Korea National Health and Nutrition Examination Survey 2010. Significant hepatic fibrosis was defined as Fibrosis-4 (FIB-4) index>1.3. Zinc level was measured using inductively coupled plasma mass spectrometry. Univariable and multivariable logistic regression analyses were performed to assess risk factors for significant hepatic fibrosis in patients with NAFLD. A total of 300 patients with NAFLD were analyzed in this study. The mean serum zinc level was 139.8±29.9 μg/dL. FIB-4 index was significantly increased as the serum zinc level decreased (Adjusted correlation coefficient = -0.177, p = 0.003). Significant liver fibrosis was observed in 62 patients (21%). The multivariable analysis showed that significant liver fibrosis in NAFLD was associated with diabetes mellitus (odds ratio [OR], 3.25; 95% confidence interval [CI], 1.71-6.19; p<0.001), male (OR, 2.59; 95% CI, 1.31-5.12; p = 0.006), and zinc level <140 μg/dL (OR, 2.14; 95% CI, 1.16-3.94; p = 0.015). There was an inverse relationship between serum zinc level and FIB-4 index in NAFLD. Low levels of serum zinc were an independent risk factor for significant hepatic fibrosis in NAFLD.
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