Diagnostic performance of three non-invasive fibrosis scores (Hepamet,FIB-4, NAFLD fibrosis score) in NAFLD patients from a mixed Latin American population

Introduction and aimsSeveral non-invasive scoring systems have been developed and validated worldwide to predict the risk of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). However, information about the performance of these systems in Latin American populations is scarce. Our aim was to evaluate the performance of the Hepamet Fibrosis Score, Fibrosis-4 (FIB-4) and the NAFLD Fibrosis Score (NFS) in a mixed Latin American group of NAFLD patients.MethodsClinical, laboratory and liver biopsy data collected from 379 biopsy-proven NAFLD patients from Latin American tertiary health centers were reviewed. Histological fibrosis stages were classified using the Kleiner score. Accuracy was determined, and new fibrosis score thresholds were calculated to better compare the performances of non-invasive tests and to explore their usefulness in excluding fibrosis.ResultsThe distribution of fibrosis stages among the sample population was as follows: F0 (45%), F1 (27%), F2 (8%), F3 (16%) and F4 (4%). Using modified thresholds, the areas under the ROC curves (AUROC) for Hepamet and FIB-4 (0.73 and 0.74, respectively) to detect significant fibrosis were higher than that of NFS (0.58). However, the AUROCs of the three scores were not significantly different in advanced fibrosis and cirrhosis. To exclude fibrosis, we calculated lower cutoffs than standard thresholds for Hepamet, FIB-4 and NFS with similar performances.ConclusionThresholds of non-invasive fibrosis scores (Hepamet, FIB-4 and NFS) can be modified to maximize diagnostic accuracy in Latin American patients with NAFLD.     

The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD

Patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis are at the highest risk for progressing to end-stage liver disease. We constructed and validated a scoring system consisting of routinely measured and readily available clinical and laboratory data to separate NAFLD patients with and without advanced fibrosis. A total of 733 patients with NAFLD confirmed by liver biopsy were divided into 2 groups to construct (n = 480) and validate (n = 253) a scoring system. Routine demographic, clinical, and laboratory variables were analyzed by multivariate modeling to predict presence or absence of advanced fibrosis. Age, hyperglycemia, body mass index, platelet count, albumin, and AST/ALT ratio were independent indicators of advanced liver fibrosis. A scoring system with these 6 variables had an area under the receiver operating characteristic curve of 0.88 and 0.82 in the estimation and validation groups, respectively. By applying the low cutoff score (-1.455), advanced fibrosis could be excluded with high accuracy (negative predictive value of 93% and 88% in the estimation and validation groups, respectively). By applying the high cutoff score (0.676), the presence of advanced fibrosis could be diagnosed with high accuracy (positive predictive value of 90% and 82% in the estimation and validation groups, respectively). By applying this model, a liver biopsy would have been avoided in 549 (75%) of the 733 patients, with correct prediction in 496 (90%). CONCLUSION: a simple scoring system accurately separates patients with NAFLD with and without advanced fibrosis, rendering liver biopsy for identification of advanced fibrosis unnecessary in a substantial proportion of patients.     

Noninvasive scoring systems in patients with nonalcoholic fatty liver disease with normal alanine aminotransferase levels

Background

The severity of liver fibrosis must be estimated to determine the prognosis, for surveillance, and for optimal treatment of nonalcoholic fatty liver disease (NAFLD). However, the severity of hepatic fibrosis tends to be underestimated in patients with normal ALT.

Methods

We investigated histological data and scoring systems (FIB-4 index, NAFLD fibrosis score, BARD score, and AST/ALT ratio) of 1,102 liver-biopsy-confirmed NAFLD patients.

Results

A total of 235 NAFLD patients with normal ALT were estimated to exist. The ratio of advanced fibrosis (stage 3–4) was seen in 16.1 % of subjects with normal ALT. Scoring systems, especially the FIB-4 index and NAFLD fibrosis score, were clinically very useful (AUROC >0.8), even in patients with normal ALT. Furthermore, with resetting of the cutoff values, the FIB-4 index (>1.659) and NAFLD fibrosis score (>0.735) were found to have a higher sensitivity and higher specificity for the prediction of advanced fibrosis, and all of these scoring systems (FIB-4 index, NAFLD fibrosis score, BARD score, and AST/ALT ratio) had higher negative predictive values (>90.3 %). By using the resetting cutoff value, liver biopsy could have been avoided in 60.4 % (FIB-4), 66.4 % (NAFLD fibrosis score), 51.9 % (BARD score), and 62.1 % (AST/ALT ratio).

Conclusions

We reset the cutoff values of numerous non-invasive scoring systems to improve their clinical usefulness in the prediction of liver fibrosis in NAFLD patients with normal ALT, and these non-invasive scoring systems with the reset cutoff values could be of substantial benefit to reduce the number of liver biopsies performed.     

NAFLD fibrosis score:A prognostic predictor for mortality and liver complications among NAFLD patients

AIM:To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease(NAFLD) fibrosis score can predict all-cause mortality,cardiac complications,and/or liver complications of patients with NAFLD over long-term follow-up.METHODS:A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project.The NAFLD fibrosis score(NFS) was used to separate NAFLD patients with and without advanced liver fibrosis.We used the NFS score to classify the probability of fibrosis as <-1.5 for low probability,>-1.5 to < 0.67 for intermediate probability,and > 0.67 for high probability.Primary endpoints included allcause death and cardiovascular-and/or liver-related mortality.From the 479 patients with NAFLD assessed,302 patients(63%) greater than 18 years old were included.All patients were followed,and medical charts were reviewed until August 31,2009 or the date when the first primary endpoint occurred.By using a standardized case record form,we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period.RESULTS:A total of 302/479(63%) NAFLD patients(mean age:47 ± 13 year) were included with a followup period of 12.0 ± 3.9 year.A low probability of advanced fibrosis(NFS <-1.5 at baseline) was found in 181 patients(60%),while an intermediate or high probability of advanced fibrosis(NSF >-1.5) was found in 121 patients(40%).At the end of the follow-up period,55 patients(18%) developed primary endpoints.A total of 39 patients(13%) died during the follow-up.The leading causes of death were non-hepatic malignancy(n = 13/39;33.3%),coronary heart disease(CHD)(n = 8/39;20.5%),and liver-related mortality(n = 5/39;12.8%).Thirty patients had new-onset CHD,whereas 8 of 30 patients(27%) died from CHD-related causes during the follow-up.In a multivariate analysis,a higher NFS at baseline and the presence of new-onset CHD were significantly predictive of d     

Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Severe NAFLD with advanced fibrosis results in substantial morbidity and mortality. Associated with metabolic syndrome, NAFLD is often initially clinically silent, yet intensive lifestyle intervention with 7% or greater weight loss can improve or resolve NAFLD. Using a Veterans Health Administration (VHA) liver biopsy cohort, we evaluated simple noninvasive fibrosis scoring systems to identify NAFLD with advanced fibrosis (or severe disease) to assist providers.

Methods

In our retrospective study of a national VHA sample of patients with biopsy-proven NAFLD or normal liver (2005–2015), we segregated patients by fibrosis stage (0–4). Non-NAFLD liver disease was excluded. We evaluated the diagnostic accuracy of the NAFLD fibrosis score (NFS), fibrosis-4 calculator (FIB-4), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT ratio), AST-to-platelet ratio index (APRI), and body mass index, AST/ALT ratio, and diabetes (BARD) score by age groups.

Results

We included 329 patients with well-defined liver histology (296 NAFLD and 33 normal controls without fibrosis), in which 92 (28%) had advanced (stage 3–4) fibrosis. Across all age groups, NFS and FIB-4 best predicted advanced fibrosis (NFS with 0.676 threshold: AUROC 0.71–0.76, LR?+?2.30–22.05, OR 6.00–39.58; FIB-4 with 2.67 threshold: AUROC of 0.62–0.80, LR?+?4.70–27.45, OR 16.34–59.65).

Conclusions

While NFS and FIB-4 scores exhibit good diagnostic accuracy, FIB-4 is optimal in identifying NAFLD advanced fibrosis in the VHA. Easily implemented as a point-of-care clinical test, FIB-4 can be useful in directing patients that are most likely to have advanced fibrosis to GI/hepatology consultation and follow-up.

     

FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎合并非酒精性脂肪性肝病进展期肝纤维化的诊断价值比较

目的评价FibroScan、GPR、APRI、NFS、FIB-4单独应用及FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)患者进展期肝纤维化的诊断价值。方法选取2014年11月-2018年8月在四川省人民医院行肝穿刺病理检查并确诊为CHB合并NAFLD的患者92例。根据肝穿刺病理SAF分级诊断标准,分为轻中度肝纤维化(F1+F2)组(n=69)和进展期肝纤维化(F3)组(n=23)。同时应用FibroScan测得肝脏硬度值,根据临床指标分别计算GPR、APRI、NFS、FIB-4。计量资料两组间比较采用Mann-Whitney U检验;相关性分析采用Spearman秩相关;多因素二元logistic回归构建联合预测因子(向前逐步回归法),绘制受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC),并采用Delong方法进行比较,评价各种无创诊断方法单独及联合应用对CHB合并NAFLD进展期肝纤维化的诊断价值。结果轻中度肝纤维化组的FibroScan、GPR、APRI、NFS及FIB-4水平明显低于进展期肝纤维化组(Z值分别为-4.910、-3.425、-3.837、-3.873、-3.990,P值均<0.05)。相关性分析结果显示,FibroScan、GPR、APRI、NFS、FIB-4与肝纤维化病理分期均呈正相关(r值分别为0.518、0.361、0.405、0.407、0.418,P值均<0.001)。FibroScan、GPR、APRI、NFS及FIB-4单独应用对诊断进展期肝纤维化均有一定价值(AUC分别为0.844、0.740、0.770、0.771、0.779,P值均<0.001),但FibroScan诊断价值并不优于GPR、APRI、NFS、FIB-4(P值均>0.05)。将FibroScan分别与GPR、APRI、NFS、FIB-4联合,诊断进展期肝纤维化的AUC均较单独应用时明显提高(Z值分别为1.977、2.076、2.361、2.206,P值均<0.05);将FibroScan与GPR+APRI+NFS+FIB-4同时联合诊断进展期肝纤维化的AUC及95%可信区间为0.896(0.813~0.950)。结论FibroScan、GPR、APRI、NFS及FIB-4诊断进展期肝纤维化均有一定的临床价值,FibroScan分别与GPR、APRI、NFS、FIB-4联合诊断进展期肝纤维化的效能优于单项血清学模型,其中FibroScan联合NFS或FIB-4的临床价值可能最佳。     

Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis

OBJECTIVES:  Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. This study aimed to validate the NAFLD fibrosis score in the Chinese population.
METHODS:  NAFLD patients were prospectively recruited for liver biopsy and blood tests. The NAFLD fibrosis score was calculated as −1.675 + 0.037 × age (yr) + 0.094 × BMI (kg/m²) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio–0.013 × platelet (×10⁹/L)−0.66 × albumin (g/dL). Advanced fibrosis was defined as stage 3 to 4 fibrosis.
RESULTS:  One hundred sixty-two patients (age 46 ± 10 yr, male 59%) were included in the study. Advanced fibrosis was found in 18 (11%) patients. Only 11 of 128 patients with the NAFLD fibrosis score below the proposed low cutoff point (<−1.455) were under-staged, resulting in a high negative predictive value of 91%. Only two patients exceeded the proposed high cutoff point (>0.676), but neither had advanced fibrosis. If the NAFLD fibrosis score was implemented in the Chinese population, 79% of liver biopsies could be avoided.
CONCLUSIONS:  The NAFLD fibrosis score has high negative predictive value in excluding advanced fibrosis in the Chinese population, and can reduce the burden of liver biopsy in the vast majority of cases. Since there were few cases of advanced fibrosis in this cohort, this study had limited power in validating the high cutoff point.     

Non‐invasive diagnosis of non‐alcoholic steatohepatitis and advanced fibrosis in Japan: A targeted literature review

Despite the invasive nature of liver biopsy, it remains the current standard for diagnosing non‐alcoholic steatohepatitis (NASH) and fibrosis staging. Given the rising prevalence of non‐alcoholic fatty liver disease (NAFLD) in Japan, there is a need for reliable non‐invasive tests to accurately and efficiently identify NASH and advanced (F3/F4) fibrosis. A review of published works from English and Japanese sources was undertaken in PubMed, Embase, and Ichushi Web to identify studies reporting diagnostic characteristics of NITs in biopsy‐proven Japanese NAFLD/NASH patients including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve. The performance of non‐invasive tests for two diagnostic questions were assessed, namely: (i) identifying NASH cases among NAFLD; and (ii) distinguishing advanced fibrosis (F3–4) from milder fibrosis (F0–2). Twenty‐five studies reported outcomes for serum biomarkers, imaging, scoring systems, and novel complex techniques (based on multivariable regression models) for both diagnostic questions. Serum biomarkers were the most commonly assessed method for NASH identification, whereas scoring systems and imaging techniques were most commonly studied for fibrosis staging. In general, tests for NASH identification showed higher PPVs than NPVs, suggesting their usefulness in identifying probable NASH cases. The reverse was observed for fibrosis staging, with higher NPVs than PPVs, suggesting their use in excluding patients at low risk of F3/F4 disease rather than identifying definite F3/F4 fibrosis. In Japanese studies, simple scoring systems and imaging techniques showed particular usefulness in prediction of fibrosis staging, and combinations of serum biomarkers showed diagnostic potential for NASH screening.     

Postprandial glucose is correlated with an increasing risk of liver fibrosis in Chinese patients with nonalcoholic fatty liver disease

AimType 2 diabetes (T2DM) is closely related to nonalcoholic fatty liver disease (NAFLD) and is an important risk factor for the progression of liver fibrosis, but the role of 2-h postprandial blood glucose (PPG) as a biomarker in this process remains unclear. This study was designed to investigate the relationship between PPG and liver fibrosis in Chinese NAFLD populations with or without T2DM.MethodsThis study included three independent NAFLD populations: 1) 618 inpatients with T2DM or pre-diabetes, 2) 255 patients with T2DM or pre-diabetes who underwent liver biopsy, and 3) a prospective community-based cohort without diabetes who completed a median of 4.22 years follow-up. The degree of liver fibrosis was assessed by liver fibrosis stage in subjects with a liver biopsy, and by NAFLD fibrosis score (NFS) in subjects without liver biopsy.ResultsIn the first population, PPG {OR 0.02, [95% CI (0.01–0.03)], P< 0.001} was positively correlated with NFS. In the second population, an increasing PPG was associated with increase in the proportion of advanced liver fibrosis (P = 0.012). Multivariate line regression revealed that PPG {OR 0.03 [95% CI (0.00–0.06)], P = 0.049}was positively associated with liver fibrosis stages. In the third population, PPG {OR 0.103, [95% CI (0.011–0.194) P = 0.028} at baseline was positively associated with NFS at follow-up. Furthermore, changes in PPG were significantly associated with NFS change after follow-up. We did not find a similar association between fasting glucose or HbA1c and liver fibrosis.ConclusionsPPG was independently associated with the severity of liver fibrosis in the Chinese NAFLD population.     

Non-invasive fibrosis scoring systems can predict future metabolic complications and overall mortality in non-alcoholic fatty liver disease (NAFLD)

Background and aim: Progression to fibrosis in non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of liver-related events, overall mortality and possibly metabolic comorbidities. Our aim was to determine if non-invasive fibrosis scoring systems can predict the future risk of diabetes mellitus, cardiovascular disease (CVD), chronic kidney disease (CKD), liver-related events and overall mortality.

Methods: Patients with biopsy-proven NAFLD 1978 to 2006 were identified from a computerised register in Malmö, Sweden. Medical records were scrutinised in detail to collect data from inclusion to endpoint (death or end of 2016). Non-invasive fibrosis scoring systems (FIB-4-index, NAFLD fibrosis score (NFS), APRI and BARD score) were calculated and the scores classified into three risk categories (low, intermediate and high risk for advanced fibrosis). Chronic kidney disease was evaluated using the CKD-EPI equation.

Results: One hundred and forty-four patients with biopsy-proven NAFLD were included, with a mean age of 53.2 years and a mean follow-up time of 18.8 years. At inclusion, 18% had advanced fibrosis. NFS was the only score that could predict the future risk of all included outcomes with fairly good accuracy (Area-under-ROC curve). Multivariate-adjusted hazard ratios revealed that both the intermediate and high-risk category of FIB-4-index and NFS could significantly predict metabolic outcomes. All four scoring systems significantly predicted overall mortality in the high-risk category.

Conclusions: Non-invasive fibrosis scoring systems, especially NFS and FIB-4-index, can be used to identify patients at risk of future liver-related events, overall mortality, metabolic comorbidities and CKD.     

A novel non-invasive model for the prediction of advanced liver fibrosis in chronic hepatitis B patients with NAFLD

There are still lack of non-invasive models to evaluate liver fibrosis in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). We aimed to establish a predictive model for advanced fibrosis in these patients. A total of 504 treatment-naive CHB patients with NAFLD who underwent liver biopsy were enrolled and randomly divided into a training set (n = 336) and a validation set (n = 168). Receiver operating characteristic (ROC) curve was used to compare predicting accuracy for the different models. One hundred fifty-six patients (31.0%) had advanced fibrosis. In the training set, platelet, prothrombin time, type 2 diabetes, HBeAg positivity and globulin were significantly associated with advanced fibrosis by multivariable analysis. A predictive model namely PPDHG for advanced fibrosis was developed based on these parameters. The areas under the ROC curve (AUROC) of PPDHG with an optimal cut-off value of −0.980 in predicting advanced fibrosis was 0.817 (95% confidence interval 0.772 to 0.862), with a sensitivity of 81.82% and a specificity of 66.81%. The predicting accuracy of PPDHG for advanced fibrosis was significantly superior to AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS). Further analysis revealed that the AUROC of PPDHG remained significantly higher than FIB-4 and NFS indexes, while it was comparable with APRI for predicting advanced fibrosis in the validation set. PPDHG had a better predicting performance than established models for advanced fibrosis in CHB patients with NAFLD. The application of PPDHG can reduce the necessary for liver biopsy in these patients.     

Validation of Non-invasive Fibrosis Scores for Predicting Advanced Fibrosis in Metabolic-associated Fatty Liver Disease

Background and AimsMetabolic-associated fatty liver disease (MAFLD) is a newly proposed terminology from 2020; yet, the applicability of conventional noninvasive fibrosis models is still unknown for it. We aimed to evaluate the performance of conventional noninvasive fibrosis scores in MAFLD.MethodsThe NHANES 2017-2018 datasets were used to compare the performances of different noninvasive fibrosis scores in MAFLD, including the aspartate aminotransferase (AST) to platelet ratio index (APRI), body mass index (BMI)-AST/alanine aminotransferase (ALT) ratio and diabetes score (BARD), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS). Moreover, Asian patients with biopsy-proven MAFLD were enrolled to further validate the findings.ResultsA total of 2,622 participants in the National Health and Nutrition Examination Survey (NHANES) cohort and 293 patients with MAFLD in the Asian cohort were included. Patients in the Asian cohort had a lower BMI and higher liver enzymes (p<0.001). The area under the receiver operating characteristic curve (AUROC) of NFS was the largest in the NHANES cohort and Asian cohorts (0.679 and 0.699, respectively). The AUROC of NFS was followed by APRI, FIB-4, and BARD in the NHANES cohort (0.616, 0.601, and 0.589, respectively). In the Asian cohort, the AUROC of APRI, FIB-4, and BARD for predicting advanced fibrosis were 0.625, 0.683, and 0.615, respectively. The performance of FIB-4 was better in the Asian cohort than that in the NHANES cohort.ConclusionsNFS is better for predicting advanced fibrosis in MAFLD. FIB-4 can be an alternative choice for MAFLD with high liver enzymes when NFS is unavailable. Novel efficient noninvasive fibrosis scoring systems are highly required for patients with MAFLD.     

New FIB-4 and NFS cutoffs to guide sequential non-invasive assessment of liver fibrosis by magnetic resonance elastography in NAFLD

Introduction and ObjectivesLiver fibrosis is an important prognosis marker in non-alcoholic fatty liver disease (NAFLD). Biopsy has been considered the gold-standard method for measuring liver fibrosis; however, it is an invasive procedure. Non-invasive diagnostic tools have been developed, such as clinical scores and magnetic resonance elastography (MRE), which is the most accurate non-invasive method to determine liver fibrosis. Thus, the aim was to determine the NAFLD Fibrosis Score (NFS) and the Fibrosis-4 Score (FIB-4) cut-off points that best identify NAFLD patients at risk for developing liver fibrosis.Patients and MethodsSingle-center cross-sectional study with prospective recruitment of NAFLD (training-cohort) and MAFLD (validation-cohort) patients undergoing MRE. The NFS and the FIB-4 cut-off points that best-differentiated patients with fibrosis, using the MRE as the standard method, were determined.ResultsTwo cohorts were analyzed, a training cohort that included the initial 183 patients with NAFLD and a validation cohort that included 289 patients. In the training cohort, 60.1% had mild steatosis and 11.5% had liver fibrosis ≥ F1 by MRE. ROC curves were developed for FIB-4 and NFS, and the cut-off points chosen were 1.505 (sensitivity=85% and specificity=86%) for FIB-4 and -0.835 (sensitivity=100% and specificity=70%) for NFS, showing greater specificity than the cut-off points currently used (51% and 76%, respectively). The two cohorts exhibited similar characteristics and similar sensitivity and specificity results for the chosen cut-off points.ConclusionsThis study has shown cut-off points with greater specificity and excellent sensitivity to guide the indication for further liver evaluation by MRE in NAFLD patients.     

Importance of non-invasive liver fibrosis scores for mortality and complications development in individuals with type 2 diabetes

AimsTo evaluate the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 score (FIB4) as predictors of complications development and mortality in a cohort of type 2 diabetes.Methods554 type 2 diabetic subjects had NFS and FIB4 calculated at baseline. Multivariate Cox and Poisson analyses evaluated the associations between fibrosis scores and the occurrence of microvascular and cardiovascular complications, and all-cause mortality.ResultsAccording to recommended cut-offs of NFS, 12.8% had advanced fibrosis and 45.9% had absence of advanced fibrosis and of FIB4, 3.8% and 86.1%, respectively. During a median follow-up of 11 years, 217subjects died, 172 had cardiovascular events (CVEs), 184 had renal events, and 139 had retinopathy and 185 neuropathy events. As continuous variables, both scores predicted all-cause mortality: NFS, HR: 1.30 (p = 0.032) and FIB4, HR: 1.24 (p = 0.021); an increased NFS implied in a significant 90% excess risk of mortality, whereas a higher FIB4 in a borderline 69% higher risk. The scores were mainly predictors of mortality in women and for non-cardiovascular deaths. The NFS was a predictor of renal events, mainly for renal function deterioration.ConclusionsThe NFS and FIB4 predicted all-cause mortality, particularly in women and for non-cardiovascular causes. The NFS predicted adverse renal outcomes. These liver fibrosis scores may improve stratification risk in individuals with diabetes and NAFLD.     

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD)

Introduction and aimThe gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD.Material and methodsNAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard.ResultsA total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6 kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78–0.97).ConclusionWhen compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score.     

High prevalence of undiagnosed liver cirrhosis and advanced fibrosis in type 2 diabetic patients

Background. Patients with type 2 diabetes mellitus (T2DM) are at risk for developing end-stage liver disease due to nonalcoholic steatohepatitis (NASH), the aggressive form of non-alcoholic fatty liver disease (NAFLD). Data on prevalence of advanced fibrosis among T2DM patients is scarce. Aim. To evaluate prevalence of steatosis, advanced fibrosis and cirrhosis using non-invasive methods in T2DM patients.Material and methods. 145 consecutive T2DM patients (> 55 years-old) were prospectively recruited. Presence of cirrhosis and advanced fibrosis was evaluated by magnetic resonance imaging (MRI) and NAFLD fibrosis score (NFS) respectively. Exclusion criteria included significant alcohol consumption, markers of viral hepatitis infection or other liver diseases. Results are expressed in percentage or median (interquartile range).Results. 52.6% of patients were women, the median age was 60 years old (57-64), mean BMI was 29.6 ± 4.7 kg/m² and diabetes duration was 7.6 ± 6.9 years. A high prevalence of liver steatosis (63.9%), advanced fibrosis assessed by NFS (12.8%) and evidence of liver cirrhosis in MRI (6.0%) was observed. In a multivariate analysis GGT > 82 IU/L (P = 0.004) and no alcohol intake (P = 0.032) were independently associated to advanced fibrosis.Conclusion. A high frequency of undiagnosed advanced fibrosis and cirrhosis was observed in non-selected T2DM patients. Screening of these conditions may be warranted in this patient population.     

Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

It is estimated that 30%of the adult population in Japan is affected by nonalcoholic fatty liver disease(NAFLD).Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography(US)and computed tomography(CT),but the sensitivity of these imaging techniques is low in cases of mild steatosis.Alanine aminotransferase levels may be normal in some of these patients,warranting the necessity to establish a set of parameters useful for detecting NAFLD,and the more severe form of the disease,nonalcoholic steatohepatitis(NASH).Although liver biopsy is currently the gold standard for diagnosing progressive NASH,it has many drawbacks,such as sampling error,cost,and risk of complications.Furthermore,it is not realistic to perform liver biopsies on all NAFLD patients.Diagnosis of NASH using various biomarkers,scoring systems and imaging methods,such as elastography,has recently been attempted.The NAFIC score,calculated from the levels of ferritin,fasting insulin,and typeⅣcollagen 7S,is useful for the diagnosis of NASH,while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis.This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.     

Comments on validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

To evaluate and predict liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), several non-invasive scoring systems were built and widely used in the progress of diagnosis and treatment, which showed great diagnostic efficiency, such as aspartate aminotransferase to platelet ratio index, fibrosis-4 index, body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes score and NAFLD fibrosis score. Since the new concept of metabolic associated fatty liver disease (MAFLD) was proposed, the clinical application value of the non-invasive scoring systems mentioned above has not been assessed in MAFLD. The evaluation of the diagnostic performance of these non-invasive scoring systems will provide references for clinicians in the diagnosis of MAFLD.     

Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis

Hepatic steatosis has been associated with fibrosis, but it is unknown whether the latter is independent of the etiology of fat infiltration. We analyzed the relationship between clinical characteristics, insulin resistance (HOMA-R) and histological parameters in 132 patients with "viral" steatosis caused by genotype 3 chronic hepatitis C (CHC-3) and 132 patients with "metabolic" steatosis caused by nonalcoholic fatty liver disease (NAFLD), matched by age, BMI, and degree of liver fat accumulation. Tests of liver function were comparable in the two study populations. The prevalence of features of insulin resistance was higher in NAFLD, as was HOMA-R (P = .008). Logistic regression analysis confirmed that steatosis was associated with a high viral load and low serum cholesterol in CHC-3, and with high aminotransferase, glucose, ferritin and hypertriglyceridemia in NAFLD. At univariate analysis, advanced fibrosis was associated with steatosis in NAFLD, but not in CHC-3. Other parameters related to fibrosis severity were HOMA-R and a low platelet count in CHC-3, and high aminotransferases, HOMA-R, ferritin and low HDL-cholesterol in NAFLD. On multivariate analysis, only low platelet count (OR = 0.78; 95% CI, 0.67-0.92) and HOMA-R (OR = 2.98; 1.13-7.89) were independent predictors of advanced fibrosis in CHC-3. In NAFLD, severe fibrosis was predicted by fat grading (OR = 3.03; 1.41-6.53), ferritin (OR = 1.13; 1.03-1.25) and HOMA-R (OR = 1.16; 1.02-1.31). In conclusion, insulin resistance is an independent predictor of advanced fibrosis in both NAFLD and CHC-3, but the extent of steatosis contributes to advanced disease only in NAFLD. Virus-induced hepatic steatosis as seen in CHC-3 does not contribute significantly to liver fibrosis.