No association of serum ferritin levels with advanced liver fibrosis in untreated German patients with autoimmune hepatitis.
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ABSTRACT:
SUBMITTER: Engel B
PROVIDER: S-EPMC9764512 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
No association of serum ferritin levels with advanced liver fibrosis in untreated German patients with autoimmune hepatitis.
Engel Bastian B Jaeckel Elmar E Taubert Richard R
BMC gastroenterology 20221219 1
In the January 2022 issue of BMC Gastroenterology, Chen et al. report an association between serum ferritin levels and the presence of advanced liver fibrosis in patients with treatment-naïve autoimmune hepatitis (AIH). The odds ratio for ferritin in this study was marginally above 1.0. We analyzed our own published data from a German cohort for an association between ferritin levels and the presence of advanced fibrosis in treatment-naïve AIH and were not able to validate the findings of Cheng ...[more]
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Project description:Background & aimsSeries studies have associated increased serum levels of ferritin with liver fibrosis in patients with nonalcoholic fatty liver disease. We aimed to determine the accuracy with which measurements of serum ferritin determine the presence and severity of liver fibrosis, and whether combining noninvasive scoring systems with serum ferritin analysis increases the accuracy of diagnosis of advanced liver fibrosis.MethodsWe performed a retrospective analysis of data from 1014 patients with liver biopsy-confirmed nonalcoholic fatty liver disease. Three cut points of serum ferritin level, adjusted for sex, were established based on receiver operating characteristic curve analysis: 1.0-, 1.5-, and 2.0-fold the upper limit of normal. Three multiple logistic regression models were created to determine the association of these cutoff values with liver fibrosis, adjusting for age, sex, race, diabetes, body mass index, and level of alanine aminotransferase.ResultsA greater proportion of patients with increased serum levels of ferritin had definitive nonalcoholic steatohepatitis and more-advanced fibrosis than patients without increased levels. In all models, serum level of ferritin was significantly associated with the presence and severity of liver fibrosis. However, for all 3 cutoff values, area under the receiver operating characteristic curve values were low (less than 0.60) for the presence of fibrosis or any stage of liver fibrosis; ferritin level identified patients with fibrosis with 16%-41% sensitivity and 70%-92% specificity. The accuracy with which noninvasive scoring systems identified patients with advanced fibrosis did not change with inclusion of serum ferritin values.ConclusionsAlthough serum levels of ferritin correlate with more-severe liver fibrosis, based on adjusted multiple logistic regression analysis, serum ferritin levels alone have a low level of diagnostic accuracy for the presence or severity of liver fibrosis in patients with nonalcoholic fatty liver disease.
| S-EPMC4057997 | biostudies-literature
Project description:Abstract Background and Aim The aim was to analyze the concordance of liver stiffness measurement (LSM) either by transient elastography (TE) or ARFI with liver biopsy in autoimmune hepatitis (AIH) patients with biochemical remission and to identify those with histological remission. Liver biopsy is still the golden standard for AIH diagnosis. However, it is an invasive procedure and these patients, most of the time, require many biopsies, so it would be valuable to search for noninvasive method that could select all these patients and keep under observation. Methods Thirty‐three patients with AIH were submitted for liver biopsy to evaluate histological remission after at least 18 months of normal aminotransferases. The efficiency of LSM and fibrosis stages was tested by a receiver operating characteristic curve analysis (AUROC). Results One patient (3%) was F0, 6 (18.2%) were F1, 8 (24.2%) were F2, 10 (30.3%) were F3, and 8 (24.2%) were F4, according to METAVIR. Thirteen of thirty‐three (39.4%) patients did not achieve histological remission. AUROC for F4 stage was 0.83 (IC: 0.76–0.99) for TE and 0.78 (IC: 0.65–0.95) for ARFI. Optimal LSM cutoff values were 12.3 kPa (Se = 87.5%, Sp = 88%) for TE and 1.65 m/s (Se = 87.5%, Sp = 76%) for ARFI. The tests were unable to differentiate patients with histological activity from those in histological remission (P < 0.05). Conclusion TE and ARFI accurately identify liver fibrosis by METAVIR score in AIH patients with biochemical remission. No cutoff value was detected to indicate whether the patient achieved histological remission. We present the results of the assessment of liver fibrosis by noninvasive methods (TE/ARFI) in 33 patients with autoimmune hepatitis in biochemical remission and defined the optimal cutoff values for advanced fibrosis. For fibrosis stage F ≥ 3, optimal stiffness cutoff values were 8.7kPa (Se = 72.2%, Sp = 80%) for TE, and 1.5 m/s (Se = 66.7%, Sp = 80%) for fibrosis stage F = 4, cutoff values were 12.3 kPa (Se = 87.5%, Sp = 88%) for TE, and 1.65 m/s (Se = 87.5%, Sp = 76%) for ARFI. This is the first study to evaluate the accuracy of the method to evaluate remission only in patients already under immunosuppressive treatment with biochemical remission, with clearly defined end points of treatment, which enhances its results.
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Project description:BackgroundThe evaluation of liver fibrosis is essential in the management of patients with autoimmune hepatitis (AIH). We aimed to establish and validate an easy-to-use nomogram to identify AIH patients with advanced liver fibrosis.MethodsAIH patients who underwent liver biopsies were included and randomly divided into a training set and a validation set. The least absolute shrinkage and selection operator (LASSO) regression was used to select independent predictors of advanced liver fibrosis from the training set, which were utilized to establish a nomogram. The performance of the nomogram was evaluated using the receiver characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsThe median age of 235 patients with AIH was 54 years old, with 83.0% of them being female. Six independent factors associated with advanced fibrosis, including sex, age, red cell distribution width, platelets, alkaline phosphatase, and prothrombin time, were combined to construct a predictive AIH fibrosis (AIHF)-nomogram. The AIHF-nomogram showed good agreement with real observations in the training and validation sets, according to the calibration curve. The AIHF-nomogram performed significantly better than the fibrosis-4 and aminotransferase-to-platelet ratio scores in the training and validation sets, with an area under the ROCs for predicting advanced fibrosis of 0.804 in the training set and 0.781 in the validation set. DCA indicated that the AIHFI-nomogram was clinically useful. The nomogram will be available at http://ndth-zzy.shinyapps.io/AIHF-nomogram/as a web-based calculator.ConclusionsThe novel, easy-to-use web-based AIHF-nomogram model provides an insightful and applicable tool to identify AIH patients with advanced liver fibrosis.
| S-EPMC10229817 | biostudies-literature
Project description:In animal models and human cross-sectional studies, vitamin D deficiency has been associated with liver disease progression. Vitamin D supplementation has been suggested as a treatment to prevent disease progression. We sought to evaluate the role of vitamin D levels in predicting chronic liver disease development. We conducted a nested case-control study of vitamin D levels in subjects with (cases) and without (controls) liver histologic progression or clinical decompensation over the course of the HALT-C Trial. Vitamin D levels were measured at 4 points over 45 months. 129 cases and 129 aged-matched controls were included. No difference in baseline vitamin D levels were found between cases and controls. (44.8 ng/mL vs. 44.0 ng/mL, P = 0.74). Vitamin D levels declined in cases and controls over time (P = 0.0005), however, there was no difference in the level of decline (P = 0.37). Among study subjects with diabetes mellitius, baseline vitamin D levels were higher in cases, 49.9 ng/mL, than controls, 36.3 ng/mL. (P = 0.03) In addition, baseline vitamin D levels were higher in black case subjects, 32.7 ng/mL, than in black control subjects, 25.2 ng/mL (P = 0.08) No difference in vitamin D levels was found between patients with and without progression of hepatitis C-associated liver disease over 4 years. Our data do not suggest any role for vitamin D supplementation in patients with advanced chronic hepatitis C and raise the possibility that higher vitamin D levels may be associated with disease progression.
| S-EPMC3281016 | biostudies-other
Project description:Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver damage progresses to cirrhosis or hepatocellular carcinoma (HCC). The mainstay therapy for AIH is steroids and other immunosuppressive treatments. Currently, there are no validated markers for monitoring immune-mediated hepatic inflammation. Galectin-9 has recently been identified as a potential biomarker in patients with chronic liver disease. The objective of this study was to determine whether Galectin-9 and other serum proteins are associated with active disease in AIH patients.We enrolled 77 Japanese patients with well-documented AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 27 patients with SLE, and 17 healthy control subjects. Serum levels of galectin-9, and markers of liver injury were measured and compared between groups.Serum levels of galectin-9 were significantly higher in AIH patients than in CHC patients (13.8 ± 4.9 ng/mL vs 8.9 ± 3.0 ng/mL, P < .001) or healthy controls (13.8 ± 4.9 ng/mL vs 5.0 ± 1.3 ng/mL, P < .001). In AIH group, serum galectin-9 levels weakly correlated with alanine aminotransferase levels or total bilirubin (TB) and strongly correlated with C-X-C motif chemokine 10 (CXCL10) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum galectin-9 levels (14.1 ± 4.9 ng/mL vs 8.3 ± 3.8 ng/mL, P < .001). SLE patients exhibited higher galectin-9 levels, whereas the galectin-9 levels did not correlate with liver function tests such as alanine aminotransferase levels.Serum galectin-9 correlated with disease status in AIH patients and could thus be useful biomarkers to detect hepatic autoimmunity. Because circulating galectin-9 reflects autoimmune-mediated inflammation, it may have additional utility as a biomarker for other autoimmune disorders.
| S-EPMC6736219 | biostudies-literature
Project description:AimsThis study aimed to investigate associations between ceruloplasmin (CP) levels, inflammation grade and fibrosis stages in patients with chronic hepatitis B (CHB) and to establish a noninvasive model to predict cirrhosis.MethodsLiver biopsy samples and sera were collected from 198 CHB patients randomized into a training group (n=109) and a validation group (n=89). CP levels were determined using nephelometric immunoassays. Relationships between CP and liver inflammation and fibrosis were analyzed by Spearman rank correlation. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of CP for determining liver fibrosis in CHB. The liver pathology-predictive model was built using multivariate logistic regression analysis to identify relevant indicators.ResultsCP levels were lower in males than in females, lower in patients with inflammation stage G4 compared to other stages and lower in cirrhotic compared to non-cirrhotic patients. Using area under the curve (AUC) values, CP levels distinguished different stages of inflammation and fibrosis. Multivariate analysis showed that CP levels were all significantly associated with cirrhosis in males. A model was developed combining routine laboratory markers APPCI (alpha-fetoprotein [AFP], prothrombin time, and platelets [PLT] with CP) to predict fibrosis in CHB patients. The APPCI had a significantly greater AUC than FIB-4 (aspartate aminotransferase [AST]/ alanine aminotransferase [ALT]/PLT/age), APRI (AST/PLT ratio index), GPI (globin/PLT), and APGA (AST/PLT/gammaglutamyl transpeptidase [GGT]) models (all P-values<0.001).ConclusionsCP levels correlate negatively and indirectly with inflammation and fibrosis stages in male CHB patients. The APPCI model uses routine laboratory variables with CP to accurately predict liver fibrosis in CHB.
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Project description:ObjectiveTo examine the accuracy of noninvasive inflammatory markers in predicting liver fibrosis stage in patients with autoimmune hepatitis (AIH).Patients and methodsWe enrolled 55 patients with AIH and 60 healthy controls in this study, and divided them into three groups: F0 (control); F1-F3 (noncirrhotic fibrosis); and F4 (cirrhosis). The following markers were analyzed for all participants: lymphocyte-to-neutrophil ratio (LNR); lymphocyte-to-platelet ratio (LPR); lymphocyte-to-monocyte ratio (LMR); immunoglobulin-to-platelet ratio (IGPR); aminotransferase-to-platelet ratio index (APRI); aspartate aminotransferase-to-alanine aminotransferase ratio (AAR); and fibrosis-4 score (FIB-4). The predictive accuracy of these noninvasive markers was assessed using area under the receiver operating characteristic curve. Multivariate ordinal logistic regression models were used to analyze associations between the noninvasive markers and liver fibrosis stage.ResultsAAR, LPR, LMR, IGPR, APRI, and FIB-4 were linked to liver fibrosis-stage (P < 0.05), with correlation indices of - 0.219, 0.258, - 0.149, 0.647, 0.841, and 0.704, respectively, but not LNR (P = 0.093). area under the receiver operating characteristic curves of LPR, IGPR, AAR, LMR, APRI, and FIB-4 for detecting cirrhosis (F4 vs. F0-F3) were 0.936 (95% confidence interval: 0.870-1.000, P < 0.001), 0.939 (0.875-1.000, P < 0.001), 0.528 (0.319-0.738, P = 0.768), 0.555 (0.409-0.700, P = 0.568), 0.798 (0.694-0.902, P = 0.002), and 0.881 (0.796-0.967, P < 0.001). Our multivariate ordinal regression analysis showed that LPR and IGPR were associated independently with liver fibrosis stage, with a coefficient of 0.385 (95% confidence interval: 0.103-0.667, P = 0.007) and 14.903 (2.091-27.786, P = 0.023), respectively.ConclusionLPR and IGPR were associated independently with liver fibrosis stage in treatment-naive AIH, and were superior to APRI and FIB-4 in detecting cirrhosis.
| S-EPMC7333545 | biostudies-literature
Project description:ObjectivesChronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications.MethodsA Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI).ResultsA total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis.ConclusionsThe Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.
| S-EPMC6602766 | biostudies-literature
Project description:Background/aimsSerum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients.MethodsFifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort.Results180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70-0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted.ConclusionA novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.
| S-EPMC8273639 | biostudies-literature
Project description:BackgroundPatients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome have a worse prognosis compared to AIH or PBC alone and accurately predicting the severity and dynamically monitoring the progression of disease are therefore essential. We aimed to develop a nomogram-based model to predict advanced liver fibrosis in patients with AIH-PBC overlap syndrome.MethodsA total of 121 patients with AIH-PBC overlap syndrome were retrospectively included and randomly assigned to a development set and a validation set. Backward stepwise regression's best model with the lowest AIC was employed to create a nomogram. Diagnose accuracy was evaluated using the area under the receiver operator characteristic curve (AUROC), calibration analysis, and decision curve analysis (DCA) and was compared with aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors-4 (FIB-4) score.ResultsThe median age of patients was 53.0 years (IQR: 46.0-63.0), and female patients accounted for 95.0 %. Platelets, globulin, total bilirubin, and prothrombin time were associated with advanced fibrosis (≥S3) and used to construct an AIH-PBC overlap syndrome fibrosis (APOSF)-nomogram (available online at https://ndth-zzy.shinyapps.io/APOSF-nomogram/). The AUROCs of APOSF-nomogram were 0.845 (95 % CI: 0.754-0.936) and 0.843 (95 % CI: 0.705-0.982) in development set and validation set respectively, which was significantly better than APRI and FIB-4. Calibration revealed that the estimated risk fits well with biopsy-proven observation. DCA outperformed APRI and FIB4 in terms of net benefit, demonstrating clinical utility.ConclusionThis novel non-invasive web-based online APOSF-nomogram provided a convenient tool for identifying advanced fibrosis in patients with AIH-PBC overlap syndrome. Further prospective, multicenter studies with large sample size are necessary to validate the applicability of APOSF-nomogram.
| S-EPMC10590873 | biostudies-literature