Prediction Of Significant Fibrosis Research Articles

Relationship between disease severity and myeloperoxidase in chronic viral hepatitis: a prospective study.

Aim: To measure serum myeloperoxidase (MPO) levels and to evaluate the relationship between this parameter and histological findings in chronic hepatitis B and C patients. Materials & methods: Three groups were formed: chronic hepatitis B, chronic hepatitis C and a control group. Serum MPO levels were determined by ELISA. Results: MPO level was found to be higher in both patient groups compared with the control group (p<0.05). It was also higher in chronic hepatitis B and C patients with significant fibrosis compared with patients with mild fibrosis (p<0.05). Conclusion: Our results show that increased MPO level can be used as an important noninvasive marker in both the early detection of liver fibrosis and the prediction of significant fibrosis.

Prevalence and factors associated with liver fibrosis among first-degree relatives of Mexican Americans with hepatocellular carcinoma.

Whether hepatocellular carcinoma (HCC) increases the familial risk for hepatic fibrosis has not been thoroughly explored, particularly in Mexican Americans who are disproportionately affected by obesity and metabolic syndrome. We evaluated the risk of significant hepatic fibrosis in first-degree relatives of Mexican American adults with HCC. We performed a cross-sectional analysis of a prospective cohort of Mexican American probands with HCC and first-degree relatives enrolled in the Hispanic Liver Cancer Cohort study. We evaluated the prevalence of hepatic fibrosis in first-degree relatives, defined by liver stiffness measurement (LSM) >= 7.0kPa with transient elastography (TE). Secondary outcomes included the prevalence of definite hepatic steatosis, defined by controlled attenuation parameter >=288 dB/m. We identified 70 probands diagnosed with HCC; 47% were female and the mean age was 62 years (±13 years). Among 112 first-degree relatives with a mean age of 43 years (±14 years), 19 (17%) had significant fibrosis and 47 (42%) had definite hepatic steatosis, respectively. The prevalence of significant fibrosis was 20% in first-degree relatives 40 years of age or older. Regression analysis revealed that diabetes (OR 3.2, 95% CI: 1.1-9.2, p=0.03) and aspartate aminotransferase >=30 units/L (OR 4.0, 95% CI: 1.4-11.7, p=0.01) were predictors of significant fibrosis in first-degree relatives. Using a well-phenotyped familial cohort, we found that the prevalence of significant fibrosis and definite hepatic steatosis are high in first-degree relatives of Mexican Americans with HCC, particularly those with diabetes, suggesting that this population may benefit from screening for liver disease.

Prevalence and risk factors of nonalcoholic steatohepatitis with significant fibrosis in people with HIV.

Objective:Metabolic risk factors and nonalcoholic fatty liver disease (NAFLD) in people with HIV (PWH) have been increasing. Patients exhibiting the inflammatory subtype nonalcoholic steatohepatitis (NASH) are at increased risk of liver-related complications. Therefore, the aim was to investigate the prevalence of NASH with significant fibrosis in PWH using noninvasive tests (NITs).Design:In this prospectively enrolling cohort study, 282 PWH were explored for hepatic steatosis, fibrosis and steatohepatitis using vibration-controlled transient elastography (VCTE) and the Fibroscan-AST (FAST) score.Methods:On the basis of controlled attenuation parameter (CAP; dB/m) and liver stiffness measurement (LSM; kPa), patients were categorized according to the presence of steatosis (≥275 dB/m) and significant fibrosis (≥8.2 kPa). The FAST score was calculated according to established cut-offs.Results:The prevalence of hepatic steatosis in this cohort was 35.5% (n = 100) with 75 (75%) of these patients fulfilling the criteria of NAFLD. The prevalence of significant fibrosis (≥ F2) was 6.7% (n = 19). The FAST score identified a total of 32 (12.3%) patients with a cut-off greater than 0.35, of whom 28 (87.5%) PWH qualified as NASH. On multivariable analysis, waist circumference was a predictor of hepatic steatosis and type 2 diabetes was a predictor of significant fibrosis. Type 2 diabetes and ALT remained independent predictors of a FAST score greater than 0.35.Conclusion:NASH with significant fibrosis is highly prevalent among PWH. The FAST score may be helpful to identify patients at risk for significant liver disease.

Evaluation of liver fibrosis in chronic hepatitis B patients with 2D shear wave elastography with propagation map guidance: a single-centre study

BackgroundThe aims of this study were to evaluate liver fibrosis with two-dimensional (2D) shear wave elastography (SWE) in patients with chronic hepatitis B (CHB), to compare 2D-SWE with histopathology and to determine the change in liver stiffness values after antiviral therapy.Material and methodsA total of 253 patients with CHB were included in this prospective study. 2D-SWE with propagation map guidance to measure liver stiffness, fibrosis-4 index (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) scoring and additional liver biopsy were performed in patients with CHB. Liver stiffness was measured again at 24 and 48 weeks in all patients. The Spearman rank correlation test was used to analyse the correlation between variables, and receiver operating curve analysis was used to evaluate the diagnostic performance in terms of fibrosis.ResultsLiver stiffness measurements made with 2D-SWE demonstrated a significant positive correlation with the fibrosis stage and FIB-4 score (rs = 0.774 and 0.337, respectively, p < 0.001 for both). The area under the curve value for kPa for the prediction of significant fibrosis was 0.956 (95% CIs) (0.920–0.991), and the optimal cut-off value was 8.2 kPa (sensitivity: 92.7% and specificity: 78.9%); these values were 0.978 (95% CIs, 0.945–1.000) and 10.1 kPa (sensitivity: 92.9% and specificity: 96.4%) for the prediction of severe fibrosis. After antiviral treatment, a decrease in liver stiffness values measured by 2D-SWE was detected (mean kPa values at 0 and 48 weeks; 9.24 and 7.36, respectively, p < 0.001).ConclusionIn conclusion, the measurement of liver stiffness with 2D-SWE has high diagnostic performance in the determination of hepatic fibrosis and can be used to evaluate the response to treatment in patients receiving antiviral therapy.

A Model Incorporating Serum Alkaline Phosphatase for Prediction of Liver Fibrosis in Adults with Obesity and Nonalcoholic Fatty Liver Disease.

We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy was performed, and liver histology was evaluated by a pathologist blinded to the patients’ data. The endpoint was significant fibrosis defined as fibrosis stage ≥ 2. Independent predictors of fibrosis were identified by logistic regression. Two hundred ten patients were recruited. Liver histology revealed steatosis in 87.1%, steatohepatitis in 21.9%, and significant fibrosis in 10%. Independent predictors of significant fibrosis were ALP (Odds Ratio (OR) 1.03; 95% Confidence interval (CI), 1.01–1.05), alanine aminotransferase (OR 1.02; 95% CI, 1.01–1.03), HbA1c (OR 1.58; 95% CI, 1.20–2.09), and body mass index (OR 1.06; 95% CI, 1.00–1.13). A tree-based model was developed to predict significant fibrosis, with a receiver operating characteristic (ROC) area of 0.845, sensitivity of 0.857, specificity of 0.836, and accuracy of 0.931. The applicability of serum ALP as an independent biomarker of liver fibrosis should be considered in obesity surgery patients, and in the broader context of obese patients with nonalcoholic fatty liver disease.

Validity of routine biochemical and ultrasound scores for prediction of hepatic fibrosis and steatosis in NAFLD

BackgroundWe evaluated the validity of some non-invasive scores and ultrasound findings to predict fibrosis and steatosis in a cohort of NAFLD patients who underwent liver biopsy. Ninety-seven NAFLD patients were enrolled and classified into NASH (66) and simple steatosis groups (31) based on liver biopsy. ROC curves were constructed for Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) in fibrosis prediction, also for (hepatic steatosis index; HSI, fatty liver index; FLI) and ultrasonographic subcutaneous and visceral adipose tissue measurements (SAT and VAT) for steatosis prediction.ResultsFIB4 had AUC of 0.6, APRI and NFS at cutoffs of 0.3 and -.2.4 had AUC of 0.64 and 0.63 in detecting the presence of any grade of fibrosis, and of (0.52, 0.55, and 0.58) for significant fibrosis. FIB4 at a cut-off of (0.76) had the highest AUC in detecting any grade of fibrosis in the simple steatosis group (0.81). SAT (at cutoff of 2.1 and 2.5) was superior to VAT. HSI (at cutoff 45.35 and 45.7) was superior to FLI in detecting moderate or marked steatosis.ConclusionFIB4 and NFS can be used in screening for silent liver disease with ongoing fibrosis in simple steatosis. They are unsatisfactory predictors for significant fibrosis in NAFLD. SAT is better than VAT in predicting moderate steatosis and is slightly better than biochemical HSI.

Evaluation of red cell distribution width to platelet ratio as a novel non-invasive index for predicting hepatic fibrosis in patients with chronic hepatitis C

Background and study aimsAssessing the extent of fibrosis is an essential part of therapeutic decisions in patients with chronic hepatitis C (CHC). Liver biopsies are the “gold standard” for evaluating liver fibrosis but have many limitations. Thus, noninvasive predictors of fibrosis have been developed. This study aimed to determine the effectiveness of red cell distribution width (RDW) to platelet ratio as a simple noninvasive method for predicting the hepatic fibrosis stage in patients with CHC. Patients and methodsThis cross-sectional study included 197 Egyptian patients with CHC. A routine pretreatment reference needle liver biopsy was performed. Fib-4, transient elastography (TE) by Fibroscan, AST to Platelet Ratio Index (APRI), and RDW to platelet ratio (RPR) were measured. Predictors of significant fibrosis (Metavir score ≥ F2) and advanced fibrosis (Metavir score ≥ F3) were identified. ResultsFib-4, TE, APRI, and RPR values differed significantly when comparing different stages of fibrosis (p < 0.01). Fib-4, TE, APRI, and RPR were reliable diagnostic tools at cutoff values of 1.17, 7.75, 0.18, and 0.07, respectively, for predicting significant fibrosis and cutoff values of 1.99, 8, 1.77, and 0.08, respectively, for predicting advanced fibrosis. Using logistic regression analysis, TE was identified as an independent predictor associated with significant and advanced fibrosis. Fib-4 was significantly associated with advanced fibrosis only. ConclusionThe use of Fib-4, TE, APRI, and RPR measurements may decrease the need for liver biopsies for predicting significant and advanced fibrosis. RPR showed fair sensitivity, specificity, positive and negative predictive values, and overall accuracy for predicting significant fibrosis in patients with CHC.

Assessment of The Performances of Hepatitis C Virus Viral Markers, Age-Platelet Index and Aspartate aminotransferase to Alanine Aminotransferase Ratio Scores, in Predicting Liver Histopathology

Introduction This study aimed to reveal the utility of age-platelet (AP) index and aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), which are non-invasive markers, in patients with chronic Hepatitis C virus (HCV) infection in prediction of fibrosis and evaluate whether viral markers could be used for that purpose or not. Methods A total of treatment-naïve 49 patients with chronic HCV who underwent liver biopsy were included in this retrospective study. Anti-HCV S/CO and HCV-RNA viral load (copy/ml) values measured simultaneously with biopsy were determined. AP index and AAR score were calculated and compared. Results Staging of liver biopsy samples of 49 HCV patients was assessed. Comparable diagnostic accuracies of AP index and AAR in prediction of significant fibrosis (F≥2) were showed with ROC curve analysis. The areas under the ROC (AUROCs) were 0.713 and 0.506 respectively. Diagnostic accuracy of API in prediction of significant fibrosis was superior to that of AAR (p=0.03). AUROC of HCV-RNA viral load in prediction of F≥2 was 0.531. Anti-HCV S/CO value (AUROC=0.464) was not found as a suitable marker in prediction of fibrosis. Conclusions AP index, AAR score and HCV viral load among non-invasive markers assessed in this study were useful in predicting significant fibrosis. Especially API was the most useful test in predicting significant fibrosis. AP index can be preferred in patients with near normal ALT values.

Muscle alterations are independently associated with significant fibrosis in patients with nonalcoholic fatty liver disease.

Anthropometric data are associated with nonalcoholic fatty liver disease (NAFLD) development and progression. We investigated whether the quantity and quality of muscle and visceral fat assessed by computed tomography (CT) are associated with fibrosis severity in NAFLD. In a prospective biopsy-confirmed NAFLD cohort of 521 patients, we measured skeletal muscle index (SMI), muscle attenuation (MA) and visceral adipose tissue index (VATI) via CT. Low skeletal muscle mass (LSMM) was defined using previously validated cut-offs. Myosteatosis and visceral adiposity were defined as the lowest and highest quartile, respectively. Significant fibrosis was defined as F2-F4 in liver histology. Patients with significant fibrosis had lower SMI and MA and higher VATI than those without. The significant fibrosis prevalence was significantly higher in subjects with LSMM (45.1% vs 30.8%, P=.005), myosteatosis (46.1% vs 29.7%, P=.001) and visceral adiposity (46.9% vs 29.9%, P=.001) than those without. The significant fibrosis risk increased with increasing numbers of body composition components (24.5%, 35.6%, 53.0% and 72.7% in patients with 0, 1, 2 and 3 components respectively). Multivariable analysis revealed that LSMM (OR, 1.72; 95% CI, 1.05-2.84), myosteatosis (OR, 1.65; 95% CI, 1.01-2.68) and visceral adiposity (OR, 1.75; 95% CI, 1.09-2.83) were independent predictors of significant fibrosis. Subjects with sarcopenia had a higher risk of significant fibrosis (OR, 2.17; 95% CI, 1.03-4.56). Muscle alterations and visceral adiposity assessed by CT are associated with significant fibrosis in NAFLD. LSMM and myosteatosis have additive values in prediction of significant fibrosis.

Lifestyle and silymarin: a fight against liver damage in NAFLD associated - prediabetic disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is common in both prediabetic patients and healthy overweight individuals, yet it remains understudied. This study investigates the effects of hepatic steatosis on fibrosis and evaluates the major predictors of liver injury in prediabetes and whether this damage is reversible with Mediterranean diet and administration of the nutraceutical silymarin.MethodsFirst, a case-control study was conducted in which 212 patients with prediabetes, not known to have NAFLD, and 126 healthy controls underwent clinical evaluation, transient elastography with measurement of liver stiffness (LS) and controlled attenuation parameter (CAP). Subsequently, the 212 prediabetic patients were enrolled into a prospective randomized interventional study: 104 were allocated to Mediterranean diet alone while 108 followed Mediterranean diet plus supplementation with silymarin (a flavonolignan complex isolated from Silybum marianum and Morus alba). The administered silymarin dose was 210 mg twice daily for 6 months. Clinical and instrumental evaluations were repeated at the end of the 6 month-study period. Prediabetics were genotyped for patatin like phospholipase domain containing 3 (PNPLA3).ResultsIn the case-control study, 29% of prediabetic patients have significant fibrosis defined as LS ≥ 7.9 kPa vs only 3% of controls (p < 0.001). PNPLA3 genotype CG/GG are significantly associated with significant fibrosis LS ≥ 7.9 relative to CC genotype χ2(1) = 76.466, p < 0.001. Binomial regression analysis shows that increase in BMI, ALT and AST are significantly associated with increased likelihood of significant fibrosis (χ2(7) = 191.9, p < .001) prior to intervention. In the randomized interventional study, prediabetics following Mediterranean diet alone (group 1) experienced a significant regression of fibrosis and decrease in ALT, HbA1c, FBS after 6 months (p < 0.001); similar findings were observed in patients following Mediterranean diet plus silymarin regimen (group 2); group 2 had a significant decrease in HbA1c relative to group 1 (95% CI: 37.8–38.6 vs 39.5–40.3, p < 0.001).ConclusionPNPLA3 genotype CG/GG and elevated BMI are the major predictors of significant fibrosis in prediabetic patients prior to intervention in this study. Mediterranean diet either alone or with silymarin treatment for 6 months leads to significant regression of liver damage and improvement of the glycemic profile in prediabetic patients. Yet, as combination treatment of silymarin with Mediterranean diet shows significant reduction of HbA1c when compared to diet alone, this suggests that silymarin may exert an independent anti-glycemic action.

Significant Burden of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Iranian Population: A Cross-Sectional Analysis

The main cause of chronic liver disease in Iran is Non-alcoholic fatty liver disease (NAFLD). A common pathological feature of chronic liver disease is fibrosis, so particular vigilance against patients with liver fibrosis is necessary to lead healthcare resource planning. The aims of the current study were to determine the prevalence and predictors of significant fibrosis and advanced ones among individuals with NAFLD. In the current cross-sectional study conducted during 2013-2016, the presence of fibrosis among NAFLD patients was assessed using the NAFLD fibrosis score (NFS) and AST to Platelet Ratio Index (APRI) systems. Multivariate logistic regression models were used to predict significant fibrosis or advanced fibrosis among NAFLD patients. Analysis of the results of over 999 patients (569 females and 430 males) with the mean age of 43.28±14.034 years in Iran during 2015-2016 showed that the overall prevalence of NAFLD among Iranian adults was 19.6%. NAFLD prevalence was not significantly higher in males compared to females (51.5% vs. 48.5%, P=0.66). On multivariate logistic regression analyses, females were less likely to have NAFLD compared to males (OR 0.32, 95% CI 0.24-0.42, P&lt;0.001). The overall prevalence of liver fibrosis among NAFLD patients was 38.8%.20.4% and 6.12% of NAFLD patients had evidence of significant and advanced fibrosis, respectively. Our most recent dataset analysis emphasized the major burden of NAFLD among people of Iranian origin. A high prevalence of individuals with NAFLD and advanced fibrosis was observed.

Fibro-indices versus liver stiffness for prediction of significant fibrosis in hepatitis B virus-infected Egyptian patients; a single-center experience

ABSTRACTBackground: Liver fibrosis assessment is a key factor for disease management in hepatitis B virus (HBV). Several serum biomarkers have been introduced for noninvasive fibrosis assessment. This study aims to evaluate the validity of simple noninvasive indices, namely Fibrosis-4 score (FIB4), aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), Goteborg University Cirrhosis Index (GUCI), and fibrosis index in evaluation of liver fibrosis in chronic HBV.Methods: 226 patients with chronic HBV genotype D were included. FIB4, APRI, GUCI, and fibrosis index were performed. Receiver operating characteristic (ROC) curves were used to predict ≥F2 fibrosis.Results: The mean age of patients was 39.00 years and 72.27% of patients were treatment naïve. Patients with ≥F2 hepatic fibrosis had significantly higher FIB-4 (1.58 ± 1.46 vs. 1.15 ± 1.09), APRI (0.68 ± 0.71 vs. 0.43 ± 0.37), GUCI score (0.75 ± 0.94 vs. 0.42 ± 0.29) and Fibrosis index (2.18 ± 0.84 vs. 1.84 ± 0.69). All studied indices were able to diagnose ≥F2 fibrosis. APRI had the highest area under the ROC (AUROC) of 0.67. Predictivity of all indices was higher in on-treatment vs naive patients.Conclusion: FIB4, APRI, and GUCI scores are acceptable, noninvasive, and cheap simple indices that can be helpful on treatment follow-up of fibrosis regression in the setting of low socioeconomic conditions compared to the relatively expensive fibroscan modality.

A pragmatic non-invasive assessment of liver fibrosis in patients with psoriasis, rheumatoid arthritis or Crohn's disease receiving methotrexate therapy

The reported hepatotoxicity of methotrexate underlines the need for a repeated non-invasive and reliable evaluation of liver fibrosis. We estimated, using a non-invasive strategy, the prevalence of significant liver fibrosis in patients treated by methotrexate and the predictors of significant fibrosis (fibrosis≥F2). Fibrosis was prospectively evaluated using 9 non-invasive tests in consecutive patients with psoriasis, rheumatoid arthritis, or Crohn's disease. Significant fibrosis was assessed without liver biopsy by defining a "specific method" (result given by the majority of the tests) and a "sensitive method" (at least one test indicating a stage≥F2). One hundred and thirty-one patients (66 Psoriasis, 40 rheumatoid arthritis, and 25 Crohn's disease) were enrolled, including 83 receiving methotrexate. Seven tests were performed on average per patient, with a complete concordance in 75% of cases. Fibroscan® was interpretable in only 61% of patients. The best performances (AUROC>0.9) for predicting significant fibrosis were obtained by tests dedicated to steatohepatitis (FibroMeter NAFLD, NFS and FPI). The prevalence of fibrosis≥F2 according to the "specific" or the "sensitive" assessment of fibrosis was 10% and 28%, respectively. Methotrexate exposure did not influence the fibrosis stage. Factors independently associated with significant fibrosis according our "sensitive method" were age, male gender, and metabolic syndrome. We provided a non-invasive approach for identifying liver fibrosis≥F2 by using 8 biochemical tests and Fibroscan®. In this population, the risk of significant fibrosis was related to age, male gender, and presence of metabolic syndrome, but was not influenced by methotrexate.

Prevalence and Predictors of Significant Fibrosis Among Subjects with Transient Elastography-Defined Nonalcoholic Fatty Liver Disease.

Transient elastography (TE) can be used to assess the degree of liver fibrosis and steatosis. We investigated the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) with or without significant liver fibrosis in the general population. A total of 3033 subjects without alcoholic or chronic viral liver diseases who underwent a medical health check-up including TE were recruited from April 2013 to August 2014. TE-defined NAFLD was defined as a controlled attenuation parameter of ≥250dB/m, and significant liver fibrosis was defined as a liver stiffness (LS) value of ≥8kPa. Overall, 1178 (42.9%) subjects had NAFLD. Subjects with NAFLD had significantly higher alanine aminotransferase (ALT) levels and a higher prevalence of parameters related to metabolic syndrome, such as high blood pressure, a high body mass index (BMI), glucose intolerance, and dyslipidemia than did subjects without NAFLD (all P<0.05). Age, male gender, ALT level, serum albumin, BMI, diabetes, hypertriglyceridemia, and LS values independently showed positive associations with the presence of NAFLD (all P<0.05). In addition, concomitant significant liver fibrosis was identified in 60 (5.1%) subjects with NAFLD, and its independent predictors were age [odds ratio (OR) 1.054], ALT level (OR 1.019), BMI (OR 1.217), and diabetes (OR 1.987) (all P<0.05). We found that the prevalence of subjects with NAFLD was high (42.9%), and 5.1% of them had concomitant significant liver fibrosis. The risk factors found in this study can help identify which subjects with NAFLD are vulnerable to fibrosis progression.

Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis

Background and rationaleMany different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. Material and methodsA systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. ResultsEight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastogra-phy and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. ConclusionIn conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis.

Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

Increased liver stiffness measurement values using transient elastography in Egyptian patients with acute viral hepatitis

Transient Elastography (TE) is one of the non-invasive and reproducible tools for assessment of liver fibrosis/ cirrhosis. However, it remains to be determined if ALT flare interferes with fibrosis assessment. 1.1.Aim: To determine the effect of increased serum ALT and AST on liver stiffness measurement in patients with acute viral hepatitis. 1.2.Methods: Thirty consecutive patients with acute hepatitis of viral etiology with elevated liver enzymes (>10 folds of ULN) were prospectively included. Blood samples were collected and TE was done initially and after resolution of hepatitis and after normalization of liver enzymes. Patients with high BMI which could affect TE (> 40 kg/m2) and patients with ascites or liver cirrhosis were excluded. For determination of the etiology of hepatitis, history taking, a detailed physical examination and laboratory tests were performed in all patients. 1.3.Results: The mean age of patients was 32.87 ± 10.2 years old and males represented 46.7% (n=14). In all patients, the degree of liver stiffness at the time of the peak increase in aminotransferases exceeded the cutoff values proposed for the prediction of significant fibrosis or cirrhosis. The mean value of LSM at the time of inclusion in the study was 13.91±6.7 kPa and the mean value of LSM after resolution of hepatitis was 7.7±3.08 kPa. A progressive significant reduction in liver stiffness values was observed (P 0.05). Reduction of mean value of LSM to 6.21 ± 1.14 kPa was observed in 10 patients after 1 year of ALT normalization. 1.4.Conclusion: TE has not demonstrated reliable diagnostic accuracy in patients with acute viral hepatitis.

Imaging biomarkers for steatohepatitis and fibrosis detection in non-alcoholic fatty liver disease.

There is a need, in NAFLD management, to develop non-invasive methods to detect steatohepatitis (NASH) and to predict advanced fibrosis stages. We evaluated a tool based on optical analysis of liver magnetic resonance images (MRI) as biomarkers for NASH and fibrosis detection by investigating patients with biopsy-proven NAFLD who underwent magnetic resonance (MR) protocols using 1.5T General Electric (GE) or Philips devices. Two imaging biomarkers (NASHMRI and FibroMRI) were developed, standardised and validated using area under the receiver operating characteristic curve (AUROC) analysis. The results indicated NASHMRI diagnostic accuracy for steatohepatitis detection was 0.83 (95% CI: 0.73–0.93) and FibroMRI diagnostic accuracy for significant fibrosis determination was 0.85 (95% CI: 0.77–0.94). These findings were independent of the MR system used. We conclude that optical analysis of MRI has high potential to define non-invasive imaging biomarkers for the detection of steatohepatitis (NASHMRI) and the prediction of significant fibrosis (FibroMRI) in NAFLD patients.

AST-to-platelet ratio index in non-invasive assessment of long-term graft fibrosis following pediatric liver transplantation.

Long-term graft fibrosis occurs in the majority of pediatric liver transplant recipients. Serial biopsies to monitor graft health are impractical and invasive. The APRI has been evaluated in pediatric liver disease, but not in the context of post-transplantation fibrosis. We aimed to investigate the validity of APRI as a predictor of long-term graft fibrosis in pediatric liver transplant recipients. This was a retrospective, observational study of a cohort of children who underwent liver transplantation at King's College Hospital between 1989 and 2003, with a relevant dataset available. Protocol liver biopsies were performed at 10-yr follow-up and fibrosis was graded using the Ishak scoring system, with S3-6 denoting "significant fibrosis." APRI was calculated concurrently with biopsy. A total of 39 asymptomatic patients (20 males; median age at transplant, 1.43 yr) underwent protocol liver biopsies at a median of 10.39 yr post-transplantation. APRI was associated with significant fibrosis (p = 0.012). AUROC for APRI as a predictor of significant fibrosis was 0.74 (p = 0.013). The optimal cutoff APRI value for significant fibrosis was 0.45 (sensitivity = 0.67; specificity = 0.79; PPV = 0.67; NPV = 0.79). APRI appears to be a useful non-invasive adjunct in the assessment of significant graft fibrosis in the long-term follow-up of pediatric liver transplant survivors.

Can Serum ST2 Levels Be Used as a Marker of Fibrosis in Chronic Hepatitis B Infection?

Interleukin 33 (IL-33) is a cytokine belonging to the IL-1 superfamily. Soluble ST2 (sST2) binds to IL-33 and by functioning as trap receptor inhibits signal sending to Th2 via transmembrane ST2. Because Th2-type cytokines play an important role in fibrosis, the aim of this study is to determine whether sST2 can be used as a marker of fibrosis in chronic hepatitis B (CHB) patients or not.The study included 19 healthy controls, 54 patients with CHB, and 14 patients with cirrhosis because of CHB. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4) scores also calculated, and correlations between liver biopsies, sST2 levels, and these scores were analyzed in CHB and cirrhosis patients.The sST2 levels in patients with CHB were significantly higher than those in the control group subjects (median: 1133 pg/mL vs 762.5 pg/mL, respectively [P = 0.035]). In CHB patients, the METAVIR fibrosis score (stages from 0 to 4) showed a moderate correlation with serum sST2 level (r = 0.396, P = 0.004) and a weak correlation with FIB-4 score (r = 0.359, P = 0.008), but no correlation with APRI score (r = 0.253, P = 0.06). The under the curve value of serum sST2 was 0.68, and its prediction of significant fibrosis (METAVIR score ≥2) in values >674 pg/mL had a sensitivity of 91.7% and specificity of 40% (P = 0.009). According to multiple logistic regression analysis, only METAVIR fibrosis stage was found to be an independent predictor of serum sST2 elevation in CHB patients (P = 0.04).The sST2 level can be used for differentiating significant fibrosis from mild fibrosis in CHB patients. However, the efficacy of this marker should be verified by larger studies in the future.