Non-invasive Biomarkers Of Fibrosis Research Articles

The contribution of imaging to non-invasive fibrosis biomarkers in the diagnosis and staging of chronic liver disease

Aims: Gold standard technique for determining the stage of fibrosis in cirrhosis is a biopsy. Non-invasive tests are used when a biopsy is contraindicated. However, their specificity and sensitivity still fall short of expectations. Aim of the study is to develop a model capable of determining fibrosis using serum biomarkers and liver ultrasonography. Methods: A retrospective study was designed including patients with chronic hepatitis B and C underwenting liver biopsies between the time frame of 2015 to 2020 years at Trakya University School of Medicine. Epidemilogical data, ltrasonography and pathology reports were noted. Blood values were recorded and used to calculate AST / Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), Gothenburg University Cirrhosis Index (GUCI) noninvasive fibrosis indices. The fibrosis stages of the patients were assessed accoridng to pathology reports into three categories: advanced (F5-F6), moderate (F3-F4), and lower Ishak scores. Results: A total of 259 patients were included in the study. The median age of the patients was 54 (19-90), and 40.9% (106) were female. The median values of APRI, GUCI and FIB-4 scores were respectively: 0.6 (0-21.8), 0.6 (0-26.2) and 1.6 (0.2-8.5). The effects of ultrasonography findings were examined to improve the diagnostic performance of APRI, GUCI and FIB-4 indices. Accompanied by statistical analysis, it was observed that the FIB-4 index and the presence of hepatosteatosis in the liver had a significant effect on the detection of F?3 (respectively; p<0.001, p=0.033). A new model named FIB4u (ultrasonography) was developed. The AUC values of indices for differentiation of intermediate and advanced stages of fibrosis (?3) were respectively:FIB4u 0.760; FIB-4 0.753; GUCI 0.676; APRI 0.667 (p<0.001). The FIB4u index demonstrated considerably better performance compared to both APRI and GUCI. Conclusion: The FIB4u index, developed by combining ultrasonography and laboratory data, can be used as a new index for fibrosis assessment in the absence of advanced elastography techniques. It needs to be validated in larger patient cohorts to be used safely in the long term.

P013 Magnetic Resonance Imaging-Based Average T2 Signal as A Non-Invasive Measure of Fibrosis In Enteric Crohn’s Disease

Abstract Background In Crohn’s Disease (CD), 10% of patients present with fibrostenosis with a further 10% progressing from inflammatory to a fibrostenotic disease behaviour over 7 years. 40% of fibrostenotic CD patients need surgery at 5 years compared to ~10% with inflammatory disease. Present non-invasive fibrosis biomarkers lack the required accuracy needed to be used routinely for clinical decision making. T1, T2, diffusion weighted imaging, motility and bowel volumes have shown promise in the non-invasive measure of fibrosis. Methods The primary objective of this study is to undertake biological validation of MRI measures as independent imaging biomarkers of histological fibrosis with the primary outcome being the correlation between MRI measures and histological fibrosis measures. GI-Seg (Motilent, London, UK) is an image analysis tool used to segment the gastrointestinal tract on T2W MRI scans. Patients with CD histological diagnosis and in need of surgical resection for stenosis attended a one-hour 3T MRI scanning session within 12 weeks prior to their intestinal resection surgery. Histological samples were scored by a specialized gastrointestinal pathologist for inflammation, fibrosis, and muscular hypertrophy. An expert radiologist with the help of the histopathologist located the strictures on DWI, quantitative T2&T2 scans, and T2 weighted clinical MRI scans. GI-Seg was used to generate a 3D model of the stricture on T2W scans measuring bowel wall volume and average signal intensity of each stricture. Pearson correlation coefficient was used to quantify the correlation between the variables. Results A total of 10 CD patients, encompassing 20 strictures, were included in the study. The analysis revealed that the average T2 signal has a significant correlation with global fibrosis scores (r(20) = .563, p = .010) (Figure) and total inflammation scores (r(20) = .451, p = .046). Additionally, stricture volume showed a fair correlation with chronic inflammation component scores (r(20) = .453, p = .045). Notably, quantitative T1 values correlated with total inflammation scores (r(17) = .493, p = .045). Conclusion The study reveals fair correlations between the T2 signal average and both global fibrosis and global inflammation scores, as well as between stricture volume and chronic inflammation in CD strictures. While these findings indicate that the GI-seg tool's measurements of bowel wall volume and signal intensity have potential utility as imaging biomarkers for fibrosis and inflammation, the results also underscore the necessity for additional markers that are specifically correlated with fibrosis. Such markers are essential to distinctly identify fibrotic changes, independent of inflammatory processes.

Prevalence and characteristics of cystic fibrosis liver disease: a study highlighting the lack of histological diagnosis

Background and aimsCystic fibrosis liver disease (CFLD) is the third leading cause of death in patients with cystic fibrosis (CF). We aim to determine the prevalence of CFLD in a cohort of adult patients with CF and to characterise liver involvement in this population highlighting the importance of histological diagnosis. MethodsWe retrospectively studied a cohort of patients with CF. Inclusion criteria were age ≥ 18 and minimum 1 year of follow-up. We excluded lung transplant patients. CFLD was defined as having 2 out of 3 criteria: persistent elevation of transaminases and/or gamma-glutamyltransferase; abnormal ultrasound; and abnormal transient elastography. Non-invasive fibrosis biomarkers were calculated in CFLD patients. Adult-onset CFLD (Ad-CFLD) was defined as CFLD ≥18 years. Severe CFLD (s-CFLD) was defined as CFLD with cirrhosis and/or portal hypertension. ResultsWe included 113 patients. Median age was 29 years, 58 were male. Forty patients had CFLD. Median age at CFLD diagnosis was 10 years. Twenty-one patients had s-CFLD. Two s-CFLD patients had nodular regenerative hyperplasia, 1 had hepatocellular carcinoma and 4 underwent liver transplantation. Six patients had ad-CFLD. Both CFLD and s-CFLD groups were compared to a non-CFLD group. The CFLD group had significantly more males (p = 0.034). S-CFLD group had worse pulmonary function (p = 0.015). ConclusionThirty five percent of adult patients with CF, mainly males, had CFLD. Nineteen percent had s-CFLD and had worse pulmonary function. With recent reports unravelling different pathophysiological mechanisms in CFLD, we believe it is important to better characterise liver involvement using liver biopsy.

Among simple non-invasive scores, Pro-C3 and ADAPT best exclude advanced fibrosis in Asian patients with MAFLD

BackgroundWith metabolic dysfunction-associated fatty liver disease (MAFLD) incidence and prevalence increasing, it is necessary to identify patients with advanced fibrosis (F3-F4 stages). We evaluated the performance of new biomarkers and algorithms for diagnosing advanced fibrosis in an Asian population. MethodsData from two Asian cohorts (including 851 biopsy-proven MAFLD [578 from Wenzhou, 273 from Hong Kong]) were studied. The association between N-terminal propeptide of type 3 collagen (PRO-C3) and the histologic stage of liver fibrosis was analyzed by multivariable linear regression. The area under the receiver operating characteristic curve (AUROC) was used to test the diagnostic performance of serum PRO-C3 and the ADAPT score for advanced fibrosis and compared them to other established non-invasive tests. ResultsSerum PRO-C3 levels increased progressively across liver fibrosis stages and correlated with advanced fibrosis (P < 0.001). The ADAPT score had an AUROC of 0.865 (95% confidence interval 0.829–0.901) for advanced fibrosis; the accuracy, sensitivity and negative predictive values were 81.4%, 82.2% and 96.1%, respectively. This result was better compared to that of PRO-C3 alone or other non-invasive fibrosis biomarkers (aspartate aminotransferase-to-platelet ratio index, Fibrosis-4, BARD, and NAFLD fibrosis score). In subgroup analyses (including sex, age, diabetes, NAFLD activity score, body mass index or serum alanine aminotransferase levels), the ADAPT score had good diagnostic performance. ConclusionPRO-C3 and the ADAPT score reliably exclude advanced fibrosis in MAFLD patients and reduce the need for liver biopsy.

The efficacy of novel metabolic targeted agents and natural plant drugs for nonalcoholic fatty liver disease treatment: A PRISMA-compliant network meta-analysis of randomized controlled trials.

Background:Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis.Methods:Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed.Results:Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels.Conclusions:Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.

NON-INVASIVE TOOLS TO ASSESS THE RISK OF VARICES-NEEDING-TREATMENT IN CIRRHOSIS SECONDARY TO HCV

Objective: To assess the non-invasive biomarkers of fibrosis for predicting varices-needing-treatment in patients with cirrhosis secondary to chronic-hepatitis-C.&#x0D; Study Design: Cross sectional comparative study.&#x0D; Place and Duration of Study: Department of Gastroenterology, Pak Emirates Military Hospital Rawalpindi, from Jan 2017 to Dec 2017.&#x0D; Methodology: A total of 153 patients aged 18-79 with cirrhosis, whether compensated or decompensated, secondary to chronic-hepatitis-C were enrolled. Relevant serum tests were used to calculate non-invasive fibrosis indices and their diagnostic performance to predict the presence of varices and varices-needing-treatment was calculated.&#x0D; Results: King’s score showed the best performance in detecting varices due to high positive predictive value of 96.4% and positive likelihood ratio of 2.4. Overall, all the non-invasive fibrosis indices exhibited good performance with positive predictive value &gt;85% but none could rule out the presence of varices with adequate reliability due to low negative-predictive-value (&lt;65%). King’s score exhibited relatively higher positive-predictivevalue (70%) and negative predictive value (51.1%) and the lowest negative-likelihood-ratio (0.6) for predicting varices needing treatment. Taken together, none of the non-invasive biomarkers of fibrosis could predict the presence of varices-needing-treatment with adequate accuracy due to low positive-predictive-value (&lt;85%) andlow negative-predictive-value (&lt;65%).&#x0D; Conclusion: The calculated non-invasive biomarkers of fibrosis and their optimum cutoff values showed modest accuracy for predicting varices and varices-needing-treatment. These indices may be used as first-line screening method for segregation of clinically significant portal hypertension and high risk esophageal varices-needingtreatment but may not be able to replace the gold standards like Fibroscan liver and Hepatic Venous Pressure Gradient measurements.

Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold.

Kidney fibrosis is the common histological end-point of progressive, chronic kidney diseases (CKDs) regardless of the underlying etiology. The hallmark of renal fibrosis, similar to all other organs, is pathological deposition of extracellular matrix (ECM). Renal ECM is a complex network of collagens, elastin, and several glycoproteins and proteoglycans forming basal membranes and interstitial space. Several ECM functions beyond providing a scaffold and organ stability are being increasingly recognized, for example, in inflammation. ECM composition is determined by the function of each of the histological compartments of the kidney, that is, glomeruli, tubulo-interstitium, and vessels. Renal ECM is a dynamic structure undergoing remodeling, particularly during fibrosis. From a clinical perspective, ECM proteins are directly involved in several rare renal diseases and indirectly in CKD progression during renal fibrosis. ECM proteins could serve as specific non-invasive biomarkers of fibrosis and scaffolds in regenerative medicine. The gold standard and currently only specific means to measure renal fibrosis is renal biopsy, but new diagnostic approaches are appearing. Here, we discuss the localization, function, and remodeling of major renal ECM components in healthy and diseased, fibrotic kidneys and the potential use of ECM in diagnostics of renal fibrosis and in tissue engineering.

Longitudinal effects of Nucleos(t)ide analogue therapy in chronic hepatitis B patients and the utility of non-invasive fibrosis markers during treatment: A single-center experience for up to 17 years

BackgroundFibrosis regression has been associated with nucleoside analogue (NA) treatment in chronic hepatitis B (CHB) patients. Although non-invasive fibrosis markers have been evaluated in CHB, their utility for monitoring on-treatment histologic regression has not been evaluated. AimsTo characterize improvements in disease severity and the utility of non-invasive biomarkers in CHB NA treated patients. MethodsHistology, labs, AST-to-platelet ratio index, and Fibrosis-4 (Fib-4) from treatment-naïve CHB patients were evaluated at baseline and longitudinally. Relative change from baseline to various time points during treatment were evaluated. Correlative analysis of APRI and Fib-4 with histology was performed longitudinally. Results80 CHB patients (84% male, median age 45 (IQR 32, 54)) with histology up to 17 years (median 6(IQR 3.9, 8.0)) years were studied. Median baseline Ishak fibrosis was 3 (IQR 2, 4), histologic activity index (HAI) inflammation was 9 (IQR 7, 11), and AUROC of fibrosis markers for detecting cirrhosis (Ishak ≥ 5) was >0.64. HAI improved at a rate of 54% during year 1 and 37% in year 2, both greater than in the remaining follow-up periods. Within the first year, fibrosis improved by 35%, greater than all other time periods. Non-invasive biomarkers began to correlate with histology beyond 4 years (APRI: 4–6 years: r = 0.33, p = 0.03; ≥6 years: r = 0.41, p = 0.009; Fib-4: ≥6 years: r = 0.35, p = 0.03). ConclusionEarly dynamic changes in histology occur in CHB patients on NA followed by linear improvements. Non-invasive fibrosis biomarkers do not capture these dynamic changes and may demonstrate clinical utility beyond 4 years of treatment.

Non-alcoholic fatty liver disease and increased risk of all-cause mortality in elderly patients admitted for acute heart failure

BackgroundNonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for incident heart failure (HF). It is currently unknown whether NAFLD predicts all-cause mortality in patients admitted for acute HF. We aimed to assess whether NAFLD and its severity (diagnosed by ultrasonography and non-invasive fibrosis biomarkers) were associated with increased all-cause mortality in this particularly high-risk patient population. MethodsWe studied 264 elderly patients, who were consecutively admitted for acute HF to the hospital between years 2013 and 2015, after excluding those with acute myocardial infarction, severe valvular heart diseases, kidney failure, cancer, cirrhosis of any etiology or known chronic liver diseases. Follow-up of patients continued until November 1, 2017. ResultsOver a mean follow-up of 23.2 months (range: 1 day-58 months), there were 140 (53%) total deaths. Of these, 24 deaths occurred during the first hospital admission (in-hospital death) and 116 deaths occurred after the hospital discharge during the follow-up period. Patients with NAFLD at hospital admission had significantly higher cumulative incidence rates of in-hospital and post-discharge all-cause mortality (singly or in combination) compared with those without NAFLD. This mortality risk was particularly high among patients with advanced NAFLD fibrosis. In Cox regression analysis, NAFLD was associated with an increased risk of all-cause mortality (adjusted-hazard ratio 1.82, 95% confidence intervals 1.22–2.81, p < 0.005) even after adjustment for established risk factors and potential confounding variables. ConclusionsNAFLD and its severity were independently associated with increased risk of in-hospital and post-discharge all-cause mortality in elderly patients admitted for acute HF.

Basement Membrane Type IV Collagen and Laminin: An Overview of Their Biology and Value as Fibrosis Biomarkers of Liver Disease.

Basement membranes provide structural support to epithelium, endothelium, muscles, fat cells, Schwann cells, and axons. Basement membranes are multifunctional: they modulate cellular behavior, regulate organogenesis, promote tissue repair, form a barrier to filtration and tumor metastasis, bind growth factors, and mediate angiogenesis. All basement membranes contain type IV collagen (Col IV), laminin, nidogen, and perlecan. Col IV and laminin self-assemble into two independent supramolecular networks that are linked to nidogen and perlecan to form a morphological discernable basement membrane/basal lamina. The triple helical region, 7S domain and NCI domain of Col IV, laminin and laminin fragment P1 have been evaluated as noninvasive fibrosis biomarkers of alcoholic liver disease, viral hepatitis, and nonalcoholic fatty liver disease. Elevated serum Col IV and laminin are related to degrees of fibrosis and severity of hepatitis, and may reflect hepatic basement membrane metabolism. But the serum assays have not been linked to disclosing the anatomical sites and lobular distribution of perisinusoidal basement membrane formation in the liver. Hepatic sinusoids normally lack a basement membrane, although Col IV is a normal matrix component of the space of Disse. In liver disease, laminin deposits in the space of Disse and codistributes with Col IV, forming a perisinusoidal basement membrane. Concomitantly, the sinusoidal endothelium loses its fenestrae and is transformed into vascular type endothelium. These changes lead to capillarization of hepatic sinusoids, a significant pathology that impairs hepatic function. Accordingly, codistribution of Col IV and laminin serves as histochemical marker of perisinusoidal basement membrane formation in liver disease. Anat Rec, 300:1371-1390, 2017. © 2017 Wiley Periodicals, Inc.

Incidence and Predictors of Advanced Liver Fibrosis by a Validated Serum Biomarker in Liver Transplant Recipients.

Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the liver transplant (LT) population. We employed a simple serum biomarker to elucidate incidence and predictors of advanced fibrosis after LT over a long follow-up period. Methods. We included 440 consecutive patients who underwent LT between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond 12 months after LT. Results. Over 2030.5 person-years (PY) of follow-up, 189 (43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95% confidence interval [CI], 8.1–10.7). Advanced fibrosis was predicted by chronic HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92–5.36, p < 0.001), hypoalbuminemia (aHR = 2.31, 95% CI 1.72–3.09; p < 0.001), and hyponatremia (aHR = 1.48, 95% CI 1.09–2.01; p = 0.01). LT recipients with more than 1 predictor had a higher incidence of advanced fibrosis, the highest being when all 3 predictors coexisted (log-rank: p < 0.001). Conclusions. Chronic HCV infection, hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis following LT. Patients with these risk factors should be serially monitored using noninvasive fibrosis biomarkers and prioritized for interventions.

Comparison of Acoustic Radiation Force Impulse/Serum Noninvasive Markers for Fibrosis Prediction in Liver Transplant

Fibrosis, related to several causes, can be diagnosed in children and adolescents' liver grafts that are >1 year old. At present, liver biopsy is the gold standard for assessing liver damage in the posttransplant setting. We aimed to evaluate the accuracy of noninvasive biomarkers of fibrosis, namely, acoustic radiation force impulse (ARFI), aspartate-to-platelet ratio index, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio index, either alone or in combination, for predicting fibrosis in pediatric patients submitted to liver transplantation. We prospectively assessed liver fibrosis in 30 children/adolescents with liver transplant through biopsy (liver transplant follow-up during 12 months). ARFI with Virtual Touch Software (Acuson 2000) was performed, and blood samples were taken to determine liver function and platelet count. Two groups were analyzed according to the histopathologic stage of fibrosis, namely, none/mild (F0-F1) versus significant fibrosis (F2-4). The mean age of the 30 patients was 11 years (3-18 years), with a mean posttransplant period of assessment of 6.5 years. Twenty-four patients (80%) presented stage F0-F1 fibrosis and 6 patients (20%) presented stage F2-4. The area under the curve using receiver operating characteristic analysis for ARFI, aspartate-to-platelet ratio index, and AST/ALT ratio index for significant fibrosis was 0.76 (P = 0.052), 0.74 (P = 0.066), and 0.69 (P = 0.162), respectively. Through multivariate logistic regression analysis, the only independent predictor of significant fibrosis was ARFI (odds ratio 10.7, 95% confidence interval 1.2-95.7; P = 0.045). The combination of ARFI and AST/ALT ratio index presented a good diagnostic accuracy of fibrosis (area under the curve of 0.83; P = 0.013). ARFI may serve as a potential method for assessing significant fibrosis in pediatric patients with liver transplant, particularly in combination with AST/ALT ratio index.

Liver fibrosis markers in alcoholic liver disease.

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

Angiopoietin-2 Serum Levels Improve Noninvasive Fibrosis Staging in Chronic Hepatitis C: A Fibrogenic-Angiogenic Link

AimsAccurate liver fibrosis staging is crucial for the management of chronic hepatitis C (CHC). The invasiveness and cost burden of liver biopsy have driven the search for new noninvasive biomarkers of fibrosis. Based on the link between serum angiopoietin-1 and 2 levels and CHC progression, we aimed to determine the value of these angiogenic factors as noninvasive biomarkers of liver fibrosis.MethodsSerum levels of angiopoietin-1 and -2 were measured by ELISA in 108 CHC patients who underwent pretreatment liver biopsy. The correlation between angiopoietins and clinical and demographic variables with liver fibrosis was analyzed by univariate regression. Significant factors were then subjected to multivariate analysis, from which we constructed a novel noninvasive liver fibrosis index (AngioScore), whose performance was validated in an independent series of 71 CHC patients. The accuracy of this model was compared with other documented fibrosis algorithms by De Long test.ResultsAngiopoietins correlated significantly with hepatic fibrosis; however, only angiopoietin-2 was retained in the final model, which also included age, platelets, AST, INR, and GGT. The model was validated and behaved considerably better than other fibrosis indices in discriminating all, significant, moderate and severe liver fibrosis (0.886, 0.920, 0.923). Using clinically relevant cutoffs, we classified CHC patients by discarding significant fibrosis and diagnosing moderate and severe fibrosis with greater accuracy, sensitivity, and specificity.ConclusionsOur novel noninvasive liver fibrosis model, based on serum angiopoietin-2 levels, outperforms other indices and should help substantially in managing CHC and monitoring long-term follow-up prognosis.

Non-invasive fibrosis biomarkers - APRI and Forns - are associated with liver stiffness in HIV-monoinfected patients receiving antiretroviral drugs

HIV-monoinfected patients are susceptible to liver injury by different factors and may develop liver fibrosis, which requires adequate clinical management in terms of therapy and disease monitoring. We aimed to evaluate the presence of liver fibrosis identified by transient elastography (TE), its relationships with indirect biochemical markers [the aspartate aminotransferase/platelet ratio index (APRI), the Forns index and FIB-4] and its predictive factors in HIV-monoinfected patients receiving antiretroviral therapy (ART). Seventy-two HIV-monoinfected patients underwent TE and were evaluated using APRI, Forns and FIB-4. The clinical, immunological, virological and other biochemical characteristics were evaluated at the time of TE, together with their history of ART. Seven patients (10%) had liver stiffness (LS) values predicting cirrhosis, and 12 (17%) had values predicting significant or advanced fibrosis. Higher indirect biochemical scores of liver fibrosis were significantly associated with higher LS values [APRI rs =0.4296 (P<0.001); Forns rs =0.4754 (P<0.001); FIB-4 rs =0.285 (P=0.015)]. At multivariable analysis, APRI (β=2.7405; P=0.036), Forns (β=1.4174; P=0.029) and triglyceride levels (β=1.3028; P=0.007) were independently associated with LS. Indirect fibrosis biomarkers may increase the probability to detect liver injury enhancing a specific diagnostic workup and so contribute to improving the clinical management of HIV-monoinfected patients with clinically suspected liver disease.

Biomarkers of Fibrosis and Fibrosis Progression in Chronic Hepatitis C

The majority of patients exposed to the hepatitis C virus develop chronic infection. The morbidity and mortality associated with chronic hepatitis C (CHC) is a consequence of progressive liver fibrosis, leading to cirrhosis, decompensated liver disease and hepatocellular carcinoma. As fibrosis is the key determinant of prognosis and influences treatment decisions and enrolment in surveillance programs, accurate assessment of fibrosis is crucial in the management of CHC. Currently liver biopsy is the “gold standard” for fibrosis assessment, but has a number of limitations including morbidity and mortality, sampling error and inter/intra-observer variability. The identification of non-invasive biomarkers of fibrosis has expanded rapidly over the last 10 years, providing an attractive alternative to liver biopsy. This article will review non-invasive biomarkers (serum biochemistry, imaging-based and genetic) for the assessment of fibrosis and fibrosis progression in CHC.

Liver biopsy in modern clinical practice: a pediatric point-of-view.

Liver biopsy remains the foundation of evaluation and management of liver disease in children, although the role of the liver biopsy is changing with development of alternative methods of diagnosis and advancement of hepatic imaging techniques. The indications for liver biopsy are evolving as current knowledge of etiologies, noninvasive biomarker alternatives, and treatment options in pediatric liver disease are expanding. The procedure can often be complicated in children by technical difficulties, cost, and smaller specimen size. Communication and partnership of clinicians with pathologists experienced in pediatric liver diseases are essential. DNA sequencing, novel imaging modalities, noninvasive biomarkers of fibrosis and apoptosis, proteomics, and genome-wide association studies offer potential alternative methods for evaluation of liver disease in children. This review presents specific indications, considerations, methods, complications, contraindications, and alternatives for pediatric liver biopsy.

Usefulness of noninvasive biomarkers of fibrosis in chronic liver disease

Usefulness of noninvasive biomarkers of fibrosis in chronic liver disease

The impact of liver disease aetiology and the stages of hepatic fibrosis on the performance of non-invasive fibrosis biomarkers: an international study of 2411 cases

Performance of non-invasive fibrosis biomarkers may be influenced by aetiology of chronic liver disease (CLD) and the stages of hepatic fibrosis, but large-scale studies are pending. To investigate the effect of aetiogy and stages of hepatic fibrosis on the performance of fibrosis biomarkers. A total of 2411 patients with compensated CLD (HCV=75.1%, HBV=10.5%, NASH=7.9%, HIV/HCV=6.5%) were consecutively enrolled in 9 centres. APRI, Forns'index, Lok index, AST-to-ALT ratio, Fib-4, platelets and Fibrotest-Fibrosure were tested against liver biopsy, considered the gold standard. The effect of the stages of hepatic fibrosis to diagnose significant fibrosis and cirrhosis (≥F2 and F4 respectively) was investigated through difference between advanced and non-advanced fibrosis stages (DANA). Performance was expressed as observed area under the ROC curve (ObAUROC) and AUROC adjusted for DANA (AdjAUROC). Performance of APRI and Fibrotest-Fibrosure was higher than other biomarkers. In all aetiologies, AdjAUROC was higher than ObAUROC. APRI showed its best performance in HCV monoinfected cases, with an AdjAUROC of 0.77 and 0.83 for ≥F2 and F4 respectively. In HBV and non-alcoholic steatohepatitis (NASH) patients, its performance was poor (AdjAUROC <0.70). Performance of Fibrotest-Fibrosure was good in all aetiologies for both ≥F2 and F4 (AdjAUROC >0.73), except for ≥F2 in NASH (AdjAUROC = 0.64). Performance of all biomarkers was reduced in HCV cases with normal ALT. Aetiology is a major factor influencing the performance of liver fibrosis biomarkers. Even after correction for DANA, APRI and Fibrotest-Fibrosure exhibit the best performance. However, liver biopsy is not replaceable, especially to diagnose ≥F2 and in HCV carriers with normal ALT.

P03 The diagnostic value of transient elastography compared to clinical acumen, laboratory tests and ultrasound? Is there added value?

IntroductionThe diagnostic performance of transient elastography (TE), and other non-invasive biomarkers of fibrosis, is assessed by direct comparison with liver biopsy. However clinical acumen, laboratory tests and ultrasonography are utilised...