Non-invasive Biomarkers Of Liver Fibrosis Research Articles

Probiotics may be useful for drug-induced liver dysfunction in patients with depression – A secondary analysis of a randomized clinical trial

Background & AimsThere is a need to identify new treatment options for depression with its comorbidities. Depression often coexists with liver steatosis and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Probiotics might represent a safe option as an adjunctive therapy in patients with depression and possible liver steatosis. The paper presents the secondary analysis of a clinical trial of the effect of probiotic supplementation on the levels of non-invasive markers of liver steatosis and fibrosis in adult patients with depressive disorders. MethodsThe research had a two-arm, parallel-group, prospective, randomized, double-blind, controlled design on probiotics in depression. 116 participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. Here, data from 92 subjects was analyzed. The following were assessed: alanine aminotransferase (ALT), alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, Hepatic Steatosis Index, Framingham Steatosis Index, as well as non-invasive biomarkers of liver fibrosis (AST to Platelet Ratio Index, Fibosis-4 Index), or baseline socio-demographic, clinical, and laboratory parameters. ResultsThe probiotics did not influence liver steatosis and fibrosis parameters compared with placebo (p=.940 for HSI). However, the subgroup analysis revealed significant differences in liver-related parameters when stratified by the main diagnosis group (better improvement in steatosis indices after probiotics in depressive episode than mixed depression and anxiety disorder patients) or psychotropic medications use (better improvement in ALT-based indices after probiotics in antidepressant-treated subjects than those non-antidepressant-treated). The interplay between probiotics, medications, clinical and metabolic profiles of depression, and the changes in liver-related parameters has been discussed. ConclusionsMultiple factors may modulate the postulated hepatoprotective properties of probiotics efficacy in patients with depression. Further studies with larger sample sizes, different probiotic strains, and longer intervention period are necessary to assess the real significance of probiotics for liver health in this population. ClinicalTrials.gov identifierNCT04756544.

Value of Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) in Assessing Liver Fibrosis in Metabolic Dysfunction-Associated Liver Disease: A Comprehensive Review of its Serum Biomarker Role.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a broad condition characterized by lipid accumulation in the liver tissue, which can progress to fibrosis and cirrhosis if left untreated. Traditionally, liver biopsy is the gold standard for evaluating fibrosis. However, non-invasive biomarkers of liver fibrosis are developed to assess the fibrosis without the risk of biopsy complications. Novel serum biomarkers have emerged as a promising tool for non-invasive assessment of liver fibrosis in MAFLD patients. Several studies have shown that elevated levels of Mac-2 binding protein glycosylation isomer (M2BPGi) are associated with increased liver fibrosis severity in MAFLD patients. This suggests that M2BPGi could serve as a reliable marker for identifying individuals at higher risk of disease progression. Furthermore, the use of M2BPGi offers a non-invasive alternative to liver biopsy, which is invasive and prone to sampling errors. Overall, the usage of M2BPGi in assessing liver fibrosis in MAFLD holds great promise for improving risk stratification and monitoring disease progression in affected individuals. Further research is needed to validate its utility in clinical practice and establish standardized protocols for its implementation.

Investigating the correlation between polyunsaturated fatty acids intake and non-invasive biomarkers of liver fibrosis

BackgroundPolyunsaturated fatty acids (PUFAs) have potentially beneficial effects on the liver tissue. Noninvasive biomarkers, including imaging techniques and blood-based biomarkers, are important tools for assessing liver fibrosis. This study aims to investigate the relationship between dietary intake of PUFAs and noninvasive biomarkers for liver fibrosis in the general population. MethodsThe National Health and Nutrition Examination Survey 2017-2018 (NHANES 2017-2018) datasets were used. Fibrosis-4 index (FIB-4), FIB-8, and Fatty Liver Index (FLI) were calculated for each subject. The fibrosis groups were compared based on their intake of PUFA. The correlation between each score and PUFA intake was calculated. Correlation analysis was performed. ResultsA total of 5087 subjects (50.36% female) with a mean age of 49.37±12.14 were evaluated. The mean of median liver stiffness measurement (LSM) was 5.92±5.20 kilo Pascal (kPa). The mean PUFA intake was reported as 20.2±13.9 gm. Fibrosis (F) grouping revealed that 190 subjects had F3, and 154 F4. HDL had a significant correlation with Docosapentaenoic acid (DPA) intake (r = -0.038, p = 0.007). Moreover, AST and ALT had a significant correlation with Docosahexaenoic acid (DHA) intake (r = 0.033 and 0.059, p = 0.019 and <0.001, respectively). FIB-4 and FIB-8 had no correlation with PUFA intake. FLI had a significant correlation with DPA acid (r = 0.062, p <0.001). ConclusionA significant correlation between FLI, and PUFA intake suggests that increasing PUFA consumption could have a positive impact on liver health.

WED-207 Non-invasive biomarkers of liver fibrosis may be used for diagnosing fibrosis and prognostication in patients with metabolic dysfunction-associated steatotic liver disease

WED-207 Non-invasive biomarkers of liver fibrosis may be used for diagnosing fibrosis and prognostication in patients with metabolic dysfunction-associated steatotic liver disease

Serum α-SMA is a potential noninvasive biomarker of liver fibrosis

The severity of fibrosis is central to the therapeutic course for patients with chronic liver disease; therefore, early detection of liver fibrosis is critical for timely therapeutic interventions. Liver biopsy is the gold standard for the diagnosis of liver fibrosis; however, it is contraindicated in several pathological conditions. Activated hepatic stellate cells (HSCs) are the main cells for fibrotic tissue synthesis, such as that of alpha-smooth muscle actin (α-SMA). This study aimed to determine whether serum α-SMA levels are a suitable noninvasive, sensitive, and reliable liver fibrosis marker. Fibrosis was induced in male Wistar rats via chronic CCl4 administration. Fibrosis was determined in the liver tissues by quantifying the hydroxyproline content and visualized using Masson’s trichrome staining. Rats chronically administered CCl4 exhibited a progressive increment in the hepatic collagen content, as well as both hepatic and serum α-SMA levels in a time-dependent manner. Moreover, serum levels of α-SMA significantly correlated with hepatic α-SMA levels (p ≤ 0.001), as well as with the severity of liver fibrosis (p ≤ 0.001). These findings suggest that increased levels of serum α-SMA can be considered a potential reliable and noninvasive biomarker for early liver fibrosis.

The Influence of Probiotic Supplementation on Depression, Anxiety, and Stress Level, as well as Inflammation, Anthropometric and Metabolic Parameters in Patients with Depressive Disorders - preliminary results of an RCT

IntroductionThere is a huge need to search for new treatment options for depression but as well as its comorbidities. Particularly, depression and metabolic abnormalities often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. Thus, the trials of microbiota interventions (e.g., probiotics) may establish a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacological treatment.ObjectivesThe paper presents preliminary results of an RCT on the effect of probiotic supplementation on depression, anxiety and stress level, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders.MethodsThe trial was a two-arm, parallel-group, prospective, randomized, double-blind, controlled design that included 43 participants and lasted 60 days. The probiotic preparation contained Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 in the amount of 3 × 109 colony forming units (CFU). We assessed depression level with Montgomery-Asberg Depression Rating Scale (MADRS), depressiveness, anxiety and stress level with 21-item version of Depression, Anxiety and Stress Scale (DASS-21), quality of life, blood pressure, body mass index and waist circumference, complete blood count, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, selected secondary markers of inflammation and metabolic risk, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4).ResultsThere were no differences in sociodemographic traits and psychometric questionnaires scores, as well as in anthropometric and basic laboratory findings between placebo and probiotic group at the start of the intervention period. Interestingly, there was a statistically significant improvement in MADRS score in both, placebo (p=0,010) and probiotic group (p=0,037) after intervention (see figure). The same finding was observed in total DASS-21 score as well as anxiety subscale of DASS-21. However, there were no differences in anthropometric, inflammation or metabolic laboratory parameters at the end of the study regardless of intervention.Image:ConclusionsWhilst probiotics may benefit some individuals who do not fully respond to antidepressant medications, our study did not show the superiority of probiotics over placebo in managing depressive and anxiety symptoms. However, the target clinical sample, as well as the intervention period and dosage of preparation for this intervention is not fully recognized. Moreover, larger clinical sample may be needed to detect differences between placebo and probiotics.Disclosure of InterestNone Declared

Performance of Non-invasive Biomarkers of Liver Fibrosis Amongst Hispanics and African Americans.

Liver biopsy is the gold standard for fibrosis staging. However, it is limited by significant complications. Non-invasive markers of fibrosis have been developed as an alternative to liver biopsy. The performance of these different markers varies with the etiology of liver fibrosis and possibly amongst different ethnicities. We aim to assess the performance of non-invasive markers of liver fibrosis amongst Hispanics and African Americans. This is a retrospective cohort analysis of patients who had liver biopsy as part of their evaluation of chronic liver disease. One hundred and twenty-six records were analyzed. Univariate and multivariate analyses were performed. Probit regression receiver operating characteristic curve analysis was used to assess the sensitivity of the different non-invasive biomarkers and underlying variables with respect to liver biopsy. The following non-invasive markers for fibrosis were used: Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), age-platelet, AST/alanine aminotransferase (AST/ALT) ratio, fibrosis cirrhosis index (FCI), and fibrosis index (FI). About two-thirds of the study population were African Americans with majority of the study population having chronic liver disease from viral infection. Minimal to no fibrosis by the METAVIR (an acronym for Meta-analysis of Histological Data in Viral Hepatitis) score was found in 58% of patients compared to 42% with moderate to severe fibrosis. Hispanics were more likely than Blacks to have hepatic steatosis. Age significantly increased the sensitivity and specificity of APRI and age-platelet scores. The AST/ALT score had a lower sensitivity for liver fibrosis in women compared to men in our study population. The sensitivity of FIB-4 and age-platelet was higher in Hispanics compared to African Americans while the opposite was the case for APRI, AST/ALT, FCI, and FI. Non-invasive biomarkers are useful in detecting liver fibrosis. FIB-4 and age-platelet have a high sensitivity in Hispanics while African Americans have a high sensitivity for APRI, AST/ALT, FCI, and FI. It is worth noting that these non-invasive biomarkers had variable performances when ethnicity, age, and sex were considered in our population.

Prevalence and Specific Manifestations of Non-alcoholic Fatty Liver Disease (NAFLD) and Diabetes Mellitus Type 2 Association in a Moroccan Population: A Cross-sectional Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is recognized as a common cause of chronic liver disease worldwide. Its association with type 2 diabetes mellitus (T2DM) is known to increase the risk of degenerative complications of diabetes and the likelihood of developing severe hepatic injuries. The objective of this study was to assess the prevalence of NAFLD and to describe the characteristics of its association with T2DM. METHODS: This was a descriptive analytical study, involving patients with T2DM with no history of alcohol consumption, viral hepatitis, hepatotoxic medications, or other chronic liver diseases. The patients underwent an investigation of NAFLD including abdominal ultrasound, non-invasive biomarkers of liver fibrosis, elastography and ultrasound-guided liver biopsy. RESULTS: We collected data from 180 patients with a mean age of 59.3 ± 10.9 years with strong female predominance. The mean duration of diabetes progression was 9.2 ± 7.3 years. Hepatic sonography showed signs of NAFLD in 45.6% of cases. Non-invasive hepatic biomarkers indicated significant fibrosis in 18.3% of cases. Overall, 21% of patients underwent an elastography evaluation, revealing severe fibrosis or cirrhosis in 15.4% of patients. The diagnosis of NASH (Non-alcoholic steatohepatitis) was confirmed histologically in 3 patients. The overall prevalence of NAFLD was 45.6%. Patients with NAFLD had a statistically significant incidence of obesity, metabolic syndrome, hypertension, dyslipidemia, macrovascular complications, and hypertriglyceridemia (p < 0.05). CONCLUSIONS: The combination of NAFLD and T2DM is often found in patients with obesity or metabolic syndrome. The presence of NAFLD can be responsible for increased morbidity and important cardiovascular risks in patients with T2DM.

Serum amyloid P component and pro-platelet basic protein in extracellular vesicles or serum are novel markers of liver fibrosis in chronic hepatitis C patients.

Extracellular vesicles (EVs) contain proteins, mRNAs, and microRNAs, and their cargos have emerged as novel diagnostic markers in various diseases. We aimed to discover novel and noninvasive biomarkers of liver fibrosis by proteomic analysis using serum EVs in patients with chronic hepatitis C. We performed shotgun proteomics using serum EVs isolated from 54 patients with histologically assessed liver fibrosis. Shotgun proteomics identified a total of 974 proteins, and 445 proteins were detected in more than half of the patients. Among them, a total of 9 proteins were identified as proteins that tended to increase or decrease with liver fibrosis with a significance of p<0.005 and that were different between F1-2 patients and F3-4 patients with a significance of p<0.01. Among the 9 proteins, targeted proteomics using serum EVs isolated from the sera of another 80 patients with histologically assessed liver fibrosis verified that serum amyloid P component (SAP) and pro-platelet basic protein (PPBP) levels in EVs significantly decreased with the progression of liver fibrosis and were significantly lower in F3-4 patients than in F1-2 patients. The diagnostic accuracies of SAP and PPBP in EVs for the liver fibrosis stage were comparable to those of type IV collagen 7S, hyaluronic acid, and the fibrosis-4 index (FIB-4 index). Moreover, serum SAP and PPBP levels correlated with the levels in EVs, and the ability of serum SAP and PPBP to diagnose liver fibrosis stage was also comparable to the abilities of type IV collagen 7S, hyaluronic acid, and the FIB-4 index. In conclusion, proteomic analysis of serum EVs identified SAP and PPBP as candidate biomarkers for predicting liver fibrosis in patients with chronic hepatitis C. In addition, SAP and PPBP levels in serum are strongly correlated with those in EVs and could represent markers of liver fibrosis.

Comparison of Mac‐2 binding protein glycosylation isomer (M2BPGi) with AST to platelet ratio index (APRI), fibrosis 4 Score (FIB‐4), and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for NAFLD patients

AbstractThe serum level of Mac‐2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis in biopsy‐proved nonalcoholic fatty liver disease (NAFLD). However, the comparison of M2BPGi with noninvasive fibrosis markers such as AST to platelet ratio index (APRI), Fibrosis 4 Score (FIB‐4), and NAFLD fibrosis score (NFS) in NAFLD patients remains unclear. The participants of Tzu Chi NAFLD cohort (TCNC) including health controls or NAFLD patients were enrolled in Taipei Tzu Chi Hospital. NAFLD was defined as fatty liver in imaging without hepatitis B virus (HBV), hepatitis C virus (HCV), drug, alcohol, or other known causes of chronic liver disease. A total of 777 subjects were included for final analysis. The serum levels of M2BPGi correlated with APRI, FIB‐4 score, and NFS, respectively (P &lt; .001). Of them, 376 (48.4%) were NAFLD patients and 401 were healthy controls. In the group of health controls or NAFLD patients, the M2BPGi levels were significantly higher in female subjects than those of male subjects (P = .027 and 0.006, respectively). Categorized by age, the levels of M2BPGi were significantly higher in elder age groups either in healthy controls or NAFLD patients (P &lt; .05). Compared with healthy controls, NAFLD patients had significantly higher levels of BMI, waist circumference, metabolic components, and liver fibrosis markers such as APRI, NFS, and M2BPGi (P &lt; .05), but no difference in FIB‐4 score (P = .685). According to FIB‐4 score, “intermediate‐ or high‐risk group” had higher APRI, NFS, and M2BPGi than low‐risk group. The serum M2BPGi levels correlated with three noninvasive biomarkers of liver fibrosis including APRI, FIB‐4 score, and NFS. They were significantly higher in female or elder population. Furthermore, APRI, NFS, and M2BPGi were different between NAFLD patients and healthy controls, but no FIB‐4 score. According to FIB‐4 score to determine the risk of liver fibrosis, APRI, NFS, and M2BPGi were also different between low risk and “intermediate or high risk” of NAFLD patients, suggesting a surrogate marker for assessing liver fibrosis of NAFLD patients.

Liver Fibrosis: Point-Ultrasound Elastography Is a Safe, Widely Available, Low-Cost, Noninvasive Biomarker of Liver Fibrosis That Is Suitable for Broad Community Use.

Liver Fibrosis: Point-Ultrasound Elastography Is a Safe, Widely Available, Low-Cost, Noninvasive Biomarker of Liver Fibrosis That Is Suitable for Broad Community Use.

Higher Levels of Plasma Hyaluronic Acid and N-terminal Propeptide of Type III Procollagen Are Associated With Lower Kidney Function in Children With Non-alcoholic Fatty Liver Disease.

ObjectiveHyaluronic acid (HA) and N-terminal propeptide of type III procollagen (PIIINP) are two non-invasive biomarkers of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). We examined the relationships of plasma levels of HA and PIIINP with kidney function in children with NAFLD.MethodsPlasma HA and PIIINP levels were measured using two commercially available enzyme-linked immunosorbent assay kits in a cohort of 106 Caucasian overweight or obese children with biopsy-proven NAFLD. Glomerular filtration rate (eGFR) was estimated using the Bedside Schwartz equation. Genotyping for the patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 variant was performed using an allelic discrimination assay.ResultsChildren with fibrosis F2 had significantly higher plasma PIIINP and HA levels than those with F0 or F1 fibrosis. Liver fibrosis was positively associated with plasma HA and PIIINP, as well as with the presence of the risk allele G of PNPLA3 rs738409 variant, and negatively with eGFR. Moreover, eGFR showed significant inverse associations with HA and PIIINP levels, as well as the presence of G of PNPLA3 rs738409, and liver fibrosis stage. Notably, our multivariable regression models showed that higher plasma PIIINP (standardized beta coefficient: −0.206, P = 0.011) and HA levels (standardized beta coefficient: −0.531, P < 0.0001) were associated with lower eGFR values, even after adjustment for age, sex, systolic blood pressure, PNPLA3 rs738409 genotype, and any stage of liver fibrosis.ConclusionsHigher levels of HA and PIIINP were associated with lower eGFR values in Caucasian children with biopsy-proven NAFLD, independently of PNPLA3 rs738409 genotype and other potential confounding factors.

Post-treatment serum Wisteria floribunda agglutinin-positive mac-2-binding protein level is a useful predictor of hepatocellular carcinoma development after hepatitis C virus eradication.

AimsRecent advances of direct‐acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin‐positive mac‐2‐binding protein (WFA+‐M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA+‐M2BP level and HCC development after the achievement of an SVR is unclear.Methods and ResultsWe examined the association between WFA+‐M2BP and HCC development in 522 HCV patients who achieved an SVR (Interferon [IFN]‐based therapy, n = 228; IFN‐free therapy, n = 294). Multivariate analysis revealed that a high WFA+‐M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR] = 1.215, P = 0.020), low platelet counts (HR = 0.876, P = 0.037), and old age (HR = 1.073, P = 0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that a WFA+‐M2BP level at SVR24 of ≥1.62 cut‐off index (COI) was the cut‐off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501–45.092, P < 0.001). The 3‐ and 5‐year cumulative incidences of HCC were 1% and 1.6% in patients with low WFA+‐M2BP at SVR24 (<1.62 COI), and 4.7% and 12.5% in patients with high WFA+‐M2BP (≥1.62 COI) were, respectively (P < 0.001).ConclusionsThe assessment of liver fibrosis using the WFA+‐M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN‐free therapy era.

Two-dimensional (2D) morphologic measurements can quantify the severity of liver disease in children with autosomal recessive polycystic kidney disease (ARPKD).

To evaluate the correlation of 2D shape-based features with magnetic resonance elastography (MRE)-derived liver stiffness and portal hypertension (pHTN) in children with ARPKD-associated congenital hepatic fibrosis. In a prospective IRB-approved study, 14 children with ARPKD (mean age ± SD = 13.8 ± 5.8years) and 14 healthy controls (mean age ± SD = 13.7 ± 3.9years) underwent liver MRE. A 2D region of interest (ROI) outlining the left liver lobe at the level of the abdominal aorta was drawn on sagittal T2-weighted images. Eight shape features (perimeter, major axis length, maximum diameter, perimeter to surface ratio (PSR), elongation, sphericity, minor axis length, and mesh surface) describing the 2D-ROI were calculated. Spearman's correlation was calculated between shape features and MRE-derived liver stiffness (kPa) (n = 28). Shape features were compared between participants with ARPKD with pHTN (splenomegaly and thrombocytopenia), (n = 4) and without pHTN (n = 8) using the Mann Whitney U test. Receiver operating characteristic (ROC) curves were generated to examine the diagnostic accuracy of shape features in identifying cases with liver stiffness > 2.9kPa. In ARPKD participants and healthy controls, all eight shape features, except elongation, showed moderate to strong correlation with liver stiffness (kPa); the perimeter surface ratio had the strongest correlation (rho = - 0.75, p < 0.001). In ROC analysis, a cut-off of PSR ≤ 0.057mm-1 gave 100% (95% CI: 59.0-100.0) sensitivity and 100% (95% CI: 83.9-100.0) specificity in identifying ARPKD participants with liver stiffness > 2.9kPa, with an area under the ROC curve (AUC) of 1.0 (95% CI: 0.88-1.00). Individuals with pHTN had a lower median PSR (mean ± SD = 0.05 ± 0.01) than those without (0.07 ± 0.01; p = 0.027) with an AUC of 0.91 (95% CI: 0.60-0.99) in differentiating the participants with and without pHTN. Shape-based features of the left liver lobe show potential as non-invasive biomarkers of liver fibrosis and portal hypertension in children with ARPKD.

FibroMeter scores for the assessment of liver fibrosis in patients with autoimmune liver diseases

Introduction and ObjectivesWe assessed FibroMeter virus (FMvirus) and FibroMeter vibration-controlled transient elastography (FMVCTE) in 134 patients with autoimmune liver diseases [ALD, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC)], in order to assess new potential non-invasive biomarkers of liver fibrosis in patients with ALD, as similar data are missing. Patients and MethodsThe following groups were included: group 1: n = 78 AIH; group 2: n = 56 PBC. FMvirus and FMVCTE were determined in all 134 patients who underwent liver biopsy and TE the same day with sera collection. In addition, APRI and FIB-4 scores were calculated. ResultsThe AUCs for TE and FMVCTE were significantly better (0.809; p < 0.001 and 0.772; p = 0.001, respectively for AIH and 0.997; p < 0.001 and 1; p < 0.001, for PBC) than the other three markers in predicting ≥ F3 fibrosis irrespective of the biochemical activity. FMVCTE and TE had good diagnostic accuracy (75.6% and 73%, respectively) for predicting severe fibrosis in AIH and performed even better in PBC (94.6% and 96.4%, respectively). The cut-offs of TE and FMVCTE had the best sensitivity and specificity in predicting ≥ F3 fibrosis in both AIH and PBC. ConclusionsFMVCTE seems to detect severe fibrosis equally to TE in patients with ALD but with better specificity. Biochemical disease activity did not seem to affect their diagnostic accuracy in ALD and therefore, could be helpful for the assessment of fibrosis, especially if they are performed sequentially (first TE with the best sensitivity and then FMVCTE with the best specificity).

A longitudinal assessment of non-invasive biomarkers to diagnose and predict cystic fibrosis-associated liver disease

Background & AimsA practical, inexpensive, and non-invasive biomarker of liver fibrosis is needed as a reliable screening test for cystic fibrosis-associated liver disease (CFLD). Studies have shown the utility of AST to Platelet Ratio Index (APRI), fibrosis index based on 4 factors (FIB-4), and gamma-glutamyl transferase (GGT) as good biomarkers for identifying CFLD. The goal of the study was to evaluate the effectiveness of APRI, FIB-4, AST/ALT ratio, platelet count, GGT, and GGT platelet ratio (GPR) in predicting CFLD development. MethodsData was collected from CF Foundation Patient Registry for patients aged 3–21 years at Johns Hopkins from January 1, 2002 to December 31, 2014. Collected data included demographic characteristics, presence of splenomegaly, hepatomegaly, ascites, and variceal bleeding, AST, ALT, GGT, platelet count, and FEV1. The sensitivity and specificity of each biomarker were analyzed and reported by the area under receiver operating characteristic (AUROC) curve. ResultsBy the end of the study, 144 “healthy” CF, 12 CFLD, 19 CF-associated pulmonary disease (CFPD), and 4 CFLD with CFPD cases were identified. APRI scores were higher in CFLD, 0.85 versus 0.28 in “healthy” CF and 0.23 in CFPD groups (p<0.001). GPR had the highest AUROC curve at 0.91. ConclusionsGPR, GGT, APRI score, and platelet count were potentially useful biomarkers while FIB-4 did not predict CFLD development. Cost-effectiveness studies are needed to analyze the utility of these biomarkers in clinical practice.

The Enhanced Liver Fibrosis Index Predicts Hepatic Fibrosis Superior to FIB4 and APRI in HIV/HCV Infected Patients.

Accurate noninvasive biomarkers of fibrotic progression are important for hepatitis C virus (HCV) management, but commonly used modalities may have decreased efficacy in human immunodeficiency virus (HIV)/HCV-coinfected persons. The enhanced liver fibrosis (ELF) index is a highly sensitive noninvasive marker of hepatic fibrosis that has had limited assessment in the HIV/HCV population. We compared ELF index performance to FIB4 and aspartate to platelet ratio index (APRI) at different stages of liver fibrosis as determined by liver histology, and validated the efficacy of the three noninvasive biomarkers in HIV/HCV-coinfected versus HCV-monoinfected. The ELF index was determined in 147 HIV/HCV-coinfected and 98 HCV-monoinfected persons using commercial ELISA assays for the component elements of the index. Area under the receiver-operator curve was used to validate ELF and to compare its performance to liver histology as well as to other noninvasive biomarkers of liver fibrosis, FIB4, and APRI. The ELF index increased with histological stage of liver fibrosis and exhibited a linear relationship with Metavir score in all subjects. ELF performance was comparable between HIV/HCV and HCV with advanced liver fibrosis/cirrhosis. In the HIV/HCV cohort ELF cutoffs of 8.45 and 9.23 predicted mild and moderate fibrosis with 85% sensitivity, whereas the ELF cutoff of 9.8 had the highest specificity for advanced fibrosis and the cutoff of 10.4 was 99% specific for cirrhosis. ELF performance was superior to FIB4 and APRI in all subjects regardless of HIV status. ELF index demonstrated excellent characteristics toward accurate prediction of liver fibrosis and cirrhosis with superior performance to APRI and FIB4 in HIV/HCV coinfection. Applying this noninvasive biomarker index for diagnosis of liver fibrosis and progression in HIV/HCV is warranted.

Plasma eicosanoids as noninvasive biomarkers of liver fibrosis in patients with nonalcoholic steatohepatitis.

Background:Eicosanoid and related docosanoid polyunsaturated fatty acids (PUFAs) and their oxygenated derivatives have been proposed as noninvasive lipidomic biomarkers of nonalcoholic steatohepatitis (NASH). Therefore, we investigated associations between plasma eicosanoids and liver fibrosis to evaluate their utility in diagnosing and monitoring NASH-related fibrosis.Methods:Our analysis used baseline eicosanoid data from 427 patients with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), and longitudinal measurements along with liver fibrosis staging from 63 patients with NASH and stage 2/3 fibrosis followed for 24 weeks in a phase II trial.Results:At baseline, four eicosanoids were significantly associated with liver fibrosis stage: 11,12-DIHETE, tetranor 12-HETE, adrenic acid, and 14, 15-DIHETE. Over 24 weeks of follow up, a combination of changes in seven eicosanoids [5-HETE, 7,17-DHDPA, adrenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), 16-HDOHE, and 9-HODE) had good diagnostic accuracy for the prediction of ⩾1 stage improvement in fibrosis (AUROC: 0.74; 95% CI: 0.62–0.87), and a combination of four eicosanoids (7,17-DHDPA, 14,15-DIHETRE, 9-HOTRE, and free adrenic acid) accurately predicted improvement in hepatic collagen content (AUROC: 0.72; 95% CI: 0.50–0.77).Conclusion:This study provides preliminary evidence that plasma eicosanoids may serve as noninvasive biomarkers of liver fibrosis and may predict liver fibrosis improvement in NASH.

The Effect of Moderate Weight Loss on a Non-Invasive Biomarker of Liver Fibrosis: A Randomised Controlled Trial

Background: Referral to weight loss programmes is the only effective treatment for non-alcoholic fatty liver disease (NAFLD). Clinicians should advise weight loss and screen for liver fibrosis using the Enhanced Liver Fibrosis (ELF) score. Aim: To examine if the ELF score changes with weight loss. Design and Setting: Randomised controlled trial (ISRCTN85485463) in UK primary care during 2007–2008. Method: Adults with a BMI of 27–35 kg/m² and ≥1 risk factor for obesity-related disease were randomised to attend a community weight loss programme (n = 45) or receive usual weight loss advice from a practice nurse (n = 28). Weight and the ELF score were measured at baseline and 1 year. Analysis of covariance examined mean changes in the ELF score between groups and its relationship with weight loss. Results: Mean (SD) BMI was 31.10 kg/m² (2.55) with evidence of moderate levels of liver fibrosis at baseline (mean ELF score: 8.93 [0.99]). There was no evidence that the community weight loss programme reduced the ELF score compared with usual care (difference +0.13 points, 95% CI: –0.25 to 0.52) despite greater weight loss (difference: –2.66 kg, 95% CI: –5.02 to –0.30). Mean weight loss in the whole cohort was 7.8% (5.9). There was no evidence of an association between weight change and change in ELF; the coefficient for a 5% weight loss was –0.15 (95% CI: –0.30 to 0.0002). Conclusion: We found no evidence that the ELF score changed meaningfully following moderate weight loss. Clinicians should not use the ELF score to measure improvements in NAFLD fibrosis following weight loss programmes.

DOWN REGULATION OF CLASSICAL MONOCYTES SUBSET IN PATIENTS WITH HCV RELATED LIVER FIBROSIS

data demonstrated a significant down regulation (p< 0.01) in the proportion of classical monocytes subset (CD45+ve, CD 14+ve and CD 16-ve) in patients with chronic hepatitis C related liver disease compared to healthy subjects. Data also demonstrate that down regulation of the expression of classical monocyte subset paralleled the worsening severity of liver disease and the progression of liver fibrosis.