Fibrosis Stage In Patients Research Articles

Liver Fibrosis Assessment with Diffusion-Weighted Imaging: Value of Liver Apparent Diffusion Coefficient Normalization Using the Spleen as a Reference Organ.

Liver fibrosis staging is of great clinical importance because it is used to assess the severity of the underlying chronic liver disease. Among various imaging-based methods, apparent diffusion coefficient (ADC) measurement using diffusion-weighted imaging (DWI) has the potential to be used as an imaging biomarker for liver fibrosis assessment. In this study, we investigated the usefulness of liver ADC normalization using the spleen as a reference organ in liver fibrosis staging with 66 patients who underwent liver magnetic resonance imaging (MRI), transient elastography (TE), and surgical resection of a hepatic mass. ADC values of the liver (ADCliver) and spleen were analyzed, and the spleen was used for ADCliver normalization (nADCliver). ADCliver showed a weak negative correlation with TE (r = −0.246; p = 0.047) and fibrosis stage (r = −0.269; p = 0.029), while n ADCliver showed a moderate negative correlation with TE (r = −0.504; p < 0.001) and fibrosis stage (r = −0.579; p < 0.001). AUC values for nADCliver (0.777–0.875) were higher than those for ADCliver for each stage of fibrosis (0.596–0.713, p = 0.037–0.157). AUC values for TE (0.726–0.884) and nADCliver were not statistically different. In conclusion, normalized liver ADC can be useful in diagnosing liver fibrosis stage in patients with variable DWI acquisitions.

Determination of liver fibrosis stages in Egyptian chronic hepatitis B patients by a noninvasive tool

Background/aimHepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF). The prognosis and management of patients with chronic hepatitis B virus depend on the amount and progression of liver fibrosis. Angiopoietin-like protein 2 (Angptl2) is not only a chronic inflammatory mediator, but also a tissue-remodeling factor. The aim of this study is to explore the predictive value of Angptl2 in different fibrosis stages in patients chronically infected with HBV. Materials and methods Eighty patients with chronic HBV infection undergoing Fibroscan were included. Serum concentrations of Angptl2 were detected using a commercial ELISA kit.Results Angptl2 levels were significantly associated with liver fibrosis stages (P = 0.02). The area under the curve (AUC) of Angptl2 for distinguishing patients who showed significant fibrosis (F2–F4) was70.2%. Angptl2 with fibrosis-4 (FIB-4) and Angptl2 with AST/platelets ratio (APRI) performed best with an AUC of 92.5%. ConclusionIn patients with chronic HBV infection, Angptl2 level represents a potential biomarker independently associated with fibrosis stages. The combination of Angptl2 with FIB-4 or Angptl2 with APRI performed better than the existing models for diagnosing significant fibrosis.

From the Editor’s desk…: August 2019

From the Editor’s desk…: August 2019

Clinical value of prothrombin time and hepatic thromboplastin test in the diagnosis of hepatic fibrosis staging of chronic hepatitis B virus

Objective To investigate the clinical value of prothrombin time(PT) and hepatic thromboplastin test(HPT) in the diagnosis of hepatic fibrosis stage in patients with chronic hepatitis B. Methods A total of 76 patients with chronic hepatitis B in Yuncheng Central Hospital from January 2015 to January 2016 were selected.The plasma PT and HPT levels were measured in patients with different stages of liver fibrosis and healthy people.The sensitivity, specificity and accuracy were determined.The clinical value of PT and HPT indicators in liver fibrosis stages was analyzed. Results The levels of PT and HPT in patients with chronic viral hepatitis B increased significantly with the severity of hepatic fibrosis.The level of PT in stage S4 [(14.86±0.96)s] was significantly higher than that in stage S1[(13.31±0.49)s], S2[(13.43±0.52)s] and S3[(13.66±0.53)s](P S2, S4) were higher by drawing ROC curve analysis. Conclusion The sensitivity and specificity of PT and HPT are high.They have good clinical diagnostic value in staging liver fibrosis in patients with chronic hepatitis B. Key words: Hepatitis B, chronic; Liver cirrhosis; Prothrombin time; Liver thromboplastin time; Stage; Liver reserve function; Contrast sensitivity

Non-Invasive Imaging Modalities in Nonalcoholic Fatty Liver Disease: Where Do We Stand?

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in patients with NAFLD; however, it is invasive, costly, and may be associated with morbidity and even mortality, so is not suitable for screening the large number of individuals who are at risk of, or have, NAFLD. Therefore, there has been tremendous focus on finding non-invasive diagnostic modalities, including imaging. New imaging modalities are emerging and may potentially replace biopsy. This review discusses the different non-invasive imaging modalities for the assessment of NAFLD.

Albumin-Bilirubin Score Differentiates Liver Fibrosis Stage and Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Virus Infection: A Retrospective Cohort Study.

.The albumin–bilirubin (ALBI) score was originally established to stratify prognosis in patients with cirrhosis. The diagnostic accuracy of ALBI score in liver fibrosis staging in patients with chronic hepatitis B remains to be investigated. The present retrospective study, therefore, aimed to evaluate the ability of this score to stage liver fibrosis in these patients. Briefly, consecutive patients with hepatitis B virus (HBV) infection who underwent liver biopsy examinations in Kagawa University Hospital were enrolled. Liver fibrosis stage was assessed using a modified Meta-Analysis of Histological Data in Viral Hepatitis score. Albumin–bilirubin scores were calculated according to the following equation: (log10 total bilirubin [T-Bil] × 0.66) + (albumin [Alb] × −0.085). A total of 91 patients were enrolled in this study. Albumin–bilirubin score was able to differentiate stage 4 from stage 3 fibrosis (P < 0.05). When an ALBI score of −2.190 was adopted as the cutoff value for differentiating stage 4 from stages 1–3, the sensitivity, specificity, and positive likelihood ratio were 85.7%, 74.0%, and 3.300, respectively. Kaplan–Meier analysis showed that baseline ALBI scores < −2.190 correlated with better hepatocellular carcinoma (HCC)–free survival (P < 0.05). In conclusion, ALBI score can be used for liver fibrosis staging in Japanese chronic hepatitis B patients and can help distinguish cirrhotic from non-cirrhotic status. Furthermore, ALBI score was useful as a prognosis biomarker in our patients, with smaller ALBI scores predicting better HCC-free survival. Because calculating ALBI score is easy using serum T-Bil and Alb alone, ALBI score will help clinicians with decision-making in management of HBV-infected patients.

Albumin-bilirubin score indicates liver fibrosis staging and prognosis in patients with chronic hepatitis C.

AimAlbumin–bilirubin (ALBI) grade was investigated to predict prognosis of patients with cirrhosis. It was defined using the ALBI score calculated based on serum total bilirubin and albumin, which represent liver function. The diagnostic accuracy for liver fibrosis staging in patients with chronic hepatitis using the ALBI score has not been investigated well. This study aimed to evaluate the diagnostic abilities of the ALBI score for liver fibrosis staging in chronic hepatitis and cirrhosis in Japanese patients with hepatitis C virus (HCV) infection.MethodsJapanese patients with HCV infection who underwent liver biopsy examinations were enrolled in a retrospective study. Fibrosis staging and activity grading were assessed using the modified METAVIR score. The ALBI score was calculated according to the following equation: Log10 total bilirubin (μmol/L) × 0.66 + albumin (g/L) × (−0.085).ResultsA total of 382 patients were enrolled in this study. The ALBI score differentiated fibrosis stage 4 from 3 and stage 3 from 2 (P < 0.05). When an ALBI score of −2.125 was adopted as a cut‐off value, the sensitivity and specificity were 73.2% and 87.1%, respectively, with a positive likelihood ratio of 5.67 to differentiate stage 4 from stages 1–3. Kaplan–Meier analysis showed that smaller ALBI scores at baseline correlated with better hepatocellular carcinoma (HCC)‐free and overall survival (P < 0.05).ConclusionsThe ALBI score indicates liver fibrosis staging in Japanese patients with HCV infection. Furthermore, smaller ALBI scores predict better HCC‐free survival and overall survival. The ALBI score has the potential to expand its application from cirrhosis to chronic hepatitis.

Baseline Hepatic Levels of miR-29b and Claudin are Respectively Associated with the Stage of Fibrosis and HCV RNA in Hepatitis C

We sought to determine if the baseline hepatic levels of miR-122, miR-29b, Claudin, Occludin, Protein Kinase R (PKR) or PKR activator (PRKRA) were correlated with HCV RNA or stage of fibrosis in patients with chronic hepatitis C (CHC). A total of 25 CHC patients (genotype 1) who were treatment naive at the time of sample collection enrolled in this study. By multivariate analysis, CLDN RNA was found as the single independent factor positively correlated with HCV RNA levels (p=0.003), while hepatic miR-29b levels was found as the single independent factor for predicting advanced stage of fibrosis (p=0.028). Conclusion: Our results highlight miR-29b and CLDN as novel predictors of advanced stage of liver fibrosis and baseline HCV RNA in CHC.

THU-073-The use of APRI and FIB-4 scores versus transient elastography for the assessment of liver fibrosis stage in patients with chronic hepatitis C: Is it possible to reduce the need for elastography?

THU-073-The use of APRI and FIB-4 scores versus transient elastography for the assessment of liver fibrosis stage in patients with chronic hepatitis C: Is it possible to reduce the need for elastography?

SAT-322-Comparison of point shear wave elastography (ElastPQ-pSWE) and FibroScan Transient Elastography (F-TE) for liver fibrosis staging in patients with NAFLD

SAT-322-Comparison of point shear wave elastography (ElastPQ-pSWE) and FibroScan Transient Elastography (F-TE) for liver fibrosis staging in patients with NAFLD

Accuracy of Transient Elastography Data Combined With APRI in Detection and Staging of Liver Disease in Pediatric Patients With Cystic Fibrosis

Liver disease develops in 15%-72% of patients with cystic fibrosis, and 5%-10% develop cirrhosis or portal hypertension, usually during childhood. Transient elastography (TE) is a noninvasive method to measure liver stiffness. We aimed to validate its accuracy in detection of liver disease and assessment of fibrosis in children with cystic fibrosis. We performed a cross-sectional study to evaluate the accuracy of TE in analysis of liver disease in 160 consecutive children who presented with cystic fibrosis (9.0 ± 0.4 years old, 53% male) at a tertiary referral pediatric center in Australia, from 2011 through 2016. Patients were classified as having cystic fibrosis-associated liver disease (CFLD) or cystic fibrosis without liver disease (CFnoLD) based on clinical, biochemical, and imaging features. Fibrosis severity was determined from histologic analysis of dual-pass liver biopsies from children with CFLD, as the reference standard. Data from healthy children without cystic fibrosis (n = 64, controls) were obtained from a separate study. Liver stiffness measurements (LSMs) were made by Fibroscan analysis, using the inter-quartile range/median ≤30% of 10 valid measurements. Children with macronodularity or portal hypertension with heterogeneous changes on ultrasound without available biopsy were assigned to the category of stage F3-F4 fibrosis. LSM was made reliably in 86% of children; accuracy increased with age. LSMs were significantly higher in children with CFLD (10.7 ± 2.4 kPa, n = 33) than with CFnoLD (4.6 ± 0.1 kPa, n = 105) (P < .0001) or controls (4.1 ± 0.1kPa) (P < .0001); LSMs were higher in children with CFnoLD than controls (P < .05). At a cut-off value of 5.55kPa, LSM identified children with CFLD with an area under the receiver operating characteristic (AUROC) curve of 0.82, 70% sensitivity, and 82% specificity (P < .0001). Classification and regression tree models that combined LSM and aspartate aminotransferase to platelet ratio index (APRI) identified children with CFLD with an AUROC curve of 0.89, 87% sensitivity, and 74% specificity (odds ratio, 18.6). LSMs correlated with fibrosis stage in patients with CFLD (r = 0.67, P = .0001). A cut-off value of 8.7kPa differentiated patients with stage F3-F4 fibrosis from patients with stage F1-F2 fibrosis (AUROC, 0.87; 75% sensitivity; 100% specificity, P=.0002). The combination of LSMs and APRI improved the differentiation of patients with F3-F4 fibrosis vs F1-F2 fibrosis (AUROC, 0.92; 83% sensitivity; and 100% specificity (P < .01). LSMs made by TE accurately detect liver disease in children with cystic fibrosis; diagnostic accuracy increases when LSMs are combined with APRI. LSMs also differentiate between children with cystic fibrosis with mild-moderate fibrosis vs advanced fibrosis.

Relationship between three commonly used non‐invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non‐alcoholic steatohepatitis

Non-invasive biomarkers are needed for monitoring changes in liver histology in patients with non-alcoholic steatohepatitis (NASH). Obeticholic acid (OCA) was shown to improve fibrosis in patients with NASH in the FLINT trial; a post hoc analysis of these data was performed to determine the relationship between 3 non-invasive fibrosis markers and liver fibrosis improvement. In the Phase 2b FLINT trial, patients were randomised (1:1) to receive 25mg OCA or placebo once daily for 72weeks. Aspartate aminotransferase:platelet ratio index (APRI), fibrosis-4 (FIB-4) index and non-alcoholic fatty liver disease fibrosis score (NFS) were evaluated in serum at baseline and weeks 24, 48, 72 and 96. Liver biopsies were obtained at baseline and 72weeks. In patients with fibrosis improvement at week 24, scores were reduced by a median of 34% for APRI, 10% for FIB-4 and 4% for NFS. Reductions in APRI (P=0.015) and FIB-4 (P=0.036), but not NFS (P=0.201) at week 24, significantly correlated with ≥1-stage improvement in histologic fibrosis at week 72. Reductions in APRI at week 72 were significantly correlated with fibrosis improvement at week 72 (P=0.012). Patients receiving OCA had significant reductions in all markers compared with patients receiving placebo at week 72 [APRI and FIB-4 (P<0.0001); NFS (P<0.05)]. Readily available non-invasive markers may predict improvement in liver fibrosis in patients with NASH. Upon external confirmation and further refinement in larger populations, these markers may serve as surrogate endpoints in NASH clinical trials.

Immunological measurement of aspartate/alanine aminotransferase in predicting liver fibrosis and inflammation.

Background/AimsEnzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis or inflammation. Immunoassay for AST (cytoplasmic [c] AST/mitochondrial [m] AST) and ALT (ALT1/ALT2) has been suggested as one alternatives for enzymatic analysis. The objective of this study was to evaluate the efficacy of immunoassay in predicting liver fibrosis and inflammation.MethodsA total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic venous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. Results of biochemical parameters including enzymatic AST/ALT and immunological assays of cAST, mAST, ALT1, and ALT2 through sandwich enzyme-linked immunosorbent assay (ELISA) immunoassay with fluorescence labeled monoclonal antibodies were compared with the results of METAVIR stage of live fibrosis and the Knodell grade of inflammation.ResultsMETAVIR fibrosis stages were as follows: F0, six (3%); F1, 52 (24%); F2, 88 (40%); F3, 45 (20%); and F4, 28 patients (13%). Mean levels of AST and ALT were 121 ± 157 and 210 ± 279 IU/L, respectively. Mean HVPG score of all patients was 4.7 ± 2.5 mmHg. According to the stage of liver fibrosis, HVPG score (p < 0.001, r = 0.439) and ALT1 level (p < 0.001, r = 0.283) were significantly increased in all samples from patients with CHB. ALT (p < 0.001, r = 0.310), ALT1 (p < 0.001, r = 0.369), and AST (p < 0.001, r = 0.374) levels were positively correlated with Knodell grade of inflammation.ConclusionsALT1 measurement by utilizing sandwich ELISA immunoassay can be useful method for predicting inf lammation grade and fibrosis stage in patients with CHB.

Diagnostic Performance of Serum Asialo-α1-acid Glycoprotein for Advanced Liver Fibrosis or Cirrhosis in Patients with Chronic Hepatitis B or Nonalcoholic Fatty Liver Disease.

The utility of asialo-α1-acid glycoprotein (AsAGP) for assessing the fibrotic burden is unknown. This study examined the diagnostic performance of the AsAGP level for advanced liver fibrosis or cirrhosis in patients with chronic hepatitis B (CHB) or nonalcoholic fatty liver disease (NAFLD). From July to December 2018, 48 patients with CHB and 75 with NAFLD were recruited prospectively. Transient elastography was used as the reference standard for liver fibrosis, and the cutoff liver stiffness values were defined as 10.0 kilopascal (kPa) for ≥F3 and 12.0 kPa for F4 in CHB patients, and 9.0 kPa for ≥F3 and 11.8 kPa for F4 in NAFLD patients. To predict stage ≥F3 and F4 fibrosis, the areas under the receiver operating characteristic curves of the AsAGP level in patients with CHB were 0.788 (95% CI 0.647-0.930; p=0.005) and 0.825 (95% CI 0.674-0.976; p=0.004), respectively. The cutoff AsAGP levels in patients with CHB that maximized the sum of the sensitivity and specificity values were 1.31 (sensitivity 100.0%, specificity 52.6%) and 1.55 (sensitivity 75.0%, specificity 80.0%), respectively. In contrast, the AsAGP level was similar regardless of the fibrosis stage in patients with NAFLD (all p>0.05 between the stages). The AsAGP level showed acceptable diagnostic accuracy in predicting advanced liver fibrosis and cirrhosis in patients with CHB but not in those with NAFLD. Further studies will be needed to validate the diagnostic performance of the AsAGP level in patients with NALFD.

Plasma microRNA: A novel non-invasive biomarker for HBV-associated liver fibrosis staging.

The aim of the present study was to evaluate the potential use of 7 plasma miRNAs for liver fibrosis staging in patients with chronic hepatitis B virus (HBV) infection. Relative levels of miRNAs were measured using quantitative polymerase chain reaction and used to develop a diagnostic panel. A receiver operating characteristic (ROC) curve was drawn to evaluate the performance of individual miRNAs and the whole panel. It was identified that hsa-miR-122 exhibited significantly different expression levels between F4 and F3, F2, F1, and F0 fibrosis stages (P<0.05), and between F2 and F1 stages (P=0.045); hsa-miR-146a-5p, hsa-miR-29c-3p and hsa-miR-223 exhibited significantly different expression levels between F4 and F0 stages. ROC analysis revealed that hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with ≥F2 fibrosis with area under the curve (AUC) =0.745, 0.631 and 0.670, respectively. hsa-miR-122-5p identified patients with ≥F3 disease (AUC=0.783). hsa-miR-122-5p, hsa-miR-223 and hsa-miR-29c-3p identified patients with cirrhosis with AUC=0.776, 0.617 and 0.619, respectively. The miRNA panel exhibited a higher accuracy compared with individual miRNAs in discriminating between ≥F2, ≥F3 and F4 fibrosis stages with AUC=0.904, 0.889 and 0.835, respectively. hsa-miR-122-5p, hsa-miR-146a, hsa-miR-29c and hsa-miR-223 were positively correlated with fibrosis stage. hsa-miR-122-5p and hsa-miR-381-3p were negatively correlated with alanine aminotransferase, aspartate transaminase and HBV viral DNA load. These 7 miRNAs may serve as potential biomarkers of liver fibrosis in patients with HBV-associated fibrosis. The miRNA panel may serve as a novel non-invasive method for liver fibrosis staging.

Serum bile acid patterns are associated with the presence of NAFLD in twins, and dose-dependent changes with increase in fibrosis stage in patients with biopsy-proven NAFLD.

The fasting-state serum bile acid profile in nonalcoholic fatty liver disease (NAFLD) has been reported to differ when nonalcoholic steatohepatitis is compared to nonalcoholic fatty liver. However, there are few data comparing changes in NAFLD vs non-NAFLD, or whether the bile acid profile differs according to the degree of fibrosis. To examine the serum bile acid profile across the entire spectrum of NAFLD. We performed a cross-sectional analysis of two complementary cohorts: a Twin and Family cohort of 156 participants, and a biopsy-proven-NAFLD cohort of 156 participants with fasting bile acid profiling using liquid chromatography/mass spectrometry. In the Twin and Family cohort (mean age 46.3years and body mass index (BMI) 26.6kg/m2 ), 36 (23%) participants had NAFLD (magnetic resonance imaging proton density fat fraction≥5%). Higher chenodeoxycholyl conjugates (9.0% vs 6.5%, P=0.019) and lower glycohyocholate (1.2% vs 3.6%, P<0.001) were observed in NAFLD compared to non-NAFLD-controls. In the biopsy-proven-NAFLD cohort (mean age 49.8years, BMI 32.0kg/m2 ), no differences in total bile acid were seen between nonalcoholic fatty liver vs nonalcoholic steatohepatitis. The total unconjugated bile acid significantly decreased across nonalcoholic steatohepatitis categories (P=0.044). The distribution of stage of fibrosis was F0: 42.3%, F1: 32.7%, F2: 10.3%, F3: 8.3% and F4: 6.4%. The total serum bile acid increased with increase in fibrosis stage (P<0.001). The primary conjugated bile acid proportion increased (P<0.001) whereas unconjugated bile acid (P=0.006), unconjugated cholyl (P<0.001) and chenodeoxycholyl conjugates (P<0.002) significantly decreased with increase in liver fibrosis stage. Fasting-state serum bile acid profile alterations are seen across the entire spectrum of NAFLD. The total serum bile acids did not differ significantly between NAFLD vs non-NAFLD and nonalcoholic fatty liver vs nonalcoholic steatohepatitis, but were significantly perturbed progressively as liver fibrosis increases.

Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis.

Fibrosis is the major determinant of morbidity and mortality in patients with nonalcoholic steatohepatitis (NASH) but has no approved pharmacotherapy in part because of incomplete understanding of its pathogenic mechanisms. Here, we report that hepatocyte Notch activity tracks with disease severity and treatment response in patients with NASH and is similarly increased in a mouse model of diet-induced NASH and liver fibrosis. Hepatocyte-specific Notch loss-of-function mouse models showed attenuated NASH-associated liver fibrosis, demonstrating causality to obesity-induced liver pathology. Conversely, forced activation of hepatocyte Notch induced fibrosis in both chow- and NASH diet-fed mice by increasing Sox9-dependent Osteopontin (Opn) expression and secretion from hepatocytes, which activate resident hepatic stellate cells. In a cross-sectional study, we found that OPN explains the positive correlation between liver Notch activity and fibrosis stage in patients. Further, we developed a Notch inhibitor [Nicastrin antisense oligonucleotide (Ncst ASO)] that reduced fibrosis in NASH diet-fed mice. In summary, these studies demonstrate the pathological role and therapeutic accessibility of the maladaptive hepatocyte Notch response in NASH-associated liver fibrosis.

High Mobility Group Box-1 Drives Fibrosis Progression Signaling via the Receptor for Advanced Glycation End Products in Mice.

High-mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) increased in response to liver injury. Because HMGB1 is a ligand for the receptor for advanced glycation endproducts (RAGE), we hypothesized that induction of HMGB1 could participate in the pathogenesis of liver fibrosis though RAGE cell-specific signaling mechanisms. Liver HMGB1 protein expression correlated with fibrosis stage in patients with chronic hepatitis C virus (HCV) infection, primary biliary cirrhosis (PBC), or alcoholic steatohepatitis (ASH). Hepatic HMGB1 protein expression and secretion increased in five mouse models of liver fibrosis attributed to drug-induced liver injury (DILI), cholestasis, ASH, or nonalcoholic steatohepatitis (NASH). HMGB1 was up-regulated and secreted mostly by hepatocytes and Kupffer cells (KCs) following CCl4 treatment. Neutralization of HMGB1 protected, whereas injection of recombinant HMGB1 promoted liver fibrosis. Hmgb1 ablation in hepatocytes (Hmgb1ΔHep ) or in myeloid cells (Hmgb1ΔMye ) partially protected, whereas ablation in both (Hmgb1ΔHepΔMye ) prevented liver fibrosis in vivo. Coculture with hepatocytes or KCs from CCl4 -injected wild-type (WT) mice up-regulated Collagen type I production by hepatic stellate cells (HSCs); yet, coculture with hepatocytes from CCl4 -injected Hmgb1ΔHep or with KCs from CCl4 -injected Hmgb1ΔMye mice partially blunted this effect. Rage ablation in HSCs (RageΔHSC ) and RAGE neutralization prevented liver fibrosis. Last, we identified that HMGB1 stimulated HSC migration and signaled through RAGE to up-regulate Collagen type I expression by activating the phosphorylated mitogen-activated protein kinase kinase (pMEK)1/2, phosphorylated extracellular signal-regulated kinase (pERK)1/2 and pcJun signaling pathway. Conclusion: Hepatocyte and KC-derived HMGB1 participates in the pathogenesis of liver fibrosis by signaling through RAGE in HSCs to activate the pMEK1/2, pERK1/2 and pcJun pathway and increase Collagen type I deposition.

A novel, non-invasive model for diagnosing liver fibrosis stage in patients with hepatocellular carcinoma

The aim of this study was to investigate the diagnostic value of the platelet count-to-spleen volume ratio (PSR) for diagnosing hepatic fibrosis in patients with hepatocellular carcinoma (HCC). In this interim analysis of an on-going prospective study, 117 patients with HCC and with or without cirrhosis or fibrosis in different stages were analyzed. Fibrosis staging negatively correlated with PSR and the liver volume-to-spleen volume ratio (LSR), while it positively correlated with aspartate aminotransferase-to-platelet ratio index (APRI), Frons’ index, S-index and a fibrosis index based on four factors (FIB-4). The area under the receiver operating characteristic curve (AUROC) was significantly larger for PSR (0.777) than LSR (0.633, P = 0.002). Among patients with significant fibrosis, AUROC for PSR did not differ significantly from the AUROCs for APRI (0.789, P = 0.825), Frons’ index (0.674, P = 0.102), FIB-4 (0.704, P = 0.251) or S-index (0.696, P = 0.204). Among patients with severe fibrosis, AUROC was significantly higher for PSR (0.808) than for LSR (0.685, P = 0.003), Frons’ index (0.673, P = 0.014), FIB-4 (0.684, P = 0.029), or S-index (0.672, P = 0.016); in contrast, the AUROC for PSR was not significantly different from that for APRI (0.739, P = 0.215). Among patients with cirrhosis, AUROC was significantly higher for PSR (0.814) than for LSR (0.671, P = 0.001) or S-index (0.679, P = 0.022), while the AUROC for PSR did not differ significantly from those for APRI (0.711, P = 0.105), Frons’ index (0.722, P = 0.061) or FIB-4 (0.708, P = 0.079). Our results suggest that PSR may be a useful non-invasive model for diagnosing liver fibrosis stage in patients with HCC in China.

Correlations between serum hepatitis B surface antigen and hepatitis B core antibody titers and liver fibrosis in treatment-naïve CHB patients

BackgroundPrevious studies have revealed that quantitative hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (qAnti-HBc) levels can be used as predictors of treatment response in both interferon-α and nucleoside analogue therapies. Few data have been published regarding the relationship between quantitative HBsAg or Anti-HBc levels and liver fibrosis stages in patients with chronic hepatitis B (CHB). MethodsWe conducted a cross-sectional study of treatment-naïve CHB patients. A total of 624 CHB patients were recruited. We assessed the serum HBsAg and qAnti-HBc levels, HBV DNA levels, HBV genotypes, BCP/PC mutations, histological fibrosis staging by Scheuer classification. ResultsIn HBeAg (+) patients, the S0-1 subjects had significantly higher serum HBsAg and lower qAnti-HBc levels than the S2-4 subjects (both p < 0.001). A moderate inverse correlation was present between serum HBsAg levels and fibrosis scores (r = −0.381, p < 0.001), and a moderate positive correlation was found between qAnti-HBc levels and fibrosis scores (r = 0.408, p < 0.001). In the HBeAg (−) patients, the S0-1 subjects also had significantly lower qAnti-HBc levels than the S2-4 subjects (p < 0.001); however, no significant difference in the HBsAg levels was observed between the S0-1 and S2-4 subjects (p > 0.05). Serum qAnti-HBc levels showed a moderate positive correlation with fibrosis scores (r = 0.383, p < 0.001), while serum HBsAg levels exhibited a low inverse correlation with fibrosis scores (r = −0.171, p < 0.001). Multiple logistic regression analysis showed that the parameters for predicting significant fibrosis (S ≥ 2) included age, PLT, qAnti-HBc levels, HBV genotype and BCP/PC mutations in HBeAg (+) group, and age, PLT, qAnti-HBc levels in HBeAg (−) group (all p < 0.05). The AUC of qAnti-HBc levels associated with the diagnosis of significant fibrosis abnormalities in HBeAg (+) and HBeAg (−) patients were 0.734 (95%CI 0.689 to 0.778) and 0.707 (95%CI 0.612 to 0.801), respectively. ConclusionOur study found an association between high serum qAnti-HBc levels and significant fibrosis in both HBeAg (+) and HBeAg (−) treatment-naïve CHB patients. However, low serum HBsAg levels were correlated with moderate to severe fibrosis in HBeAg (+) subjects only.