New Tools for Assessing Disease Sererity, progression and regression in HBV and HCV
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1 New Tools for Assessing Disease Sererity, progression and regression in HBV and HCV Jidong Jia, MD, PhD Beijing Friendship Hospital, Capital Medical University
2 Disclosure Consultation for Abbvie BMS Gilead Roche
3 Liver fibrosis is a common pathway to advanced liver disease Pellicoro A,et al. Nat Rev Immunol 2014;14:181-94
4 Evaluation of liver fibrosis Baranova A, et al. BMC Gastroenterology. 2011
5 Liver Histopathology Semi-quantitative scoring systems: Metavir Ishak Knodell Quantitative morphometry : Collagen proportionate area (CPA) Fibro-C-index qfibrosis Limitations Invasive Expensive Sampling error Inter- and intra-observer variation
6 Noninvasive Assessment for Liver Fibrosis Currently available tests Biological (serum biomarker algorithms) Physical (imaging assessment of tissue stiffness) Physiological (breath test) Emerging novel tests Functional genomic, microparticle, protein-profiling and bioimaging tools Assessment of dynamic nature of fibrogenesis Key to evaluation of efficacy of antifibrotic compounds Semin Liver Dis 2015;35:
7 Serum Biomarkers for Liver Fibrosis Direct serum markers Glycoproteins/proteoglycan: laminin, hyaluronate. collagens: Procollagen III, type IV collagen. collagenases and their inhibitors: MMP, TIMP-1 Reflect ECM turnover ( matrix synthesis or degradation ) Not routinely available Not specific to liver Indirect serum markers Platelet count, PT, AST/ALT ratio FibroTest: α2-mg, ApoA1, haptoglobin, γgt, and bilirubin APRI: AST to Platelet Ratio Idex FIB-4: Age, ALT, AST, Platelet Reflect alterations in hepatic function (more on diagnosis of cirrhosis) Routinely available Usually no extra cost
8 Meta-analysis of APRI for F2 fibrosis/cirrhosis in CHB F 2 F4 Xu XY, et al. PlosOne 2014
9 Meta-analysis of FIB-4 for F2 and F4 in CHB F 2 F4 Xu XY, et al. PlosOne 2014
10 The predictive ability of APRI, FIB-4 and AST/ALT, for F3 fibrosis in 2372 US patients with CHC Holmberg SD, et al. CID 2013
11 FibroTest /Fibrosure for significant fibrosis (F2-4) or cirrhosis (METAVIR F4)in CHB Significant fibrosis (F2-F4) Cirrhosis (F4) AUROC=0.84 (95 % CI: ) AUROC=0.87 (95 % CI: ) Salkic NN, et al. AJG 2014
12 Meta-analysis of FibroTest for significant fibrosis and cirrhosis in CHB F 2 F4 Xu XY, et al. PlosOne 2014
13 AUROCs for ELF and TE diagnosis of significant fibrosis (F 2) (A) and cirrhosis (F4) in CHC (ELF: HA+PIIIP+TIMP-1) F 2 F=4 Fernandes FF, et al. JCG 2015
14 Imaging Assessments For Liver Fibrosis Ultrasound elastography Transient elastography (TE) Fibroscan- EchoSense Real-time elastography (RTE) HI Vision-Hitachi Shear Wave Elastography(SWE) VTTQ(ARFI)- Siemens system Shear Wave Elastography-SuperSonic system ElastQP-Phillips system Magnetic Resonance Elastography (MRE) Ferraioli G, et al. J Ultrasound Med 2014
15 Normal Values
16 Meta-analysis of AUROCs TE for significant fibrosis and cirrhosis in CHB Cho YE, et al. PloS ONE 2012
17 TE for each METAVIR fibrosis stage in 469 patients with CHB Jia JD, et al. JGH 2015
18 AUROC of TE, FIB-4 and APRI for the diagnosis of F 2 and F4 METAVIR stages in 469 CHB patients F 2 F4 Jia JD, et al. JGH 2015
19 AUROC for 10 models, according to METAVIR Fibrosis Stages in 259 CHB patients Cheng J, et al. PLoS ONE 2015
20 Real-Time Elastography (RTE, Hitachi) for F1-F4 fibrosis in CHB Wu T, et al. Dig Dis 2014
21 AUROC for LFI from RTE (Hitachi) and LSM from TE (Fibroscan) for diagnoses of fibrosis F2 and cirrhosis (F4) in CHB F 2 F=4 Meng F, et al. J Ultrasound Med 2015
22 3 major techiques for Sear Wave Elastography (SWE) Siemens system (ARFI, VTTQ=Virtual Touch Tissue Quantification) Super-Sonic system (Sear Wave Elastography) Phillips System (ElastPQ) Ferraioli G, et al. J Ultrasound Med 2014
23 ROC for SWE (ARFI, Siemens) and TE for diagnosis of significant fibrosis (F 2) in CHB Friedrich-Rust M, et al. JVH 2013
24 AUROC for SWE (SuperSonic) in 303 Chinese patients with CHB Zeng J, et al. Eur Radiol 2014
25 AUROC for SWE (SuperSonic) for identifying F2 and F4 in patients with CHC F 2 F=4 Samir AE, et al. Radiology 2015
26 Venkatesh SK, et al. Magn Reson Med 2014
27 Correlations between MRE and Metavir score in 32 patients with CHB. Venkatesh SK, et al. Magn Reson Med 2014; 72:
28 Meta-analysis: Composite box plot graph showing MRE values for various stages (METAVIR) of fibrosis Singh S, et al. CGH 2014
29 Meta-analysis: Diagnostic Performance of MRE for Fibrosis of Different Etiology Singh S, et al. CGH 2014
30 Changes of LSM in CHB after NA therapy The mean interval between two LSMs was ±149.5 (180-1,062) days Kim JK, et al. J Korean Med Sci 2014
31 Changes of LSM after ETV therapy ( with mean interval of 52.8 and 61.9 weeks in the 2 groups) P<0.01 P<0.01 n-=233 n-=13 Kuo YH, et al. PloS ONE 2014
32 Changes of Ishak score and APRI and FIB-4 in CHB patients on TDF therapy APRI FIB-4 Kim WR, et al. J Hepatol 2015
33 Multivariate analysis of negative prognostics of sustained virologic response in CHC on dual or triple therapy N=65 N=20 Stasi C, et al. WJG 2015
34 LSM by TE and LFI by RTE correlates treatment response by antiviral therapy in CHC patients LSM and LFI correlated well before and after therapy (r = 0.567, p = and r = 0.576, p = 0.002, respectively). In the group without a sustained virological response (SVR), LSM increased in 4 of 5 patients. In the SVR group, both LSM and LFI decreased in all patients except 1 (18/19, 94.7%) In the patient with an increase in LSM despite achieving SVR, LSM decreased quickly after alcohol cessation. Yada N, et al. Oncology 2014
35 MALDI-TOF MS Identified Serum Peptide Pattern for Prediction of HBV-Cirrhosis Complete mass spectrum of serum samples between HBV-cirrhosis and non-lc groups in the ,000 m/z range. Red line=hbv-cirrhosis group Blue line=non-lc group. Cao Y, et al. BioMed Research International
36 High Throughput LC-IMS-MS Identified relative log2 intensity proteins with significant differential abundance in CHC Baker ES, et al. Molecular & Cellular Proteomics 2014
37 EASL-ALEH Proposed algorithm for Tx-naïve patients with CHC ± HIV EASL-ALEH. J Hepatol 2015
38 EASL-ALEH Proposed algorithm for Tx-naive patients with CHB EASL-ALEH. J Hepatol 2015
39 Thank you for your attention!
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