Fibrosis Staging In Chronic Hepatitis Research Articles

Retrospective Evaluation of Non-Invasive Assessment Based on Routine Laboratory Markers for Assessing Advanced Liver Fibrosis in Chronic Hepatitis B Patients.

BackgroundAt present, there is a lack of cheap, effective and convenient detection methods for hepatitis B-related liver fibrosis, especially in the developing area.AimTo evaluate the non-invasive methods for the significant and advanced fibrosis stage in chronic hepatitis B virus (HBV) patients in basic hospitals and to assess their diagnostic utility.MethodsThe study included 436 consecutive naive HBV individuals who had their livers biopsied. They were examined in one week using aspartate aminotransferase-to-aspartate aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), Forns, gamma-glutamyl transpeptidase-to-platelet ratio (GPR), S-index and transient elastography (TE). Scheuer scoring system was used to determine the histologic fibrosis grades (S0–S4). The diagnostic effectiveness was assessed using AUROCs and the DeLong test, both of which were based on statistical comparisons.ResultsFor both substantial (≧S2) and advanced (≧S3) fibrosis phases, TE had good diagnostic performance in determining the hepatic fibrosis. Similar diagnostic performance was shown with Forns and S-index when it came to detecting fibrosis stages lower than S3. One model’s diagnostic value was not significantly improved by combining serum models. Correlation coefficients between clinical features and fibrosis phases were greatest for Forns (r = 0.397), S-index (r = 0.382) and TE (r = 0.535) when compared to other variables.ConclusionThis investigation showed that Forns and S-index may be helpful strategies for detecting advanced fibrosis in HBV patients admitted to community hospitals.

Relationship Between Histological Stage and Neutrophil to Lymphocyte Ratio in Chronic Hepatitis C

Objective: The histological stage is crucial for the management of the patients with chronic hepatitis C. Because of the invasiveness and some limitations of liver biopsy a lot of noninvasive tests are in search intensively to use instead of liver biopsy. In this study, we searched the relationship of neutrophil to lymphocyte ratio with the stage of inflammation and fibrosis in histology in patients with chronic hepatitis C. Materials and Methods: This study retrospectively investigated datas of 62 patients with chronic hepatitis C and 40 healthy controls. Results: Mean neutrophil to lymphocyte ratio values in chronic hepatitis C and control groups were 1.86 (0.89-3.94) and 1.38 (0.73-2.93) respectively (p=0.001). In the chronic hepatitis C group there were 23 (%37) patients with advanced fibrosis (Ishak score>2) and 39 (%63) patients with mild fibrosis (Ishak score≤ 2). In patients with advanced fibrosis, mean neutrophil to lymphocyte ratio was high according to patients with mild fibrosis (2.10 (1.21-3.54) and 1.71(0.89-3.94) respectively, p=0.006). In receiver operating characteristic (ROC) curve analysis, cut off value for neutrophil to lymphocyte ratio in advanced fibrosis was 1.76 (sensitivity 86.9%, specifity 61.5%, NPV 88.9%, PPV 57.1%, AUC: 0.711). Conclusion: Neutrophil to lymphocyte ratio can predict fibrosis stage in chronic hepatitis C. But more studies are necessary to use neutrophil to lymphocyte ratio in clinic practice or how this parameter change with treatment.

Serum biomarkers as an alternative to vibration controlled transient elastography in liver fibrosis staging in chronic hepatitis C.

Assessment of liver disease severity in chronic Hepatitis C (CHC) is essential both in pretreatment and posttreatment period. We assessed the impact of direct-acting antiviral therapy on liver stiffness regression measured by Vibration Controlled Transient Elastography (VCTE) in patients with CHC and evaluated the diagnostic performance of the APRI and FIB-4 scores compared to VCTE in detecting advanced fibrosis and cirrhosis (F3/F4). Retrospective analysis of consecutive patients with CHC who underwent VCTE before and after DAA therapy was done. APRI and FIB-4 scores were compared to VCTE. 88 (56.78%) patients-12 (F3) and 76 (F4) according to VCTE, had advanced fibrosis pretreatment, which reduced to 69 (44.52%) - 10 (F3) and 59 (F4) after 12 weeks DAA therapy. Significant reduction in VCTE value from 14.08 ± 9.05 KPa to 11.84 ± 8.31 KPa (p=0.002) was noted. There is significant reduction in APRI, FIB-4 and GUCI score posttreatment which was not the case with Lok score and Bonacini score. Before therapy, FIB-4 outperformed others to predict advanced fibrosis with score >2.13 (AUC 0.93), having sensitivity 76%, specificity 96% and accuracy 86%. However posttreatment, APRI and GUCI score performed best to predict F3/F4 fibrosis with score >0.63 (AUC 0.97) and >0.64 (AUC 0.96), having sensitivity, specificity and accuracy of 85%, 96.6% and 92% ; 85%, 6.6% and 92% respectively. Before therapy, FIB-4 had the best accuracy in predicting advanced fibrosis whereas APRI and GUCI score were the best indices post-treatment.

Performance Assessment Techniques of Liver Fibrosis Non-invasive Diagnostic Methods in an Approach without a “Gold” Standard: Saying Goodbye to Liver Biopsy?

Aims: 1. To evaluate the applicability of The Expert Assessment (EA) based on the algorithm developed by the authors in performance assessment of transient elastography by M-probe (TE-M) and XL-probe (TE-XL), Fibrotest® (FT), shear wave elastography (SWE) and liver biopsy (LB) in fibrosis staging in chronic hepatitis C (CHC) patients in an approach without a «gold» standard; 2. To evaluate the quality of the proposed model (EA efficacy) in comparison with the results of the Rasch Model (MR) being an extension of the Latent Variable Analysis.Material and methods. Using the five studied diagnostic methods liver fibrosis staging was performed in chronic hepatitis C patients. Based on the algorithm developed EA was applied to each patient of the cohort and as a result fibrosis stage was established. That fibrosis stage considered a virtual reference. Sensitivity and specificity estimation as well as AUC calculation for studied methods was performed against the reference standard. The quality of the model (EA efficacy) estimated in the Rasch Model (MR) being an extension of the Latent Variable Analysis.Results. 99 patients with reliable results of each of the five diagnostic methods were included into the study. The main characteristics of the cohort were: 59.6% individuals of male gender, average age of 37 years (21–63), median BMI of 25.8 kg / m2. As per the results of the EA in detecting of mild fibrosis (F1), the values of AUC, sensitivity and specificity were, respectively: 0,972; 94,3; 91,3 for TE-M; 0,964; 90,6; 91,3 for TE-XL; 0,806; 81,1; 73,9 for FT; 0,907; 88,7; 71,7 for SWE; 0,832; 92,5; 37,0 for LB. In detecting of moderate fibrosis (F2), the appropriate values were: 0,981; 93,8; 94,0 for TE-M; 0,967; 90,6; 97,0 for TE-XL; 0,873; 75,0; 80,6 for FT; 0,957; 84,4; 91,0 for SWE; 0,937; 90,6; 94,0 for LB. In detecting of significant fibrosis (F3), the corresponding values were: 0,994; 95,5; 96,1 for TE-M; 0,987; 90,9; 97,4 for TE-XL; 0,870; 63,6; 84,4 for FT; 0,961; 86,4; 97,4 for SWE; 0,990; 90,9; 98,7 for LB. In detecting cirrhosis (F4), the appropriate values were: 0,995; 92,3; 97,7 for TE-M; 0,994; 100,0; 98,8 for TE-XL; 0,874; 38,5; 93,0 for FT; 0,996; 92,3; 100,0 for SWE; 0,964; 69,2; 100,0 for LB. The EA was shown to have high degree of consistency (correlation coefficient = 0,923; p <0,05) when compared to the MR.Conclusion. The EA was shown as a highly informative approach, applicable for performance assessment of the diagnostic methods for liver fibrosis staging without using LB as the “gold” standard. Non-invasive methods have demonstrated higher diagnostic characteristics with changing the standard from the traditional (LB) to virtual (EA). The high degree of consistency of the results of EA and MR confirm the high quality of the algorithm developed by the authors.

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.

The association of semaphorins 3C, 5A and 6D with liver fibrosis stage in chronic hepatitis C.

Semaphorins are a diverse family of immunoregulators recently recognized to play a major role in various phases of immune responses. Their role in chronic viral hepatitis C (CHC) and contribution to the progression of liver disease is unknown. The aim of this study was to analyse the association of secreted semaphorins with the severity of liver disease in patients with CHC. Serum concentrations of semaphorins were measured in 114 treatment-naive CHC patients and 36 healthy controls. Serum concentrations of SEMA3A, SEMA3C, SEMA5A, SEMA6B and SEMA6D were significantly increased in patients with CHC compared to controls. While serum concentrations of SEMA3C and SEMA6D significantly increased with fibrosis stage in both HCV-g1 and HCV-g3 infections, the concentration of SEMA5A inversely correlated with fibrosis stage in both HCV genotypes. ROC analysis showed that serum concentrations of SEMA3C (>4.0ng/mL, AUC 0.88) and SEMA6D (>4.5, AUC 0.82) had higher AUC than widely used APRI (AUC 0.71) and FIB-4 (AUC 0.74) scores. Serum concentrations of SEMA3C and SEMA6D significantly decreased after DAA and PEG IFN-α/ribavirin therapy, while the serum concentration of SEMA5A significantly increased after DAAs therapy. Immunohistochemistry confirmed the expression of SEMA3C and SEMA5A in hepatocytes, endothelial cells and lymphocytes of cirrhotic livers from CHC patients but not in controls. In conclusion, we provide the first evidence that SEMA3C, SEMA5A and SEMA6D can be considered as markers of liver injury in CHC.

Comparison and correlation of fibrosis stage assessment by collagen proportionate area (CPA) and the ELF panel in patients with chronic liver disease

BackgroundFibrosis progression is the common consequence of most chronic liver diseases. AimsTo evaluate the performance of Collagen Proportionate Area (CPA) and ELF using Ishak’s score in patients with chronic liver diseases. MethodsRetrospective analysis of medical data from patients on whom a liver biopsy was performed as part of the diagnostic assessment. CPA was calculated by using digital image analysis and then compared with Ishak and ELF scores. Results143 patients (84 men (59%); mean age 48.8 ± 12.8 years) were evaluated. Patients were mainly affected by viral hepatitis (92 HCV and 8 HBV). CPA and ELF values increased with worsening Ishak stage (P < 0.001) and their median values were significantly different among Ishak stages (P < 0.001). There was a significant correlation between CPA and ELF (r = 0.5). In AUROC analysis, CPA and ELF had similar diagnostic accuracy in identifying cirrhosis, but CPA had higher diagnostic accuracy than ELF in identifying significant or absent fibrosis. High ELF scores were observed in non-cirrhotic patients who suffered non-liver related deaths. ConclusionsThis study demonstrated that CPA and ELF values successfully identified patients with advanced fibrosis or cirrhosis, thus confirming the role of ELF as a clinical method for non-invasive assessment of fibrosis stage in chronic hepatitis.

21. Validity of serum markers for fibrosis staging in chronic hepatitis B and C

21. Validity of serum markers for fibrosis staging in chronic hepatitis B and C

Value of gamma-glutamyl transpeptidase-to-platelet ratio in predicting liver fibrosis stage in chronic hepatitis B patients in Guangdong, China

Objective To investigate the value of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in predicting liver fibrosis stage in chronic hepatitis B (CHB) patients in Guangdong, China. Methods A total of 501 patients who were diagnosed with CHB by liver biopsy in Guangzhou 8 th People's Hospital from January 2010 to December 2016 were enrolled, among whom 335 had HBe Ag-positive CHB and 166 had HBe Ag-negative CHB. The value of GPR, gamma-glutamyl transpeptidase (GGT) , aspartate aminotransferase-to-platelet ratio index (APRI) , and fibrosis-4 (FIB-4) in predicting liver fibrosis stage (F1-F4) was analyzed. The Spearman correlation coefficient was used to analyze the correlation between diagnostic models and liver fibrosis stage, and the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the value of each model in predicting liver fibrosis stage. Results With liver biopsy as the gold standard, of all patients, 141 had F1 stage, 183 had F2 stage, 139 had F3 stage, and 38 had F4 stage disease. The Spearman correlation analysis showed that in HBe Ag-positive and HBe Ag-negative patients, GGT, GPR, APRI, and FIB-4 were positively correlated with liver fibrosis stage (r = 0. 459, 0. 526, 0. 320, 0. 470, 0. 272, 0. 366, 0. 288, and 0. 388, all P 0. 05) ; in HBe Ag-negative CHB patients, GPR had a significantly better value in predicting marked fibrosis (≥F2) than GGT and APRI (both P 0. 05) . Conclusion GPR can be used as a noninvasive biochemical index for liver fibrosis stage in CHB patients in Guangdong, and in HBe Ag-positive CHB patients, GPR has a comparable predictive value to FIB-4 and APRI.

Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B.

Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P<.001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n=219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P<.01) and tended to better than the fibrosis-4 (P=.0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P=.1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P<.05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P=.2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P<.05) models and was comparable with Forn (P=.1649). These results was validated by a validation set (n=198). FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis.

Evaluation of Plasma Urokinase-Type Plasminogen Activator Receptor (UPAR) in Patients With Chronic Hepatitis B, C and Non-Alcoholic Fatty Liver Disease (NAFLD) as Serological Fibrosis Marker

Progressive hepatic fibrosis is the main predictor of outcome and prognosis in chronic liver diseases. The importance of the coagulation cascade has been defined in liver fibrosis; however, the role of the fibrinolytic pathway has not been clear yet. We aimed to evaluate the association between the plasma levels of soluble urokinase Plasminogen Activator Receptor (uPAR) and the severity of liver fibrosis in chronic hepatitis B, C and Non-Alcoholic Fatty Liver Disease (NAFLD). 96 chronic hepatitis B, 22 chronic hepatitis C and 11 NAFLD patients together with 47 healthy controls were enrolled in the study. uPAR plasma levels were detected by Enzyme-Linked Immunosorbent Assay (ELISA) method. The plasma levels of uPAR in patients with chronic hepatitis B and C significantly exceeded those of healthy controls (P<0.001) while mean uPAR levels in patients with NAFLD were not different from healthy controls. Mean uPAR levels in chronic viral hepatitis patients with F1-F3 fibrosis and F4-F6 fibrosis were higher than those of control group (P<0.001). Mean uPAR level in patients with F4-F6 fibrosis was significantly higher than that of patients with F1-F3 fibrosis (P<0.001). This is the first study that investigated uPAR as a fibrosis marker in NAFLD and chronic hepatitis B patients. It is suggested that plasma levels of uPAR are closely related to the fibrosis stage in chronic hepatitis B and C and that uPAR might be a noninvasive marker of liver fibrosis.

Elastogram quality assessment score in vibration‐controlled transient elastography: Diagnostic performance compared to digital morphometric analysis of liver biopsy in chronic hepatitis C

Vibration-controlled transient elastography (VCTE) is widely used for noninvasive fibrosis staging in chronic hepatitis C. However, internal validation is based solely on variability and success rate and lacks reproducible quality indicators. We analysed the graphic representation of shear wave propagation in comparison with morphometric results of liver biopsy, eliminating observer variability bias. Individual elastograms were classified according to two morphologic criteria: extension of wave propagation (length of the graphic representation) and shear wave dispersal (level of parallelism displayed in the elastogram). Then, a score based on these criteria stratified the elastogram in classes I through III (highest to lowest technical quality). Liver stiffness results of each measurement were compared with collagen contents in liver biopsy by morphometric analysis. A total of 3243 elastograms were studied (316 patients). Digital morphometry in liver biopsy showed significant fibrosis in 66% of samples and advanced fibrosis in 31%. Elastogram quality analysis resulted in 1438 class I measurements (44%), 1070 class II (34%) and 735 class III. Area under the receiver operating curve (AUROC) for severe fibrosis according to class (I, II and III) was 0.941, 0.887 and 0.766, respectively. For advanced fibrosis, AUROCs were 0.977, 0.883 and 0.781, respectively. Spearman's correlation testing for all classes and levels of fibrosis demonstrated significant independent association (r2 =-.95, P<.01). Our study is the first to propose measurable quality criteria for VTCE and to validate them against objective assessment of liver biopsy through digital morphometric imaging analysis. We concluded that VCTE performance is significantly influenced by quality assessment of individual measurements. Considering these criteria in clinical practice may improve accuracy.

Establishing ultrasound based transient elastography cutoffs for different stages of hepatic fibrosis and cirrhosis in Egyptian chronic hepatitis C patients

Background and study aimTransient elastography is widely used to assess fibrosis stage in chronic hepatitis C (CHC). We aimed to establish and validate different transient elastography cut-off values for significant fibrosis and cirrhosis in CHC genotype 4 patients. Patients and MethodsThe data of 100 treatment-naive CHC patients (training set) and 652 patients (validation set) were analysed. The patients were subjected to routine pretreatment laboratory investigations, liver biopsy and histopathological staging of hepatic fibrosis according to the METAVIR scoring system. Transient elastography was performed before and in the same week as liver biopsy using FibroScan (Echosens, Paris, France). Transient elastography results were correlated to different stages of hepatic fibrosis in both the training and validation sets. ResultsROC curves were constructed. In the training set, the best transient elastography cut-off values for significant hepatic fibrosis (≥F2 METAVIR), advanced hepatic fibrosis (≥F3 METAVIR) and cirrhosis (F4 METAVIR) were 7.1, 9 and 12.2 kPa, with sensitivities of 87%, 87.5% and 90.9% and specificities of 100%, 99.9% and 99.9%, respectively. The application of these cut-offs in the validation set showed sensitivities of 85.5%, 82.8% and 92% and specificities of 86%, 89.4% and 99.01% for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, respectively. ConclusionTransient elastography performs well for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, with validated cut-offs of 7.1, 9 and 12.2 kPa, respectively, in genotype 4 CHC patients.

Fibrogenic/Angiogenic Linker for Non-Invasive Assessment of Hepatic Fibrosis Staging in Chronic Hepatitis C Among Egyptian Patients

Background and rationale for the studyLiver biopsy is the golden standard for staging liver fibrosis, but it may be accompanied by complications. Because of this complication, the aim of this study is to evaluate a simple noninvasive score to assess hepatic fibrosis in chronic hepatitis C genotype 4 patients which is very may have an important in diagnosis and therapeutic decision. This score [HA vascular (HAV) score] is a combination of direct markers [hyaluronic acid (HA) and vascular endothelial growth factor (VEGF)] and indirect markers [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)]. ResultsSamples were collected from 220 patients (F0-F4): an estimated group (n = 120) and a validated group (n = 100). HA and VEGF levels, HCV RNA, liver function tests, platelet counts were assayed, Fibroscan was done and liver biopsy was taken and the stage of liver fibrosis and the grade of inflammatory activity was calculated according to Metavir score system. HA vascular (HAV) score = -35.1 + 0.14 (HA) (ng/L) + 0.03 (VEGF) (pg/mL) + (-6.7) [AAR (AST/ALT ratio)]. The HAV score produced areas under curve of 0.979 and 0.994 for significant (F2-F4) and advanced fibrosis (F3-F4) (cut off = 0.583 and 6.3, respectively). Surprisingly, the validation study of this score gave very good values of AUCs i.e. 0.990, 0.996 and 0.995 for significant, advanced and liver cirrhosis. ConclusionsOur developed score can not only help to assess liver fibrosis staging effectively but also avoid the invasiveness and the limitations of liver biopsy in Egyptian hepatitis C virus patients.

Fibrogenic/Angiogenic Linker for Non-invasive assessment of hepatic fibrosis staging in chronic hepatitis C genotype 4 patients

Fibrogenic/Angiogenic Linker for Non-invasive assessment of hepatic fibrosis staging in chronic hepatitis C genotype 4 patients

Transient elastography and APRI score: looking at false positives and false negatives. Diagnostic performance and association to fibrosis staging in chronic hepatitis C

Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis.

The Association among Serum Quantitative Hepatitis B Surface Antigen (qHBsAg), Intrahepatic HBV Markers and Liver Fibrosis in Chronic Hepatitis B (CHB) Patients

Background: Recently, quantitative HBsAg has been used as a predictor for successful antiviral therapy in chronic hepatitis B (CHB) patients. Intrahepatic HBV-DNA levels have also been tested to know their relevance with clinical manifestation. However, their associations with liver fibrosis are still debatable. Objective: This study was aimed to evaluate the association between serum qHBsAg, serum HBV-DNA, intrahepatic HBV markers and hepatic fibrosis in CHB patients. Method: A cross-sectional study was done on naive CHB patients from September 2009 to June 2011. Quantitative serum HBsAg measurement was performed using the automated chemiluminescent microparticle immunoassay (Architect HBsAg QT assay, Abbott Laboratories, IL, USA). Serum qHBsAg was measured using the automated chemiluminescent microparticle immunoassay (Architect HBsAg QT assay, Abbott Laboratories, IL, USA). Intrahepatic cccDNA was measured quantitatively from biopsy specimen (QiAmp DNA Mini Kit, Qiagen, Germany). Values were log-transformed before being analyzed. Biopsy specimens should include at least 5 portal systems and 1.5 cm length to be eligible for evaluation using the METAVIR score. Results: 103 patients enrolled; 53 (51.9%) of them were men. Mean age was 42+11.6 (range 19-70) years old. There were 60 (58.3%) patients with HbeAg negative. Mean of log serum quantitative HBsAg was 2.54 for F0-F1 patients vs. 3.48 for F2-F4 patients (p < 0.001, student t test). The mean log serum HBV-DNA was 4.65 for F0-F1 vs. 6.69 for F2-F4 patients (p < 0.001; student t test). Intrahepatic rcDNA levels was higher in F2-F4 (median 14.37; range 0-3258.4 copies/GEq) than F0-F1 patients (median 0.50; range 0-514.4 copies/GEq); p < 0.001 (Mann-Whitney U test). In contrast, virion productivity was not differed statistically between the two groups (p 0.096). Conclusion: Quantitative serum HbsAg, HBV-DNA serum, and intrahepatic cccDNA are associated with fibrosis stage in chronic hepatitis B patients. HBV seromarkers might be used to predict disease severity.

Diagnostic value of acoustic radiation force impulse imaging for evaluating the degree of liver fibrosis in chronic hepatitis B

Objective To investigate the clinical value of the acoustic radiation force impulse imaging (ARFI) in the quantitative evaluation of fibrosis staging in chronic hepatitis B. Methods A total of 373 patients with chronic hepatitis B were grouped in accordance with the depth of the right anterior lobe and posterior lobe of the liver and underwent ARFI to measure ARFI values. Liver biopsy was performed in all patients to investigate the relationship between liver fibrosis stages and ARFI values in different groups. Results The ARFI values in different pathological grades with the same depth of the right anterior and right posterior lobe of the liver were statistically significant (P<0.001); the ARFI values between the middle and deep parts of the right anterior lobe and the same location of the right posterior lobe were statistically significant (P<0.01); for the right anterior lobe, the ARFI value of the shallow part showed statistical significance from that of the middle and the deep part (P<0.05). Receiver operating characteristic (ROC) curve analysis for different sampling locations showed that the largest area under the ROC curve, which was 0.818, existed in the middle part of the right anterior lobe, indicating that it could be the optimal sampling location for the measurement of ARFI values. Liver stiffness at ARFI imaging was significantly correlated with liver fibrosis stage in chronic hepatitis B and spearman coefficient of correlation was 0.530 (P<0.001). The areas under the ROC curves for the chronic hepatitis B patients with severe liver fibrosis (≥S3) and early cirrhosis (=S4) were 0.818 and 0.860, respectively. Conclusions ARFI imaging was promising for clinical application and could be utilized as a noninvasive method for the quantitative evaluation of fibrosis staging in chronic hepatitis B. Key words: Ultrasonography; Hepatitis B, chronic; Liver cirrhosis; Acoustic radiation force impulse

Fibro-check: a combination of direct and indirect markers for liver fibrosis staging in chronic hepatitis C patients

Background and rationale for the study. The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decision. This study was concerned with determining the levels of collagen III and its degrading enzyme matrix metalloproteinase-1 (MMP-1) as direct and complementary markers for liver fibrosis staging.Results. A total of 269 chronic hepatitis C patients constituted this study. Western blotting was used for identifying collagen III and MMP-1 in serum samples. As a result, collagen III and MMP-1 were identified, respectively, at 70 and 245 kDa using their respective mono-specific antibodies. These two markers were quantified in sera of patients using ELISA. Next, Fibro-check was constructed combining collagen III and MMP-1 together with other indirect markers which reflect alteration in hepatic functions that proved useful to stage liver fibrosis. Fibro-check produced area under the receiver-operating characteristic curve (AUC) 0.91 and 0.83 for significant (F2-F4) and cirrhosis (F4), respectively. Additionally, we estimated the performance of Fibro-check in comparison with aspartate to platelet ratio index (APRI) and fibrosis index. Fibro-check seems to be more efficient than both of them. Fibro-check was then applied to the validation study to test its accuracy and reproducibility showing AUCs 0.90 for F2-F4 and 0.86 for F4.Conclusions. Fibro-check combining ‘direct’ and ‘indirect’ markers using a mathematical formula may improve the staging of liver fibrosis with a high degree of accuracy and seems more efficient than APRI and Fibrosis index in this group of Egyptian patients.

Association between vitamin D level and viral load or fibrosis stage in chronic hepatitis B patients from Southern China

The role of vitamin D playing in patients with chronic hepatitis C has been intensively studied. However, studies on the potential interaction between vitamin D level and chronic hepatitis B are still limited. This study aimed to explore whether any association existed between serum vitamin D level and liver histology or virological parameters in patients with chronic hepatitis B infection in Southern China. 25-Hydroxyvitamin D serum levels were determined in a cohort of 242 treatment-naïve chronic hepatitis B patients. Histologic assessment was based on Knodell histologic activity index and Ishak fibrosis staging. Predictors of vitamin D insufficiency were identified using multivariate analysis. Mean 25-hydroxyvitamin D value was 33.90 ng/mL. The percentage of patients with different concentration of 25-hydroxyvitamin D (≥ 30 ng/mL, 20-30 ng/mL, < 20 ng/mL) were 59.9%, 31.4%, and 8.7%, respectively. Gender, season, age, and viral genotype were independent predictors of vitamin D insufficiency (< 30 ng/mL). Patients with genotype B virus infection had a lower mean 25-hydroxyvitamin D level (P = 0.023) and higher prevalence of vitamin D insufficiency than those with genotype C (P = 0.021), while no association was found between vitamin D status and viral load. In addition, 25-hydroxyvitamin D level did not significantly vary according to activity grade or fibrosis stage. The prevalence of vitamin D insufficiency is relatively low in our cohort. Patients infected with genotype B had a higher prevalence of vitamin D insufficiency than genotype C. 25-Hydroxyvitamin D serum level is not associated with viral load or fibrosis stage in chronic hepatitis B patients.