Significant Fibrosis In Chronic Hepatitis Research Articles

Prevalence and risk factors of significant fibrosis in chronic hepatitis B patients with concurrent metabolic dysfunction-associated steatotic liver disease

Introduction and objectivesSignificant fibrosis is an indicator of clinical intervention for both chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD). There remains a paucity of data regarding the clinical impact of biopsy-defined MASLD on significant fibrosis in CHB patients. The current study aims to elucidate whether patients with concomitant MASLD are at higher risk of significant fibrosis in patients with CHB. Patients and methodsThis retrospective research of two tertiary hospitals comprised 1818 patients between 2009 and 2021 with CHB and hepatic steatosis who had not received antiviral therapy. Pathologic findings by liver biopsy were contrasted between CHB group (n = 844) and CHB + MASLD (n = 974) group. METAVIR values of F≥2 were used to categorize significant fibrosis. ResultsPatients with CHB + MASLD had more significant fibrosis (35.5 % vs. 23.5 %, p < 0.001) than CHB group. The presence of MASLD [adjusted odds ratio (aOR) 2.055, 95 % confidence interval (CI) 1.635–2.584; p < 0.001] was strongly associated with significant fibrosis in all CHB patients. There was a trend for patients with more cardiometabolic risk factors (CMRFs) to have a higher prevalence of significant fibrosis: (25.7 % in CMRF1 subgroup v.s. 34.9 % in CMRF2 subgroup v.s. 53.7 % in CMRF≥ 3 subgroup, p < 0.001). Patients with CMRF≥3 had a three-fold higher significant fibrosis than those with just one CMRF. ConclusionsMASLD was associated with higher fibrosis stage in patients with CHB. Early detection and intervention are crucial to patients with three or more cardiometabolic risk factors.

The Reduced Accuracy of Non-invasive Tests for Significant Fibrosis in Chronic Hepatitis B Patients with Metabolic Dysfunction-associated Steatotic Liver Disease.

The Reduced Accuracy of Non-invasive Tests for Significant Fibrosis in Chronic Hepatitis B Patients with Metabolic Dysfunction-associated Steatotic Liver Disease.

Diagnostic Accuracy of Red Cell Distribution Width to Platelet Ratio for Detection of Liver Fibrosis Compared with Fibroscan in Chronic Hepatitis B Egyptian patients

Background and Aims: The decision to treat chronic hepatitis B Virus infection (CHB) may necessitate an assessment of the degree of liver fibrosis. Guidelines recommend Fibroscan examination in such cases. However, it is costly and not widely available. Red cell distribution width (RDW) and platelet count are simple parameters obtained from the blood pictures; and their ratio RDW to platelet ratio (RPR) was claimed to correlate with liver fibrosis. We aimed to assess the ability of RPR to replace the costly fibroscan in the detection of significant fibrosis in chronic hepatitis B patients. Patients and Methods: This cross-sectional study was conducted in the Tropical medicine department, Tanta University, Egypt, between December 2018 and September 2019. One hundred and twenty-five patients with CHB were included and divided according to the fibroscan examination into: Group I: patients with no significant fibrosis (n=66), Group II: patients with significant (≥ F2) fibrosis (n=59). RPR was calculated for all patients and tested against Fibroscan results. Results: Both groups were matched in regards to age, sex, viral load, and steatosis. There was a significant positive correlation between the degree of stiffness measured by FibroScan in patients with a significant degree of fibrosis and serum bilirubin, a quantitative polymerase chain reaction of hepatitis B virus DNA (HBV DNA PCR), and fibrosis-4 score (FIB-4 score) (P value= 0.020, 0.049, and 0.0402, respectively). However, RPR was not correlated to the degree of fibrosis in fibroscan examination. Conclusions: The accuracy of RDW to platelet ratio (RPR) for the detection of fibrosis in CHB patients is questionable. FIB-4 is correlated with liver stiffness measurement (LSM) in patients with significant fibrosis (F2 or more). Neither RPR, AST to Platelet Ratio Index (APRI) or FIB4 can replace fibroscan for grading of fibrosis in CHB patients for evaluation to start therapy.

To determine the diagnostic accuracy of aspartate aminotransferase to platelet ratio index in detecting significant fibrosis in chronic hepatitis C patients by using histopathology as gold standard.

Objective: The objective of the study was to: determine the diagnostic accuracy of AST to platelet ratio index in detecting significant fibrosis in chronic hepatitis C patients by using histopathology as gold standard. Study Design: Cross Sectional study. Settings: Department of Medicine, DHQ Hospital, Faisalabad. Period: 1st Oct 2017 to March 2018. Results: In this study, out of 158 cases, 48.73%(n=77) were between 25-40 years while 51.27%(n=81) were between 41-60 years, mean+SD was calculated as 40.94+9.10 years, 55.06%(n=87) were male and 44.94%(n=71) were females, mean AST and platelet count was calculated as 1.68+0.54 and 191.0+43.75, frequency of significant fibroids in chronic hepatitis C patients by using histopathology as gold standard reveals as 53.16%(n=84) while 46.84%(n=74) had no findings of this morbidity. The diagnostic accuracy of AST to platelet ratio index in detecting significant fibrosis in chronic hepatitis C patients by using histopathology as gold standard was recorded which shows 51.27%(n=81) as true positive, 2.53%(n=4) false positive, 1.89%(n=3) false negative and 44.31%(n=70) were recorded as true negative, sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate was computed as 96.43%, 94.59%, 95.29%, 95.89% and 95.57% respectively. Conclusion: The results of the study reveal that diagnostic accuracy of AST to platelet ratio for detection of significant fibrosis in chronic Hepatitis C patients was satisfactory and it may be used for the avoidance of invasive liver biopsy to initiate the antiviral therapy in these patients.

The Importance of Serum Leptin Level in Chronic Viral Hepatitis B and C

OBJECTIVE: Leptin plays an important role in inflammation and liver fibrogenesis in viral liver diseases. In this study, determination of serum leptin level and the effect of leptin levels on liver inflammation and fibrosis in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) cases were evaluated.MATERIALS AND METHODS: In this prospective clinical research study, a total of 75 CHB patients, 36 CHC patients, and a 51 control group were included. Liver biopsy specimens were scored using Ishak histological scoring system. Serum leptin levels were determined by ELISA method.RESULTS: Overall, 39 of CHB cases were female while 36 was male, there were 18 female and 18 male cases of CHC, while the control group consisted of 26 female and 25 male. Serum leptin levels were statistically significantly higher in CHB (2.81±0.38) and CHC (2.97±0.35) cases than in the control group (1.39±0.08) (p: 0.001). However, there was no statistically significant difference in serum leptin level between CHC and CHB cases. There was no statistically significant difference between serum leptin levels and age, gender, and biochemical parameters (P&amp;gt; 0.05). Serum leptin levels were statistically significantly higher in patients with significant fibrosis in chronic hepatitis B and KHC patients compared to those with mild fibrosis (P&amp;lt;0.05).CONCLUSION: Leptin plays a role in liver inflammation and fibrosis in CHB and CHC. In CHB and CHC patients, leptin levels can be used to evaluate the degree of advanced fibrosis and in clinical follow-up, but larger studies are needed.

Alanine aminotransferase influencing performances of routine available tests detecting hepatitis B-related cirrhosis.

The performances of routine tests such as FIB-4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width-platelet ratio (RPR), γ-glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut-offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB-4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was∝for APRI cut-off 2 diagnosing cirrhosis in ALT<2 upper limit of normal (ULN), 14.6 for APRI cut-off 1.5 determining significant fibrosis in ALT≤5ULN and 20.6 for FIB-4 cut-off 3.2 diagnosing≥F3 in the total cohort, respectively. The optimal cut-offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut-offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut-offs may be a preferred alternative. In resource-limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.

Limitations of non-invasive tests for assessment of liver fibrosis.

SummaryThe diagnostic assessment of liver injury is an important step in the management of patients with chronic liver disease (CLD). Although liver biopsy is the reference standard for the assessment of necroinflammation and fibrosis, the inherent limitations of an invasive procedure, and need for repeat sampling, have led to the development of several non-invasive tests (NITs) as alternatives to liver biopsy. Such non-invasive approaches mostly include biological (serum biomarker algorithms) or physical (imaging assessment of tissue stiffness) assessments. However, currently available NITs have several limitations, such as variability, inadequate accuracy and risk factors for error, while the development of a newer generation of biomarkers for fibrosis may be limited by the sampling error inherent to the reference standard. Many of the current NITs were initially developed to diagnose significant fibrosis in chronic hepatitis C, subsequently refined for the diagnosis of advanced fibrosis in patients with non-alcoholic fatty liver disease, and further adapted for prognostication in CLD. An important consideration is that despite their increased use in clinical practice, these NITs were not designed to reflect the dynamic process of fibrogenesis, differentiate between adjacent disease stages, diagnose non-alcoholic steatohepatitis, or follow longitudinal changes in fibrosis or disease activity caused by natural history or therapeutic intervention. Understanding the strengths and limitations of these NITs will allow for more judicious interpretation in the clinical context, where NITs should be viewed as complementary to, rather than as a replacement for, liver biopsy.

SHFI: A Novel Noninvasive Predictive Model for Significant Fibrosis in Patients With Chronic Hepatitis B

Background: This study aimed at creating a new predictive model of significant fibrosis in chronic hepatitis B using direct and indirect parameters and comparing this model with other noninvasive models for its validation in clinical settings. Methods: Patients (n = 81), according to the ISHAK score, were classified as mild and significant fibrosis. Serum matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-2, beta-nerve growth factor levels, and indirect parameters were analyzed. To evaluate the presence of significant hepatic fibrosis, well-known conventional models were also evaluated. The cut-off values of each model were determined using receiver operating characteristic curves to distinguish patients with mild and significant fibrosis. Results: Significant hepatic fibrosis index-1 was constructed using the following equation: (matrix metalloproteinase-2 × age × prothrombin time × direct bilirubin) / (albumin × platelet). The sensitivity and specificity for significant hepatic fibrosis index-1 were 73.3% and 95.6%, respectively. Area under the curve of significant hepatic fibrosis index-1 was 0.895 (P < 0.001), which was higher than the other models. Due to limitations of matrix metalloproteinase-2, significant hepatic fibrosis index-2 was constructed using a formula without matrix metalloproteinase-2. However, there were no significant differences between significant hepatic fibrosis index-1 and significant hepatic fibrosis index-2 or other models, except for 3 models. Conclusions: Significant hepatic fibrosis index-1 employs a new marker; matrix metalloproteinase-2 along with routine parameters had the best diagnostic performance for significant fibrosis in patients with chronic hepatitis B. Using significant hepatic fibrosis index-1 or even significant hepatic fibrosis index-2 might be an alternative approach in place of liver biopsy to predict significant fibrosis in chronic hepatitis B cohort.

Fibrosis assessment using FibroMeter combined to first generation tests in hepatitis C.

AIMTo evaluate the performance of FibroMeterVirus3G combined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC).METHODSFirst generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G combination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C.RESULTSSeven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeterVirus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P < 0.001). The best FibroMeterVirus3G cut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population, P = 0.134). The sequential combination of APRI or Forns with FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G used alone (79% vs 78% vs 80%, respectively, P = 0.791). Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49% and 54%, respectively, of the total sample. However, the combination of APRI or Forns with FibroMeterVirus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3).CONCLUSIONThe stepwise combination of APRI or Forns with FibroMeterVirus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.

Serum soluble urokinase-type plasminogen activator receptor and interferon-γ-induced protein 10 levels correlate with significant fibrosis in chronic hepatitis B.

Hepatitis B virus (HBV) presents an important public health problem. Liver biopsy is currently the gold standard for assessing the degree of intrahepatic inflammation and for staging liver fibrosis. However, the value of liver biopsies is limited by sampling errors, understaging and interobserver variability in interpretation. There is, therefore, a need to identify novel, non-invasive serologic biomarkers for the development of new predictive models of fibrosis. We enrolled patients with chronic hepatitis B infection (CHB) and examined the relationships between serum soluble urokinase plasminogen activator receptor (suPAR) and interferon-induced protein-10 (IP-10), and the results of liver biopsies. Healthy volunteers with normal aminotransferase levels and negative serological results for HBV, hepatitis C virus and human immunodeficiency virus were recruited as controls. Mean platelet volume, serum suPAR and IP-10 were significantly elevated in patients with CHB compared with controls. Median serum suPAR and IP-10 levels were significantly higher in patients with liver fibrosis compared with patients with mild fibrosis. There was no significant difference in mean platelet volume or aspartate aminotransferase-to-platelet ratio index scores between patients with mild and significant fibrosis. suPAR and IP-10 were able to distinguish between significant and mild fibrosis with good sensitivity and specificity, and may thus represent useful biomarkers for identifying patients with significant fibrosis.

Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients.

Background and AimDetection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as potential biomarkers for clinically significant and advanced fibrosis.MethodsSpecific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy.ResultsPro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p<0.05), while the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (p<0.05). C1M showed no difference between fibrosis stages. Using Receiver Operating Characteristics analysis, the best marker for detecting ≥F2 and ≥F3 was Pro-C3 with AUC = 0.75 and AUC = 0.86. Combination of Pro-C3 and C4M with age, BMI and gender in a multiple ordered logistic regression model improved the diagnostic value for detecting ≥F2 and ≥F3 with AUC = 0.80 and AUC = 0.88.ConclusionThe Pro-C3 protein fragment provided clinically relevant diagnostic accuracy as a single marker of liver fibrosis. A model combining Pro-C3 and C4M along with patient’s age, body mass index and gender increased the diagnostic power for identifying clinically significant fibrosis.

A Scoring System for Predicting Significant Fibrosis in Chronic Hepatitis B Patients With Normal or Mildly Elevated Alanine Aminotransferase Levels

We aimed to develop a clinically useful scoring system to predict the probability of significant fibrosis (the Scheuer score ≥S2) in patients with chronic hepatitis B infection (CHB) and alanine aminotransferase (ALT) levels 2-fold lower than the upper limit of normal (ULN), in order to facilitate the clinical decision to perform a subsequent liver biopsy. Consecutive subjects who underwent percutaneous liver biopsy were examined. The predictors evaluated included demographic, clinical, and laboratory variables. A clinical scoring system was developed by rounding the estimated regression coefficients for the independent predictors in multivariate logistic models for the diagnosis of significant fibrosis. A total of 283 patients with ALT levels 2-fold lower than the ULN were divided into 2 groups to develop (n=190) and validate (n=93) the scoring system. Of the 190 subjects examined, 52 (27.4%) had significant fibrosis. Aspartate transferase levels, platelet counts, and hepatitis B surface antigen levels were independently associated with significant liver fibrosis. A fibrosis clinical scoring system comprising these 3 variables in CHB patients with ALT levels 2-fold lower than the ULN was developed to predict the probability of significant fibrosis in 4 categories (low, intermediate, high, and very high risk). The proposed fibrosis scoring system predicted the probability of significant fibrosis in CHB patients with ALT levels 2-fold lower than the ULN with sufficient accuracy. It identified individuals with a very high risk for significant fibrosis in whom liver biopsy would most likely yield a diagnostic benefit. It also identified individuals with a low risk of moderate fibrosis in whom a liver biopsy can be delayed or avoided.

Contribution of the ELFG Test in Algorithms of Non-Invasive Markers towards the Diagnosis of Significant Fibrosis in Chronic Hepatitis C

Background and AimsWe aimed to determine the best algorithms for the diagnosis of significant fibrosis in chronic hepatitis C (CHC) patients using all available parameters and tests.Patients and MethodsWe used the database from our study of 507 patients with histologically proven CHC in which fibrosis was evaluated by liver biopsy (Metavir) and tests: Fibrometer®, Fibrotest®, Hepascore®, Apri, ELFG, MP3, Forn's, hyaluronic acid, tissue inhibitor of metalloproteinase-1 (TIMP1), MMP1, collagen IV and when possible Fibroscan™. For the first test we used 90% negative predictive value to exclude patients with F≤1, next an induction algorithm was applied giving the best tests with at least 80% positive predictive value for the diagnosis of F≥2. The algorithms were computed using the R Software C4.5 program to select the best tests and cut-offs. The algorithm was automatically induced without premises on the part of the investigators. We also examined the inter-observer variations after independent review of liver biopsies by two pathologists. A medico-economic analysis compared the screening strategies with liver biopsy.ResultsIn “intention to diagnose” the best algorithms for F≥2 were Fibrometer ®, Fibrotest®, or Hepascore® in first intention with the ELFG score in second intention for indeterminate cases. The percentage of avoided biopsies varied between 50% (Fibrotest® or Fibrometer®+ELFG) and 51% (Hepascore®+ELFG). In “per-analysis” Fibroscan™+ELFG avoided liver biopsy in 55% of cases. The diagnostic performance of these screening strategies was statistically superior to the usual combinations (Fibrometer® or Fibrotest®+Fibroscan™) and was cost effective. We note that the consensual review of liver biopsies between the two pathologists was mainly in favor of F1 (64–69%).ConclusionThe ELFG test could replace Fibroscan in most currently used algorithms for the diagnosis of significant fibrosis including for those patients for whom Fibroscan™ is unusable.

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

ObjectiveWe determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients.MethodsFrom 1994 to 2008, liver biopsy was performed on 319 treatment-naïve CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis.Results211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading ≥7 or fibrosis score ≥3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1–2×upper limit of normal (ULN) and >×2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease.ConclusionAn elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.

Diagnostic value of multiple biomarker panel for prediction of significant fibrosis in chronic hepatitis C

Objectives Whether new biomarkers contribute significantly to the existing, simple noninvasive test (comprising of routine laboratory parameters such as the AST to platelet ratio index (APRI)) for predicting liver fibrosis remains unknown. Methods We measured 7 biomarkers in 91 patients with chronic hepatitis C (CHC): haptoglobin, apolipoprotein A1, α2-macroglobulin, hyaluronic acid, type III procollagenic peptide, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinase-1. Results The “multibiomarker” score (based on regression coefficients of significant biomarkers) is an independent predictive factor for significant fibrosis [APRI-adjusted odds ratio, 2.41 (95% CI, 1.28 to 4.55)]. However, the incorporation of the multibiomarker score into the APRI resulted in only a small diagnostic improvement [0.83 (95% CI, 0.74 to 0.92) vs. 0.79 (0.69 to 0.89); p = 0.19]. Conclusions For assessing significant fibrosis in individual CHC patients, the 7 contemporary biomarkers that we studied add only modestly to the readily available, simple noninvasive index.

A New Model Using Routinely Available Clinical Parameters to Predict Significant Liver Fibrosis in Chronic Hepatitis B

ObjectiveWe developed a predictive model for significant fibrosis in chronic hepatitis B (CHB) based on routinely available clinical parameters.Methods237 treatment-naïve CHB patients [58.4% hepatitis B e antigen (HBeAg)-positive] who had undergone liver biopsy were randomly divided into two cohorts: training group (n = 108) and validation group (n = 129). Liver histology was assessed for fibrosis. All common demographics, viral serology, viral load and liver biochemistry were analyzed.ResultsBased on 12 available clinical parameters (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP, GGT and AFP), a model to predict significant liver fibrosis (Ishak fibrosis score ≥3) was derived using the five best parameters (age, ALP, AST, AFP and platelet). Using the formula log(index+1) = 0.025+0.0031(age)+0.1483 log(ALP)+0.004 log(AST)+0.0908 log(AFP+1)−0.028 log(platelet), the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index predicts significant fibrosis with an area under the receiving operating characteristics (AUROC) curve of 0.776 [0.797 for patients with ALT <2×upper limit of normal (ULN)] The negative predictive value to exclude significant fibrosis was 88.4%. This predictive power is superior to other non-invasive models using common parameters, including the AST/platelet/GGT/AFP (APGA) index, AST/platelet ratio index (APRI), and the FIB-4 index (AUROC of 0.757, 0.708 and 0.723 respectively). Using the PAPAS index, 67.5% of liver biopsies for patients being considered for treatment with ALT <2×ULN could be avoided.ConclusionThe PAPAS index can predict and exclude significant fibrosis, and may reduce the need for liver biopsy in CHB patients.

Prediction of Significant Fibrosis in Chronic Hepatitis C Patients with Normal ALT

Prediction of significant fibrosis (F=2) using non-invasive methods for chronic hepatitis C (CHC) patients with persistently normal alanine aminotransferase (PNALT) levels remains a challenging problem. We aimed to develop a novel non-invasive model for predicting the presence of significant fibrosis in CHC patients with PNALT. We prospectively enrolled 40 treatment-naïve CHC patients with PNALT who underwent liver biopsy and liver stiffness measurements (LSM). Age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), LSM and LSM to platelet ratio index (LPRI) were compared with liver histology results. Significant fibrosis was diagnosed in 17 patients (42.5%). The diagnostic accuracy of LPRI was the highest for the prediction of significant fibrosis (AUROC = 0.859) when compared to that of APRI (0.770), LSM (0.769) and API (0.703). Using a cutoff value of LPRI =37, the significant fibrosis could be correctly identified with high accuracy (100% PPV) in 6 (15.0%) patients. While, using an LPRI cutoff value <20, it could be excluded with 94.1% NPV in 17 (42.5%) patients. Consequently, 57.5% of the CHC patients with PNALT levels could avoid liver biopsy. The LPRI was useful in predicting significant fibrosis. Screening CHC patients PNALT using LPRI has the potential to reduce the number of liver biopsies and might help designing appropriate management plans.

Usefulness of Multiple Biomarkers for the Prediction of Significant Fibrosis in Chronic Hepatitis B

It has not been explicitly addressed whether new biomarkers, in addition to readily available clinical data, make a contribution to the prediction of liver fibrosis. A total of 209 patients with chronic hepatitis B who underwent liver biopsy were recruited. The Clinical Score (CS) model using only routine clinical data and the Biomarker Score (BS) model using 7 putative biomarkers were derived from the derivation set (n=105), and these models were applied to a separate patients group (n=104) to investigate whether the addition of BS improved the diagnostic accuracy in predicting significant fibrosis beyond an assessment based solely on CS. The most informative biomarkers for predicting significant fibrosis were hyaluronic acid and matrix metalloproteinase-2. The BS was an independent predictive factor for significant fibrosis even after accounting for CS in both sets. Among the derivation set, the incorporation of the BS into the CS model did not significantly increase the receiver operating characteristic area, with only a small improvement of about 2% (P=0.11). Similarly, in the validation set, a combined model with CS and BS showed no superior diagnostic accuracy over the CS model alone, with an improvement of approximately 2% [0.83 (0.75 to 0.92) vs. 0.81 (0.70 to 0.91); P=0.16]. The simultaneous addition of several biomarkers adds only modestly to clinical predictive factors for risk assessment of individual patients. These results highlight the need for the models to be validated in another cohort with a broader distribution of fibrosis severity.

T1957 Utility of Serum Fibrosis Marker to Screen Significant Fibrosis in Patients With Chronic Hepatitis; New Scoring System Consisted of Type IV Collagen and AP Index

(Backgrounds)To detect significant fibrosis in chronic hepatitis is important to determine the timing of treatment intervention. Liver biopsy is still a gold standard until now, though it is quite invasive. In this study, we evaluate the utility of some laboratory tests and indeces that are related to liver fibrosis and found new formulas that is considered to be more effective than previously reported indeces and proposed as one of the noninvasive and easy diagnostic tool. (Patients and Methods) 95 patients with chronic hepatitis who have also done liver biopsy were included in this study. We evaluated the relationship between significant fibrosis (Metavir score≧2) and age, sex, serum AST, ALT, γGTP, hyaruronan, Procollagen-III-peptide (P-III-P), type IV collagen, platelet counts (Plt) as single serum marker, and AST/ALT ratio (AAR), AP index, and AST to platelet ratio index (APRI) as fibrosis indeces. In univariate analysis, Students' t-test was applied in continuous values and Chi-square test was applied in categorical values. In multivariate analysis, logistic regression analysis was done. P<0.05 was considered as statistically significant. And to evaluate the utility of new diagnostic index, ROC analysis was done and AUROCwas evaluated. (Results)In univariate analysis, higher age (p=0.0067), higher AST (p=0.0073), higher hyaruronan (p= 0.0015), higher P-III-P (p<0.0001), higher type IV collagen (p<0.0001), lower Plt (p<0.0001),higher AP index (p<0.0001), and higher APRI (p<0.0001) was selected, and in multivariate analysis, Type IV collagen (p=0.0360) and AP index (p=0.0106) were selected as significant factors. Then we made new scoring system consisted of type IV collagen (≧150:1point,<150:0point) and AP index (≧6: 1 point, <6: 0 point). AUROC of this new score was 0.834. Score 2 points predicted 86.7% (26/30) of patients with significant fibrosis and Score 0 ruled out 96.9% (31/32) of patients with mild fibrosis. (Conclusions)This new diagnostic score consisted of routine laboratory test might be one of the effective and convenient tools to determine the indication of liver biopsy that is quite invasive for the patients, and the timing of treatment intervention in patients with chronic hepatitis.

Prospective validation of a non-invasive index for predicting liver fibrosis in hepatitis C virus-infected liver transplant recipients

We read with interest the article by Benlloch et al. regarding the use of the Hospital Universitario La Fe index for the prediction of significant fibrosis in chronic hepatitis C (CHC)–infected liver transplant recipients. However, the complexity of the calculation is likely to limit its utility, as this is not something that can easily be committed to memory or calculated in a busy clinic. Furthermore, the authors have failed to integrate the frequency of each fibrosis stage into the model. It is known that different fibrosis-stage frequencies can skew the area under the receiver operating characteristic curve (AUROC) and thereby influence the accuracy of such tests. This factor leads to differences in the AUROC when the accuracy of a noninvasive test is being assessed in different study populations. Therefore, for such studies, standardization of the AUROC is imperative, and it should be calculated to correct for this with the method described by Poynard and colleagues. Alternatives to the Hospital Universitario La Fe index are available for posttransplant hepatitis C patients. An initial study of 602 nontransplant patients with CHC gave rise to the King’s score, which uses the following simple parameters: the patient’s age, aspartate aminotransferase level, platelet level, and international normalized ratio. Subsequently, we applied this test to the setting of liver transplantation and analyzed retrospectively 185 patients who underwent liver transplantation for CHC. The median age of the study group was 53 years, and 76% of the patients were male. The test had to be modified to incorporate the time from liver transplant in place of patient age. We called the modified test the London Transplant Centres’ score. The method described by Ishak was used for histological analysis. The AUROCs for Ishak stages F2, F3, F4, and F5-F6 were 0.78, 0.82, 0.8, and 0.8, respectively. The London Transplant Centres’ score awaits validation and prospective study, but it compared well with the initial retrospective study performed by Benlloch and colleagues. However, the histological methods applied were different in Valencia and London, so direct comparisons between the tests are problematic. At a cutoff of 6.3, the test distinguished patients with mild or no fibrosis with a sensitivity of 88%, a specificity of 60%, a negative predictive value of 67%, and a positive predictive value of 84%. The authors contend that the role of noninvasive markers of liver fibrosis, particularly in CHC patients post–liver transplantation, is likely to become an area of increasing interest. Future studies are needed to determine which test, alone or in combination, is likely to be of greatest value to patients.