Significant Fibrosis In Patients Research Articles

Clinical predictive score for detecting nonalcoholic fatty liver disease with significant fibrosis in patients with metabolic syndrome.

Patients with metabolic syndrome are at a higher risk of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis than the general population. Still, accessibility of screening method for NAFLD with significant fibrosis, such as transient elastography (FibroScan) are limited in some settings. This study aimed to develop a simple clinical predictive score for detecting NAFLD with significant fibrosis in patients with metabolic syndrome.A cross-sectional study was designed to obtain the data from medical records of all relevant patients who underwent transient elastography between January 2011 and December 2020 at Siriraj Hospital, Thailand. A liver stiffness cutoff value of 7.0 kilopascal was used to define the presence of significant liver fibrosis. To examine potential predictors, medical history and clinical data commonly assessed in routine practice were selected by following expert opinions and univariable statistical analysis. Backward and forward stepwise logistic regression was performed to acquire a final prediction model. To simplify the model, a weighted score was assigned for each categorized predictor. In addition, eligible cutoff values of the score and their predictive performances were determined.A total of 745 medical records were reviewed. The prevalence of NAFLD with significant fibrosis in patients with metabolic syndrome was 12.6%. Most clinical characteristics of patients with NAFLD with significant fibrosis and those non-NAFLD and NAFLD with no/mild fibrosis were quite disparate. The most practical model comprised globulin, aspartate transaminase, platelet count, and type 2 diabetes. It provided a good predictive performance with an area under the receiver operating characteristic curve of 0.828 (95% confidence interval [CI]: 0.782, 0.874). At the proper cutoff value, sensitivity and specificity were 76.6% (95% CI: 66.7%, 84.7%) and 72.4% (95% CI: 68.7%, 75.8%), respectively. The likelihood ratio of testing positive for NAFLD with significant fibrosis was 2.8 (95% CI: 2.34, 3.27) among patients with scores above the cutoff value.The first score for detecting of NAFLD with significant fibrosis in patients with metabolic syndrome was developed. This practical score, providing a good predictive performance, should be useful to help clinicians prioritize needs for further investigations among high-risk patients, especially in resource-limited settings.

P-32 EVALUATION OF HEPATIC FIBROSIS THROUGH NON-INVASIVE METHODS IN PATIENTS WITH CHRONIC VIRAL HEPATITIS B AND C

Biopsy has been considered the method of choice for staging fibrosis in liver disease. However, as it is an invasive method subject to sampling errors and morbidity, new non-invasive methods have been proposed for the assessment of liver fibrosis. To evaluate and compare serum fibrosis biomarkers (APRI and FIB4) with transient liver elastography (THE), gold standard in this study in patients with chronic viral hepatitis B and C. Cross-sectional study of patients with chronic hepatitis B or C virus undergoing THE. The patients were evaluated using serum liver fibrosis markers APRI and FIB4. The degree of fibrosis ≥ 2 of the Metavir classification was defined as significant fibrosis. The diagnostic performance of both methods was calculated and compared using the ROC curve (AUROC). The study included 73 patients, 50 with HBV and 23 with HCV; 50.7% were female, mean age 48.6 ± 13.3 years. Significant fibrosis was observed in 31 patients. The accuracy of serum markers in the diagnosis of liver fibrosis was determined by AUROC, APRI 0.79 and FIB4 0.76 (P = .0.42); PPV and NPV APRI 91.7% and 76.9% respectively; FIB4, PPV = 87.5% and NPV = 77.8%. The study demonstrated that there was no difference in diagnostic performance between the APRI and FIB4 methods, which were considered tests with good accuracy in the diagnosis of significant fibrosis in patients with chronic viral hepatitis.

The LAC Score Indicates Significant Fibrosis in Patients With Chronic Drug-Induced Liver Injury: A Large Biopsy-Based Study.

Currently, there are no satisfactory noninvasive methods for the diagnosis of fibrosis in patients with chronic drug-induced liver injury (DILI). Our goal was to develop an algorithm to improve the diagnostic accuracy of significant fibrosis in this population. In the present study, we retrospectively investigated the biochemical and pathological characteristics of consecutive patients with biopsy-proven chronic DILI, who presented at our hospital from January 2013 to December 2017. A noninvasive algorithm was developed by using multivariate logistic regression, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) to diagnose significant fibrosis in the training cohort, and the algorithm was subsequently validated in the validation cohort. Totally, 1,130 patients were enrolled and randomly assigned into a training cohort (n = 848) and a validation cohort (n = 282). Based on the multivariate analysis, LSM, CHE, and APRI were independently associated with significant fibrosis. A novel algorithm, LAC, was identified with the AUROC of 0.81, which was significantly higher than LSM (AUROC 0.78), CHE (AUROC 0.73), and APRI (AUROC 0.68), alone. The best cutoff value of LAC in the training cohort was 5.4. When the LAC score was used to diagnose advanced fibrosis and cirrhosis stages, the optimal cutoff values were 6.2 and 6.7, respectively, and the AUROC values were 0.84 and 0.90 in the training cohort and 0.81 and 0.83 in the validation cohort. This study proved that the LAC score can contribute to the accurate assessment of high-risk disease progression and the establishment of optimal treatment strategies for patients with chronic DILI.

Diagnostic value of magnetic resonance parametric mapping for non-invasive assessment of liver fibrosis in patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by bile duct inflammation and destruction, leading to biliary fibrosis and cirrhosis. The purpose of this study was to investigate the utility of T1 and T2 mapping parameters, including extracellular volume fraction (ECV) for non-invasive assessment of fibrosis severity in patients with PSC.MethodsIn this prospective study, patients with PSC diagnosis were consecutively enrolled from January 2019 to July 2020 and underwent liver MRI. Besides morphological sequences, MR elastography (MRE), and T1 and T2 mapping were performed. ECV was calculated from T1 relaxation times. The presence of significant fibrosis (≥ F2) was defined as MRE-derived liver stiffness ≥ 3.66 kPa and used as the reference standard, against which the diagnostic performance of MRI mapping parameters was tested. Student t test, ROC analysis and Pearson correlation were used for statistical analysis.Results32 patients with PSC (age range 19–77 years) were analyzed. Both, hepatic native T1 (r = 0.66; P < 0.001) and ECV (r = 0.69; P < 0.001) correlated with MRE-derived liver stiffness. To diagnose significant fibrosis (≥ F2), ECV revealed a sensitivity of 84.2% (95% confidence interval (CI) 62.4–94.5%) and a specificity of 84.6% (CI 57.8–95.7%); hepatic native T1 revealed a sensitivity of 52.6% (CI 31.7–72.7%) and a specificity of 100.0% (CI 77.2–100.0%). Hepatic ECV (area under the curve (AUC) 0.858) and native T1 (AUC 0.711) had an equal or higher diagnostic performance for the assessment of significant fibrosis compared to serologic fibrosis scores (APRI (AUC 0.787), FIB-4 (AUC 0.588), AAR (0.570)).ConclusionsHepatic T1 and ECV can diagnose significant fibrosis in patients with PSC. Quantitative mapping has the potential to be a new non-invasive biomarker for liver fibrosis assessment and quantification in PSC patients.

Magnetic resonance quantitative susceptibility mapping in the evaluation of hepatic fibrosis in chronic liver disease: a feasibility study.

Noninvasive methods for the early diagnosis and staging of hepatic fibrosis are needed. The present study aimed to investigate the alteration of magnetic susceptibility in the liver of patients with various fibrosis stages and to evaluate the feasibility of using susceptibility to stage hepatic fibrosis. A total of 30 consecutive patients with chronic liver diseases (CLDs) underwent magnetic resonance imaging (MRI) and liver biopsy evaluation of hepatic fibrosis, necroinflammatory activity, iron load, and steatosis. Quantitative susceptibility mapping (QSM), R2* and proton density fat fraction (PDFF) images were postprocessed from the same gradient-echo data for quantitative tissue characterization using region of interest (ROI) analysis. The differences for MRI measurements between cohorts of non-significant (Ishak-F <3) and significant fibrosis (Ishak-F ≥3) and the correlation of MRI measurements with fibrosis stages and necroinflammatory activity grades were tested. Receiver operating characteristic (ROC) analysis was also performed. There was a significant difference in liver susceptibility between the cohorts of significant and non-significant fibrosis (Z=-2.880, P=0.004). A moderate negative correlation between the stages of liver fibrosis and liver susceptibility was observed (r=-0.471, P=0.015). Liver magnetic susceptibility differentiated non-significant from significant hepatic fibrosis with an area under the receiver operating curve (AUC) of 0.836 (P=0.004). A highly sensitive diagnostic performance with an AUC of 0.933 was obtained using magnetic susceptibility and PDFF together (P<0.001). A noninvasive liver QSM-based evaluation promises an accurate assessment of significant fibrosis in patients with CLDs.

Evaluation of red cell distribution width to platelet ratio as a novel non-invasive index for predicting hepatic fibrosis in patients with chronic hepatitis C

Background and study aimsAssessing the extent of fibrosis is an essential part of therapeutic decisions in patients with chronic hepatitis C (CHC). Liver biopsies are the “gold standard” for evaluating liver fibrosis but have many limitations. Thus, noninvasive predictors of fibrosis have been developed. This study aimed to determine the effectiveness of red cell distribution width (RDW) to platelet ratio as a simple noninvasive method for predicting the hepatic fibrosis stage in patients with CHC. Patients and methodsThis cross-sectional study included 197 Egyptian patients with CHC. A routine pretreatment reference needle liver biopsy was performed. Fib-4, transient elastography (TE) by Fibroscan, AST to Platelet Ratio Index (APRI), and RDW to platelet ratio (RPR) were measured. Predictors of significant fibrosis (Metavir score ≥ F2) and advanced fibrosis (Metavir score ≥ F3) were identified. ResultsFib-4, TE, APRI, and RPR values differed significantly when comparing different stages of fibrosis (p < 0.01). Fib-4, TE, APRI, and RPR were reliable diagnostic tools at cutoff values of 1.17, 7.75, 0.18, and 0.07, respectively, for predicting significant fibrosis and cutoff values of 1.99, 8, 1.77, and 0.08, respectively, for predicting advanced fibrosis. Using logistic regression analysis, TE was identified as an independent predictor associated with significant and advanced fibrosis. Fib-4 was significantly associated with advanced fibrosis only. ConclusionThe use of Fib-4, TE, APRI, and RPR measurements may decrease the need for liver biopsies for predicting significant and advanced fibrosis. RPR showed fair sensitivity, specificity, positive and negative predictive values, and overall accuracy for predicting significant fibrosis in patients with CHC.

Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening.

OBJECTIVEAssess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSA total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.RESULTSThe prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).CONCLUSIONSModerate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4years and post-LT survival was 87.9% at 5years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

Development and validation of a noninvasive clinical scoring system to predict significant fibrosis in patients with nonalcoholic fatty liver disease

BackgroundThe aims of this study were to identify risk factors for significant fibrosis (SF) by assessing physical and laboratory parameters and develop and validate a clinical score and nomogram for the prediction of SF in patients with nonalcoholic fatty liver disease (NAFLD). MethodsThis retrospective study included 225 patients with histologically confirmed NAFLD who were divided into two cohorts using 10-fold cross validation for model training and validation. The clinical score and nomogram were used to predict the NAFLD outcome. ResultsThe model for predicting SF (stage ≥ 2) including the free T4/free T3 ratio, low-density lipoprotein cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), percentage of appendicular skeletal muscle mass and aspartate aminotransferase (AST) level in the training and validation cohorts yielded an area under the receiver operator characteristic curve (AUROC) of 0.79 and 0.78, respectively. The AUROC of the combined clinical score for the prediction of SF was 0.82 (95% CI, 0.75–0.89) at a cutoff value of 3 points, with a sensitivity (SE) of 77.19%, specificity (SP) of 82.88%, positive predictive value (PPV) of 63.77%, and negative predictive value (NPV) of 90.30%. The nomogram had good performance in quantitatively predicting the risk probability of SF. ConclusionOur study showed that a noninvasive clinical scoring system using easily available physical and laboratory variables can identify patients with NAFLD with or without SF with a high degree of accuracy. Application of this system may decrease the need for staging liver biopsy specimens and allow early identification and intervention in these high-risk patients.

Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD.

This study explored the relationship between patatin-like phospholipase domain-containing 3 gene (PNPLA3 rs738409), nutrient intake, and liver histology severity in patients with nonalcoholic fatty liver disease (NAFLD). PNPLA3-rs738409 variant was genotyped in 452 non-Hispanic whites with histologically confirmed NAFLD who completed Food Frequency Questionnaire within 6 months of their liver biopsy. The fibrosis severity on liver histology was the outcome of interest. The distribution of PNPLA3 genotypes was CC: 28%, CG: 46%, and GG: 25%. High-carbohydrate (% of energy/d) intake was positively associated (adjusted [Adj] odds ratio [OR]: 1.03, P < 0.01), whereas higher n-3 polyunsaturated fatty acids (n-3 PUFAs) (g/d) (Adj. OR: 0.17, P < 0.01), isoflavones (mg/d) (Adj. OR: 0.74, P = 0.049), methionine (mg/d) (Adj. OR: 0.32, P < 0.01), and choline (mg/d) (Adj. OR: 0.32, P < 0.01) intakes were inversely associated with increased risk of significant fibrosis (stage of fibrosis ≥2). By using an additive model of inheritance, our moderation analysis showed that PNPLA3 rs738409 significantly modulates the relationship between carbohydrate (%), n-3 PUFAs, total isoflavones, methionine, and choline intakes and fibrosis severity in a dose-dependent, genotype manner. These dietary factors tended to have a larger and significant effect on fibrosis severity among rs738409 G-allele carriers. Associations between significant fibrosis and carbohydrates (Adj. OR: 1.04, P = 0.019), n-3 PUFAs (Adj. OR: 0.16, P < 0.01), isoflavones (Adj. OR: 0.65, P = 0.025), methionine (Adj. OR: 0.30, P < 0.01), and total choline (Adj. OR: 0.29, P < 0.01) intakes remained significant only among rs738409 G-allele carriers. This gene-diet interaction study suggests that PNPLA3 rs738409 G-allele might modulate the effect of specific dietary nutrients on risk of fibrosis in patients with NAFLD.

Muscle alterations are independently associated with significant fibrosis in patients with nonalcoholic fatty liver disease.

Anthropometric data are associated with nonalcoholic fatty liver disease (NAFLD) development and progression. We investigated whether the quantity and quality of muscle and visceral fat assessed by computed tomography (CT) are associated with fibrosis severity in NAFLD. In a prospective biopsy-confirmed NAFLD cohort of 521 patients, we measured skeletal muscle index (SMI), muscle attenuation (MA) and visceral adipose tissue index (VATI) via CT. Low skeletal muscle mass (LSMM) was defined using previously validated cut-offs. Myosteatosis and visceral adiposity were defined as the lowest and highest quartile, respectively. Significant fibrosis was defined as F2-F4 in liver histology. Patients with significant fibrosis had lower SMI and MA and higher VATI than those without. The significant fibrosis prevalence was significantly higher in subjects with LSMM (45.1% vs 30.8%, P=.005), myosteatosis (46.1% vs 29.7%, P=.001) and visceral adiposity (46.9% vs 29.9%, P=.001) than those without. The significant fibrosis risk increased with increasing numbers of body composition components (24.5%, 35.6%, 53.0% and 72.7% in patients with 0, 1, 2 and 3 components respectively). Multivariable analysis revealed that LSMM (OR, 1.72; 95% CI, 1.05-2.84), myosteatosis (OR, 1.65; 95% CI, 1.01-2.68) and visceral adiposity (OR, 1.75; 95% CI, 1.09-2.83) were independent predictors of significant fibrosis. Subjects with sarcopenia had a higher risk of significant fibrosis (OR, 2.17; 95% CI, 1.03-4.56). Muscle alterations and visceral adiposity assessed by CT are associated with significant fibrosis in NAFLD. LSMM and myosteatosis have additive values in prediction of significant fibrosis.

Estimation of visceral fat is useful for the diagnosis of significant fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUNDObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), although obese patients with NAFLD do not always develop significant fibrosis. The distribution of body fat could predict the risk of NAFLD progression. AIMTo investigate the role of bioelectrical impedance-estimated visceral fat (VF) in assessing NAFLD severity.METHODSIn this cross-sectional study, patients with biopsy-proven NAFLD were prospectively included. All patients underwent anthropometric evaluation, blood tests and bioelectrical impedance analysis.RESULTSBetween 2017 and 2020, 119 patients were included [66.4% male, 56 years (SD 10.7), 62.2% obese, 61.3% with metabolic syndrome]. Sixty of them (50.4%) showed significant fibrosis (≥ F2) in liver biopsy. Age, VF and metabolic syndrome were associated with significant fibrosis (61 years vs 52 years, 16.4 vs 13.1, 73.3% vs 49.2%, respectively; P < 0.001 for all). In the multivariate analysis, VF and age were independently associated with significant fibrosis (VF, OR: 1.11, 95%CI: 1.02-1.22, P = 0.02; age, OR: 1.08, 95%CI: 1.03-1.12, P < 0.01). A model including these variables showed and area under the receiver operating characteristic curve (AUROC) of 0.75, which was not inferior to transient elastography or NAFLD fibrosis score AUROCs. We developed a nomogram including age and VF for assessing significant fibrosis in routine practice.CONCLUSIONVF is a surrogate marker of liver fibrosis in patients with NAFLD. Bioelectrical impedance analysis is an inexpensive and simple method that can be combined with age to guide patient referral when other resources may be unavailable.

Serum gamma-glutamyl transpeptidase as a simple and useful indicator for predicting significant fibrosis in patients with chronic hepatitis B

Serum gamma-glutamyl transpeptidase as a simple and useful indicator for predicting significant fibrosis in patients with chronic hepatitis B

FRI015 - Identification of significant fibrosis in patients with non-alcoholic steatohepatitis using non-invasive tests: determination of optimal thresholds based on cross-sectional analyses of patients screened for a phase 3 randomised controlled trial

FRI015 - Identification of significant fibrosis in patients with non-alcoholic steatohepatitis using non-invasive tests: determination of optimal thresholds based on cross-sectional analyses of patients screened for a phase 3 randomised controlled trial

Safely restarting GI endoscopy in the era of COVID-19

<h3>Background:</h3> The factors that influence liver fibrosis progression in patients co-infected with human immunodeficiency virus/hepatitis C virus (HIV/HCV) are not completely understood. It is not known if insulin resistance (IR),...

Performance of Non-invasive Blood Parameters for Ruling Out Significant Liver Fibrosis in Patients with Chronic Hepatitis B.

Background and Aims: Evaluation of significant liver fibrosis is important for treatment decision and treatment response evaluation in patients with chronic hepatitis B. Since liver biopsy is invasive and transient elastography (TE) has limited availability, various non-invasive blood parameters need evaluation for their capabilities for detection of significant fibrosis.Methods: In this retrospective study, records of patients who had undergone liver biopsy for treatment-naïve chronic hepatitis B were evaluated to obtain various non-invasive blood parameters (aspartate aminotransferase-to-platelet ratio index [referred to as APRI], Fibrosis-4 score [referred to as FIB-4], gamma-glutamyl transpeptidase-to-platelet ratio [referred to as GPR], and gamma-glutamyl transpeptidase-to-albumin ratio [referred to as GAR]), in addition to TE, to assess significant liver fibrosis and compare these to fibrosis stage in liver biopsy.Results: A total of 113 patients were included in the study (median age 33 [interquartile range: 11-82 years], 74% males). Most (75%) patients were HBeAg-negative. The liver biopsy revealed significant fibrosis (Ishak ≥3) in 13% of the patients and nil or mild fibrosis (Ishak <3) in 87% of the patients. TE findings were available for 85 patients, APRI and FIB-4 for 95 patients, GPR for 79 patients, and GAR for 78 patients. The median values of all the parameters were significantly higher in patients with significant fibrosis, as compared to patients with non-significant fibrosis, and all the blood parameters as well as TE were able to identify patients with significant fibrosis significantly well (p<0.05). All non-invasive parameters had low positive predictive value but negative predictive value above 92%. Compared to TE, all the non-invasive blood parameters had similar area under the curve for detecting significant fibrosis, with excellent negative predictive value (≥93%).Conclusions: Non-invasive blood parameters (APRI, FIB-4, GPR, and GAR) with negative predictive values above 93% are excellent parameters for ruling-out significant fibrosis in patients with chronic hepatitis B. These can be used at bedside in place of TE.

Comparison of serum fibrosis biomarkers for diagnosing significant liver fibrosis in patients with chronic hepatitis B.

Chronic hepatitis B (CHB) virus continues to be a leading cause of morbidity and mortality worldwide. The diagnosis of liver fibrosis has a key role in selecting patients with CHB for antiviral treatment. However, serum biomarkers demonstrate limited diagnostic utility. The present study aimed to compare the performances of fibrosis biomarkers for diagnosing significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB and to identify the most appropriate biomarker for these patients. The current study included 96 antiviral-naïve patients with CHB who underwent liver biopsy. METAVIR scoring system was used to assess liver fibrosis and necroinflammation. The diagnostic performances were evaluated of the platelet (PLT) count; the levels of hyaluronan, serum 7S domain of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer (M2BPGi) and N-terminal type III collagen propeptide (Pro-C3); the fibrosis index based on four factors; the aspartate aminotransferase-to-platelet ratio index; and enhanced liver fibrosis score for identifying significant liver fibrosis [≥fibrosis stage 2 (F2)]. All fibrosis biomarkers, except the Pro-C3 level, correlated with the fibrosis stage. M2BPGi was better than other biomarkers for diagnosing ≥F2, with the highest area under the curve of 0.902. M2BPGi demonstrated a higher diagnostic accuracy for significant fibrosis than mild/severe fibrosis or cirrhosis. However, no significant correlation was observed between the M2BPGi level and fibrosis stage in patients with CHB having significant liver necroinflammation defined as ≥ necroinflammatory activity 2. The M2BPGi level and PLT count were exclusively correlated with the fibrosis stage in 73 patients without significant liver necroinflammation. M2BPGi demonstrated the highest diagnostic performance for significant fibrosis in patients having significant liver fibrosis with no significant liver necroinflammation. In conclusion, the M2BPGi level can accurately diagnose significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB.

Issue highlights

Issue highlights

Accurate prediction of significant liver fibrosis using the Pentra score model in patients with chronic hepatitis C.

Noninvasive methods are increasingly used in the clinical assessment of patients with chronic hepatitis C (CHC). We aimed to develop a predictive model for the evaluation of significant fibrosis in patients with CHC, based on serum biomarkers. We compared the accuracy of our model in detecting significant fibrosis with currently known markers / models of fibrosis (such as the aspartate aminotransferase to platelet ratio index [APRI], the Fibrosis‑4 [FIB-4] score, and the Forns index). A total of 242 patients with CHC not receiving antiviral treatment were divided into 2 groups: training group (n = 150) and validation group (n = 92). Significant fibrosis was defined as F2 or higher on the Meta‑analysis of Histological Data in Viral Hepatitis (METAVIR) scale. Multivariable analysis revealed that age (P <0.001), pentraxin 3 (PTX3) levels (P = 0.009), γ‑glutamyl transpeptidase (GGT) to platelet count (PLT) ratio (P = 0.08), and hyaluronic acid levels (HA) (P = 0.07) were independent predictors of significant fibrosis. Based on that, we developed a model for predicting significant fibrosis: Pentra score = 0.176 × PTX3 (ng/ml) + 0.522 × HA (ng/ml) + 0.29 × GGT (IU/l) to PLT (×109/l) ratio + 0.14 × age (years) - 3.9346. Then, we compared our model with the biomarkers and models currently used to predict liver fibrosis. The Pentra score yielded the largest area under the receiver operating characteristic curve for predicting significant fibrosis in the training and validation groups (0.894 and 0.867, respectively). It also had the highest diagnostic accuracy in both groups (90.6% and 87.0%, respectively). Our model for detecting significant fibrosis in patients with CHC using pentraxin 3 and other serum biomarkers compares well with the existing and previously published indices. However, further validation in larger cohorts is needed.

The clinical and histological characteristics of patients with biopsy-proven non-alcoholic fatty liver disease in the absence of insulin resistance.

Background and AimNon-alcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance (IR). While a minority of patients with NAFLD does not have evidence of IR, no detailed characterization of this specific phenotype is currently available. This study was undertaken to investigate the clinical and histological characteristics of this patient group.Materials and MethodsWe retrospectively reviewed the clinical records of 263 patients with biopsy-proven NAFLD. IR was defined by a Homeostatic Model Assessment of IR (HOMA-IR) score >2.73. The histological diagnosis of non-alcoholic steatohepatitis (NASH) was performed using 1) the steatosis, activity and fibrosis score and 2) the NASH Clinical Research Network (NASH CRN) criteria. Significant fibrosis was defined by the presence of a histological fibrosis score higher than F≥2. Patients with and without evidence of IR were compared concerning clinical, laboratory, and histological characteristics.ResultsOf the 263 patients with biopsy-proven NAFLD, 53 (20.2%) patients had no evidence of IR. Patients without IR were younger [IR (-): 42 (22–65) years versus IR (+): 49 (22−71) years, p=0.001] and had a higher prevalence of men [IR (-): 39 (73.6%) versus IR (+): 113 (53.8%), p=0.009]. Moreover, they were characterized by a lower body mass index [IR (-): 30.06±3.61 kg/m2 versus IR (+): 33.19±5.06 kg/m2, p=0.000] and lower frequencies of metabolic risk factors–including the metabolic syndrome, diabetes, hypertension, hyperlipidemia, and lower waist/hip circumference. Liver histology was generally less severe in patients without IR; specifically, they showed a lower prevalence of NASH [IR (-): 38 (71.7%) versus IR (+): 190 (90.5%), p=0.000] and significant fibrosis [IR (-): 9 (17.0%) versus IR (+): 106 (50.5%), p=0.000] than did patients with IR. Multivariate analysis identified obesity [odds ratio (OR): 9.321, 95% confidence interval (CI): 1.031−84.261, p<0.05] and an international normalized ratio >1.1 (OR: 10.116, 95% CI: 1.325−77.225, p<0.05) as independent predictors of significant fibrosis in patients with NAFLD and no IR.ConclusionPatients with NAFLD and no IR has less severe liver histology than patients with IR. However, obesity appears to be independently associated with significant fibrosis in this patient group.