Systematic Review with Meta-Analysis: Diagnostic Accuracy of Pro-C3 for Hepatic Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease

The prevalence and severity of non-alcoholic fatty liver disease (NAFLD) is increasing, yet adequately validated tests for care paths are limited and non-invasive markers of disease progression are urgently needed. The aim of this work was to summarize the performance of Pro-C3, a biomarker of active fibrogenesis, in detecting significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), cirrhosis (F4) and non-alcoholic steatohepatitis (NASH) in patients with NAFLD. A sensitive search of five databases was performed in July 2021. Studies reporting Pro-C3 measurements and liver histology in adults with NAFLD without co-existing liver diseases were eligible. Meta-analysis was conducted by applying a bivariate random effects model to produce summary estimates of Pro-C3 accuracy. From 35 evaluated reports, eight studies met our inclusion criteria; 1568 patients were included in our meta-analysis of significant fibrosis and 2058 in that of advanced fibrosis. The area under the summary curve was 0.81 (95% CI 0.77–0.84) in detecting significant fibrosis and 0.79 (95% CI 0.73–0.82) for advanced fibrosis. Our results support Pro-C3 as an important candidate biomarker for non-invasive assessment of liver fibrosis in NAFLD. Further direct comparisons with currently recommended non-invasive tests will demonstrate whether Pro-C3 panels can outperform these tests, and improve care paths for patients with NAFLD.

The Prevalence of Liver Steatosis and Fibrosis Assessed by Vibration-Controlled Transient Elastography and Controlled Attenuation Parameter in Apparently Healthy Romanian Medical Students

Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP) is used as a non-invasive method for evaluating liver steatosis and fibrosis simultaneously. In this prospective study, we aimed to assess the prevalence of liver steatosis and fibrosis, as well as the associated risk factors in Romanian medical students by VCTE and CAP score. We used a cut-off CAP score of ≥248 dB/m for the diagnosis of mild steatosis (S1), ≥268 dB/m for moderate steatosis (S2), and ≥280 dB/m to identify severe steatosis (S3). For liver fibrosis, the cut-off values were: ≤5.5 kPa, indicating no fibrosis (F0), 5.6 kPa for mild fibrosis (F1), 7.2 kPa for significant fibrosis (F2), 9.5 kPa for advanced fibrosis (F3), and 12.5 kPa for cirrhosis (F4). In total, 426 Romanian medical students (67.8% females, mean age of 22.22 ± 1.7 years) were evaluated. Among them, 352 (82.6%) had no steatosis (S0), 32 (7.5%) had mild steatosis (S1), 13 (3.1%) had a moderate degree of steatosis (S2), and 29 (6.8%) had severe steatosis (S3). Based on liver stiffness measurements (LSM), 277 (65%) medical students did not have any fibrosis (F0), 136 (31.9%) had mild fibrosis (F1), 10 (2.4%) participants were identified with significant fibrosis (F2), 3 (0.7%) with advanced fibrosis (F3), and none with cirrhosis (F4). In conclusion, the prevalence of liver steatosis and fibrosis is low among Romanian medical students.

Low Screening Rates Despite a High Prevalence of Significant Liver Fibrosis in People with Diabetes from Primary and Secondary Care

Diabetes is a driver of non-alcoholic fatty liver disease (NAFLD) and fibrosis. We determine current practices in examining liver fibrosis in people with diabetes and record prevalence levels in primary and secondary care. We extracted HbA1c results ≥48 mmol/mol to identify people with diabetes, then examined the proportion who had AST, ALT, and platelets results, facilitating calculation of non-invasive fibrosis tests (NIT), or an enhanced liver fibrosis score. Fibrosis markers were requested in only 1.49% (390/26,090), of which 29.7% (n = 106) had evidence of significant fibrosis via NIT. All patients at risk of fibrosis had undergone transient elastography (TE), biopsy or imaging. TE and biopsy data showed that 80.6% of people with raised fibrosis markers had confirmed significant fibrosis. We also show that fibrosis levels as detected by NIT are marginally lower in patients treated with newer glucose lowering agents (sodium-glucose transporter protein 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists). In conclusion by utilising a large consecutively recruited dataset we demonstrate that liver fibrosis is infrequently screened for in patients with diabetes despite high prevalence rates of advanced fibrosis. This highlights the need for cost-effectiveness analyses to support the incorporation of widespread screening into national guidelines and the requirement for healthcare practitioners to incorporate NAFLD screening into routine diabetes care.

Prognostic Value of Inflammatory Indicators in Chronic Hepatitis B Patients With Significant Liver Fibrosis: A Multicenter Study in China

Diagnosis of significant liver fibrosis is essential to facilitate the optimal treatment decisions and improve prognosis in patients with chronic hepatitis B (CHB). We aimed to evaluate the value of inflammatory indicators and construct a nomogram that effectively predicts significant liver fibrosis among CHB patients. 563 CHB patients from two centers in China from 2014 to 2019 were divided into three cohorts (development, internal validation, and independent validation cohorts), assigned into cases with significant fibrosis (liver fibrosis stages ≥2) and those without. Multiple biochemical and serological inflammatory indicators were investigated. Inflammatory indicators, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly associated with significant liver fibrosis in CHB patients but limited predictive performance, and then we combined them with prothrombin time activity percentage (PTA) and liver stiffness measurement (LSM) were identified by multivariate logistic regression analysis. Based on these factors, we constructed the nomogram with excellent performance. The area under the receiver operating characteristic curve (AUROC) for the nomogram in the development, internal validation, and independent validation cohorts were 0.860, 0.877, and 0.811, respectively. Our nomogram based on ALT and AST that had excellent performance in predicting significant fibrosis of CHB patients were constructed.

Comparison and Validation of APRI and FIB-4 for Evaluating Liver Fibrosis in Chinese Hepatitis B Virus-infected Patients with Persistently Normal ALT, Mildly and Significantly Elevated ALT

Background: Many noninvasive models based on serum markers composition are used for the assessment of liver fibrosis, reducing the need for liver biopsy. However, most of the models have rarely been validated in Chinese hepatitis B patients. We aim to evaluate and validate chronic hepatitis B(CHB) patients with normal ALT, mildly and significantly elevated ALT levels.Methods: This single-center retrospective study enrolled 285 patients with CHB who underwent liver biopsy. There were 156 patients in normal ALT group, 85 patients in mildly elevated ALT group, and 44 patients in significantly elevated ALT group. The diagnostic accuracy of APRI and FIB-4 was evaluated by areas under the characteristic curves (AUROC) using the histological assessment of the fibrosis stages of the biopsy specimens as the standards.Results: Among 285 patients with CHB, 156 patients had normal ALT level, of which 65 (41.7%) had significant fibrosis(S2-4). The evaluation of significant fibrosis, AUROC in APRI and FIB-4 were 0.608, 0.634, 0.708 and 0.638, 0.679, 0.734 in normal ALT, mildly and significantly elevated ALT, respectively. The assessment of advanced fibrosis, AUROC in APRI and FIB-4 were 0.636, 0.751, 0.708 and 0.652, 0.763, 0.734 in normal ALT, mildly and significantly elevated ALT groups, respectively. Conclusions: APRI and FIB-4 may not be ideal noninvasive markers for evaluating liver fibrosis in Chinese HBV-infected patients with normal ALT levels. Compared with HBV-infected patients with normal ALT, APRI and FIB-4 had high accuracies in diagnosing liver fibrosis in patients with mildly and significantly elevated ALT.

The Diagnostic Accuracy of LOGIQ S8 and E9 Shear Wave Elastography for Staging Hepatic Fibrosis, in Comparison with Transient Elastography

Background: The aim of this study was to evaluate the usefulness of two different types of 2-dimensional shear wave elastography (2D-SWE) for predicting liver fibrosis stages in comparison to transient elastography (TE), using a histologic METAVIR scoring system as the reference method. Methods: A total of 203 patients with chronic liver disease were prospectively enrolled in the study. Two different 2D-SWEs (LOGIQ S8 and E9 systems, GE Healthcare, Chalfont St Giles, UK) were assessed for liver stiffness in patients with chronic liver diseases. Patients received 2D-SWE examinations with the S8 and E9 systems, and also underwent TE (FibroScan®, Echosens, France) tests and liver biopsies on the same day. Results: The most common etiology of chronic liver disease was non-alcoholic fatty liver disease (28.7%), followed by chronic hepatitis B (25.1%). Liver fibrosis stages consisted of F0 (22.6%), F1 (29.7%), F2 (16.9%), F3 (12.8%) and F4 (17.9%). Overall, S8 and E9 were well correlated with the histologic fibrosis stages. The optimal cut-off values for S8 and E9 to differentiate significant fibrosis (≥F2) were 6.70 kPa and 6.42 kPa, respectively, while the cut-off values for S8 and E9 in distinguishing liver cirrhosis were 9.15 kPa and 8.88 kPa, respectively. Among the 195 patients who had successful measurements in both S8 and E9, liver stiffness showed good inter-equipment correlation (ICC: 0.900, p < 0.001). Regarding diagnostic ability, upon comparison (FibroScan®), there were no significant differences between 2D-SWEs and TE for detecting every stage of liver fibrosis. Conclusion: In comparison to TE, 2D-SWE with LOGIQ S8 and E9 (GE Healthcare) are useful non-invasive tools for predicting significant fibrosis and liver cirrhosis.

Real time ultrasound tissue Elastography in post-hepatitis chronic liver disease; role, limitations and pitfalls

Assessment of liver fibrosis stage is important in determining the prognosis and treatment strategy in chronic liver diseases. To overcome the limitations of liver biopsy, great efforts have been made to develop and validate non-invasive methods for detecting liver fibrosis, including serological indicators and imaging methods. Among these noninvasive methods, ultrasound-based elastography techniques are increasingly employed to assess parenchymal stiffness. Real-time transient elastography is most accurate one of them and rapidly evolving technique that can reveal the elastic properties of tissues, and display it as real time images. This technique can avoid unnecessary invasive liver biopsy. Patients and methods This descriptive study was done on 20 chronic HCV patients as diagnosed by seropositivity for HCV antibodies and HCV RNA by PCR, Patients were recruited from police hospitals outpatient clinics to find an alternative method to assess liver fibrosis. Results showed highly significant agreement between fibroscan scores and biopsy results (p value was &lt; 0.001), the identification of patients with significant fibrosis (F ≥ 2) “F2, 3, 4” We reported that the cut off level of significant fibrosis (F ≥ 2) assessed by the METAVIR scoring system was 10.2 kpa, with sensitivity 86.7 % and specificity 80 %. However, cut-off level of 13.8 kpa for the detection of cirrhosis (F4) with an area under the ROC of 0.913, and a very high sensitivity and specificity (sensitivity 90.1% and specificity 85.7%). Conclusion Transient Elastography is an easy and quick clinical non-invasive method to perform. Results are available immediately, and this technique is accurate in predicting significant fibrosis ≥f2. Hence, Transient Elastography could be useful not only to evaluate liver fibrosis as to monitor liver disease progression, but also to monitor anti-viral or antifibrotic therapy effects and to help taking decisions in daily clinical practice.