Algorithms for early detection of silent liver fibrosis in the primary care setting - a scoping review

Introduction Fatty liver disease affects almost 30% of the adult population worldwide. Most patients are asymptomatic, and there is not a linear relationship between exposure to risk factors and the risk of developing fibrosis. The combination of a very large, asymptomatic risk population where only a few percent will develop life-threatening liver disease is a growing diagnostic challenge for the health services. Accurate fibrosis assessment in primary care is limited by poor correlation with liver blood tests and low availability of elastography. Non-invasive tests are promising tools, but little is known about their diagnostic accuracy in low-risk populations. Areas covered A scoping review was conducted to identify articles that focused on the current use of biomarkers and algorithms in primary care for the detection of patients with fatty liver disease in need of referral for further work-up. Expert opinion Currently available algorithms for targeted screening for liver fibrosis perform better than the individual routine liver blood tests or liver ultrasonography. However, primary care physicians urgently need algorithms with even higher diagnostic accuracies than what is available today. The main limitation of the existing widely accessible algorithms, such as the FIB-4, is the large number of false-positive tests, resulting in overdiagnosis and futile referrals to secondary care.publishedVersio

Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease

Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory processes may provide optimized disease monitoring and diagnostics. We investigated the tissue remodelling in IBD and IBS patients by using novel blood-based biomarkers reflecting ECM remodelling.Five ECM biomarkers (VICM, BGM, EL-NE, C5M, Pro-C5) were measured by competitive ELISAs in serum from 72 CD patients, 60 UC patients, 22 patients with irritable bowel syndrome (IBS), and 24 healthy donors. One-way analysis of variance, Mann-Whitney U-test, logistic regression models, and receiver operator characteristics (ROC) curve analysis was carried out to evaluate the diagnostic accuracy of the biomarkers.The ECM remodelling was significantly different in UC compared to CD. The best biomarker combination to differentiate UC from CD and colonic CD was BGM and VICM (AUC = 0.98, P<0.001; AUC = 0.97, P<0.001), and the best biomarker combination to differentiate IBD from IBS patients were BGM, EL-NE, and Pro-C5 (AUC = 0.8, P<0.001). When correcting for the use of immunosuppressant and elevated CRP levels (CRP>5mg/mL), correlation of Pro-C5 (r = 0.36) with CDAI was slightly improved compared to CRP (r = 0.27) corrected for the use of immunosuppressant. Furthermore, BGM and EL-NE biomarkers were highly associated with colon inflammation in CD patients.ECM fragments of tissue remodelling in IBD affect UC and CD differently, and may aid in differentiating IBD from IBS (EL-NE, BGM, Pro-C5), and UC from CD patients (BGM, VICM). Formation of type V collagen is related to the level of inflammation in CD and may reflect disease activity in CD

The EASL–<em>Lancet</em> Commission on liver health in Europe: prevention, case-finding, and early diagnosis to reduce liver-related mortality

In December, 2021, the first report from the Lancet Commission on liver disease in Europe, a joint project with the European Association for the Study of the Liver (EASL), was published. 1 The Commission explored the harm to liver health in Europe that results from a combination of increasing obesity, the highest level of alcohol consumption in the world, and delays in viral hepatitis elimination. The Commission emphasised the importance of structural factors that drive risk behaviours and poor outcomes in liver disease, with disproportionate effects on disadvantaged and vulnerable populations. Such structural drivers include the heterogeneous landscape of alcohol policy in Europe, fragmented access to testing and therapy for viral hepatitis, and stigmatisation faced by individuals at risk of liver disease at the societal level and within health-care settings. 2 , 3 This stigma contributes to care avoidance and delayed diagnosis, ultimately leading to a bias in clinical pathways that prioritise managing advanced liver disease rather than early diagnosis and primary and secondary prevention of liver disease. The Commission report included ten recommendations to facilitate a shift towards health promotion, prevention, proactive case-finding, early identification of progressive liver fibrosis, and early management and treatment of liver diseases (figure). 1 The key message of the Commission was paraphrased by Ursula von der Leyen, the President of the European Commission, in her remarks made at the launch event: “in most cases, liver disease can be prevented. Prevention is the best cure that we have.

2D shear wave liver elastography by aixplorer to detect portal hypertension in cirrhosis: an individual patient data meta-analysis

Background & Aims: Liver stiffness measured with 2-dimensional shear wave elas- tography by Supersonic Imagine (2DSWE-SSI) is well-established for fibrosis diagnos- tics, but non-conclusive for portal hypertension. Methods: We performed an individual patient data meta-analysis of 2DSWE-SSI to identify clinically significant portal hypertension (CSPH), severe portal hyperten- sion and large varices in cirrhosis patients, using hepatic venous pressure gradient and upper endoscopy as reference. We used meta-analytical integration of diagnos- tic accuracies with optimized rule-out (sensitivity-90%) and rule-in (specificity-90%) cut-offs. Results: Five studies from seven centres shared data on 519 patients. After exclu- sion, we included 328 patients. Eighty-nine (27%) were compensated and 286 (87%) had CSPH. 2DSWE-SSI < 14 kPa ruled out CSPH with a summary AUROC (sROC), sensitivity and specificity of 0.88, 91% and 37%, and correctly classified 85% of pa- tients, with minimal between-study heterogeneity. The false negative rate was 60%, of which decompensated patients accounted for 78%. 2DSWE-SSI ≥ 32 kPa ruled in CSPH with sROC, sensitivity, specificity and correct classifications of 0.83, 47%, 89% and 55%. In a subgroup analysis, the 14 kPa cut-off showed consistent sensitivity and higher specificity for patients with compensated cirrhosis, without ascites, viral 2 aetiology or BMI < 25 kg/m . 2DSWE-SSI ruled out severe portal hypertension and large varices with fewer correctly classified and lower sROC, and with minimal benefit for ruling in. Conclusion: Liver stiffness using 2-dimensional shear wave elastography below 14 kPa may be used to rule out clinically significant portal hypertension in cirrhosis patients, but this would need validation in populations of compensated liver disease. 2DSWE-SSI cannot predict varices needing treatment

A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease

The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.Peer reviewe