Non-invasive Liver Fibrosis Tests Research Articles

Hepatic Arterial Blood Flow Index Is Associated with the Degree of Liver Fibrosis in Patients with Chronic Hepatitis B Virus Infection

Background: Liver fibrosis due to Hepatitis B Virus (HBV) infection is an important public health concern worldwide. An accurate assessment of liver fibrosis is crucial for the identification of susceptible patients to severe clinical conditions and selection of treatment for patients with Chronic Hepatitis B (CHB) infection. Today, the development of simple, accurate, cost-effective, and non-invasive liver fibrosis tests is essential in clinical practice. Methods: According to liver biopsy as the reference standard, we compared the efficacy of hepatic arterial blood flow index (HBI) versus liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet count ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) to predict various degrees of liver fibrosis among 87 patients with CHB infection. Results: Spearman’s rank correlation coefficient of HBI versus the degree of liver fibrosis, according to the METAVIR scoring system, was 0.672 (P < 0.001). The area under the receiver operating characteristic curve (AUROC) of HBI (0.884; 95% CI: 0.806 - 0.961; P = 0.000) was greater than that of LSM (0.807; 95% CI: 0.703 - 0.912; P = 0.00), APRI (0.684; 95% CI: 0.556 - 0.812; P = 0.009), and FIB-4 (0.757; 95% CI: 0.641 - 0.873; P = 0.000) for the diagnostic analysis of significant liver fibrosis (≥ F2); similar results were obtained for the prediction of other liver fibrosis stages. Conclusions: The present findings shed new light on the association of HBI with the degree of liver fibrosis in patients with CHB infection. Hepatic Arterial Perfusion Scintigraphy (HAPS) with the measurement of HBI is a promising diagnostic method of liver fibrosis stage, which can guide therapy in CHB patients, although further large-scale studies are needed.

Plateletcrit as a potential index for predicting liver fibrosis in chronic hepatitis B.

Noninvasive tests (NITs) for liver fibrosis are highly needed for chronic hepatitis B (CHB) patients. We aimed to investigate whether plateletcrit (PCT) could be used as a NIT in predicting liver fibrosis for CHB patients. Five hundred and sixty-seven treatment-naïve CHB patients with available liver biopsies were included. Patients were randomly divided into a derivation cohort (n=378) and a validation cohort (n=189). The diagnostic accuracy of PCT was evaluated using receiver operating characteristic (ROC) curves. In the derivation cohort, PCT in CHB patients with S2-S4 (0.14%), S3-S4 (0.13%) and S4 (0.12%) was lower than patients with S0-S1 (0.17%, P<.001), S0-S2 (0.17%, P<.001) and S0-S3 (0.16%, P<.001), respectively. PCT was an independent predictor of significant fibrosis (≥S2), advanced fibrosis (≥S3) and cirrhosis (S4). The area under the ROC curve (AUROC) of PCT in predicting significant fibrosis, advanced fibrosis and cirrhosis was 0.645, 0.709 and 0.714, respectively. The AUROC of PCT was higher than the aspartate transaminase to platelet ratio index (APRI) in identifying advanced fibrosis and cirrhosis, while this was comparable with APRI in identifying significant fibrosis. The diagnostic value of PCT was comparable with fibrosis-4 score (FIB-4) in predicting significant fibrosis, advanced fibrosis and cirrhosis. In the validation cohort, PCT could also identify significant fibrosis, advanced fibrosis and cirrhosis with similar diagnostic accuracy as in the derivation cohort. PCT represents a simple and inexpensive indictor for liver fibrosis in CHB patients. PCT is just as good or better than other more complex tools for staging liver fibrosis in CHB patients.

Non-invasive tests for liver fibrosis in NAFLD: Creating pathways between primary healthcare and liver clinics.

Despite affecting around one-fourth of the general population worldwide, non-alcoholic fatty liver disease (NAFLD) remains a largely under-recognized disease in primary healthcare, with not more than 10% of patients diagnosed with NAFLD referred to specialists. The main challenge in clinical practice is the identification of those with advanced liver fibrosis or cirrhosis, as they are at the greatest risk of developing complications. Liver biopsy appears to be an unrealistic and unsuitable option because of the large number of high-risk patients and the well-known limitations of this technique. This has favoured the development of non-invasive tests, which have been an area of intensive research in the past decade. Transient elastography, FIB-4 and the NAFLD fibrosis score are the most extensively used and best validated tests, with summary AUROC values for detecting advanced fibrosis in NAFLD patients of 0.88, 0.84 and 0.84 respectively. Although much work remains to be done to establish cost-effective strategies for the screening for advanced fibrosis, the sequential use of non-invasive tests (serum biomarkers, then measurement of liver stiffness using transient elastography) appears to be the most promising strategy. The next step is to establish effective pathways in primary healthcare and/or diabetes clinics where most NAFLD patients are seen, to identify those who need to be referred to liver clinics for further assessment.

From the Editor’s desk…: August 2019

From the Editor’s desk…: August 2019

Cost-comparison analysis of FIB-4, ELF and fibroscan in community pathways for non-alcoholic fatty liver disease

BackgroundThe identification of patients with advanced liver fibrosis secondary to non-alcoholic fatty liver disease (NAFLD) remains challenging. Using non-invasive liver fibrosis tests (NILT) in primary care may permit earlier detection of patients with clinically significant disease for specialist review, and reduce unnecessary referral of patients with mild disease. We constructed an analytical model to assess the clinical and cost differentials of such strategies.MethodsA probabilistic decisional model simulated a cohort of 1000 NAFLD patients over 1 year from a healthcare payer perspective. Simulations compared standard care (SC) (scenario 1) to: Scenario 2: FIB-4 for all patients followed by Enhanced Liver Fibrosis (ELF) test for patients with indeterminate FIB-4 results; Scenario 3: FIB-4 followed by fibroscan for indeterminate FIB-4; Scenario 4: ELF alone; and Scenario 5: fibroscan alone. Model estimates were derived from the published literature. The primary outcome was cost per case of advanced fibrosis detected.ResultsIntroduction of NILT increased detection of advanced fibrosis over 1 year by 114, 118, 129 and 137% compared to SC in scenarios 2, 3, 4 and 5 respectively with reduction in unnecessary referrals by 85, 78, 71 and 42% respectively.The cost per case of advanced fibrosis (METAVIR ≥F3) detected was £25,543, £8932, £9083, £9487 and £10,351 in scenarios 1, 2, 3, 4 and 5 respectively. Total budget spend was reduced by 25.2, 22.7, 15.1 and 4.0% in Scenarios 2, 3, 4 and 5 compared to £670 K at baseline.ConclusionOur analyses suggest that the use of NILT in primary care can increases early detection of advanced liver fibrosis and reduce unnecessary referral of patients with mild disease and is cost efficient. Adopting a two-tier approach improves resource utilization.

Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation

Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant. Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion. In studies ofAATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals whocarry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940.

Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease

The development of non-invasive liver fibrosis tests may enable earlier identification of patients with non-alcoholic fatty liver disease (NAFLD) requiring referral to secondary care. We developed and evaluated a pathway for the management of patients with NAFLD, aimed at improving the detection of cases of advanced fibrosis and cirrhosis, and avoiding unnecessary referrals. This was a prospective longitudinal cohort study, with analyses performed before and after introduction of the pathway, and comparisons made to unexposed controls. We used a 2-step algorithm combining the use of Fibrosis-4 score followed by the ELF™ test if required. In total, 3,012 patients were analysed. Use of the pathway detected 5 times more cases of advanced fibrosis (Kleiner F3) and cirrhosis (odds ratio [OR]5.18;95%CI2.97-9.04; p <0.0001), while reducing unnecessary referrals from primary care to secondary care by 81% (OR0.193; 95%CI 0.111-0.337; p <0.0001). Although it was used for only 48% of referrals, significant benefits were observed in practices exposed to the pathway compared to those which were not, with unnecessary referrals falling by 77% (OR0.23; 95% CI0.658-0.082; p = 0.006) and a 4-fold improvement in detection of cases of advanced fibrosis and cirrhosis (OR4.32; 95% CI1.52-12.25; p = 0.006). Compared to referrals made before the introduction of the pathway, unnecessary referrals fell from 79/83 referrals (95.2%) to 107/152 (70.4%), representing an 88% reduction in unnecessary referrals when the pathway was followed (OR0.12; 95%CI0.042-0.349; p <0.0001). The use of non-invasive blood tests for liver fibrosis improves the detection of advanced fibrosis and cirrhosis, while reducing unnecessary referrals in patients with NAFLD. This strategy improves resource use and benefits patients. Non-alcoholic fatty liver disease effects up to 30% of the population but only a minority of cases develop liver disease. Our study has shown that established blood tests can be used in primary care to stratify patients with fatty liver disease, leading to a reduction in unnecessary referrals by 80% and greatly improving the detection of cases of advanced fibrosis and cirrhosis.

The enhanced liver fibrosis (ELF) test in diagnosis and management of liver fibrosis.

Liver disease is a major cause of mortality both globally and in the UK. The earlier liver fibrosis is detected, the sooner interventions can be implemented, including lifestyle changes and medications. Non-invasive tests for liver fibrosis are beginning to augment and replace liver biopsy in assessment of liver fibrosis because of their ease of use, lack of complications and reproducibility. The enhanced liver fibrosis (ELF) test is a blood test that measures three molecules involved in liver matrix metabolism to give a score reflecting the severity of liver fibrosis. This article reviews the evidence supporting ELF as a diagnostic test, a prognostic marker and its use in disease monitoring. In doing so it highlights the important role ELF plays in the early recognition of liver fibrosis facilitating timely referral to a liver specialist. The ELF test is useful in primary, secondary and tertiary care, not only allowing earlier diagnosis and more accurate prognosis, but also providing the opportunity to personalize treatment based on the patient's response.

Systematic review: diagnostic accuracy of non-invasive tests for staging liver fibrosis in autoimmune hepatitis.

Non-invasive fibrosis assessment has been highly recommended in many liver diseases. However, comparative diagnostic accuracy of laboratory markers, ultrasound and magnetic resonance elastography (MRE) for fibrosis in autoimmune hepatitis (AIH) patients has not been established. Medline, Embase and Cochrane Library were searched. Primary outcome was significant fibrosis (SF), advanced fibrosis (AF) and cirrhosis, defined as Metavir stage F ≥ 2, F ≥ 3 and F = 4 according to liver biopsy. Hierarchical summary receiver operating characteristic curve (ROC) model was used to evaluate diagnostic accuracy of non-invasive methods. Summary area under ROC (AUROC) and diagnostic odds ratio (DOR) with 95% confidence interval (CI) were calculated. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess quality of evidence. Overall, 16 studies with 861 patients were included, comparing aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), aspartate aminotransferase/alanine aminotransferase ratio, transient elastography (TE), acoustic radiation force impulse, shear wave elastography and MRE versus liver biopsy. Among all non-invasive markers, TE had good performance for fibrosis staging. Summary AUROCs and DORs of TE were 0.90 (95% CI 0.87, 0.92) and 23.7, 0.91 (95% CI 0.89, 0.93) and 31.6, 0.89 (95% CI 0.86, 0.92) and 80.5 for staging SF, AF and cirrhosis, whereas APRI and FIB-4 showed poor performance for detecting AF (DOR, 4.6 and 4.7) and cirrhosis (DOR, 5.5 and 12.9). TE performs well to stage liver fibrosis in patients with AIH, compared with other laboratory non-invasive indexes. Nevertheless, diagnostic accuracy of APRI and FIB-4 is poor.

Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B.

AIMTo explore the effect of alanine aminotransferase (ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B (CHB) patients.METHODSA total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT (ALT ≤ 40), slightly elevated ALT (40 < ALT ≤ 80) and elevated ALT (ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis (stages S2-4), including the aspartate aminotransferase (AST)-to-platelet (PLT) ratio index (APRI), fibrosis index based on 4 factors (FIB-4), King’s score, Forns index and gamma-glutamyl transpeptidase (GGT)-to-PLT ratio (GPR), were evaluated for each group.RESULTSHigher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher non-invasive test scores. The areas under the receiver operating characteristics curves (AUROCs) of the non-invasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L (range 0.705-0.755) and 40 < ALT ≤ 80 U/L (range 0.726-0.79) than for patients with ALT > 80 U/L (range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L (range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L (range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L (range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT.CONCLUSIONALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these non-invasive tests.

Comparative Study between Fibro-Test and Egy-Score as Non-Invasive Markers for Assessment of Hepatic Fibrosis in Chronic Hepatitis C

Backgound: Liver fibrosis (LF) occurs in response to almost all causes of chronic liver injury. Assessing LF is important for both predicting disease progression and monitoring efficacy of therapeutic measures. Most noninvasive tests of liver fibrosis were developed with the aim of discriminating between “insignificant”, (F0-F1) by METAVIR and clinically “significant” fibrosis (≥ F2) by METAVIR or for identifying or excluding established cirrhosis in patients with well compensated chronic liver disease. Both these aims are clinically the most relevant. Aim: We aimed to compare the diagnostic accuracy of FibroTest and Egy-Score as predictors of stage of hepatic fibrosis in a prospectively enrolled cohort of Egyptian patients with chronic hepatitis C. Patients and Methodlogy: Twenty patients, treatment naive chronic hepatitis C patients were enrolled. They were 16 males (80%) and 4 females (20%) mean age of these patients was 53.55 +14.3 (rang 18_73 years). The study was carried out in the Department of Gastroenterology and Hepatology, Elhussin hospital, Al-Azhar University during the period between March 2016 and March 2018. Results: Our results showed a highly significant positive correlation between stage of hepatic fibrosis by METAVIR and fibrotest. Our results showed a highly significant positive correlation between stage of hepatic fibrosis by METAVIR and EGY-SCOR. Our scores depend mainly on simple routinely used laboratory parameters (total bilirubin, albumin, platelet count) in addition to age and 2 non routine tests (CA 19-9 and Alpha-2-Macroglobulin). Although this panel needs to be done in validated laboratories, the cost of our score is much cheaper than other well-known and patented tests such as FibroTest and the net results of both methods nearly the same. Conclusion: Egy-Score can be applied easily in clinical practice to exclude severe hepatic fibrosis/cirrhosis in patients with contraindication for liver biopsy or those who are reluctant to do it. Egy-score would need further valida‌tion to be regarded as an alternative to liver biopsy. Recommendations: Physician should be careful when interpreting elevated levels of tu‌mor markers CA 19-9 and CA 125 in patients with chronic liver disease as this could be a benign elevation related to hepatic fibrosis and not necessarily due to underlying malignancies. Elevation of the tumor markers such as CA19.9 have been associated with cholestasis in liver disease patients and this may give false positive results for our scores which give Limitations to our study.

Comparative Study between Fibro-Test and Egy-Score as Non-Invasive Markers for Assessment of Hepatic Fibrosis in Chronic Hepatitis C

Backgound: Liver fibrosis (LF) occurs in response to almost all causes of chronic liver injury. Assessing LF is important for both predicting disease progression and monitoring efficacy of therapeutic measures. Most noninvasive tests of liver fibrosis were developed with the aim of discriminating between “insignificant”, (F0-F1) by METAVIR and clinically “significant” fibrosis (≥ F2) by METAVIR or for identifying or excluding established cirrhosis in patients with well compensated chronic liver disease. Both these aims are clinically the most relevant. Aim: We aimed to compare the diagnostic accuracy of FibroTest and Egy-Score as predictors of stage of hepatic fibrosis in a prospectively enrolled cohort of Egyptian patients with chronic hepatitis C. Patients and Methodlogy: Twenty patients, treatment naive chronic hepatitis C patients were enrolled. They were 16 males (80%) and 4 females (20%) mean age of these patients was 53.55 +14.3 (rang 18_73 years). The study was carried out in the Department of Gastroenterology and Hepatology, Elhussin hospital, Al-Azhar University during the period between March 2016 and March 2018. Results: Our results showed a highly significant positive correlation between stage of hepatic fibrosis by METAVIR and fibrotest. Our results showed a highly significant positive correlation between stage of hepatic fibrosis by METAVIR and EGY-SCOR. Our scores depend mainly on simple routinely used laboratory parameters (total bilirubin, albumin, platelet count) in addition to age and 2 non routine tests (CA 19-9 and Alpha-2-Macroglobulin). Although this panel needs to be done in validated laboratories, the cost of our score is much cheaper than other well-known and patented tests such as FibroTest and the net results of both methods nearly the same. Conclusion: Egy-Score can be applied easily in clinical practice to exclude severe hepatic fibrosis/cirrhosis in patients with contraindication for liver biopsy or those who are reluctant to do it. Egy-score would need further valida‌tion to be regarded as an alternative to liver biopsy. Recommendations: Physician should be careful when interpreting elevated levels of tu‌mor markers CA 19-9 and CA 125 in patients with chronic liver disease as this could be a benign elevation related to hepatic fibrosis and not necessarily due to underlying malignancies. Elevation of the tumor markers such as CA19.9 have been associated with cholestasis in liver disease patients and this may give false positive results for our scores which give Limitations to our study.

Noninvasive Liver Fibrosis Tests in Patients with Nonalcoholic Fatty Liver Disease: An External Validation Cohort.

The main aim of this study was the comparative evaluation of nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), fibrosis 4 index (FIB-4), AST-to-Platelet Ratio Index (APRI), and enhanced liver fibrosis (ELF) test in distinguishing none/early (F0/F1) from significant/advanced (F2/F3) fibrosis in NAFLD patients, thereby providing an external validation cohort. Thirty-one patients with biopsy-proven NAFLD and 10 matched controls without NAFLD were prospectively enrolled. Serum hyaluronic acid (HA), aminoterminal propeptide of type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases (TIMP)-1, and biochemical tests were measured. NFS, FIB-4, APRI, and ELF were calculated. ELF, FIB-4, and APRI, but not NFS, were higher in F2/F3 than F0/F1 group. Specifically, ELF [area under the ROC curve (AUROC): 0.86±0.10; p=0.004) and APRI (AUROC: 0.86±0.07; p=0.005], but not NFS (AUROC: 0.68±0.12; p=0.16), and FIB-4 (AUROC: 0.71±0.11; p=0.10), could similarly discriminate F0/F1 from F2/F3 stage. The sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were: a) for cut-off of APRI=0.5, 85.7%, 70.8%, 46.2%, and 94.4%, respectively, and b) for cut-off of ELF=9.0, 85.7%, 83.3%, 60.0%, and 95.2%, respectively. When ln(PIIINP) or TIMP-1 were combined with APRI, the combined AUROCs could distinguish F2/F3 from F0/F1, but without significantly higher accuracy compared with APRI alone. APRI could also distinguish patients with simple steatosis from nonalcoholic steatohepatitis, and those with from those without lobular inflammation and ballooning, findings warranting further research. In conclusions: The application of ELF test and APRI can distinguish F0/F1 from F2/F3 fibrosis stages in NAFLD patients.

Concordance of non-invasive tests for liver fibrosis in HCV patients proposed for treatment with direct acting antivirals

Concordance of non-invasive tests for liver fibrosis in HCV patients proposed for treatment with direct acting antivirals

A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis

Chronic liver diseases (CLD) are common, and are therefore mainly managed by non-hepatologists. These physicians lack access to the best non-invasive tests of liver fibrosis, and consequently cannot accurately determine the disease severity. Referral to a hepatologist is then needed. We aimed to implement an algorithm, comprising a new first-line test usable by all physicians, for the detection of advanced liver fibrosis in all CLD patients. Diagnostic study: 3754 CLD patients with liver biopsy were 2:1 randomized into derivation and validation sets. Prognostic study: longitudinal follow-up of 1275 CLD patients with baseline fibrosis tests. Diagnostic study: the easy liver fibrosis test (eLIFT), an "at-a-glance" sum of points attributed to age, gender, gamma-glutamyl transferase, aspartate aminotransferase (AST), platelets and prothrombin time, was developed for the diagnosis of advanced fibrosis. In the validation set, eLIFT and fibrosis-4 (FIB4) had the same sensitivity (78.0% vs. 76.6%, p=0.470) but eLIFT gave fewer false positive results, especially in patients ≥60years old (53.8% vs. 82.0%, p<0.001), and was thus more suitable as screening test. FibroMeter with vibration controlled transient elastography (VCTE) was the most accurate among the eight fibrosis tests evaluated. The sensitivity of the eLIFT-FMVCTE algorithm (first-line eLIFT, second-line FibroMeterVCTE) was 76.1% for advanced fibrosis and 92.1% for cirrhosis. Prognostic study: patients diagnosed as having "no/mild fibrosis" by the algorithm had excellent liver-related prognosis with thus no need for referral to a hepatologist. The eLIFT-FMVCTE algorithm extends the detection of advanced liver fibrosis to all CLD patients and reduces unnecessary referrals of patients without significant CLD to hepatologists. Blood fibrosis tests and transient elastography accurately diagnose advanced liver fibrosis in the large population of patients having chronic liver disease, but these non-invasive tests are only currently available in specialized centers. We have developed an algorithm including the easy liver fibrosis test (eLIFT), a new simple and widely available blood test. It is used as a first-line procedure that selects at-risk patients who need further evaluation with the FibroMeterVCTE, an accurate fibrosis test combining blood markers and transient elastography result. This new algorithm, called the eLIFT-FMVCTE, accurately identifies the patients with advanced chronic liver disease who need referral to a specialist, and those with no or mild liver lesions who can remain under the care of their usual physician. No registration (analysis of pooled data from previously published diagnostic studies).

Reply

We thank Drs. Sarikaya, Turan, and Celikbilek for their interest in our work. Our recommendation against screening for nonalcoholic fatty liver disease (NAFLD) in patients with suspected or confirmed coronary artery disease was based on several key points.1 First, despite the strong association between NAFLD and coronary artery disease, most such patients died of cardiovascular complications and not hepatocellular carcinoma or cirrhosis. Second, NAFLD did not predict cardiovascular outcomes in patients with already established coronary artery disease. Third, in line with the recommendations of the American Association for the Study of Liver Diseases, we agree that the optimal screening tool is yet to be defined.2 After all, it is the severity of liver disease and not the mere presence of hepatic steatosis that counts. In that regard, the use of noninvasive tests of liver fibrosis as a screening tool deserves further evaluation.3 As for the apparently lower cardiovascular mortality in patients with NAFLD and coronary artery disease, our additional analysis suggests that aggressive treatment of this high-risk group such as the use of statins has probably altered the natural history of disease.4 Patients with NAFLD were more likely to receive statins than those without (91% versus 73%; P < 0.0001), and statin users had much lower risk of death (hazard ratio 0.30, 95% confidence interval 0.20-0.45; P < 0.0001). The importance of proper management of metabolic factors cannot be overemphasized. On the other hand, we agree with Drs. Sarikaya, Turan, and Celikbilek that coronary intervention does not improve survival in patients with stable angina and should be reserved for those with stronger indications. Vincent Wai-Sun Wong, M.D.1,2 Grace Lai-Hung Wong, M.D.1,2 Henry Lik-Yuen Chan, M.D.1,2 1Department of Medicine and Therapeutics 2State Key Laboratory of Digestive Disease The Chinese University of Hong Kong Hong Kong

Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis

The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis.

SAT-429 - National Survey Investigating the Potential Role of Non-Invasive Liver Fibrosis Tests in the UK

SAT-429 - National Survey Investigating the Potential Role of Non-Invasive Liver Fibrosis Tests in the UK

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation.

SummaryWe compared the cost‐effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta‐analysis to calculate the diagnostic accuracy of various NITs using a bivariate random‐effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality‐adjusted‐life‐years (QALYs) using data from the meta‐analysis, literature, and national UK data. We compared the cost‐effectiveness of four decision‐making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost‐effectiveness ratio (ICER) of £28 137 per additional QALY gained for HBeAg‐negative patients. For HBeAg‐positive patients, using Fibroscan was the most cost‐effective option with an ICER of £23 345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥F2 prevalence and the benefit of treatment in patients with F0–F1. For HBeAg‐negative patients, strategies excluding NITs were the most cost‐effective: treating all patients regardless of fibrosis level if the high cost‐effectiveness threshold of £30 000 is accepted; watchful waiting if not. For HBeAg‐positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost‐effective option.

Biomarcadores, índices y algoritmos para el diagnóstico de fibrosis hepática en pacientes con hepatitis crónica por virus C

Precise staging of liver fibrosis is essential in the management of liver disease activity in chronic hepatitis C patients. Liver biopsy has been considered the reference method for diagnosing disease, grading necroinflammatory activity, and staging fibrosis, but it has some technical limitations and risks. Taking into account these limitations, there is a need to introduce non-invasive serum markers for fibrosis that would be able to partially replace liver biopsy. Ideal serum markers should be specific for the liver and easy to perform. Serum markers of hepatic fibrosis are divided into direct and indirect. Direct markers reflect extracellular matrix turnover, whereas indirect markers reflect alterations in hepatic function. The degree of implementation of non-invasive diagnostic tests for liver fibrosis still remains limited. This review provides a current overview of biomarkers, indexes and algorithms for hepatic fibrosis diagnosis in chronic hepatitis C patients.