Non-invasive Assessment Of Liver Fibrosis Research Articles

Noninvasive Assessment of Liver Fibrosis in Patients with Sickle Cell Disease

Complications affecting multiple organs, including the liver, contribute to early mortality in patients with sickle cell disease (SCD). Earlier diagnosis and monitoring of "sickle hepatopathy", preferably using non-invasive methods, would enable earlier intervention and therefore, potentially a better outcome for patients.In many non-SCD chronic liver diseases, fibrosis stage is the most important predictor of morbidity and mortality. Two non-invasive methods of assessing liver fibrosis are used: Transient Elastography (TE, Echosens) and Enhanced Liver Fibrosis Score™ (ELF, iQUR). TE detects fibrosis using ultrasound and low frequency elastic waves with a propagation velocity directly related to the stiffness of the liver. The ELF score examines the balance between matrix deposition and degradation using levels of three proteins analysed using a patented formula.We report a prospective study correlating liver function tests (LFTs) with the level of liver fibrosis (as ascertained by TE and ELF) in a cohort of patients with SCD. Ethical approval for this study was obtained from the NHS ethics committee (11/LO/0005) and patients were consecutively recruited in the steady-state sickle cell clinic at Kings' College Hospital, London, during 2012. Patients were excluded if they had viral hepatitis or were pregnant. Clinical (transfusion and hydroxyurea therapy), imaging (liver iron concentration, LIC) and laboratory data were collected during steady-state.TE and ELF were performed on 194 patients. The patients ranged from 17-72 years (mean age 35 years); 78 (40%) were male, 134 (68%) had HbSS or HbSb0 (SCA), 48 (26%) Hb SC, and the remainder, Hb Sβ+ (excluded due to low numbers). Statistical analysis was undertaken in IBM SPSS version 20.There was significant correlation between both TE and ELF with age, when corrected for sickle genotype (TE β = 0.19, p = 0.006 and ELF β = 0.2, p = 0.005) (Figure). Patients with SCA had significantly higher TE results and mean ELF scores than those with HbSC (TE, 6.8 vs 5.3, p<0.0001 and ELF, 9.2 vs 8.6 p <0.0001) (Table).In SCA patients, TE correlated significantly with all serum LFTs (Albumin R = -0.35 p<0.0001, AST R = 0.44 p<0.0001, ALP R = 0.29 p<0.0001, GGT R = 0.40 p<0.0001, conjugated bilirubin R = 0.26 p = 0.004). Positive correlation was found with LDH (R = 0.24 p = 0.004) and negative correlation with Hb (R= -0.25 p = 0.002). In the Hb SC group, TE correlations were weaker for AST (R = 0.39 p = 0.004), ALP (R = 0.30 p = 0.03), WBC (R = 0.39 p = 0.02) and reticulocyte count (R = 0.35 p = 0.01). All markers of iron loading correlated with TE values, when corrected for sickle genotype (serum ferritin β = 0.25, p <0.0001, total top-up units β = 0.22, p = 0.001, total units transfused β = 0.25, p <0.0001 and LIC β = 0.32, p = 0.046).In SCA patients, ELF score correlated with serum LFTs (Albumin R = -0.30 p<0.0001, AST R = 0.39 p<0.0001, ALP R = 0.25 p = 0.003, GGT R = 0.28 p = 0.001, conjugated bilirubin R = 0.36 p<0.0001). Positive correlation was seen with LDH (R = 0.26 p = 0.002) and negative correlation with Hb (R = -0.25 p = 0.004). Negative correlation was also seen with HbF levels (R = -0.24 p = 0.01). In the HbSC group, there were no significant correlations between ELF and serum LFTs. However associations were seen between ELF score and LDH (R = 0.40 p = 0.004) and Hb level (R = -0.31 p = 0.01). ELF score correlated with serum ferritin (β = 0.25 p <0.0001), and total blood transfusion units (β = 0.24 p = 0.001).These data show significant levels of liver dysfunction in our SCD population using both TE and ELF score which correlated significantly with abnormal LFTs and markers of hemolysis and iron overload. The role of TE and ELF in monitoring liver dysfunction in SCD needs to be further validated, preferably with longitudinal, and if possible histological data.Table 1Range and mean TE results and ELF score for whole cohort and subgroups.Whole cohort n = 194 (%)SCA n = 134 (%)Hb SC n = 48 (%)p valueFibroScan results (kPa)Mean (range)6.3 (2.0 - 21.3)6.8 (2.0 - 21.3)5.3 (2.0 - 16.0)< 0.0001None/mild (0-7.65)153 (79)98 (73)43 (90)Moderate (7.66-13.00)33 (17)29 (22)4 (8)Severe (≥13.01)8 (4)7 (5)1 (2)ELF scoreMean (range)9.1 (7.1 - 11.6)9.2 (7.1 - 11.6)8.6 (7.5 - 10.3)<0.0001None/mild (≤9.7)164 (84)107 (79)46 (96)Moderate (9.8 - 11.2)27 (14)24 (19)2 (4)Severe (≥11.3)3 (2)3 (2)0 (0) [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Non-invasive assessment of liver fibrosis in chronic viral hepatitis.

Hyaluronic acid (HA), ASAT to Platelet Ratio Index (APRI), ASAT/ALAT ratio, Fibrosis 4 score (FIB4) and FibroScan were studied as non-invasive markers of liver fibrosis (F) in chronic viral hepatitis B (CHB) and C (CHC), in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of F. The aim of our research was to study whether HA, APRI, ASAT/ALAT ratio, FIB4 and FibroScan are useful non-invasive markers in predicting severe F in Romanian patients. This was a prospective multicenter transversal and observational study, which included 76 patients with CHB/CHC. The independent effect of studied markers was tested using multiple binary logistic regression. In patients with CHB and CHC, the APRI cut-off value for F4 was 0·70 ng/mL (Se = 77%, Sp = 78%), the FIB4 cut-off value was 2·01 (Se = 77%, Sp = 69%), and the FibroScan cut-off value was 13·15 (Se = 92%, Sp = 88%). For patients with CHB/CHC, there was a significant linear positive correlation between F and HA (r = 0·42, P = 0·001), FibroScan (r = 0·67, P < 0·001), APRI (r = 0·46, P < 0·001) and FIB4 (r = 0·51, P < 0·001). Considering age, sex and body mass index as possible confounding factors or covariates in multivariable logistic modelling, FibroScan was the unique test that able to significantly highlight the presence of F4 score in CHB/CHC patients (P = 0·009) while FIB4 test seems to have a tendency to statistical significance. FibroScan, APRI and FIB4 are useful non-invasive tests for the evaluation of F4 in patients with CHB and CHC.

Indications of Liver Biopsy in the Era of Noninvasive Assessment of Liver Fibrosis

Liver biopsy (LB) has been used as diagnostic modality in liver diseases (LD). Over last two decades, there has been remarkable improvement in understanding of natural history, molecular diagnostics of viral hepatitis, genetic of LD, and also limitations of LB. There is current trend in avoiding LB in the management of various LDs. To determine utility of LB in clinical practice. In a prospective study, 2413 patients of LD were followed up, 219 (9%) were acute, and remaining 2194 (90.9%) were chronic LD. Patients were evaluated by biochemical parameters, virological studies, and imaging endoscopy as and when required. LB was performed in 176 (7.2%) patients when no conclusion could be drawn from the noninvasive workup. Patients with platelet count <50,000/cm(2), ascites, and overt bleeding were excluded. Patients with international normalization ratio (INR) more than 1.5 were not excluded. No prophylactic use of fresh frozen plasma and platelet transfusion was done. There was no major complication related to the procedure. Indications for LB were as follows: cryptogenic LD 38 cases, hepatitis B infection 35, suspected autoimmune hepatitis 30, mass lesion in the liver and lymphoma 29, evaluation of portal hypertension 15, elevated liver enzymes 11, hepatitis C infection 9, and drug-induced LD 4, and miscellaneous 5 cases which were primary biliary cholangitis, primary sclerosing cholangitis, cholestatic LD, sarcoidosis, and amyloidosis. LB changed the diagnosis in 55 (31.2%). These were cryptogenic LD in 24 cases, portal hypertension 15, elevated liver enzymes 11, and 5 others. In remaining, LB confirmed clinical diagnosis and helped in making management decisions. LB was required in 7.2% of patients with chronic LD. In 31.2% cases, LB changed the diagnosis. LB was a safe procedure even in presence of low platelet count and abnormal INR.

Assessment of liver fibrosis in chronic hepatitis B using acoustic structure quantification: quantitative morphological ultrasound.

To prospectively investigate the usefulness of acoustic structure quantification (ASQ) for noninvasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). Consecutive patients with CHB scheduled for liver biopsy or partial liver resection underwent standardized ASQ examinations. The ASQ parameter, named focal disturbance (FD) ratio, were compared with METAVIR scores. The analysis was based on receiver operating characteristic (ROC) curves and multiple regression analysis. A total of 114 patients were enrolled in the final analysis. The area under the ROC curve for the FD ratio was 0.84 for significant fibrosis (≥ F2), 0.86 for severe fibrosis (≥ F3), and 0.83 for cirrhosis (= F4). The optimal cutoff values for the FD ratio were 0.25, 0.30 and 0.50 for fibrosis stages ≥ F2, ≥ F3 and = F4, respectively. The prevalence of a difference of at least two stages between the FD ratio and the histological stage was 12.3% (14 of 114). The fibrosis stage (P < 0.001), degree of steatosis (P < 0.001) were independent factors associated with the FD ratio. FD ratio should be an effective noninvasive imaging biomarker for the assessment of liver fibrosis in patients with CHB. • Focal disturbance (FD) ratio increased with the increasing histological fibrosis stages. • FD ratio showed promising diagnostic accuracy in assessing liver fibrosis. • Degree of fibrosis and steatosis were independent factors associated with FD ratio.

Applying non-invasive assessment of liver fibrosis in chronic hepatitis B patients with equivocal indication for antiviral therapy

Applying non-invasive assessment of liver fibrosis in chronic hepatitis B patients with equivocal indication for antiviral therapy

Prediction of posthepatectomy liver failure based on liver stiffness measurement in patients with hepatocellular carcinoma

Posthepatectomy liver failure (PHLF) is a potentially fatal complication, and the accurate prediction of PHLF is essential. Liver stiffness measurement (LSM) has been accepted widely as a noninvasive assessment for liver fibrosis. We aimed to evaluate the usefulness of LSM in predicting PHLF. One hundred seventy-seven patients with hepatocellular carcinoma who underwent liver resection between August 2011 and October 2014 were analyzed prospectively. LSM was performed by Virtual Touch Tissue Quantification based on acoustic radiation force impulse imaging, and its value was expressed as the shear wave velocity (Vs) [m/s]. The remnant liver volume rate (Rem) was calculated by computed tomography volumetry. PHLF was diagnosed on the basis of the definition from the International Study Group of Liver Surgery. PHLF occurred in 38 patients (21.5%): grade A, 17 patients (9.6%); grade B, 15 patients (8.5%); and grade C, 6 patients (3.4%). The area under the receiver operating characteristic curve of the Vs for predicting PHLF was 0.67 for grade ≥A, 0.78 for grade ≥B, and 0.74 for grade C, which was greater than any other preoperative factor for each grade. Multivariate stepwise selection identified 2 significant factors associated with PHLF grade ≥B: Vs (odds ratio, 2.66; 95% confidence interval, 1.69-4.41, P<.01) and Rem (odds ratio, 0.47; 95% confidence interval, 0.27-0.79, P<.01). The logistic model that included the Vs and Rem resulted in an area under the receiver operating characteristic curve of 0.80 for predicting PHLF grade ≥B. LSM was useful for the prediction of PHLF and the estimation of the safe Rem range.

Liver disease knowledge and acceptability of non-invasive liver fibrosis assessment among people who inject drugs in the drug and alcohol setting: The LiveRLife Study

BackgroundThe aim of this study was to assess factors associated with baseline knowledge of HCV and liver disease, acceptability of transient elastography (TE) assessment (FibroScan®), and willingness and intent to receive HCV treatment among persons with a history of injection drug use participating in a liver health promotion campaign. MethodsThe LiveRLife campaign involved three phases: (1) campaign resource development; (2) campaign resource testing; and (3) campaign implementation. Participants were enrolled in an observational cohort study with recruitment at four clinics – one primary health care facility, two OST clinics, and one medically supervised injecting centre – in Australia between May and October 2014. Participants received educational material, nurse clinical assessment, TE assessment, dried blood spot testing, and completed a knowledge survey. ResultsOf 253 participants (mean age 43 years), 68% were male, 71% had injected in the past month, and 75% self-reported as HCV positive. Median knowledge score was 16/23. In adjusted analysis, less than daily injection (AOR 5.01; 95% CI, 2.64–9.51) and no daily injection in the past month (AOR 3.54; 95% CI, 1.80–6.94) were associated with high knowledge (≥16). TE was the most preferred method both pre- (66%) and post-TE (89%) compared to liver biopsy and blood sample. Eighty-eight percent were ‘definitely willing’ or ‘somewhat willing’ to receive HCV treatment, and 56% intended to start treatment in the next 12 months. Approximately 68% had no/mild fibrosis (F0/F1, ≥2.5 to ≤7.4kPa), 13% moderate fibrosis (F2, ≥7.5 to ≤9.4kPa), 10% severe fibrosis (F3, ≥9.5 to ≤12.4kPa), and 9% had cirrhosis (F4, ≥12.5kPa). ConclusionLiver disease and HCV knowledge was moderate. High acceptability of TE by PWID provides strong evidence for the inclusion of TE in HCV-related care, and could help to prioritise HCV treatment for those at greatest risk of liver disease progression.

Assessment of Liver Fibrosis with 2-D Shear Wave Elastography in Comparison to Transient Elastography and Acoustic Radiation Force Impulse Imaging in Patients with Chronic Liver Disease

Two-dimensional shear wave elastography (2-D SWE) is an ultrasound-based elastography method integrated into a conventional ultrasound machine. It can evaluate larger regions of interest and, therefore, might be better at determining the overall fibrosis distribution. The aim of this prospective study was to compare 2-D SWE with the two best evaluated liver elastography methods, transient elastography and acoustic radiation force impulse (point SWE using acoustic radiation force impulse) imaging, in the same population group. The study included 132 patients with chronic hepatopathies, in which liver stiffness was evaluated using transient elastography, acoustic radiation force impulse imaging and 2-D SWE. The reference methods were liver biopsy for the assessment of liver fibrosis (n = 101) and magnetic resonance imaging/computed tomography for the diagnosis of liver cirrhosis (n = 31). No significant difference in diagnostic accuracy, assessed as the area under the receiver operating characteristic curve (AUROC), was found between the three elastography methods (2-D SWE, transient elastography, acoustic radiation force impulse imaging) for the diagnosis of significant and advanced fibrosis and liver cirrhosis in the “per protocol” (AUROCs for fibrosis stages ≥2: 0.90, 0.95 and 0.91; for fibrosis stage [F] ≥3: 0.93, 0.95 and 0.94; for F = 4: 0.92, 0.96 and 0.92) and “intention to diagnose” cohort (AUROCs for F ≥2: 0.87, 0.92 and 0.91; for F ≥3: 0.91, 0.93 and 0.94; for F = 4: 0.88, 0.90 and 0.89). Therefore, 2-D SWE, ARFI imaging and transient elastography seem to be comparably good methods for non-invasive assessment of liver fibrosis.

PWE-124 Role of acoustic radiation force impulse (arfi) elastography in non-invasive assessment of liver fibrosis in iron overload: a single centre experience

Introduction The predictive accuracy of ARFI elastography (virtual touch quantification, VTq ™) for the non-invasive assessment of liver fibrosis is increasingly recognised, particularly in viral hepatitis. There is less information on its role in other aetiologies of chronic liver disease. We report the results of a preliminary study examining liver stiffness (LS) measurements by ARFI in patients with iron overload. Method Forty-nine measurements of LS in 43 patients were performed to investigate possible iron overload. LS estimation by ARFI was performed using a standard validated protocol with a Siemens Acuson S2000 + 4C1 probe. Biopsies were performed in 19 (39%) from the same region of liver, immediately after LS measurement. Clinical, biochemical, ultrasonic and histopathological data were collated retrospectively. Predictive accuracy variables were determined for fibrosis stage, using both standard published and local 1 calibrations. Results Aetiologies of iron overload in the biopsy cohort were: genetic haemochromatosis (n = 4); hyperferritinaemia with NAFLD or alcohol excess (8); hyperferritinaemia of unknown cause (3); transfusion-dependent thalassaemia (2); C282Y/H63D compound heterozygote (1); and high ferritin from renal cell carcinoma (1). Validation criteria for ARFI technical quality (SD/mean 1 ; b) the exclusion of ≥F2 fibrosis were 0.80, 0.78, 0.80 and 0.78, respectively, with both calibrations. No correlation was seen between LS and either a) necro-inflammation, histological grade of siderosis or scan technical quality; or b) serum ferritin levels. Conclusion ARFI elastography may prove a useful non-invasive technique for excluding F2 fibrosis and identifying F4 cirrhosis secondary to iron overload. The high incidence of dual pathology, particularly NAFLD and alcohol-related, may have influenced predictive accuracy in this small “real world” cohort. The degree of hepatic iron overload did not correlate with LS. Further biopsy-controlled studies are needed to validate the role of ARFI in this patient group. Disclosure of interest None Declared. Reference Sherman D, et al . J Hepatol. 2014;60(1):S413

Angiotensin-converting enzyme for noninvasive assessment of liver fibrosis in autoimmune hepatitis.

There are no validated noninvasive markers of liver fibrosis in autoimmune hepatitis (AIH). An activated renin-angiotensin system (RAS) and its key element angiotensin-converting enzyme (ACE) have been implicated in the pathogenesis of hepatic fibrogenesis. We aimed to study the assumed role of activated RAS in the fibrogenic process and whether the serum concentration of ACE can predict different fibrosis stages in AIH. Serum samples of 73 consecutive patients who were diagnosed with AIH were analysed for ACE concentration. All patients underwent a liver biopsy. Serum ACE levels increased significantly for each fibrosis score. The median ACE was 45 U/l in patients with fibrosis score I, 54 U/l in patients with fibrosis score II, 68 U/l in patients with fibrosis score III and 87 U/l in patients with fibrosis score IV. For significant fibrosis (≤F2), a 56 U/l cut-off value of ACE had 95.5% sensitivity and 74.5% specificity, and receiver-operating characteristic curves showed an area under the curve (AUC) of 0.89. For advanced fibrosis (≤F3), a 64 U/l cut-off level of ACE had 85.2% sensitivity and 94.8% specificity, and AUC was 0.91. For cirrhosis, a 68 U/l cut-off level of ACE had 100% sensitivity and 84.4% specificity, and AUC was 0.95. Our results suggest that activated RAS may sustain hepatic fibrogenesis in AIH. Measurement of serum ACE offers an easy, accurate and inexpensive noninvasive method that differentiates significant from nonsignificant liver fibrosis in AIH. Blockade of RAS may exert beneficial effects on fibrosis progression in AIH.

Vibration-controlled transient elastography: a practical approach to the noninvasive assessment of liver fibrosis.

Therapeutic advances for hepatitis C and the increasing prevalence on nonalcoholic fatty liver disease are reshaping the diagnostic approach to disease staging in clinical hepatology. Well tolerated, inexpensive and reliable alternatives to liver biopsy are a critical need for clinicians and patients alike. Vibration-controlled transient elastography (VCTE, also known as 'transient elastography') is a robust, point-of-care tool for the noninvasive assessment of liver fibrosis. This tool efficiently prioritizes the treatment for patients with viral hepatitis at risk for advanced liver disease and identifies the subgroups with metabolic or cholestatic liver disease who are at the highest risk. Rather than staging fibrosis, VCTE provides an accurate risk estimate of advanced fibrosis. In addition, it is increasingly recognized that elastography can predict outcomes including hepatic decompensation and mortality. The ideal use of this tool is to perform it in conjunction with a serologic marker of fibrosis to confirm its findings. When combined with serologic markers of fibrosis, VCTE allows the vast majority of patients to avoid a liver biopsy.

P0526 : Accuracy of point shear wave elastography technique (elastpq) in the non-invasive assessment of liver fibrosis in various liver diseases

P0526 : Accuracy of point shear wave elastography technique (elastpq) in the non-invasive assessment of liver fibrosis in various liver diseases

P0049 : Evaluation of acoustic radiation force impulse imaging (ARFI) elastography for non-invasive liver fibrosis assessment in patients after liver transplantation

P0049 : Evaluation of acoustic radiation force impulse imaging (ARFI) elastography for non-invasive liver fibrosis assessment in patients after liver transplantation

Clinical application of noninvasive diagnosis of liver fibrosis

Hepatic fibrosis is the common outcome of chronic liver diseases of various causes. At present,liver biopsy is the “gold standard”for the diagnosis of liver fibrosis,but it has limitations and is invasive,which leads to the development of noninvasive assessment of liver fibrosis. The article mainly introduces the technology and application of noninvasive diagnosis of liver fibrosis from the aspects of clinical manifestation,serology,and radiology. It has pointed out the clinical value of these noninvasive diagnosis techniques,and it discusses the progress in clinical research and its limitations for noninvasive diagnosis of liver fibrosis.

Two are better than one: noninvasive assessment of liver fibrosis in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in many regions, affecting 15–40 % of the general population [1, 2]. One of the key challenges in managing NAFLD is differentiating simple steatosis from advanced disease, i.e., those with nonalcoholic steatohepatitis (NASH), advanced fibrosis or even cirrhosis [3]. The challenge is further substantiated by the poor correlation between liver fibrosis and routine blood tests, e.g., the serum alanine aminotransferase (ALT) level [4]. Patients may have progressed to advanced fibrosis or cirrhosis without any abnormalities in these common blood parameters [5]. Liver biopsy is not always feasible or acceptable to patients, especially to those largely asymptomatic subjects; this has promoted the popularity of noninvasive assessments of liver fibrosis for NAFLD patients (Table 1) [6, 7]. Among the numerous noninvasive assessments, liver stiffness measurement (LSM) by transient elastography is one of the most popular tools [8]. This tool out-performed other serum parameters in detecting advanced fibrosis or cirrhosis [9]. Nonetheless, a false-positive diagnosis of advanced fibrosis is not uncommon, in addition to LSM results lying in the gray zone [9]. This would be an even more serious problem in obviously obese subjects, as the LSM is higher among those with a body mass index (BMI) above 30 kg/m in the same fibrosis stage [10]. On the other hand, the NAFLD fibrosis score (NFS) is the beststudied serum-based combined clinical algorithm; it was recommended in the latest American practice guidelines for NAFLD [11]. All these observations have raised the interest in combining these two well-studied noninvasive parameters. On the other hand, magnetic resonance elastography (MRE) is probably even more accurate than LSM and NFS [12]. Nonetheless, MRE is not as widely available as these two tools. Recently, Chan et al. [13] evaluated the diagnostic performance a novel two-step approach combining NFS and LSM. The beauty of this study was the robust methodology of including two independent groups of patients as the training and validation cohort, respectively. The detailed comparison of the performance of various approaches, be it either parameter alone or combining two parameters in different fashions, established this novel twostep approach as the best among the five to avoid liver biopsy. Similar approaches have been proposed in patients with chronic hepatitis B [14, 15]; this was the first time in NALFD patients. The unresolved questions remaining include the suboptimal performance of NFS in Asian subjects because of the different BMI cutoffs for obesity [16]. This was echoed by the relatively low sensitivity (40 %) of NFS to predict advanced fibrosis in Chan’s study. Investigators should pay special attention when applying any parameters derived from the west to Asian patients, such that different cutoffs or even different algorithms should be considered. It would be helpful if another serum parameter with better performance could be found. Cytokeratin-18 (CK18) fragments have been investigated extensively as novel biomarkers for G. L.-H. Wong H. L.-Y. Chan Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong

Noninvasive assessments of liver fibrosis with transient elastography and Hui index predict survival in patients with chronic hepatitis B.

The prognostic role of noninvasive assessments of liver fibrosis has been evolving. Our aim was to investigate the prognostic value of liver stiffness measurement (LSM) with transient elastography and serum-based Hui index to predict hepatic events and deaths in chronic hepatitis B (CHB) patients. The main prospective cohort included 1555 consecutive CHB patients referred for transient elastography examination; a subgroup of 980 patients underwent follow-up assessments at least 3 years later formed the serial cohort. Cox proportional hazard model was performed to determine the relationship of LSM, Hui index and other clinical variables with hepatic events and deaths. During a mean follow-up of 69 ± 9 months, 119 patients (7.6%) developed hepatic events or deaths. Hepatic event-free survival was significantly decreased with increasing stages of LSM and Hui index. The 5-year cumulative probability of hepatic event-free survival of patients of Stage 1-7 of LSM were 99.3%, 98.8%, 95.7%, 90.9%, 89.6%, 74.6%, and 50.0%, respectively; that of Stage 1 to 3 of Hui index were 98.2%, 93.1%, and 77.5%, respectively. Independent predictors of hepatic event-free survival were age, baseline LSM, and follow-up Hui index. Serum ALT and body mass index affected the accuracy of prediction by LSM. Patients remained early stages of LSM or Hui index at follow-up visit had better survival compared to those remained at late stages. Baseline and change in noninvasive parameters of liver fibrosis, LSM and Hui index, are accurate to predict hepatic event-free survival in CHB patients.

Non-invasive assessment of liver fibrosis in C282Y homozygous HFE hemochromatosis.

C282Y homozygotes with serum ferritin (SF) levels >1000μg/L and/or increased serum transaminase levels are at risk of severe F3/F4 fibrosis. Current practical guidelines recommend liver biopsy in such individuals. This prospective observational cohort study aimed to evaluate non-invasive alternative means such as hyaluronic acid (HA) and transient elastography (TE) for the assessment of severe fibrosis in patients with SF >1000μg/L or elevated transaminases. Between September 2005 and April 2013, 77 patients diagnosed C282Y homozygotes underwent a liver biopsy because of SF >1000μg/L and/or increased transaminases according to current guidelines, with concomitant TE. All of them had clinical and biological evaluation, including HA measurement in 52 cases. A total of 19.5% of patients had F3-F4 severe fibrosis. HA was higher in patients with severe fibrosis, but did not accurately predict severe fibrosis. TE was significantly higher in patients with severe fibrosis (17.2 vs. 4.9 kPa; P<0.05) and was able to accurately predict fibrosis stage in 47/61 (77%) patients with valid measurement using a lower threshold of 6.4 kPa and an upper threshold of 13.9 kPa. Efficient assessment of severe fibrosis was not possible in patients with intermediate TE values. An algorithm that successively employed SF and TE can accurately classify severe fibrosis in 61% of patients, restricting the need for liver biopsy to the 39% of patients with intermediate or unvalid TE values. This algorithm should be validated in independent cohorts before extended use.

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Evaluation of Liver Fibrosis Using Texture Analysis on Combined-Contrast-Enhanced Magnetic Resonance Images at 3.0T

Purpose. To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis. Materials and Methods. In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). Using L 1 regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses. Results. The texture-based predicted fibrosis score significantly correlated with qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001) histology. The prediction model for qualitative histology had 0.814–0.976 areas under the curve (AUC), 0.659–1.000 sensitivity, 0.778–0.930 specificity, and 0.674–0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742–0.950 AUC, 0.688–1.000 sensitivity, 0.679–0.857 specificity, and 0.696–0.848 accuracy, depending on the binary classification threshold. Conclusion. CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.

Options for non-invasive assessment of liver fibrosis based on clinical data

Liver cirrhosis is one of the leading causes of death worldwide. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Studies have focused on non-invasive markers for liver fibrosis because of the dangers and complications of liver biopsy. The authors review the non-invasive direct as well as indirect methods for liver fibrosis assessment and present the positive and negative predictive value, sensitivity and specificity of those. Clinical utilities of transient elastography (Fibrsocan) is also reviewed. Non-invasive methods are useful in the assessment of liver fibrosis, monitoring disease progression and therapeutic response. Their accuracy can be increased by the combined or sequential use of non-invasive markers.