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Background and Aims: Metabolic dysfunction‐associated steatotic liver disease (MASLD) recurrence after liver transplantation (LT) seems unavoidable and gradual. We aimed to evaluate the diagnostic accuracy in the post‐LT setting of patients transplanted for metabolic dysfunction‐associated steatohepatitis (MASH) of recurrent hepatic steatosis and fibrosis identified with FibroScan, compared to biopsy findings. Methods: This prospective cohort study included adults transplanted for MASH between 2010 and 2022 in three LT centres in Spain who underwent FibroScan and biopsy at least 1‐year after LT. Results: In total, 44 patients transplanted for MASH after LT were included. The median time from LT to biopsy and FibroScan was 24.5 (interquartile range [IQR]:16–46) and 26.0 (IQR: 16.8–41.5) months, respectively. The median time between biopsy and FibroScan was 2.0 (IQR: 0–5) months. On FibroScan, significant steatosis was diagnosed in about half of the patients (n = 21, 47.7%), yet advanced fibrosis in only two cases (4.6%). On biopsy, a quarter of biopsied patients (n = 11, 25%) had a MASH diagnosis, two (4.6%) with significant fibrosis and one (2.3%) with cirrhosis. All patients with liver stiffness measurement (LSM) values <8 kPa (n = 35, 79.5%) had a fibrosis stage ≤F1 (negative predictive value = 100%). The combination of post‐LT hypertension (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 1.8–80.4, p =.010) and post‐LT dyslipidaemia (OR: 7.9, 95% CI: 1.3–47.1, p =.024) with LSM (OR: 1.7, 95% CI: 1.1–2.8, p =.030) was independently associated with MASLD. Conclusions: Although biopsy remains the gold standard for detecting fibrosis, our results suggest that LSM values <8 kPa after LT for MASH are strongly correlated with absence of significant/advanced fibrosis. [ABSTRACT FROM AUTHOR]

Most ultrasound-based methods for assessing liver fibrosis still need further validation with liver biopsy used as gold standard to assess their accuracy. To assess accuracy of three shear wave elastography (SWE) methods: 1) Philips Elast Point Quantification (ElastPQTM), 2) Siemens Virtual TouchTM Quantification (VTQ) acoustic radiation force impulse (ARFI), and 3) transient elastography (TE) measured by Echosens FibroscanTM. 160 patients underwent liver stiffness measurements (LSM) with three SWE methods immediately prior to liver biopsy. The number of LSM required for reliable studies could be reduced to 6 for ElastPQ and to 7 for VTQ from standard recommendations of 10. Significant fibrosis and interquartile range/median (IQR/M)> 30 were independent predictors for lower reliability for detection of liver fibrosis. Ordinal logistic regression corrected for age showed that there was a significant interaction between steatosis (p = 0.008) and lobular inflammation (p = 0.04) and VTQ (ARFI) and between lobular inflammation and TE (p = 0.006). We showed variations in SWE measurements using different ARFI technologies. TE and ElastPQ achieved good diagnostic performance, whereas VTQ showed lower diagnostic accuracy. The number of measurements required for reliable studies can be reduced to 6 for ElastPQ and to 7 for VTQ, which have important clinical implications. [ABSTRACT FROM AUTHOR]

Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background The liver biopsy is an essential element of evaluating progression of liver disease in children with Progressive Familial Intrahepatic Cholestasis (PFIC) and Allagille Syndrome (AGS). Several noninvasive techniques, including radiological imaging and blood biomarkers assay, can be used to evaluate liver stiffness. Objectives To identify whether liver Transient elastography (FibroScan) and AST/PLT Ratio Index (APRI) could be reliable tools to assess the degree of fibrosis prior to partial biliary diversion (PBD). Methods A prospective cohort in which all patients with PFIC and AGS who underwent PBD from July 2019 to July 2021 were included. Preoperative liver functions, pelvic-abdominal ultrasonography and FibroScan assessments were performed while intraoperative liver biopsy was obtained. Results Eight patients with chronic cholestatic liver disease who were candidates for PBD due to intractable pruritus were enrolled, including PFIC (n = 6; 75%), and AGS (n = 2; 25%). The liver FibroScan results were similar to the liver biopsy histopathological assessment in 87.5% of cases. APRI ranged from 0.1 to 3.2 (median = 1.2). In four cases (50%), APRI was consistent with histological evaluation of liver samples. The FibroScan results were in concordance with APRI results in three patients (37.5%). Conclusion The current cohort demonstrated that fibroScan was consistent with histopathology in 87.5% of patients, highlighting its value in determining the degree of liver fibrosis prior to surgery, whereas the APRI was only consistent with histopathology in half of cases.

Purpose: The Controlled Attenuation Parameter (CAP score) is based on ultrasonic properties of retropropagated radiofrequency signals acquired by FibroscanTM (Echosens, Paris, France). Since ultrasound propagation is influenced by the presence of fat, CAP score was developed to quantify steatosis. The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. Patients and Methods: A total of 150 patients underwent same-day liver biopsy and measurement of hepatic steatosis with Fibroscan. Only examinations with 10 satisfactory measurements, and an inter-quartile range of less than 30% of the median liver stiffness values were included for data analysis. Histological staging was then correlated with median values and Spearman correlation calculated. P values of < 0.05 were considered statistically significant. Results: For diagnosis of hepatic steatosis (HS), CAP could predict the steatosis S2 with AUROC 0.815 (95% CI 0.741– 0.889), sensitivity (0.81) and specificity (0.73) when the optimal cut-off value was set at 288 dB/m. CAP detected histological grade S3 with AUROC 0.735 (95% CI 0.618– 0.851), sensitivity (0.71) and specificity (0.74), with a cut-off value of 330 dB/m. The AUROC for steatosis grade S1 was 0.741 (95% CI 0.650– 0.824), with a cut-off value of 263 dB/m with sensitivity 0.75 and specificity 0.70. Univariate analysis showed a correlation between CAP and diabetes (p 0.048). Conclusion: The performance of CAP to diagnose steatosis severity decreases as steatosis progresses. CAP is associated with diabetes but not other clinical factors and parameters of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Most studies to date have focused on liver stiffness measurement (LSM) in patients with different chronic liver diseases, and normal LSM is defined based on normal liver function tests or the absence of fibrosis. Very few studies have defined LSM based on completely normal liver biopsies. The current study was done to define the distribution of LSM values in individuals with normal liver biopsies. All prospective liver donors presenting to Medanta, the Medicity hospital between September 2020 and September 2021 fulfilling the eligibility criteria were included in this study. A total of 63 donors (36 females and 27 males) were included in the study, 37 (58.7%) donors had normal liver biopsies, and 26 (41.2%) donors showed the presence of non-alcoholic fatty liver disease. LSM values in the normal liver histology group were 5.01 ± 1.99 kPa by the M probe and 5.34 ± 2.25 kPa by the XL probe. Even though the correlation was weak (r = 0.29, P = 0.03), M probe LSM correlated positively with body mass index. There was a good correlation between the LSM measured by the M probe and the XL probe (r = 0.73, P = <0.001). LSM value in the biopsy-proven normal liver histology group was 5.01 ± 1.99 by the M probe and 5.34 ± 2.25 by the XL probe. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the diagnostic accuracy of the B1 inhomogeneity-corrected variable flip angle (VFA) method using native T1 values in the staging of liver fibrosis. Eighty-three patients who presented for liver biopsy due to varying degrees of liver damage, underwent MR examinations and had T1-mapping images of the liver acquired using the B1 inhomogeneity-corrected VFA VIBE method. Among them, 65 patients underwent Fibroscan, and their results were used to evaluate the elasticity of liver tissue. Additionally, T1-mapping images were collected from 19 normal control patients. Independent sample t -tests were used to analyze the correlation between T1 mapping and Fibroscan. The diagnostic efficacy of T1 mapping in patients with different stages of liver fibrosis was evaluated using receiver operating characteristic (ROC) curves. The consistency between different observer groups was intraclass correlation coefficient (ICC) =0.802. T1 mapping demonstrated significant differences between mid-stage liver fibrosis (S = 2) and late-stage liver fibrosis (S = 3), as well as moderate inflammation (G = 2) and severe inflammation (G = 3), P < 0.05. The Area Under Curve(AUC) values of T1 mapping for early liver fibrosis (S ≥ 1), significant liver fibrosis (S ≥ 2), advanced liver fibrosis (S ≥ 3), and end-stage liver fibrosis (S = 4) were 0.760, 0.709, 0.790, and 0.768, respectively. T1 mapping combined with Fibroscan had an AUC value of 0.860. The B1 inhomogeneity-corrected VFA T1 mapping may be useful for the staging of liver fibrosis. It has a superior diagnostic efficiency for diagnosing advanced fibrosis (≥S3), while native T1 values combined with Fibroscan have potential value for the staging of liver fibrosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis. Methods: Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement. Results: Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4 kPa vs. 8.1 kPa; p = 0.001) and SAP scintigraphy (median 20.9 kPa vs. 6.2 kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4 kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard. Conclusion: Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement. [ABSTRACT FROM AUTHOR]

Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD. A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrell's C-index. FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrell's C-indexes >0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrell's C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with "FIB4 <1.30", those with "FIB4 ≥1.30 then VCTE <8.0 kPa" had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3–6.8), whereas the risk of LREs significantly increased in patients with "FIB4 ≥1.30 then VCTE 8.0-12.0 kPa" (aHR 3.8; 95% CI 1.3–10.9), and even more for those with "FIB4 ≥1.30 then VCTE >12.0 kPa" (aHR 12.4; 95% CI 5.1–30.2). VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of specialized management. The amount of fibrosis in the liver is closely associated with the risk of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Liver biopsy currently remains the reference standard for the evaluation of fibrosis, but its application is limited by its invasiveness. Therefore, we evaluated the ability of non-invasive liver fibrosis tests to predict liver-related complications in NAFLD. Our results show that the blood test FIB4 and transient elastography stratify the risk of liver-related complications in NAFLD, and that transient elastography has similar prognostic accuracy as liver biopsy. These results support the use of non-invasive liver fibrosis tests instead of liver biopsy for the management of patients with NAFLD. [Display omitted] • At their published cut-offs, FIB4 and VCTE stratify patients with NAFLD into subgroups with significantly different prognoses. • Compared to liver biopsy in NAFLD, VCTE has similar accuracy for the prediction of liver-related events. • With regards to clinical events, the FIB4-VCTE stepwise algorithm accurately discriminates at-risk patients with NAFLD. • This algorithm should be used in the referral pathway to a liver specialist. [ABSTRACT FROM AUTHOR]

The FibroScan-AST (FAST) score was recently described to detect patients with nonalcoholic steatohepatitis (NASH) having elevated nonalcoholic fatty liver disease (NAFLD) activity score (NAS ≥ 4) and significant fibrosis (≥ F2) on liver biopsy (NASH+ NAS ≥ 4 + F ≥ 2). The aim of this study was to validate the FAST score in Indian patients with NAFLD and to derive optimal cut-offs. Sixty patients with biopsy-proven NAFLD [men: 38 (63.3%), age 40 (32–52) years] with all parameters for assessing the FAST score within 3 months of liver histology were retrospectively analysed. Histological NASH was present in 17 patients (28.3%), while 11 (18.3%) patients had NASH + NAS ≥ 4 + F ≥ 2. The area under the curve (AUROC) of the FAST score for discriminating NASH + NAS ≥ 4 + F ≥ 2 was 0.81. Using cut-offs by Newsome et al , the rule-out cut-off (FAST: ≤ 0.35) had a negative predictive value (NPV) of 0.88 [sensitivity: 0.91, specificity: 0.14, negative likelihood ratio (LR): 0.64], while the rule-in cut-off (FAST: ≥ 0.67) had a positive predictive value (PPV) of 0.33 (sensitivity: 0.73, specificity: 0.67, positive LR: 2.22). Fifteen (25%) patients were correctly classified as per histology, while 28 (46.67%) patients fell in the grey zone. On recalculating the optimal cut-offs for our patients, the rule-out cut-off (FAST: ≤ 0.55) had an NPV of 0.95 (sensitivity: 0.90, specificity: 0.45, negative LR: 0.21), while the optimal rule-in cut-off (FAST: ≥ 0.78) had a PPV of 0.70 (sensitivity: 0.64, specificity 0.94, positive LR: 10.39). With these cut-offs, 27 (45%) patients fell in the grey zone and 29 (48.3%) were correctly classified as per histology, performing better than the cut-offs by Newsome et al (P < 0.001). The FAST score demonstrates good AUROC for detecting NASH with significant fibrosis and inflammation on histology. Cut-offs should be recalibrated based on prevalence of disease. India has a high burden of NAFLD with an estimated 25 million patients at potential risk for significant liver disease. Liver biopsy remains the gold standard for diagnosing NASH, although its application in routine clinical practice is limited. Noninvasive tests for the simultaneous detection of steatosis, inflammation and fibrosis are thus the need of the hour. The FAST score has been recently suggested for the noninvasive detection of NASH with significant fibrosis (≥ F2) and inflammation (NAS ≥ 4) on liver biopsy. We validated the utility of the FAST score for detecting NASH with significant fibrosis and inflammation on liver biopsy in Indian patients with NAFLD. This noninvasive, easy-to-use and nonproprietary FAST score can correctly classify disease severity in more than 50% patients. However, our results suggest that cut-offs should be recalibrated based on the anticipated prevalence of NASH + NAS ≥ 4 + F ≥ 2 in the given population. [ABSTRACT FROM AUTHOR]

Oxaliplatin remains an essential component of many chemotherapy protocols for gastrointestinal cancers; however, neurotoxicity and hepatotoxicity may be dose-limiting. The gold standard for the diagnosis of oxaliplatin-induced hepatotoxicity is liver biopsy, which is invasive and costly. Splenomegaly has also been used as a surrogate for liver biopsy in detecting oxaliplatin-induced sinusoidal obstruction syndrome (SOS), but splenic measurement is not routine and can be inaccurate and complex. We investigated the correlation between increased liver elasticity assessed by Fibroscan and the increase in spleen volume on cross-sectional imaging after oxaliplatin as a noninvasive technique to assess liver stiffness associated with oxaliplatin-induced SOS. Forty-six patients diagnosed with gastrointestinal cancers and planned to take oxaliplatin containing regimens were included in this prospective study at the American University of Beirut Medical Center (AUBMC). Measurement of spleen volume using cross-sectional imaging and of liver elasticity using Fibroscan was performed at baseline, 3 and 6 months after starting oxaliplatin. Mean liver elasticity measurements were compared between patients stratified by the development of splenomegaly using the Student t- test. Splenomegaly was defined as 50% increase in spleen size compared with baseline. Patients who developed splenomegaly after oxaliplatin use had significantly higher mean elasticity measurements as reported by Fibroscan at 3 (16.2 vs. 7.8 kPa, P = 0.036) and 6 (9.3 vs. 6.7 kPa, P = 0.03) months. Measurement of elasticity using Fibroscan could be potentially used in the future as a noninvasive test for predicting oxaliplatin-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Management of long-term immunosuppression following liver transplantation (LT) remains empirical. Surveillance liver biopsies in combination with transcriptional profiling could overcome this challenge by identifying recipients with active alloimmune-mediated liver damage despite normal liver tests, but this approach lacks applicability. Our aim was to investigate the utility of non-invasive tools for the stratification of stable long-term survivors of LT, according to their immunological risk and need for immunosuppression. We conducted a cross-sectional multicentre study of 190 adult LT recipients assessed to determine their eligibility to participate in an immunosuppression withdrawal trial. Patients had stable liver allograft function and had been transplanted for non-autoimmune non-replicative viral liver disease >3 years before inclusion. We performed histological, immunogenetic and serological studies and measured the intrahepatic transcript levels of an 11-gene classifier highly specific for T cell-mediated rejection (TCMR). In this cohort, 35.8% of patients harboured clinically silent fibro-inflammatory liver lesions (13.7% had mild damage and 22.1% had moderate-to-severe damage). The severity of liver allograft damage was positively associated with TCMR-related transcripts, class II donor-specific antibodies (DSAs), ALT, AST, and liver stiffness measurement (LSM), and negatively correlated with serum creatinine and tacrolimus trough levels. Liver biopsies were stratified according to their TCMR transcript levels using a cut-off derived from biopsies with clinically significant TCMR. Two multivariable prediction models, integrating ALT+LSM or ALT+class II DSAs, had a high discriminative capacity for classifying patients with or without alloimmune damage. The latter model performed well in an independent cohort of 156 liver biopsies obtained from paediatric liver recipients with similar inclusion/exclusion criteria. ALT, class II DSAs and LSM are valuable tools to non-invasively identify stable LT recipients without significant underlying alloimmunity who could benefit from minimisation of immunosuppression. A large proportion of liver transplant patients with normal liver tests have inflammatory liver lesions, which in 17% of cases are molecularly indistinguishable from those seen at the time of rejection. ALT, class II donor-specific antibodies and liver stiffness are useful in identifying patients with this form of subclinical rejection. We propose these markers as a useful tool to help clinicians determine if the immunosuppression administered is adequate. [Display omitted] • 22% of stable liver recipients harbour moderate-to-severe subclinical immune allograft damage. • Subclinical damage is linked to allograft immunogenicity and degree of immunosuppression. • Recipients with active underlying alloimmunity can be identified using non-invasive markers. [ABSTRACT FROM AUTHOR]

Background: (NAFLD) is currently the most common cause of liver disease in the Western world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation status. Aim of the Work: The study is aimed to develop and validate noninvasive scoring system for assessment liver fibrosis in morbidly obese patients with NAFLD. Subjects and Methods: This is a Prospective cohort study, was carried out on 50 morbidly obese patients selected from internal medicine department, El Demerdash Hospital, through a period of six months. Results: There were 32(64.0%) male and 18(35.0%) female with mean age 40.48 (± 12.16) SD. There were 14(27.0%) between (20 - 30), 11(22.0%) between (30-40), 9(18.0%) between (40-50) and 16(32.0%) ≥50. Mean Weight (Kg) was 106.6 (± 13.31) SD with range (82.50 - 145.5), mean Height (Cm) was 171.7 (± 6.25) SD with range (158.0 - 185.0), mean BMI (Kg/m2) was 36.17 (± 4.15) SD with range (29.30-43.40), mean Waistcircumference 113.1 (±7.64) SD with range (92.0 - 129.0). There were 37(74.0%) with Co-morbidity. 10(20.0%) have DM, 11(22.0%) have HTN, 11(22.0%) have CDK and 5(10.0%) have COPD. Conclusion: That the combination of Fibroscan and, APRI, FGF-21 and FIB-4 methods provides a valuable approach for assessing liver fibrosis in NAFLD patients. This can eliminate the need for liver biopsy in patients without clear indication. In addition, several recent studies have also validated the used of non-invasive markers in the diagnosis of NAFLD. The establishment of a national program for the recognition of NAFLD is therefore essential to reduce the risk of liver disease progression. [ABSTRACT FROM AUTHOR]

Background: The performance of liver stiffness measurements (LSMs) obtained using FibroScan can be affected by several factors, and cut-off values are different for fibrosis caused by various aetiologies. The study aims to evaluate the diagnostic accuracy of LSM in nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism and investigate whether the LSM value would be affected by metabolic indicators. Methods: The study involved 91 NAFLD patients with abnormal glucose metabolism who underwent liver biopsy. The diagnostic accuracy of LSM value was evaluated by the receiver operator characteristic (ROC) curves, with the biopsy results taken as the gold standard. Multivariate linear regression and subgroup analysis were performed to determine the correlated indicators. Results: The areas under the ROC curves (AUROCs) of LSM values for detecting fibrosis stage ≥1, 2, 3 and 4 were 0.793 (95% confidence interval [CI]: 0.695–0.871), 0.764 (95% CI: 0.663–0.846), 0.837 (95% CI: 0.744–0.906) and 0.902 (95% CI: 0.822–0.955), with cut-off values of 6.3, 7.6, 8.3 and 13.8 kPa, respectively. Multivariate linear regression demonstrated that haemoglobin A1c (HbA1c, β = 0.205, P = 0.026) and alanine aminotransferase (ALT, β = 0.192, P = 0.047) were independently associated with the LSM value after adjustment for fibrosis stage, ballooning and inflammation grade from liver biopsy. Subgroup analysis demonstrated that LSM values were slightly higher in patients with HbA1c ≥7% than in those with HbA1c < 7% and in patients with body mass index (BMI) ≥30 kg/m2 than in those with BMI < 30 kg/m2. Conclusions: FibroScan was valuable for the evaluation of liver fibrosis in NAFLD patients with abnormal glucose metabolism. FibroScan is recommended to evaluate severe fibrosis, especially to exclude advanced fibrosis. Glucose metabolism state may affect LSM values. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery is associated with a positive impact on the degree of hepatic steatosis and inflammation in nonalcoholic associated fatty liver disease (NAFLD), although its effect on fibrosis is contentious. The role of Fibroscan in the post-bariatric assessment of hepatic steatosis and fibrosis is unclear. Objectives: This work aims to study the impact of bariatric surgery on the course of NAFLD using both invasive (liver biopsy) and non-invasive tests (biochemical parameters and Fibroscan). Methods: In this prospective study, the impact of bariatric surgery on the course of NAFLD was assessed using paired liver biopsy (intra-operative and post-bariatric surgery 1-year follow-up). The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) cutoffs for the assessment of hepatic fibrosis and steatosis, respectively, were calculated in both pre- and post-bariatric settings. Results: Fifty-eight patients (70.7% females, mean age 39.2 years) underwent paired liver biopsy. Post-bariatric surgery 1-year liver biopsy showed significant improvement in all the histopathological parameters of NAFLD. The mean NAFLD Activity Score declined from 2.81 (± 1.08) to 1.31 (± 1.39) post-bariatric surgery. Thirty (51.7%) patients showed improvement in fibrosis, eighteen (31%) no change, and ten (17.2%) had worsening. Worsening of fibrosis was associated with a higher median age of 44.5 versus 38 years (p value = 0.033). The CAP cutoff values for the various stages of hepatic steatosis were higher pre-operatively as compared with those obtained post-bariatric surgery. Conclusions: Bariatric surgery is associated with significant improvement in histopathological parameters of NAFLD. Fibroscan shows good diagnostic accuracy in detecting advanced stage and grade of NAFLD. [ABSTRACT FROM AUTHOR]

Background: There is limited data on the safety and efficacy of metabolic and bariatric (MBS) surgery in patients with advanced liver fibrosis. Methods: This is a retrospective analysis of data of patients with advanced liver fibrosis undergoing MBS at a tertiary care centre. Weight loss and complications were analysed. Transient elastography and liver biopsy findings 1 year after surgery were compared with baseline. Results: Twenty-two patients had cirrhosis and 16 had stage 3 fibrosis; all were Child Pugh A. Majority (76%) underwent sleeve gastrectomy. Mean excess BMI loss was 65.8 ± 18.9%. There were no leaks or 30-day mortality. One patient with cirrhosis had late mortality due to liver decompensation. Preoperative and postoperative median LSM were 15.5 kPa (interquartile range IQR = 24.4–11.6) and 10.9 kPa (IQR 19.3–7.6), respectively. Preoperative and postoperative median CAP were 352.5 dB/m (IQR = 372–315.5) and 303 dB/m (IQR 331–269.5), respectively. On follow-up biopsy, nine of twelve patients had improvement in fibrosis, while three had no change. Four out of five patients in the cirrhotic cohort had improvement in fibrosis stage and LSM improved in all of them. Five out of seven patients with stage 3 fibrosis had an improvement in fibrosis stage and none progressed to cirrhosis. LSM improved in three of these five patients. Conclusion: MBS has the potential to ameliorate advanced liver fibrosis, including cirrhosis. Transient elastography can be used as an effective tool for screening and follow-up of liver disease in patients undergoing MBS. [ABSTRACT FROM AUTHOR]

Background and Aim: Repeating liver stiffness measurement (LSM) was recently reported to improve accuracy to diagnose fibrosis stage in patients with non‐alcoholic fatty liver disease (NAFLD). There are to date no other studies confirming this finding. This aims to evaluate the accuracy of repeating LSM for the diagnosis of fibrosis stage in NAFLD patients. Methods: Retrospective analysis of prospectively collected data on adult NAFLD patients who had two FibroScan examination within 6 months prior to liver biopsy. F3–F4 fibrosis was excluded using LSM cut‐off of 7.9 kPa. Results: A total of 136 patients were recruited. Eighty‐five percent (115/136) of patients had high baseline LSM (≥ 7.9 kPa). Among them, 25% (29/115) had low repeat LSM (< 7.9 kPa), with only two patients having F3 fibrosis. Forty‐eight percent (41/86) of patients with high baseline and repeat LSMs had greater than or equal to F3–F4 fibrosis. All 21 patients with low baseline LSM had F0–F2 fibrosis, except one patient with high repeat LSM who had F3 fibrosis. A strategy of repeating LSM, where only patients with high LSM on both baseline and repeat scans are considered for liver biopsy, will be able to reduce the number of patients being considered for liver biopsy from 85% to 63%. The sensitivity, specificity, positive predictive value, and negative predictive value based on only the baseline scan was 98%, 22%, 37%, and 95%, respectively, while based on the strategy of repeating LSM was 93%, 51%, 48%, and 94%, respectively. Conclusion: False positive diagnosis of advanced fibrosis in NAFLD patients can be reduced, and unnecessary liver biopsy can be avoided by repeating LSM. [ABSTRACT FROM AUTHOR]

Introduction: Transient tissue elastography (TTE) may estimate the degree of hepatic fibrosis in patients with obesity, but the method has restrictions that are mainly related to patients' BMI. Purpose: To compare the results of the evaluation of hepatic fibrosis by biochemical methods and TTE with those determined by liver biopsy in patients after RYGB. Methods: This was a cross-sectional study involving patient data, TTE, and liver biopsy 1 year after RYGB. Results: Of the 94 selected patients, 33 underwent TTE and liver biopsy. The average weight of patients was 84.4 ± 15.4 kg. The mean APRI was 0.2 ± 0.1, and 36 patients (97.3%) were classified as F0–F1. The average NFS was − 2.0 ± 1.0, with 25 patients (67%) classified as F0–F1 and 12 patients (32.4%) classified as F2. The agreement rate between Fibroscan and liver biopsy was 80.0%. Histological analysis revealed regression of inflammatory changes in all patients: 26 patients (72.2%) had some degree of non-alcoholic steatohepatitis (NAS ≥ 5), and after surgery, no patient presented inflammation upon biopsy. Nine patients (24.3%) had fibrosis at surgery, and only two (5.4%) still had fibrosis 1 year later (p < 0.008). Conclusions: The use of APRI and Fibroscan is promising, but more studies are needed to evaluate patients with an advanced degree of NAFLD and confirm the entire spectrum of the disease. [ABSTRACT FROM AUTHOR]

Background and Aim: In patients with liver disease, etiology and body mass index (BMI) affects controlled attenuation parameter (CAP) assessment using FibroScan. We aimed to assess the performance characteristics of CAP for hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) stratified into obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. Methods: In this prospective study, 219 consecutive adult NAFLD patients, with an available FibroScan value (liver stiffness measurement—[LSM] and CAP) and liver biopsy, were included. Receiver operating characteristic curves were used for assessment of the CAP cut-off values predicting different stages of hepatic steatosis. Results: The mean ± standard deviation age of patients was 39.7 ± 10.5 years, 116 (53%) were males, and median (interquartile range) BMI was 31.8 (25.7–43.8) kg/m2. One hundred (45.7%) and 119 (54.3%) patients were non-obese and obese, respectively. The median values of CAP and LSM were significantly higher among obese patients as compared with the non-obese ones: 333 (304–368) vs. 320 (296–345) dB/m, p = 0.002 and 8.3 (6.1–11.4) vs. 6.6 (5.7–10.3) kPa, p = 0.012, respectively. Among non-obese NAFLD, optimal CAP cut-off values for steatosis (S) ≥ S1, ≥ S2, and ≥ S3 were 275 dB/m, 319 dB/m, and 337 dB/m, respectively. The corresponding CAP values among obese patients were higher as 285 dB/m, 340 dB/m, and 355 dB/m, respectively. BMI independently predicted CAP on multivariate analysis. The discordance of 2-grades between CAP and biopsy measured steatosis was seen in 13% in non-obese and 19.3% in obese NAFLD. CAP overestimated steatosis more often than underestimating it, with a higher proportion in obese NAFLD. Conclusion: In patients with NAFLD, interpretation of CAP requires consideration of BMI. [ABSTRACT FROM AUTHOR]

Background and Aim: The recommendation in regard to screening for non‐alcoholic fatty liver disease (NAFLD) among type 2 diabetes mellitus (T2DM) patients differs in major guidelines. The aim of this paper was to study the prevalence of NALFD and advanced fibrosis among T2DM patients. Methods: This is a cross‐sectional study of consecutive adult T2DM patients attending the Diabetes Clinic of a university hospital. Significant hepatic steatosis and advanced fibrosis was diagnosed based on transient elastography if the controlled attenuation parameter was ≥ 263 dB/m, and the liver stiffness measurement was ≥ 9.6 kPa using the M probe or ≥ 9.3 kPa using the XL probe, respectively. Patients with liver stiffness measurement ≥ 8 kPa were referred to the Gastroenterology and Hepatology Clinic for further assessment, including liver biopsy. Results: The data of 557 patients were analyzed (mean age 61.4 ± 10.8 years, male 40.6%). The prevalence of NAFLD and advanced fibrosis based on transient elastography was 72.4% and 21.0%, respectively. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR 4.856, 95% confidence interval [CI] 2.749–8.577, P = 0.006), serum triglyceride (OR 1.585, 95% CI 1.056–2.381, P = 0.026), and alanine aminotransferase levels (OR 1.047, 95% CI 1.025–1.070, P < 0.001) while advanced fibrosis was associated with serum high‐density lipoprotein cholesterol (OR 0.355, 95% CI 0.126–0.997, P = 0.049), alanine aminotransferase (OR 1.023, 95% CI 1.009–1.037, P = 0.001), γ‐glutamyltransferase (OR 1.005, 95% CI 1.001–1.008, P = 0.017), and platelet levels (OR 0.995, 95% CI 0.992–0.999, P = 0.010). Seventy‐one patients underwent liver biopsy. The majority had non‐alcoholic steatohepatitis (83.1%) and ≥ F1 fibrosis (87.3%) while advanced fibrosis was seen in 36.6%. Conclusion: The prevalence of NAFLD and advanced fibrosis based on transient elastography is high among T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub‐classify cirrhosis. Aim: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD. Methods: We assessed consecutive patients with biopsy‐proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow‐up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub‐group of patients. Results: Of 437 patients, 32 (7.3%) decompensated and/or died from liver‐related causes during a median follow‐up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0‐F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01‐1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01‐1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02‐47.84) were independent predictors of liver‐related clinical outcomes at standard and competing risk multivariate Cox‐regression analysis. Conclusions: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials. [ABSTRACT FROM AUTHOR]

Aim of the study: Autoimmune hepatitis (AIH) may result in liver fibrosis and cirrhosis. While the gold standard for staging fibrosis is biopsy, transient elastography (TE) represents a non-invasive alternative. TE has been validated in several chronic liver diseases, but no data exist to establish an association between histologic fibrosis on biopsy and TE liver stiffness measurements among a United States cohort of AIH patients. Material and methods: We conducted a retrospective cohort study of 53 AIH patients who received TE assessment and liver biopsy. Histologic fibrosis was classified as advanced (F3-F4) or mild/moderate (F0-F2). Liver stiffness by TE was measured in kilopascals (kPa). We performed a score test for trend to test the association between histologic fibrosis stage and increasing TE kPa categories. Analyses incorporated probe type (medium or extra-large) and body mass index (BMI). Linear regression was used to generate predicted associations between median kPa and histologic fibrosis score with the medium probe. Results: The cohort was primarily female (83%) with median age 56.3 years. Increasing kPa category was associated with worsening fibrosis stage when using the medium probe (p = 0.04), but not the extra-large probe (p = 0.40). BMI, however, differed between these groups (median 25.8 vs. 33.1, respectively, p < 0.001). In adjusted linear regression, increasing median kPa corresponded well to worsening fibrosis stage (p = 0.003). Conclusions: In a United States AIH cohort, increasing TE kPa measurements are associated with worsening histologic fibrosis staging. While medium probe performance was superior to the extra-large probe, significant variation in BMI between groups may explain this difference. [ABSTRACT FROM AUTHOR]

Background and Aim: The Baveno VI Consensus recommends repeating examination in patients with high liver stiffness measurement (LSM) by transient elastography to reduce false‐positive diagnosis of advanced liver disease. We tested whether repeating transient elastography can increase the overall diagnostic accuracy. Methods: Ninety‐seven patients with non‐alcoholic fatty liver disease who underwent two FibroScan examinations within 6 months prior to liver biopsy were evaluated. An LSM cut‐off of 7.9 kPa was used to exclude F3‐4 fibrosis. Results: Seventy‐eight patients had high LSM at baseline, among whom 27 had low LSM on repeated testing; only four had F3 and none had cirrhosis. In contrast, 31 of 51 patients with high LSM at both examinations had F3‐4. Nineteen patients had low LSM at baseline; none of them had F3‐4 regardless of the second LSM results. If we took LSM <7.9 kPa at either examination as sufficient to exclude F3‐4, the negative predictive value remained high at 91%. The positive predictive value for F3‐4 increased from 45% in patients with high LSM at baseline to 61% in those with high LSM at both examinations. Sensitivity analysis using different cut‐offs yielded similar results, with 76% of patients with LSM >12 kPa at both examinations having F3‐4. Conclusions: Transient elastography is a highly sensitive screening test to exclude F3‐4 fibrosis in non‐alcoholic fatty liver disease patients. One‐third of patients with high LSM may have normal results on repeated examination. By repeating examination in cases with high LSM, one may spare patients from unnecessary liver biopsy. [ABSTRACT FROM AUTHOR]

Background We evaluated the performance of serum hyaluronan (HA), procollagen type III N-terminal peptide (PIIINP), type IV collagen (IVC), laminin (LN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), compared to transient elastography (FibroScan) in predicting significant liver fibrosis. Methods We therefore determined 4 serum fibrosis markers, FibroScan and liver biopsy in 70 consecutive adult patients with chronic hepatitis B. According to a modified Scheuer scoring system, significant fibrosis was defined as fibrosis stage ≥S2. We compared serum fibrosis markers to histological staging and FibroScan results using Spearman correlation analysis and area under receiver operating characteristic (ROC) curves (AUROCs). Results Of the 212 patients who had the results of FibroScans and four serum fibrosis markers for HBV, 70 had concurrent liver biopsy. Significant liver fibrosis was found in 24/70 patients. The serum levels of HA, PIIINP, IVC, LN, ALT, AST was all positively correlated with fibrosis stage of Liver biopsy. The coefficients with stages were respectively 0.468, 0.392, 0.538, 0.213, 0.350, 0.375. There was a significant difference between mild fibrosis (

Abstract: As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow‐up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non‐invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non‐invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100‐fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval ‐0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non‐invasive, reliable tool for the assessment of graft fibrosis in the follow‐up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies. [ABSTRACT FROM AUTHOR]

Background and Aims The diagnostic accuracy of a novel serological panel (BioFibroScore®) to predict hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection is unknown. Methods Three markers of BioFibroScore, including urokinase plasminogen activator, matrix metalloproteinase-9, and beta-2 microglobulin, were retrospectively evaluated in 635 HCV-infected patients who received percutaneous liver biopsy and FibroScan®. The formula of BioFibroScore to predict the severity of hepatic fibrosis was developed by adaptive boosting algorithm. The diagnostic accuracy of hepatic fibrosis was assessed both for BioFibroScore and FibroScan, taking METAVIR fibrosis score as the reference standard. Results Urokinase plasminogen activator and beta-2 microglobulin were positively and matrix metalloproteinase-9 was negatively associated with the severity of hepatic fibrosis. Thirty-five (5.5%) patients had failed FibroScan assessment. By adaptive boosting model for BioFibroScore and the established reference ranges for FibroScan, 85.7% and 89.0% of the patients had an identical result for F0-1, F2, F3, and F4, as compared with liver biopsy. The concordance rate between BioFibroScore and FibroScan was 80.7%. BioFibroScore overestimated and underestimated the stage of hepatic fibrosis in 8.3% and 6.0% patients, and most patients had one stage error. Among patients with failed FibroScan assessment, 82.9% of them were correctly diagnosed by BioFibroScore. Bootstrap analysis for BioFibroScore showed the diagnostic accuracy was 80.9-88.4%. Conclusions BioFibroScore is accurate to assess the stage of hepatic fibrosis in HCV-infected patients. Applying this noninvasive test can substantially reduce the need for invasive liver biopsy and can play a role for fibrosis evaluation when FibroScan assessment was unavailable or unreliable. [ABSTRACT FROM AUTHOR]

Introduction: The value of repeated liver stiffness measurement (LSM) in non-alcoholic fatty liver disease (NAFLD) has not been shown before.Methods: A longitudinal study of biopsy-proven NAFLD patients was conducted at the Asian tertiary hospital from November 2012 to January 2017. Patients with paired liver biopsies and LSM were followed prospectively for liver-related and non-liver related complications, and survival.Results: The data for 113 biopsy-proven NAFLD patients (mean age 51.3 ± 10.6 years, male 50%) were analyzed. At baseline, advanced fibrosis based on histology and LSM was observed in 22 and 46%, respectively. Paired liver biopsy and LSM at 1-year interval was available in 71 and 80% of patients, respectively. High-risk cases (defined as patients with advanced fibrosis at baseline who had no fibrosis improvement, and patients who developed advanced fibrosis on repeat assessment) were seen in 23 and 53% of patients, based on paired liver biopsy and LSM, respectively. Type 2 diabetes mellitus was independently associated with high-risk cases. The median follow-up was 37 months with a total follow-up of 328 person-years. High-risk cases based on paired liver biopsy had significantly higher rates of liver-related complications (p = 0.002) but no difference in other outcomes. High-risk patients based on paired LSM had a significantly higher rate of liver-related complications (p = 0.046), cardiovascular events (p = 0.025) and composite outcomes (p = 0.006).Conclusion: Repeat LSM can predict liver-related complications, similar to paired liver biopsy, and may be useful in identifying patients who may be at an increased risk of cardiovascular events. Further studies in a larger cohort and with a longer follow-up should be carried out to confirm these observations. [ABSTRACT FROM AUTHOR]

Background. In the management of chronic hepatitis C (CHC) patients, liver biopsy is the gold standard for liver fibrosis assessment despite some technical limits and risks. Non-invasive approaches have been proposed as alternative methods to evaluate structural liver damage.Aim. To investigate the diagnostic accuracy of transient elastography, 13C-aminopyrine breath test (13C-ABT), serum hyaluronic acid (HA) and cytokeratin 18 Asp396 fragment (CK-18) as non-invasive methods of liver fibrosis assessment ad their correlation to METAVIR score.Material and methods. In a cohort of 57 CHC patients, liver stiffness, cumulative percentage of administered dose of 13C-aminopyrine at 120 min, serum HA and serum CK-18 concentration were determined. Diagnostic accuracy in detecting significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was assessed by the area under the receiver operating characteristic curve.Results. Liver fibrosis score showed a strong correlation with liver stiffness (r = 0.667; p < 0.0001) and a significant inverse correlation with 13C-ABT results (r = -0.418; p = 0.0012). A weaker correlation was found with CK18 (r = 0.329; p = 0.0126) and no correlation with HA. Areas under the curve of elastography, 13C-ABT, HA and CK18 were: 0.98, 0.75, 0.69, 0.64, respectively, for F ≥ 2; 0.97, 0.69, 0.80, 0.66, respectively, for F ≥ 3; 0.95, 0.64, 0.70, 0.56, respectively, for F = 4.Conclusion. Elastography has the best diagnostic accuracy for the assessment of the degree of liver fibrosis in CHC patients. Its application can provide an alternative useful tool for monitoring the disease evolution.

Background and aim In tropical regions, Hepatitis C virus (HCV) − Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. Methodology Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. Results The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. Conclusion Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the predictors for advanced liver fibrosis in patients with chronic hepatitis B virus (HBV) infection with persistently normal alanine aminotransferase (PNALT), or persistently or intermittently mildly elevated ALT (PIEALT). A total of 305 patients were included in the present study. Liver biopsies were evaluated using the METAVIR scoring system. Liver stiffness (LS) was measured using Fibroscan. Multivariate logistic regression and the area under the receiver operating characteristic curve (AUROC) were used to examine the diagnostic value of the predictors for advanced liver fibrosis. HBV DNA viral load in the PNALT group was significantly lower compared with the PIEALT group (4.57±1.68 vs. 5.71±1.69 log10 IU/ml; P<0.001). Body mass index and LS were also significantly lower in the PNALT group compared with the PIEALT group (P<0.001). The proportion of patients with liver fibrosis was significantly higher in the PIEALT group compared with the PNATL group (P=0.001). High ALT levels were an independent predictor for liver fibrosis, with an odds ratio (OR) of 2.69 (P=0.002). Male sex (OR=0.34, P=0.007), high ALT levels (OR=2.37, P=0.029) and a high HBV DNA load (OR=1.39, P=0.005) were independent predictors for advanced liver fibrosis. The AUROC was 0.65 (P=0.003) when using ALT levels to predict advanced liver fibrosis. ALT levels at ≥0.88 upper limit of normal (ULN; 35 IU/l) were considered as positive for advanced liver fibrosis, the sensitivity and specificity were 87.8 and 47.4%, respectively. The AUROC was 0.64 (P=0.004) when using the HBV DNA value to predict advanced liver fibrosis. When an HBV DNA value of ≥4.99 log10 IU/ml was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 78.0 and 49.5%, respectively. The AUROC was 0.72 (P<0.001) when combining ALT, HBV DNA load and sex into a formulation to predict advanced liver fibrosis. When the formulation score at >-2.22 was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 61.5 and 70.7%, respectively. Therefore, normal ALT levels do not always indicate the absence of hepatic fibrosis. A combination of ALT levels, sex and serum HBV DNA load may more effectively identify patients with CHB at high risk of developing fibrosis. These patients may benefit from liver biopsy. [ABSTRACT FROM AUTHOR]

Introduction: Controlled attenuation parameter (CAP) is a new method for the diagnosis of steatosis. Until now, CAP was available only with the M probe of the Fibroscan. The aim of this study was to evaluate the diagnostic performance of CAP with the XL probe versus CAP with the M probe, using liver biopsy (LB) as gold standard.Patients and Methods: A total of 236 patients with chronic liver disease undergoing LB had CAP measurement with M and XL probes the same day. All LB were analyzed independently by two experienced pathologists.Results: Median CAP was 240.5 and 239.5 dB/m with the M and XL probes, respectively. For the detection of steatosis grade with the M and XL probes, AUROCs were 0.82/0.83 for S ≥ 1, 0.89/0.88 for S ≥ 2, and 0.92/0.93 for S3, respectively. Cutoffs were (M and XL probes) 246/242 for S ≥ 1, 269/267 for S ≥ 2, and 285/286 dB/m for S3, respectively. The factor significantly associated with CAP with the M and XL probes was steatosis grade. In multivariate analysis, a low CAP value with XL probe was negatively associated with waist circumference, triglycerides, albumin, and the alcohol consumption, and positively with alkaline phosphatases. In multivariate analysis, a high CAP value with the XL probe was positively associated with waist circumference and triglycerides.Conclusion: CAP with the XL probe is a new tool for the diagnosis of steatosis. This parameter could be useful for the diagnosis and the follow-up of obese patients. [ABSTRACT FROM AUTHOR]

Background & Aims Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. Methods CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n = 340; validation cohort, n = 414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52 ± 14; body mass index 27.2 ± 5.3 kg/m 2 ). The primary outcome was the diagnosis of fatty liver, defined as steatosis involving ≥5% of hepatocytes. Results The area under the receiver-operating characteristics curve (AUROC) for CAP diagnosis of fatty liver was 0.85 (95% CI 0.82–0.88). The interquartile range (IQR) of CAP had a negative correlation with CAP (r = −0.32, p <0.001), suggesting the IQR-to-median ratio of CAP would be an inappropriate validity parameter. In the derivation cohort, the IQR of CAP was associated with the accuracy of CAP (AUROC 0.86, 0.89 and 0.76 in patients with IQR of CAP <20 [15% of patients], 20–39 [51%], and ≥40 dB/m [33%], respectively). Likewise, the AUROC of CAP in the validation cohort was 0.90 and 0.77 in patients with IQR of CAP <40 and ≥40 dB/m, respectively ( p = 0.004). The accuracy of CAP in detecting grade 2 and 3 steatosis was lower among patients with body mass index ≥30 kg/m 2 and F3-4 fibrosis. Conclusions The validity of CAP for the diagnosis of fatty liver is lower if the IQR of CAP is ≥40 dB/m. Lay summary: Controlled attenuation parameter (CAP) is measured by transient elastography (TE) for the detection of fatty liver. In this large study, using liver biopsy as a reference, we show that the variability of CAP measurements based on its interquartile range can reflect the accuracy of fatty liver diagnosis. In contrast, other clinical factors such as adiposity and liver enzyme levels do not affect the performance of CAP. [ABSTRACT FROM AUTHOR]

Aims: To assess the value of transient elastography for predicting significant fibrosis or cirrhosis in chronic hepatitis B or C (CHB or CHC) patients. Methods: 75 patients (CHB: 45, CHC: 32) were included. All underwent elastography and liver biopsy concurrently. Biopsies were evaluated using Ishak’s classification. Fibrosis was mild, moderate or severe/cirrhosis when scores were 0–1 (n = 30), 2–3 (n = 20), 4–6 (n = 25), respectively. Results: Median liver stiffness values were higher in patients with severe fibrosis or cirrhosis than in those with moderate or mild fibrosis (14.8 vs. 6.4 vs. 5.3 kPa, p Conclusion: Transient elastography has an excellent diagnostic accuracy for severe fibrosis and cirrhosis in CHB and CHC, but the cutoffs need further evaluation.

Liver biopsy (LB) is the gold standard method for assessment of liver histology. It provides valuable, otherwise unobtainable information, regarding the degree of fibrosis, parenchymal integrity, degree and pattern of inflammation, bile duct status and deposition of materials and minerals in the liver. This information provides immense help in the diagnosis and prognostication of a variety of liver diseases. With careful selection of patients, and performance of the procedure appropriately, the complications become exceptionally rare in current clinical practice. Furthermore, the limitations of sampling error and inter-/intra-observer variability may be avoided by obtaining adequate tissue specimen and having it reviewed by an experienced liver pathologist. Current noninvasive tools are unqualified to replace LB in clinical practice in the face of specific limitations for each tool, compounded by a poorer performance towards the assessment of the degree of liver fibrosis, particularly for intermediate stages.

Percutaneous liver biopsy (LB) remains an important tool in the diagnosis and management of parenchymal liver diseases. In current practice, it is most frequently performed to assess the inflammatory grade and fibrotic stage of commonly encountered liver diseases, with the diagnostic role relegated to secondary importance. The role of LB remains a vastly controversial and debated subject, with an ever-increasing burden of evidence that questions its routine application in all patients with liver dysfunction. It remains, essentially, an invasive procedure with certain unavoidable risks and complications. It also suffers shortcomings in diagnostic accuracy since a large liver sample is required for an ideal assessment, which in clinical practice is not feasible. LB is also open to observer interpretation and prone to sampling errors. In recent years, a number of noninvasive biomarkers have evolved, each with an impressive range of diagnostic certainty approaching that achieved with LB. These noninvasive tests represent a lower-cost option, are easily reproducible, and serve as suitable alternatives to assess hepatic inflammation and fibrosis. This article aims to debate the shortcomings of LB while simultaneously demonstrating the diagnostic accuracy, reliability and usefulness of noninvasive markers of liver disease thereby making the case for their utilization as suitable alternatives to LB in many, although not all, circumstances.

Both the prognosis and potential treatment of chronic liver disease greatly depend on the progression of liver fibrosis, which is the ultimate outcome of chronic liver damage. Historically, liver biopsy has been instrumental in adequately assessing patients with chronic liver disease. Histological assessment allows clinicians both to obtain diagnostic information and initiate adequate therapy. However, the technique is not exempt of deleterious effects. Multiple diagnostic tests have been developed for the staging of fibrosis using noninvasive methods, most of them in the setting of chronic hepatitis C. The goal of this paper is to review available data on the staging and assessment of liver fibrosis with two methods: serum markers and transient elastography (FibroScan®).

Liver stiffness, which correlates well with liver fibrosis stage, can be measured noninvasively by transient elastography, also known as Fibroscan. The present study aimed to determine the independent factors influencing Fibroscan detection by multiple regression analysis. A total of 181 patients who required liver biopsy were enrolled. Liver stiffness measurement (LSM) was detected by Fibroscan on the day of liver biopsy, while clinical information and routine biochemical examination results were also collected. Correlation was analyzed by Spearman's correlation, and multiple regression analysis was performed to analyze the independent influencing factors. The results demonstrated that platelet (PLT) levels, serum albumin (ALB), prothrombin activity (PTA) and body mass index (BMI) were independent predictors of liver stiffness. The contribution of these four predictors to the regression equation was in the following descending order: PLT (negative correlation) > ALB (negative correlation) > PTA (negative correlation) > BMI (positive correlation). In conclusion, the parameters of PLT, ALB, PTA and BMI are independent predicting factors affecting Fibroscan detection. Therefore, the diagnosis and evaluation of liver fibrosis should comprehensively consider the results of Fibroscan, and clinical and laboratory examinations. [ABSTRACT FROM AUTHOR]

Background and Aim: The association between nonalcoholic fatty liver disease (NAFLD) and apolipoprotein C3 gene (APOC3) promoter region single-nucleotide polymorphisms (SNPs) rs2854117 and rs2854116 is controversial. The aim of this study was to investigate the relationship between other polymorphisms of APOC3 and NAFLD in Chinese.Methods: Fifty-nine liver biopsy-proven NAFLD patients and 72 healthy control subjects were recruited to a cohort representing Chinese Han population. The polymorphisms in the exons and flanking regions of APOC3 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphisms were genotyped.Results: Among the five SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) in APOC3, only rs2070666 (c.179 + 62 T/A) was significantly different in genotype and allele frequency (both p < 0.01) between groups of NAFLD and control. After adjusting for sex, age, serum triglycerides, total cholesterol, body mass index, and the PNPLA3 rs738409 polymorphism, the APOC3 rs2070666 A allele was an independent risk factor for NAFLD with an odds ratio (OR) of 3.683 and 95 % confidence interval (CI) of 1.037-13.084. The APOC3 rs2070666 A allele was linked to the fourth quartile of the controlled attenuation parameter values (OR 2.769, 95 % CI 1.002-7.651) in 131 subjects, and also linked to the significant histological steatosis (OR 4.986, 95 % CI 1.020-24.371), but neither to liver stiffness measurement values nor to hepatic histological activity and fibrosis in NAFLD patients.Conclusions: The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the diagnostic accuracy of Fibroscan for liver fibrosis in patients with chronic hepatitis B (CHB) with alanine aminotransferase (ALT) levels <2 times the upper normal limit. A total of 263 consecutive patients with CHB and ALT levels <2 times the upper normal limit were enrolled in the present study. Liver biopsies and liver stiffness measurements (LSM) were conducted. Receiver operating characteristic (ROC) analysis was used to determine the predictive ability of LSM for the development of liver fibrosis in patients with stage S1, S2 and S3 liver fibrosis. Bivariate Spearman rank correlation analysis was performed in order to determine the association between liver stiffness value, which was measured by Fibroscan, and liver fibrosis stage, which was measured by liver biopsy. The liver stiffness value was found to be positively correlated with the liver fibrosis stage (r=0.522, P<0.001) and necroinflammatory activity (r=0.461, P<0.001), which was measured by liver biopsy. The optimal cut-off value in the patients with stage S1, S2 and S3 liver fibrosis was 5.5, 8.0 and 10.95 kPa, respectively. The area under the ROC curve for the prediction of the development of liver fibrosis in these patients was 0.696, 0.911 and 0.923, respectively. The threshold of the optimal cut-off value exhibited a high sensitivity and specificity. The results of the present study suggested that Fibroscan may improve the sensitivity of the diagnosis of liver fibrosis in patients with CHB and ALT levels <2 times the upper normal limit, and that this sensitivity may increase with the progression of liver fibrosis. [ABSTRACT FROM AUTHOR]

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