Median Liver Stiffness Measurement Research Articles

Reference values and associated factors of controlled attenuation parameter and liver stiffness in adults: A cross-sectional study

Background & aimsThe utilization of non-invasive techniques for liver fibrosis and steatosis assessment has gained acceptance as a viable substitute for liver biopsy in clinical practice. This study aimed to establish normative data for the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by age and gender, as well as to explore the relationship between anthropometric measures and CAP/LSM in a U.S. adult population. Methods and resultsIn this cross-sectional analysis, 7.522 US adults aged 20–80 years from the National Health and Nutrition Examination Survey (NHANES 2017–2020) were included. CAP and LSM were quantified using the FibroScan® 502-v2 device. A comprehensive range of data was collected, including sociodemographic, anthropometric, biochemical, lifestyle, and clinical conditions. Participants were segmented by sex and age. The median ± standard deviation (SD) for CAP was significantly lower in women (258.27 ± 61.02 dB/m) than in men (273.43 ± 63.56 dB/m), as was the median ± SD for LSM (women: 5.50 ± 4.12 kPa, men: 6.36 ± 5.63 kPa). Although median CAP and LSM values displayed an upward trend with age, statistical significance was not achieved. Notably, higher liver CAP values (above the 90th percentile) correlated with more pronounced clinical and biochemical profile differences compared to lower CAP values (below the 90th percentile) (p < 0.001). ConclusionsOur study provides age- and sex-stratified standard values for CAP and LSM in a sizeable, nationally representative cohort of adults. The evidence of sex-specific variations in TE test results from our study sets the stage for future research to further corroborate these findings.

Liver stiffness measurements predict Sinusoidal Obstructive Syndrome after hematopoietic stem cell transplantation.

Sinusoidal Obstructive Syndrome (SOS) is a life-threatening complication after hematopoietic stem-cell transplantation (HSCT), characterized by post-sinusoidal portal hypertension. FibroScan is used to assess portal hypertension non-invasively. We assessed transient elastography (TE) applicability in diagnosing SOS. The study included 27 adult patients, 11 underwent TE for high SOS risk pre-HSCT, 17 underwent TE post-HSCT due to bilirubin ≥2 mg/dl with no definite diagnosis of SOS. The first group had median Liver Stiffness Measurement (LSM) of 7.4 kPa (range, 3.3-22.5). Based on LSM results, conditioning regimen was modified for six patients and two of them developed SOS. Only one patient who did not have protocol adjustment experienced SOS. No patient with LSM < 7 kPa developed SOS. The second group had median LSM of 7.7 kPa (4.4-31.5). Median LSM after HSCT was significantly higher in patients who subsequently developed established SOS (n = 10) compared to patients who did not (n = 8), with values of 10.7 kPa (5.6-31.5) and 5.9 kPa (4.4-13.8), respectively (p = 0.02). An LSM cut-off of 7.5 kPa had a sensitivity and specificity of 75 and 80% for diagnosing SOS. In conclusion, pre-HSCT LSM can help adjustment of conditioning regimen in patients with high-risk for SOS. Post-HSCT LSM can help in early diagnosis of SOS.

Liver Elastography for the Detection of Methotrexate-Induced Liver Injury: A Retrospective Study

Background: Liver biopsy, the gold standard for monitoring of methotrexate-induced liver injury, is associated with significant morbidity and mortality. Transient elastography (TE) has been used as a non-invasive alternative to detect liver stiffness. Aim: To assess the utility of TE in detecting liver fibrosis in patients with methotrexate use. Methods: A retrospective chart review was performed for 35 patients referred to the liver clinic for evaluation of suspected methotrexate-induced liver injury. Demographic, clinical, histopathological, and elastographic data were collected and interpreted. Liver stiffness measurement (LSM) and controlled attenuation parameter were recorded from TE results. Results: Thirty-five patients with a mean age of 58 years, including 23 females (66%), were included. The median LSM by TE was 10.8 kPa and the median controlled attenuation parameter was 303 dB/m. A total of 12 out of 35 patients (34%) had evidence of clinical and pathological advanced fibrosis. Using a cut-off elastography value of 10 kPa, the TE yielded 92% sensitivity and 93% negative predictive value for ruling out methotrexate-induced advanced liver fibrosis. Using a higher LSM cut-off point of kPa ≥15.0, specificity was calculated at 87% and positive predictive value at 80%. Area under the receiver operating characteristic curve was 0.80 (95% confidence interval). Conclusion: FibroScan® (Echosens, Paris, France) has a high sensitivity and specificity for kPa 10 and 15, respectively, for detecting advanced liver fibrosis in patients on methotrexate.

Shear-wave elastography for monitoring Fontan-associated liver disease: A prospective cohort study.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD.

Barriers to Exercise in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Patient Survey.

Although adequate physical activity is an essential component of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD), the majority of people with MASLD do not engage in regular exercise and lead sedentary lifestyles. We aimed to identify perceived barriers to exercise and to examine awareness about the role of exercise in the treatment of MASLD. Individuals aged 18 years and above were recruited from a hepatology outpatient clinic. MASLD severity was assessed using controlled attenuation parameter (CAP) and transient elastography (TE) determined liver stiffness measurement (LSM) for the severity of hepatic steatosis and fibrosis, respectively. An online questionnaire was administered to record self-reported exercise patterns, barriers to exercise, and knowledge regarding effectiveness of different types of exercise for MASLD. Eighty-one participants (57% female) with a mean age of 55.3 ± 13.4 years and a mean body mass index (BMI) of 33.8 ± 6.4 answered the questionnaire. The mean CAP score was 335.7 ± 47.8 dB/m, and the median LSM was 12.45 kPa. While most patients (83%) considered MASLD to be a serious health concern, 73% did not achieve the recommended exercise levels of ≥ 150 min of moderate-intensity physical activity per week, and 54% were unsure about the role of exercise in the treatment of MASLD. Commonly reported barriers to exercise included physical and mental health issues (57%), lack of time (43%), lack of enjoyment in exercising (31%), fatigue caused by exercise (24%), and others (25%). Most participants with MASLD were unaware of the role of exercise as a potential treatment option and were not achieving recommended exercise levels. Inadequate time, physical and mental health problems, lack of enjoyment in exercise, and fatigue were major barriers.

Assessing the Severity of Portal Hypertension: Is Liver or Spleen Stiffness Measurement an Alternative to the Gold Standard, Hepatic Vein or Porto-Systemic Pressure Gradient?

Introduction: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) are increased in patients with cirrhosis and portal hypertension (PH). However, increased SSM values are associated with presence of esophageal varices. Currently, the gold standard for risk stratification in patients with compensated advanced chronic liver disease (cACLD) is by measurement of portal pressure through assessment of hepatic vein or porto-systemic pressure gradient (HVPG and PSPG). However, these procedures are invasive, and either LSM or SSM may be a non-invasive alternative.&#x0D; Aim: We aimed to investigate the relationship between LSM or SSM and HVPG/PSPG and examined the diagnostic accuracy for identification of clinically significant PH (≥10 mm Hg) or severe PH (≥12 mm Hg).&#x0D; Methods: A retrospective study (IRB Protocol #19230) allowed us to identify patients who had who undergone portal pressure measurements (HVPG or PSPG). A total of 36 patients also had SSM values. Of these, 29 patients carried a hepatic cause of PH, while the remaining had pre-hepatic (n=4) and post-hepatic (n=3) etiology.&#x0D; Results: The median age was 58 years (range: 25-71) with 52% male and 83% with cirrhosis. The median LSM and SSM were 35.7 kPa (range:7.4-75.0, normal ≤7.0 kPa) and 43.8 kPa (range: 20.7-100, normal ≤ 21.0 kPa). Both LSM (r = 0.42, P-value = 0.02) and SSM (r = 0.45, P-value: 0.01) correlated significantly with HVPG/PSPG. The diagnostic accuracy for both LSM and SSM for clinically significant PH was good for LSM (AUROC 0.76, 95% CI:0.58-0.94) and excellent for SSM (AUROC: 0.81, 95% CI:0.65-0.98). The diagnostic accuracy of LSM and SSM was lower for severe PH [AUROC 0.71 (P-value = 0.06) and 0.67 (P-value = 0.1) for LSM and SSM, respectively].&#x0D; Conclusion: Both LSM and SSM correlate with portal pressure measurements and provide diagnostic accuracy to identify patients with clinically significant, but not severe, PH.

Use of transient elastography to assess hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis during methotrexate treatment

ObjectivesThis study aimed to assess the prevalence and identify predictors of hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis (JIA) during methotrexate treatment.MethodThis cross-sectional study included JIA patients who had received methotrexate for > 1 year. Laboratory data including liver chemistry and lipid profiles were collected. Liver stiffness measurements (LSM) and controlled attenuation parameters (CAP) were determined by transient elastography. Significant hepatic fibrosis was defined as LSM > 7 kilopascal (kPa), and hepatic steatosis was defined as CAP > 225 decibel/meter (dB/m). Logistic regression analysis was performed to identify predictors associated with hepatic steatosis and fibrosis.ResultsOf 60 patients, 66.7% were female, and the median age (IQR) was 12.8 (10.6–15.0) years. The median duration of methotrexate usage (IQR) was 45 (22–85) months, and the median cumulative dose of methotrexate (IQR) was 3768 (1806–6466) mg. The median LSM (IQR) and CAP (IQR) were 4.1 (3.4–4.6) kPa and 191.0 (170.3–223.8) dB/m, respectively. No patients had transient elastography-defined hepatic fibrosis, whereas 21.7% had hepatic steatosis. A body mass index Z-score > 1 (OR 5.71 [95%CI 1.31–24.98], p = 0.021) and higher cumulative dose of methotrexate (OR 1.02 [95%CI 1.00–1.04], p = 0.041) were associated with hepatic steatosis, whereas the cumulative dose of steroids was not (OR 1.00 [95%CI 1.00–1.01], p = 0.097).ConclusionsHepatic steatosis is common among JIA patients receiving methotrexate, but none had transient elastography-defined hepatic fibrosis. Overweight/obese JIA adolescents and patients with a high cumulative dose of methotrexate are at risk for hepatic steatosis.Key Points•Long-term low-dose methotrexate usage and the concomitant use of other DMARDs did not increase the risk of hepatic fibrosis in JIA patients.•The prevalence of hepatic steatosis in JIA patients receiving methotrexate was higher than in a healthy pediatric population.•Overweight/obesity and a higher cumulative dose of methotrexate were predictors of hepatic steatosis.

Prediction of Sinusoidal Obstructive Syndrome after Allogeneic Stem Cell Transplantation Using Liver Stiffness Measurement By Fibroscan

Background: Sinusoidal Obstructive Syndrome/ Veno-Occlusive Disease (SOS/VOD) is a potentially life-threatening complication post allogeneic transplantation (HSCT) with an incidence of ~ 10% in adults. The sensitivity of SOS symptoms (hyperbilirubinemia ≥2 mg/dl, weight gain&amp;gt;5%, painful hepatomegaly and ascites) is good, but the specificity is relatively low because other conditions such as infections, GvHD, and exacerbation of previous liver disease may cause similar symptoms. Transient elastography (TE) using FibroScan has been implemented as a non-invasive assessment of post-sinusoidal portal hypertension (PHTN) one of the hallmarks of SOS. We aimed to assess TE's applicability in predicting and diagnosis of SOS. Methods: This single-center study was conducted between January 2021 and June 2023. Twenty-seven patients (pts) underwent TE, 11 before HSCT (group 1) due to high risk of developing SOS in order to guide subsequent treatment, and 17 after HSCT (group 2) (1 pt was in both groups) due to an elevation of bilirubin ≥2 mg/dl. SOS was defined using the EBMT criteria. Results: Eleven pts were included in the 1 st group (M 5, F 6). The median age was 43 (22-65) years. 7 pts had acute myelogenous leukemia (AML) -4/7 secondary AML (sAML), and 4 pts had myelofibrosis (MF). 5/7 AML pts received a median of 4 (2-5) lines of chemotherapy before HSCT; 2/4 sAML pts got azacytidine/ venetoclax and all 4 MF pts received Ruxolitinib before HSCT. Two pts had chemotherapy for antecedent malignancy. Donors were HLA-matched siblings (n=5), matched unrelated (n=2), or haploidentical (n=4). Risk factors for developing VOD included: active disease (n=9), multiple lines of chemotherapy (n=7), elevated serum ferritin (n=5), splenomegaly (n=5 including 1 pt with overt PHTN), severe liver toxicity during previous treatment (n=4), age ≥60 (n=3), second transplantation (n=3), pre-existing liver disease including fatty liver (n=3, including 1 pt with liver cirrhosis), severe obesity (n=2), prior treatment with GO (n=2), baseline liver enzymes elevation (n=2), and alcohol abuse(n=1). The conditioning regimen included total body irradiation (n=1), busulphan (BU) alone (n=5), or double alkylating agents (DAC, n=5), respectively. Four patients had myeloablative conditioning (MAC). Most pts had several risk factors for VOD median 5 (3-8). This group had a median liver stiffness measurement (LSM) of 10.1 kPa (range, 3.3-28.3). In 6/11 pts with LSM ≥7.2 kPa, the conditioning was modified; Treosulfan was given instead of BU (n=3), non-DAC instead of DAC protocol (n=3), reduced intensity instead of MAC (n=4), methotrexate was omitted (n=2). One pt received Defibrotide prophylaxis. With these modifications only 2 pts developed SOS (1 died). The second group included 17 pts (M 10, F 7), median age 49 (32-62) years with AML/myelodysplastic syndrome (n=7), acute lymphoblastic leukemia (n=5), MF (n=4), and lymphoma (n=1). Ten had MAC, and 5 had DAC. Five had active disease at HSCT. Three had prior liver disease. All pts had bilirubin elevation ≥2 mg/dl after HSCT but only 10 fulfilled additional criteria for the diagnosis of SOS based on the EBMT criteria. Pts who developed SOS had significantly higher LSM compared to those who did not; 10.7 kPa (IQR, 7.5-25.2) versus 5.9 kPa (IQR, 5.1-7.4), respectively (p=0.007) (Figure 1A). There was a positive correlation between the diagnosis of SOS and LSM levels, with a correlation coefficient of 0.6 (p= 0.04) as determined by the Spearman correlation test. LSM was able to diagnose SOS with an AUC of 0.89 (p=0.008) (Figure 1B). The cut-off value for SOS diagnosis was 7.5 kPa, with a sensitivity of 80% and specificity of 88%. Pts with severe VOD were treated with defibrotide and none of them died .of VOD. Conclusions: Pts with a high risk for VOD may have a high baseline LSM. In these pts, modifying the planned conditioning and GVHD prophylaxis regimens to less hepato-toxic ones may reduce the incidence of subsequent VOD. LSM elevation after HSCT should increase awareness of SOS, while pts with hyperbilirubinemia and low LSM usually suffered from other causes of liver toxicity. High LSM could support the diagnosis of VOD in borderline cases. Therefore, LSM may be an additional diagnostic tool in diagnosing SOS after HSCT, but more studies are needed to confirm these findings.

The effect of endoscopic gastric plication on portosystemic pressure gradient in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease.

The goals of therapy for patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease include weight loss and reduction of the portosystemic pressure gradient (PPG) to decrease the risk of hepatic decompensation. Endoscopic gastric plication (EGP) is an effective endoscopic weight loss procedure. This study aimed to assess the effect of EGP on PPG. In this prospective pilot study, patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease underwent endoscopic ultrasound-guided PPG measurement prior to and at 6 months following EGP. Primary outcomes were the change in PPG and proportion of patients experiencing ≥ 20 % reduction in PPG at 6 months. Secondary outcomes included percent total weight loss (TWL) and changes in noninvasive tests of fibrosis. 20 patients were included. Baseline median body mass index and liver stiffness measurement were 40.2 kg/m2 (range 30.1-56.7) and 14.7 kPa (range 8.2-36), respectively. At 6 months, median PPG decreased from 5.4 mmHg (range 0.7-19.6) to 1.8 mmHg (range 0.4-17.6) (P = 0.002), with 79 % (11/14) experiencing ≥ 20 % reduction. Patients experienced 12.5 % (6.5 %-26.1 %) TWL (P < 0.001) at 6 months, with 89 % (17/19) achieving ≥ 7 % and 68 % (13/19) achieving ≥ 10 % TWL. There were significant improvements in noninvasive tests of fibrosis. EGP appeared to be effective at reducing PPG in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease.

Poor correlation of 2D shear wave elastography and transient elastography in Fontan-associated liver disease: A head-to-head comparison.

Fontan-associated liver disease (FALD) is a long-term complication of the Fontan procedure. Guidelines recommend elastography, but the utility of transient elastography (TE) and two-dimensional shear wave elastography (2D SWE) is unknown. We aimed to evaluate the relationship between TE and 2D SWE in FALD. This prospective cohort study included 25 patients managed in a specialist clinic between January 2018 and August 2021. Trained clinicians performed 2D SWE (GE Logiq-E9) and TE (FibroScan 503 Touch) on the same day under the same conditions. Laboratory, echocardiography, and imaging data were collected. The atrioventricular systolic-to-diastolic duration (AVV S/D ratio) was calculated as a measure of cardiac diastolic function. We analyzed 40 paired measurements. Median age was 22 years. Median liver stiffness measurement (LSM) was 15.4 kPa (12.1-19.6) by TE and 8.0 kPa (7.0-10.3) (P = 0.001) by 2D SWE. There was weak correlation between the modalities (r = 0.41, P = 0.004). There was no correlation between time since Fontan and LSM by TE (r = 0.15, P = 0.19) or 2D SWE (r = 0.19, P = 0.13). There was no difference in LSM irrespective of whether sonographic cirrhosis was present or absent by TE (17.4 kPa [15.9-23.6] vs. 14.9 kPa [12.0-19.4], respectively, P = 0.6) or 2D SWE (9.0 kPa [2.8-10.5] vs. 8.0 kPa [6.7-10.1], P = 0.46). There was no correlation between AVV S/D ratio and LSM by TE (r = 0.16, P = 0.18) or 2D SWE (r = 0.02, P = 0.45). In FALD, TE and 2D SWE are poorly correlated. LSM by either modality was not associated with known risk factors for liver fibrosis or Fontan function. Based on these data, the role of elastography in FALD is uncertain.

Association between Di-2-ethylhexyl phthalate and nonalcoholic fatty liver disease among US adults: Mediation analysis of body mass index and waist circumference in the NHANES.

Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer and is ubiquitous in the environment and food. As a result, diet is the most significant source of exposure to DEHP in the general population. However, there is little research about the impact of DEHP on the risk of nonalcoholic fatty liver disease (NAFLD) or significant fibrosis in human beings. A cross-sectional analysis was performed using the National Health and Nutrition Examination Survey (NHANES) 2017-2018 data. Controlled attenuation parameter (CAP) and median liver stiffness measurement (LSM) were acquired by vibration-controlled transient elastography for diagnosis of NAFLD and significant fibrosis. The concentration of DEHP (∑DEHP) was calculated by each metabolite and split into quartiles for analysis. Results of logistic regression models showed that the risk of NAFLD was increased in those with higher concentration of urinary DEHP [ΣDEHP (OR=1.22, 95%CI=1.09-1.36)]. However, no significant association was found between urinary DEHP and significant fibrosis in the fully adjusted model. Mediation analyses suggested that the total effect of urinary DEHP on NAFLD risk mediated by BMI was 46.28% and by WC was 65.89%.

Multisample Ultrasound Point Shear Wave Elastography of the Liver: Repeatability and Agreement With Conventional Point Shear Wave Elastography.

To characterize the technical performance of a multisample ultrasound point shear wave elastography (pSWE) technique that allows 15 individual measurements of liver stiffness in a single acquisition. In 56 overweight and obese adults, research ultrasound examinations were performed using conventional pSWE and multisample pSWE (Sequoia; Siemens Healthineers). Five independent measurements were acquired with the conventional technique over five consecutive breath holds (5C1 and DAX transducers). A single multisample acquisition (DAX transducer) of up to 15 unique measurements was acquired during a single breath hold. All imaging was performed before (baseline) and after a "coffee break" (repeat). Median liver stiffness measurements between techniques and between baseline and repeat imaging were compared using Pearson correlation (r) and intra-class correlation (ICC) coefficients. Mean participant age was 33.7 ± 11.4 years; 40 participants were female. There was high correlation between conventional pSWE measurements obtained using the 5C1 and DAX transducers at baseline (r = .75 [95% CI: 0.61-0.85], P < .0001) and repeat (r = .88 [95% CI: 0.78-0.92], P < .0001). There was moderate agreement between conventional pSWE measurements obtained using the 5C1 and DAX transducers at baseline (ICC = 0.69 [95% CI: 0.52-0.81]), and good agreement at repeat (ICC = 0.81 [95% CI: 0.65-0.90]). There was moderate correlation (r = .59 [95% CI: 0.39-0.74], P < .0001) and moderate agreement (ICC = 0.58 [95% CI: 0.38-0.73]) between baseline conventional and multisample pSWE measurements acquired using the DAX transducer; there was high correlation (r = .73 [95% CI: 0.57-0.83], P < .0001) and moderate agreement (ICC = 0.72 [95% CI: 0.56-0.82] between techniques at repeat. There was moderate correlation (r = .65 [95% CI: 0.46-0.78], P < .0001) and moderate agreement (ICC = 0.64 [95% CI: 0.45-0.77]) between baseline and repeat multisample pSWE measurements. Multisample pSWE, allowing up to 15 measurements in a single breath hold, showed moderate to high correlation and moderate agreement with conventional pSWE.

Frequency of significant steatosis and compensated advanced chronic liver disease among adults with chronic liver disease.

With changes in the epidemiology and treatment of chronic liver disease (CLD), the impact of various etiologies of liver disease on steatosis and advanced fibrosis are uncertain. A retrospective study was conducted among liver disease patients of various etiologies undergoing transient elastography (TE) over a 9-year duration. Data for 2886 patients were analyzed and had the following demographics: The median age was 60 (IQR: 45-69) years, 51% were males, and ethnicity was predominantly Chinese (52.5%), followed by Malays (34%) and Indians (12.3%). The median CAP score was 272 (IQR: 219-319) dB/m and the median liver stiffness measurement (LSM) score was 6.5 (IQR: 4.9-9.7) kPa. Hepatic steatosis occurred across the spectrum of etiologies of CLD. Among patients with steatosis, the most common etiologies were nonalcoholic fatty liver disease (NAFLD) at 62% and chronic hepatitis B (CHB) at 26.3%. TE findings suggestive of cACLD (10.1-15kPa) and highly suggestive of cACLD (>15kPa) were observed in 11.3% and 12.4% of patients, respectively. NAFLD was found to be the most common etiology for cases with suggestive of cACLD (47.2%) and highly suggestive of cACLD (41.5%). Hepatic steatosis is common in CLD, regardless of etiology. Compared with other etiologies, NAFLD is now the leading cause of cACLD.

Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study.

Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan® for the non-invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3-4.0) kPa, 2nd tertile: 5.3 (4.9-5.9) kPa and 3rd tertile: 7.9 (6.7-9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1-147) vs. 85.8 (48.3-139) vs. 111 (59.3-203) μg/L, p = 0.021; median hepcidin: 2.5 (1.1-5.2) vs. 4.4 (2.5-7.3) vs. 4.1 (1.9-6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA-insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted-odds ratio 2.10, 95% confidence interval 1.23-3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted-odds ratio 1.90, 95% confidence interval 1.15-3.13, p = 0.013). Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD-related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes-related variables and other potential confounders.

Two-dimensional shear wave elastography (ElastQ) accurately rules out liver fibrosis and rules in advanced chronic liver disease across liver disease etiologies: a prospective multicenter study.

This study evaluated ElastQ, a two-dimensional shear wave elastography (2D-SWE) technique, for the non-invasive assessment of liver fibrosis risk using liver stiffness measurement (LSM). The aim was to determine its diagnostic accuracy and establish LSM cutoffs for clinical risk stratification. A prospective multicenter study was conducted, employing vibration-controlled transient elastography (VCTE) as a reference standard. The statistical analysis utilized Pearson correlations and Lin concordance correlation coefficients, diagnostic areas under the curve (AUCs), and 90%-specific rule-in and 90%-sensitive rule-out ElastQ cutoffs. The study included 875 patients at risk for liver disease, of whom 816 (376 women, 46.1%; median age, 57.0 years [interquartile range, 19.0]) had successful and reliable VCTE- and ElastQ-LSMs. The median LSM was 13.0 kPa (range, 2.0 to 75.0 kPa) for VCTE and 6.6 kPa (range, 2.9 to 26.5 kPa) for ElastQ. The correlation between VCTE-LSM and ElastQ-LSM was adequate for VCTE-LSM <15 kPa (Pearson r=0.63) but lower for VCTE-LSM ≥15.0 kPa (Pearson r=0.27). VCTE-LSM indicated no fibrosis risk (<5.0 kPa) in 178 cases (21.8%), gray zone (5.0-9.9 kPa) in 347 cases (42.5%), and advanced chronic liver disease (ACLD; ≥10.0 kPa) in 291 cases (35.7%). The diagnostic AUC for ElastQ-LSM was 0.82 for fibrosis risk and 0.90 for ACLD. The clinically relevant ElastQ cutoffs for ruling out fibrosis risk and ruling in compensated ACLD (cACLD) were <5.0 kPa and ≥9.0 kPa, respectively. ElastQ 2D-SWE enables accurate, non-invasive assessments of liver fibrosis and cACLD risk. In clinical practice, ElastQ-LSM <5.0 kPa rules out fibrosis, while ElastQ-LSM ≥9.0 kPa rules in cACLD.

Sodium-glucose cotransporter-2 inhibitors improve FibroScan-aspartate aminotransferase scores in patients with nonalcoholic fatty liver disease complicated by type 2 diabetes.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by excessive lipid accumulation in the liver, and its global incidence is increasing. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are oral antidiabetes drugs that promote glucose excretion into the urine and have been reported to exert therapeutic effects in NAFLD, but liver stiffness measurements (LSMs) determined by transient elastography are inconsistent. In addition, the effects of SGLT2is on the FibroScan-aspartate aminotransferase (FAST) scores have not been reported. We evaluated the effect of SGLT2is on patients with NAFLD complicated by type 2 diabetes using biochemical tests, transient elastography, and FAST scores. Fifty-two patients with type 2 diabetes complicated by NAFLD who started SGLT2i treatment between 2014 and 2020 at our hospital were selected from the database. Pre- and post-treatment serum parameters, transient elastography, and FAST scores were compared. After 48 weeks of SGLT2i treatment, body weight, fasting blood glucose, hemoglobin A1c, AST, alanine aminotransferase, gamma-glutamyltransferase, uric acid, fibrosis-4 index, and AST to platelet ratio index improved. Median LSM decreased from 7.0 kPa to 6.2 kPa ( P = 0.023) and the median controlled attenuation parameter decreased from 304 dB/m to 283 dB/m ( P = 0.022). Median FAST score decreased from 0.40 to 0.22 ( P < 0.001), and the number of cases with a cutoff value of ≥0.35 decreased from 15 to 6 ( P = 0.001). SGLT2i use not only improves weight loss and blood glucose levels but also improves hepatic fibrosis by ameliorating hepatic steatosis and inflammation.

Kistik Fibrozisli Çocuklarda Karaciğer Tutulumunun Shear-Wave Elastografi ile Non-invaziv Değerlendirilmesi

Objectives: Hepatobiliary complications commonly occur in cystic fibrosis with increasing prevalence due to longer life expectancies and widespread screening efforts. Shear-wave elastography is a novel noninvasive method that involves application of local mechanical compression on soft tissue using focused ultrasonography and acquiring strain images that show tissue response. We aimed to compare abdominal ultrasonography and Shear-wave elastography and also clinical and laboratory findings of children with cystic fibrosis prospectively. Methods: This study is a prospective study conducted in 13 cystic fibrosis patients followed between February 2018 and March 2019. The severity of cystic fibrosis-related liver disease was categorized according to international criteria. Elastography measurement was performed in the same session with the evaluation of the liver by abdominal ultrasonography in the patients. The liver stiffness measurements were compared with clinical data, biochemistry parameters and ultrasound findings. Results: Measurements were performed in 13 cystic fibrosis children (3 boys, 10 girls). The mean kiloPascal values of liver stiffness measurements with shear-wave elastography were 8.68 (4.1-20.2). The median liver stiffness measurement in subjects without cystic fibrosis-related liver disease was 7.79 kiloPascals (n=5); The median liver stiffness measurement in subjects with cystic fibrosis-related liver disease was 9.23 kiloPascals. Conclusion: Cystic fibrosis-related liver disease has a significantly varying disease burden, its prevalence is increasing, and its early recognition is crucial for treatment and follow-up. Although there are no clear range values determined for children in tissue stiffness measurements in Shear-wave elastography, clinical and other laboratory and imaging methods and follow-up and evaluation are important.

An LSM Based Strategy is Comparable to HVPG Measurement to Predict Further Events in Patients with Cirrhosis with Variceal Bleeding as Their Index Decompensation

Limited data exist on strategies other than hepatic venous pressure gradient (HVPG) estimation to predict future events in patients with cirrhosis presenting with variceal bleed (VB) but are otherwise compensated. We assessed whether liver stiffness measurement (LSM) during VB episode could accurately predict this risk. Consecutive patients with cirrhosis with VB as their index decompensation event underwent HVPG and LSM estimation during the VB episode in this prospective study. New onset further decompensation events (ascites, VB, encephalopathy) was assessed over follow-up. The performance characteristics of postbleed LSM were compared with model for end stage liver disease (MELD) score and HVPG to predict future decompensation and were cross-validated. Mean age of the cohort (n= 68) was 44.2 years and alcohol-related liver disease (55.9%) was the most common etiology. Over a median follow-up of 14 (9-18) months, 18(26.4%) patients developed further decompensation with ascites being the most common event. Patients with further decompensation had a higher median postbleed LSM [60.5kPa (53-70) vs. 25kPa (18-34), P < 0.001], HVPG [ 19mm Hg vs. 16mmHg, P= 0.005], and MELD score [ 12.5 (11-14.7) vs. 10 (8-12)P < 0.001]. The area under receiver-operator characteristics curve for postbleed LSM [0.928 (95%CI: 0.868-0.988)] was higher than both HVPG [0.733(0.601-0.865), P= 0.003] and MELD score [0.776(0.664-0.889), P= 0.019] to predict further decompensation. Optimism-corrected c-statistic using MELD and postbleed LSM was similar to a combination of HVPG, MELD, and postbleed LSM. Postbleed LSM is comparable to HVPG estimation in predicting further decompensation events in patients with otherwise compensated cirrhosis presenting with VB.

Initial outcomes of a dedicated multidisciplinary non-alcoholic fatty liver disease clinic: a retrospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) is a major healthcare burden. Real-world outcomes in dedicated tertiary care settings in Australia remain unknown. To evaluate the initial outcomes of patients referred to a dedicated multidisciplinary tertiary care NAFLD clinic. Retrospective review of all adult patients with NAFLD who attended a dedicated tertiary care NAFLD clinic between January 2018 and February 2020 and who had two clinic visits and FibroScans at least 12 months apart. Demographic and health-related clinical and laboratory data were extracted from electronic medical records. Key outcome measures were serum liver chemistries, liver stiffness measurement (LSM) and weight control at 12 months. A total of 137 patients with NAFLD were included. Median (interquartile range (IQR)) follow-up time was 392 days (343-497 days). One hundred and eleven patients (81%) achieved weight control (i.e. weight loss or stability). Markers of liver disease activity were significantly improved, including median (IQR) serum alanine aminotransferase (48 (33-76) vs 41 (26-60) U/L, P=0.009) and aspartate aminotransferase (35 (26-54) vs 32 (25-53) U/L, P=0.020). Median (IQR) LSM across the whole cohort was significantly improved (8.4 (5.3-11.8) vs 7.0 (4.9-10.1) kPa, P=0.001). No significant reduction was observed in mean body weight or the frequency of metabolic risk factors. This study highlights a new model of care for patients with NAFLD and demonstrates promising initial outcomes in relation to significant reductions in markers of liver disease severity. Although most patients achieved weight control, further refinements are needed to achieve significant weight reduction including more frequent and structured dietetic and/or pharmacotherapeutic interventions.

Transient Elastography as the First-Line Assessment of Liver Fibrosis and Its Correlation with Serum Markers.

Background and objectives: Recently, rapid progress has been made in the development of noninvasive methods for liver fibrosis assessment. The study aimed to assess the correlation between LSM and serum fibrosis markers to identify patients with advanced liver fibrosis in daily clinical practice. Methods: Between 2017 and 2019, 89 patients with chronic liver disease of various etiology, 58 males and 31 females, were enrolled in the study and underwent ultrasound examination, vibration-controlled transient elastography (VCTE), AST to Platelet Ratio Index (APRI score), Fibrosis-4 (FIB-4) score, and enhanced liver fibrosis (ELF) test. Results: The diagnoses were as follows: NAFLD (30.3%), HCV (24.3%), HBV (13.1%), ALD (10.1%), other (7.8%). Their median age was 49 (21-79), and their median BMI was 27.5 (18.4-39.5). The median liver stiffness measurement (LSM) was 6.7 kPa (2.9-54.2 kPa), the median of the ELF test was 9.0 (7.3-12.6), and the median APRI was 0.40 (0.13-3.13). Advanced fibrosis assessed by LSM was present in 18/89 (20.2%) patients. The LSM values correlated with the ELF test results (r2 = 0.31, p < 0.0001), with the APRI score (r2 = 0.23, p < 0.0001), the age of the patients (r2 = 0.14, p < 0.001), and with the FIB-4 values (r2 = 0.58, p < 0.0001). The ELF test values correlated with the APRI score (r2 = 0.14, p = 0.001), the age (r2 = 0.38, p < 0.0001), and the FIB-4 (r2 = 0.34, p < 0.0001). By determining the confidence intervals of the linear model, we proved that patients younger than 38.1 years have a 95% probability of absence of advanced liver fibrosis when assessed by VCTE. Conclusions: We identified APRI and FIB-4 as simple tools for screening liver disease in primary care in an unselected population of patients. The results also showed that individuals younger than 38.1 years had a negligible risk of advanced liver fibrosis.