Liver Stiffness Measurement Research Articles

Type 2 diabetes and the minor allele of PNPLA3 consistently identify high-risk metabolic dysfunction associated steatotic liver disease.

Association of genetic factors with non-invasive tests (NITs) for MASLD has not been well established. Clinical and laboratory data, liver biopsy and/or liver stiffness measurement (LSM) by transient elastography were collected from MASLD patients seen in tertiary care hepatology practices. Minor allele frequency for genomic loci rs641738 (MBOAT7), rs58542926 (TM6SF2), rs738409 (PNPLA3), rs62305723 (HSD1713B) were evaluated for association with high ELF (≥11.3), high FIB-4 (≥3.25), high LSM (≥10 kPa), histologic fibrosis (stage 3/4 vs. stages 0-2). Among 2289 MASLD patients with available polymorphism and liver fibrosis/NIT data [52 ± 13 years, 46 % male, BMI 36.6 ± 9.9, 35 % type 2 diabetes (T2D)], 53 % had high-risk allele (C > G) at rs738409 (PNPLA3), 70 % high-risk allele (C > T) at rs641738 (MBOAT7), 18 % high-risk minor allele (C > T) at rs58542926 (TM6SF2), 11 % low-risk minor allele (G > A) at rs62305723 (HSD17b13). Only PNPLA3-rs738409 (47 % CC, 40 % CG, 13 % GG) was significantly associated with higher NIT scores and histologic fibrosis: high ELF 2.8 % CC vs. 8.1 % CG/GG; high FIB-4 4.7 % CC vs. 11.6 % CG/GG; high LSM 10 % vs. 19 %; advanced histologic fibrosis 34 % CC vs. 60 % CG/GG (all p < 0.01). Similar associations of PNPLA3-rs738409 with NITs were observed in a subgroup of MASLD patients with T2D (n = 799; all p < 0.05). The PNPLA3-rs738409 CG/GG genotype, older age and T2D were independently associated with high ELF [OR (95 % CI) = 3.25 (2.03-5.20)], FIB-4 [OR = 2.75 (1.90-3.98)], LSM [OR = 2.71 (1.60-4.59)] scores and advanced histologic fibrosis [OR = 2.56 (1.81-3.62)]. The polymorphism rs738409 in the PNPLA3 gene, T2D, and older age were independent predictors of high-risk MASLD.

Standard technique in Japan for measuring hepatic venous pressure gradient.

Direct measurement of portal venous pressure (PVP) is invasive, so the hepatic venous pressure gradient (HVPG) is commonly measured to evaluate portal hypertension (PH). HVPG is the gold standard for estimating PVP but few reports have covered standardized measurement techniques. This study validated standardized techniques for PVP measurement. In Western countries, electronic transducers are commonly used to measure PVP, whereas the water column method is still frequently applied in Japan. Setting a reference point for accurate PVP measurement is important but complicated. According to Japanese guidelines, the reference point for PVP measurement is 10cm above the dorsal surface or in the midaxillary line. For simpler determination, the anterior axillary point, defined as the point of convergence between the proximal pectoralis major muscle and arm when both arms are positioned against the trunk in a supine position, can be used as the reference point. New methods, such as endoscopic ultrasound-guided portal pressure gradient, offer less invasive alternatives. Non-invasive methods like elastography measure liver and spleen stiffness, which correlate with HVPG. The Baveno VII criteria incorporate measurements of liver and splenic stiffness for risk stratification. Biomarkers such as type IV collagen, M2BPGi, and FIB-4 score also predict HVPG. The Baveno VII consensus emphasizes the status of HVPG as the gold standard while advocating for non-invasive alternative methods to improve patient care and monitor treatment efficacy. Continued development of non-invasive tests is crucial for safer, more convenient PH management.

Head-to-head comparison among FAST, MAST, and multiparametric MRI-based new score in diagnosing at-risk MASH.

New scores were developed to identify at-risk metabolic dysfunction-associated steatohepatitis (MASH) using multiparametric MRI (mpMRI). A prospective study was conducted on 176 patients with suspected or diagnosed metabolic dysfunction-associated steatotic liver disease (MASLD) paired with an MR scan, vibration-controlled transient elastography (VCTE), and liver biopsy. Liver stiffness measurement (LSM) using magnetic resonance elastography (MRE), proton density fat fraction (PDFF), and mpMRI-based corrected T1 (cT1) were combined to develop a one-step strategy, named MPcT (MRE + PDFF + cT1, combined score), and a two-step strategy-MRE-based LSM followed by PDFF with cT1 (M-PcT, paired score) for diagnosing at-risk MASH. Each model was categorized using rule-in and rule-out criteria (three categorized analyses). To avoid overfitting, the diagnostic accuracies were evaluated based on 5-fold cross-validation. PDFF + cT1 (PcT) had the highest diagnostic performance for severe activity (hepatic inflammation plus ballooning grade ≥ 3) and for NAS ≥ 4 (active MASH). Areas under receiver operating characteristic curves (AUROCs) of M-PcT (0.832) for detecting at-risk MASH were significantly higher than those of Fibroscan-AST (FAST) (0.744, p = 0.017), MRI-AST (MAST) (0.710, p = 0.002), and MPcT (0.695, p < 0.001) in three categorized analysis. Following the rule-in criteria, positive predictive values of M-PcT (84.5%) were higher than those of FAST (73.5%), MAST (70.0%), and MPcT (66.7%). Following the rule-out criteria, negative predictive values of M-PcT (88.7%) were higher than those of FAST (84.0%), MAST (73.9%), and MPcT (84.9%). The two-step strategy, M-PcT (paired score), showed the reliability of rule-in/-out for at-risk MASH, with better predictive performance compared with FAST and MAST (combined score). This study is registered with ClinicalTrials.gov (number, UMIN000012757). Question There is no mpMRI-based method for detecting as-risk MASH (NAFLD activity score ≥ 4 with fibrosis stage ≥ 2) like FAST and MAST scores. Findings MRE-based LSMs followed by PDFF with cT1 (M-PcT) were more useful in detecting at-risk MASH than the combined score (FAST and MAST). Clinical relevance By combining MRE and PDFF with cT1, it becomes possible to evaluate the pathology of MASH without the need for a liver biopsy, assisting in prognosis prediction and decision-making for treatment options.

The fibrosis investigating navigator in diabetes (FIND): A tool to predict liver fibrosis risk in subjects with diabetes.

Type 2 diabetes increases the risk of cirrhosis and liver cancer. Noninvasive and early assessment of liver fibrosis is essential. We aimed to develop a score to aid in the initial assessment of liver fibrosis in the diabetic population. A fibrosis investigating navigator in diabetes (FIND) score was developed and validated in the NHANES dataset (2017-2020). Fibrosis was defined as a liver stiffness measurement (LSM) ≥8.0 kPa. The diagnostic accuracies of FIB-4, NFS, LiverRisk, steatosis-associated fibrosis estimator (SAFE) and metabolic dysfunction-associated fibrosis (MAF-5) were compared. FIND was also externally validated in various liver diseases via biopsy as a reference in an Asian centre between 2016 and 2020. Finally, we examined the prognostic implications of the FIND index utilizing data from the UK Biobank cohort (2006-2010). The FIND score model yielded an AUROC of 0.781 for the prediction of an LSM ≥8 kPa in the validation set, which was consistently greater than that of other available models (all p < 0.05). In the whole NHANES dataset, the 85% sensitivity cut-off of 0.16 corresponded to a NPV of 91.9%, whereas the 85% specificity cut-off of 0.31 corresponded to a PPV of 50.6%. FIND displayed overall accuracies similar to those of the other models in staging fibrosis stages, with biopsy used as a reference. In the UK Biobank cohort, FIND >0.31 was associated with an increased risk of all-cause and liver-related mortality in the diabetic population in adjusted models (HR, 1.75; 95% CI, 1.62-1.89; HR, 23.59; 95% CI, 13.67-40.69). In diabetes patients, the novel FIND score performs well in identifying subjects at risk of liver fibrosis and predicting all-cause and liver-related mortality.

Diagnostic performance of FibroTouch® in assessing hepatic steatosis and fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: An Asian experience.

FibroTouch® has shown efficacy in staging hepatic fibrosis in patients with chronic viral hepatitis B, but its performance in assessing liver steatosis and fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients remains understudied. We aimed to evaluate the diagnostic performance of FibroTouch® in assessing steatosis and fibrosis in the MASLD population. Liver stiffness measurements and steatosis were assessed using FibroTouch® and FibroScan®, with FibroScan® as the reference standard. Pearson's correlation test evaluated correlations, and kappa statistics determined agreement between the two methods. Optimal cut-off values of FibroTouch® for predicting hepatic steatosis and fibrosis stages were determined through ROC curve analysis with the Youden index method. Strong correlations were observed between FibroTouch® UAP and FibroScan® CAP (rho=0.74) and LSM values (rho=0.87) (p<0.001 for both) in a total of 380 patients. The mean CAP value for the entire cohort was 285±51 dB/m, and the median LSM for the cohort was 5.3kPa. The optimal FibroTouch® UAP cutoffs were 229 dB/m for S0 vs. S1, 267 dB/m for S1 vs. S2, and 294 dB/m for S2 vs. S3. For FibroTouch® LSM, the optimal cutoffs were 6.0kPa for F0-F1 vs. F2, 7.9kPa for F2 vs. F3, and 10.6kPa for F3 vs. F4. Moreover, FibroTouch® effectively assessed hepatic steatosis and fibrosis in patients with different BMIs. FibroTouch® proved valuable in assessing hepatic steatosis and liver fibrosis staging in MASLD patients, enhancing its applicability in various clinical settings as a suitable and convenient option for MASLD patients.

Higher levels of plasmatic saturated fatty acid were significantly associated with liver fibrosis in HIV mono-infection: A case-control study

BackgroundThe relationship between plasmatic fatty acid (FA) composition and liver fibrosis remains scarce in people living with HIV/AIDS (PLWHA). We aimed to evaluate the association of plasmatic FAs and liver fibrosis in HIV mono-infected individuals. MethodsThis case-control study included PLWHA with liver fibrosis (cases) and randomly selected subjects without fibrosis (controls) from the PROSPEC-HIV study (NCT02542020). Participants with viral hepatitis, abusive alcohol consumption and lipid supplements use were excluded. Liver fibrosis was defined using transient elastography (TE) by liver stiffness measurement (LSM) ≥ 7.1 kPa or ≥ 6.2 kPa with M or XL probe, respectively. All HIV mono-infected participants with liver fibrosis identified at the baseline PROSPEC-HIV visit were included. Controls (1:1) were randomly selected among those HIV mono-infected participants without liver fibrosis. Plasmatic FA profile, dietary lipid intake, anthropometric measures, and blood samples were assessed. Plasmatic fatty acid was analyzed using gas chromatography and intake of fats lipids were assessed by two 24-h dietary recall (24-HDR). Multivariate logistic regression models adjusted by age, sex at birth and duration of antiretroviral therapy (ART) were performed. ResultsA total of 142 participants (71 cases and 71 controls) [62 % female, median age = 46 (IQR, 37–53) years, 14.8 % with diabetes, median CD4 count = 655 cells/mm3, 96.5 % under ART] were included. Higher percentages of plasmatic palmitc acid (16:0) and saturated fatty acids (SFA) were observed in participants with liver fibrosis (cases) compared to those without (controls). Presence of higher percentage of plasmatic palmitc acid (16:0) was associated with an increased odds for liver fibrosis [adjusted OR = 1.23 (95%CI 1.04–1.46); p = 0.02] in multivariate models. ConclusionThis study showed the potential role of the plasmatic FA composition in the pathogenesis of liver fibrosis in PLWHA.

Advanced liver fibrosis, but not MASLD, is associated with accelerated biological aging: a population-based study

BackgroundThe process of biological aging in patients diagnosed with chronic liver disease remains unclear.AimThe current study aims to investigate if there is an accelerated biological aging process in participants with advanced fibrosis (AF) and metabolic dysfunction-associated steatotic liver disease (MASLD).MethodsData from the 2017–2018 NHANES cycle were analyzed. AF was determined based on the values of liver stiffness measurement (LSM) and MASLD was defined according to new consensus nomenclature. Klemera-Doubal method biological age (KDM bioage) and Phenotypic age (Phenoage) were adopted to quantify biological age. Phenoage advancement (Phenoage_advance) and KDM advancement (KDM_advance) were generated as the difference between the calculated biological age and chronological age, and a positive residual was regarded as an indicator of accelerated biological aging.ResultsA total of 3974 participants was enrolled. The weight mean KDM_advance and phenoage_advance in AF group was 4.22 years (95%CI: 2.96–5.49 years) and 2.61 years (95%CI: 1.80–3.41 years), while in MASLD group was 0.37 years (95%CI: -0.28–1.03 years) and 0.04 years (95%CI: -0.64–0.72 years), respectively. Multivariate linear regression analysis showed that participants with AF had older KDM_advance and phenoage_advance compared with those without AF (1.50 years (95%CI: 0.23–2.77 years), P = 0.02; 1.00 years (95%CI: 0.18–1.82 years), P = 0.02; respectively), in models adjusting demographic characteristics, socioeconomic status, lifestyle factors, and comorbidities. No significant association was found between MASLD and KDM_advance and phenoage_advance.ConclusionsAF, not MASLD, was independently associated with accelerated biological aging in adults from a US representative sample.

MASLD, At-Risk MASH and Increased Liver Stiffness Are Associated With Young Adulthood Obesity Without Residual Risk After Losing Obesity.

Obesity can result in persistent metabolic changes despite weight loss, which may affect liver health. We aimed to investigate associations between young adulthood obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), at-risk steatohepatitis and increased liver stiffness measurement (LSM) in a general population setting. We studied NHANES 2017-2020 community-dwelling participants aged > 40 years with BMI ≥ 18.5 and no heart failure. Weight at age 25 was obtained through questionnaires and compared to current weight. Assessment included controlled attenuation parameter (CAP) and LSM. Associations between obesity status change with MASLD or at-risk metabolic dysfunction-associated steatohepatitis (MASH) and increased LSM were investigated and adjusted for demographics and metabolic health. The cohort comprised 4,580 participants (57% stable non-obesity, 33% gained obesity, 2% lost obesity and 8% stable obesity). Compared to stable no-obesity, stable obesity was strongly associated with MASLD (odds ratio [OR]: 5.47, 95% confidence interval [95%CI]: 3.97-7.66) as was gained obesity (OR: 4.68, 95% CI: 3.93-5.59), whereas no increased risk was demonstrated for lost obesity (OR: 1.26, 95% CI: 0.76-2.10). Similar associations for stable obesity and gained obesity with at-risk MASH and LSM ≥ 8 kPa were demonstrated. No residual risk was found for lost obesity (MASH-OR: 1.05 95% CI: 0.36-2.49; LSM ≥ 8 kPa-OR: 0.85, 95% CI: 0.29-1.97). Results were consistent in sensitivity analysis where obesity change was calculated over the past 10 years and weight change was stratified in normal weight/overweight/obesity. Young adulthood obesity is an important risk factor for MASLD, at-risk MASH and increased LSM among the general population aged 40-80 years. Losing obesity resulted in normalisation of odds for MASLD, at-risk MASH and increased LSM. These findings underline the importance of preventing and treating young adulthood obesity to maintain liver health.

Liver Elastography-based Risk Score for Predicting Hepatocellular Carcinoma Risk.

Liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) accurately assesses fibrosis. We aimed to develop a universal risk score for predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis. We systematically selected predictors and developed the risk prediction model (HCC-LSM) in the HBV training cohort (n = 2,251, median follow-up of 3.2 years). The HCC-LSM model was validated in an independent HBV validation cohort (n = 1,191, median follow-up of 5.7 years) and a non-viral chronic liver disease (CLD) extrapolation cohort (n = 1,189, median follow-up of 3.3 years). A HCC risk score was then constructed based on a nomogram. An online risk evaluation tool (LEBER) was developed using ChatGPT4.0. Eight routinely available predictors were identified, with LSM levels showing a significant dose-response relationship with HCC incidence (P < .001 by log-rank test). The HCC-LSM model exhibited excellent predictive performance in the HBV training cohort (C-index = 0.866) and the HBV validation cohort (C-index = 0.852), with good performance in the extrapolation CLD cohort (C-index = 0.769). The model demonstrated significantly superior discrimination compared to six previous models across the three cohorts. Cut-off values of 87.2 and 121.1 for the HCC-LSM score categorized participants into low-, medium-, and high-risk groups. An online public risk evaluation tool (LEBER; http://ccra.njmu.edu.cn/LEBER669.html) was developed to facilitate the use of HCC-LSM. The accessible, reliable risk score based on LSM accurately predicted HCC development in patients with chronic hepatitis, providing an effective risk assessment tool for HCC surveillance strategies.

A clinical study showing the expression characteristics of cuproptosis markers in cases with Wilson disease

This study investigates levels of cuproptosis markers in Wilson disease (WD) and their role in the occurrence and development of WD. We retrospectively collected clinical data from 76 patients with Leipzig score ≥ 4 hospitalized in the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to September 2023. The participants were given copper chelators (sodium dimercaptosulphonate (20 mg·kg−1), 4 courses of treatment, 32 days). The levels of clinical indicators (ALT, AST, ALP, HA, LN, PIIINP, CIV, liver stiffness measurement, United Wilson disease rating scale), oxidative stress indexes (SOD, MDA, GSH), cuproptosis markers (FDX1, DLAT, LIAS, ACO-2, SDHB, PLOD1, DPYD) of the participants were measured before and after treatment. Compared with the control group, FDX1, DLAT, DPYD, and POLD1 in WD were significantly up-regulated before treatment (6464.34 ± 2980.66 vs 4125.43 ± 2230.13 pg ⋅ mL−1, P &lt; .001, 1364.36 ± 376.81 vs 884.22 ± 175.42 pg ⋅ mL−1, P &lt; .001, 279.74 ± 123.63 vs 155.68 ± 67.32 pg ⋅ mL−1, P &lt; .001, 3536.11 ± 1404.83 vs 1487.76 ± 658.26 pg ⋅ mL−1, P &lt; .001), while SDHB was significantly down-regulated (2458.75 ± 1103.75 vs 5338.22 ± 921.54 pg ⋅ mL−1, P &lt; .05). SOD was significantly down-regulated before treatment (13.20 ± 2.06 vs 13.27 ± 1.79 U ⋅ mgprot−1, P &lt; .05), while MDA and GSH were significantly up-regulated (10.53 ± 4.76 vs 4.92 ± 1.81 nmol ⋅ mL−1, P &lt; .001, 49.28 ± 25.55 vs 24.70 ± 12.01 µol ⋅ L−1, P &lt; .001). POLD1 were down-regulated (3536.11 ± 1404.83 vs 1487.76 ± 658.26 pg ⋅ mL−1, P &lt; .001), and SDHB was up-regulated after treatment (2458.75 ± 1103.75 vs2709.61 ± 906.95 pg ⋅ mL−1, P &lt; .05), while SOD, MDA and GSH were significantly down-regulated (13.20 ± 2.06 vs 12.48 ± 1.52 U ⋅ mgprot−1, P &lt; .05, 10.53 ± 4.76 vs 7.65 ± 3.65 nmol ⋅ mL−1, P &lt; .001, 49.28 ± 25.55 vs 34.09 ± 15.02 µmol ⋅ L−1, P &lt; .001). The expression levels of cuproptosis markers and oxidative stress indexes are abnormal in WD patients. However, chelation therapy can improve the recovery of cuproptosis markers, oxidative stress indexes, and hepatic fibrosis indexes.

Analysis of the clinical characteristics of HBeAg-negative chronic HBV infection in indeterminate phase with a low viral load

Objective: To analyze the clinical characteristics of HBeAg-negative chronic hepatitis B virus (HBV) infection in indeterminate phase with a low viral load. Methods: One hundred and thirty-nine cases with persistent normal alanine aminotransferase (ALT) and HBeAg-negative chronic HBV infection with low viral load who visited the Department of Infectious Diseases of the Affiliated Hospital of Yan'an University from September 2013 to July 2021 were retrospectively collected. Patients were divided into low hepatitis B surface antigen (HBsAg) group (n=59) and high HBsAg group (n=80) according to the baseline hepatitis B surface antigen (HBsAg) level. The changes of various indicators at baseline and follow-up endpoints were analyzed between the two groups. The rate of HBsAg decrease ≥0.5 log10IU/ml, HBV DNA negative conversion rate, ALT persistently normal rate, and liver stiffness measurement (LSM) persistently normal rate at the end of the follow-up were compared. The t-test, or non-parametric Mann-Whitney U test, and Wilcoxon signed rank test were used for comparison of continuous data between the two groups. The χ2 test, or Fisher's exact probability method, was used for comparing count data between the two groups. Results: There were statistically significant differences in age, gender, and HBsAg at baseline, but there was no statistically significant difference in terms of family history of hepatitis B, follow-up time, anti-HBe, anti-HBc, HBV DNA, ALT, aspartate aminotransferase (AST), albumin (Alb), and LSM between the two groups. There were statistically significant differences in HBsAg, anti-HBc, and ALT levels before and after follow-up in the low HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, AST, Alb, and LSM levels. There were statistically significant differences in HBsAg and anti-HBc before and after follow-up in the high HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, ALT, AST, Alb, and LSM. A liver biopsy was performed in 66 patients during follow-up, and 27.27% of the patients had moderate liver damage. In the low HBsAg group, 45.76% of patients had a HBsAg decrease rate of ≥0.5 log10IU/ml, 10.17% of patients had HBV DNA negative conversion, 88.14% of patients had a persistently normal ALT, and 96.61% of patients had a persistently normal LSM at the end of follow-up. In the high HBsAg group, 3.75% of patients had a HBsAg decrease of ≥0.5 log10IU/ml, no patient had a HBV DNA negative conversion, 90% of patients had a persistently normal ALT, and 98.75% of patients had a persistently normal LSM. There were statistically significant differences in the HBsAg decrease rate (45.76% vs. 3.75%, χ2=32.975, P＜0.001) and HBV DNA negative conversion rate (10.17% vs. 0, χ2=6.219, P=0.013) between the two groups at the end of follow-up, but there were no statistically significant differences in the persistently normal ALT and LSM rates. Conclusion: The vast majority of patients with HBeAg-negative chronic HBV infection in the indeterminate phase with low viral load had persistent hypoviremia over the long term. Some patients have liver tissue damage and may progress to cirrhosis and liver cancer as a result of HBV DNA positivity, so antiviral treatment should be initiated in all.

Liver and spleen stiffness measurement using the new FibroScan module for prediction of esophageal varices and monitoring response to beta blockers in portal hypertension

BackgroundThis study aimed to assess the clinical use of the new FibroScan module for measurement of liver and spleen stiffness (LS and SS), comparing their usefulness in prediction of esophageal varices (EV) in patients with portal hypertension (PH) and their clinical value for monitoring response to non-selective beta blockers (NSBB) treatment in these cases. The study included 120 patients with compensated cirrhosis and PH, in addition to 30 healthy comparable controls. Based on gastrointestinal endoscopy, patients were classified into three groups: 48 without EV, 42 with small EV, and 30 with large varices needing treatment. Then, abdominal ultrasound and assessment of LS and SS using new FibroScan 630 Expert module were done for both patients and controls. Group 3 patients were then initiated on NSBB (propranolol), and follow-up of these parameters was done after 3 months.ResultsLS and SS were significantly increased in cirrhotic patients compared to controls and were positively correlated with ultrasonography parameters (spleen length and portal vein diameter). Moreover, they were significantly higher in patients with varices than in those without varices (compared to other noninvasive parameters), correlating with varices severity, and significantly decreased with NSBB treatment, especially SS.ConclusionScreening of cirrhotic patients for development of EV by elastography (LS and especially SS) using the new FibroScan machine seems to be an optimal method in clinical practice and superior to other noninvasive tests in the diagnosis, assessment of severity, and follow-up of response to treatment in these patients.

Significant Within-Individual Variability in VCTE Liver Stiffness Measurements at Two Intercostal Spaces in Subjects with MASLD: Implications for Evaluating Improvement in Liver Fibrosis After Weight-Loss or Liver-Directed Therapy.

Studies have compared the group-averages of liver stiffness measures (LSMs) from multiple rib spaces by vibration-controlled transient elastography (VCTE) to stage liver fibrosis. No previous study has assessed within-individual liver stiffness variation from two rib spaces in individuals with metabolic-dysfunction associated steatotic liver disease (MASLD). We evaluated within-individual LSM variation according to body weight classification and its clinical implication. From October 2019 to March 2024, VCTE was performed on MASLD patients or those at high risk, in accordance with FibroScan guidelines. The LSMs were categorized into stages: <5 kPa (stage 0), 5-7.99 kPa (stage 1), 8-9.99 kPa (stage 2), 10-13.99 kPa (stage 3), and 14+ kPa (stage 4). Measurements with 10 values and IQR/median ≤ 0.30 were included, using SPSS V25.0 for analysis. Among 1107 subjects (age 54.4 ± 13.9 years, 56.9% female), 7.7% were normal weight, 20.7% overweight, 28.9% class 1 obesity, 21.3% class 2 obesity, and 21.2% class 3 obesity. Significant within-individual variation was noted: 67% (0-2 kPa) variation, 23.4% (2.1-6 kPa), and 10% (≥6.1 kPa). Class 3 obese individuals had the maximum variation. Comparing the group-average of LSM at each ICS site showed that 95% of individuals were within one fibrosis stage. While LSM group-averages at different rib sites provides reliable fibrosis staging, significant within-individual variability exists especially in class 3 obesity. This should be considered when serial LSM assessments are used to assess medical therapeutic efficacy.

LiMAx test and ultrasound elastography to measure biomarkers of declining liver function in patients with liver fibrosis: A correlation analysis.

Monitoring liver changes is crucial in the management of liver fibrosis. Current diagnostic methods include liver function tests such as the Liver Maximum Capacity (LiMAx) test and measurements of liver stiffness. While the LiMAx test quantifies liver function through 13C-methacetin metabolism, ultrasound (US) elastography noninvasively assesses liver stiffness. The relationship between the findings of these methods in patients with liver fibrosis is not fullyunderstood. This study evaluated the correlation between LiMAx measurements of liver function and US elastography-based liver stiffness measurements to better understand the interplay between functional and structural liver parameters in fibrotic liver disease. Additionally, the relationship between body mass index (BMI) and these parameters isevaluated. This retrospective study analysed data from 97 patients who underwent both LiMAx testing and real-time elastography, resulting in a total data set of 108 examinations. The correlations between the results of the LiMAx test and elastography and their relationships with body mass index (BMI) were analysed. There was a significant negative correlation (r = -0.25, p < 0.05) between LiMAx test values and liver stiffness measurements. BMI was significantly negatively correlated with LiMAx values (r = -0.29, p < 0.001) but not significantly correlated with liver stiffness values. This retrospective study confirms the results of previous studies showing a notable but weak association between liver function and liver stiffness. Our results highlight the potential value of both tests as complementary tools for the evaluation of liver health, reinforcing the necessity for a multimodal approach to liver assessment.

Host and Viral Factors Influencing Chronic Hepatitis B Infection Across Three Generations in a Family.

Chronic hepatitis B (CHB) infection is influenced by both virological and host factors. A total of 5,920 CHB patients were classified into four groups based on HBV seromarkers: three-generation families (CHB grandmother, mother, and child), two-generation families (CHB mother/child pairs), individuals recovered from HBV infection, and a control group. Serological markers, viral load, liver function tests (LFT), HBV mutations, HLA-DQ variations, cytokine polymorphisms, and liver stiffness measurements (LSM) were analyzed using FibroScan. Point mutations in genes such as core/pre-core (G1896A/G1899A), polymerase (H248N, H267Q, N263D), S (G145R, S143L), and X (C1500T, T1464C) were observed in 30% of three-generation pairs and 20% of two-generation pairs. The three-generation group exhibited the highest mean liver stiffness measurement (LSM) (4.94 ± 1.24kPa), which is considered a predictor for the development of hepatocellular carcinoma (HCC). Subsequent HLA allele analysis identified HLA-DQB105:01 (OR = 0.27) as a risk factor for treatment resistance, while HLA-DQB105 (OR = 0.98), HLA-DQB103 (OR = 0.80), and HLA-DQB104:01 (OR = 0.70) were associated with HBV persistence in both three- and two-generation groups. Higher frequencies of specific polymorphisms, including G/G (TNF-α: 75%; IL-18: 74%), A/A (IL-10: 74.28%), and C/C (IL-1ß: 80%), were significantly linked to persistent infection. Analysis of viral sequences, HLA-DQB1 variations, cytokine polymorphisms, and genetic relationships within the phylogenetic tree revealed that 40% of CHB patients from three-generation families were infected by a shared source of transmission, as indicated by the presence of the same HBV genotype. This study underscores the complex interplay of host and viral factors that influence hepatitis B infection outcomes and suggests potential familial transmission pathways.

CT and MR Imaging of Hepatocellular Carcinoma and Liver Cirrhosis

Liver masses are routinely evaluated using ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI). MRI may be used for further investigation in cases with atypical findings and difficult diagnoses. Hepatocellular carcinoma (HCC) is a common malignancy, and it is important to know the exact spread and number of HCCs, as there are numerous treatment options. In addition, it is important to know how the differentiations of HCCs are reflected on the images, and what the subtypes of HCCs look like on the images. Elastography with US and MRI is increasingly used to measure liver stiffness, and non-invasive assessment of liver fibrosis is also possible. This review describes the diagnosis of HCC on commonly used CT and MRI, and also touches on the frontiers of imaging diagnosis of liver parenchymal changes such as liver cirrhosis.

Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study

Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms. We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort. Participants underwent transient elastography to assess liver steatosis (controlled attenuation parameter (CAP)≥263dB/m) and -fibrosis (liver stiffness measurement (LSM)≥7.0kPa). Plasma protein concentrations (n=2367) (Olink® Explore Panel) were compared between PLHIV with vs. without liver steatosis and PLHIV with vs. without fibrosis. Enriched pathways (using GO, KEGG and Reactome libraries) and correlations with clinical characteristics wereassessed, and analyses were stratified by BMI category. In addition, concentrations of 242 proteins werecompared between individuals ("controls") with and without liver steatosis (ratio of methylene:methylene and water >5.6% on magnetic resonance spectroscopy) from a separate cohort (300-OB), all having a BMI >26kg/m2. Steatosis and fibrosis were associated with 67/2367 (2.2%) and 17/2367 (0.7%) differentially expressed proteins (DEP), respectively, enriched in mostly metabolic pathways. Immunoglobulin superfamily member 9 (IGSF9) was amongst the top DEP associated with both steatosis and fibrosis. Stratifying by BMI revealed 8/2367 DEP associated with steatosis in lean- and 12/2367 DEP in overweight/obese individuals, with two shared DEP (IGSF9 and GHR). Conversely, protein signatures of overweight/obese PLHIV (32/242 DEP) and overweight/obese HIV-uninfected individuals (32/242 DEP) exhibited substantial overlap with 16 shared DEP. Notably, DEP correlated with HIV characteristics in lean individuals but not in overweight/obese PLHIV. Lean and overweight/obese PLHIV exhibit distinct proteomic signatures associated with liver steatosis, with the former being more strongly correlated with HIV-specific factors and ART. In addition, we identified a protein, IGSF9, strongly related to liver fibrosis and steatosis across BMI categories. The 2000HIV study is funded by ViiV Healthcare.

ICG-r15 predicts esophageal varices in compensated liver cirrhosis: a noninvasive approach

ObjectiveThe aim of our study was to evaluate the indocyanine green (ICG) retention test as a noninvasive marker of esophageal varices(EV).MethodsThe clinical data of patients diagnosed with compensated liver cirrhosis in Tianjin Second People’s Hospital between January 2018 and January 2021 were analysed with SPSS 23.0.ResultA total of 144 patients (88 M/56 F, 51.7 ± 11.06 years) were enrolled. The ICG retention at 15 min(ICG-r15), PVD, TBIL, Cholinesterase(CHE), AST to ALT ratio(ARR), APRI, splenic area, Lok index, Park index and liver stiffness measurement in the absent or small EV group were lower than those in the medium or large EV group, while the ICG disappareance rate(ICG-K), Effective hepatic blood flow(EHBF), ALB, PLT, and Platelet to Spleen Diameter Ratio(PSDR) were higher, and the differences were significant (P < 0.05). ICG-r15, splenic area, APRI and PLT were independent predictors for medium or large esophageal varices (OR = 1.115, 1.025, 0.281, and 0.987, respectively,P < 0.05). The predictive value of ICG-r15 for medium or large varices was 17.95%, the specificity was 0.849, and the sensitivity was 0.662, the AUROC was 0.815. The cut-off value of PLT for M/L EV was 113.5, and the specificity and sensitivity were 0.616 and 0.887, the AUROC was 0.759. The AUROC of ICG-r15 combined with PLT was 0.866, which was more superior than others.ConclusionAlthough we are far from the replacement of endoscopy, ICG-r15 combined with PLT seems to be able to identify patients with medium or large EV in patients with compensated liver cirrhosis.

Reproducibility of EUS-guided shear wave elastography for assessment of hepatic fibrosis: a prospective pilot cohort study

Non-invasive assessment of liver fibrosis is important in the management of liver disease. EUS-guided shear wave elastography (EUS-SWE) is a newer technology that can measure liver stiffness, thereby estimating hepatic fibrosis. There is limited data comparing EUS-SWE to vibration controlled transient elastography (VCTE) using liver biopsy as the gold standard, and the reproducibility of EUS-SWE measurements is not known. 52 patients referred for EUS-guided liver biopsy (EUS-LB) were prospectively enrolled. Patients first underwent VCTE, then 2 consecutive EUS-SWE measurements done first in the left and then another 2 in the right. Bilobar EUS-LB was then done. Receiver operating characteristic curves were developed to compare EUS-SWE to VCTE and correlate to histology. Analysis was done to determine EUS-SWE variability in paired measurements for each lobe and between right and left liver lobes. The most common indication for EUS-LB was non-alcoholic steatohepatitis fibrosis staging in 46% of patients. Right lobe SWE had a strong correlation with fibrosis stage ρ = 0.571 (P < .0001) whereas left lobe EUS-SWE had a moderate correlation ρ = 0.368 (P < .0079). Both EUS-SWE and VCTE were similar for discrimination of all stages of fibrosis based on empiric ROC curves. However, the variance between paired consecutive EUS-SWE measurements was 3.5 times higher in the left lobe compared to the right lobe (P < .0001). EUS-SWE provides an assessment of hepatic fibrosis comparable to VCTE. EUS-SWE in the left lobe has 3.5 times higher variance between consecutive measurements compared to the right.

Body posture can modulate liver stiffness measured by transient elastography: a prospective observational study

BackgroundNon-invasive measurement of liver stiffness (LS), traditionally performed in the supine position, has been established to assess liver fibrosis. However, fibrosis degree is not the sole determinant of LS, necessitating the identification of relevant confounders. One often-overlooked factor is body posture, and it remains unclear whether normal daily postures interfere with LS irrespective of fibrosis. A prospective two-group comparison study was conducted to investigate the relationship between posture and LS.MethodsSixty-two adults participated, divided into two groups: patients with chronic liver disease and healthy controls. Both groups were assessed using transient elastography (TE) under the supine, seated, and standing postures. Randomization was applied to the order of the two upright postures. A two-way mixed ANOVA was conducted to assess the posture-dependence of LS and its variations between two groups.ResultsResults showed that posture differentially affected LS depending on the presence of liver fibrosis. In 31 healthy individuals (baseline LS range: 3.5–6.8 kPa), a transition from the supine (5.0 ± 1.0 kPa) to seated (5.7 ± 1.4 kPa; p = 0.036) or standing (6.2 ± 1.7 kPa; p = 0.002) positions increased LS, indicating liver stiffening. Conversely, in 31 patients with varying fibrosis stages (baseline LS range: 8.8–38.2 kPa), posture decreased LS from the supine (15.9 ± 7.3 kPa) to seated (13.8 ± 6.2 kPa; p < 0.001) or standing (13.9 ± 6.2 kPa; p = 0.001) positions. No significant difference in LS was observed between the seated and standing positions in both groups (control group: 5.7 vs. 6.2 kPa, p = 0.305; patient group: 13.8 vs. 13.9 kPa, p = 1). Additionally, different postures did not elicit significant changes in the success rate (supine, 98.6 ± 4%; seated, 97.6 ± 6%; standing, 99.1 ± 3%; p = 0.258) and IQR/median value (supine, 25 ± 8%; seated, 29 ± 15%; standing, 29 ± 12%; p = 0.117), implying no impact on both measurement feasibility and reliability.ConclusionsWe demonstrated, for the first time, the feasibility of utilizing upright postures as an alternative measurement protocol for TE. We further unravel a previously unrecognized role of transitioning between different postures to assist the diagnosis of cirrhosis. The findings suggested that daily physiological activity of postural changes suffices to alter LS. Therefore, body positioning should be standardized and carefully considered when interpreting LS.