Transient Elastography Research Articles

Dynamics of Splenic Transient Elastography in Patients With Alcohol Use Disorder.

Splenic stiffness (SS) measurement (SSM) is an evolving noninvasive assessment to evaluate portal hypertension. Studies with respect to SSM in patients with alcohol use disorder are limited. We studied patients seeking treatment for alcohol use disorder in an inpatient treatment protocol at the National Institutes of Health and parsed SSM into 3 groups based on degree of change. The improved SS group had statistically higher initial SSM and a nonstatistically increased liver stiffness measurement compared with others. SS is dynamic in a subset of patients immediately after alcohol cessation, and improved SS is associated with a normalization of platelet count.

Daily Orange Consumption Reduces Hepatic Steatosis Prevalence in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Exploratory Outcomes of a Randomized Clinical Trial.

Background: Consumption of flavonoid-rich orange juice has been shown to reduce adiposity and liver steatosis in murine models of diet-induced obesity. However, little is known about the effects of whole orange intake, independent of body weight changes, on liver function and steatosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). The goal is to understand the direct impact of orange consumption on metabolic health. Methods: Sixty-two men and women aged 30-65 with MASLD (Controlled Attenuation Parameter, (CAP) > 275 dB/m) were randomly assigned to consume either 400 g of whole oranges or non-citrus fruits daily for 4 weeks. Baseline evaluations included medical assessments, blood tests, and body composition. Liver health was assessed using transient elastography (FibroScan®) for steatosis and fibrosis, conducted by blinded personnel. This clinical trial was registered at ClinicalTrials.gov (NCT05558592). Results: After 4 weeks of orange supplementation, liver steatosis decreased in the treatment group, with 70.9% showing steatosis compared to 100% in controls (p < 0.004), indicating a 30% reduction in liver disease prevalence. There were no significant changes in fibrosis or plasma liver enzymes, though plasma gamma glutaril transferase (GGT) levels decreased significantly. Body weight, waist circumference, body composition, lipid profile, fasting glucose, insulin, and C-reactive protein levels remained unchanged. Dietary analysis revealed no change in caloric intake, but vitamins C, A, thiamine, and riboflavin increased in the orange group. Conclusions: Our findings suggest that phytochemical-rich foods, especially whole fruits like oranges, may enhance liver function as an adjunct treatment for MASLD. The notable reduction in liver steatosis prevalence occurred independently of body weight changes. Further studies are needed to investigate the long-term effects of orange supplementation on steatosis and fibrosis progression and to identify the specific bioactive compounds and mechanisms involved.

Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children. Liver biopsy is considered the gold standard for diagnosis. Magnetic resonance elastography (MRE) and transient elastography (TE) are imaging modalities that can monitor fibrosis and steatosis noninvasively. More studies are needed to identify whether imaging modalities can provide accurate and reproducible data. We hypothesize that MRE provides reliable data similar to that of TE when compared to liver biopsy in children with MASLD/metabolic dysfunction-associated steatohepatitis. We conducted a retrospective chart review of children with liver biopsy-proven MASLD at Children's Hospital Los Angeles between September 2017 and January 2023, investigating and comparing the predictive accuracy of MRE and TE in the detection of high-grade fibrosis on liver biopsy. Seventy-seven patients were reviewed, all of whom had undergone liver biopsy, MRE and TE for evaluation of MASLD. Fibrosis was identified in 90% of liver biopsies. The area under the receiver operating characteristic curves (AUROC) of MRE and TE for detection of high-grade fibrosis were 0.817 and 0.750, respectively, and not significantly different (p = 0.4785). We demonstrate that MRE and TE did not accurately predict high-grade fibrosis on liver biopsy. Between the two noninvasive imaging modalities, the correlation of identifying high-grade fibrosis was not statistically different; however, the AUROC for MRE was slightly superior to that of TE. Studies with larger cohorts will be required to validate these findings.

Associations between dietary fatty acid and plasma fatty acid composition in non-alcoholic fatty liver disease: secondary analysis from a randomised trial with a hypoenergetic low-carbohydrate high-fat and intermittent fasting diet.

Dietary fatty acids (FA) affect metabolic risk factors. The aim of this study was to explore if changes in dietary fat intake during energy restriction were associated with plasma FA composition. The study also investigated if these changes were associated with changes in liver fat, liver stiffness and plasma lipids among persons with non-alcoholic fatty liver disease. Dietary and plasma FA were investigated in patients with non-alcoholic fatty liver disease (n 48) previously enrolled in a 12-week-long open-label randomised controlled trial comparing two energy-restricted diets: a low-carbohydrate high-fat diet and intermittent fasting diet (5:2), to a control group. Self-reported 3 d food diaries were used for FA intake, and plasma FA composition was analysed using GC. Liver fat content and stiffness were measured by MRI and transient elastography. Changes in intake of total FA (r 0·41; P = 0·005), SFA (r 0·38; P = 0·011) and MUFA (r 0·42; P = 0·004) were associated with changes in liver stiffness. Changes in plasma SFA (r 0·32; P = 0·032) and C16 : 1n-7 (r 0·33; P = 0·028) were positively associated with changes in liver fat, while total n-6 PUFA (r -0·33; P = 0·028) and C20 : 4n-6 (r -0·42; P = 0·005) were inversely associated. Changes in dietary SFA, MUFA, cholesterol and C20:4 were positively associated with plasma total cholesterol and LDL-cholesterol. Modifying the composition of dietary fats during dietary interventions causes changes in the plasma FA profile in patients with non-alcoholic fatty liver disease. These changes are associated with changes in liver fat, stiffness, plasma cholesterol and TAG. Replacing SFA with PUFA may improve metabolic parameters in non-alcoholic fatty liver disease patients during weight loss treatment.

Increasing engagement with liver disease management across the UK: follow-up cross-sectional survey.

Liver disease is an increasing cause of premature mortality. Early detection of liver disease in primary care gives opportunity to intervene and change outcomes. Engagement in liver disease care by NHS bodies responsible for primary care pathway development could drive improvements. The formation of integrated care systems (ICS) in England provides an opportunity to reassess engagement with liver disease nationally. To update the level of engagement with community chronic liver disease management amongst ICSs and health authorities across the UK. A cross-sectional follow up survey to ICS and UK Health Boards. Questions used for a previous survey in 2020 were adapted and sent electronically to NHS bodies responsible for health care across the UK using a Freedom of Information request. Quantitative analysis used Microsoft Excel. There were 67 responses from 68 possible ICS and Health Board areas representing 99% UK coverage. 27% had a named individual responsible for liver disease. Monitoring of local liver disease health statistics happened in 34% of all UK areas. Comprehensive care pathways were available in 24/67 (36%) of areas, an increase from 26% in the 2020 survey. Areas with no liver pathways in place fell from 58% to 36% between the two surveys. Regional variations persist, with Wales and Scotland moving towards comprehensive coverage. Almost double the number of areas were making use of transient elastography within community pathways of care, up from 25% to 46%. The results of this re-survey highlight improvements, but emphasise the need to build on regional success to further reduce inequality in care commissioning.

Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes.

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of Inoviridae was associated with both diabetes and liver steatosis. Diabetes was further associated with the enrichment of predominantly temperate Escherichia phages, some of which possessed virulence factors. Liver steatosis was associated with the depletion of Lactococcus phages r1t and BK5-T, and enrichment of the globally prevalent Crassvirales phages, including members of genus cluster IX (Burzaovirus coli, Burzaovirus faecalis) and VI (Kahnovirus oralis). The Lactococcus phages showed strong correlations and co-occurrence with Lactococcus lactis, while the Crassvirales phages, B. coli, B. faecalis, and UAG-readthrough crAss clade correlated and co-occurred with Prevotella copri. In conclusion, we identified the gut phageome signatures for two closely linked metabolic diseases with significant global burden. These phage signatures may have utility in risk modeling and disease prevention in this high-risk population, and identification of potential bacterial targets for phage therapy.IMPORTANCEPhages influence human health and disease by shaping the gut bacterial community. Using stool samples from a high-risk Mexican American population, we provide insights into the gut phageome changes associated with diabetes and liver steatosis, two closely linked metabolic diseases with significant global burden. Common to both diseases was an enrichment of Inoviridae, a group of phages that infect bacterial hosts chronically without lysis, allowing them to significantly influence bacterial growth, virulence, motility, biofilm formation, and horizontal gene transfer. Diabetes was additionally associated with the enrichment of Escherichia coli-infecting phages, some of which contained virulence factors. Liver steatosis was additionally associated with the depletion of Lactococcus lactis-infecting phages, and enrichment of Crassvirales phages, a group of virulent phages with high global prevalence and persistence across generations. These phageome signatures may have utility in risk modeling, as well as identify potential bacterial targets for phage therapy.

Associations of Cannabis Use, Metabolic Dysfunction-Associated Steatotic Liver Disease, and Liver Fibrosis in U.S. Adults.

Introduction: Following the introduction of metabolic dysfunction-associated steatotic liver disease (MASLD) as a replacement term for nonalcoholic fatty liver disease, the relationship between MASLD and cannabis use has yet to be established. With the global rise in cannabis consumption, understanding its impact on MASLD is critical for clinical guidance. Our study investigated the association between cannabis use, MASLD, and clinically significant fibrosis (CSF) among U.S. adults. Methods: Data were collected from the National Health and Nutrition Examination Survey for the period 2017 to 2018 to conduct a cross-sectional analysis. The diagnosis of hepatic steatosis and CSF was based on median values of the controlled attenuation parameter and liver stiffness measurement, with thresholds of 285 dB/m and 8.6 kPa, respectively. Information on cannabis use was obtained through self-report questionnaires. Multinomial logistic regression models and subgroup analyses were used to investigate the association between cannabis use and MASLD with CSF. Results: Our study assessed data from 2,756 U.S. adults (51.1% female; 32.2% white; mean age 39.41 ± 11.83 years), who had complete information on liver stiffness measurements through transient elastography alongside reported cannabis use. Results indicated that cannabis use overall was not associated with liver stiffness in patients with MASLD. However, among females, cannabis use was associated with MASLD accompanied by CSF, with an adjusted odds ratio (OR) of 0.47 (95% confidence interval [CI]: 0.24-0.91). Heavy cannabis use (9 to 30 times per month) was associated with MASLD accompanied by CSF among female participants, with an adjusted OR of 0.12 (95% CI: 0.02-0.88). Conclusion: In our study, cannabis use did not show a significant association with liver stiffness in patients diagnosed with MASLD. However, heavy cannabis consumption in women was associated with MASLD accompanied by CSF. These findings suggest that the effects of cannabis on liver health may differ based on gender and frequency of cannabis use, emphasizing the need for further research in this area.

Impairment of health-related quality of life among people with type 2 diabetes and advanced liver fibrosis

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p < 0.001). Obesity (β: − 0.247; 95% CI − 0.419, − 0.077) and AF (β: − 0.222; 95% CI − 0.383, − 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively affect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specific interventions may improve patient-reported and liver-related outcomes in people with T2DM.

Derivation of Splenic Stiffness in Subjects with Normal Liver Stiffness and No Vascular Liver Disease Using Transient Elastography with a Spleen-Dedicated Module: A Large Cross Sectional Study.

Liver and splenic stiffness measurements (LSM and SSM) are useful to predict varices and clinical decompensation in cirrhosis. SSM values are highly variable and overlapping and no guidelines exists on what constitutes normal SSM, that might limit interpretation of results. Consecutive subjects with LSM < 6 kPa and reliable SSM (FibroScan630 Expert device with spleen-dedicated module) and no vascular liver disease were analysed for significant correlations of SSM values with age, sex, BMI, portal and splenic vein diameter, splenic diameter, liver fat and diabetes. Based on timeline of SSM, subjects were randomly assigned in 70:30 ratio into derivation [n = 502] and validation subset [n = 214]. Of 7200 subjects with simultaneous reliable LSM and SSM, 715 fulfilled the selection criteria (mean age: 43.8 ± 12.8years, 67.2% male, mean BMI-26.4 ± 4.5kg/m2). The mean SSM was 22.6 ± 5.8kPa (c10-c90 percentile range: 15.2-31.3kPa) and followed the normal distribution curve. In the derivation subset, mean SSM for males was higher than female (23.06 ± 6.2vs. 21.78 ± 5.93kPa; p = 0.028). SSM value correlated with LSM (r = 0.454, p = 0.001). Mean SSM in subjects with LSM 3-4, 4.1-5 and 5.1-6kPa were 21.7 ± 5.8, 22.27 ± 5.67and 23.76 ± 5.88kPa (p value = 0.001). There was no difference in SSM based on age, BMI, diabetes and liver fat on ultrasound. Above results hold true for subjects in validation subset. SSM range in subjects with normal LSM and no vascular liver disease using spleen-dedicated module varies from 15.2 to 31.3kPa, values being higher in male and not affected by Age, BMI, spleen size, liver fat and diabetes. Our results may serve as reference point in evaluation of SSM in compensated advanced liver disease patients.

Diagnostic performance of new BAST score versus FIB-4 index in predicating of the liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease

Background and aimMetabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common liver condition globally. The FIB-4 test is used to detect fibrosis in fatty liver disease but has limited accuracy in predicting liver stiffness, resulting in high rates of false positives and negatives. The new BAST scoring system, incorporating waist circumference, AST, and BMI, has been developed to assess the presence of fibrosis in NAFLD patients. This study compares the effectiveness of BAST and FIB-4 in predicting liver fibrosis in MASLD patients.Patients and methodsThe study included 140 non-diabetic MASLD patients who underwent transient elastography measurement. BAST score and FIB-4 were calculated for each patient. Patients were grouped based on fibrosis severity; F1, F2, and F3–F4. The sensitivity and specificity of the BAST score and FIB-4 were assessed using receiver operating characteristic curves.ResultsThe BAST score increased significantly with fibrosis progression from F1 to F3–F4. In differentiating advanced fibrosis (F2–F3) from mild/moderate fibrosis (F1–F2), the BAST score at cutoff ≤ − 0.451 showed better diagnostic performance with 90.70% sensitivity, 74.07% specificity, 84.8% PPV and 83.3% NPV compared to FIB-4 that had 60.47% sensitivity, 50.0% specificity, 65.8% PPV and 44.3% NPV. Similarly, for differentiating between F1 and F2 fibrosis, the BAST score at cutoff ≤ − 1.11 outperformed FIB-4, with 80.23% sensitivity, 79.49% specificity, 89.6% PPV and 64.6% NPV, while FIB-4 had 59.30% sensitivity, 51.28% specificity, 72.9% PPV and 36% NPV.ConclusionsThe BAST score is a better predictor of liver fibrosis in MASLD compared to FIB-4, especially in cases of advanced fibrosis or cirrhosis.

Transient elastography, ultrasound imaging and liver enzymes in diagnosis of cystic fibrosis-related liver disease in children

Transient elastography, ultrasound imaging and liver enzymes in diagnosis of cystic fibrosis-related liver disease in children

Association of cardiovascular disease risk with liver steatosis and fibrosis in people living with hiv in low- and middle-income countries.

To understand the relationship between cardiovascular disease (CVD) risk and liver steatosis and fibrosis among people living with HIV (PLWH) ≥40 years on antiretroviral therapy (ART) in low- and middle-income countries (LMIC). We used cross-sectional behavioral and clinical data collected during study enrollment visits in 2020-2022 for the Sentinel Research Network of International epidemiology Databases to Evaluate AIDS (SRN of IeDEA). Ten-year CVD risk was calculated using 2019 World Health Organization non-laboratory and laboratory models. Transient elastography (TE) was used to assess liver disease. Presence of steatosis and significant fibrosis were defined by Controlled Attenuation Parameter (CAP) ≥248 dB/m and liver stiffness measurement (LSM) ≥7.1 kPa, respectively. Participants with viral hepatitis, hazardous alcohol consumption and unsuppressed HIV viral load were excluded from the analysis. Logistic regression was used to estimate odds ratios, adjusting for study site, CD4 T cell count, stavudine and didanosine exposure, and in models stratified by sex and geographic region. There were 1,750 participants from nine LMIC. Median CVD risk was 3% for both non-laboratory and laboratory-based models. Adjusted odds ratios (ORs) for steatosis and significant fibrosis associated with laboratory CVD risk (≥10% vs. <5%) were OR = 1.83 (95% confidence interval:(CI) = 1.21-2.76; P = 0.004) and OR = 1.62 (95% CI = 0.85-3.07; P = 0.14), respectively. Associations of CVD risk with steatosis were stronger in males and among participants at study sites outside Africa. Higher CVD risk was associated with steatosis but not with significant fibrosis in PLWH in our LMIC cohort.

Cohort Profile: the prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde, China (Speed-Shunde Cohort).

The objective of the prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde (Speed-Shunde cohort) was to evaluate the incidence of cardiovascular-kidney-metabolic (CKM) syndrome and metabolic-associated multimorbidity, such as diabetes, hypertension, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD) in Shunde, Foshan, Guangdong, China. Additionally, the study sought to identify the potential determinants that may impact the development of these conditions and the potential consequences that may result. In the Speed-Shunde cohort, data were gathered via questionnaires, physical measurements, and laboratory analyses encompassing demographic data, behavioral tendencies, anthropometric assessments, controlled attenuation parameters and liver stiffness measurement utilizing vibration-controlled transient elastography (VCTE), as well as serum and urine detection (such as oral 75g glucose tolerance tests, hemoglobin A1c levels, lipid profiles, liver and renal function tests, urinary microalbumin and creatinine levels, etc.). The baseline data were gathered from October 2021 to September 2022 from over 10,000 Chinese community-based adults and the follow-up surveys would be conducted every two or three years. Blood and urine samples were obtained and stored for future omics data acquisition. Initial analyses revealed the prevalence and risk factors associated with metabolic-associated multimorbidity. The Speed-Shunde Cohort study is a longitudinal community-based cohort with comprehensive CKM health and metabolic-associated multimorbidity assessment. It will provide valuable insights into these conditions' development, progression, and interrelationships, potentially informing future prevention and treatment strategies.

Non-invasive assessment of esophageal and fundic varices in patients with primary biliary cholangitis.

The Baveno VII consensus recommends endoscopic screening for varicose veins in cases of liver stiffness measurement (LSM) ≥ 20 kPa or platelet count ≤ 150 × 109/L. Whether this approach was appropriate for patients with primary biliary cholangitis (PBC) remains uncertain. This study expanded the observed risk factors by adding analysis of ultrasound images as a non-invasive tool to predict the risk of esophageal or fundic varices. We enrolled 111 patients with PBC whose complete ultrasound images, measurement data, and LSM data were available. The value of the periportal hypoechoic band (PHB), splenic area, and LSM in determining the risk of varicose veins and variceal rupture was analyzed. A prospective cohort of 67 patients provided external validation. The area under the receiver operating characteristic curve (AUC) for predicting varicose veins using LSM > 12.1 kPa or splenic areas > 41.2 cm2 was 0.806 (95% confidence interval (CI): 0.720-0.875) and 0.852 (95% CI: 0.772-0.912), respectively. This finding could assist in avoiding endoscopic screening by 76.6% and 83.8%, respectively, with diagnostic accuracy surpassing that suggested by Baveno VII guidelines. The AUCs for predicting variceal rupture using splenic areas > 56.8 cm2 was 0.717 (95% CI: 0.623-0.798). The diagnostic accuracy of PHB for variceal rupture was higher than LSM and splenic areas (75.7% vs. 50.5% vs. 68.5%). We recommend LSM > 12.1 kPa as a cutoff value to predict the risk of varicosity presence in patients with PBC. Additionally, the splenic area demonstrated high accuracy and relevance for predicting varicose veins and variceal rupture, respectively. The method is simple and reproducible, allowing endoscopy to be safely avoided. The measurement of the splenic area and identification of the periportal hypoechoic band (PHB) on ultrasound demonstrated high accuracy and relevance for predicting the risk of esophageal or fundic varices presence and variceal rupture, respectively. Predicting varices in patients with primary biliary cholangitis (PBC) can reduce the morbidity and mortality of gastrointestinal hemorrhage. Transient elastography (TE) and ultrasound play an important role in predicting patients with PBC with varices. TE and ultrasound can predict varicose veins and variceal rupture. Liver stiffness measurement and splenic area measurements can allow endoscopy to be safely avoided.

Dynamic Changes in ELF Score Predict Hepatocellular Carcinoma in Chronic Hepatitis B Patients Receiving Antiviral Treatment.

Enhanced liver fibrosis (ELF) score is a noninvasive assessment for liver fibrosis. We aimed to evaluate the performance of changes in ELF score 3 years apart in combination with liver stiffness measurement (LSM)-hepatocellular carcinoma (HCC) score to predict HCC in chronic hepatitis B (CHB) patients. This is a prospective cohort study. Patients who underwent transient elastography (TE) examinations and at intermediate or high risk of HCC defined by LSM-HCC score were invited to repeat the examination about 3 years later. Their serum samples at these two time points were retrieved to assess the ELF score changes. The primary endpoint was HCC. There were 445 CHB patients (males: 73.9%; mean age: 51.6 ± 10.3 years) who received two TE examinations and ELF scores. Among them, 252 (56.6%) and 193 (43.4%) patients were at intermediate and high HCC risk at first assessment defined by LSM-HCC score, respectively. Kaplan-Meier analysis showed that the changes in ELF score could stratify the HCC risk in both intermediate- and high-risk patients defined by LSM-HCC score (p < 0.001 for intermediate-risk group; p = 0.011 for high-risk group). Patients remained having mild or moderate fibrosis at both assessments had the lowest risk of HCC (4.0%), followed by patients with fibrosis regressed (11.3%; p = 0.014) during a mean follow-up of 163 months. Patients remained having or progressed to severe fibrosis were at highest risk of HCC (>20%). Consistent findings were demonstrated in patients at both intermediate and high risk of HCC defined by LSM-HCC score. Dynamic changes in ELF score provided additional value to LSM-HCC score for stratifying HCC risk in CHB patients.

Navigating the Maze: A Mini-Guide for the Management and Therapy of Metabolic Dysfunction-associated Steatotic Liver Disease

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Nonalcoholic Fatty Liver Disease (NAFLD), poses a significant global health challenge with a prevalence of 30% worldwide. Alarming projections anticipate a substantial increase in MASLD cases, highlighting the urgent need for preparedness and effective policies. The pathophysiology of MASLD involves a complex interplay of metabolic, genetic and lifestyle factors. Although liver biopsy remains the gold standard for the diagnosis of MASLD, non-invasive methods such as abdominal ultrasound, transient elastography with controlled attenuation parameter, shear wave elastography, and non-invasive serum fibrosis scores have been developed and validated. Effective risk stratification in primary care with non-invasive fibrosis scores, such as fibrosis 4 (FIB-4) index and NAFLD fibrosis score (NFS), optimizes healthcare resource utilization, ensuring appropriate referrals for high-risk patients while minimizing unnecessary referrals. Lifestyle intervention, including diet and physical activity, remains the primary therapy for MASLD. Notably, with the FDA approval of resmetirom, the first authorized medication for fibrotic metabolic dysfunction-associated steatohepatitis (MASH), and several antifibrotic agents under investigation, the therapeutic landscape for MASLD is rapidly evolving. Despite its increasing prevalence, morbidity and mortality, MASLD is frequently underdiagnosed in primary care. In this review, we aim to provide primary care physicians an update on the diagnosis, management and treatment of MASLD.

Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice

AbstractAdeno-associated virus–based gene therapy (valoctocogene roxaparvovec) is an attractive treatment for hemophilia A. Careful clinical management is required to minimize the risk of hepatotoxicity, including assessment of baseline liver condition to determine treatment eligibility and monitoring liver function after gene therapy. This article describes recommendations (developed by a group of hemophilia experts) on hepatic function monitoring before and after gene therapy. To prevent harmful liver-related effects, gene therapy is contraindicated in patients with uncontrolled liver infections, autoimmune hepatitis, liver stiffness ≥8 kPa, or cirrhosis. Before using gene therapy in patients with liver steatosis or other liver disorders, the risk of liver damage should be considered using a highly individualized approach. Treatment is not recommended in patients with abnormal liver enzymes, including alanine aminotransferase (ALT) at any level above the upper limit of normal (ULN). Therefore, pretreatment assessment of liver health should include laboratory tests, abdominal ultrasound, and liver stiffness measurements by transient elastography (TE). In the first year after therapy, ALT levels should be monitored 1 to 2 times per week to detect elevations ≥1.5× ULN, which may require immunosuppressant therapy. Patients with ALT elevation should receive prednisone 60 mg/d for 2 weeks, followed by stepwise tapering when ALT returns to baseline. ALT monitoring should continue long term (every 3-6 months), along with abdominal ultrasound (every 6 months) and TE (yearly) evaluations. When patients with good liver health are selected for treatment and closely monitored thereafter, ALT elevations can be promptly treated and are expected to resolve without long-term hepatic sequelae.

Early screening for chronic liver disease: impact of a FIB-4 first integrated care pathway to identify patients with significant fibrosis

Liver fibrosis is often undetected whereas it is the determinant of liver-related mortality. We evaluate a pathway based on the systematic calculation of FIB-4 to screen for advanced hepatic fibrosis. Systematic calculation of FIB-4 was implemented in the centralized laboratory of a French University Hospital in 4 pilot departments. If ≥ 2.67, the FIB-4 result was returned to the prescribers, for patients between 18 and 70 years of age, with an incentive to measure liver stiffness by vibration controlled transient elastography. During a 2-years period, a FIB-4 was calculated in 2963 patients and 135 were ≥ 2.67 (4.6%). After exclusion of patients with a known cause of elevated FIB-4, 47 patients (34.8%) were eligible for elastography. Forty patients underwent elastography, but only 15% (7/47) at the spontaneous request of the referring physician. Fifteen patients were identified with significant fibrosis, among which 8 attended the scheduled specialist consultation, all with a confirmed diagnosis of cirrhosis. A sequential pathway based on the systematic calculation of FIB-4 enables the identification of patients with significant unknown liver fibrosis, allowing to refer them to specialized care. Raising awareness is essential to improve the care pathway.

Correlation between ratio of fasting blood glucose to high density lipoprotein cholesterol in serum and non-alcoholic fatty liver disease in American adults: a population based analysis.

Based on previous research, elevated fasting blood glucose (FBG) and decreased high-density lipoprotein cholesterol (HDL-C) levels are associated with non-alcoholic fatty liver disease (NAFLD). It is hypothesized that the prevalence of NAFLD may be proportional to the FBG-to-HDL-C ratio (GHR). In this study, 3,842 participants from the National Health and Nutrition Examination Survey (NHANES) (2013-2020) were investigated. Liver steatosis was assessed using vibration-controlled transient elastography (VCTE). NAFLD was defined as controlled attenuation parameter (CAP) ≥288 dB/m. After adjusting for race, gender, age, diabetes, BMI, moderate activities, uric acid, albumin, ALT, GGT, ALP, total bilirubin and creatinine, multiple logistic regression analysis indicated a positive correlation between GHR and the prevalence of NAFLD (OR = 1.22, 95% CI = 1.17-1.28). Additionally, multiple linear regression analysis showed a positive correlation between GHR and the severity of liver steatosis according to CA p-values (β = 4.97, 95% CI: 4.28, 5.66). According to the subgroup analysis, the correlation was stronger in other race, participants at the age <50 years old and those with non-diabetes. In this study, a non-linear relationship and saturation effect between GHR and the prevalence of NAFLD was also revealed, characterized by an inverted L-shaped curve, with an inflection point of 7.443. Finally, the receiver operating characteristic (ROC) analysis suggested that the area under the curve (AUC) of GHR (AUC = 0.731) significantly exceeded that of FBG and HDL-C. Elevated GHR levels are independently associated with the severity of liver steatosis and the increased prevalence of NAFLD in American adults.

Compensated advanced chronic liver disease in patients with metabolic dysfunction-associated steatotic liver disease: association with cardiometabolic factors

Aim. Тo study cardiometabolic factors and the PNPLA3 I148M (rs738409 C&gt;G) gene polymorphism in association with the compensated advanced chronic liver disease (cACLD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).Materials and methods. А retrospective cross-sectional study was conducted. The total of 108 patients with MASLD (33 men and 75 women aged 28 to 89 years) involved were divided into two groups based on results of transient elastography: group 1 – with the presence of cACLD (liver stiffness ≥ 8.0 kPa) – 18 patients and group 2 – without cACLD (&lt;8.0 kPa) – 90 patients. Cardiometabolic risk factors and the PNPLA3 I148M (rs738409 C&gt;G) gene polymorphism were studied in both groups. Odds ratios (OR) and 95% confidence intervals (CI) were calculated, and a logistic regression model was constructed for the detection of cACLD.Results. Compared to group 2, patients with cACLD had statistically significant higher prevalence of: arterial hypertension (p &lt; 0.05), type 2 diabetes mellitus (p &lt; 0.01), obesity (p &lt; 0.05), dyslipidemia (p &lt; 0.05), and PNPLA3 gene polymorphism (p &lt; 0.05). The OR for cACLD in individuals with arterial hypertension was 5.58 (95% CI: 1.21–25.71; p &lt; 0.05), with type 2 diabetes mellitus – 4.58 (95% CI: 1.59–13.21; p &lt; 0.01), with obesity – 3.83 (95% CI: 1.17–12.52; p &lt; 0.05), with dyslipidemia – 6.12 (95% CI: 1.33–28.20; p &lt; 0.05), in the presence of a polymorphic variant of the PNPLA3 gene in a hetero or homozygous state – 3.9 (95% CI: 1.28–11.89; p &lt; 0.05). The binary logistic regression model for detecting cACLD included type 2 diabetes mellitus, dyslipidemia, and waist circumference. The area under the ROC curve was 0.81 (95% CI: 0.70–0.92), sensitivity was 72.2%, specificity was 74.4%, and accuracy was 84.3%.Conclusion. Type 2 diabetes mellitus, dyslipidemia, and waist circumference are the determining factors for the development of cACLD in patients with MASLD. The PNPLA3 I148M gene polymorphism does not play a leading role in the development of progressive MASLD in the study cohort.