Vibration-controlled Transient Elastography Research Articles

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

BackgroundThe development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease.MethodsThis study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program.DiscussionThis study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country.Trial registrationThis study is registered on Clinicaltrials.gov (NCT03789825).

Accuracy of steatosis and fibrosis NAFLD scores in relation to vibration controlled transient elastography: An NHANES analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent and increasing in the United States. Based on patient characteristics and biochemical profiles, predictive indices have been formulated to evaluate the presence and severity of NAFLD. This study evaluates the accuracy of these indices versus vibration-controlled transient elastography (VCTE™) to screen at-risk populations for NAFLD. MethodsSubjects from the NHANES datasets (2017-2018) without other liver diseases with completed VCTE™ data were studied (n = 5062). Hepatic steatosis and fibrosis scores were calculated and compared with controlled attenuation parameter (CAP) and elastography measurements of VCTE™, respectively. ResultsThe prevalence of NAFLD was 58.5%. Against a CAP cut-off value of ≥238 dB/m for diagnosing fatty liver, the US fatty liver index [US-FLI] had the highest positive predictive value (90%) and specificity (63.7%). The coefficient of correlation against CAP was strong for fatty liver index [FLI] (r = 0.645) and US-FLI (r = 0.608). The hepatic steatosis index [HSI] had the highest negative predictive value (82.1%) and sensitivity (75%) for ruling out steatosis. HSI and FLI, which use commonly obtained clinical parameters, had a high diagnostic odds ratios (21.2 and 18.6, respectively) compared to US-FLI (4.97), which requires insulin levels in the calculation. These findings were similar across all ethnicities studied. ConclusionUS-FLI is a reliable scoring system to diagnose patients with fatty liver. HSI and FLI are more easily calculated and can be used in clinical practices to diagnose NAFLD in at-risk populations.

Unmixing multi-spectral electrical impedance tomography (EIT) predicts clinical-standard controlled attenuation parameter (CAP) for nonalcoholic fatty liver disease classification: a feasibility study.

Here, we tested the feasibility of predicting CAP with multi-spectral EIT. Conductivity and CAP were acquired from nonalcoholic fatty liver disease patients using a portable EIT system and vibration-controlled transient elastography (VCTE). We then used frequency-difference conductivity and waist-over-height as prediction features to estimate CAP and found an adj. R2 of 0.92. We further developed a novel prediction method by incorporating EIT spectral unmixing reconstruction and demonstrated an improvement in CAP estimation. Last, we optimized the EIT acquisition process by minimizing the total variance of the CAP estimator. Clinical Relevance: EIT can estimate clinical-standard liver disease classification. This portable EIT system is potentially cost-effective and self-administrable with short acquisition time (3 mins), while VCTE are costly and usually requires a trained personnel to operate with longer acquisition time (5-10 mins).

Assessment of Predictive Factors of Hepatic Steatosis Diagnosed by Vibration Controlled Transient Elastography (VCTE) in Chronic Hepatitis C Virus-Infected Patients

This retrospective, cross-sectional study aimed to evaluate the predictive factors of moderate/severe hepatic steatosis diagnosed by vibration-controlled transient elastography (VCTE). It included 158 adult patients with suspected nonalcoholic fatty liver disease (NAFLD) evaluated by VCTE in an outpatient setting of a community-based teaching hospital. Patients with significant alcohol consumption, oral contraceptive use, hepatitis B disease, autoimmune hepatitis, and primary biliary cirrhosis were excluded. Steatosis was categorized as S0-S1 (mild) and S2-S3 (moderate/severe) based on the controlled attenuation parameter (CAP) score. Results demonstrated the mean values of BMI (p = 0.001), kiloPascals [kPa] (fibrosis) raw score (p = 0.009), obesity (p = 0.001), diabetes mellitus [DM] (p = 0.014), and comorbidities status [chronic hepatitis C(HCV), DM, obesity, HCV+DM] (p = 0.028) were significantly different between the two arms of the study viz. S0-S1 (mild) and S2-S3 (moderate/severe). A multinomial logistic regression analysis of the comorbidities associated with hepatic steatosis revealed a good level of prediction (R2-0.584) for hepatic steatosis. Of all the variables analyzed, obesity was the most impactful vavriable. Furthermore, the -2 log-likelihood of the regressed model in patients with HCV and hepatic steatosis did not show a significant correlation when adjusted for obesity. Obesity had a significant independent association with steatosis (chi-square value = 52, df = 12). Interestingly, DM independently predicted a weak association with steatosis (chi-square value = 0.825, df = 3). In conclusion, our study demonstrates that hepatic steatosis is independently associated with metabolic parameters like obesity and DM. Management of these risk factors in patients with HCV may be vital to reducing the risk of steatosis and progression to fibrosis.

Prevalence and risk factors of nonalcoholic steatohepatitis with significant fibrosis in people with HIV.

Objective:Metabolic risk factors and nonalcoholic fatty liver disease (NAFLD) in people with HIV (PWH) have been increasing. Patients exhibiting the inflammatory subtype nonalcoholic steatohepatitis (NASH) are at increased risk of liver-related complications. Therefore, the aim was to investigate the prevalence of NASH with significant fibrosis in PWH using noninvasive tests (NITs).Design:In this prospectively enrolling cohort study, 282 PWH were explored for hepatic steatosis, fibrosis and steatohepatitis using vibration-controlled transient elastography (VCTE) and the Fibroscan-AST (FAST) score.Methods:On the basis of controlled attenuation parameter (CAP; dB/m) and liver stiffness measurement (LSM; kPa), patients were categorized according to the presence of steatosis (≥275 dB/m) and significant fibrosis (≥8.2 kPa). The FAST score was calculated according to established cut-offs.Results:The prevalence of hepatic steatosis in this cohort was 35.5% (n = 100) with 75 (75%) of these patients fulfilling the criteria of NAFLD. The prevalence of significant fibrosis (≥ F2) was 6.7% (n = 19). The FAST score identified a total of 32 (12.3%) patients with a cut-off greater than 0.35, of whom 28 (87.5%) PWH qualified as NASH. On multivariable analysis, waist circumference was a predictor of hepatic steatosis and type 2 diabetes was a predictor of significant fibrosis. Type 2 diabetes and ALT remained independent predictors of a FAST score greater than 0.35.Conclusion:NASH with significant fibrosis is highly prevalent among PWH. The FAST score may be helpful to identify patients at risk for significant liver disease.

Prevalence of elevated liver stiffness in patients with type 1 and type 2 diabetes: A systematic review and meta-analysis

Background & AimsLiver stiffness is an indirect marker of liver fibrosis, which predicts clinical outcomes in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present systematic review and meta-analysis is to summarize evidence on the prevalence of elevated liver stiffness in patients with diabetes. MethodsWe systematically searched PubMed-MEDLINE and Scopus from inception to May 2022 for observational studies reporting the prevalence of elevated liver stiffness diagnosed by vibration controlled transient elastography (VCTE) in adult patients with either type 1 (T1D) or type 2 diabetes (T2D). Prevalence values from individual studies were meta-analyzed using random effects models. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. ResultsOf the 428 titles initially scrutinized, 29 studies fulfilled the criteria and were included, providing data on 390 patients with T1D and 10,487 patients with T2D. Prevalence rates of elevated liver stiffness were 5.2% (95% CI 1.1–9.2) in patients with T1D and 19.8% (95% CI 16.8–22.8) in patients with T2D. In studies performed in patients with T2D, multivariate meta-regression analysis showed that higher body mass index, higher age, a higher proportion of males, lower VCTE cut-off and Asian ethnicity were associated with increased prevalence rates. This model explained 32.7% of the observed heterogeneity. No signs of publication bias were identified by visual inspection of the funnel plot or by Egger’s test. ConclusionsThis meta-analysis indicates that 1 in 20 patients with T1D and 1 in 5 patients with T2D has elevated liver stiffness, indicative of potential significant or advanced liver fibrosis.

Association of Metabolic Dysfunction-Associated Fatty Liver Disease and Liver Stiffness With Bone Mineral Density in American Adults.

ContestThe relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and liver stiffness and bone mineral density (BMD) remains unclear.ObjectivesWe aimed to investigate the association between MAFLD and liver stiffness and BMD in the United States population.MethodsA cross-sectional study among 2031 participants over 50 years old in the National Health and Nutrition Examination Survey (NHANES) 2017-2018 was performed. All patients underwent vibration controlled transient elastography (VCTE) and dual-energy x-ray absorptiometry (DXA). The linear and logistic regression model were used to analyze the association between the MAFLD and liver stiffness and osteoporosis, with adjustments for known covariates. Furthermore, the sensitive analyses were conducted to explore the relationship between MAFLD and liver stiffness and whole osteoporosis (include femoral and lumbar osteoporosis).ResultsMAFLD was prevalent in the study population, with a prevalence of 50.9% for men and 40.7% for women. The multiple linear models demonstrated positive associations between MAFLD and liver stiffness and total femur BMD, femur neck BMD, trochanter BMD, intertrochanter BMD. In multiple logistic regression models, both MAFLD and significant liver fibrosis were negatively associated with femoral osteoporosis (OR=0.41, 95% CI: 0.27 to 0.63; OR=0.67, 95% CI: 0.33-1.37, respectively). Nonetheless, when BMI was adjusted, the association between MAFLD and liver stiffness and osteoporosis became insignificant. Besides, as showed in the sensitive analyses, the relationship between MAFLD and liver stiffness and whole osteoporosis were stable.ConclusionsThese results suggest that MAFLD and liver stiffness were associated with higher femoral and lumbar bone mineral density in individuals aged over 50 years. But the results may be confounded by BMI.

Associations of Uric Acid With Liver Steatosis and Fibrosis Applying Vibration Controlled Transient Elastography in the United States: A Nationwide Cross-Section Study.

Background and objectiveSerum uric acid (UA) is related to many metabolic diseases. However, the association of UA with liver diseases was not very clear. The objective of this study is to clarify the relationship of UA with liver steatosis and fibrosis.MethodsThis is a cross-sectional study of 4364 people of National Health and Nutrition Examination Survey (NHANES) 2017-2018. Liver steatosis and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) using Vibration-controlled transient elastography (VCTE). Linear and logistic regressions were performed.ResultsAfter adjusting for potential confounders, UA levels were associated with the prevalence of liver steatosis [OR=2.097 (95%CI: 1.245, 3.534)] and liver fibrosis [OR=2.983 (95%CI: 1.797, 4.952)]. Furthermore, the results were consistent in the subgroup analyses of males and females.ConclusionsUA levels were positively associated with the prevalence of liver steatosis and fibrosis.

Associations between intake of starchy and non-starchy vegetables and risk of hepatic steatosis and fibrosis.

Current dietary guidelines generally treat all types of vegetables the same. However, whether specific vegetables are more beneficial or deleterious for preventing chronic liver disease (CLD) remains uncertain. We investigated the associations between starchy and non-starchy vegetables and the odds of hepatic steatosis and fibrosis in a US nationwide cross-sectional study. Diet was assessed by the 24-h dietary recalls. Hepatic steatosis and fibrosis were defined based on vibration-controlled transient elastography (TE). Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Among 4170 participants with reliable TE test, 1436 were diagnosed with steatosis, 255 with advanced fibrosis. Increased intake of total starchy vegetables was associated with higher odds of steatosis (OR per 1-SD increment 1.11, 95% CI 1.01-1.24) and advanced fibrosis (OR = 1.39, 95% CI 1.15-1.69). Similar positive associations were observed for potatoes. Conversely, intakes of total non-starchy (OR = 0.82, 95% CI 0.71-0.95) and dark-green vegetables (OR = 0.89, 95% CI 0.82-0.97) were inversely associated with steatosis prevalence. Replacing 5% of energy from starchy vegetables (OR = 0.65, 95% CI 0.44-0.97) or potatoes (OR = 0.65, 95% CI 0.43-0.97) with equivalent energy from dark-green vegetables was associated with lower odds of steatosis. These findings support the recommendation to limit starchy vegetable intake and increase non-starchy vegetable intake in CLD prevention, and provide evidence for the potential health benefit from dietary substitution of non-starchy vegetables for starchy vegetables.

Sex-related association of nonalcoholic fatty liver disease and liver fibrosis with body fat distribution in the general US population

Few population-based studies have investigated the association between body fat distribution and the risk of nonalcoholic fatty liver disease (NAFLD) and significant liver fibrosis. We aimed to evaluate the relations of total body fat and body fat distribution with NAFLD in the general US population. This is a cross-sectional, population-based study based on the 2017-2018 cycle of the NHANES. Participants aged 18-59 y without known liver conditions or significant alcohol consumption were studied by DXA and vibration-controlled transient elastography to assess body composition and liver steatosis and fibrosis, respectively. Multivariable logistic regression analysis was performed to evaluate the contribution of BMI and android:gynoid ratio (A:G ratio) to the prevalence of liver steatosis and fibrosis in males and females. Weighted prevalence of steatosis was 41.5% and 29.9% among the 1115 males and 1113 females included in the study, respectively, whereas 7.0% of males and 4.0% of females had elastographic evidence of significant liver fibrosis. After adjustment for age, race-Hispanic origin, diabetes, cigarette smoke, and BMI, a higher A:G ratio was associated with increased odds of steatosis in both males (OR: 1.79; 95% CI: 1.07, 2.99; P=0.029) and females (OR: 1.95; 95% CI: 1.11, 3.41; P=0.023). Conversely, a significant association between A:G ratio and liver fibrosis was identified in females (OR: 2.09; 95% CI: 1.11, 3.97; P=0.026), but not in males (OR: 0.56; 95% CI: 0.29, 1.08; P=0.078). Independently from BMI, an android fat deposition pattern is associated with increased prevalence of NAFLD in both sexes, whereas the effect on fibrosis was only evident in females.

The prevalence of nonalcoholic fatty liver disease in Chinese adults screened by vibration controlled transient elastography and its diagnostic discrepancy compared with ultrasound

BackgroundThe prevalence of non-alcoholic fatty liver disease (NAFLD) in China as assessed using vibration-controlled transient elastography (VCTE) and its consistency with ultrasound is still unknown. We aimed to conduct a head-to-head comparison of consecutive measurements of NAFLD with ultrasound or VCTE to evaluate the discrepancy in the prevalence and distribution of NAFLD screened by two non-invasive techniques. MethodsWe collected VCTE and ultrasound examination data from 4,388 participants who underwent health check-ups at the Health Promotion Center of Jiangsu Province Hospital between January 2017 and December 2019. The major outcome was the presence of hepatic steatosis, which was defined as a median controlled attenuation parameter (CAP) ≥ 248 dB/m by VCTE or the definition of steatosis by ultrasound. ResultsAmong the 4,388 participants, 2,214 were diagnosed with NAFLD by VCTE (CAP ≥ 248 dB/m, 50.46%). Participants with severe steatosis (CAP ≥ 280 dB/m) were commonly male (77.94% vs. 50.38%, P < 0.001), were obese (45.09% vs. 1.79%, P < 0.001), had a worse metabolic profile, had elevated liver enzyme levels, and had advanced fibrosis. The prevalence of ultrasound-diagnosed NAFLD was 56.42%. After consistency analysis, VCTE and ultrasound showed moderate agreement regarding the diagnosis of NAFLD (κ = 0.475). We then compared the characteristics and clinical features of the four groups classified by the diagnosis results of the two techniques. NAFLD participants diagnosed by VCTE only were older, more obese, and had worse metabolic and biochemical profiles than NAFLD participants diagnosed by ultrasound only; in particular, the former had a higher proportion of abnormal alanine aminotransferase and aspartate aminotransferase levels and a higher proportion of advanced fibrosis than the latter. ConclusionsMore than half of Chinese adults were affected by NAFLD according to VCTE. Screening based on VCTE is more likely to identify NAFLD patients with severe clinical features than ultrasound. Therefore, VCTE is a more practical non-invasive tool for the screening and follow-up of NAFLD in China.

Weight Change across Adulthood in Relation to Non-Alcoholic Fatty Liver Disease among Non-Obese Individuals

Background: To investigate the associations of weight change patterns across adulthood with the risk of non-alcoholic fatty liver disease (NAFLD). Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle, we performed a retrospective cohort study with 2212 non-obese participants aged 36 years old over. Weight change patterns were categorized as “stable non-obese”, “early adulthood weight gain”, “middle and late adulthood weight gain” and “revert to non-obese” according to the body mass index (BMI) at age 25, 10 years prior and at baseline. Vibration-controlled transient elastography (VCTE) was performed to diagnose NAFLD. Modified Poisson regression was used to quantify the associations of weight change patterns with NAFLD. Results: Compared with participants in the “stable non-obese” group, those who gained weight at early or middle and late adulthood had an increased risk of NAFLD, with an adjusted rate ratio (RR) of 2.19 (95% CI 1.64–2.91) and 1.92 (95% CI 1.40–2.62), respectively. The risk of NAFLD in “revert to the non-obese” group showed no significant difference with the stable non-obese group. If the association of weight change and NAFLD was causal, we estimated that 73.09% (95% CI 55.62–82.93%) of incident NAFLD would be prevented if the total population had a normal BMI across adulthood. Conclusions: Weight gain to obese at early or middle and late adulthood was associated with an evaluated risk of NAFLD. A large proportion would have been prevented with effective weight intervention.

Risk stratification of adolescents for the screening of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver conditions in adolescence are associated with premature mortality in adulthood. Effective screening could impact the population burden of this disease. We sought to determine which adolescents should be screened for non-alcoholic fatty liver using vibration-controlled transient elastography. We simulated a non-alcoholic fatty liver screening program of 938 adolescents from the National Health and Nutritional Examination Survey of 2017/2018. We stratified subjects by body mass index and metabolic parameters and analyzed our data using standard diagnostic statistical measures. The weighted prevalence of non-alcoholic fatty liver and non-alcoholic fatty liver disease was 24.4%, and 3.8%, respectively. For all subjects with obesity (21.8% of the population), screening identified 61.8% of the non-alcoholic fatty liver cases. In a category of all subjects with obesity and overweight subjects with metabolic abnormalities (26.7% of the population), screening identified 71.2% of non-alcoholic fatty liver cases. The two groups most likely to benefit by transient elastography screening are adolescents with obesity and overweight adolescents with one metabolic abnormality. These criteria reduce the number of individuals to be tested by approximately 80% (from an approximate 32 million adolescents to 6-7.5 million adolescents), while retaining a diagnostic accuracy of 84%-85%.

Impact of the new definition of metabolic dysfunction-associated fatty liver disease on detection of significant liver fibrosis in US adolescents.

Recently, an expert panel proposed diagnostic criteria for metabolic dysfunction–associated fatty liver disease (MAFLD) in the pediatric population. The aim of this study was to evaluate the prevalence of MAFLD among US adolescents and to investigate whether the new MAFLD definition is able to identify individuals with more advanced liver disease. We analyzed data from participants 12–18 years old included in the 2017–2020 cycles of the National Health and Nutrition Examination Survey, a large survey aimed at including individuals representative of the non‐institutionalized general US population. Participants with a complete vibration‐controlled transient elastography exam were included. Steatosis was evaluated through the median controlled attenuation parameter (CAP) and fibrosis through median liver stiffness measurement (LSM). Recently proposed criteria for the diagnosis of MAFLD were applied. Multivariable logistic regression analysis was performed to evaluate the impact of the new MAFLD definition on the odds of significant liver fibrosis. We included a total of 1446 adolescents (mean age: 14.9 years; 52.0% male; 47.3% overweight or obese). No participant reported a previous history of viral hepatitis. Steatosis (CAP ≥ 248 dB/m) was present in 25.9% (95% confidence interval [CI] 23.3–28.9) of individuals, and among these, 87.7% met the MAFLD criteria. Only 22.9% of patients with steatosis had elevated alanine aminotransferase levels. Among participants with steatosis, prevalence of significant liver fibrosis (LSM ≥ 7.4 kPa) did not differ significantly according to whether they met MAFLD criteria (9.7% vs. 15.2%, p = 0.276). In the multivariable model, odds of significant fibrosis did not differ significantly between these two groups. MAFLD criteria are met by most US adolescents with elastographic evidence of steatosis. Nonetheless, these criteria do not appear to improve detection of subjects with more advanced liver disease. Further longitudinal studies are needed to evaluate whether metabolic dysfunction is associated with faster progression toward inflammation, fibrosis, and liver‐related events.

Effect of hepatic steatosis and associated metabolic comorbidities on health-related quality of life in people living with HIV.

Hepatic steatosis (HS) related to nonalcoholic fatty liver disease (NAFLD) is increasing globally. In people living with human immunodeficiency virus (PLWH) risk factors of HS are increased. The impact of HS on outcomes and in particular health‐related quality of life (HRQL) in PLWH remains unknown. The aim of this cross‐sectional cohort study (FLASH, Prevalence of Advanced Fibrosis in Patients Living With HIV) was to determine the contribution of HS on HRQL in PLWH and to identify confounders on HRQL. A total of 245 PLWH were prospectively enrolled. HS was assessed using vibration‐controlled transient elastography and defined as a controlled attenuation parameter (CAP) of ≥ 275 dB/m. The analysis was performed between CAP < 275 and ≥ 275 dB/m. The generic European Quality‐of‐Life 5‐Dimension 5‐Level questionnaire was used to determine differences in the HRQL. Univariable and multivariable linear regression models were applied to identify predictors with impaired HRQL in both groups. In this cohort, 65% (n = 160) presented without and 35% (n = 85) with HS, of whom most had NAFLD (n = 65, 76.5%). The HRQL (UI‐value) was significantly lower in PLWH and steatosis (0.86 ± 0.18) in comparison with no steatosis (0.92 ± 0.13). Unemployment (p = 0.025) and waist circumference (p = 0.017) remained independent predictors of a poor HRQL in the steatosis subgroup. In turn, age (p = 0.045), female sex (p = 0.030), body mass index (p = 0.010), and arterial hypertension (p = 0.025) were independent predictors of a low HRQL in the subgroup without steatosis. Conclusion: HS and metabolic comorbidities negatively affect the HRQL. Addressing these factors may improve patient‐reported and liver‐related outcomes in PLWH.

Noninvasive assessment of liver fibrosis and its clinical significance in nonalcoholic fatty liver disease.

Liver fibrosis is the most important prognostic factor in patients with nonalcoholic fatty liver disease (NAFLD). Several noninvasive markers for fibrosis, including blood-based markers and imaging based-markers have been developed. Indirect fibrosis markers (e.g., fibrosis-4 index and NAFLD fibrosis score) consist of standard laboratory data and clinical parameters. Given its availability and high negative predictive value for advanced fibrosis, these markers are suitable for screening at primary care. Blood-based fibrogenesis markers (enhanced liver fibrosis and N-terminal propeptide of type 3 collagen), ultrasound-based modalities (vibration-controlled transient elastography, point shear wave elastography [SWE], and two-dimensional SWE), and magnetic resonance elastography have high diagnostic accuracy for liver fibrosis and are suitable for diagnosing liver fibrosis at secondary care centers. Sequential use of these markers can increase diagnostic accuracy and reduce health care costs. Furthermore, combining noninvasive makers may assist in identifying candidates for pharmacological trials and reducing screening failure. Emerging data suggest that these noninvasive markers are associated with liver-related events (hepatocellular carcinoma and decompensation) and mortality. Furthermore, delta change in noninvasive markers over time is also associated with time-course change in fibrosis, liver-related event risk, and mortality risk. However, the association between liver fibrosis and cardiovascular disease (CVD) risk is still controversial. CVD risk may decrease in patients with decompensated liver disease and noninvasive markers may be useful for assessing CVD risk in these patients. Therefore, noninvasive markers may be utilized as measures of fibrosis as well as real-time prognostic tools, in place of liver biopsy.

Magnetic resonance imaging metrics and the predictability of adverse outcomes in on-treatment Asian chronic hepatitis B.

Liver fibrosis and steatosis are important factors affecting chronic hepatitis B (CHB) disease outcome. Multiparametric magnetic resonance (MR) imaging of the liver measures fibroinflammation, fat, and iron through iron-corrected T1 relaxation time (cT1), proton density fat fraction (PDFF), and T2*-weighted imaging, respectively. We assessed the utility of MR metrics for prognostication in CHB. Chronic hepatitis B patients receiving nucleos(t)ide analogs with advanced fibrosis documented by vibration-controlled transient elastography were recruited. Paired multiparametric MR liver and transient elastography were performed at baseline and after at least 2years. Adverse outcomes including death, hepatocellular carcinoma (HCC), and liver decompensation were monitored. One hundred and ninety-two patients (mean age 60.3±8.5years; 76.0% male) were recruited. Eight patients (4.2%) developed HCC after 11.6 (8.8-22.8) months, and increased baseline liver iron independently predicted HCC (hazard ratio 2.329 [1.030-5.266]; P=0.042). Liver MR metrics were not predictive of death or hepatic decompensation. Among 150 patients with follow-up liver MR at 30.3 (25.2-35.6) months, longitudinal liver PDFF increase was associated with liver cT1 increase (odds ratio 1.571 [1.217-2.029]; P=0.001). Ninety patients received simultaneous multiparametric MR pancreas during the follow-up MR. Pancreatic PDFF correlated with liver PDFF (r=0.501, P<0.001), while pancreatic T1 had no correlation with liver cT1 (r=-0.092, P=0.479). Pancreatic T1 and PDFF were not associated with adverse outcomes. Among CHB patients with advanced disease, liver iron level on MR predicts HCC. Multiparametric MR can also simultaneously assess the pancreas and the liver. Multiparametric MR should be further studied as a one-stop option for monitoring and prognosticating CHB.

Multisite prospective Liver Disease and Reproductive Ageing (LIVRA) study in US women living with and without HIV.

PurposeThe Liver Disease and Reproductive Ageing (LIVRA) study leverages the infrastructure of the decades-long multicentre prospective Women’s Interagency HIV Study (WIHS) to examine the contributions of HIV, hepatitis C virus (HCV) and ageing to liver disease progression in women.ParticipantsFrom 2013 to 2018, LIVRA enrolled 1576 participants (77 HCV-seropositive only, 248 HIV/HCV-seropositive, 868 HIV-seropositive only and 383 HIV/HCV-seronegative) who underwent vibration controlled transient elastography (VCTE). A VCTE quality assurance programme was established to ensure consistency and accuracy for longitudinal assessment of steatosis (fatty liver) via the controlled attenuation parameter (CAP) and fibrosis via liver stiffness (LS). Demographic, lifestyle factors, anthropometry, clinical and medication history, host genetics, immune markers and hormone levels were collected as part of the WIHS.Findings to dateAt baseline, 737 of 1543 women with CAP measurements had steatosis (CAP ≥248 dB/m) and 375 of 1576 women with LS measurements had significant fibrosis (LS ≥7.1 kPa), yielding a prevalence of 48% and 24%, respectively. On multivariable analysis, waist circumference (WC) and insulin resistance were independently associated with higher CAP (17.8 dB/m per 10 cm (95% CI:16.2 to 19.5) and 1.2 dB/m per doubling (95% CI:0.8 to 1.6), respectively). By contrast, HIV/HCV seropositivity and HCV seropositivity alone were associated with less steatosis compared with HIV/HCV-seronegative women, although the latter did not reach statistical significance (−9.2 dB/m (95% CI:–18.2 to –0.3) and −10.4 dB/m (95% CI: −23.8 to 3.1), respectively). Factors independently associated with higher LS were age (4.4% per 10 years (95% CI: 0.4% to 8.4%)), WC (5.0% per 10 cm (95% CI: 3.3% to 6.6%)), CAP steatosis (0.6% per 10 dB/m (95% CI: 0.1% to 1.0%)), HIV/HCV seropositivity (33% (95% CI: 24% to 44%)) and HCV seropositivity alone (43% (95% CI: 28% to 60%)). Excluding scans that were invalid based on traditional criteria for unreliability did not affect the results.Future plansEnrolled women undergo VCTE at 3-year intervals unless LS is ≥9.5 kPa, indicating advanced fibrosis, in which case VCTE is performed annually. Participants also undergo VCTE every 6 months until 18 months after HCV treatment initiation. Analysis of the data collected will provide insights into the impact of ageing/ovarian function, host genetics, immune function and contemporary HIV and HCV treatments on liver disease progression.

Predicting NAFLD prevalence in the United States using National Health and Nutrition Examination Survey 2017-2018 transient elastography data and application of machine learning.

This cohort analysis investigated the prevalence of nonalcoholic fatty liver disease (NAFLD) and NAFLD with fibrosis at different stages, associated clinical characteristics, and comorbidities in the general United States population and a subpopulation with type 2 diabetes mellitus (T2DM), using the National Health and Nutrition Examination Survey (NHANES) database (2017–2018). Machine learning was explored to predict NAFLD identified by transient elastography (FibroScan®). Adults ≥20 years of age with valid transient elastography measurements were included; those with high alcohol consumption, viral hepatitis, or human immunodeficiency virus were excluded. Controlled attenuation parameter ≥302 dB/m using Youden’s index defined NAFLD; vibration‐controlled transient elastography liver stiffness cutoffs were ≤8.2, ≤9.7, ≤13.6, and >13.6 kPa for F0–F1, F2, F3, and F4, respectively. Predictive modeling, using six different machine‐learning approaches with demographic and clinical data from NHANES, was applied. Age‐adjusted prevalence of NAFLD and of NAFLD with F0–F1 and F2–F4 fibrosis was 25.3%, 18.9%, and 4.4%, respectively, in the overall population and 54.6%, 32.6%, and 18.3% in those with T2DM. The highest prevalence was among Mexican American participants. Test performance for all six machine‐learning models was similar (area under the receiver operating characteristic curve, 0.79–0.84). Machine learning using logistic regression identified male sex, hemoglobin A1c, age, and body mass index among significant predictors of NAFLD (P ≤ 0.01). Conclusion: Data show a high prevalence of NAFLD with significant fibrosis (≥F2) in the general United States population, with greater prevalence in participants with T2DM. Using readily available, standard demographic and clinical data, machine‐learning models could identify subjects with NAFLD across large data sets.

Clinical and Laboratory Characteristics of Normal Weight and Obese Individuals with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) has had, over the past few decades, a progressively growing prevalence among the general population all over the world, in parallel with metabolic conditions such as type 2 diabetes mellitus (T2DM), dyslipidemia, and obesity. However, NAFLD is also detected in 10–13% of subjects with a body mass index (BMI) ≤ 25 kg/m² (lean-NAFLD), whose major risk factors remain unknown. In this study, we aimed to characterize the clinical features and associated risk factors of lean-NAFLD in comparison with obese-NAFLD patients. Consecutive patients diagnosed with NAFLD by vibration-controlled transient elastography and controlled attenuation parameter were prospectively enrolled. Biological and clinical data obtained from the participants were stratified according to their BMI in two groups: lean-NAFLD and obese-NAFLD. In total, 331 patients (56.8% males) were included in the final analysis. Most of the subjects were obese-NAFLD (n = 258, 77.9%) and had a higher prevalence of T2DM, dyslipidemia, and components of the metabolic syndrome, together with abnormal biological parameters. Regarding liver stiffness measurements, the proportion of subjects with at least significant fibrosis (≥F2) was approximately twofold higher among obese-NAFLD (43.81%) in comparison with lean-NAFLD patients (23.29%). Moreover, obese individuals had a higher risk for liver fibrosis (OR = 2.6, 95%, CI 1.5–4.42, p < 0.001) than lean individuals. Although associated metabolic conditions and at least significant liver fibrosis were present in approximately one-quarter of the patients, these were more frequent among obese-NAFLD patients. Therefore, individualized screening strategies for NAFLD should be established according to BMI.