Repeatability of vibration-controlled transient elastography versus magnetic resonance elastography in patients with cirrhosis: A prospective study.

BACKGROUND AND AIMS: Magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE) have the potential to assess disease progression; however, repeatability data in people with cirrhosis are lacking. We aimed to assess the effect of disease severity on measurement variability and contribute to the evidentiary basis for the qualification of repeating liver stiffness measurements (LSM) in practice and research. METHODS: This prospective study included 49 adult participants (58.3% female) with cirrhosis who underwent same-day repeat LSM examinations. The primary outcome was the same-day, same-operator repeatability coefficient% (RC%) and the within-case coefficient of variation (wCV) for each modality. Secondary outcomes include the intra-class correlation coefficient (ICC). The relationship between measurement variability (interquartile for VCTE, standard deviation for MRE) and disease severity (mean liver stiffness) was evaluated by linear regression with the coefficient of determination R2 reported. RESULTS: Same-day repeat MRE and VCTE exams were prospectively conducted in 33 and 45 participants, respectively. The RC% appeared 82% higher for VCTE versus MRE (38% vs. 21%), with consistent findings in head-to-head analyses. The wCV for VCTE and MRE was 14% and 8% respectively, indicating VCTE has 75% higher within-subject measurement variation than MRE. ICC was excellent for LSM by VCTE (0.92) and MRE (0.96). Measurement variability increased with mean liver stiffness for VCTE (R2 = 0.78) and MRE (R2 = 0.93). CONCLUSION: Both VCTE and MRE demonstrated increased measurement variability with disease severity. However, MRE outperformed VCTE in terms of technical repeatability in patients with cirrhosis. These repeatability estimates may improve the qualification of NITs in practice.

Natural history of clinical outcomes and hepatic decompensation in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: The natural progression of hepatic decompensation in metabolic dysfunction-associated steatotic liver disease (MASLD) is not well-characterised. We aimed to describe it by conducting a retrospective analysis. METHODS: This longitudinal, retrospective analysis of well-characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver-related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured. RESULTS: Of the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow-up of 3.2 years. Ascites was the most common first liver-related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver-related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy-three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years. CONCLUSION: The most common first liver-related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.

A prospective study on the prevalence of at-risk MASH in patients with type 2 diabetes mellitus in the United States.

BACKGROUND: There are limited data on the prevalence and treatment of at-risk metabolic dysfunction-associated steatohepatitis (MASH) among patients with type 2 diabetes (T2DM) in the United States. AIM: To estimate the prevalence of at-risk MASH in a prospectively recruited cohort of adults with T2DM using new nomenclature endorsed by multiple societies. METHODS: This prospective study enrolled adults aged ≥50 with T2DM from primary care and endocrinology clinics in southern California from 2016 to 2023. Metabolic dysfunction-associated steatotic liver disease (MASLD) was defined by an magnetic resonance imaging proton density fat fraction ≥5% and at least one metabolic risk factor without any other chronic liver disease or secondary cause for hepatic steatosis. RESULTS: We included 530 adult patients with T2DM. The mean (±SD) age and body mass index (BMI) were 64.4 (±8.1) years and 31.5 (±6.1) kg/m2, respectively. Among patients with T2DM, the prevalence of MASLD, at-risk MASH and cirrhosis was 69.6%, 13.6% and 6.8%, respectively. Among patients with co-existing T2DM and obesity, the prevalence of MASLD, at-risk MASH and cirrhosis was 77.8%, 15.9% and 9.0%, respectively, and was higher than in participants without obesity (p < 0.0001, 0.0543 and 0.0128, respectively). CONCLUSION: Among adults aged ≥50 years with T2DM, the prevalence of MASLD, at-risk MASH and cirrhosis is high, posing a significant risk for liver-related morbidity and mortality. Approximately 14% of patients with T2DM may be candidates for pharmacologic therapies specific to MASH-related fibrosis.

MASH Resolution Index: development and validation of a non-invasive score to detect histological resolution of MASH.

BACKGROUND: Dynamic changes in non-invasive tests, such as changes in alanine aminotransferase (ALT) and MRI proton-density-fat-fraction (MRI-PDFF), may help to detect metabolic dysfunction-associated steatohepatitis (MASH) resolution, but a combination of non-invasive tests may be more accurate than either alone. We developed a novel non-invasive score, the MASH Resolution Index, to detect the histological resolution of MASH. METHODS: This study included a derivation cohort of 95 well-characterised adult participants (67% female) with biopsy-confirmed MASH who underwent contemporaneous laboratory testing, MRI-PDFF and liver biopsy at two time points. The primary objective was to develop a non-invasive score to detect MASH resolution with no worsening of fibrosis. The most predictive logistic regression model was selected based on the highest area under the receiver operating curve (AUC), and the lowest Akaike information criterion and Bayesian information criterion. The model was then externally validated in a distinct cohort of 163 participants with MASH from a clinical trial. RESULTS: The median (IQR) age and body mass index were 55 (45-62) years and 32.0 (30-37) kg/m2, respectively, in the derivation cohort. The most accurate model (MASH Resolution Index) included MRI-PDFF, ALT and aspartate aminotransferase. The index had an AUC of 0.81 (95% CI 0.69 to 0.93) for detecting MASH resolution in the derivation cohort. The score calibrated well and performed robustly in a distinct external validation cohort (AUC 0.83, 95% CI 0.76 to 0.91), and outperformed changes in ALT and MRI-PDFF. CONCLUSION: The MASH Resolution Index may be a useful score to non-invasively identify MASH resolution.

Low liver fat in non-alcoholic steatohepatitis-related significant fibrosis and cirrhosis is associated with hepatocellular carcinoma, decompensation and mortality.

BACKGROUND: Progression to cirrhosis in non-alcoholic steatohepatitis (NASH) is associated with a decrease in liver fat. However, the prognostic significance of liver fat content in NASH-related significant fibrosis and cirrhosis is unclear. AIM: To investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH-related significant fibrosis and cirrhosis. METHODS: In this meta-analysis of individual participant data, 456 patients with both magnetic resonance elastography (MRE) and MRI-derived protein density fat fraction (MRI-PDFF) were enrolled, and 296 patients with longitudinal follow-up were analysed. MRE combined with fibrosis-4 (MEFIB-index), and MRI-PDFF were used to measure liver fibrosis and fat, respectively. MEFIB-negative, MEFIB-positive+ MRI-PDFF ≥5% and MEFIB-positive+ MRI-PDFF <5% were defined as no significant liver fibrosis, NASH with significant fibrosis and higher liver fat content, and NASH with significant fibrosis and low liver fat content groups, respectively. The primary outcome was hepatic decompensation, HCC and death. RESULTS: The rates of decompensation, HCC and mortality were highest in the NASH with significant fibrosis and low liver fat group (33%, 17% and 17%, respectively), followed by the NASH with significant fibrosis and higher liver fat group (18%, 13% and 13% respectively), and lowest in the no significant fibrosis (MEFIB-negative) group (0%, 1% and 2% respectively). In multivariable-adjusted analysis, low liver fat content was strongly associated (HR = 42.2 [95% CI: 7.5-235.5, p < 0.0001]) with HCC, decompensation and death. Sensitivity analyses for patients with cirrhosis (MRE ≥5 kPa) determined consistent findings. CONCLUSIONS: Low liver fat content in patients with burnt-out NASH-related significant fibrosis and cirrhosis is associated with an increase in hepatic decompensation, HCC and mortality.

Cost-Effectiveness Analysis of Hepatocellular Carcinoma Surveillance in Nonalcoholic Fatty Liver Disease Cirrhosis Using US Visualization Score C-Triggered Abbreviated MRI.

INTRODUCTION: Ultrasound (US) is associated with severe visualization limitations (US Liver Imaging Reporting and Data System visualization score C) in one-third of patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis undergoing hepatocellular carcinoma (HCC) screening. Data suggest abbreviated MRI (aMRI) may improve HCC screening efficacy. This study analyzed the cost-effectiveness of HCC screening strategies, including an US visualization score-based approach with aMRI, in patients with NAFLD cirrhosis. METHODS: We constructed a Markov model simulating adults with compensated NAFLD cirrhosis in the United States undergoing HCC screening, comparing strategies of US plus visualization score, US alone, or no surveillance. We modeled aMRI in patients with visualization score C and negative US, while patients with scores A/B did US alone. We performed a sensitivity analysis comparing US plus visualization score with US plus alpha fetoprotein or no surveillance. The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. Sensitivity analyses were performed for all variables. RESULTS: US plus visualization score was the most cost-effective strategy, with an ICER of $59,005 relative to no surveillance. The ICER for US alone to US plus visualization score was $822,500. On sensitivity analysis, screening using US plus visualization score remained preferred across several parameters. Even with alpha fetoprotein added to US, the US plus visualization score strategy remained cost-effective, with an ICER of $62,799 compared with no surveillance. DISCUSSION: HCC surveillance using US visualization score-based approach, using aMRI for visualization score C, seems to be the most cost-effective strategy in patients with NAFLD cirrhosis.