Venkatesh, Sudhakar

Background: Societal guidance recommends sequential noninvasive testing for metabolic dysfunction–associated steatotic liver disease (MASLD), using Fibrosis-4 (FIB-4) ≥1.3 as a gatekeeper before second-line assessment with the Enhanced Liver Fibrosis (ELF) score (<7.7 as a rule-out). The impact of this pathway design on the detection of fibrotic MASH remains uncertain. We aimed to evaluate the performance of guideline-endorsed sequential testing and to determine optimized ELF thresholds within alternative strategies. Methods: In this prospective study, patients with or at risk for MASLD underwent FIB-4, ELF testing, magnetic resonance elastography (MRE), and liver biopsy within 1 month. Fibrotic MASLD was defined as fibrosis stage ≥2 on histology or liver stiffness ≥3.1 kPa on MRE. Diagnostic performance of ELF was assessed, and sequential (ELF applied after FIB-4 ≥1.3) and concurrent (either test positive) testing strategies were compared. Results: Among 186 participants (median age 51 years; 69% women), fibrotic MASLD was present in 71 (38%). ELF demonstrated AUROC 0.77 (95% CI 0.70–0.84); the cohort-derived cutoff was 9.4 (80% sensitivity, 65% specificity). Lower cutoffs (8.7 and 7.7) increased sensitivity (≥90% and 100%) but low specificity (34% and 4%). FIB-4 ≥1.3 showed limited sensitivity (57%), resulting in 43% of fibrotic MASH cases being excluded from second-line testing. Sequential application of ELF, therefore, failed to overcome this sensitivity ceiling. A concurrent strategy using FIB-4 ≥1.3 or ELF ≥9.4 improved sensitivity to 87% with 64% specificity. Conclusions: Sequential FIB-4–based testing substantially limits the detection of fibrotic MASLD due to gatekeeping sensitivity constraints. Concurrent first-line testing with FIB-4 and ELF improves case identification, underscoring the importance of pathway design in optimizing noninvasive fibrosis assessment.

ABSTRACT Hepatoid adenocarcinoma (HAC) is a rare extrahepatic tumor of non‐germ cell origin that morphologically resembles hepatocellular carcinoma (HCC). HAC has a propensity to metastasize to the liver and therefore may be mistaken for HCC. There is a lack of standardized treatment protocols, and further studies are needed to evaluate the benefit of targeted therapy and immunotherapy. Recent studies have reported that tumor protein 53 ( TP53 ) gene mutations are associated with increased expression of programmed cell death ligand‐1 (PD‐L1), which may be a predictor of response to PD‐L1 targeted checkpoint inhibitors. This review provides a clinical guidance for the management of patients with HAC by summarizing the salient clinical features, risk factors, diagnostic criteria, differential diagnosis, new therapeutic approaches, and prognosis of this rare tumor. Furthermore, we reviewed the Mayo Clinic experience to describe the clinical characteristics of 15 patients diagnosed with HAC. HAC is usually diagnosed at an advanced stage with distant metastases. In patients diagnosed with liver lesions that have similar radiologic and histologic features to HCC, particularly in the absence of underlying chronic liver disease, further evaluation should be performed to rule out HAC. Communication between medical subspecialties is important to avoid misdiagnosis and prevent further disease progression. In our patient cohort TP53 was the most frequently mutated gene (5 out of 8, 62.5%) and PD‐L1 expression showed a positive score in 3 out of 6 patients (50%). However, only a few patients received immunotherapy (6 out of 14, 42.9%) suggesting that the numbers are too small to draw a conclusion about its efficacy in treating HAC.

Background and Aims: Endoscopic ultrasound shear wave elastography (EUS-SWE) is a novel modality for liver stiffness measurement. The aims of this study are to evaluate the performance and reliability of EUS-SWE for detecting advanced liver disease in a prospective cohort. Methods: EUS-SWE measurements were prospectively obtained from patients undergoing EUS between August 2020 and March 2023. Liver stiffness measurements were compared between patients with and without advanced liver disease (ALD), defined as stage ≥3, to determine diagnostic accuracy for advanced fibrosis and portal hypertension. Logistic regression was performed to identify variables that impact the reliability of EUS-SWE readings. Select patients underwent paired magnetic resonance elastography (MRE) for liver fibrosis correlation. Results: Patients with ALD demonstrated higher liver stiffness compared to healthy controls (left lobe: 17.6 vs. 12.7 kPa, P <0.001; median right lobe: 24.8 vs. 11.0 kPa, P <0.001). The area under the receiver operator characteristic (AUROC) for the detection of ALD was 0.73 and 0.80 for left and right lobe measurements, respectively. General anesthesia was associated with reliable EUS-SWE liver readings (odds ratio: 2.73, 95% CI: 1.07-7.39, P =0.040). Left lobe measurements correlated significantly with MRE with an increase of 0.11 kPa (95% CI: 0.05-0.17 kPA) for every 1 kPa increase on EUS-SWE. D. Conclusions: SWE is a promising technology that can readily be incorporated into standard EUS examinations for the assessment of ALD.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder characterized by inflammation and fibrosis of the intra‐ and/or extrahepatic bile ducts. Magnetic resonance imaging (MRI) is a noninvasive imaging modality that can be used to diagnose PSC and detect disease related complications. Quantitative MRI technologies also have the potential to provide valuable prognostic information. Despite the potential of this imaging technology, the clinical application of MRI in the care of PSC patients and imaging standards vary across institutions. Moreover, a unified position statement about the role of MRI in the care of PSC patients, quality imaging standards, and its potential as a research tool is lacking. Conclusion : Members of the International PSC Study Group and radiologists from North America and Europe have compiled the following position statement to provide guidance regarding the application of MRI in the care of PSC patients, minimum imaging standards, and future areas of research. (H epatology 2017;66:1675–1688).