US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study.

Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.

Clinical management, pathogen spectrum and outcomes in patients with pyogenic liver abscess in a German tertiary-care hospital.

Pyogenic liver abscesses (PLA) are life-threatening disorders and require immediate treatment, but structured evidence is sparse and treatment guidelines are not established. In a retrospective observational study of 221 adult PLA patients (mean age 63 years, 63% men) treated between 2013 and 2019 at the Leipzig University Medical Center, we characterized pathogen spectrum, clinical management and outcomes. Biliary malignancies (33%), cholelithiasis (23%) and ischemic biliary tract disease (16%) were most common causes of PLA. Comorbidities included malignancies (40%) and diabetes mellitus (35%). Abdominal ultrasound was the preferred initial imaging modality (58%). Enterobacterales (58%), enterococci (42%) and streptococci (18%) were identified as most frequent pathogens. 97% of patients were treated with antibiotics and 75% of patients underwent an invasive treatment procedure. The 30-day mortality was almost identical in patients with and without underlying malignancy (14.6% vs. 14.4%, p = 0.96), while the one-year outcome differed significantly (58.4% vs. 29.6%, p < 0.001). Positive blood cultures (OR 4.78, 95% CI 1.39 to 22.5, p = 0.023) and detection of Enterobacterales (OR 3.55, 95% CI 1.40 to 9.97, p = 0.010) were associated with increased 30-day-mortality. We conclude that ultrasound, extensive microbiologic diagnosis, adequate anti-infective therapy and early intervention are crucial for the management of PLA.

Ultrasound-guided percutaneous biopsy for focal liver lesions: Adverse events and diagnostic yield in a single-centre analysis.

PURPOSE: Ultrasound-guided biopsy of focal liver lesions (FLL) is a well-established procedure with crucial impact on therapeutic decisions. The safety and accuracy depend on needle type, tumour location and comorbidities. Modern oncological concepts often require large tumour specimens which may increase the procedural risk. MATERIALS AND METHODS: We retrospectively collected data from consecutively scheduled ultrasound-guided FLL biopsies performed in an interdisciplinary ultrasound unit at a university hospital from 2015-2020. We analysed complication rates, diagnostic accuracy, and patient outcome in a one-year period. RESULTS: Of 426 scheduled interventions, 339 were included: 322 primary biopsies (40% female, median age 65 years, median BMI 25.4 kg/m2) and 17 rebiopsies in cases with undetermined diagnosis. Indications comprised 309 (96%) cases with suspected malignant lesions. Important comorbidities were type 2 diabetes (n = 107, 33%) and cirrhosis (n = 64, 20%). A conclusive histopathological diagnosis was achieved in 270 (84%) cases with a weak association with lesion size (OR 1.12 per cm, 95%CI 0.99-1.27). Greater BMI (OR 0.60 per 10 BMI points, 95%CI 0.34-1.05) showed a trend towards an insufficient diagnosis. Relevant complications occurred in 8 (2.5%) cases (2 major; 1 life-threatening). Multiple passes showed a trend towards adverse events (OR 2.32 for > 1 pass, 95%CI 0.99-5.42). 93 (29%) patients died during a median follow-up of 171 days. CONCLUSION: Ultrasound-guided FLL biopsy is an efficient and safe diagnostic measure. The limitations of the procedure and its associated risks should be considered in patients with advanced malignancies.

Development, evaluation, and overview of standardized training phantoms for abdominal ultrasound-guided interventions.

PURPOSE: Ultrasound (US) represents the primary approach for abdominal diagnosis and is regularly used to guide diagnostic and therapeutic interventions (INVUS). Due to possible serious INVUS complications, structured training concepts are required. Phantoms can facilitate teaching, but their use is currently restricted by complex manufacturing and short durability of the materials. Hence, the aim of this study was the development and evaluation of an optimized abdominal INVUS phantom. MATERIALS AND METHODS: Phantom requirements were defined in a structured research process: Skin-like surface texture, homogeneous matrix with realistic tissue properties, implementation of lesions and abscess cavities in different sizes and depths as well as a modular production process allowing for customized layouts. The phantom prototypes were evaluated in certified ultrasound courses. RESULTS: In accordance with the defined specifications, a new type of matrix was developed and cast in multiple layers including different target materials. The phantom structure is based on features of liver anatomy and includes solid focal lesions, vessels, and abscess formations. For a realistic biopsy procedure, ultrasound-proof material was additionally included to imitate bone. The evaluation was performed by US novices (n=40) and experienced participants (n=41). The majority (73/81) confirmed realistic visualization of the lesions. The 3D impression was rated as "very good" in 64% of cases (52/81) and good in 31% (25/81). Overall, 86% (70/81) of the participants certified high clinical relevance of the phantom. CONCLUSION: The presented INVUS phantom concept allows standardized and realistic training for interventions.

Cystic fibrosis transmembrane conductance regulator function in patients with chronic pancreatitis.

BACKGROUND: Pathogenesis of chronic pancreatitis (CP) is still not entirely understood with many patients probably having more than 1 underlying etiology. Besides toxic-metabolic factors, genetics contribute to disease development. Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) are shown to increase risk for CP. Activity of CFTR can easily be accessed in vivo by measurement of nasal potential difference (PD). METHODS: We compared in this monocentric study 17 CP patients from the outpatient unit of our university hospital with 30 healthy controls regarding nasal PDs by using a superfusion protocol. Additionally, demographic and lifestyle data of all persons were recorded. RESULTS: Seventeen patients (12% female, median age 48 years) with CP and 30 healthy volunteers (47% female, 25 years) were included in the study. Patients with CP had a significant higher proportion of CFTR dysfunction (P = .04). Furthermore, demographics differed between the 2 groups with CP patients being older (P < .001). There were differences in daily alcohol consumption (P = .001) and smoking habits (smokers vs nonsmokers: P = .01, pack years: P = .002). CONCLUSIONS: PD measurement is an easily accessible way to show CFTR dysfunction as an etiological factor of CP. Cigarette smoking might impair CFTR function and therefore be 1 preventable cause of CP evolution.

[Imaging diagnostics of chronic pancreatitis]. / Bildgebende Diagnostik bei chronischer Pankreatitis.

Chronic pancreatitis is characterized by recurrent inflammatory episodes. The diagnosis is based on the detection of pathognomonic morphological alterations by ultrasound-based methods as well as computed tomography and magnetic resonance imaging. In addition, imaging techniques play an important role for the differential diagnostics of potential complications in patients with chronic pancreatitis and for regular monitoring of patients with increased cancer risk. This article summarizes the current guideline recommendations for medical imaging procedures in chronic pancreatitis.

Klebsiella Pneumoniae Liver Abscess Syndrome - A Challenge for Contrast-Enhanced Ultrasound.

Invasive liver abscess syndrome (ILAS) is caused by strains of hypervirulent Klebsiella pneumoniae (hvKp) and has emerged as the leading cause of liver abscesses in immuno-competent patients (L.K. Siu et al. Lancet Infect Dis 2012; 12: 881-87). ILAS is frequently associated with metastatic spread including the eyes, lungs, and the central nervous system. The morbidity and mortality of affected patients are increased compared to liver abscesses of other origin, especially in cases with concomitant diabetes mellitus (J. E. Choby et al. J Intern Med 2020; 287(3): 283-300). Immediate diagnosis and early intervention are essential for an optimal outcome. Therefore, ultrasound plays a crucial role if hvKp is suspected. However, experience with the characteristics of such abscesses on contrast-enhanced ultrasound (CEUS) is very limited.

Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis.

BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING: The German Federal Ministry of Education and Research and Echosens.

A young woman from an Echinococcus-endemic area with progressive abdominal distension: a case report.

BACKGROUND: Cystic echinococcosis is a zoonotic infection caused by Echinococcus granulosus. This case report shows the difficulty in differential diagnosis in a patient with highly suspected hydatid disease. CASE PRESENTATION: A 29-year-old Chinese woman presented with progressive abdominal distension. Imaging results revealed a large multicystic tumor with typical features of hydatid disease. There was no clear relationship between the cystic tumor and the liver, which led to the assumption of primary extrahepatic cystic echinococcosis. After albendazole therapy was initiated, a laparotomy was performed and a huge ovarian cystadenoma was diagnosed. CONCLUSIONS: This case highlights the possible challenges of differential diagnosis in patients with suspicion of hydatid cysts.

Biopsy rate and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD).

Background: Licensed therapies for nonalcoholic fatty liver disease (NAFLD) do not yet exist, but clinical trials are testing treatment options. Inclusion criteria often require liver biopsy showing fibrosis (F2/3) or cirrhosis (F4) and nonalcoholic steatohepatitis (NASH). However, histological criteria pose a serious obstacle for recruitment.Aims: Characterize the relevance of liver biopsies in the selection of patients with NAFLD.Methods: Patients between 2013 and 2018 with the ICD-10 code K76.0 were analyzed. Fibrosis was defined by the NASH clinical research network (CRN) fibrosis staging system, NASH by a NAFLD activity score (NAS) ≥4. Predictive factors were determined by logistic regression.Results: Liver biopsy was performed in 87/638 (13.6%) patients (49% female, age 52.5 ± 14.0, BMI 30.4 ± 5.9 kg/m2). Fibrosis stage F0/F1/F2/F3/F4 was observed in N = 7/47/7/17/9, an NAS ≥4 in N = 27. Fibrosis stage F2/F3 and F4 along with NAS ≥4 was found in 1.7% and 0.5% of cases. Liver stiffness measurement, LSM (OR 2.3 per doubling of value; CI 1.3-4.4, p = .005) and FIB-4 (OR 2.3 per doubling of value; CI 1.2-4.4, p = .012) were significant predictors for fibrosis ≥ F2. Predictive factors for NASH were not identified.Conclusion: The biopsy rate in NAFLD patients is low and fibrosis ≥ F2 along with NAS ≥4 only present in a few cases. Transient elastography and FIB-4 are useful to select patients at risk for fibrosis for liver biopsy.

Frequency and clinical presentation of alveolar and cystic echinococcosis in a tertiary medical center in Germany 2004-2018: lessons from a low-prevalence area.

INTRODUCTION: The prevalence of alveolar echinococcosis (AE) and cystic echinococcosis (CE) in Germany is increasing. The number of cases in northern and eastern regions is low, so there is little experience with regard to diagnosis and therapy. OBJECTIVES: The objective of this paper was to evaluate the management of suspected and/or diagnosed echinococcosis at a university center in a low-prevalence region. METHODS: All the patients at the Leipzig University Hospital between 2004 and 2018 who had been serologically examined for echinococci were included in a retrospective cohort study. Clinical course, imaging, histology, therapeutic characteristics, relevant comorbidities and risk factors for AE and CE were evaluated. A time-staggered prevalence estimation, as well as sensitivity and specificity calculations for the serological tests, were performed. RESULTS: A total of 382 patients were enrolled, with 11 AE and 7 CE cases identified. The mean prevalence rate of AE in this cohort was 2.9 % and that of CE was 1.8 %. Among the patients, 56 % had known risk factors for AE and CE. The serological tests showed a sensitivity of 86 % and a specificity of 91 %. Two patients with false-negative serology were diagnosed by biopsy. All CE and 5 AE patients (45 %) were operated on. Six AE patients received long-term treatment with albendazole. CONCLUSIONS: AE and CE are rare diseases in the greater Leipzig region; however, case numbers are on the rise. Due to favorable factors such as the escalation of migration, a further increase is expected. Diagnosis and therapy are challenging and should be supported by specialists (experienced infectiologists, imaging experts and skilled hepatobiliary surgeons) who should be integrated in a German network.

An unusual hypoechoic solid mass in the pancreatic head.

Solid pancreatic lesions found on imaging procedures are suspicious for malignancy and, therefore, demand immediate diagnostic evaluation and therapy. In the case of indeterminate histology, a primary resection should be considered in order to preserve the possibility of curative surgery, although rare entities may be initially disregarded. We present here the case of a 48-year-old female patient with a hypoechoic lesion of the pancreatic head, which was clearly delineated from the surrounding pancreatic tissue. The challenging diagnosis of metastatic leiomyosarcoma could only be established by considering the long-term clinical history and former histology specimens.