Thy-1 restricts steatosis and liver fibrosis in steatotic liver disease.

BACKGROUND AND AIMS: Steatotic liver disease (SLD) is generally considered to represent a hepatic manifestation of metabolic syndrome and includes a disease spectrum comprising isolated steatosis, metabolic dysfunction-associated steatohepatitis, liver fibrosis and ultimately cirrhosis. A better understanding of the detailed underlying pathogenic mechanisms of this transition is crucial for the design of new and efficient therapeutic interventions. Thymocyte differentiation antigen (Thy-1, also known as CD90) expression on fibroblasts controls central functions relevant to fibrogenesis, including proliferation, apoptosis, cytokine responsiveness, and myofibroblast differentiation. METHODS: The impact of Thy-1 on the development of SLD and progression to fibrosis was investigated in high-fat diet (HFD)-induced SLD wild-type and Thy-1-deficient mice. In addition, the serum soluble Thy-1 (sThy-1) concentration was analysed in patients with metabolic dysfunction-associated SLD stratified according to steatosis, inflammation, or liver fibrosis using noninvasive markers. RESULTS: We demonstrated that Thy-1 attenuates the development of fatty liver and the expression of profibrogenic genes in the livers of HFD-induced SLD mice. Mechanistically, Thy-1 directly inhibits the profibrotic activation of nonparenchymal liver cells. In addition, Thy-1 prevents palmitic acid-mediated amplification of the inflammatory response of myeloid cells, which might indirectly contribute to the pronounced development of liver fibrosis in Thy-1-deficient mice. Serum analysis of patients with metabolically associated steatotic liver disease syndrome revealed that sThy-1 expression is correlated with liver fibrosis status, as assessed by liver stiffness, the Fib4 score, and the NAFLD fibrosis score. CONCLUSION: Our data strongly suggest that Thy-1 may function as a fibrosis-protective factor in mouse and human SLD.

Transabdominal ultrasound for the diagnostic workup of parenchymal pancreatic diseases. / Transabdominelle Ultraschalldiagnostik bei parenchymatösen Erkrankungen des Pankreas.

This continuing medical education article highlights the central role of transcutaneous sonography in diagnosing parenchymal pancreatic diseases. It emphasizes the importance of in-depth knowledge of sonographic imaging of organ anatomy and a structured examination methodology, particularly for identifying acute and chronic pancreatitis and related complications. The article provides detailed guidance for optimized examination techniques and equipment settings, even under challenging conditions, and discusses the application of ultrasound in various scenarios of pancreatic diseases. Moreover, the relevance of advanced sonographic techniques such as high-frequency sonography, elastography, and contrast-enhanced sonography is illuminated in the context of expanded diagnostic workup.

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.

[Ultrasound systems for abdominal diagnostics - current methods, clinical applications and new technologies]. / Ultraschallgeräte für die abdominelle Diagnostik: neue Techniken und Applikationen ­ Was gibt es? Was ist möglich? Was ist sinnvoll?

Abdominal ultrasound is the method of first choice in many clinical situations. Gray scale imaging (B-mode) and conventional Doppler techniques are nowadays complemented by contrast-enhanced ultrasound (CEUS), elastography, fat quantification and further technologies which allow multimodal characterization of organs and tissue structure using panoramic imaging, 3D-techniques and image fusion. The development of small portable devices augments the spectrum for sonographic diagnostics. In this review, we describe the current status of ultrasound technology based on published evidence. In addition, we provide guidance for quality assurance.

Diagnostic Value of Ultrasound in Fatty Liver Disease.

Hepatic steatosis is a commonly seen phenomenon in clinical practice and is the result of the accumulation of lipids in the hepatocytes. In most cases steatosis refers to nonalcoholic fatty liver disease (NAFLD), but it also occurs in other diseases of the liver parenchyma of a different etiology and is the result of the dysregulation of metabolic processes. Consequently, inflammatory processes can induce progressive fibrosis. Due to the high prevalence of fatty liver disease, a further increase in metabolic liver cirrhosis with corresponding complications can be expected in the near future. Due to its broad availability, ultrasound is particularly important, especially for the management of NAFLD. In addition to diagnosis and risk stratification, the monitoring of high-risk patients in NAFLD is becoming increasingly clinically important. Multimodality ultrasound includes B-mode and duplex methods, analysis of tissue stiffness (elastography), contrast-enhanced imaging (CEUS), and steatosis quantification. When using ultrasound in fatty liver disease, a standardized approach that takes into account the limitations of the method is essential.

[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.

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.

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.

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.

Quantification of Portal Vein Vascularization Using an Automated Post-Processing Video Analysis Tool.

Purpose Blood flow dynamics represent a diagnostic criterion for many diseases. However, no established reference standard is available. In clinical practice, ultrasound pulsed-wave Doppler (PW-Doppler) is frequently used to assess visceral blood flow, despite its well-known limitations. A quantitative analysis of conventional color Doppler patterns can be performed using an innovative ultrasound-based algorithm (pixel flow analysis, PFA). This tool already shows promising results in obstetrics, but the technique has not yet been evaluated for portal venous blood flow assessment. Methods This prospective exploratory research study evaluated the applicability of PFA in the portal venous system. Measurements of portal venous flow using PFA and PW-Doppler were compared in healthy volunteers (n=20) and in patients with hepatic steatosis (n=10) and liver cirrhosis (n=10). Results In healthy volunteers (60% female, mean age 23 years, BMI 21.5 kg/m 2 [20.4-23.8]), PFA and PW-Doppler showed a strong positive correlation in fasting conditions (r=0.69; 95% CI 0.36-0.87), recording a median blood flow of 834 ml/min (624-1066) and 718 ml/min (620-811), respectively. PFA was also applicable in patients with chronic liver diseases (55% female, age 65 years (55-72); BMI 27.8 kg/m 2 (25.4-30.8)), but the correlation between PFA and PW-Doppler was poor (r=- 0.09) in the subgroup with steatosis. A better correlation (r=0.61) was observed in patients with liver cirrhosis. Conclusion PFA and PW-Doppler assessment of portal venous vascularization showed high agreement in healthy volunteers and patients with liver cirrhosis. Therefore, PFA represents a possible alternative to conventional PW-Doppler sonography for visceral blood flow diagnostics and merits further evaluation.

Non-invasive assessment of steatohepatitis indicates increased risk of coronary artery disease.

INTRODUCTION: Fatty liver diseases (FLD), especially defined as metabolic dysfunction-associated FLD (MAFLD), is of growing importance for patients and health-care providers. Extrahepatic comorbidities, predominantly coronary artery disease (CAD), contribute to excess morbidity and mortality in FLD. Although the association of FLD and CAD is well known, underlying pathophysiological links are not fully understood. Non-invasive means of liver diagnostic enable a fast and thorough characterization of FLD. We therefore assessed the severity of FLD in a cohort of patients at risk of CAD. METHODS: Patients scheduled for coronary angiography were characterized by anthropometry, serum-based indices of liver fibrosis (NFS, FIB4), abdominal ultrasound and vibration controlled transient elastography (VCTE) including controlled attenuation parameter (CAP) and the Fibroscan-AST (FAST) score. Patients were stratified according to indication of therapeutic coronary intervention. RESULTS: 120 patients were recruited, MAFLD was found in 41%, while advanced fibrosis or cirrhosis were present in only 5%. Coronary vascular intervention was indicated in 42% (n = 50). Severity of steatosis assessed by CAP and risk of fibrosis defined by elevated liver stiffness (VCTE>8 kPa) and fibrosis indices were associated with the need for coronary intervention. FAST score, a marker of fibrotic steatohepatitis, was elevated in the intervention group (0.22 vs. 0.12, p<0.001). Multivariate regression analysis revealed FAST score as strongest predictor of CAD (OR 2.3 95%, CI 1.40-2.96). DISCUSSION: MAFLD is a frequent comorbidity in patients at CAD risk, but advanced liver disease has a low prevalence in patients undergoing elective coronary angiography. Therefore, a routine VCTE-based screening for FLD cannot be recommended in cardiac patients. The association of indicators of steatohepatitis with advanced CAD points to inflammatory processes as a conjoint mechanism of both diseases.

The application of high-performance ultrasound probes increases anatomic depiction in obese patients.

This study evaluated the impact of obesity on abdominal ultrasound diagnostics and assessed effect of high-performance ultrasound probes increased imaging quality. Lean and obese subjects (n = 40; 58% female) were categorized according to body mass index (BMI, 21 to 48 kg/m2). A highly standardized ultrasound examination of the abdomen was performed by trained examiners using three different probes in randomized order (standard probe versus two high-performance probes). Quality of B-mode and duplex ultrasound were assessed using a custom scoring approach for depiction of liver and kidney anatomy and vascularization. Across probes, imaging quality of hepatic and kidney anatomy was inversely related with BMI (P < 0.03, r < - 0.35). Age, sex, and BMI explained 51% of the variance within the ultrasound quality score, with ß = - 0.35, P < 0.0001 for BMI. Compared to the standard probe, high-performance probes allowed for a better depiction of kidney and liver anatomy in subjects above BMI 35 kg/m2 (n = 20, all P < 0.05), resulting in a less pronounced deterioration of imaging quality with increased BMI (all P < 0.05). In conclusion the study shows that obesity impairs ultrasound imaging quality of abdominal anatomy. The application of high-performance probes can increase anatomic depiction in obese patients.Registration number of the German Registry of Clinical Studies: DRKS00023498.

M probe comes first: Impact of initial probe choice on diagnostic performance of vibration controlled transient elastography.

BACKGROUND & AIMS: Probe choice (M or XL) in transient elastography can be made by the user's own measure of skin-to-liver-capsule distance (SCD) or with an automated tool (AUTO). We studied how AUTO depends on initial probe choice. METHODS: Three fictive clinics were considered: The "M-first clinic" uses AUTO from the M probe, the "XL-first clinic" uses AUTO from the XL probe and a "reference clinic" measures SCD independently. Agreement and discrepancies to the reference clinic were measured. RESULTS: 200 patients with chronic liver disease were prospectively included (58% female, 56 years, BMI 28.1 kg/m²). Fleiss' kappa for agreement in probe selection was 0.11 (95% CI -0.09 to 0.31), but accuracy was above 0.8 for both. Probe failure occurred for 16 (M-first clinic), 4 (XL-first clinic) and 3 patients (reference clinic). Use of XL probe given M probe failure improved performance of the M-first approach. The odds ratio for discrepancy in the XL-first vs M-first clinic is 2.4 (95% CI 1.2 to 5.2, p = 0.012) for liver fibrosis and 4.8 (95% CI 1.8 to 16.1, p < 0.001) for steatosis. CONCLUSIONS: Agreement in AUTO between M and XL probes is poor although each has acceptable accuracy. The M-first approach leads to fewer discrepancies and should be adopted as a standard.