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.

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.

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.

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.

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.

[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.

Prevalence of Pruritus and Association with Anxiety and Depression in Patients with Nonalcoholic Fatty Liver Disease.

Patient-reported outcomes are important in nonalcoholic fatty liver disease (NAFLD). Pruritus is of special interest for evolving therapies with farnesoid X receptor (FXR) agonists. The aim of this study was to investigate the prevalence of pruritus in a real-life NAFLD cohort and analyze associations with anxiety and depression. Pruritus was assessed using a visual analogue- (VAS) and 5-D itch-scale (5-D). Anxiety and depression were evaluated by Beck's-Depression-Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS-A, HADS-D). An optimal logistic regression model was found with a stepwise procedure to investigate variables associated with pruritus. In total, 123 NAFLD patients were recruited. VAS and 5-D were highly correlated (Spearman's correlation coefficient 0.89). Moderate/severe pruritus was reported in 19% (VAS) and 21% (5-D) of patients. Anxiety and depression were present in 12% and 4% (HADS-A and HADS-D, respectively) and 12% (BDI) of cases. There was a significant association between VAS and BDI (p = 0.019). The final multivariate model for 5-D included diabetes mellitus (OR 4.51; p = 0.01), BDI (OR 5.98; p = 0.024), and HADS-A (OR 7.75; p = 0.011). One-fifth of NAFLD patients reported moderate or severe pruritus. 5-D was significantly associated with diabetes mellitus, depression, and anxiety. These findings should be tested in larger populations and considered in candidates for treatment with FXR agonists.

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.

Clinical implications of hepatic structure and function evaluation based on vibration-controlled transient elastography and liver maximum function capacity test in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Transient elastography [vibration-controlled transient elastography (VCTE)] noninvasively guides risk stratification in patients with nonalcoholic fatty liver disease (NAFLD). Patients with nonalcoholic steatohepatitis (NASH) and fibrosis can be identified using the FAST-score. The liver maximum function test (LiMAx) could be helpful in more precise risk stratification. This pilot study evaluated VCTE, FAST-score, and LiMAx in NAFLD patients. METHODS: NAFLD patients prospectively underwent VCTE and LiMAx. The cutoffs for high fibrosis risk were 9.3/9.6 kPa (M/XL-probe) and 331 dB/m for steatosis. A FAST-score greater than 0.67 was used to identify patients with NASH and LiMAx values below 315 µg/kg/h for impaired liver function. RESULTS: In total, 57 NAFLD patients (BMI 32 ± 6 kg/m2; 60% diabetes) were included. High risk for fibrosis and steatosis was observed in 26/57 and 28/57 cases, respectively. Overall, 19/57 patients presented impaired liver function. However, 14/26 of patients with a high risk for fibrosis had impaired liver function compared to 5/31 of those without (P = 0.0026). Similarly, 12/18 patients at high risk for NASH had impaired liver function compared to 7/39 without (P < 0.001). The subgroup with diabetes had a liver stiffness a factor of 1.8 higher, FAST-score was 0.13 higher and LiMAx values were 66 µg/kg/h lower compared to nondiabetics. CONCLUSION: There is a significant correlation between the functional liver capacity (LiMAx) and the structural liver assessment by VCTE. In cases with high liver stiffness or FAST-score, low LiMAx results may identify NAFLD patients at risk for disease progression and reduce the risk of false-positive categorization.

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.

[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.

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.

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.

Current NAFLD guidelines for risk stratification in diabetic patients have poor diagnostic discrimination.

Patients with type 2 diabetes (T2D) are at risk for non-alcoholic fatty liver disease (NAFLD) and associated complications. This study evaluated the performance of international (EASL-EASD-EASO) and national (DGVS) guidelines for NAFLD risk stratification. Patients with T2D prospectively underwent ultrasound, liver stiffness measurement (LSM) and serum-based fibrosis markers. Guideline-based risk classification and referral rates for different screening approaches were compared and the diagnostic properties of simplified algorithms, genetic markers and a new NASH surrogate (FAST score) were evaluated. NAFLD risk was present in 184 of 204 screened patients (age 64.2 ± 10.7 years; BMI 32.6 ± 7.6 kg/m2). EASL-EASD-EASO recommended specialist referral for 60-77% depending on the fibrosis score used, only 6% were classified as low risk. The DGVS algorithm required LSM for 76%; 25% were referred for specialised care. The sensitivities of the diagnostic pathways were 47-96%. A simplified referral strategy revealed a sensitivity/specificity of 46/88% for fibrosis risk. Application of the FAST score reduced the referral rate to 35%. This study (a) underlines the high prevalence of fibrosis risk in T2D, (b) demonstrates very high referral rates for in-depth hepatological work-up, and (c) indicates that simpler referral algorithms may produce comparably good results and could facilitate NAFLD screening.