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Summary: Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown. Methods: Overall, 107 liver biopsies from PWH with MASLD (MASLD‐PWH) were matched to 107 biopsies from individuals with MASLD and without HIV (MASLD controls) on age at biopsy, race/ethnicity, sex, type 2 diabetes, body mass index (BMI) and alanine aminotransferase (ALT) level. Biopsies were scored using NAS. Results: Compared to MASLD‐controls, MASLD‐PWH had lower steatosis grade (OR: 0.65, 95% CI: (0.47–0.90), p = 0.01), lower lobular inflammation grade (OR: 0.55, 95% CI: (0.34–0.89), p = 0.02), less portal inflammation (OR: 0.42, 95% CI: (0.25–0.72), p = 0.002) and less ballooned hepatocytes (OR: 0.60, 95% CI: (0.41–0.88), p = 0.01). Thus, NAS was lower in MASLD‐PWH (OR: 0.69, 95% CI: (0.56–0.85), p < 0.001) than in MASLD controls. There was a trend towards lower prevalence of steatohepatitis in MASLD‐PWH (OR: 0.84, 95% CI: (0.68–1.03), p = 0.09). A multivariate analysis demonstrated that MASLD‐PWH cases had significantly less steatosis (OR: 0.66, p = 0.03), portal inflammation (OR: 0.34, p = 0.001) and ballooned hepatocytes (OR: 0.55, p = 0.01), yet higher stage fibrosis (OR: 1.42, p = 0.03) compared to MASLD controls. Conclusion: The NAS and histological drivers of fibrosis (e.g. inflammation and hepatocyte ballooning) are less pronounced in MASLD‐PWH, and yet fibrosis stage was generally higher when compared to matched controls with MASLD without HIV. This suggests HIV‐specific factors beyond hepatic necroinflammation may contribute to fibrosis progression in MASLD‐PWH. [ABSTRACT FROM AUTHOR]

During recent decades, the metabolic dysfunction-associated steatohepatitis (MASH) field has witnessed several paradigm shifts, including the recognition of liver fibrosis as the main predictor of major adverse liver outcomes. Throughout this evolution, liver histology has been recognised as one of the main hurdles in MASH drug development due to its invasive nature, associated cost, and high inter- and intra-reader variability. Collective experience demonstrates the importance of consistency in the central reading process, where consensus methods have emerged as appropriate ways to mitigate against well-known challenges. Using crystalized knowledge in the field, stakeholders should collectively work towards the next paradigm shift, where non-invasive biomarkers will be considered surrogate endpoints for accelerated approval. In this review, we provide an overview of the evolution of the regulatory histology endpoints and the liver biopsy reading process, within the MASH trial landscape, over recent decades; we then review the biggest challenges associated with liver biopsy endpoints. Finally, we discuss and provide recommendations on the best practices for liver biopsy evaluation in MASH drug development. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if implementation of the 2019 Society of Interventional Radiology (SIR) guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy is associated with increased haemorrhagic adverse events, change in pre-procedural blood product utilization, and evaluation of guideline compliance rate at a single academic institution. Methods: Ultrasound guided percutaneous liver biopsies from (January 2019-January 2023) were retrospectively reviewed (n = 504), comparing biopsies performed using the 2012 SIR pre-procedural coagulation guidelines (n = 266) to those after implementation of the 2019 SIR pre-procedural guidelines (n = 238). Demographic, preprocedural transfusion, laboratory, and clinical data were reviewed. Chart review was conducted to evaluate the incidence of major bleeding adverse events defined as those resulting in transfusion, embolization, surgery, or death. Results: Implementation of the 2019 SIR periprocedural guidelines resulted in reduced guideline non-compliance related to the administration of blood products, from 5.3% to 1.7% (P =.01). The rate of pre-procedural transfusion remained the same pre and post guidelines at 0.8%. There was no statistically significant change in the incidence of bleeding adverse events, 0.8% pre guidelines versus 0.4% post (P = 1.0). Conclusion: Implementation of the 2019 SIR guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy did not result in an increase in bleeding adverse events or pre-procedural transfusion rates. The guidelines can be safely implemented in clinical practice with no increase in major adverse events. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Although nonalcoholic fatty liver disease (NAFLD) and lipoprotein(a) [Lp(a)] are associated with cardiovascular diseases, existing data on Lp(a) in NAFLD are conflicting. The aim of this systematic review and meta‐analysis was to summarize and compare data on circulating Lp(a) between NAFLD patients and non‐NAFLD controls.A systematic literature search was performed in PubMed, Scopus, and Cochrane Library. This meta‐analysis included 18 studies containing data on 74 691 individuals (20 220 patients with NAFLD and 54 471 controls).Circulating Lp(a) was similar between patients with NAFLD and controls (standardized mean difference [SMD] 0.09; 95% confidence interval [95% CI] −0.21, 0.38). The heterogeneity among studies was high (I2 = 100%); no publication bias was detected (Egger's test P = 0.941). However, in subgroup analysis, Lp(a) was lower in NAFLD patients than controls, when Lp(a) was measured with nephelometry (SMD ‐0.26; 95% CI ‐0.46, −0.06), but not turbidimetry; this analysis also resulted in mild reduction of heterogeneity within the subgroup of nephelometry (I2 = 87%). The sensitivity analyses, based on the exclusion of studies with Newcastle‐Ottawa Scale score ≤6 (n = 5), studies in which liver biopsy was used for NAFLD diagnosis (n = 4) or studies that adopted the criteria of metabolic dysfunction‐associated fatty liver disease (n = 2), and meta‐regression analysis did not explain the high heterogeneity among studies.Overall, circulating Lp(a) was similar between NAFLD patients and non‐NAFLD controls; however, patients with NAFLD had lower circulating Lp(a) compared with controls, when Lp(a) was measured with nephelometry. These results should be cautiously interpreted, because of the high heterogeneity among studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Aims Methods Results Conclusions Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a growing public health problem. The secondary stage in MASLD is steatohepatitis (MASH), the co‐existence of steatosis and inflammation, a leading cause of progression to fibrosis and mortality. MASH resolution alone improves survival. Currently, MASH diagnosis is via liver biopsy. This study sought to evaluate the accuracy of imaging‐based tests for MASH diagnosis, which offer a non‐invasive method of diagnosis.Eight academic literature databases were searched and references of previous systematic reviews and included papers were checked for additional papers. Liver biopsy was used for reference standard.We report on 69 imaging‐based studies. There were 31 studies on MRI, 27 on ultrasound, five on CT, 13 on transient elastography, eight on controlled attenuation parameter (CAP) and two on scintigraphy. The pathological definition of MASH was inconsistent, making it difficult to compare studies. 55/69 studies (79.71%) were deemed high‐risk of bias as they had no preset thresholds and no validation. The two largest groups of imaging papers were on MRI and ultrasound. AUROCs were up to 0.93 for MRE, 0.90 for MRI, 1.0 for magnetic resonance spectroscopy (MRS) and 0.94 for ultrasound‐based studies.Our study found that the most promising imaging tools are MRI techniques or ultrasound‐based scores and confirmed there is potential to utilise these for MASH diagnosis. However, many publications are single studies without independent prospective validation. Without this, there is no clear imaging tool or score currently available that is reliably tested to diagnose MASH. [ABSTRACT FROM AUTHOR]

Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute‐on‐chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first‐line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so‐called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug‐induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up‐to‐date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug‐induced, autoimmune‐like hepatitis (DI‐AIH). [ABSTRACT FROM AUTHOR]

Introduction: This report presents a case of an exceptionally delayed distant recurrence of a choroidal melanoma, occurring 4 decades after the enucleation of the affected eye. Case Presentation: In 1977, a 29-year-old man underwent enucleation for a choroidal melanoma. At the age of 68 years, he was diagnosed with advanced prostate cancer. Although the metastatic prostate cancer responded to treatment, a persistent lung lesion warranted further examination. A lung biopsy, somewhat surprisingly, confirmed the presence of melanoma metastasis, 4 decades after the enucleation. The cells were positive for Melan-A, while no BRAF mutation was identified. Two years later, new lesions appeared in the liver, and CT showed progression with multiple new sites. A liver biopsy revealed again melanoma recurrence, and its choroidal origin was verified by the presence of a GNA11 mutation. The patient underwent radiation therapy for the lung and liver lesions, followed by immunotherapy. However, the patient died 11 months after the recurrence in the liver. In this case report, the micrometastatic melanoma cells appear to have remained dormant for an extended period, before the patient’s treatment in 1977, but the reason for the late reactivation from the dormant state remains unclear. Conclusion: The recurrence of a choroidal melanoma is substantiated by the histopathological and molecular analyses, including the finding of a GNA11 mutation. This case exemplifies a remarkably delayed distant recurrence of a choroidal melanoma, which manifested clinically 40 years following enucleation. [ABSTRACT FROM AUTHOR]

Introduction: With rapidly growing interest in the use of cannabidiol (CBD) in the management of pain and other conditions, more information is needed on the safety and efficacy of this supplement, particularly its co-administration with commonly used pharmaceuticals such as non-steroidal anti-inflammatory drugs (NSAIDs). This study sought to assess the effect of CBD in dogs with mobility impairments, as well as evaluate the clinical tolerance of CBD used together with NSAIDs. Materials and methods: Forty-two client-owned dogs with diagnosed mobility impairments were enrolled in this prospective, double-blind, crossover, placebo-controlled study. Baseline data were collected for 10-14 days followed by random allocation to either placebo or CBD oil for 45 days with a 30-day washout period in between. CBD was dosed at 5 mg/kg orally every 12 h with masked placebo administered at equal volume. Outcome measures included objective gait analysis, accelerometry, and clinical metrology instruments. CBD plasma levels and serum biochemistry were also collected along with hepatic ultrasound if warranted. Results: Thirty-eight dogs finished the study with thirty-nine included for at least partial analysis. Compared to baseline, dogs receiving CBD showed evidence of improved outcomes based on blinded veterinary assessments and accelerometer data. Compared to placebo, dogs receiving CBD showed some evidence of improved outcomes on CBPI, CSOM, and blinded veterinary assessments, but not for objective outcome measures. There was evidence of increased ALP when CBD was co-administered with NSAIDs compared to CBD administration alone. Additionally, there was evidence of ALT elevations with CBD and NSAID co-administration, but this elevation did not show evidence of an increase over CBD use alone. Discussion: These results suggest a potential therapeutic benefit in the administration of CBD for the management of mobility impairments, but greater ALP elevations were seen when administered with NSAIDs. While the sample size of dogs that received further hepatic work-up for liver enzyme elevations is small, chosen diagnostics varied, and liver biopsies were not performed, there did not appear to be clinically apparent liver damage. Further research is needed to better understand the efficacy of CBD in a larger population of dogs and patient tolerance and safety when administered with NSAIDs or other medications long term. [ABSTRACT FROM AUTHOR]

AbstractBackground: Meckel-Gruber syndrome (MGS) is a rare disease with a fatal, autosomal recessive inheritance pattern. This article mentions the neonatal MGS case followed by intestinal atresia and meconium pseudocyst clinic. Case presentation: Bile-containing-fluid was aspirated from the fetus, which was found to have polyhydramnios, gastric dilatation, lung hypoplasia, and cystic formation with a diameter of 68*62mm in the abdomen at 32 weeks of gestation in the intrauterine period. The cyst recurred after 2 weeks. We operated the patient with the preliminary diagnosis of meconium pseudocyst due to intrauterine perforation. The general condition was moderate in the postoperative period, and intermittent bilious vomiting continued. We performed an ileostomy on the patient due to his inability to tolerate oral intake, lack of passage, and abdominal distension. In addition, as a result of liver biopsy, cholestasis, cholestatic changes, bile-duct loss, and ductular reaction were detected. According to the current clinical findings and genetic analysis results, the patient was diagnosed with MGS. Conclusion: Autosomal recessive, fatal diseases such as MGS are pathologies with a high probability of recurrence with each pregnancy. Therefore, awareness needs to be increased to prevent these diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Low‐level viraemia (LLV) occurs in chronic hepatitis B (CHB) patients despite antiviral treatment, which may cause failed histological regression. Our study aimed to investigate the impact of different LLV types on fibrosis regression. The prospective study enrolled CHB patients with paired liver biopsies before and after 260 weeks of entecavir treatment. Fibrosis regression was defined by the Ishak score or P‐I‐R system. Patients were grouped as the SVR (HBV DNA < 20 IU/mL persistently) or LLV (HBV DNA between 20 and 2000 IU/mL), which were further grouped as very low‐level viraemia (VLLV, HBV DNA < 50 IU/mL), occasionally LLV (OLLV, HBV DNA ≥ 50 IU/mL only once) and multiple LLV (MLLV, HBV DNA ≥ 50 IU/mL more than once). Logistic regression models were used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). The analysis included 111 CHB patients. In the SVR group (n = 54), 39 (72.2%) patients had fibrosis regression, which was higher than the LLV (56.1%, p = 0.080). The fibrosis regression rates for VLLV (30 patients), OLLV (17 patients) and MLLV (10 patients) were 70.0%, 52.9% and 30.0%, respectively. Compared with SVR, VLLV (aOR = 0.78; 95% CI: 0.28–2.21; p = 0.644) was not associated with fibrosis regression, but patients with non‐VLLV (aOR = 0.27; 95% CI: 0.09–0.85; p = 0.025), especially with MLLV (aOR = 0.19; 95% CI: 0.04–0.97; p = 0.046) is significantly associated with hindered fibrosis regression. Our study suggests that patients with detectable serum HBV DNA levels higher than 50 IU/mL need to be monitored carefully, especially in those with more than once.Trial Registration: ClinicalTrials.gov identifiers NCT01938781 and NCT01938820 [ABSTRACT FROM AUTHOR]

Purpose: We investigate the histopathology of the portal vein branches and lymphatic vessels to elucidate the mechanism of atrophy of the left lateral segment (LLS) of the liver in biliary atresia (BA). Methods: LLS and right anterior segment (RAS) liver biopsy samples obtained during Kasai portoenterostomy (KPE) from ten consecutive patients with BA underwent histopathological investigation of the portal vein and lymphatic vessels using double chromogenic immunostaining for CD31/D2-40 and the hepatitis-like findings (HLF) score. Each parameter and clinical data were compared between prognostic groups. Results: HLF scores in the LLS were always higher than those in the RAS. There was no difference in portal vein and lymphatic vascular morphology, whereas the number of lymphatic vessels was correlated with the fibrotic area of all specimen areas. Left-to-right ratio of the number of lymphatic vessels was correlated with the age at KPE (r = 0.784, p = 0.007) and the pre-KPE CRP value (r = 0.723, p = 0.018). Conclusions: Lymphangiogenesis on the LLS compared to the RAS was significantly correlated with the degree of fibrosis and the age at KPE. Further investigation is warranted to clarify the causes of LLS atrophy and lymphangiogenesis relevant to immune dysregulation. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Percutaneous liver biopsy is essential for diagnosing hepatic amyloidosis. Post biopsy hemorrhage is unusual but can occur. The potential for bleeding can result from various factors, such as the deposition of amyloid in the hepatic parenchyma or vessel wall, deficiencies in coagulation factors, hyperfibrinolysis, and platelet dysfunction. Transarterial embolization can be a safe and effective method for achieving hemostasis. [ABSTRACT FROM AUTHOR]

Objectives Severe macrovesicular steatosis in donor livers is associated with primary graft dysfunction. The Banff Working Group on Liver Allograft Pathology has proposed recommendations for steatosis assessment of donor liver biopsy specimens with a consensus for defining "large droplet fat" (LDF) and a 3-step algorithmic approach. Methods We retrieved slides and initial pathology reports from potential liver donor biopsy specimens from 2010 to 2021. Following the Banff approach, we reevaluated LDF steatosis and employed a computer-assisted manual quantification protocol and artificial intelligence (AI) model for analysis. Results In a total of 113 slides from 88 donors, no to mild (<33%) macrovesicular steatosis was reported in 88.5% (100/113) of slides; 8.8% (10/113) was reported as at least moderate steatosis (≥33%) initially. Subsequent pathology evaluation, following the Banff recommendation, revealed that all slides had LDF below 33%, a finding confirmed through computer-assisted manual quantification and an AI model. Correlation coefficients between pathologist and computer-assisted manual quantification, between computer-assisted manual quantification and the AI model, and between the AI model and pathologist were 0.94, 0.88, and 0.81, respectively (P <.0001 for all). Conclusions The 3-step approach proposed by the Banff Working Group on Liver Allograft Pathology may be followed when evaluating steatosis in donor livers. The AI model can provide a rapid and objective assessment of liver steatosis. [ABSTRACT FROM AUTHOR]

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is increasing, and translational animal models are needed to develop novel treatments for this disease. The physiology and metabolism of pigs have a relatively high resemblance to humans, and the present study aimed to characterize choline-deficient and high-fat diet (CDAHFD)-fed Göttingen Minipigs as a novel animal model of MASLD/MASH. Göttingen Minipigs were fed CDAHFD for up to 5 mo, and the phenotype was investigated by the analysis of plasma parameters and repeated collection of liver biopsies. Furthermore, changes in hepatic gene expression during the experiment were explored by RNA sequencing. For a subset of the minipigs, the diet was changed from CDAHFD back to chow to investigate whether the liver pathology was reversible. Göttingen Minipigs on CDAHFD gained body weight, and plasma levels of cholesterol, AST, ALT, ALP, and GGT were increased. CDAHFD-fed minipigs developed hepatic steatosis, inflammation, and fibrosis, which in 5 of 16 animals progressed to cirrhosis. During an 11-wk chow reversal period, steatosis regressed, while fibrosis persisted. Regarding inflammation, the findings were less clear, depending on the type of readout. MASH Human Proximity Scoring (combined evaluation of transcriptional, phenotypic, and histopathological parameters) showed that CDAHFD-fed Göttingen Minipigs resemble human MASLD/MASH better than most rodent models. In conclusion, CDAHFD-fed minipigs develop a MASH-like phenotype, which, in several aspects, resembles the changes observed in human patients with MASLD/MASH. Furthermore, repeated collection of liver biopsies allows detailed characterization of histopathological changes over time in individual animals. NEW & NOTEWORTHY: The physiology and metabolism of pigs have a relatively high resemblance to humans. This study characterizes a new animal model of MASLD/MASH using CDAHFD-fed Göttingen Minipigs. Göttingen Minipigs fed CDAHFD gained weight and developed hepatic steatosis, inflammation, fibrosis, and cirrhosis. After an 11-wk chow-reversal period, hepatic steatosis and some inflammatory parameters reversed. Combined evaluation of phenotypic, transcriptional, and histological parameters revealed the minipig model showed a higher resemblance to human disease than many rodent models. [ABSTRACT FROM AUTHOR]

Computational quantification reduces observer‐related variability in histological assessment of metabolic dysfunction‐associated steatotic liver disease (MASLD). We undertook stain‐free imaging using the SteatoSITE resource to generate tools directly predictive of clinical outcomes. Unstained liver biopsy sections (n = 452) were imaged using second‐harmonic generation/two‐photon excitation fluorescence (TPEF) microscopy, and all‐cause mortality and hepatic decompensation indices constructed. The mortality index had greater predictive power for all‐cause mortality (index >.14 vs. .31 vs.

Background and Aims: Adaptive immunity is gaining a significant role in progression of metabolic dysfunction‐associated steatotic liver disease (MASLD). B‐cell activity can be assessed by serum‐free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non‐invasive biomarkers for the stratification of MASLD. Methods: We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction‐associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay. Results: We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m2. A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction‐associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction‐associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (p <.01), and patients with CSPH showed higher sFLC levels than patients without CSPH (p <.01). At multivariable analysis, sFLCs were associated with cACLD (p <.05) independently from γ‐globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (p <.05) independently from γ‐globulins and other known dysmetabolic risk factors. Conclusion: sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction‐associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention‐induced fibrosis changes in MASH. Methods: We examined unstained sections from paired liver biopsies (baseline and end‐of‐intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. Results: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI‐induced liver fibrosis regression was concentrated in the periportal region. Conclusion: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle‐induced fibrosis regression and placebo responses, which is not captured by conventional histological staging. [ABSTRACT FROM AUTHOR]

Background and Aim: LIVERSTAT is an artificial intelligence‐based noninvasive test devised to screen for and provide risk stratification for metabolic dysfunction‐associated fatty liver disease (MAFLD) by using simple blood biomarkers and anthropometric measurements. We aimed to study LIVERSTAT in patients with MAFLD and to explore its role for the diagnosis of advanced fibrosis. Methods: This is a retrospective study of data from MAFLD patients who underwent a liver biopsy. Patients with type 2 diabetes who underwent transient elastography and had liver stiffness measurement (LSM) < 5 kPa were included as patients with no fibrosis. Among these patients, controlled attenuation parameter <248 dB/m was considered as no steatosis. The LIVERSTAT results were generated based on a proprietary algorithm, blinded to the histological and LSM data. Results: The data for 350 patients were analyzed (mean age 53 years, 45% male, advanced fibrosis 22%). The sensitivity, specificity, positive predictive value, negative predictive value, and misclassification rate of LIVERSTAT to diagnose advanced fibrosis were 90%, 50%, 30%, 95%, and 42%, respectively. The corresponding rates for Fibrosis‐4 score (FIB4) were 56%, 83%, 44%, 89%, and 22%, respectively. When LSM was used as a second test, the corresponding rates for LIVERSTAT were 60%, 97%, 76%, 94%, and 8%, respectively, while the corresponding rates for FIB4 were 38%, 99%, 83%, 89%, and 11%, respectively. Conclusion: LIVERSTAT had a higher negative predictive value compared with FIB4 and a lower misclassification rate compared with FIB4 when used in a two‐step approach in combination with LSM for the diagnosis of advanced fibrosis. [ABSTRACT FROM AUTHOR]

Background and Aim: The steatosis‐associated fibrosis estimator (SAFE) score has been developed to distinguish clinically significant fibrosis in patients with steatotic liver disease (SLD). However, validation of its performance in Asian subjects is limited. This study aimed to evaluate the performance of the SAFE score in Asian subjects with biopsy‐proven SLD and in different subgroups according to age, sex, and body mass index. Methods: We retrospectively analyzed 6383 living liver donors who underwent a liver biopsy between 2005 and 2023. Of these, 1551 subjects with biopsy‐proven SLD were included. The performance of the SAFE score was evaluated using areas under the curve and compared with those of the nonalcoholic fatty liver disease fibrosis score (NFS) and fibrosis‐4 index (FIB‐4). Results: The prevalence of clinically significant fibrosis in the cohort was 2.2%. The proportion of subjects with a "low‐risk" SAFE score was the highest (91.0%), followed by those with "intermediate‐risk" (7.8%) and "high‐risk" (1.2%) scores. The prevalence of fibrosis in subjects with low‐risk, intermediate‐risk, and high‐risk scores was 1.6%, 6.6%, and 21.1%, respectively. The SAFE outperformed FIB‐4 and NFS (area under the curve: 0.70 vs 0.64 for both NFS and FIB‐4). However, it showed low diagnostic accuracy and sensitivity (27%) at the low cutoff (SAFE < 0) in subjects aged 30–39 years (fibrosis: 1.2%), despite having a high negative predictive value (0.99). Conclusion: While the SAFE score demonstrates superior performance compared with other noninvasive tests in Asian subjects with SLD, its performance varies across age groups. In younger subjects, particularly, its performance may be more limited. [ABSTRACT FROM AUTHOR]

Metastatic uveal melanoma (mUM) is associated with poor prognosis. Ipilimumab/nivolumab has shown antitumor efficacy in phase II studies. Tebentafusp resulted in longer overall survival (OS) compared to investigator's choice in a phase III study. We sought to describe the radiological response patterns of mUM patients treated with immunotherapy. Patients with mUM treated with ipilimumab/nivolumab and tebentafusp between July 2018 and December 2022, with available radiological assessment per RECISTv1.1 and/or imPERCIST5, were retrospectively identified and included. Progression-free survival (PFS) and OS rates, liver-specific response and pathological assessment in available liver biopsies were evaluated. In the ipilimumab/nivolumab group, median PFS (mPFS) was 2.9 months (95% CI 2.2–28.6) and mOS 28.9 months (95% CI 12.7-NR). Complete (CMR) and partial (PMR) metabolic response per imPERCIST5, and partial response (PR) per RECISTv1.1 were associated with longer PFS and OS by trend, compared to morphologically and metabolically stable or progressive disease. In the tebentafusp group, mPFS was 2.7 months (95% CI 2.2–3) and mOS 18.6 months (95% CI 11.5-NR). PMR and PR were associated with longer PFS by trend. In both treatments, the overall treatment response was associated with the radiological response at the liver site. In available liver tumor biopsies, differences in pathological and radiological responses were noted. ImPERCIST5 and RECIST v1.1 are valuable tools in the radiological response assessment, but both methods display limitations. Accurate biomarkers to stratify patients at risk for disease progression and future translational studies to investigate mechanisms of response and resistance are required. [ABSTRACT FROM AUTHOR]

Introduction The native liver survival in biliary atresia (BA) depends on various factors, and one of the crucial factors is the rate of progression of liver fibrosis after portoenterostomy, but there is no reliable investigation to assess it. This study evaluated shear wave elastography (SWE) to detect liver fibrosis in BA patients and assess its utility during follow-up. Materials and Methods This was an observational study; SWE was done preoperatively and postoperatively at 3 and 6 months. The SWE values were analyzed to determine their correlations with preoperative liver histology as well as with postoperative SWE variation between different postoperative outcomes. Results Twenty-one patients were included in the study; the preoperative SWE values were strongly correlated with liver biopsy grading (p < 0.001). At the 3 months postoperatively, SWE was done for 18 children: 12 in group A (patent bilioenteric drainage on hepatobiliary iminodiacetic acid scan) and 6 (nonpatent) in group B; mean SWE value was 12.8 and 17.3 kPa, respectively (p < 0.001). Ten children from group A underwent SWE 6 months postoperatively, and the mean value was 13.23 kPa. Conclusion The SWE values correlate with liver histology grading, suggesting a reliable alternative to biopsy. Additionally, the baseline SWE values and their trend during follow-up can provide information on the disease's progression. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether international normalized ratio (INR), bilirubin, and creatinine predict bleeding risk following percutaneous liver biopsy. Methods: A total of 870 consecutive patients (age 53 ± 14 years; 53% (459/870) male) undergoing non-targeted, ultrasound-guided, percutaneous liver biopsy at a single tertiary center from 01/2016 to 12/2019 were retrospectively reviewed. Results were analyzed using descriptive statistics and logistic regression models to evaluate the relationship between individual and combined laboratory values, and post-biopsy bleeding risk. Receiver operating characteristic (ROC) curves and area under ROC (AUC) curves were constructed to evaluate predictive ability. Results: Post-biopsy bleeding occurred in 2.0% (17/870) of patients, with 0.8% (7/870) requiring intervention. The highest INR within 3 months preceding biopsy demonstrated the best predictive ability for post-biopsy bleeding and was superior to the most recent INR (AUC = 0.79 vs 0.61, p = 0.003). Total bilirubin is an independent predictor of bleeding (AUC = 0.73) and better than the most recent INR (0.61). Multivariate regression analysis of the highest INR and total bilirubin together yielded no improvement in predictive performance compared to INR alone (0.80 vs 0.79). The MELD score calculated using the highest INR (AUC = 0.79) and most recent INR (AUC = 0.74) were similar in their predictive performance. Creatinine is a poor predictor of bleeding (AUC = 0.61). Threshold analyses demonstrate an INR of > 1.8 to have the highest predictive accuracy for bleeding. Conclusion: The highest INR in 3 months preceding ultrasound-guided percutaneous liver biopsy is associated with, and a better predictor for, post-procedural bleeding than the most recent INR and should be considered in patient risk stratification. Clinical relevance statement: Despite correction of coagulopathic indices, the highest international normalized ratio within the 3 months preceding percutaneous liver biopsy is associated with, and a better predictor for, bleeding and should considered in clinical decision-making and determining biopsy approach. Key Points: • Bleeding occurred in 2% of patients following ultrasound-guided liver biopsy, and was non-trivial in 41% of those patients who needed additional intervention and had an associated 23% 30-day mortality rate. • The highest INR within 3 months preceding biopsy (AUC = 0.79) is a better predictor of bleeding than the most recent INR (AUC = 0.61). • The MELD score is associated with post-procedural bleeding, but with variable predictive performance largely driven by its individual laboratory components. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction‐associated steatohepatitis (MASH), a severe form of metabolic dysfunction‐associated steatotic liver disease (MASLD), poses a significant threat to global health. Despite extensive research efforts over the past decade, only one drug has received market approval under accelerated pathways. In this review, we summarise the pathogenesis of MASH and present a comprehensive overview of recent advances in phase 2–3 clinical trials targeting MASH. These trials have highlighted considerable challenges, including low response rates to drugs, limitations of current surrogate histological endpoints, and inadequacies in the design of MASH clinical trials, all of which hinder the progress of MASH pharmacotherapy. We also explored the potential of non‐invasive tests to enhance clinical trial design. Furthermore, given the strong association between MASLD and cardiometabolic disorders, we advocate for an integrated approach to disease management to improve overall patient outcomes. Continued investigation into the mechanisms and pharmacology of combination therapies may offer valuable insights for developing innovative MASH treatments. [ABSTRACT FROM AUTHOR]

Purpose: Current observation period post-liver biopsy is typically 4 h. This study investigates the safety of reducing the observation period after percutaneous liver biopsy. Methods: Patients who underwent percutaneous liver biopsy between 2017 and 2022 in the Radiology Department of a tertiary centre were included in this retrospective, institutional review board-approved study. Patient demographics, procedure details and complication data were collected from the electronic medical records. Complications were graded according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification. Conditional survival probabilities were calculated for the 4-h observation period. Results: Among 1125 patients, 275 complications were seen; 255 grade 1, 15 grade 2 and five grade 3. Post-procedural pain represented 93% (256) of complications, whereas post-procedural haemorrhage occurred in 17 (6%) patients: 13 were of grade 2 severity requiring prolonged observation, and 4 were of grade 3 severity. Of these grade 3 complications, two required blood transfusion whereas two required embolization. A total of 215 (78%) complications occurred within 1 h, 244 (89%) within 2 h of observation. 16 (94%) of 17 post-procedural haemorrhages occurred within 2 h post-biopsy. If complication-free after 2 h, the probability of experiencing a complication within the next 2 h was 4%. Conclusion: The majority of complications were identified within 2 h of observation. Complications recognised after this period were largely pain-related, with only one grade 3 complication seen (post-procedural haemorrhage).Our findings suggest 2 h of post-procedural observation may be safe. Level of Evidence: Level 2B, Retrospective Cohort Study. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine needle biopsy is an effective method for obtaining tissue samples from various organs; however, challenges such as inadequate specimens persist. This study compared a newly designed Tricore needle with a Franseen needle for endoscopic ultrasound-guided fine needle biopsy of porcine liver. Both needles were tested on four male Yorkshire pigs. Specimens were obtained with an 100% (36/36) success rate with no procedure-related adverse effects. The Tricore needle experienced significantly less resistance during puncture than Franseen needle (3.83 vs. 5.97 N, P < 0.001) and better ultrasound visibility (168.97 vs. 125.04, P = 0.004). The Tricore needle also achieved faster specimen acquisition time (48.94 vs. 59.90 s, P = 0.038), larger total specimen area (6.67 vs. 4.68 mm2, P = 0.049), fewer fragments (23.94 vs. 31.94, P = 0.190), lager fragment area (0.28 vs. 0.15 mm2, P < 0.001), and more the number of complete portal tracts (15.44 vs. 9.33, P = 0.017) compared to the Franseen needle. The newly designed Tricore needle showed enhanced procedural performance and specimen quantity and quality compared to commercially available Franseen needle. Although further clinical studies are required, the Tricore needle may represent a favorable option for endoscopic ultrasound-guided fine-needle biopsy procedures. [ABSTRACT FROM AUTHOR]

Background: Seronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARSCoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger. Methods: We conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022. Results: Thirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients' clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before. Conclusion: In cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement. [ABSTRACT FROM AUTHOR]

Ultrasound-guided interventions (such as biopsies) of unclear lesions are indicated if microcirculatory changes indicate possible malignant lesions. These place high demands on the ultrasound device used. In order to potentially reduce the often associated high technical effort, the wireless ultrasound device Vscan AirTM was examined as a possible ultrasound device for the intervention biopsy.As part of an advanced training course on Computertomographie- and ultrasound-guided biopsy and ablation procedures, participants were asked about the image quality of the handheld device used by means of questionnaires. Various lesions were evaluated at a depth of 1.0 to 5.0 cm in an in vitro liver model. The image quality was evaluated independently before, during and after the intervention. The rating scale contained values from 0 (no assessment possible) to 5 (maximum high image quality). A high-end device was used as a reference.A total of 11 participants took part in the study (n = 4 male [36.4%], n = 7 female [63.6%]). A total of five tumor like lesions at different depths (1 cm, 2 cm, 3 cm, 4 cm, >4 cm) were assessed separately. In all cases, an adequate biopsy of the target lesion (1 cm in length, core filling 5 mm) was successful. From a depth of 3 cm, the image quality of the mobile device increasingly decreased, but the image quality of the high-end system was still not impaired. Compared to the high-end device, there was a highly significant difference in image quality from a depth of 3 cm (p < 0.01). Assessment by inexperienced examiners using a handheld device was adequately possible.Mobile interventional ultrasound represents a potential alternative for the biopsy of unclear tumorous lesions with microcirculatory disorders with limited depth localization. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusion The course of adults with ZZ alpha‐1‐antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined.A prospective cohort, including protocol liver biopsies, was enrolled to address these questions.We enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0–6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0–1, 36% Ishak 2–3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (p = .002) and increased diffuse cytoplasmic Z polymer on biopsy (p = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (p = .007) and increased periportal inflammation on histopathology (p = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis.In AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Previous studies have reported an association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and the risk of serious bacterial infections. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta‐analysis of observational studies to quantify the association between MASLD and serious bacterial infections requiring hospital admission.We systematically searched PubMed, Scopus, Web of Science and Embase from database inception to 1 April 2024, using predefined keywords to identify studies examining the risk of serious bacterial infections among individuals with and without MASLD. MASLD was diagnosed using liver biopsy, imaging or International Classification of Diseases codes. Meta‐analysis was performed using random‐effects modelling.We identified six cross‐sectional and two prospective cohort studies with aggregate data on ~26.6 million individuals. MASLD was significantly associated with higher odds of serious bacterial infections (pooled random‐effects odds ratio 1.93, 95% confidence interval [CI] 1.44–2.58; I2 = 93%). Meta‐analysis of prospective cohort studies showed that MAFLD was associated with an increased risk of developing serious bacterial infections (pooled random‐effects hazard ratio 1.80, 95% CI 1.62–2.0; I2 = 89%). This risk further increased across the severity of MASLD, especially the severity of fibrosis (pooled random‐effects hazard ratio 2.42, 95% CI 1.89–2.29; I2 = 92%). These results remained significant after adjusting for age, sex, obesity, diabetes and other potential confounders. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias.This meta‐analysis shows a significant association between MASLD and an increased risk of serious bacterial infections requiring hospital admission. [ABSTRACT FROM AUTHOR]

Drug‐induced liver injury (DILI) presents unique challenges in clinical practice. While some types of DILI are mild and resolve quickly after removing the drug, other situations are more complex, with competing aetiologies or underlying liver disease. Guidelines from professional societies agree that the liver biopsy retains a role in understanding and managing DILI in certain situations. Liver biopsy allows characterization of the histological pattern of injury as well as assessment of severity. Inflammatory infiltrates, bile duct injury or loss and vascular injury are all revealed by liver biopsy. Communication between the hepatopathologist and clinical team with clinicopathological correlation of the findings is necessary for the best determination of causality and differentiation from other diseases of exclusion, like autoimmune hepatitis and graft‐versus‐host disease. This review highlights important aspects of the role of liver biopsy in DILI evaluation. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusions Metabolic dysfunction‐associated steatotic liver disease (MASLD) recurrence after liver transplantation (LT) seems unavoidable and gradual. We aimed to evaluate the diagnostic accuracy in the post‐LT setting of patients transplanted for metabolic dysfunction‐associated steatohepatitis (MASH) of recurrent hepatic steatosis and fibrosis identified with FibroScan, compared to biopsy findings.This prospective cohort study included adults transplanted for MASH between 2010 and 2022 in three LT centres in Spain who underwent FibroScan and biopsy at least 1‐year after LT.In total, 44 patients transplanted for MASH after LT were included. The median time from LT to biopsy and FibroScan was 24.5 (interquartile range [IQR]:16–46) and 26.0 (IQR: 16.8–41.5) months, respectively. The median time between biopsy and FibroScan was 2.0 (IQR: 0–5) months. On FibroScan, significant steatosis was diagnosed in about half of the patients (n = 21, 47.7%), yet advanced fibrosis in only two cases (4.6%). On biopsy, a quarter of biopsied patients (n = 11, 25%) had a MASH diagnosis, two (4.6%) with significant fibrosis and one (2.3%) with cirrhosis. All patients with liver stiffness measurement (LSM) values <8 kPa (n = 35, 79.5%) had a fibrosis stage ≤F1 (negative predictive value = 100%). The combination of post‐LT hypertension (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 1.8–80.4, p = .010) and post‐LT dyslipidaemia (OR: 7.9, 95% CI: 1.3–47.1, p = .024) with LSM (OR: 1.7, 95% CI: 1.1–2.8, p = .030) was independently associated with MASLD.Although biopsy remains the gold standard for detecting fibrosis, our results suggest that LSM values <8 kPa after LT for MASH are strongly correlated with absence of significant/advanced fibrosis. [ABSTRACT FROM AUTHOR]

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in the liver and bone marrow, indicative of CAEBV. The liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores the diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management. [ABSTRACT FROM AUTHOR]

Interventional radiologists mainly rely on visual feedback via imaging modalities to steer a needle toward a tumor during biopsy and ablation procedures. In the case of CT-guided procedures, there is a risk of exposure to hazardous X-ray-based ionizing radiation. Therefore, CT scans are usually not used continuously, which increases the chances of a misplacement of the needle and the need for reinsertion, leading to more tissue trauma. Interventionalists also encounter haptic feedback via needle–tissue interaction forces while steering a needle. These forces are useful but insufficient to clearly perceive and identify deep-tissue structures such as tumors. The objective of this paper was to investigate the effect of enhanced force feedback for sensing interaction forces and guiding the needle when applied individually and simultaneously during a virtual CT-guided needle insertion task. We also compared the enhanced haptic feedback to enhanced visual feedback. We hypothesized that enhancing the haptic feedback limits the time needed to reach the target accurately and reduces the number of CT scans, as the interventionalist depends more on real-time enhanced haptic feedback. To test the hypothesis, a simulation environment was developed to virtually steer a needle in five degrees of freedom (DoF) to reach a tumor target embedded in a liver model. Twelve participants performed in the experiment with different feedback conditions where we measured their performance in terms of the following: targeting accuracy, trajectory tracking, number of CT scans required, and the time needed to finish the task. The results suggest that the combination of enhanced haptic feedback for guidance and sensing needle–tissue interaction forces significantly reduce the number of scans and the duration required to finish the task by 32.1% and 46.9%, respectively, when compared to nonenhanced haptic feedback. The other feedback modalities significantly reduced the duration to finish the task by around 30% compared to nonenhanced haptic feedback. [ABSTRACT FROM AUTHOR]

The early detection of liver fibrosis is of significant importance. Deep learning analysis of ultrasound backscattered radiofrequency (RF) signals is emerging for tissue characterization as the RF signals carry abundant information related to tissue microstructures. However, the existing methods only used the time-domain information of the RF signals for liver fibrosis assessment, and the liver region of interest (ROI) is outlined manually. In this study, we proposed an approach for liver fibrosis assessment using deep learning models on ultrasound RF signals. The proposed method consisted of two-dimensional (2D) convolutional neural networks (CNNs) for automatic liver ROI segmentation from reconstructed B-mode ultrasound images and one-dimensional (1D) CNNs for liver fibrosis stage classification based on the frequency spectra (amplitude, phase, and power) of the segmented ROI signals. The Fourier transform was used to obtain the three kinds of frequency spectra. Two classical 2D CNNs were employed for liver ROI segmentation: U-Net and Attention U-Net. ROI spectrum signals were normalized and augmented using a sliding window technique. Ultrasound RF signals collected (with a 3-MHz transducer) from 613 participants (Group A) were included for liver ROI segmentation and those from 237 participants (Group B) for liver fibrosis stage classification, with a liver biopsy as the reference standard (Fibrosis stage: F0 = 27, F1 = 49, F2 = 51, F3 = 49, F4 = 61). In the test set of Group A, U-Net and Attention U-Net yielded Dice similarity coefficients of 95.05% and 94.68%, respectively. In the test set of Group B, the 1D CNN performed the best when using ROI phase spectrum signals to evaluate liver fibrosis stages ≥F1 (area under the receive operating characteristic curve, AUC: 0.957; accuracy: 89.19%; sensitivity: 85.17%; specificity: 93.75%), ≥F2 (AUC: 0.808; accuracy: 83.34%; sensitivity: 87.50%; specificity: 78.57%), and ≥F4 (AUC: 0.876; accuracy: 85.71%; sensitivity: 77.78%; specificity: 94.12%), and when using the power spectrum signals to evaluate ≥F3 (AUC: 0.729; accuracy: 77.14%; sensitivity: 77.27%; specificity: 76.92%). The experimental results demonstrated the feasibility of both the 2D and 1D CNNs in liver parenchyma detection and liver fibrosis characterization. The proposed methods have provided a new strategy for liver fibrosis assessment based on ultrasound RF signals, especially for early fibrosis detection. The findings of this study shed light on deep learning analysis of ultrasound RF signals in the frequency domain with automatic ROI segmentation. [ABSTRACT FROM AUTHOR]

This pilot study investigated the feasibility of using magnetic resonance elastography (MRE) for the non-invasive detection and quantification of liver fibrosis in the Oncopig cancer model. Seven 8-week-old Oncopigs underwent alcoholic liver fibrosis induction and serial MRE imaging and liver biopsy at 1, 2, and 3 months post procedure. MRE was utilized to quantify liver stiffness, and liver fibrosis was histologically graded using the METAVIR system. The primary outcome measure was the capability to detect and quantify liver fibrosis using MRE with radiologic–pathologic correlation. Liver fibrosis induction, MRE imaging, and liver biopsy were successfully performed. MRE liver fibrosis was evident in 57% (4/7), 50% (3/6), and 40% (2/5) animal subjects 1, 2, and 3 months after fibrosis induction, with mean liver stiffness of 2.94, 3.25, and 2.91 kPa, respectively. Histological liver fibrosis was noted in 71% (5/7), 100% (5/5), and 100% (5/5) of animal subjects with available tissue samples. There was no significant statistical correlation between the MRE-measured liver stiffness and the METAVIR fibrosis scores. In conclusion, quantifiable liver fibrosis may be induced in the Oncopig. MRE has potential utility in non-invasively detecting liver stiffness in this large-animal preclinical model, though tissue biopsy was more sensitive in demonstrating disease. [ABSTRACT FROM AUTHOR]

Objectives: In patients evaluated for hepatocellular carcinoma (HCC), magnetic resonance imaging (MRI) is often used secondarily when multiphase contrast-enhanced computed tomography (ceCT) is inconclusive. We investigated the clinical impact of adding MRI. Materials and methods: This single-institution retrospective study included 48 MRI scans (44 patients) conducted from May 2016 to July 2023 due to suspicion of HCC on a multiphase ceCT scan. Data included medical history, preceding and subsequent imaging, histology when available, and decisions made at multidisciplinary team meetings. Results: In case of possible HCC recurrence, 63% of the MRI scans were diagnostic of HCC. For 80% of the negative MRI scans, the patients were diagnosed with HCC within a median of 165 days in the suspicious area of the liver. In case of possible de-novo HCC in patients with cirrhosis, 22% of the scans were diagnostic of HCC and 33% of the negative MRI scans were of patients diagnosed with HCC within a median of 109 days. None of the non-cirrhotic patients with possible de-novo HCC and negative MRI scans (64%) were later diagnosed with HCC, but 3/5 of the indeterminate scans were of patients diagnosed with HCC in a biopsy. Conclusions: Secondary MRI to a multiphase ceCT scan suspicious of HCC is highly valuable in ruling out HCC in non-cirrhotic patients and in diagnosing HCC non-invasively in cirrhotic patients and patients with prior HCC. Patients with cirrhosis or prior HCC are still at high risk of having HCC if MRI results are inconclusive or negative. [ABSTRACT FROM AUTHOR]

Background: The development of graft fibrosis after pediatric liver transplantation (PLT) remains a major concern as it can lead to graft failure and ultimately graft loss. Elastography is a non‐invasive method to assess liver fibrosis, but its role in the posttransplant setting is unclear. The aim of our study was to evaluate shear wave elastography (SWE) in the assessment of liver fibrosis after PLT, including split‐liver recipients. Methods: We retrospectively analyzed data from PLT recipients who underwent surveillance liver biopsy and concurrent 2D‐SWE during the study period from April 2018 to July 2021. Spearman's correlation was used to compare histologic fibrosis stages with liver stiffness measurements (LSM) by 2D‐SWE. AUROC analysis was performed to evaluate the performance. One sample t‐test was used to compare results with reference values of healthy children. Results: 62 cases were included. 29% showed histologic fibrosis. LSM by 2D‐SWE were feasible in all children regardless of age or graft type. There was a significant correlation between LSM and fibrosis stage for all three scoring systems used (Ishak, p = 0.003; METAVIR, p = 0.005; LAF Score, p = 0.003). Patients with a history of biliary complications had increased liver stiffness (p = 0.015). The AUROC of 2D‐SWE for predicting significant liver graft fibrosis was 0.81. Liver stiffness after PLT without graft fibrosis was higher than in healthy subjects, but comparable to that in children with chronic liver disease without fibrosis. Conclusion: 2D‐SWE can reliably detect children with significant liver graft fibrosis, even in split‐liver recipients. This study demonstrates the value of a non‐invasive tool for fibrosis staging after PLT. 2D‐SWE has the potential to improve long‐term outcomes after PLT and to reduce the number of surveillance liver biopsies. But elastography is not a substitute for liver biopsy. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to investigate the effectiveness of strain elastography in guiding precise and sufficient tissue sampling for perihilar cholangiocarcinoma (CCA) biopsies. Methods: Our retrospective analysis included 23 liver biopsies conducted between March 2019 and July 2022 for suspected perihilar CCA. An experienced radiologist performed the biopsies via an ultrasound machine with elastography configuration. Tissue stiffness color maps were used for guiding when the biopsies were performed. Strain index value calculations were made by radiologists on recorded images. Results: Patient demographics revealed a mean age of 65.17 ± 9.25 years, with a gender distribution of six females and 17 males. Gray-scale examinations unveiled diverse echogenic characteristics in liver lesions. Elastography-guided biopsies demonstrated no need for repeats, while gray-scale biopsies necessitated re-biopsy in four patients, resulting in cholangiocarcinoma diagnosis (P = 0.037). Strain index values showcased strong inter- and intra-observer agreements (P < 0.001). Notably, no post-biopsy complications emerged in either study group. Conclusion: The diagnostic advantage of elastography, particularly in enhancing accuracy in challenging isoechoic lesions, was demonstrated, although the substantial overlap between strain index values of benign and malignant liver masses limits clinical usefulness of this technique. [ABSTRACT FROM AUTHOR]

Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) using ultrasonography holds significant clinical value. The associations between ultrasound (US)-based parameters and the pathological spectra remain unclear and controversial. This study aims to investigate the associations thoroughly. The participants with MAFLD undergoing liver biopsy and multiparametric ultrasonography were prospectively recruited from December 2020 to September 2022. Three US-based parameters, namely attenuation coefficient (AC), liver stiffness (LS) and dispersion slope (DS) were obtained. The relationship between these parameters and steatosis grades, inflammation grades and fibrosis stages was examined. In this study with 116 participants, AC values significantly differed across distinct steatosis grades (p < 0.001), while DS and LS values varied among inflammation grades (p < 0.001) and fibrosis stages (p < 0.001). The area under the receiver operating characteristic curves (AUCs) of AC ranged from 0.82 to 0.84 for differentiating steatosis grades, while AUCs of LS ranged from 0.62 to 0.76 for distinguishing inflammation grades and 0.83–0.95 for discerning fibrosis stages. AUCs for DS ranged from 0.79 to 0.81 in discriminating inflammation grades and 0.80–0.88 for differentiating fibrosis stages. Subgroup analysis revealed that LS demonstrated different trends in inflammation grade but consistent trends in fibrosis stage across subgroups, whereas DS showed consistent trends for both inflammation grade and fibrosis stage across all subgroups. AC values indicate the degree of hepatic steatosis but not inflammation or fibrosis. LS values are determined only by fibrosis stage and are not associated with inflammation grades. DS values are associated with both fibrosis and inflammation grades. [ABSTRACT FROM AUTHOR]

Objectives: To compare clinical success, procedure time, and complication rates between MRI-guided and CT-guided real-time biopsies of small focal liver lesions (FLL) < 20 mm. Methods: A comparison of a prospectively collected MRI-guided cohort (n = 30) to a retrospectively collected CT-guided cohort (n = 147) was performed, in which patients underwent real-time biopsies of small FLL < 20 mm in a freehand technique. In both groups, clinical and periprocedural data, including clinical success, procedure time, and complication rates (classified according to CIRSE guidelines), were analyzed. Wilcoxon rank sum test, Pearson's chi-squared test, and Fisher's exact test were used for statistical analysis. Additionally, propensity score matching (PSM) was performed using the following criteria for direct matching: age, gender, presence of liver cirrhosis, liver lobe, lesion diameter, and skin-to-target distance. Results: The median FLL diameter in the MRI-guided cohort was significantly smaller compared to CT guidance (p < 0.001; 11.0 mm vs. 16.3 mm), while the skin-to-target distance was significantly longer (p < 0.001; 90.0 mm vs. 74.0 mm). MRI-guided procedures revealed significantly higher clinical success compared to CT guidance (p = 0.021; 97% vs. 79%) as well as lower complication rates (p = 0.047; 0% vs. 13%). Total procedure time was significantly longer in the MRI-guided cohort (p < 0.001; 38 min vs. 28 min). After PSM (n = 24/n = 38), MRI-guided procedures still revealed significantly higher clinical success compared to CT guidance (p = 0.039; 96% vs. 74%). Conclusion: Despite the longer procedure time, freehand biopsy of small FLL < 20 mm under MR guidance can be considered superior to CT guidance because of its high clinical success and low complication rates. Clinical relevance statement: Biopsy of small liver lesions is challenging due to the size and conspicuity of the lesions on native images. MRI offers higher soft tissue contrast, which translates into a higher success of obtaining enough tissue material with MRI compared to CT-guided biopsies. Key Points: • Image-guided biopsy of small focal liver lesions (FLL) is challenging due to inadequate visualization, leading to sampling errors and false-negative biopsies. • MRI-guided real-time biopsy of FLL < 20 mm revealed significantly higher clinical success (p = 0.021; 97% vs. 79%) and lower complication rates (p = 0.047; 0% vs. 13%) compared to CT guidance. • Although the procedure time is longer, MRI-guided biopsy can be considered superior for small FLL < 20 mm. [ABSTRACT FROM AUTHOR]

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Introduction and Objectives: Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. Patients and Methods: This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017−2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999−2016) to assess the correlation with mortality. Results: In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. Conclusions: The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD. [ABSTRACT FROM AUTHOR]

The gold standard for enrollment and endpoint assessment in metabolic dysfunction‐associated steatosis clinical trials is histologic assessment of a liver biopsy performed on glass slides. However, obtaining the evaluations from several expert pathologists on glass is challenging, as shipping the slides around the country or around the world is time‐consuming and comes with the hazards of slide breakage. This study demonstrated that pathologic assessment of disease activity in steatohepatitis, performed using digital images on the AISight whole slide image management system, yields results that are comparable to those obtained using glass slides. The accuracy of scoring for steatohepatitis (nonalcoholic fatty liver disease activity score ≥4 with ≥1 for each feature and absence of atypical features suggestive of other liver disease) performed on the system was evaluated against scoring conducted on glass slides. Both methods were assessed for overall percent agreement with a consensus "ground truth" score (defined as the median score of a panel of three pathologists' glass slides). Each case was also read by three different pathologists, once on glass and once digitally with a minimum 2‐week washout period between the modalities. It was demonstrated that the average agreement across three pathologists of digital scoring with ground truth was noninferior to the average agreement of glass scoring with ground truth [noninferiority margin: −0.05; difference: −0.001; 95% CI: (−0.027, 0.026); and p < 0.0001]. For each pathologist, there was a similar average agreement of digital and glass reads with glass ground truth (pathologist A, 0.843 and 0.849; pathologist B, 0.633 and 0.605; and pathologist C, 0.755 and 0.780). Here, we demonstrate that the accuracy of digital reads for steatohepatitis using digital images is equivalent to glass reads in the context of a clinical trial for scoring using the Clinical Research Network scoring system. [ABSTRACT FROM AUTHOR]

Background: Obesity is a significant risk factor for metabolic‐associated steatotic liver disease (MASLD). The association between Helicobacter pylori (HP) infection and liver fibrosis has not been fully elucidated in patients with obesity and MASLD. Methods: This observational retrospective study included clinical and biochemical parameters of patients with obesity undergoing bariatric surgery. HP infection was confirmed by gastric endoscopy, and liver biopsies were performed during surgery. Bivariate and logistic regression analyses were employed to evaluate independent associations with liver fibrosis and steatosis by biopsy. Results: The mean age of the subjects was 42 ± 10 years, with 84.7% being women, and they had a mean BMI of 42.97 ± 7.56 kg/m2. Overall, 41.7% of patients had an HP infection. Multiple logistic regression models were conducted to assess the association between HP infection, liver steatosis, and fibrosis by biopsy. HP infection was independently associated with liver fibrosis [OR = 3.164 (95% CI 1.011–9.900)]. Conclusion: Biopsy findings associated HP infection with increased liver fibrosis. [ABSTRACT FROM AUTHOR]

Copyright of Veterinarska Stanica is the property of Croatian Veterinary Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Wounds that influence the liver are shockingly normal in more youthful individuals. This condition might introduce itself clinically as subclinical hepatitis, intense hepatitis, persistent hepatitis, remunerated liver constant infection, decompensated liver cirrhosis, intense liver disappointment, or intense on persistent liver disappointment. These indications are possible. A liver capability test would frequently take a gander at various different biochemical markers, including complete bilirubin, direct bilirubin, Serum glutamic oxaloacetic transaminase, Serum glutamate pyruvate transaminase, egg whites, supportive of thrombin time, and gamma-glutamyl transferase. Novel biomarkers are presently effectively accessible as an immediate outcome of current specialized leap forwards and applications. The utilization of creature models is the beginning stage for the examination of these biomarkers, with the concentrate then, at that point, moving to human subjects. They can offer data that is demonstrative as well as data about the visualization. They give some enlightening data on the histological condition of the liver. Notwithstanding, they are restricted by the circumstances that they think of themselves as in. By directing an examination of marks of liver harm in youngsters, this exploration shows new conceivable outcomes and philosophies for the determination of liver sickness in kids. Concentrates on that focus on individual biomarkers as a restorative place of section are something that might be plausible to investigate not long from now. Hepatology is a subspecialty that is still during the time spent developing, and one of its subspecialties is the investigation of biomarkers. The developing weight of worldwide liver sickness, the shortfall of side effects until late in the regular history of an illness that might require a very long time to show, the presence of an obtrusive reference test (liver biopsy) to evaluate infection seriousness, and the absence of powerful instruments to survey the viability of restorative mediations are a portion of the critical drivers for this exploration. Furthermore, the shortfall of side effects until late in the regular history of a sickness that might require a very long time to show is one more key driver for this examination. Moreover, one of the essential motivations behind why this study is being directed is because of the deficiency of dependable instruments with which to assess the viability of restorative methodologies. [ABSTRACT FROM AUTHOR]

Fatty liver disease that is not alcoholic, often known as non-alcoholic fatty liver disease, is a common and progressive liver ailment that is defined by an abnormal buildup of fat in the liver when significant alcohol use is avoided. Nonalcoholic fatty liver disease is a frequent and progressive liver disorder. A variety of conditions are referred to as nonalcoholic fatty liver disease, which might include nonalcoholic steatohepatitis and simple steatosis. which can eventually lead to cirrhosis and hepatocellular cancer. Among nonalcoholic fatty liver disease, simple steatosis is the most prevalent kind. Even though it is invasive and has various drawbacks, liver biopsy is still considered the gold standard for diagnosing and staging nonalcoholic fatty liver disease at the present time. As a result, there is an immediate need for noninvasive biomarkers that are capable of providing an accurate diagnosis, staging, and monitoring of the development of illness. In recent years, proteomic methods have emerged as potentially useful tools for the identification and validation of noninvasive biomarkers in nonalcoholic fatty liver disease. This development has place over the course of many years. The objective of this research study is to provide an overview of the existing situation of noninvasive proteomic biomarkers in nonalcoholic fatty liver disease as well as their possible implications in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction The native liver survival in biliary atresia (BA) depends on various factors, and one of the crucial factors is the rate of progression of liver fibrosis after portoenterostomy, but there is no reliable investigation to assess it. This study evaluated shear wave elastography (SWE) to detect liver fibrosis in BA patients and assess its utility during follow-up.