Liver Biopsy Research Articles

Molecular imaging of macrophage composition and dynamics in MASLD

Background and AimsMetabolic-dysfunction associated steatohepatitis (MASH) is associated with obesity and diabetes and is linked to liver fibrosis and cardiovascular disease. Identification of patients who have MASH is challenging and the development of non-invasive strategies to diagnose and follow this condition is an important unmet need. Recent studies in mouse and humans have identified that significant changes occur in liver macrophage composition during MASH progression, namely resident Kupffer cells decrease in number while recruited monocyte-derived macrophages increase. MethodsWe developed peptide radiotracers targeted to C-C motif chemokine receptor 2 (CCR2) and CD163 to conduct postitron emssion tomography (PET) imaging of recuited vs. resident macrophages, respectively. Mice were placed on a MASH-inducing diet and non-invasive PET imaging of the liver was performed with tissue confirmation studies using flow cytometry and immunofluorescence. Statistical analyses were conducted using t-testing, Pearson correlational analysis and linear regression. ResultsUsing a mouse model of MASH, we found that the liver uptake of both CCR2 and CD163 radiotracers detected an increase in recruited cells and a decrease in resident macrophages. These findings correlated well with tissue macrophage content assessed by flow cytometry with an r value of 0.77 (p = 0.002) and 0.78 (p=0.001) for CCR2 and CD163, respectively. Serial imaging with these radiotracers at several timepoints during MASH progression and regression, revealed good correlation between liver macrophage composition and PET signal intensity. ConclusionWe demonstrate that novel PET radiotracers targeting CCR2 and CD163 can be used to image macrophage composition in MASH. Non-invasive molecular imaging of inflammation has the potential for diagnosis and monitoring of disease activity in humans with MASH. Impact and ImplicationsMacrophage mediated inflammation contributes to MASH progression and fibrosis; however, liver biopsy is currently the only tool to assess this response. Thus, the development of non-invasive imaging modalites to identify and follow inflammatory activation is an area of need for patient care. In this study we leverage molecular imaging using PET radiotracers to follow changes in macrophage composition that are related to MASH disease activity. The results in our pre-clinical model provide important proof of concept evidence that this approach can be used to diagnose MASH and to follow disease activty in response to intervention. Ongoing studies will evaluate the utility of this modality in humans with MASH.

Helicobacter pylori infection is associated with liver fibrosis in patients with obesity undergoing bariatric surgery.

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. 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. 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)]. Biopsy findings associated HP infection with increased liver fibrosis.

Tumor in the liver: Six inflammatory pseudotumor patient

Inflammatory pseudotumor (IPT) is a rare liver disease confused with liver tumors. It is a disease that should be known in the differential diagnosis for clinicians as the correct diagnosis of IPT will prevent unnecessary surgery. Demographic datas, diagnoses and imaging modalities of six patients with radiologically and/or histopathologically diagnosed hepatic IPT between 2016 and 2023 were retrospectively analyzed. Four out of six patients were female and median age was 57.5 (47-66). C-reactive protein was higher in four patients, and carbohydrate antigen 19.9 level was higher in one patient. We used magnetic resonance imaging (MRI) for diagnosis in five patients. Only in one patient computed tomography was enough for diagnosis. Tumor locations were segment 5 for two patients, segment 7-8 in two patients, segment 7 in one patient, and 8 in one patient. Liver biopsy was performed in five patients because it could not be distinguished from malignancy by imaging methods. Histopathological results of all these biopsies defined as IPT. Initial tumor median size was 31 (17-55) mm. Two patients were operated on. The first one underwent right hepatectomy due to a 2-fold increase in size within 11 months. The second one had a mass indistinguishable from hepatic adenoma by MRI and underwent nonanatomic resection. In one patient, IPT disappeared completely in the 18th month of follow-up period while it regressed in size in two patients. Two of our patients had a history of recurrent endoscopic retrograde cholangiopancreatography, which we noticed incidentally before IPT was diagnosed. IPTs are liver masses with low malignant potential and may shrink spontaneously during follow-up. We suspected that biliary tract interventions may be the cause of IPT.

Genetic variants associated with immune-mediated liver injury from checkpoint inhibitors.

The clinical features, liver histology, and genetic variants in 57 patients with moderate to severe immune-mediated liver injury from checkpoint inhibitors (ILICI) are presented. Between 2010 and 2022, 57 high-causality ILICI cases were enrolled in the Drug-Induced Liver Injury Network. HLA and selected candidate gene variants were tested for association with ILICI risk compared to the general population and other DILI controls. The 57 high-causality cases were attributed to pembrolizumab (16), ipilimumab (15), ipilimumab and nivolumab (13), and other immune checkpoint inhibitors (13) and occurred at a median of 72 days after the first infusion. Median age was 57.8 years, 66% male, and 89% were non-Hispanic Whites. At DILI onset, 53% had hepatocellular, 35% mixed, and 15% cholestatic, with younger patients more likely to have hepatocellular injury. The incidence of ANA, smooth muscle antibody, and elevated IgG levels was low (17%, 23%, and 0%), but corticosteroids were given to 86%. Microgranulomas and hepatic steatosis were seen in 54% and 46% of the 26 liver biopsies, respectively. The HLA alleles associated with autoimmune hepatitis were not over-represented, but 2 host immune response genes (EDIL3 and SAMA5A) and 3 other genes (GABRP, SMAD3, and SLCO1B1) were associated with ILICI (OR: 2.08-2.4, p<0.01). ILICI typically arises within 12 weeks of initiating immunotherapy and is self-limited in most cases. Genetic variants involved in host T-cell regulation and drug disposition were identified, implicating these pathways in the pathogenesis of ILICI. If validated, these findings could lead to improved diagnostic instruments and possible treatments for ILICI.

Chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease: Metabolic risk factors are key drivers of hepatocellular carcinoma

ObjectiveChronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) are the leading causes of hepatocellular carcinoma (HCC). This study aimed to explore the impact of baseline MASLD on the risk of HCC development in patients with CHB receiving antiviral treatment. MethodsWe consecutively recruited 535 patients with CHB who initiated antiviral treatment between January 2007 and January 2023. The exclusion criteria included coexisting HDV, HCV, or HIV infection; other chronic liver diseases; extrahepatic malignancies; prior HCC; and HCC development within one year. A baseline liver biopsy was performed in 467 patients (87 %). MASLD was defined as hepatic steatosis diagnosed histologically or by imaging, combined with one cardiometabolic risk factor. The cumulative incidence of HCC and its associated factors was analyzed in patients with CHB, with and without MASLD. ResultsIn total, 535 treatment-naïve patients with CHB were included, with a median follow-up of 6.05 years. MASLD was not associated with an increased incidence of HCC in patients with CHB (HR: 1.17; 95 % CI: 0.77–1.79; p = 0.466). The cumulative incidence of HCC increased with the number of fulfilled cardiometabolic criteria (0–2 criteria vs. ≥ 3 criteria) (HR: 3.93; 95 % CI: 1.89–8.19; p < 0.001).Age (HR: 1.03, 95 % CI 1.01–1.06, p = 0.010), male sex (HR: 3.17; 95 % CI 1.34–7.53, p = 0.009), diabetes (HR: 2.81; 95 % CI 1.54–5.12, p < 0.001), and cirrhosis (HR:3.03; 95 % CI 1.57–5.5.86, p < 0.001) were independently associated with HCC development. ConclusionsIt was not MASLD, but rather the presence of multiple cardiometabolic risk factors in patients with CHB that was associated with the risk of HCC in those receiving antiviral treatment. Furthermore, older age, male sex, diabetes, and cirrhosis aggravated the risk of HCC in patients with CHB.

Publisher’s note on “The risk-benefit assessment of liver biopsy in times of non-invasive screening for liver fibrosis” by Ivana Ilic and Tamara Milovanovic [J Hepatol 73 (2020) 701–702]

Publisher’s note on “The risk-benefit assessment of liver biopsy in times of non-invasive screening for liver fibrosis” by Ivana Ilic and Tamara Milovanovic [J Hepatol 73 (2020) 701–702]

Hepatologists' Awareness and Knowledge of NAFLD and the Familiarity with Renaming NAFLD to MAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic; it is a negative diagnosis that depends mainly on the presence of hepatic steatosis with or without inflammation after the exclusion of other chronic liver diseases and excess alcohol intake. However, the new definition of MAFLD is a shift towards a diagnosis of inclusion based on the presence of metabolic dysfunction, regardless of alcohol consumption or other concomitant liver diseases. Given the growing relevance of the disease, data on hepatologists' views and understanding of NAFLD are limited, we aimed to determine hepatologists' awareness and expertise of NAFLD screening, diagnosis, and therapeutic options as well as the influence of changing the NAFLD name to MAFLD on awareness of the fatty liver disease (FLD). Most of the hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, necessitating a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD. A multicenter online questionnaire of 655 hepatologists was carried out, giving a sample of 207 respondents. A survey composed of 36 questions was used to assess the level of hepatologists' awareness and practices in the screening, diagnosis, and management of NAFLD/MAFLD, as well as their familiarity with the nomenclature change from NAFLD to MAFLD. A total of 207 hepatologists were included, of which 107 (51.4%) were males, with a mean age was 36.4 years. 50.2% (n = 104) of the hepatologists were oriented with NAFLD. Only 41 (19.8%) realized that NAFLD may frequently result in severe hepatic disease. NAFLD is rarely screened by the majority of the participating hepatologists (118, 57%), and (135, 65.2%) of them use liver biopsy for diagnosis of NAFLD. In (104, 50.2%) hepatologists, changing the nomenclature of NAFLD was relatively familiar. Furthermore, 71.9% of hepatologists thought that the new nomenclature offers a better awareness of FLD. A small percentage of hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, and around half of them realize that NAFLD necessitates a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.

Computed tomographic angiography of a presumed acquired transhepatic portosystemic shunt in a miniature horse filly.

A 1-year-old Miniature Horse filly was presented for chronic lethargy and hyporexia. Elevated liver enzymes, bile acids, and ammonia were noted on bloodwork. The primary differential diagnosis was a portosystemic shunt (PSS). Three-phase computed tomographic angiography findings were consistent with a transhepatic portosystemic shunt. Percutaneous liver biopsy confirmed severe diffuse hepatic changes, most likely due to chronic pyrrolizidine alkaloid toxicosis, and medical management was elected. Based on an extensive literature review, this is the first report of a transhepatic portosystemic collateral vessel in a horse. Computed tomographic angiography is feasible and useful for the diagnosis of PSS in miniature horses.

Single-cell Profiling of Intrahepatic Immune Cells Reveals an Expansion of Tissue-resident Cytotoxic CD4+ T Lymphocyte Subset Associated With Pathogenesis of Alcoholic-associated Liver Diseases

The immunological mechanisms underpinning the pathogenesis of alcoholic-associated liver disease (ALD) remain incompletely elucidated. This study aims to explore the transcriptomic profiles of hepatic immune cells in ALD compared to healthy individuals and those with metabolic dysfunction-associated steatotic liver disease (MASLD). We utilized single-cell RNA sequencing to analyze liver samples from healthy subjects, MASLD, and ALD patients, focusing on the immune cell landscapes within the liver. Key alterations in immune cell subsets were further validated using liver biopsy samples from additional patient cohorts. We observed a significant accumulation of CD4+ T cells in ALD patients' livers, surpassing the prevalence of CD8+ T cells, in contrast to MASLD and healthy counterparts, while natural killer (NK) cells and γδT cells exhibited reduced intrahepatic infiltration. In-depth transcriptional and developmental trajectory analyses unveiled that a distinct CD4+ subset characterized by granzyme K (GZMK) expression, displaying a tissue-resident signature and terminal effector state, prominently enriched among CD4+ T cells infiltrating the livers of ALD patient. Subsequent examination of an independent ALD patient cohort corroborated the substantial enrichment of GZMK+CD4+ T lymphocytes, primarily within liver fibrotic zones, suggesting their potential involvement in disease progression. Additionally, we noted shifts in myeloid populations, with expanded APOE+ macrophage and FCGR3B+ monocyte subsets in ALD samples relative to MASLD and healthy tissues. In summary, this study unravels the intricate cellular diversity within hepatic immune cell populations, highlighting the pivotal immune pathogenic role of the GZMK+CD4+ T lymphocyte subset in ALD pathogenesis.

Clinically significant portal hypertension in patients with primary biliary cholangitis: Clinicopathological features and prognostic value

Introduction and ObjectivesPrimary biliary cholangitis (PBC) may progress to clinically significant portal hypertension (CSPH) before the development of cirrhosis. This study aimed to investigate CSPH incidence as well as the clinicopathological characteristics and predictive value of these features for the prognosis of patients with PBC, especially at early histologic stage. Patients and MethodsPatients diagnosed with PBC between January 2013 and April 2022 were retrospectively enrolled. The prognostic value of baseline clinicopathological characteristics for long-term outcomes in PBC patients with CSPH was assessed using Kaplan–Meier survival analysis and COX regression analysis. ResultsAmong 280 patients with PBC, 104 underwent liver biopsy and 68 were at early histologic stage. CSPH was present in 47.2 % of participants with 20.6 % at early histologic stage. CSPH was a risk factor for predicting the liver transplant-free survival in PBC patients (hazard ratio [HR], 6.78; 95 % CI, 2.94–15.63), especially those at early stage. Perisinusoidal fibrosis and nodular regenerative hyperplasia (NRH) were common histopathological features in PBC patients with CSPH at the early stages. Fibrous septa formation in the hepatic lobules (HR, 4.85; 95 % CI, 1.51–15.52) and cholestasis (HR, 7.70; 95 % CI, 2.56–23.18) were independent predictors of adverse outcomes. ConclusionsCSPH indicates an increased risk of adverse outcomes in PBC patients, especially those in early histologic stage. Perisinusoidal fibrosis and NRH are valuable histological features of CSPH in patients with early-stage PBC. Identification of clinicopathological features and assessment of portal hypertension (especially at early stage), contribute to the development of personalized strategies.

Acute Liver Injury and Bilateral Pulmonary Artery Thrombosis Due to Hypereosinophilic Syndrome.

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/μL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

Noninvasive tools for the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously nonalcoholic fatty liver disease (NAFLD), is the number one chronic liver disorder worldwide. Progression to advanced fibrosis marks the emergence of a significant risk of liver-related negative outcomes. However, only a minority of patients will present at this stage. Since widespread liver biopsy in unfeasible at such high disease prevalence, there was a need to develop noninvasive tests (NITs) that could easily and reliably be applied to patients with MASLD, regardless of clinical setting. The NITs include simple scores, like the fibrosis-4 (FIB-4) Index, patented serum tests, like the Enhanced Liver Fibrosis test (ELF™), and imaging-based modalities, like the vibration-controlled transient elastography (VCTE). Guidelines suggests a stepwise approach that utilizes more than one NIT, with FIB-4 <1.30 being used as a first step to rule out patients that do not need further testing. Subsequent choice of NIT will be influenced by setting, cost, and local availability. While these NITs are accurate, they are not perfect. As such, research is ongoing. A promising avenue is that of omics, a group of technologies that provide concomitant results on a large number of molecules (and other variables). With the advance of artificial intelligence, new NITs may arise from large demographic, biochemical, and radiological data sets.

Validation of a whole slide image management system for metabolic-associated steatohepatitis for clinical trials.

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.

A Case Report of Unrespectable Liver Metastases from Cancer Rectosigmoid Colon with Survival Greater Than 6 Years and Clinical Benefit after Multidisciplinary Treatment

Introduction Colorectal cancer represents 1,271 new cases per year in Morocco, However, over the last 30 years we have witnessed a significant increase in the overall survival of metastatic patients due to the arrival of new molecules.  Case Presentation We report the case of a 51 years old african female patient diagnosed for a moderately differentiated adenocarcinoma of the rectosigmoid junction MSS, wild RAS/BRAF, treated with colorectal protection and lymph node dissection, followed by 6 cycles of fulfol- cisplatin as an adjuvant. the follow up revealed the appearance of hepatic masses. The liver biopsy was performed showing a secondary localization of an adenocarcinoma of digestive origin. The patient received four lines of the chemotherapy, anti-EGFR antibodies and immunotherapy following the guidelines. However, since no KRAS NRAS BRAF mutation was detected at the DNA level circulating tumor, no rechallenging of the anti- EGFR was possible. The hepatic progression continued with appearance of pulmonary lesions, the decision was made for a palliative care.  Conclusion Our case highlights that due to the emergence of new effective molecules currently available, associated with a dedicated onco-surgical approach, more patients will be able to benefit from prolonged survival that did not seem achievable at the time of diagnosis.

Magnetic Resonance Elastography for Staging Liver Fibrosis in the Oncopig.

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.

Fosfomycin-induced liver injury: A case report and literature review

Background: Fosfomycin is an antibiotic often used to treat urinary tract infections (UTIs) with only rare transient hepatotoxicity. We present a case of fosfomycin-induced liver injury and describe the histopathologic findings on biopsy. Methods: A 64-year-old female patient with no prior liver disease or risk factors was started on fosfomycin as prophylaxis for recurrent UTIs. Within a week of her first dose, she presented with fatigue, jaundice, and mixed liver enzyme elevation. Clinical workup for acute liver injury was unremarkable, and biopsy showed panacinar and portal necroinflammation with predominantly lymphocytic infiltrate and cholestasis, with no evidence of cirrhosis. This was thought to be likely related to fosfomycin exposure. Although liver enzymes trended down, bilirubin initially remained elevated. However, within 3 months the patient achieved clinical and biochemical recovery. Results: Only two other reports of fosfomycin-induced liver injury requiring biopsy were found. Both developed acute cholestatic hepatitis within days of exposure, and subsequent biopsy similarly showed lymphocytic necroinflammation. Although one patient initially developed acute liver failure, both recovered fully within a few months. Conclusion: Overall, these cases suggest potentially an idiosyncratic or immune-mediated liver toxicity of Fosfomycin, which is typically self-limited but may take months to fully resolve. Liver biopsy may be useful in confirming the diagnosis.

Association between serum remnant cholesterol level and metabolic dysfunction-associated steatotic liver histology.

Estimated remnant cholesterol (Rem-C) level, a risk factor for cardiovascular disease (CVD), is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosed via ultrasonography. However, the relationship between accurate serum Rem-C level measurements and histological findings of MASLD remains unclear. We aimed to elucidate the relationship between accurately measured serum Rem-C levels and histological findings of MASLD. Cross-sectional single-center observational study. We assessed 222 patients (94 men and 128 women; age 20-80) who were diagnosed with MASLD via liver biopsy with available medical history, physical examination, and biochemical measurement data. Serum ester-type cholesterol and free cholesterol contents in the remnant lipoproteins were measured using an enzymatic method. Serum Rem-C levels were significantly higher in patients with NAFLD activity score (NAS) 5-8, ＞66% steatosis grade, lobular inflammation with ≥5 foci, and many cells/prominent ballooning cells (a contiguous patch of hepatocytes showing prominent ballooning injury) than in patients with NAS 1-4, <33% steatosis grade, lobular inflammation with <2 foci, and few ballooning cells (several scattered balloon cells), respectively. While univariate analysis revealed no significant association between Rem-C levels and advanced fibrosis, a significant association between Rem-C levels and NAS was evident. This relationship remained significant in multivariate analysis adjusted for confounders. Furthermore, in the analysis by sex, these relationships were significant for men but not for women. High serum Rem-C levels were associated with high NAS, but not with fibrosis stage, particularly in men. Controlling serum Rem-C level may improve MASLD activity.

Endoscopic ultrasound-guided versus percutaneous liver biopsy: a systematic review and meta-analysis of randomized controlled trials.

Percutaneous liver biopsy (PC-LB) has long been the usual method for acquisition of liver tissue. Recently, endoscopic ultrasound-guided liver biopsy (EUS-LB) has gained popularity as an alternative modality. We aimed to compare the efficacy and safety of EUS-LB versus PC-LB. We systematically searched PubMed, Embase, and the Cochrane Library databases for randomized controlled trials (RCTs) comparing EUS-LB with PC-LB published until October 20, 2023. The primary outcome was diagnostic adequacy. Secondary outcomes were: the number of complete portal tracts (CPTs), longest sample length (LSL), total sample length (TSL), post-procedure pain scores, and adverse events (AEs), including overall AEs and AEs excluding minor post-procedure symptoms. We compared binary outcomes using risk ratios (RRs) and continuous outcomes using the mean difference (MD) or standardized mean difference (SMD), with 95%CIs. Four RCTs (258 patients) were included. The EUS-LB group presented lower post-procedure pain scores (SMD -0.58, 95%CI -0.95 to -0.22) than the PC-LB group. Both groups performed similarly in terms of diagnostic adequacy (RR 1.0, 95%CI 0.96 to 1.04), number of CPTs (MD 2.57, 95%CI -4.09 to 9.22), LSL (MD -2.91 mm, 95%CI -5.86 to 0.03), TSL (MD 4.16 mm, 95%CI -10.12 to 18.45), overall AEs (RR 0.54, 95%CI 0.20 to 1.46), and AEs excluding minor post-procedure symptoms (RR 1.65, 95%CI 0.21 to 13.02). This meta-analysis suggests that EUS-LB is as safe and effective as PC-LB and is associated with lower post-procedure pain scores.Registration on PROSPERO: CRD42023469469.

Association between Helicobacter pylori infection, MASLD, and liver fibrosis in patients with severe obesity: a single-center experience.

Our study sought to evaluate if an association exists between Helicobacter pylori (H. pylori), metabolic dysfunction- associated steatotic liver disease (MASLD), and liver fibrosis in patients with severe obesity (BMI > 35). Our retrospective study included 584 patients over the age of 18years with severe obesity, who underwent preoperative liver transient elastography (VCTE), upper endoscopy, blood work, and intra-operative liver biopsy concurrent with bariatric surgery at a single institution from July 2020 to September 2021. Liver fibrosis scores including FIB-4, APRI, NAFLD fibrosis score, BARD score, AST: ALT ratio, and NAFLD activity score (NAS) were calculated from the laboratory results and liver biopsy findings. The presence or absence of H. pylori was determined based on gastric biopsies obtained during upper endoscopy. Other variables collected included age, gender, mean preoperative weight, BMI, and the presence or absence of comorbidities. Student's t-test and non-parametric testing were used for the analysis of continuous variables and Chi-square analysis was used for categorical data. Of the 584 patients, 14.7% were H. pylori positive and 85.3% were negative. Liver fibrosis scores including FIB-4, APRI, and NAFLD fibrosis scores were significantly higher in the positive group (p < 0.05), but there was no difference in AST: ALT ratio and BARD score. A significantly higher VCTE steatosis and fibrosis scores were noted in the H. pylori-positive group (p < 0.05). Similarly, a significantly higher NAS (NAFLD activity score) on liver biopsies was noted in the positive group, with all the individual components of NAS (steatosis, lobular inflammation, and hepatocyte ballooning) being significantly higher in the positive group (p < 0.05). A significantly higher incidence of fibrosis on liver biopsies was noted in the positive group overall and across all stages of fibrosis (p < 0.05). There were no significant differences between the groups in relation to gender, mean weight, BMI, presence of comorbidities including Diabetes Mellitus, and laboratory values. Our study demonstrates that H. pylori colonization or infection is associated with a higher risk of development of MASLD and progression to fibrosis. Further, population-based studies are needed to corroborate our findings.

Ultrasonic Assessment of Liver Fibrosis Using One-Dimensional Convolutional Neural Networks Based on Frequency Spectra of Radiofrequency Signals with Deep Learning Segmentation of Liver Regions in B-Mode Images: A Feasibility Study.

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.