Liver Biopsy Evaluation Research Articles

Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children. Liver biopsy is considered the gold standard for diagnosis. Magnetic resonance elastography (MRE) and transient elastography (TE) are imaging modalities that can monitor fibrosis and steatosis noninvasively. More studies are needed to identify whether imaging modalities can provide accurate and reproducible data. We hypothesize that MRE provides reliable data similar to that of TE when compared to liver biopsy in children with MASLD/metabolic dysfunction-associated steatohepatitis. We conducted a retrospective chart review of children with liver biopsy-proven MASLD at Children's Hospital Los Angeles between September 2017 and January 2023, investigating and comparing the predictive accuracy of MRE and TE in the detection of high-grade fibrosis on liver biopsy. Seventy-seven patients were reviewed, all of whom had undergone liver biopsy, MRE and TE for evaluation of MASLD. Fibrosis was identified in 90% of liver biopsies. The area under the receiver operating characteristic curves (AUROC) of MRE and TE for detection of high-grade fibrosis were 0.817 and 0.750, respectively, and not significantly different (p = 0.4785). We demonstrate that MRE and TE did not accurately predict high-grade fibrosis on liver biopsy. Between the two noninvasive imaging modalities, the correlation of identifying high-grade fibrosis was not statistically different; however, the AUROC for MRE was slightly superior to that of TE. Studies with larger cohorts will be required to validate these findings.

Role of liver biopsy in the management of idiosyncratic DILI.

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.

Role of splenic hepatic elastography ratio in differentiating non-cirrhotic portal fibrosis and chronic liver disease in children and adolescents.

Differentiation of Non-cirrhotic Portal Fibrosis (NCPF) from chronic liver disease (CLD) in children and adolescents with portal hypertension (PHT) is challenging especially in cases where liver stiffness measurement (LSM) and hepatic venous pressure gradient are higher. This objective of the current study was to evaluate the diagnostic accuracy of the splenic stiffness measurement (SSM)/LSM ratio in the diagnosis of NCPF. From January 2019 to December 2023, consecutive children and adolescents of 6months to 18years of age with PHT (CLD and NCPF) were prospectively enrolled. Transient elastography (TE) for SSM and LSM, upper gastrointestinal endoscopy (UGIE), liver biopsy/trans-jugular liver biopsy, abdominal imaging, and laboratory evaluation were done. The relationship of TE parameters for diagnosis of NCPF and CLD was evaluated. Receiver-operating characteristic (ROC) statistics were applied using R Studio-4.2.2 statistical software. One hundred and forty seven with CLD and 27 patients with NCPF were evaluated. Median age was 10.0 (IQR 2.4-14.0) years; 68.4% were males. The AUROC of SSM/LSM ratio was better (0.992, 95%CI 0.982-1.0001) than LSM (0.945, 95%CI0.913-0.977) and SSM (0.626, 95%CI0.258-0.489) for the diagnosis of NCPF. SSM/LSM ratio cut-off of 3.67 predicted NCPF with an excellent sensitivity (100%), specificity (95.9%), and diagnostic accuracy (95.91%). The AUROC of SSM/LSM ratio was excellent and outperformed other TE parameters in the subgroups, i.e., LSM between 10 and 20kPa (0.982, 95%CI 0.947-1.000), without clinically significant varices (CSV) (1.000, 95%CI 1.000-1.000) and with CSV (0.993, 95%CI 0.983-1.000). Diagnostic performance of SSM/LSM Ratio was better than LSM for discriminating NCPF from CLD using McNemar test (p = 0.01). The SSM/LSM ratio is an excellent tool in differentiating NCPF from CLD.

Challenges of automation in quantitative evaluation of liver biopsies : Automatic quantification of liver steatosis

Metabolic dysfunction-associated steatotic liver disease (MASLD), or non-alcoholic fatty liver disease (NAFLD), is acommon disease that is diagnosed through manual evaluation of liver biopsies, an assessment that is subject to high interobserver variability (IBV). IBV can be reduced using automated methods. Many existing computer-based methods do not accurately reflect what pathologists evaluate in practice. The goal is to demonstrate how these differences impact the prediction of hepatic steatosis. Additionally, IBV complicates algorithm validation. Fortytissue sections were analyzed to detect steatosis, nuclei, and fibrosis. Data generated from automated image processing were used to predict steatosis grades. To investigate IBV, 18liver biopsies were evaluated by multiple observers. Area-based approaches yielded more strongly correlated results than nucleus-based methods (⌀ Spearman rho [ρ] = 0.92 vs. 0.79). The inclusion of information regarding tissue composition reduced the average absolute error for both area- and nucleus-based predictions by 0.5% and 2.2%, respectively. Our final area-based algorithm, incorporating tissue structure information, achieved ahigh accuracy (80%) and strong correlation (⌀ Spearman ρ = 0.94) with manual evaluation. The automatic and deterministic evaluation of steatosis can be improved by integrating information about tissue composition and can serve to reduce the influence of IBV.

FIB-4, APRI, and NFS Scores Compared to FibroScan for the Assessment of Liver Fibrosis in Patients with NAFLD

Background: NAFLD is a spectrum of liver disease ranging from fatty liver to steatohepatitis, fibrosis and cirrhosis. Due to the epidemic proportion of individuals with NAFLD worldwide, liver biopsy evaluation is impractical, and noninvasive assessment for the diagnosis of NASH and fibrosis is needed. In this study we aimed to compare FIB-4, APRI, and NFS score to FibroScan for the assessment of hepatic fibrosis in patients with NAFLD. Methods: This prospective study included 103 patients with NAFLD and was conducted in the Hepato-Gastroenterology Unit of Functional Digestive Explorations at CHU Ibn SINA in RABAT MOROCCO and covers the period from 01/2016 to 04/2023. A checklist was used to record the demographic features and biological data of the patients. Then, all patients underwent FibroScan using the FibroScan compact 530 device (Echosens, France). Results: Of the 103 patients with NAFLD included in this study, with a mean age of 54.4 ± 11.4 years, 35(34%) were male and 68 (66%) were female. Based on FibroScan results, 58 patients (56.3%) were classified as F1, 13 (12.6%) as F2, 5 (4.9 %) as F3, and 27 (26.2 %) as F4. A significant correlation was found between FibroScan and FIB-4 (r = 0.365), APRI (r = 0.376), and NFS score (r = 0.356) (P < 0.001). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of APRI at the 0.64 cut-off for the differentiation of F3F4 from F2F1 were 59.4, 84.5, 63.3, 82.2 and 76.7%. FIB-4 at the 1.8 cut-off 68.8, 83.1, 64.7, 85.5, 78.6% and NFS at the 0.89 cut-off 71.9, 69, 51.1, 84.5 and 69.9% respectively. Moreover, the area under the receiver operating curve of APRI, FIB-4, and NFS for the differentiation of F3F4 from F1F2 was 0.782, 0.779, and 0.723, respectively. Conclusions: Based on these results, APRI appears to be the most appropriate substitute of FibroScan for the detection of significant fibrosis in NAFLD patients.

Pathologic approach to Neonatal cholestasis with a simple scoring system for biliary atresia

A liver biopsy is essential for the diagnostic workup of persistent neonatal cholestasis (NC). The differential diagnosis of NC is broad, including obstructive and non-obstructive causes. In addition, histologic features of certain disorders may be non-specific in the early course of the disease. To evaluate liver biopsies using a practical histopathologic approach for NC and to define a simple scoring system for biliary atresia (BA) for routine clinical practice. From June 2006 to December 2021, liver biopsy specimens from infants with persistent NC were examined by two independent pathologists. The cases diagnosed as BA were correlated with clinical, radiologic, and laboratory data to calculate the final score. Four hundred and fifty-nine cases were enrolled in the study. They had a mean age of 63.94 ± 20.62 days and were followed for a median time of 58 (1–191) months. They included 162 (35.3%) cases of BA. On multivariate analysis, portal edema, ductular proliferation, cholangiolitis, and bile duct/ductular plugs were the histopathologic predictors of BA. A liver biopsy did perform well with a 95.1% sensitivity, 91.6% specificity, 86% PPV, and 97.1% NPV. At a cutoff of 5 of the scoring system, diagnosis of BA could be done with a sensitivity of 95.1% and a specificity of 100%. We have shown detailed histopathologic features of BA with more depth to infants aged ≤ 6 weeks. We have developed a simple scoring system using a combination of liver biopsy with non-invasive methods to increase the diagnostic accuracy of BA.

Prevalence and significance of antimitochondrial antibodies in autoimmune hepatitis (AIH): Results from a large multicentre study of the International AIH Group

Background & AimsAntimitochondrial antibodies (AMA) are specific markers for the diagnosis of primary biliary cholangitis (PBC) but can also be found occasionally in patients with autoimmune hepatitis (AIH). The present large multicentre cohort study assessed the prevalence and significance of AMA in AIH-patients. Methods123 AMA-positive AIH-patients were investigated and compared with 711 age-matched AMA-negative AIH-patients and 69 patients with AIH/PBC variant. ResultsAMA prevalence in AIH-patients was 5.1% (range: 1.2%-11.8%). AMA-positivity was associated with female sex (p = 0.031) in AMA-positive AIH-patients but not with liver biochemistry, bile duct injury on liver biopsy, disease severity at baseline and response to treatment compared to AMA-negative AIH-patients. Comparing AMA-positive AIH-patients to those with AIH/PBC variant, there was no difference in disease severity. Regarding liver histology, AIH/PBC variant patients were characterized by the presence of at least one feature of bile duct damage (p<0.001). Response to immunosuppressive treatment was similar among groups. From AMA-positive AIH patients only those with evidence of non-specific bile duct injury had higher risk to progress to cirrhosis (HR=4.314, 95%CI: 2.348–7.928; p<0.001). During follow-up, AMA-positive AIH-patients had higher risk to develop histological bile duct injury (HR 4.654, 95%CI 1.829–11.840; p = 0.001). ConclusionsAMA presence is relatively common among AIH-patients, but their clinical significance seems important only when they co-exist with non-specific bile duct injury at the histological level. Therefore, a careful evaluation of liver biopsy seems of utmost importance in these patients.

A Case of Hepatosplenic γ/δ T-Cell Lymphoma Debuting With Massive Hemoptysis

Summary Hepatosplenic γ/δ T-cell lymphoma (HSTL) is a very rare, aggressive extranodal lymphoma affecting mainly young adults. Clinically, presents with a symptomatic hepatosplenomegaly and systemic symptoms but without lymphadenopathy. The diagnosis is confirmed after careful evaluation of bone marrow and liver biopsies or, in some cases, after diagnostic splenectomy. Overall, survival is short regardless of chemotherapy regimens applied, including autologous stem cell transplantation. We present a case of γ/δ HSTL with massive pulmonary hemoptysis requiring bronchial artery embolization.

(397) Long-term Testosterone Therapy in Men with Functional Hypogonadism and Obesity Improves Surrogate Parameters of Liver Function in a Urological Registry Study

Abstract Introduction Hepatic steatosis is highly prevalent in patients with hypogonadism and obesity. Fatty liver is increasingly recognized as cardiovascular risk factor. The gold standard assessment – histological evaluation of liver biopsies – cannot be performed in routine clinical practice. However, the fatty liver index (FLI) can be calculated using the formula by Bedogni: FLI = (e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) / (1 + e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) * 100 (Bedogni G et al. BMC Gastroenterol 2006;6:33). A FLI &amp;lt;30 rules out and a FLI ≥60 rules in fatty liver. Objective to investigate effects of long-term testosterone therapy (TTh) up to 13 years on surrogate parameters of liver function in men with functional hypogonadism and obesity in comparison to an untreated control group. Methods In an ongoing registry study in men with hypogonadism (total testosterone ≤350 ng/mL and at least moderate symptoms on the Aging Males’ Symptoms scale, AMS) in a single urology office, 491 men had functional hypogonadism and obesity (BMI ≥30 kg/m2). 292 men received testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group), 199 opted against TTh and served as controls (CTRL). Height was measured at baseline, weight, waist circumference, triglycerides and γ-GT were assessed at each visit and the fatty liver index (FLI) calculated. AST, ALT, and bilirubin were also measured at each visit. Mean absolute measures with standard deviations (SDs) are reported for a duration of 13 years. Results Mean (median) follow-up: T-group 10.1±3.1 (11), CTRL 9.4±3.3 (10) years. Baseline age was 59.5±6.0 (T-group) and 63.0±5.0 years (CTRL) (p&amp;lt;0.0001). Triglycerides decreased from 3.4±0.5 to 2.2±0.1 in the T-group and increased from 3.2±0.5 to 3.9±0.5 in CTRL (p&amp;lt;0.0001 for both). γ-GT (U/L) decreased from 42.9±22.8 to 20.5±6.4 in the T-group and increased from 35.5±11.6 to 61.7±5.9 in CTRL (p&amp;lt;0.0001 for both). AST (U/L) decreased from 38.4±13.3 to 20.8±1.9 in the T-group and increased from 28.6±9.0 to 54.1±11.9 in CTRL (p&amp;lt;0.0001 for both). ALT (U/L) decreased from 41.4±13.7 to 24.7±2.1 in the T-group and increased from 32.7±9.4 to 60.2±13.8 in CTRL (p&amp;lt;0.0001 for both). Bilirubin decreased from 0.53±0.27 to 0.18±0.05 mg/dL in the T-group and increased from 0.44±0.23 to 1.09±0.27 mg/dL in CTRL (p&amp;lt;0.0001 for both). Waist circumference from 115.0±13.2 to 97.5±4.6 cm in the T-group and increased from 118.6±11.4 to 121.2±6.1 cm in CTRL (p&amp;lt;0.0001 for all). BMI decreased from 36.8±3.6 to 28.3±2.1 kg/m2 in the T-group and increased from 33.9±3.3 to 34.9±2.2 kg/m2 in CTRL (p&amp;lt;0.0001 for all). FLI decreased from 95.1±4.6 to 61.3±11.2 in the T-group and increased from 94.1±4.4 to 98.0±1.3 in CTRL (p&amp;lt;0.0001 for both). Conclusions Long-term testosterone therapy in men with functional hypogonadism and obesity improved surrogate parameters of liver function indicating an improvement in hepatic steatosis. All measures deteriorated over time in untreated obese hypogonadal control patients. Disclosure Yes, this is sponsored by industry/sponsor: Bayer AG, Berlin, Germany. Clarification Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Bayer AG.

(Rare) infectious hepatitis as an important differential diagnosis of unclear hepatopathy

Liver biopsies to determine the cause of unclear hepatopathy and acute liver failure represent adiagnostic hallmark and require close cooperation between clinicians and pathologists. The commonly acute presentation of hepatic dysfunction warrants arapid diagnosis. Infectious causes of hepatitis may be identified by the pathologist, supporting further diagnostic and therapeutic steps. Rare infectious causes of hepatic dysfunction with distinct histomorphological features are presented. Retrospective cases of liver biopsies for evaluation of hepatic dysfunction with infection confirmed by laboratory tests were selected from the archive of the institute of pathology of TUM and evaluated for morphologic diagnostic criteria. Infections with adenovirus, Herpes simplex virus, HepatitisA virus, and coxiella burnettii are rare findings in liver core biopsies but able to cause hepatic dysfunction that present with distinct histomorphologic alterations that can contribute to the identification of the causative agent. Rare infectious causes should be considered in any patient presenting with hepatic dysfunction of unknown etiology. Knowledge of the histomorphologic criteria by the pathologist is crucial to initiate further diagnostic testing and treatment.

Non-alcoholic fatty liver disease: the pathologist's perspective.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases characterized by fatty accumulation in hepatocytes, ranging from steatosis, non-alcoholic steatohepatitis, to cirrhosis. While histopathological evaluation of liver biopsies plays a central role in the diagnosis of NAFLD, limitations such as the problem of interobserver variability still exist and active research is underway to improve the diagnostic utility of liver biopsies. In this article, we provide a comprehensive overview of the histopathological features of NAFLD, the current grading and staging systems, and discuss the present and future roles of liver biopsies in the diagnosis and prognostication of NAFLD.

A feasibility study using sodium alginate injection for penetrating abdominal trauma in a swine model

Penetrating abdominal injury is a major cause of death in trauma. Sodium alginate hydrogel, a hemostatic agent, offers a platform for targeting both mechanical and biological injuries. The current study assessed the effect of Very Low Viscosity (high) G (VLVG) alginate following abdominal trauma in a swine model of penetrating abdominal injury. Seven anesthetized pigs were instrumented with invasive monitoring catheters and abdominal trauma was introduced by laparoscopic hepatectomy. Ten minutes after the induction of hypovolemic shock, three animals were intra-abdominally administered with VLVG alginate (study group) and four animals with saline (control group). During 8 h of continuous monitoring, various hemodynamic and biochemical variables were measured and liver biopsies for histological evaluation were taken. Hemodynamically, VLVG alginate-treated animals were more stable than controls, as reflected by their lower heart rate and higher blood pressure (p < 0.05 for both). They also had lower levels of liver enzymes and lactate, and less histopathological damage. We show that VLVG alginate might be a promising new agent for reducing penetrating intra-abdominal injury, with hemostatic and biocompatibility efficiency, and tissue preserving properties. Future effort of integrating it with a dispersal device may turn it into a valuable pre-hospital emergency tool to improve survival of trauma casualties.

Role of Liver Biopsy in Evaluation of Fibrosis: Review Article

Role of Liver Biopsy in Evaluation of Fibrosis: Review Article

S1237 Association of Liver Biopsy Pathology on Outcome of Patients Undergoing Heart Transplantation

Introduction: Patients with advanced heart failure needing heart transplant (HT) commonly have some degree of liver dysfunction. Liver biopsies are the gold-standard for evaluating the severity of liver disease and are commonly performed prior to listing a patient for HT. However, there is limited data on the impact of liver fibrosis on outcomes for HT candidates. The objective of this study was to determine the relationship between liver fibrosis severity and mortality rates for patients on the HT waitlist and post-HT. Methods: A retrospective cohort study of adults listed for HT who underwent a liver biopsy for evaluation of liver fibrosis from 08/12/2004-02/16/2022 at a large heart transplant center was performed. Degree of fibrosis was categorized as either early (only fibrosis expansion of portal areas with or without short fibrous septa or no fibrosis) or advanced (evidence of portal-to-portal bridging or cirrhosis). Trend analysis was performed on clinical, laboratory and mortality data using Cox proportional hazard model, controlling for MELD-XI. At-risk period starts at the time of waitlist and extends into the post-transplant phase. The end of the follow-up period was defined as mortality on the waitlist, mortality post-HT, or administrative censoring at the end of the study period. Results: Of 42 patients with liver biopsies, 14 (33%) had advanced fibrosis, 28 (67%) had early fibrosis, and 2 (5%) patients had cirrhosis. There was no significant difference in the survival of patients with advanced fibrosis and early fibrosis over time (HR 1.37, CI 0.47- 3.98, p = 0.56). Fifteen waitlisted patients did not eventually receive transplants, and there was no significant difference in survival within group (HR 0.65, CI 0.18-2.32, p = 0.51); 9 of these 15 patients died on the waitlist. Twenty-seven patients did eventually receive transplants, and there was no significant difference in survival within this group (HR 1.00, CI 0.09-11.43, p = 1.00). (Figure) Conclusion: There was no significant difference in the survival rates between HT candidates with and without advanced fibrosis on the waitlist and post-HT, suggesting that patients on the transplant waitlist may not need liver biopsy for heart transplant workup. However, our sample population was derived from patients who were already on the transplant waitlist. Therefore, our results cannot be extrapolated to the general advanced heart failure population undergoing HT evaluation, many of whom are not waitlisted due to cirrhosis (Table). Table 1. - Predicted survival percentages for transplanted patients, non-transplanted patients, and both groups combined at 30 days, 1 year and 5 years with early liver fibrosis or advanced liver fibrosis from time of listing Transplanted Patients (% [CI]) Non-transplanted Patients (% [CI]) Transplanted and Non-transplanted Patients (% [CI]) Early Liver Fibrosis 30 Days 100 (0-100) 84.6 (66.0-100) 95.8 (90.0-100) 1 Year 96.2 (88.8-100) 53.5 (29.2-97.9) 84.5 (73.2-97.4) 5 Years 88.1 (74.6-100) 17.3 (3.6-84.0) 68.2 (52.4-88.9) Advanced Liver Fibrosis 30 Days 100 (0-100) 89.7 (75.7-100) 94.3 (86.1-100) 1 Year 96.2 (86.6-100) 66.6 (42.4-100) 79.3 (63.0-99.9) 5 Years 88.2 (67.4-100) 32.1 (9.8-100) 59.2 (37.6-93.1) CI = confidence interval. Figure 1.: (1) Survival curve of waitlisted patients with and without advanced liver fibrosis, including patients who received and did not receive transplants. Time 0 is the time of listing. Fibrosis score 0 = early liver fibrosis. Fibrosis score 1 = advanced liver fibrosis. (2). Survival curve of only those patients who did not receive transplants. Time 0 is the time of listing. Fibrosis score 0 = early liver fibrosis. Fibrosis score 1 = advanced liver fibrosis. (3) Survival curve of only those patients who received transplants. Time 0 is the time of listing. Fibrosis score 0 = early liver fibrosis. Fibrosis score 1 = advanced liver fibrosis.

Identification and clinical significance of nodular regenerative hyperplasia in primary sclerosing cholangitis.

Background and AimPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of intrahepatic and extrahepatic bile ducts. PSC is frequently associated with inflammatory bowel disease (IBD). Nodular regenerative hyperplasia (NRH) can occur in IBD with the use or even in the absence of thiopurine treatment. We aimed to study the significance of the presence of NRH and obliterative portal venopathy (OPV), both causes of non‐cirrhotic portal hypertension (NCPH), in patients having PSC.MethodsPatients with PSC and concurrent NRH on liver biopsy were identified from the digital pathology database covering the period 2003–2019. Evaluation of liver biopsy and the original diagnoses were confirmed on review based on standard histological features diagnostic for NRH and OPV. Clinical and laboratory data were obtained from electronic medical records.ResultsThirty‐one patients (21 male, 10 female; median age at biopsy 40.1 years) were included in the study. Twelve (38.7%) patients had OPV in addition to NRH on the liver biopsy. Nineteen (61.2%) patients had IBD including 11 with Crohn's disease (CD), 7 with ulcerative colitis (UC), and 1 with indeterminate colitis. Thirteen (41.9%) patients had evidence of portal hypertension, 10 (32.2%) with esophageal varices, 4 (12.9%) with history of variceal bleeding, 6 (19.3%) with ascites, and 14 (12.9%) with splenomegaly. Eleven (35.4%) patients had a cirrhotic‐appearing liver on imaging. Twelve (38.7%) patients had a history of prior or current thiopurine use.ConclusionsThe current study suggests that NRH with or without OPV independently occurs in patients having PSC and may lead to NCPH, even in the absence of concurrent IBD and/or thiopurine therapy.

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

BackgroundThe development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease.MethodsThis study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program.DiscussionThis study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country.Trial registrationThis study is registered on Clinicaltrials.gov (NCT03789825).

Quantitative evaluation of hepatic steatosis using novel ultrasound technology normalized local variance (NLV) and its standard deviation with different ROIs in patients with metabolic-associated fatty liver disease: a pilot study

PurposeThe purpose of this study was to evaluate the diagnostic performance of novel ultrasound technology normalized local variance (NLV) and the standard deviation of NLV (NLV-SD) using different ROIs for hepatic steatosis in patients with metabolic-associated fatty liver disease (MAFLD) and to identify the factors that influence the NLV value and NLV-SD value, using pathology results as the gold standard.MethodsWe prospectively enrolled 34 consecutive patients with suspected MAFLD who underwent percutaneous liver biopsy for evaluation of hepatic steatosis from June 2020 to December 2020. All patients underwent ultrasound and NLV examinations. NLV values and NLV-SD values were measured using different ROIs just before the liver biopsy procedure.ResultsThe distribution of hepatic steatosis grade on histopathology was 4/19/6/5 for none (< 5%)/ mild (5–33%)/ moderate (> 33–66%)/ and severe steatosis (> 66%), respectively. The NLV value with 50-mm-diameter ROI and NLV-SD value with 50-mm-diameter ROI showed a significant negative correlation with hepatic steatosis (spearman correlation coefficient: − 0.449, p = 0.008; − 0.471, p = 0.005). The AUROC of NLV (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.875, 0.735, and 0.583, respectively. The AUROC of NLV-SD (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.900, 0.745, and 0.603, respectively. NLV (50 mm) values and NLV-SD (50 mm) values between two readers showed excellent repeatability and the intraclass correlation coefficient (ICC) was 0.930 (p < 0.001) and 0.899 (p < 0.001). Hepatic steatosis was the only determinant factor for NLV value and NLV-SD value (p = 0.012, p = 0.038).ConclusionThe NLV (50 mm) and NLV-SD (50 mm) provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with great reproducibility. This study showed that the degree of steatosis was the only significant factor affecting the NLV value and NLV-SD value.

Liver tumors in children with chronic liver diseases.

Liver tumors are rare in children, but the incidence may increase in some circumstances and particularly in chronic liver diseases. Most liver tumors consequent to chronic liver diseases are malignant hepatocellular carcinoma. Other liver tumors include hepatoblastoma, focal nodular hyperplasia, adenoma, pseudotumor, and nodular regenerative hyperplasia. Screening of suspected cases is beneficial. Imaging and surrogate markers of alpha-fetoprotein are used initially as noninvasive tools for surveillance. However, liver biopsy for histopathology evaluation might be necessary for patients with inconclusive findings. Once the malignant liver tumor is detected in children with cirrhosis, liver transplantation is currently considered the preferred option and achieves favorable outcomes. Based on the current evidence, this review focuses on liver tumors with underlying chronic liver disease, their epidemiology, pathogenesis, early recognition, and effective management.

Diagnostic performance of ultrasound attenuation imaging for assessing low-grade hepatic steatosis.

To investigate the diagnostic performance of attenuation imaging (ATI) for the assessment of low-grade hepatic steatosis using liver biopsy as the reference standard. The study included 57 potential donor candidates for living liver transplantation who underwent ATI, transient elastography (TE), and liver biopsy for evaluation of hepatic steatosis between February 2020 and April 2020. The attenuation coefficient (AC) from ATI and the controlled attenuation parameter (CAP) from TE were measured for each participant in a random and blind manner. The histologic hepatic fat fraction (HFF) was graded (S0, < 5%; S1, 5-33%; S2, 33-66%; S3, > 66%). The accuracy of ATI for diagnosing hepatic steatosis was compared with that of CAP using ROC analysis. Correlations between AC and HFF were evaluated, and factors affecting AC were determined by linear regression analysis. The median HFF was 3% (range: 0-35%), with 31 (54.4%), 24 (42.0%), and 2 (3.5%) participants being graded as S0, S1, and S2, respectively. The AUCs for the ROCs of AC and CAP for the detection of hepatic steatosis were 0.808 (95% CI: 0.682-0.900) and 0.829 (95% CI: 0.706-0.916), respectively, with the difference not being statistically significant (p = 0.762). AC showed 61.5% of sensitivity and 90.3% of specificity. AC was positively correlated with HFF (p < 0.001). HFF was the only factor significantly affecting AC. ATI showed moderate sensitivity and high specificity in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. Only HFF significantly affected AC. • Attenuation imaging showed moderate sensitivity and high specificity performance in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. • The diagnostic performance of the attenuation coefficient by attenuation imaging did not significantly differ from that of the controlled attenuation parameter by transient elastography in quantifying low-grade steatosis. • The histopathologically determined hepatic fat fraction was the only factor significantly affecting the attenuation coefficient.

Doppler Ultrasound and Fibroscan Parameters Versus Liver Biopsy ‎in Evaluation of Hepatic Fibrosis in Egyptian Patients with Chronic ‎Hepatitis C‎

Background and study aim: Liver biopsy is the gold standard method to assess hepatic ‎inflammation and fibrosis in chronic hepatitis C infection (HCV). The ‎non-invasive assessment of liver fibrosis is the key target that has ‎inspired many new methods because of the limitations of liver biopsy. ‎The aim of the work was to improve the efficiency of non-invasive liver ‎fibrosis assessment in Egyptian patients with chronic hepatitis C by ‎comparing Doppler ultrasound (US) of hepatic blood flow and ‎fibroscan with liver biopsy‎. Patients and Method: ‎ In this retrospective analysis, 78 patients with HCV had already ‎undergone liver biopsies as part of work panel prior to HCV treatment. ‎Fibroscan examination, abdominal ultrasonography and Doppler ‎ultrasound were done to the patients by experienced operators‎‎.‎ Results: There was a strong positive‏ ‏correlation between the degree of liver ‎fibrosis by fibroscan and the degree of inflammation in the ‎histopathological analysis. Receiver Operator Characteristic (ROC) ‎curve analysis revealed that fibroscan failed to detect FII fibrosis. ‎However, fibroscan was more accurate in detecting FIII ‎fibrosis.The Doppler ultrasound parameter ROC curve analysis, ‎the portal vein blood flow volume (PVBFV) was shown to be ‎more accurate in detecting lower grades of fibrosis than ‎higher‎. Conclusion: For detection higher degrees of fibrosis, Fibroscan has a strong match ‎with liver biopsy; however, Doppler US is more sensitive in detecting ‎lower grades of fibrosis in patients infected with HCV‎ ‎‎‎.