Liver Biopsy Research Articles

Elexacaftor-tezacaftor-ivacaftor use after solid organ transplant.

In 2019, the United States Food and Drug Administration approved a breakthrough therapeutic for cystic fibrosis, elexacaftor-tezacaftor-ivacaftor (ETI), because of its profound effect on lung function in large phase III clinical trials. ETI acts directly on the dysfunctional protein that causes the systemic manifestations of cystic fibrosis and also leads to improvement in nonpulmonary symptoms of cystic fibrosis. Transplant recipients were excluded from the pivotal clinical trials of ETI but may stand to benefit from correction of the underlying protein defect. Drug interactions between the three drugs in ETI and immunosuppression medications are one of the primary concerns about using ETI after transplant. No rigorous studies exist to assess the safety of ETI in transplant recipients. Multiple recent publications describe the use of ETI after solid organ transplantation, including lung and nonlung transplants, and the real-world evidence for drug interactions between ETI and immunosuppression medications. In nonlung transplant recipients, the pulmonary benefits of ETI have been confirmed, but adverse events occur and may have implications for their transplanted organ (e.g. liver biopsy in the setting of elevated transaminases). Lung transplant recipients may have higher rates of ETI discontinuation than nontransplant recipients given a lack of direct pulmonary benefit and frequency of side effects. Drug interactions have not been difficult to manage, with most studies reporting variable rates of mild to moderate increased tacrolimus levels after initiation of ETI. Limited data exist to support the use of ETI after solid organ transplantation and further research is warranted. Given the unknown risks and benefits, case by case consideration of ETI use is indicated when extra-pulmonary manifestations are present in lung transplant recipients with cystic fibrosis. Given the proven benefit in cystic fibrosis lung disease, benefits likely outweigh the risks of ETI for nonlung solid organ transplant recipients.

IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab

Background and aimShort-term mortality in alcohol-related hepatitis (AH) is high and no current therapy results in durable benefit. A role for IL-1ß has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1ß, in the treatment of patients with AH. MethodsParticipants with biopsy-confirmed AH and discriminant function ≥32 but MELD ≤27 were randomly allocated 1:1 to receive either CAN 3mg/kg or placebo (PBO). Liver biopsies were taken before, and 28 days after treatment. The primary endpoint was the overall histological improvement in inflammation analysed by modified Intention-To-Treat (mITT). ResultsFifty-seven participants were randomised: 29 to CAN and 28 to PBO. Two participants had histology that did not corroborate the clinical diagnosis. Of the remaining 55 participants, paired histology data was evaluable from 48 participants. In CAN-treated participants, 14/24 (58%) demonstrated histological improvement compared to 10/24 (42%) in the PBO group (p=0.25). There was no improvement in prognostic scores of liver function. Four of the 55 participants (7%) died within 90 days; 2 in each group. The number of serious adverse events was similar between CAN vs PBO. In post-hoc exploratory analyses after adjustment for baseline prognostic factors, CAN therapy was associated with overall histological improvement (p=0.04). ConclusionCAN therapy in severe AH participants with MELD≤27 did not alter biochemical or clinical outcomes compared to PBO. Non-significant histological improvements did not translate into clinical benefit.

Binge drinking at time of bariatric surgery is associated with liver disease, suicides, and increases long-term mortality.

Alcohol use disorder has been reported in patients undergoing bariatric procedures, but the pattern of alcohol consumption has not been evaluated. We investigated the prevalence, risk factors, and impact of binge drinking (BD) at the time of surgery and during follow-up. A prospective, longitudinal study of subjects undergoing bariatric surgery was included in the LABS-2 registry between 2006 and 2009. Participants with AUDIT questionnaire at the time of surgery and a minimum of 12 months follow-up were included. BD was defined as consuming ≥5 drinks on at least 1 occasion in the previous month. Liver biopsies were obtained during bariatric procedures in not all cases. Survival analysis was performed with the adjusted Cox regression model and competing risk. A total of 2257 subjects were included, with a median follow-up of 79 months. The prevalence of BD at time of surgery was 12%, and it raised up to 23% during follow-up. Patients with BD predominantly had a binge eating disorder (OR=1.35 [95% CI: 1.04-1.76]), regularly consumed fast food [OR=1.4 (95% CI: 1.07-1.85)] and used other drugs (OR=2.65 [95% CI: 1.74-4.04]). Within liver biopsies evaluation, BD showed higher hepatic iron deposits (OR=3.00 [95% CI: 1.25-7.21]). BD at the time of surgery was associated with a higher risk of BD during follow-up (OR=10.49 [95% CI: 7.86-14.00]) and long-term mortality (HR: 3.21 [95% CI: 1.67-6.18]). Specific causes of death in these patients with BD were liver disease (p=0.020), suicide (p=0.015), neoplasms (p=0.034), and respiratory (p=0.025). The prevalence of BD in patients undergoing bariatric surgery is high and increases the risk of postoperative liver disease, suicides, and long-term mortality.

Histological Findings in Antigen E Positive and Negative in Chronic Hepatitis B.

To determine the histopathological findings in patients with HBeAg-positive chronic HBV infection (immunotolerant phase in old terminology) and HBeAg-negative chronic HBV infection (inactive carrier phase in old terminology). Observational study. Place and Duration of the Study: Department of Gastroenterology, University of Health Sciences, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkiye and Diyarbakir and Mersin University School of Medicine, Diyarbakir, Turkiye, from May 2014 to August 2022. The difference between fibrosis and histological activity indices of 289 patients in the immunotolerant and inactive carrier phase who had liver biopsy was examined statistically. Additionally, the relationship of these data with age and gender was investigated. While 236 (81.7%) of the patients were in the inactive carrier phase, 53 (18.3%) patients were in the immunotolerant phase. The mean fibrosis score of patients in the immunotolerant stage was 2.0 ± 1.2, while it was 2.0 ± 1.0 in inactive carriers (p = 0.753). The number of patients with a fibrosis score of two and above was 21 (39.6%) in immunotolerant patients and 52 (22.0%) in inactive carrier patients (p = 0.004). In patients under 30 years of age, the mean fibrosis score was 1.7 ± 1.0. It was 2.0 ± 1.1 in those over 30 years of age (p = 0.016). Biochemical parameters or viral load cannot clearly reflect cellular damage in the liver. In the future, HBV DNA positivity alone may be the only criterion for the treatment. Chronic viral hepatitis B, Fibrosis, Immune tolerance phase, Inactive carrier phase.

Development of hepatic fibrosis in common variable immunodeficiency-related porto-sinusoidal vascular disorder.

Liver involvement is an increasingly recognised complication of common variable immunodeficiency (CVID). Nodular regenerative hyperplasia (NRH), a subgroup of porto-sinusoidal vascular disorder, and manifestations of portal hypertension (PH) unrelated to cirrhosis are the most common findings. Nonetheless, the evolution of liver disease over time remains unknown. Retrospective review of patients followed at the National Institutes of Health with CVID-related liver disease and liver biopsy from 1990 to 2020. Clinical, imaging and histological follow-up were recorded as part of clinical research protocols. Forty patients were included, with a median age of 37.5 years at initial biopsy, 73% presenting with clear evidence of NRH, and a median fibrosis stage of 1. At biopsy, median platelet count was 100 × 109/L, spleen size 19.5 cm, hepatic venous pressure gradient 9.5 mmHg and 37.5% of patients had signs of PH. Cumulative incidence of PH was 65% at 5 years. In a subgroup of 16 patients, a follow-up liver biopsy, performed at a median time of 3 years after the index biopsy, revealed an increase in fibrosis by ≥2 stages in 31% of cases and an increase to an overall stage of 2.2 (p = 0.001). No clinical or histological factors were associated with progression of fibrosis. In this CVID cohort, NRH is the most common initial histological finding; however, unexpectedly fibrosis progresses over time in a subgroup of patients. A better understanding of the underlying causal process of liver disease CVID might lead to improved outcomes.

Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD

ObjectivesCurrently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes. Research design and methodsData were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI. Paired biopsies from interventional studies (n = 421) were used to assess the impact of change in weight, HbA1c and active vs. placebo treatment on improvements in steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis. ResultsIn the discovery cohort (n = 687), risk of severe steatosis, NASH and advanced fibrosis correlated positively with HbA1c, after adjustment for obesity and age. These data were endorsed in a separate validation cohort (n = 170). Predictive modelling using HbA1c and age was non-inferior to the established non-invasive biomarker, Fib-4, and allowed the generation of HbA1c, age, and BMI adjusted risk charts to predict NAFLD severity. Following intervention, reduction in HbA1c was associated with improvements in steatosis and NASH after adjustment for weight change and treatment, whilst fibrosis change was only associated with weight change and treatment. ConclusionsHbA1c is highly informative in predicting NAFLD severity and contributes more than BMI. Assessments of HbA1c must be a fundamental part of the holistic assessment of patients with NAFLD and, alongside age, can be used to identify patients with highest risk of advanced disease.

Agile 3+ and Metabolic Dysfunction-Associated Fatty Liver Disease: Detecting Advanced Fibrosis based on Reported Liver Stiffness Measurement in FibroScan and Laboratory Findings

: Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), formerly known as Non-alcoholic fatty liver disease (NAFLD), is characterized by fat accumulation in the liver and is associated with obesity, insulin resistance, and metabolic syndrome. Early detection and inter-vention are crucial to prevent disease progression to advanced fibrosis, cirrhosis, and liver failure. Non-invasive tests like transient elastography (TE), the Fibrosis-4 (FIB-4) index, the Enhanced Liver Fibrosis (ELF) score, and magnetic resonance imaging (MRI) are safer and more convenient than invasive procedures like liver biopsy for detecting advanced fibrosis in MAFLD patients. Agile 3+ is a non-invasive test that combines liver stiffness measurement (LSM) with clinical and laboratory findings to detect advanced fibrosis in MAFLD patients. It has shown high accuracy in detecting advanced fibrosis in MAFLD patients. The combination of LSM and laboratory find-ings provides a more accurate assessment of disease severity, making Agile 3+ a reliable, non-invasive test for assessing liver fibrosis in MAFLD patients. In summary, MAFLD is a common condition that can progress to advanced fibrosis and liver failure if left untreated. Non-invasive tests such as Agile 3+ have emerged as valuable tools for detecting advanced fibrosis in MAFLD patients, providing a more accurate assessment of disease severity and making it a reliable non-invasive test for assessing liver fibrosis in MAFLD patients

Predictors of liver fibrosis changes assessed by paired liver biopsies in chronic hepatitis C patients treated with direct-acting antivirals

Background/PurposeThere are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients. MethodsFrom March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment. ResultsAmong the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 103/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m2 (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 103/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026). ConclusionFor DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 103/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m2, sofosbuvir/ribavirin use, platelet counts <119 103/μL, or the absence of early ALT normalization at 4 weeks after baseline.

Mild-moderate alcohol consumption and diabetes are associated with liver fibrosis in patients with biopsy-proven MASLD.

It is unclear whether patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are allowed variable low levels of alcohol. This study aimed to evaluate the effect of mild-moderate alcohol consumption on the biochemical and histological characteristics of patients with MASLD. Alcohol consumption was assessed in 713 patients with steatotic liver disease (SLD) who underwent liver biopsy. Non-drinking, mild-moderate drinking, and excessive drinking were defined as 0g/day, 1-<20g/day, and >20g/day for women and 0g/day, 1-<30g/day, and >30g/day for men, respectively. Liver biopsies were scored according to the NASH CRN system. A total of 713 participants (median age 39.0years and 77.1% male) with biopsy-proven SLD were enrolled, including 239 nondrinkers, 269 mild-moderate drinkers and 205 excessive drinkers. Excessive drinking was associated with increased risks for lobular inflammation and liver fibrosis compared to nondrinkers and mild-moderate drinkers. Compared with non-drinkers, mild-moderate drinkers had significantly lower odds for steatosis (OR = 0.60, 95% CI = 0.38-0.93, p = 0.025), hepatocellular ballooning (OR = 0.52, 95% CI = 0.29-0.91, p = 0.020) and fibrosis (OR = 0.50, 95% CI = 0.31-0.81, p = 0.005). However, in non-excessive drinkers with type 2 diabetes mellitus (T2DM), there was no association between mild-moderate alcohol consumption and liver fibrosis (OR = 0.562, 95% CI = 0.207-1.530, p = 0.257). Mild-moderate alcohol consumption might be protective against liver fibrosis in MASLD patients, which is modified by the presence of T2DM. However, further longitudinal studies are needed to determine the effect of ongoing alcohol consumption on disease severity.

LiverColor: An Artificial Intelligence Platform for Liver Graft Assessment.

Hepatic steatosis, characterized by excess fat in the liver, is the main reason for discarding livers intended for transplantation due to its association with increased postoperative complications. The current gold standard for evaluating hepatic steatosis is liver biopsy, which, despite its accuracy, is invasive, costly, slow, and not always feasible during liver procurement. Consequently, surgeons often rely on subjective visual assessments based on the liver's colour and texture, which are prone to errors and heavily depend on the surgeon's experience. The aim of this study was to develop and validate a simple, rapid, and accurate method for detecting steatosis in donor livers to improve the decision-making process during liver procurement. We developed LiverColor, a co-designed software platform that integrates image analysis and machine learning to classify a liver graft into valid or non-valid according to its steatosis level. We utilized an in-house dataset of 192 cases to develop and validate the classification models. Colour and texture features were extracted from liver photographs, and graft classification was performed using supervised machine learning techniques (random forests and support vector machine). The performance of the algorithm was compared against biopsy results and surgeons' classifications. Usability was also assessed in simulated and real clinical settings using the Mobile Health App Usability Questionnaire. The predictive models demonstrated an area under the receiver operating characteristic curve of 0.82, with an accuracy of 85%, significantly surpassing the accuracy of visual inspections by surgeons. Experienced surgeons rated the platform positively, appreciating not only the hepatic steatosis assessment but also the dashboarding functionalities for summarising and displaying procurement-related data. The results indicate that image analysis coupled with machine learning can effectively and safely identify valid livers during procurement. LiverColor has the potential to enhance the accuracy and efficiency of liver assessments, reducing the reliance on subjective visual inspections and improving transplantation outcomes.

Gamma-glutamyltransferase (GGT) is a predictor of NAFLD activity score for diagnosing non- alcoholic steatohepatitis (NASH)

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from simple steatosis to steatohepatitis, advanced fibrosis and end stage liver disease. Despite the high prevalence and severity of hepatic illness, NAFLD remains underdiagnosed, because of few symptoms, lack of accurate laboratory markers. The study was aimed at to evaluate a bio-chemical score for diagnosing non-alcoholic steatohepatitis. A hospital based cross-sectional observational study was carried out for a period of two years from July 2013 to June 2015 in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. The study was conducted among 50 patients of NAFLD attending at department of Hepatology and underwent for biochemical investigations and liver biopsy with NAFLD Activity Score (NAS). All data were presented as mean ± SD and analyzed by SPSS (version 16). Qualitative data were analyzed by Chi-square test and quantitative data were analyzed by student’s t-test. Performance of the test were assessed by sensitivity and specificity test. Statistically significant result were considered when p value &lt; 0.05. Total patients were divided into two groups 25 were NASH and 25 were non- NASH. Mean GGT was found 73.6±48.6 U/L in NASH group and 49.9±25.4 U/L in non-NASH group. There was significant difference in the NAFLD activity score for diagnosing NASH between elevated and normal GGT (P value 0.035). Higher GGT values correlated with higher specificity. The Gamma-lutamyltransferase (GGT) has been proposed as a noninvasive and available marker for assessment of NASH. Bangladesh Med J. 2023 May; 52(2): 6-10

Efficacy of Ultrasound for the Detection of Possible Fatty Liver Disease in Children.

Pediatric MASLD (previously referred to as NAFLD) incidence has continued to rise along with the obesity pandemic. Pediatric MASLD increases the risk of liver fibrosis and cirrhosis in adulthood. Early detection and intervention can prevent and reduce complications. Liver biopsy remains the gold standard for diagnosis, although imaging modalities are increasingly being used. We performed a retrospective study of 202 children seen in a pediatric gastroenterology clinic with a complaint of abdominal pain, elevated liver enzymes or MASLD, or a combination of the three to evaluate screening methods for MASLD. A total of 134 of the 202 patients included in the study underwent laboratory testing and abdominal ultrasound. Ultrasound images were reviewed with attention to liver size and echotexture by a fellowship-trained pediatric radiologist for liver size and echotexture. Overall, 76.2% of the initial radiology reports correctly identified hepatomegaly based on age and 75.4% of the initial radiology reports correctly described hepatic echogenicity that was consistent with increased hepatic fat deposition. Use of screening ultrasound in concert with other clinical evaluations can be helpful to identify children at risk of MASLD. Utilizing ranges for liver span according to age can help to diagnose hepatomegaly, and understanding how to identify hepatic echogenicity is important for identifying possible hepatic steatosis.

Assessment of Metabolic and Bariatric Surgery Safety in Patients with Advanced Liver Fibrosis.

The well-established relationship between obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) is a key etiological factor in the development of liver cirrhosis. Bariatric surgery is an effective treatment for weight loss in patients with moderate-to-severe obesity, also playing a role in controlling MASLD. However, surgical safety in patients with advanced fibrosis remains to be established. This study aimed to evaluate the safety and repercussions of bariatric surgery according to fibrosis stage. Patients undergoing bariatric surgery who had an intraoperative liver biopsy were retrospectively evaluated. Preoperative and postoperative data were collected from medical records, and results were stratified according to fibrosis stage into early fibrosis (no fibrosis or stages 1 and 2) and advanced fibrosis (stages 3 and 4). The study included 1185 patients: 1129 with early fibrosis and 56 with advanced fibrosis. The advanced fibrosis group had higher percentage of men (35.7% vs 21.6%, p = 0.014) and of people with diabetes (42.9% vs 16.5%, p < 0.001) and hypertension (57.1% vs 41.4%, p = 0.012). Patients with advanced fibrosis also required longer hospitalizations (4.64 vs 4.06days, p < 0.001) and were more frequently admitted to the intensive care unit (7.1% vs 2.9%, p = 0.038). The groups did not differ significantly in other outcomes. There were no deaths in either group. Bariatric surgery proved to be safe, with similar complication rates in patients with advanced fibrosis and in those with early fibrosis.

Association between serum cytokeratin 18 and N-terminal procollagen III propeptide in patients with biopsy-proven nonalcoholic fatty liver disease*

ABSTRACT Liver biopsy is still the gold standard in the staging of nonalcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease worldwide. However, being an invasive method, liver biopsy has limited use in clinical practice. The aim of this study was to determine the relationship between serum levels of cytokeratin 18 (CK-M30) and N-terminal procollagen III propeptide (PIIINP) in patients with biopsy-proven NAFLD. The study was carried out on volunteers, including both healthy individuals and patients pre-diagnosed with NAFLD. The liver biopsies were re-assessed by applying the Steatosis, Activity, Fibrosis/Fatty Liver Inhibition of Progression (SAF/FLIP) algorithm. At the end of the study, frozen serum samples (−80 °C) were analyzed using commercial kits. CK18-M30 and PIIINP levels significantly differed in all study groups. There was no significant correlation between serum levels of CK18-M30 and PIIINP in healthy individuals but there was a significant positive correlation between CK18-M30 and PIIINP levels in NAFLD (NAFL-nonalcoholic steatohepatitis (NASH)) groups. CK18-M30 was better than PIIINP at distinguishing between NAFL and NASH. The results obtained for biopsy-proven NAFLD demonstrated that both PIIINP and CK18-M30 were partly associated with histological parameters and could aid in distinguishing between NASH and NAFL.

Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery.

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1-9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine.

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.

Elastography-The New Standard in the Assessment of Fibrosis After Pediatric Liver Transplantation?

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. 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. 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. 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.

What is the Safe Observation Period for Image-Guided Percutaneous Liver Biopsies?

Current observation period post-liver biopsy is typically 4h. This study investigates the safety of reducing the observation period after percutaneous liver biopsy. 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. 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 1h, 244 (89%) within 2h of observation. 16 (94%) of 17 post-procedural haemorrhages occurred within 2h post-biopsy. If complication-free after 2h, the probability of experiencing a complication within the next 2h was 4%. The majority of complications were identified within 2h of observation. Complications recognised after this period were largely pain-related, with only one grade 3 complication seen (post-procedural haemorrhage).Our findings suggest 2h of post-procedural observation may be safe. Level 2B, Retrospective Cohort Study.

Liver Tissue Proteins Improve the Accuracy of Plasma Proteins as Biomarkers in Diagnosing Metabolic Dysfunction-Associated Steatohepatitis.

Biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) have been considered based on proteomic and lipidomic data from plasma and liver tissue without clinical benefits. This study evaluated proteomics-based plasma and liver tissue biomarkers collected simultaneously from patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Liver tissue and plasma samples were collected during liver biopsy to diagnose MASLD. Untargeted proteomics was performed on 64 patients. Twenty plasma proteins were up- or downregulated in patients with MASH compared with those without MASH. The potential biomarkers utilizing the best combinations of these plasma proteins had an area under the receiver operating curve (AUROC) of 0.671 for detecting those with MASH compared with those without it. However, none of the 20 plasma proteins were represented among the significantly regulated liver tissue proteins in patients with MASH. Ten of them displayed a trend and relevance in liver tissue with MASLD progression. These 10 plasma proteins had an AUROC of 0.793 for MASH identification and higher positive and negative predictive values. The plasma and liver protein expressions of patients with MASH were not directly comparable. Plasma protein biomarkers that are also expressed in liver tissue can help improve MASH detection.

Clinical cohort of nonalcoholic fatty liver disease in a primary care setting.

Nonalcoholic fatty liver disease (NAFLD) is increasingly common, and primary care physicians (PCPs) are often the first to diagnose NAFLD. While guidelines on NAFLD management in primary care exist, there are limited data on clinical practice patterns. We gathered data from over 370,000 patients with at least one PCP visit between July 2016 and September 2023. Using ICD-10 codes to identify patients with a diagnosis of NAFLD or Nonalcoholic Steatohepatitis (NASH), we extracted demographics, comorbidities, laboratory results, prescriptions, imaging orders, and referrals to describe their care. We identified 10,334 patients with a diagnosis code of NAFLD (93.1%) and/or NASH (16.7%) during a PCP visit. Just over half (54.8%) were female, mean age was 52.8 years, and mean BMI was 33.2 kg/m2 with 90% having overweight or obese. More than 50% had hypertension and hyperlipidemia, and 38% had diabetes. At the diagnosis visit, 2.7% had ultrasound elastography ordered, 2.7% liver biopsy, and less than 1% magnetic resonance elastography. During follow-up ranging from 0 to 7 years, patients had a mean of 15 encounters, during which 4% were diagnosed with fibrosis or cirrhosis. Only 24.2% of patients were referred to a nutritionist and 18% had an appointment, and only 0.7% were referred to hepatology and 3.8% saw a hepatologist. PCPs have not widely implemented clinical practice guidelines for NAFLD, resulting in suboptimal care including for the substantial minority with fibrosis or cirrhosis. Patients might benefit from targeted NAFLD education for PCPs and improved decision and management support.