Liver Biopsy For Assessment Research Articles

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]

Quantitative digital pathology enables automated and quantitative assessment of inflammatory activity in patients with autoimmune hepatitis

BackgroundChronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component. MethodsWhole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC). ResultsID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation. ConclusionQuantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.

Histopathological Spectrum of Liver Allograft Biopsies and Association with Clinical and Pathological Parameters in Transplant Patients: A Cross-sectional Study

Introduction: Transplantation is vital for acute and terminal irreversible liver conditions. While imaging and functional measurements are valuable for evaluating post-transplant hepatocellular or biliary issues, liver allograft biopsies are used to determine the underlying causes of these changes. Long-term Immunosuppression (IMS), complex clinical circumstances, and de novo complications present challenges in transplant pathology, necessitating a multidisciplinary approach. Aim: To conduct a histopathological assessment of allograft liver biopsies for differential diagnosis, timing (postoperative day), and prevalence of post-transplantation complications, including identifying the causes of graft damage. Materials and Methods: This retrospective cross-sectional study was conducted between January 2019 and June 2022 at Vayalil Parambath Shamsheer (VPS) Lakeshore Hospital, Kochi, Kerala, India. A total of 45 post-transplant needle biopsy samples were analysed, examining histological characteristics and clinical data extracted from hospital records. Over 3.5 years, 45 post-liver transplant biopsies were performed. All clinical records and biopsy findings were examined using staining, and immunohistochemical analysis was performed. The Banff Working Group’s criteria were used to grade rejection based on a semiquantitative index, the Rejection Activity Index (RAI), into indeterminate (Score 1, 2); mild (Score 3, 4); moderate (Score 5, 6); and severe (>6). The classic histologic findings are characterised by predominant portal-based lesions, including a classical triad of mixed inflammatory cell infiltrates, venous endothelial inflammation, and inflammatory infiltration of bile ducts. Results: Among 38 patients, a total of 45 needle biopsies were performed. The first specimen was collected within a few hours of transplantation, and the final specimen was collected after 770 days. Notably, T-Cell-Mediated Rejection (TCMR) was diagnosed in 9 out of 45 (20.00%) specimens. Other complications included Intrahepatic Cholestasis (IHC) in 11 out of 45 (24.44%) cases, biliary obstruction in 5 out of 45 (11.11%) patients, Herpes Simplex Virus (HSV) hepatitis in 3 out of 45 (6.67%) specimens, Plasma Cell-Rich Rejection (PCRR) in 2 out of 45 (4.44%), and Isolated Central Perivenulitis (ICP), Dengue Haemorrhagic Fever (DHF), and veno-occlusive-like disease in 2 out of 45 (4.44% each) specimens. One patient had ethanolinduced liver injury (1 out of 45, 2.22%). Conclusion: Post-transplant liver biopsies are essential for accurate and timely diagnosis of rejection and other complications, guiding therapeutic interventions. This study offers insights into the types, prevalence, and timing of critical complications following liver transplantation (LTx).

Metabolic Dysfunction-Associated Steatohepatitis Detected by Neutrophilic Crown-Like Structures in Morbidly Obese Patients: A Multicenter and Clinicopathological Study.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), and closely associated with a high risk of liver-related morbidity and mortality. Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH, the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown. This clinicopathological study aimed to determine the association of neutrophilic crown-like structures (CLSs) in liver biopsies and evaluate their relevance to the histological diagnosis of MASH. A total of 483 morbidly obese adults who underwent bariatric surgery were recruited. Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3. All participants were classified into 4 histological subgroups: no MASLD (118, 24.4%), MASLD (76, 15.7%), borderline MASH (185, 38.3%), and definite MASH (104, 21.5%). In the discovery cohort (n = 379), the frequency of neutrophilic CLSs increased in line with the severity of liver disease. The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH. At a cutoff value of <0.3 per 20× microscopic field, the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH; a cutoff at >1.3 per 20× microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups (no MASLD, MASLD, and borderline MASH). The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort (n = 104). The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs. In conclusion, neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

Tacrolimus-associated sinusoidal obstruction syndrome after living-related liver transplantation

Sinusoidal obstruction syndrome (SOS), previously known as hepatic veno-occlusive disease, is manifested by obliterating inflammation of the terminal hepatic veins, characterized by hepatomegaly, right upper quadrant pain, jaundice and ascites, and most often occurs in patients after hematopoietic stem cell transplantation and usually in those who received platinum-based drugs. Cases of SOS development in patients after transplantation of solid organs (lungs, pancreas, liver) are also reported in the world literature. These incidents are rare, and isolated and poorly studied after living-related liver lobe transplantation. The diagnosis is based on clinical signs, imaging techniques (according to ultrasound and radiological methods of examination), histological assessment of liver biopsy. Tacrolimus has been reported to be a causative agent that potentially plays a role in the pathophysiological mechanism of SOS. Aim. To study the relationship between the use of prolonged-release tacrolimus and the development of SOS in patients after living-related liver transplantation. Clinical case. In this article, we present a case of SOS after living-related liver transplantation which was associated with a toxic effect of prolonged-release tacrolimus (“Envarsus”). In a 55-year-old man, after living-related liver transplantation, high blood concentrations of tacrolimus associated with uncontrolled drug intake were detected. When performing a number of laboratory and instrumental methods of examination due to a massive ascites manifestation, the diagnosis of SOS was made. The study was carried out in accordance with the principles of the Helsinki Declaration. The informed consent was obtained from the patient for conducting the studies. Conclusions. By ruling out other possible contributing factors, including an acute rejection crisis, it was concluded that prolonged-release tacrolimus (“Envarsus”) was the cause of SOS.

FRI-248 - Intrahepatic characterization of virological and immunological markers in two distinct populations of chronic hepatitis B: baseline assessment of core liver and fine needle aspiration biopsies from the investigational INSIGHT study

FRI-248 - Intrahepatic characterization of virological and immunological markers in two distinct populations of chronic hepatitis B: baseline assessment of core liver and fine needle aspiration biopsies from the investigational INSIGHT study

SAT-461 - MorphoQuant, the first fully-automated morphometric software for the assessment of liver biopsy, identified significant differences between non-alcoholic fatty liver disease and steatohepatitis biopsies

SAT-461 - MorphoQuant, the first fully-automated morphometric software for the assessment of liver biopsy, identified significant differences between non-alcoholic fatty liver disease and steatohepatitis biopsies

Banff 2016 Global Assessment and Quantitative Scoring for T Cell-Mediated Liver Transplant Rejection are Interchangeable.

Histopathological assessment of liver biopsies is the current "gold standard" for diagnosing graft dysfunction after liver transplantation (LT), as graft dysfunction can have nonspecific clinical presentations and inconsistent patterns of liver biochemical dysfunction. Most commonly, post-LT, graft dysfunction within the first year, is due to acute T-cell mediated rejection (TCMR) which is characterised histologically by the degree of portal inflammation (PI), bile duct damage (BDD), and venous endothelial inflammation (VEI). This study aimed to establish the relationship between global assessment, which is the global grading of rejection using a "gestalt" approach, and the rejection activity index (RAI) of each component of TCMR as described in revised Banff 2016 guidelines. Liver biopsies (n = 90) taken from patients who underwent LT in 2015 and 2016 at the Australian National Liver Transplant Unit were identified from the electronic medical records. All biopsy slides were microscopically graded by at least two assessors independently using the revised 2016 Banff criteria. Data were analysed using IBM SPSS v21. A Fisher-Freeman-Halton test was performed to assess the correlation between the global assessment and the RAI scores for each TCMR biopsy. Within the cohort, 60 (37%, n = 164) patients underwent at least 1 biopsy within 12 months after LT. The most common biopsy outcome (total n = 90) was acute TCMR (64, 71.1%). Global assessment of TCMR slides strongly positively correlated with PI (p value <0.001), BDD (p value <0.001), VEI (p value <0.001), and total RAI (p value <0.001). Liver biochemistry of patients with TCMR significantly improved within 4 to 6 weeks post-biopsy compared to the day of the biopsy. In acute TCMR, global assessment and total RAI are strongly correlated and can be used interchangeably to describe the severity of TCMR.

Challenges and opportunities in NASH drug development

Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), represent a growing worldwide epidemic and a high unmet medical need, as no licensed drugs have been approved thus far. Currently, histopathological assessment of liver biopsies is mandatory as a primary endpoint for conditional drug approval. This requirement represents one of the main challenges in the field, as there is substantial variability in this invasive histopathological assessment, which leads to dramatically high screen-failure rates in clinical trials. Over the past decades, several non-invasive tests have been developed to correlate with liver histology and, eventually, outcomes to assess disease severity and longitudinal changes non-invasively. However, further data are needed to ensure their endorsement by regulatory authorities as alternatives to histological endpoints in phase 3 trials. This Review describes the challenges of drug development in NAFLD-NASH trials and potential mitigating strategies to move the field forward.

FibroScan Predicts Liver Fibrosis Progression in Chronic HBV Infection Patients with No Clear Indication for Antiviral Therapy: A Retrospective Cohort Study.

Chronic hepatitis B virus (HBV) infection patients who do not fulfill the typical treatment indications should be followed up. This study aimed to evaluate the risk of liver fibrosis progression (LFP) and assess the role of noninvasive tests (NITs) of liver fibrosis in monitoring LFP in these patients. A total of 116 patients with active HBV replication, persistently normal or minimally elevated alanine aminotransferase (ALT) levels, and no or mild hepatic necroinflammation or fibrosis based on liver biopsy tests at baseline and followed by a repeated liver biopsy assessment during follow-up. LFP was defined as increase in METAVIR fibrosis score by 1 score or more. Among 116 patients, 40 (34.5%) progressed by at least one fibrosis stage, 16 (13.8%) progressed by at least two fibrosis stages at a median follow-up interval of 27 months (IQR: 12-36). Multivariate analysis confirmed the significant association of an increase in liver stiffness measurement (LSM) value with LFP on histology (p =0.005). The AUROC of LSM value increase rate is significantly higher than that of serum-based NITs of liver fibrosis for the prediction of LFP (p < 0.05). An increase in LSM by 20% is the optimal cutoff for the prediction of LFP. LFP is non-negligible in patients with active HBV replication, persistently normal or minimally elevated ALT, and initially no or minimal hepatic necroinflammation or fibrosis. Serial LSM tests would be more reliable in identifying LFP than serum-based NITs, and easier to obtain than serial liver biopsy tests.

Non-invasive Assessment of Liver Fibrosis Regression in Patients with Chronic HepatitisB: A Retrospective Cohort Study.

Non-invasive tests (NITs) have been alternative methods of liver biopsy for the cross-sectional assessment of liver fibrosis in patients with chronic hepatitisB (CHB). However, there are limited data on the longitudinal association between NITs and histological changes of liver fibrosis. This study aimed to evaluate whether NITs can be used to assess liver fibrosis regression (LFR) during anti-HBV treatment. This retrospective study included 337 patients with CHB who underwent contemporaneous NITs, such as liver stiffness measurement (LSM), the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and the γ-glutamyl transpeptidase to platelet ratio (GPR), and liver biopsy at baseline and followed by a repeated liver biopsy and NITs assessment. The LFR was defined as fibrosis regression by at least one stage assessed by METAVIR scoring system. The median interval between the two paired liver biopsy assessment was 31months (IQR 24-45). At the first liver biopsy, the fibrosis stage was F2 in 159 (47.2%), F3 in 68 (20.2%), and F4 in 110 (32.6%) patients. At the second liver biopsy, the number of patients with fibrosis stages F0-1, F2, F3, and F4 was 102 (30.3%), 106 (31.5%), 63 (18.7%), and 66 (19.6%), respectively. At follow-up liver biopsy, 169 patients (50.1%) had LFR, 128 patients (38.0%) had no change in fibrosis stage, and 40 patients (11.9%) had liver fibrosis progression on histology. A decrease in liver stiffness measurement (LSM) by 25% is the optimal cutoff for predicting LFR. Patients with a 25% or larger decrease in LSM value had more LFR than those with a less than 25% decrease in LSM value (78.1% vs 22.9%, p < 0.001). LSM might be used to monitor regression of liver fibrosis during antiviral treatment using nucleos(t)ide analogues (NUCs) in patients with CHB.

Stellate cell expression of SPARC-related modular calcium-binding protein 2 is associated with human non-alcoholic fatty liver disease severity

Histological assessment of liver biopsies is the gold standard for diagnosis of non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), despite its well-established limitations. Therefore, non-invasive biomarkers that can offer an integrated view of the liver are needed to improve diagnosis and reduce sampling bias. Hepatic stellate cells (HSCs) are central in the development of hepatic fibrosis, a hallmark of NASH. Secreted HSC-specific proteins may, therefore, reflect disease state in the NASH liver and serve as non-invasive diagnostic biomarkers. We performed RNA-sequencing on liver biopsies from a histologically characterised cohort of obese patients (n= 30, BMI >35kg/m2) to identify and evaluate HSC-specific genes encoding secreted proteins. Bioinformatics was used to identify potential biomarkers and their expression at single-cell resolution. We validated our findings using single-molecule fluorescence in situ hybridisation (smFISH) and ELISA to detect mRNA in liver tissue and protein levels in plasma, respectively. Hepatic expression of SPARC-related modular calcium-binding protein 2 (SMOC2) was increased in NASH compared to no-NAFLD (p.adj <0.001). Single-cell RNA-sequencing data indicated that SMOC2 was primarily expressed by HSCs, which was validated using smFISH. Finally, plasma SMOC2 was elevated in NASH compared to no-NAFLD (p <0.001), with a predictive accuracy of AUROC 0.88. Increased SMOC2 in plasma appears to reflect HSC activation, a key cellular event associated with NASH progression, and may serve as a non-invasive biomarker of NASH. Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are the most common forms of chronic liver diseases. Currently, liver biopsies are the gold standard for diagnosing NAFLD. Blood-based biomarkers to complement liver biopsies for diagnosis of NAFLD are required. We found that activated hepatic stellate cells, a cell type central to NAFLD pathogenesis, upregulate expression of the secreted protein SPARC-related modular calcium-binding protein 2 (SMOC2). SMOC2 was elevated in blood samples from patients with NASH and may hold promise as a blood-based biomarker for the diagnosis of NAFLD.

Iron overload disorders.

Iron overload disorders represent a variety of conditions that lead to increased total body iron stores and resultant end‐organ damage. An elevated ferritin and transferrin‐iron saturation can be commonly encountered in the evaluation of elevated liver enzymes. Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D, mutations most encountered in hereditary hemochromatosis, should be pursued in evaluation of hyperferritinemia. Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy (especially if liver disease is a cause of iron overload) should be used as appropriate. A secondary cause for iron overload should be considered if HFE genetic testing is negative for the C282Y homozygous or C282Y/H63D compound heterozygous mutations. Differential diagnosis of secondary iron overload includes hematologic disorders, iatrogenic causes, or chronic liver diseases. More common hematologic disorders include thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency. If iron overload has been excluded, evaluation for causes of hyperferritinemia should be pursued. Causes of hyperferritinemia include chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions, such as adult‐onset Still's disease or hemophagocytic lymphohistiocytosis. In this review, we describe the diagnostic testing of patients with suspected hereditary hemochromatosis, the evaluation of patients with elevated serum ferritin levels, and signs of secondary overload and treatment options for those with secondary iron overload.

New Approaches to the Diagnosis of Rejection and Prediction of Tolerance in Liver Transplantation.

Immunosuppression after liver transplantation is essential for preventing allograft rejection. However, long-term drug toxicity and associated complications necessitate investigation of immunosuppression minimization and withdrawal protocols. Development of such protocols is hindered by reliance on current paradigms for monitoring allograft function and rejection status. The current standard of care for diagnosis of rejection is histopathologic assessment and grading of liver biopsies in accordance with the Banff Rejection Activity Index. However, this method is limited by cost, sampling variability, and interobserver variation. Moreover, the invasive nature of biopsy increases the risk of patient complications. Incorporating noninvasive techniques may supplement existing methods through improved understanding of rejection causes, hepatic spatial architecture, and the role of idiopathic fibroinflammatory regions. These techniques may also aid in quantification and help integrate emerging -omics analyses with current assessments. Alternatively, emerging noninvasive methods show potential to detect and distinguish between different types of rejection while minimizing risk of adverse advents. Although biomarkers have yet to replace biopsy, preliminary studies suggest that several classes of analytes may be used to detect rejection with greater sensitivity and in earlier stages than traditional methods, possibly when coupled with artificial intelligence. Here, we provide an overview of the latest efforts in optimizing the diagnosis of rejection in liver transplantation.

Expression of concern: “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

Expression of concern: “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

Banff consensus recommendations for steatosis assessment in donor livers.

Background and AimsNo consensus criteria or approaches exist regarding assessment of steatosis in the setting of human donor liver suitability for transplantation. The Banff Working Group on Liver Allograft Pathology undertook a study to determine the consistency with which steatosis is assessed and reported in frozen sections of potential donor livers.Approach and ResultsA panel of 59 pathologists from 16 countries completed a questionnaire covering criteria used to assess steatosis in donor liver biopsies, including droplet size and magnification used; subsequently, steatosis severity was assessed in 18 whole slide images of donor liver frozen sections (n = 59). Survey results (from 56/59) indicated a wide variation in definitions and approaches used to assess and report steatosis. Whole slide image assessment led to a broad range in the scores. Findings were discussed at a workshop held at the 15th Banff Conference on Allograft Pathology, September 2019. The aims of discussions were to (i) establish consensus criteria for defining “large droplet fat” (LDF) that predisposes to increased risk of initial poor graft function and (ii) develop an algorithmic approach to determine fat droplet size and the percentage of hepatocytes involved. LDF was defined as typically a single fat droplet that expands the involved hepatocyte and is larger than adjacent nonsteatotic hepatocytes. Estimating severity of steatosis involves (i) low magnification estimate of the approximate surface area of the biopsy occupied by fat, (ii) higher magnification determination of the percentage of hepatocytes within the fatty area with LDF, and (iii) final score calculation.ConclusionsThe proposed guidelines herein are intended to improve standardization in steatosis assessment of donor liver biopsies. The calculated percent LDF should be provided to the surgeon.

Adiponutrin and Adiponectin Gene Variants in Indonesian Patients with Non-Alcoholic Fatty Liver Disease: a Preliminary Study

BackgroundVariants of adiponutrin (PNPLA3) and adiponectin (ADIPOQ) genes were considered to be associated with non-alcoholic fatty liver disease (NAFLD). Although the prevalence of NAFLD is increasing, there are limited numbers of studies about the association in Indonesian population.ObjectiveTo confirm whether specific variants of adiponutrin (PNPLA3) and adiponectin (ADIPOQ) genes are associated with NAFLD in Indonesian patients.MethodsData and DNA of 152 participants were obtained from a previous study in Dr. Kariadi Hospital, Semarang, Indonesia. PCR-RFLP analysis was performed for detection of PNPLA3 rs738409 and ADIPOQ rs2241767 variants. The diagnosis and severity of NAFLD were assessed according to NAFLD activity score (NAS) based on histopathology assessment of liverbiopsy.ResultsAllele G of PNPLA3rs738409 was associated with NAFLD in both bivariate (p=0.009, OR 2.52, CI 95% 1.25–5.07) and multivariate (p=0.008, OR 2.62, CI 95% 1.29%–5.32%) analysis, while ADIPOQ rs2241767 had no significant association. In NAFLD participants, both genotypes showed allele G was higher in the group of possible non-alcoholic steatohepatitis (NASH) – NASH (NAS &gt;2) than in the simple steatosis group (NAS &lt;2) i.e. 40.0% vs. 3.75% for the rs2241767 variant and 23.75% vs. 1.25% for the rs738409 variant, without significant association.ConclusionVariant PNPLA3 rs738409 was associated with NAFLD incidence in studied population. Among NAFLD participants, the frequency of both variants were found higher in the possible NASH – NASH group, yet needs to be confirmed with more participants and a multicenter study.Data and DNA of 152 participants were obtained from a previous study in Dr. Kariadi Hospital, Semarang, Indonesia. PCR-RFLP analysis was performed for detection of PNPLA3 rs738409 and ADIPOQ rs2241767 variants. The diagnosis and severity of NAFLD were assessed according to NAFLD activity score (NAS) based on histopathology assessment of liverbiopsy.

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation.

BACKGROUNDIn a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIMTo clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODSWe performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication.RESULTSDSA-positive pediatric patients showed a higher prevalence of chronic rejection (P = 0.01), fibrosis (P < 0.001) and re-transplantation (P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development.CONCLUSIONDSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.

Pain assessment of ultrasound-guided liver biopsy for diffuse parenchymal diseases: a randomized trial comparing intercostal and subcostal techniques

Objectives: Percutaneous liver biopsy is widely used in diffuse liver parenchymal diseases. Comparison of the severity of pain is not properly studied. In this randomized study, pain intensity between the intercostal and subcostal techniques of US-guided Tru-Cut liver biopsy in diffuse liver diseases was compared. Methods: Between March 2016 and May 2017, all potential study participants referred to the interventional radiology department for ultrasound-guided liver biopsy (n = 245), were assessed for enrollment. The pain intensity at 0, 2, and 4 h post-procedure was compared in two groups using a Numeric Rating Scale (NRS). Premedication was not used. After applying local anesthesia under US-guidance, 18-G automatic biopsy needle free-hand US-guided biopsy was performed. Results: Immediately after the biopsy (p = 0.0024), and at the 2nd hour (p = 0.0298), NRS of the subcostal group was significantly less than the intercostal group. Furthermore, the need for oral (p = 0.0492) or intramuscular (p = 0.0094) analgesics after the biopsy in the subcostal group was significantly less than the intercostal group. At the evaluation of both groups together, 55.62% of the patients had a mild and 27.22% had a moderate pain score. NRS score decreased with time in each group. Conclusions: The pain intensity and the need for analgesics were less in the subcostal biopsies. Since intense pain and anxiety may be the cause of loss of the patients after the first biopsy, a subcostal biopsy could be preferred primarily.

Diagnostic Accuracy of FibroScan and Factors Affecting Measurements.

Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is qualitative and subjective. The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) determined using FibroScan are the evidence-based non-invasive measures of liver fibrosis and steatosis, respectively. The LSM and CAP measurements are carried out simultaneously, and the median values of more than ten valid measurements are used to quantify liver fibrosis and steatosis. Here, we demonstrate that the reliability of the LSM depends on the interquartile range to median ratio (IQR/Med), but CAP values do not depend on IQR/Med. In addition, the LSM is affected by inflammation, congestion, and cholestasis in addition to fibrosis, while CAP values are affected by the body mass index in addition to steatosis. We also show that the M probe provides higher LSM values but lower CAP values than the XL probe in the same population. However, there was no statistically significant difference between the diagnostic accuracies of the two probes. These findings are important to understand the reliability of FibroScan measurements and the factors influencing measurement values for all patients.