Requires Liver Biopsy Research Articles

Pediatric endoscopic ultrasound-guided liver biopsy: 3-year experience.

Liver biopsy is the gold standard for diagnosing and staging liver diseases. Endoscopic ultrasound-guided liver biopsy (EUS-LB) has been reported in adults with equivalent or better safety profiles than percutaneous liver biopsies. The aim of this study was to retrospectively assess the safety and efficacy of EUS-LB in pediatric patients. This was a retrospective chart review of consecutive pediatric patients undergoing EUS-LB at Cincinnati Children's Hospital Medical Center from March 2020 to April 2023. Patients ≤21 years old were included. EUS-LB was performed via fine-needle biopsy technique with transduodenal and/or transgastric approach. Histology was independently reviewed by one of two expert pathologists, including length (cm) and complete portal tract (CPT) number per the American Association for the Study of Liver Diseases (AASLD) adequacy criteria. Demographics, clinical data, technical information, diagnostic success, and adverse events were recorded. Eighty-three patients were included in the analysis, with various indications that required liver biopsy. All biopsies achieved diagnostic and technical success, with 77 (93%) meeting both AASLD criteria for adequacy. Most patients (57, 69%) underwent biopsy of both hepatic lobes, with an overall median of two needle passes. Total specimen length was a median of 7.9 cm (interquartile range [IQR] 5.2-10.3), and the median maximum intact specimen was 4.2 cm (IQR 3.1-5.4). The median CPT number was 24 (IQR 17-32) per patient. Four mild adverse events (5%) occurred; none involved bleeding. EUS-LB was well tolerated and yielded samples that were technically and diagnostically successful in a pediatric population, with comparable safety to percutaneous liver biopsy.

Autotaxin: A Potential biomarker for primary biliary cholangitis

BackgroundIn some patients especially those AMA negative, the diagnosis may be a challenge requiring liver biopsy. This study determined whether autotaxin, a secreted lysophospholipase D encoded by the exonucleotide pyrophosphatase phosphodiesterase 2 gene, can be used as a serum biomarker for primary biliary cholangitis. MethodsPlasma samples were collected from 103 patients with PBC and 74 healthy controls. autotaxin levels were determined by Enzyme-linked immunosorbent assay, and its predictive value for diagnosing primary biliary cholangitis was analysed. The relationship between autotaxin and the clinical data was also evaluated. ResultsAutotaxin levels in patients with primary biliary cholangitis were significantly higher than those in healthy control (median: 60.7 ng/ml vs. 32.6 ng/ml, P < 0.001). The cut-off value of autotaxin in patients with primary biliary cholangitis was 38.5 ng/ml, and the positivity rate was 33.9 %, calculated twice. The sensitivity, specificity, positive predictive value, and negative predictive value were 54.3 %, 93.1 %, 84.4 %, and 74.8 %, respectively, and the area under the curve was 0.73. Autotaxin level positively correlated with immunoglobulin M level (r = −0.22, P < 0.05) and Ludwig's classification (r = 0.76, P < 0.01) in patients with primary biliary cholangitis. The positivity rate of autotaxin (50.0 %) was higher than that of anti-sp100 (16.7 %) and anti-gp210 (11.1 %) antibodies in anti-mitochondrial antibody -negative patients with primary biliary cholangitis. ConclusionsAutotaxin may be an effective noninvasive biomarker used in diagnosis, prognosis of primary biliary cholangitis, particularly in anti-mitochondrial antibody -negative patients.

THU384 Too Sweet To Digest; A Case Of Persistent Lactic Acidosis Secondary To Glycogenic Hepatopathy

Abstract Disclosure: T. Ayub: None. L.A. Robles: None. F. Sami: None. S. Saleem: None. S. Guntupalli: None. Glycogenic hepatopathy (GH) is an under-recognized cause of persistent lactic acidosis and hepatomegaly in patients with uncontrolled DM and diabetic ketoacidosis (DKA). A 19-year-old female with history of type 1 DM with recurrent DKA presented with complaints of nausea, vomiting and abdominal pain for 1 week. Physical exam showed normal vitals and lower abdominal tenderness. Her initial labs showed glucose 250 mg/dl, high anion gap metabolic acidosis with beta hydroxy butyrate of 11.3 mmol/l, lactic acid 3.2mm/l, and mild transaminitis. She was diagnosed with DKA and started on insulin drip. Anion gap responded to IV insulin and fluid therapy and was transitioned to SQ insulin. However, she had increase in her lactic acid (8.2mm/l), without hemodynamic compromise, despite fluid resuscitation. Secondary work up including blood, urine, sputum cultures were non diagnostic for an infectious etiology. Abdominal imaging showed a liver span of 26 cm. There were no signs of end organ hypoperfusion, medication or toxin mediated insult as evident by normal transthoracic echo, iron studies, urine drug screen, alcohol level and negative hepatitis panel. Review of prior hospitalizations showed recurrent episodes of DKA with similar uptrend in lactic acid levels with negative secondary work up. Prior imaging revealed hepatomegaly during DKA episodes with resolution after strict glycemic control. Given uncontrolled DM type 1 with reversible and recurrent hepatomegaly, transaminitis, hyperlipidemia and elevated lactic acid, a clinical diagnosis of glycogenic hepatopathy was made. Patient declined liver biopsy due to concerns for complications. She was discharged on home insulin regimen with outpatient follow up. GH or hepatic glycogenosis is a reversible cause of lactic acidosis and hepatomegaly seen in uncontrolled DM type 1. Pathogenesis involves presence of fluctuating levels of hyperglycemia and insulin, concomitantly, that leads to glycogen storage. Insulin inhibits gluconeogenesis resulting in decreased conversion of pyruvate to glucose and high lactic acid levels, in the absence of any infectious, metabolic and hypoxic etiology. Lactic acidosis can be worsened when treated with high dose Insulin. Definite diagnosis of GH requires liver biopsy or gradient dual-echo MRI but can be made clinically in the setting of uncontrolled DM1, hepatomegaly, transaminitis and elevated lactic acid levels. Prompt recognition of GH can prevent unnecessary diagnostic testing and can decrease the duration of hospital stay. Treatment is strict glycemic control with resolution of condition and no long-term complications. Presentation: Thursday, June 15, 2023

Expedited Laparoscopic Cholangiogram and Liver Biopsy in the Workup of Biliary Atresia.

Recent studies demonstrate the success of Kasai portoenterostomy for biliary atresia (BA) is linearly related to infant age at time of Kasai. We sought to review the feasibility and safety of laparoscopic needle micropuncture cholangiogram with concurrent core liver biopsy (if needed) for expedited exclusion of BA in patients with direct conjugated hyperbilirubinemia. Expedited laparoscopic cholangiogram and liver biopsy were instituted at our facility for infants with direct hyperbilirubinemia for whom clinical exam and laboratory workup failed to diagnose. A retrospective chart review was performed in infants <1 year with hyperbilirubinemia from 2016 to 2021. Demographics, preoperative evaluation, procedure details, and complications were reviewed. Two hundred ninety-seven infants with unspecified jaundice were identified, of which, 86 (29%) required liver biopsy. Forty-seven percutaneous liver biopsies were obtained including 8 (17%) in whom BA could not be excluded. Laparoscopic cholangiogram was attempted in 47 infants following basic workup; BA was diagnosed in 22 infants (47%) of which 3 were <18 days old. Biliary patency was demonstrated laparoscopically in 22 of 25 (88%); 3 (12%) required conversion to open cholangiogram. Infants with percutaneous liver biopsy had an average delay of 3 days (range: 2-36) to cholangiogram. Preoperative studies and liver biopsy alone did not reliably exclude the diagnosis of BA. Laparoscopic cholangiogram with liver biopsy is a safe procedure resulting in the confirmation or exclusion of BA in infants. Forty-seven percent of infants who underwent laparoscopic cholangiogram were found to have BA; those who were surgical candidates underwent Kasai during the same operation.

Development and validation of a video-assisted liver biopsy technique using a minimally-invasive device

BackgroundPercutaneous liver biopsy is the gold standard technique for establishing the cause of cirrhosis and liver disease activity assessment. However, some cases of steatohepatitis or other chronic liver diseases show a high number of false negative results in samples obtained via the percutaneous route. This fact justifies performing a liver biopsy via the laparoscopic route. However, this is an expensive technique, with morbidities associated with pneumoperitoneum and anesthetic complications. The main objective of this study is to develop a video-assisted technique that uses only a minimally-invasive device for the liver biopsy and the optical trocar. Without additional trocars, this technique constitutes a less invasive procedure than the existing techniques in clinical practice.MethodsThis is a device development and validation study and patients submitted to abdominal laparoscopic surgery and required liver biopsy for moderate to severe steatosis were recruited. The patients were randomized into two groups: laparoscopic liver biopsy technique (n = 10, control group) and mini-laparoscopic liver biopsy technique (n = 8, experimental group). The times associated with procedure performance in both groups were evaluated using the Mann–Whitney or Kruskal–Wallis tests according to data distribution.ResultsAt baseline, there was no statistical difference regarding gender and type of surgery. The experimental group had a significantly shorter time compared with the group that underwent the traditional procedure in mean procedure time (p = 0.003), biopsy time (p = 0.002) and hemostasis time (p = 0.003).ConclusionsThe mini-laparoscopic biopsy device and technique showed to be capable of safely obtaining sufficient tissue samples, which was minimally invasive and in a shorter time than the classic technique.

Controlled attenuation parameter-insulin resistance (CIR) score to predict non-alcoholic steatohepatitis

The diagnosis of non-alcoholic steatohepatitis (NASH) requires liver biopsy. Patients with NASH are at risk of progression to advanced fibrosis and hepatocellular carcinoma. A reliable non-invasive tool for the detection of NASH is needed. We aimed at developing a tool to diagnose NASH based on a predictive model including routine clinical and transient hepatic elastography (TE) data. All subjects undergoing elective cholecystectomy in our center were invited to participate, if alcohol intake was < 30 g/d for men and < 15 g/d for women. TE with controlled attenuation parameter (CAP) was obtained before surgery. A liver biopsy was taken during surgery. Multivariate logistic regression models to predict NASH were constructed with the first 100 patients, the elaboration group, and the results were validated in the next pre-planned 50 patients. Overall, 155 patients underwent liver biopsy. In the elaboration group, independent predictors of NASH were CAP value [adjusted OR (AOR) 1.024, 95% confidence interval (95% CI) 1.002–1.046, p = 0.030] and HOMA value (AOR 1.847, 95% CI 1.203–2.835, p < 0.001). An index derived from the logistic regression equation to identify NASH was designated as the CAP-insulin resistance (CIR) score. The area under the receiver operating characteristic curve (95%CI) of the CIR score was 0.93 (0.87–0.99). Positive (PPV) and negative predictive values (NPV) of the CIR score were 82% and 91%, respectively. In the validation set, PPV was 83% and NPV was 88%. In conclusion, the CIR score, a simple index based on CAP and HOMA, can reliably identify patients with and without NASH.

S3181 TB or Not TB? That Is the Question: A Case of Granulomatous Hepatitis

Introduction: Granulomatous hepatitis is characterized by the presence of granulomas within the liver parenchyma. This disease has multiple etiologies with the most common being primary biliary cholangitis and sarcoidosis in the US, and tuberculosis (TB) worldwide. Despite TB being a leading cause of granulomatous hepatitis globally, it is exceedingly rare to have presentation of this disease isolated in the liver without the presence of pulmonary or disseminated infection. Increased awareness of this presentation, especially in HIV/AIDs patients can lead to a decrease in unnecessary testing and procedures as well as, efficient resource allocation. Case Description/Methods: A 53-year-old female with a history of HIV, not on antiretrovirals (ARVs), presented with fever for several days, and was found to be septic secondary to pneumonia. After resolution of her acute illness, she was restarted on ARVs, and was doing well until she developed fevers of unknown origin and transaminitis. Leading differential diagnosis included immune reconstitution inflammatory syndrome, drug-induced liver injury, and autoimmune hepatitis. Initial work-up revealed an elevated ANA and anti-smooth muscle antibody. However, given the low antibody titers and marginal improvement with steroids it was determined that an autoimmune etiology was unlikely. Additional workup led to a liver biopsy which was significant for necrotizing granulomas favored to be tuberculous over necrotizing sarcoidosis by pathology. Although the acid fast bacillus stain was negative, the patient was started on empiric therapy for TB given a high clinical suspicion, and she subsequently had a significant decrease in her transaminases. Discussion: The diagnosis of granulomatous hepatitis presents a challenge given the multiple etiologies of the disease. This difficulty is confounded in the setting of uncontrolled HIV/AIDs, especially when the underlying causes is from TB without pulmonary or disseminated TB infection. Diagnosis requires liver biopsy, with the initial analysis including direct microscopic visualization; and AFB staining. The problem that arose in this case is that tissue stains have a relatively low sensitivity of ∼72.7%, and ∼88% with PCR. It is important for providers to acknowledge that these diagnostic tests are not infallible, and the clinical context and medical history surrounding the patient can be the most important factor in clinical decision making when these test fail to yield the expected results.

Noninvasive fibrosis tools in NAFLD: validation of APRI, BARD, FIB-4, NAFLD fibrosis score, and Hepamet fibrosis score in a Portuguese population

ABSTRACT Objectives The burden of nonalcoholic fatty liver disease (NAFLD) is increasing, with an estimated prevalence in Europe of 20–30%. Although most patients present with simple steatosis, some progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Definite diagnosis and staging require liver biopsy, which is not feasible given the high prevalence of NAFLD. As such, several noninvasive tools have been formulated. However, to date, none have been validated in the Portuguese population. The aim of this study was to determine the diagnostic accuracy of the aspartate aminotransferase to platelet ratio (APRI), the BMI, AST/ALT ratio and Diabetes (BARD), the FIB-4 Index (FIB-4), the Hepamet fibrosis score (HFS), and the NAFLD fibrosis score (NFS) in a Portuguese population. Methods A retrospective review of liver biopsies from two hospital centers was performed. Patients with NAFLD and no decompensated cirrhosis, liver cancer, or terminal illness were included. APRI, BARD, FIB-4, HFS, and NFS were calculated for each patient. Results A total of 121 individuals were included, of which 21.5% had advanced fibrosis (F ≥ 3). There was a moderate or high correlation between most tools. The negative predictive factor (NPV) and area under receiver operating curve (AUROC) were 89.9% and 0.80 for APRI, 91.8% and 0.84 for BARD, 95.7% and 0.88 for FIB-4, 96.4% and 0.88 for HFS, and 93.0% and 0.86 for NFS, respectively. Conclusion The tools analyzed had excellent performance (AUROC ≥ 0.80) and were adequate for ruling out advanced fibrosis (NPV ≥ 89.9%) in a Portuguese population. As such, they are adequate for use in clinical practice or as a part of referral and follow-up programs wherever this population is treated. Abbreviations APRI – aspartate aminotransferase to platelet ratio, ALT – alanine aminotransferase, AST – aspartate aminotransferase, BARD – BMI, AST/ALT ratio and Diabetes, BMI – body mass index, FIB-4 – FIB-4 index, HCC – hepatocellular carcinoma, HFS – Hepamet fibrosis score, HOMA-IR – homeostatic model assessment for insulin resistance, IQR – interquartile range, MAFLD – metabolic associated fatty liver disease, NAFLD – nonalcoholic fatty liver disease, NASH – nonalcoholic steatohepatitis, NFS – NAFLD fibrosis score, OMIC – genomics, transcriptomics, proteomics, and metabolomics, T2DM – type 2 diabetes mellitus

Assessing liver fibrosis in all patients with type 2 diabetes and fatty liver disease: It's time to act now.

Assessing liver fibrosis in all patients with type 2 diabetes and fatty liver disease: It's time to act now.

Selective Isolation of Liver-Derived Extracellular Vesicles Redefines Performance of miRNA Biomarkers for Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Definitive diagnosis of the progressive form, non-alcoholic steatohepatitis (NASH), requires liver biopsy, which is highly invasive and unsuited to early disease or tracking changes. Inadequate performance of current minimally invasive tools is a critical barrier to managing NAFLD burden. Altered circulating miRNA profiles show potential for minimally invasive tracking of NAFLD. The selective isolation of the circulating extracellular vesicle subset that originates from hepatocytes presents an important opportunity for improving the performance of miRNA biomarkers of liver disease. The expressions of miR-122, -192, and -128-3p were quantified in total cell-free RNA, global EVs, and liver-specific EVs from control, NAFL, and NASH subjects. In ASGR1+ EVs, each miR biomarker trended positively with disease severity and expression was significantly higher in NASH subjects compared with controls. The c-statistic defining the performance of ASGR1+ EV derived miRNAs was invariably >0.78. This trend was not observed in the alternative sources. This study demonstrates the capacity for liver-specific isolation to transform the performance of EV-derived miRNA biomarkers for NAFLD, robustly distinguishing patients with NAFL and NASH.

AGILE 3+ Score for Assessing Hepatic Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) – Validation in an Indian Cohort

Background: Non-invasive tests have emerged as important tools for ruling out the presence of advanced fibrosis in NAFLD. However, many patients still require liver biopsy due to the comparatively poor positive predictive value (PPV) and substantial grey-zone associated with non-invasive tests. AGILE-3+ score is a novel, non-invasive score which includes liver stiffness measurement (LSM) on transient elastography and commonly measured clinical parameters (age, gender, AST, ALT, platelet count and presence or absence of diabetes mellitus).

Improved pathology reporting in NAFLD/NASH for clinical trials

Non-alcoholic fatty liver disease (NAFLD), a disorder characterised by pathological accumulation of non-visible free fatty acids and visible triglyceride in hepatocytes, is on the rise globally in both adult and...

Hematological and biochemical characteristics and diagnostic imaging results in acute T cell–mediated rejection after pediatric liver transplantation

Liver biopsy is the gold standard for diagnosing TCMR after LT. However, complications caused by liver biopsy may occur especially during the immediate post-transplantation period and other effective methods for predicting TCMR have not been established. Thus, we investigated whether hematological and biochemical characteristics and Doppler ultrasonography findings are associated with acute TCMR. A multiple logistic regression analysis was performed to identify the prognostic factors of acute TCMR, defined as a RAI ≥4. Then, a ROC curve analysis was conducted to evaluate for diagnostic performance. The relationship between prognostic factors and each histological category of RAI was investigated. Eighty-nine liver biopsies were performed on 85 patients between January 2012 and December 2019. The RAI of 62 (69.7%) liver biopsies was ≥4. AEC (×104 /μl), direct bilirubin level (mg/dl), and MHVV (cm/s) were found to be associated with acute TCMR (OR: 4.96, 95% CI: 1.44-17.0, p=.011; OR: 1.41, 95% CI: 1.04-1.91, p=.025; OR: 1.05, 95% CI: 1.02-1.08, p<.001, respectively). The area under the ROC curves for predicting acute TCMR was 0.86 (95% CI: 0.78-0.94). There was a correlation between AEC, direct bilirubin level, and MHVV as well as the severity of RAI. AEC, direct bilirubin level, and MHVV were the independent risk factors for acute TCMR. This study could provide information regarding the identification of patients requiring liver biopsy.

Evidence-based clinicalpractice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020.

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary pro- vides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.

Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis

SummaryAutoimmune cholestatic liver diseases are rare hepato-biliary disorders characterized by a progressive, inflammatory destruction of bile ducts. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. Both may evolve into secondary biliary cirrhosis and its complications. Therapeutic options are limited and liver transplantation remains the only definitive treatment for PBC and PSC.Most PBC and PSC patients have a typical presentation, which does not require liver biopsy. However, in routine clinical practice, important variants or specific subgroups that benefit from liver biopsy for proper management may be observed. Herein, we provide a general overview of clinical and pathological characteristic of PBC and PSC, highlighting the most important features for routine diagnostic practice.

Transient Versus Two-Dimensional Shear-Wave Elastography in a Multistep Strategy to Detect Advanced Fibrosis in NAFLD.

The combination of laboratory and elastography tests allows the accurate diagnosis of advanced liver fibrosis in patients with NAFLD. In this study, we compared the diagnostic performances of a two-step strategy (laboratory tests and vibration-controlled transient elastography [VCTE] or two-dimensional shear-wave elastography with SuperSonic Imagine [2D-SWE-SSI]) and the added value of a three-step strategy (laboratory tests and two elastography methods). From a prospective registry, we retrospectively selected 577 consecutive patients with suspicion of NAFLD who underwent laboratory tests to calculate the Fibrosis-4 (FIB-4) score, liver stiffness evaluation by VCTE (M and XL probes) and 2D-SWE-SSI, and liver biopsy. The diagnostic performances and need for liver biopsy in unclassified patients for the diagnosis of advanced fibrosis (F≥3) in multistep strategies were compared. The area under the curve of FIB-4, VCTE, and 2D-SWE-SSI was 0.74, 0.82, and 0.88, respectively. Using the same thresholds, the FIB-4/2D-SWE-SSI and FIB-4/VCTE diagnostic performances were comparable (sensitivity, 71.4% and 66%; specificity, 91.4% and 91.5%; and accuracy, 83.7% and 81.4%; all P=not significant). Conversely, more patients required liver biopsy after 2D-SWE-SSI (24.6% versus 15.3%, P<0.001). Performing a second elastography technique in patients with unreliable or gray zone (between 8 and 10kPa) results greatly decreased the need for liver biopsy (42/577, 7.3%). The diagnostic performances (accuracy, sensitivity, and specificity) of FIB-4/2D-SWE-SSI/VCTE and FIB-4/VCTE/2D-SWE-SSI were comparable (81.1%, 71.5%, and 87.9% versus 81.3%, 69.7%, and 89.5%, respectively; all P=not significant). Using the same cutoff values, 2D-SWE-SSI is as accurate as VCTE for advanced liver fibrosis diagnosis in NAFLD. The three-step strategy in selected patients strongly decreased the need for liver biopsy while maintaining excellent accuracy.

Abstract No. 87 Retrospective comparison of noninvasive evaluation of liver fibrosis and portal hypertension utilizing ultrasound shear wave elastography and FibroTest technologies with liver biopsy

Liver fibrosis is a progressive disease of varying etiologies affecting millions worldwide. Traditional management required liver biopsy for pathological fibrosis staging and monitoring using the METAVIR scale (F0 [normal] to F4 [cirrhosis]). More recently, noninvasive tests have been developed to help monitor progression of liver fibrosis. Our institution uses FibroTest (FT; BioPredictive, France), an algorithm using 6 laboratory values to calculate a FT score (0-1), and Shear Wave Elastography (SWE; GE, USA), an ultrasound evaluation of tissue stiffness via shear force measurements (kPa).

Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease.

Background and AimsNonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.MethodsA total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis.ResultsMetabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004–5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083–9.725, p<0.001) were significantly associated with advanced fibrosis. Using these two metabolic disorders as a screening tool, a sensitivity, specificity and accuracy of 92%, 81% and 83% was achieved, respectively. With the new algorithms combining metabolic disorders with noninvasive measurements, the number of patients requiring liver biopsy was reduced, especially in combination with the Fibrosis-4 score and metabolic disorders (36% to 17%, p<0.001). In addition, this stepwise algorithm could achieve a high accuracy (85%) and high negative predictive value (93%).ConclusionsMetabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis. With further validation and investigation, new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.

Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism

Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3+) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.

Biopsy rate and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD)

Background: Licensed therapies for nonalcoholic fatty liver disease (NAFLD) do not yet exist, but clinical trials are testing treatment options. Inclusion criteria often require liver biopsy showing fibrosis (F2/3) or cirrhosis (F4) and nonalcoholic steatohepatitis (NASH). However, histological criteria pose a serious obstacle for recruitment.Aims: Characterize the relevance of liver biopsies in the selection of patients with NAFLD.Methods: Patients between 2013 and 2018 with the ICD-10 code K76.0 were analyzed. Fibrosis was defined by the NASH clinical research network (CRN) fibrosis staging system, NASH by a NAFLD activity score (NAS) ≥4. Predictive factors were determined by logistic regression.Results: Liver biopsy was performed in 87/638 (13.6%) patients (49% female, age 52.5 ± 14.0, BMI 30.4 ± 5.9 kg/m2). Fibrosis stage F0/F1/F2/F3/F4 was observed in N = 7/47/7/17/9, an NAS ≥4 in N = 27. Fibrosis stage F2/F3 and F4 along with NAS ≥4 was found in 1.7% and 0.5% of cases. Liver stiffness measurement, LSM (OR 2.3 per doubling of value; CI 1.3–4.4, p = .005) and FIB-4 (OR 2.3 per doubling of value; CI 1.2–4.4, p = .012) were significant predictors for fibrosis ≥ F2. Predictive factors for NASH were not identified.Conclusion: The biopsy rate in NAFLD patients is low and fibrosis ≥ F2 along with NAS ≥4 only present in a few cases. Transient elastography and FIB-4 are useful to select patients at risk for fibrosis for liver biopsy.