Liver Biopsy Results Research Articles

Identification of hepatic steatosis in living liver donors by machine learning models.

Selecting an optimal donor for living donor liver transplantation is crucial for the safety of both the donor and recipient, and hepatic steatosis is an important consideration. We aimed to build a prediction model with noninvasive variables to evaluate macrovesicular steatosis in potential donors by using various prediction models. The study population comprised potential living donors who had undergone donation workup, including percutaneous liver biopsy, in the Republic of Korea between 2016 and 2019. Meaningful macrovesicular hepatic steatosis was defined as >5%. Whole data were divided into training (70.5%) and test (29.5%) data sets based on the date of liver biopsy. Random forest, support vector machine, regularized discriminant analysis, mixture discriminant analysis, flexible discriminant analysis, and deep neural network machine learning methods as well as traditional logistic regression were employed. The mean patient age was 31.4 years, and 66.3% of the patients were men. Of the 1652 patients, 518 (31.4%) had >5% macrovesicular steatosis on the liver biopsy specimen. The logistic model had the best prediction power and prediction performances with an accuracy of 80.0% and 80.9% in the training and test data sets, respectively. A cut‐off value of 31.1% for the predicted risk of hepatic steatosis was selected with a sensitivity of 77.7% and specificity of 81.0%. We have provided our model on the website (https://hanseungbong.shinyapps.io/shiny_app_up/) under the name DONATION Model. Our algorithm to predict macrovesicular steatosis using routine parameters is beneficial for identifying optimal potential living donors by avoiding superfluous liver biopsy results.

The Correlation of Mean Platelet Volume and Neutrophil-lymphocyte Ratio Measurements, and the Ishak Fibrosis Score in Our Patients with Chronic Hepatitis B

Background:The ishak score determined by liver biopsy is the most reliable indicator of fibrosis, but biopsy is an invasive procedure. Numerous noninvasive tests have been investigated to determine the hepatic fibrosis score. We aimed to investigate the relationship between the mean platelet volume(MPV) and neutrophillymphocyte ratio (NLR) measurements in patients with chronic hepatitis B virus (CHB) infection, and liver fibrosis stage, which was determined by biopsy and ishak score. Material and Method:CHB patients followed between 2016 and 2020 in our gastroenterology outpatient clinic were included in our study. CHB patients; They were divided into two groups as non-cirrhotic group (ishak fibrosis score in biopsy; F0-F4) and cirrhotic group (F5-F6). Then, 30 healthy control (HC) groups consisting of health personnel who had routine health screenings and blood tests in the same period were formed. MPV, NLR measurements of these two main groups and CHB subgroups and liver biopsy results of CHB patients were evaluated retrospectively, and possible relationships between the groups were investigated. Results:There was no statistically significant difference between the mean age and gender of the cases in the CHB and HC groups. A total of 54 patients with CHB were identified, of which 13 patients were cirrhotic and 41 patients were non-cirrhotic. MPV measurements were found to be significantly higher in the CHB group than in the SC group (11.15±1.77; 10.02±0.92; p=0.002). While there was no significant difference between NLR measurements, it was found to be higher in the CHB group (1.98±0.81; 1.81±0.69). While there was no significant difference between the cirrhotic and non-cirrhotic subgroups of the CHB group in terms of NLR (1.86±0.68; 2.36±1.04) and MPV (11.09±1.89; 11.35±1.36) measurements, NLR and MPV measurements were higher in the cirrhotic group. Conclusion:In our study, MPV values were found to be significantly increased in patients in the CHB group compared to the HC group. In addition, although not statistically significant, NLR and MPV measurements were found to be higher in the cirrhotic group than in the non-cirrhotic group. According to our study, it can be thought that with increasing MPV and NLR measurements in HBV patients, there may be an increase in chronicity and fibrosis scores without an invasive procedure such as biopsy.

Analysis of the sensitivity and specificity of ultrasound elastometry of the liver in women with chronic hepatitis C

Introduction. Despite the success in the treatment of chronic hepatitis C (HCV), the incidence of HCV remains at a high level, and the assessment of the degree of liver fibrosis is relevant in all patients with HCV.The aim of the study was to conduct a comparative diagnosis of the stages of liver fibrosis in women with chronic hepatitis C according to ultrasound elastometry and biopsy.Materials and Methods. To achieve this goal, a comprehensive clinical, laboratory (including virological), instrumental examination of 93 patients with HCV of reproductive age was conducted.Results. When interpreting the results, it was found that ultrasound elastometry in women with chronic hepatitis C is comparable to the results of percutaneous puncture liver biopsy.Discussion. Chronic hepatitis causes significant economic damage to health systems. The main factor affecting the reduction of morbidity and the risk of complications is the early diagnosis of HCV infection and timely antiviral therapy. The main objective of therapy is to achieve a stable virological response (SVR), as well as to reduce the activity of inflammation and the stage of AF in patients with HCV. The isolated use of serum markers of fibrosis and ultrasound elastometry of the liver at the early stages of the disease is not informative enough, so it is advisable to use a combination of different techniques, and at the CP stage, a puncture biopsy can be safely replaced with ultrasound elastometry of the liver, especially for the purpose of dynamic monitoring of patients with HCV.Conclusion. According to the comparative ROC-analysis of the results of ultrasound elastography and puncture liver biopsy, the high sensitivity and specificity of these methods for diagnosing liver fibrosis was established. The comparability of ultrasound elastography of the liver with the results of puncture biopsy, in young women, increases with the progression of liver fibrosis, and can be used to determine its degree.

Metabolomic profiling and discrimination of autoimmune hepatitis, primary biliary cholangitis, and overlap syndrome

<p indent="0mm">Autoimmune liver disease (AILD) is a kind of liver disease caused by immune dysfunction, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and overlap syndrome (OS). In AILD patients, the immune system attacks the liver, and elevated autoantibodies can be found in serum. AIH and PBC are two kinds of AILD with high incidence, and their pathogenesis is different. AIH is characterized by interfacial hepatitis caused by the autoimmune system attacking hepatocytes. The clinical features of PBC are non-suppurative, destructive cholestasis resulting from immune damage affecting the interlobular bile ducts. Due to the complex and promiscuous pathogenesis of autoimmune diseases and the low specificity of clinical features, challenges remain in the clinical diagnosis of AILD. Liver biopsy results are necessary for the accurate diagnosis of AILD, but biopsy is not conducive to the prognosis of patients, and the pathological changes of patients may be non-specific. Therefore, the need of finding serological metabolites with low high specificity and invasive features becomes urgent. Metabolomics has unique advantages in reflecting the overall pathophysiological changes of the body by analyzing the metabolites. Untargeted metabolomics has been widely used in the study of liver-related diseases and has good application value for clinical diagnosis. In this study, we attempted to characterize the metabolic signatures of autoimmune liver diseases by serum metabolomics. A mass spectrometry-based untargeted metabolomics study was performed on the serum of AIH (<italic>n</italic>=42), PBC (<italic>n</italic>=103), and AIH-PBC OS (<italic>n</italic>=57) patients. The differentiable metabolites for PBC and AIH samples were obtained by principal component analysis and orthogonal partial least-squares-discriminant analysis, which consisted of the metabolomic signatures. Among the metabolomic signatures, the fingerprint metabolites were further extracted by clustering analysis using the values of area under the curve (AUC) of each differentiable metabolite, binary logistic regression model, and variable importance projection scores. 101 signature metabolites from all metabolite variables were identified, and 29 fingerprint metabolites were further screened out and enriched in bile, phospholipids, and amino acids metabolisms pathway, with most classification ability to distinguish PBC and AIH. The eigenmetabolite compressed from the fingerprint metabolites visualized the significant difference between PBC and AIH (<italic>P</italic>&lt;0.0001) and achieved a good potential for classification (AUC=0.797). Based on fingerprint metabolites, AIH and PBC samples could be separated into three zones, the “pure zone” of PBC, the “pure zone” of AIH, and the mixture zone of PBC and AIH. We put OS samples into the model and found that samples showed different distribution characteristics in three zones, indicating that OS patients according to the current diagnostic criteria have different metabolic characteristics and etiological tendencies, requiring a more accurate diagnosis. This study revealed a metabolic outlook for AIH, PBC, and their overlap syndrome, and the diagnostic model based on fingerprint metabolites with the potential ability to facilitate precise diagnosis and management of patients with autoimmune liver diseases.

Studying the correlation between ferritin and non-alcoholic fatty liver disease

Objective: To analyze the correlation between serum ferritin and steatosis in non-alcoholic fatty liver disease. Methods: Data of 167 cases who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were collected. Hydrogen proton magnetic resonance spectroscopy were performed within one week. The pathological results of liver biopsy were used as the gold standard to analyze the case data, serological indicators, magnetic resonance spectroscopy-proton density fat fraction. Results: Pathological monitoring result showed that the serum ferritin in patients without steatosis, and with mild, moderate and severe steatosis were (206.20 ± 189.83), (286.65 ± 200.80), (326.55 ± 214.71), (391.50 ± 184.93) ng/ml, respectively, P < 0.005. Serum ferritin was correlated to body mass index, PDFF, alanine aminotransferase, gamma glutamyltransferase, low-density lipoprotein, high-density lipoprotein. The area under ​​the receiver operating characteristic curve with ferritin for the diagnosis of non-alcoholic fatty liver disease was 0.716, and the optimal diagnostic threshold was 214.56 ng/ml. The sensitivity and specificity were 80.1%, and 68.8%, respectively. There was no statistically significant difference between the intralobular inflammation, fibrosis, and ferritin. Prussian blue iron staining had no apparent deposition of iron particles. Conclusion: Ferritin has significant positive correlation with the results of pathological and magnetic resonance imaging for liver steatosis. Therefore, it can be used as a non-invasive diagnostic method for liver steatosis evaluation.

O-02: Elastography for the Diagnosis and Graduation of Liver Disease in Patients with Long Term Parenteral Nutrition

Introduction: Liver disease is a major complication in long-term parenteral nutrition (PN) and its diagnosis usually depends on liver biopsy. Noninvasive methods such as transient elastography (TE) simplified the diagnosis and graduation of chronic liver disease; however, there are few studies assessing TE in liver dysfunction associated to long-term PN. HC-FMUSP is one of the world pioneer and reference of home PN and intestinal transplantation in Brazil (1-3). Our aim was to compare the results of TE and liver biopsy for the diagnosis and staging of liver disease due to long-term PN in a single center. Method: Patients from HC-FMUSP presenting liver dysfunction associated to long-term PN were included in this survey. Liver injury degree assessed by TE and biopsy (Brunt’s method) were classified as grade I, II, III e IV. TE and histological graduation values of liver disease for each patient were compared by Bland -Altman and Fisher’s statistical tests. Results: From the period between 2017 to 2019, twenty adults (8 female / 12 male) with long-term PN were selected for this study. Median time of patient’s PN use was 30.5 months. They all presented liver dysfunction observed by abnormal image exams and liver enzymes blood test. We observed in these patients a high agreement rate of liver injury graduation using both, TE and histology analysis by biopsy with Kappa index of 0.839 (p <0.005). Conclusion: In the current study we observed that TE is correlated with liver biopsy and histological analysis to assess liver disease associated with long-term PN.

Demonstration of the protective effect of ghrelin in the livers of rats with cisplatin toxicity.

Despite the various and newly developed chemotherapeutic agents in recent years, cisplatin is still used very frequently as a chemotherapeutic agent, even though cisplatin has toxic effects on many organs. The aim of our study is to show whether ghrelin reduces the liver toxicity of cisplatin in the rat model. Twenty-eight male Sprague Dawley albino mature rats were chosen to be utilized in the study. Group 1 rats (n = 7) were taken as the control group, and no medication was given to them. Group 2 rats (n = 7) received 5 mg/kg/day cisplatin and 1 ml/kg/day of 0.9% NaCl, Group 3 rats (n = 7) received 5 mg/kg/day cisplatin and 10 ng/kg/day ghrelin, Group 4 rats (n = 7) received 5 mg/kg/day cisplatin and 20 ng/kg/day ghrelin for 3 days. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), plasma alanine aminotransferase (ALT) levels, and liver biopsy results were measured in rats. It was determined that, especially in the high-dose group, the MDA, plasma ALT, and SOD levels increased less in the ghrelin group as compared to the cisplatin group, and the glutathione level decreased slightly with a low dose of ghrelin, while it increased with a higher dose. In histopathological examination, it was determined that the toxic effect of cisplatin on the liver was reduced with a low dose of ghrelin, and its histopathological appearance was similar to normal liver tissue when given a high dose of ghrelin. These findings show that ghrelin, especially in high doses, can be used to reduce the toxic effect of cisplatin.

Association Between Hepatic Steatosis and Metabolic Syndrome in Patients With Non-alcoholic Fatty Liver Disease

ObjectivesEvaluate the association between the degree of hepatic steatosis and the development of metabolic syndrome in outpatients care. MethodsProspective cross-sectional study with outpatients care at the Gastroenterology Service of a hospital in southern Brazil. The study was approved by the Ethics Committee with protocol 57,328,416.8.0000.5335. Patients aged over 18 years and with non-alcoholic fatty liver disease were included. Patients were excluded from hepatitis B and C, with significant alcohol consumption and hepatocellular carcinoma. Data collection occurred during nutritional consultations, where we collected data of age, gender, lifestyle, diagnosis of comorbidities and biochemical tests. The result of liver biopsy was evaluated for the degree of hepatic steatosis. Anthropometric parameters were assessed for the diagnosis of metabolic syndrome, in addition to electrical bioimpedance for body composition. Data were presented as mean, median, standard deviation, interquartile range and percentages according to distribution. Student T, ANOVA and Pearson correlation tests were applied. The significance level was 5%. ResultsWe evaluated 71 patients with mean age 59.08 ± 8.92 years, 67.6% (n = 48) women, 60.6% (n = 43) sedentary, 52.2% (n = 37) no smoking and mean body mass index of 32.91 ± 5.27 kg/m2. Systemic arterial hypertension were diagnosed in 80.3% (n = 57), 73.2% (n = 52) were diabetic, 66.2% (n = 47) were dyslipidemic and 28.2% (n = 20) of patients with metabolic syndrome. As liver biopsy, 25.4% (n = 18) mild steatosis, 23.9% (n = 17) moderate and 26.8% (n = 19) intense. In the comparison between the levels of hepatic steatosis and the variables, it was observed that patients with severe steatosis had metabolic syndrome (p = 0.041). Patients with metabolic syndrome have higher fat mass (p = 0.044), diastolic blood pressure (p = 0.019) and higher levels of serum triglycerides (p = 0.043). Severe hepatic steatosis correlated with the diagnosis of metabolic syndrome (r = 0.319; p = 0.019). ConclusionsSevere hepatic steatosis is related to the diagnosis of metabolic syndrome.Patients with metabolic syndrome had a higher amount of fat mass, increased diastolic blood pressure and serum triglycerides. Funding SourcesThis study was not funded.

Validating controlled attenuation parameter in the assessment of hepatic steatosis in living liver donors.

Hepatic steatosis (HS) negatively impacts transplant outcomes in living liver donors. To date, liver biopsy is preferred for HS evaluation. This study aims to evaluate the measurement of controlled attenuation parameter (CAP) as a diagnostic tool of HS in living liver donors. Candidates recruited to this study, conducted from April 2016 to February 2020, were potential donors who had undergone transient elastography using Fibroscan® and CAP measurements at liver segments VI and VII, followed by liver biopsy. The HS grades from liver biopsy were classified as S0 (<5%), S1 (5-33%), S2 (33-66%), and S3 (>66%). For CAP, they were S0 (≤218dB/m), S1 (218-249dB/m)), S2 (250-305dB/m)), and S3 (>305dB/m)). The CAP measurements were compared with the liver biopsy results. Of the 150 potential donors [male, 73.3%; mean age, 30.0±7.0 years; body mass index (BMI), 24.7±3.5kg/m2], 92 (61.3%) had no or mild HS, while 58 (38.7%) and 10% had moderate to severe HS based on CAP and liver biopsy, respectively. Subjects with moderate to severe HS per CAP were mostly males (0.014), and had higher BMI (p = .006), alanine aminotransferase (ALT) (.001), gamma-glutamyl transferase (.026), and high-density lipoprotein (.008). On multivariate analysis, high ALT (OR, 1.051; 95% CI, 1.016-1.087; p = .004) was a predictor of significant HS. The sensitivity, specificity, positive and negative predictive values of CAP to detect significant HS were 93.3%, 67.4, 24.1%, and 98.9%, respectively. The high sensitivity and negative predictive values of CAP make it a good screening test to exclude significant HS in potential living liver donors which, in turn, can help avoid unnecessary liver biopsies.

Validation of a machine learning approach using FIB-4 and APRI scores assessed by the metavir scoring system: A cohort study

Background and Study AimThe study aim was to improve and validate the accuracy of the fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) scores for use in a potential machine-learning (ML) method that accurately predicts the extent of liver fibrosis. Patients and MethodsThis retrospective multicenter study included 69,106 patients with chronic hepatitis C planned for antiviral therapy from January 2010–December 2014 with liver biopsy results. FIB-4 and APRI scores were calculated and their performance for predicting significant liver fibrosis (F3–F4) assessed against the Metavir scoring system. ML was used for feature selection and reduction to identify the most relevant attributes (CfsSubseteval/best first) for prediction. ResultsIn this study, 57,492 (83.2%) patients were F0–F2, and 11,615 (16.8%) patients were F3–F4. The revalidation of FIB-4 and APRI showed lower accuracy and higher disagreement with the biopsy results, with AUCs of 0.68 and 0.58, respectively. FIB-4 diagnosed fewer (14%) F3–F4 patients, and the high specificity and negative predictive values of FIB-4 and APRI reflected the low prevalence of F3–F4 in the study population. Out of 15 attributes, age (>35 years), AFP (>6.5 ng/ml), and platelet count (<150,000/mm3) were the most relevant risk attributes, and patients with one or more of these risk factors were likely to be F3–F4, with a classification accuracy of ≤ 92% and receiver operating characteristics area of 0.74. ConclusionFIB-4 and APRI scores were not very accurate and missed diagnosing most of the F3–F4 patients. ML implementation improved medical decisions and minimized the required clinical data to three risk factors.

The role of quantitative HBsAg in patients with HBV DNA between 2000-20,000 IU/ml.

We aimed to determine the contribution of quantitative HBsAg in differentiating chronic infections from chronic hepatitis in HBeAg negative patients with HBV DNA 2000-20,000 IU/ml. Atotal of 79untreated HBeAg negative patients were included. Patients were divided into 3groups based on HBV DNA levels: group1 (HBV DNA ≤ 2000 IU/ml), group2 (HBV DNA: 2000-20,000 IU/ml) and group3 (HBV DNA > 20,000 IU/ml). We collected serum from all patients for quantitative HBsAg analysis. We compared serum quantitative HBsAg levels with biochemical parameters, HBV DNA and liver biopsy results. In this study 46 patients were female and the mean age was 42years. Serum quantitative HBsAg levels were found to be significantly lower in chronic infections compared with chronic hepatitis. There was apositive correlation between quantitative HBsAg and HBV DNA, ALT (alanine aminotransferase), HAI score (histological activity index), fibrosis score and disease stage. The cut-off level of quantitative HBsAg was determined as 4425 IU/ml to differentiate chronic infection from chronic hepatitis. With the test specificity of 95%, we found quantitative HBsAg cut-off values 1026 IU/ml and 20,346 IU/ml for the diagnosis of chronic infection and chronic hepatitis, respectively. Our study suggests that the quantitative HBsAg ≤ 1000 IU/ml limit value might be used for the diagnosis of chronic infection not only in HBV DNA ≤ 2000 IU/ml but also in patients with HBV DNA between 2000-20,000 IU/ml. In addition, antiviral treatment could be considered in patients with quantitative HBsAg > 20,000 IU/ml and HBV DNA > 2000 IU/ml without further examinations such as liver biopsy.

Cardiac Morphology, Function, and Hemodynamics in Patients With Morbid Obesity and Nonalcoholic Steatohepatitis.

BackgroundThe patients with nonalcoholic fatty liver disease demonstrate an increased cardiovascular risk. The adverse influence of liver abnormalities on cardiac function are among many postulated mechanisms behind this association. The aim of the study was to evaluate cardiac morphology and function in patients with morbid obesity referred for bariatric surgery with liver biopsy.Methods and ResultsWe evaluated with echocardiography 171 consecutive patients without known cardiac disease (median age 42 [interquartile range, 37–48] years, median body mass index 43.7 [interquartile range, 41.0–47.5], 67% female patients. Based on the liver biopsy results, there were 44 patients with nonalcoholic steatohepatitis (NASH), 69 patients with isolated steatosis, and 58 patients without steatosis. Patients with NASH demonstrated signs of left ventricular concentric remodeling and hyperdynamic circulation, including indexed left ventricular end‐diastolic diameter [cm/m2]: NASH 1.87 [0.22]; isolated steatosis 2.03 [0.33]; without steatosis 2.01 [0.19], P=0.001; relative wall thickness: NASH 0.49±0.05, isolated steatosis 0.47±0.06, without steatosis 0.46±0.06, P=0.011; cardiac index [L/m2]: NASH 3.05±0.54, isolated steatosis 2.80±0.44, without steatosis 2.79±0.50, P=0.013. After adjustment for sex, age, blood pressure, and heart rate, most of the measures of the left ventricular systolic and diastolic function, left atrial size, right ventricular function, and right ventricular size did not differ between groups.ConclusionsIn a group of patients with extreme obesity, NASH was associated with left ventricular concentric remodeling and hyperdynamic circulation. Increased cardiac output in NASH may represent an additional risk factor for incident cardiovascular events in this population.

The efficacy of novel metabolic targeted agents and natural plant drugs for nonalcoholic fatty liver disease treatment: A PRISMA-compliant network meta-analysis of randomized controlled trials.

Background:Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis.Methods:Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed.Results:Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels.Conclusions:Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.

Usefulness of Preoperative Magnetic Resonance Spectroscopy to Improve the Safety of a Living Liver Donor

The steatosis of graft liver is an important factor in liver transplant that determines the graft function in the recipient and the recovery of the remnant liver in the living donor. We analyzed the data of living donors from our center to evaluate whether magnetic resonance imaging and magnetic resonance spectroscopy can replace liver biopsy. From May 2010 to May 2019, data from a total of 239 living donors was collected. There were 84 patients who had no magnetic resonance imaging or magnetic resonance spectroscopy data, and they were excluded. The result of preoperative liver biopsy was compared with preoperative magnetic resonance imaging and magnetic resonance spectroscopy data. The steatosis was defined by the degree of macrosteatosis. The magnetic resonance imaging of the fat fraction was a good parameter to predict fatty changes between normal and fatty liver groups (3.09 ± 3.38% for normal 7.48 ± 4.07% for fatty liver; P < .001). The magnetic resonance spectroscopy was also a good parameter to predict fatty changes between normal and fatty liver groups (2.09 ± 1.43% for normal and 6.89 ± 2.68% for fatty liver; P < .001). Linear regression showed that pathology results were significantly correlated with magnetic resonance spectroscopy (P < .001, R2 = 0.604) but not with magnetic resonance imaging (P < .001, R2 = 0.227). Magnetic resonance spectroscopy has several benefits for quantifying hepatic steatosis during a living donor liver transplant evaluation, including no radiation exposure, and a noninvasive procedure. Moreover, preoperative magnetic resonance spectroscopy can determine an anatomic variation of the bile duct, which helps improve the safety of the living donor. However, more clinical data and further studies are needed to ensure that preoperative magnetic resonance spectroscopy is essential.

Application of MRI-based Radiomics Models in the Assessment of Hepatic Metastasis of Rectal Cancer

To explore the clinical value of using radiomics models based on different MRI sequences in the assessment of hepatic metastasis of rectal cancer. 140 patients with pathologically confirm edrectal cancer were included in the study. They underwent baseline magnetic resonance imaging (MRI) between April 2015 and May 2018 before receiving any treatment. According to the results of liver biopsy, surgical pathology, and imaging, patients were put into two groups, the patients with hepatic metastasis and those without. T2 weighted images (T2WI), diffusion weighted images (DWI) and apparent diffusion coefficient (ADC) images were used to draw the region of interest (ROI) of primary lesions on consecutive slices on ITK-SNAP. 3-D ROIs were generated and loaded into Artificial Intelligent Kit for extraction of radiomics features and 396 features were extracted for each sequence. The feature data were preprocessed on Python and the samples were oversampled, using Support Vector Machine-Synthetic Minority Over-Sampling Technique (SVM-SMOTE) to balance the number of samples in the group with liver metastasis and the group with no liver metastasis at the end of the follow-up. Then, the samples were divided into the training cohort and the test cohort at a ratio of 2∶1. The logistic regression models were developed with selected radionomic features on R software. The receiver operating characteristics (ROC) curves and calibration curves were used to evaluate the performance of the models. In total, 52 patients with liver metastasis and 88 patients without liver metastasis at the end of follow-up were enrolled. Carcinoembryonic antigen (CEA) and T stage and N stage evaluated on the MRI images showed statistically significant difference between the two groups ( P<0.05). After data preprocessing and selecting, except for 17 non-radiomic features, the model combining T2WI, DWI and ADC features, the model of T2WI features alone, the model of DWI features alone and the model of ADC features alone were developed with 32 features, 10 features, 30 features and 15 features, respectively. The combined model (T2WI+DWI+ADC), the T2WI model, and the ADC model can assess hepatic metastasis accurately, with the area under curve ( AUC) on the train set reaching 93.5%, 89.2%, 90.6% and that of the test set reaching 80.8%, 80.5%, 81.4%, respectively. The combined model did not show a higher AUC than those of the T2WI and ADC alone models. Model based on DWI features has a slightly insufficient AUC of 90.3% in the train set and 75.1% in the test set. The calibration curve showed the smallest fluctuation in the combined model, which is closest fit to the diagonal reference line. The fluctuation in the three independent data set models were similar. The calibration curves of all the four models showed that as the risk increased, the prediction of the models turned from an underestimation to an overestimating the risk. In brief, the combined model showed the best performance, with the best fit to the diagonal reference line in calibration curve and high AUC comparable to the AUC of the T2WI model and ADC model. The performance of T2WI and ADC alone models were second to that of the combined model, while the DWI alone model showed relatively poor performance. Radiomics models based on MRI could be effectively used in assessing liver metastasis in rectal cancer, which may help determine clinical staging and treatment.

Alteration on hepatocyte nuclear factor 1α expressions and significance in the process of occurrence and development of liver inflammation and fibrosis in patients with chronic hepatitis B

Objective: To investigate the relationship between the expression of hepatocyte nuclear factor-1 α (HNF-1α) and the occurrence and development of liver inflammation and fibrosis in liver tissues of patients with chronic hepatitis B. Methods: Sixty-four patients with chronic hepatitis B who were diagnosed and treated in our hospital from 2011 to 2018 were selected. All patients underwent ultrasound-guided aspiration liver biopsy. The pathological results of liver biopsy were collected for inflammation grading and fibrosis staging. The liver puncture biopsies was collected by paraffin sectioning. The expression of HNF1α in the liver tissue was detected by immunohistochemical staining. Mantel-Haenszel χ(2) test was used for bidirectional ordered grouping data, and Spearman's rank-correlation test was used for rank correlation analysis. Results: There were varying degrees of inflammatory necrosis and fibrosis in the liver tissues of patients with chronic hepatitis B. There was a linear relationship between the expression of HNF1α and the level of inflammation in liver tissues (χ (2)(MH) = 40.70, P < 0.05). The expression of HNF1α in liver tissues of patients with chronic hepatitis B was decreased with the increase of liver inflammation. The expression intensity of HNF1α was negatively correlated with the inflammation grade (r(s) = -0.815, P < 0.05). There was a linear relationship between the expressions of HNF1α and the degree and stage of liver fibrosis (χ (2)(MH) = 31.95, P < 0.05). The expression level of HNF1α in liver tissue was gradually decreased with the aggravation of liver fibrosis. The expression intensity of HNF1α was negatively correlated with fibrosis stage (r(s) = -0.713, P < 0.05). Conclusion: HNF1α is closely related to the occurrence and development of liver tissue inflammation and fibrosis, and is expected to be a sensitive indicator for evaluating the level of liver tissue inflammation and fibrosis in patients with chronic hepatitis B. In addition, its down-regulation may be involved in the process of occurrence and development of liver inflammation and liver fibrosis, and may become a new target for the treatment of chronic hepatitis B.

Concordancia entre el resultado de la biopsia hepática y el índice APRI (Ast to Platelet Ratio Index) en el diagnóstico de cirrosis en pacientes con enfermedad hepática autoinmune

Introduction and objectivesIt has been proposed that non-invasive methods may replace liver biopsy for the diagnosis of tissue damage in patients with autoimmune liver disease (ALD). The aim of this study was to determine diagnostic performance and degree of concordance between the APRI index and liver biopsy for diagnosing cirrhosis in these patients. Material and methodsIn a cohort of patients with ALD, the value of the APRI index and liver biopsy results were determined according to the METAVIR score. The AUC and the degree of concordance between an APRI value >2 and a METAVIR score of F4 were evaluated as markers of liver cirrhosis, through a kappa statistic. ResultsIn total, 70 patients (age 51 ± 13 years) were included. The most common autoimmune liver diseases were primary biliary cirrhosis (PBC) (40%), autoimmune hepatitis (AIH) (24.3%) and AIH-PBC overlap syndrome (32.9%). Cirrhosis was confirmed by biopsy in 16 patients (22.9%). 15 patients (21.4%) had an APRI index >2 (Cirrhosis) and only six met both criteria. The AUC of the APRI was 0.77 (95% CI 0.65-0.88). The degree of concordance between the tests was low for an APRI cut-off point >2 (kappa 0.213; 95% CI 0.094-0.332), as well as for cut-off points >1.5, >1 and >0.5 (kappa 0.213, 0.255, 0.257, respectively) ConclusionOur results suggest that there is little concordance between APRI and liver biopsy for the diagnosis of cirrhosis in patients with ALD. It should therefore not be used as a single diagnostic method to determine cirrhosis.

Novel PRKAG2 variant presenting as liver cirrhosis: report of a family with 2 cases and review of literature

BackgroundMutations in the PRKAG2 gene encoding the 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), specifically in its γ2 regulatory subunit, lead to Glycogen storage disease of heart, fetal congenital disorder (PRKAG2 syndrome). These mutations are rare, and their functional roles have not been fully elucidated. PRKAG2 syndrome is autosomal dominant disorder inherited with full penetrance. It is characterized by the accumulation of glycogen in the heart tissue, which is clinically manifested as hypertrophic cardiomyopathy. There is little knowledge about the characteristics of this disease. This study reports a genetic defect in an Iranian family with liver problems using targeted-gene sequencing.Case presentationA 4-year-old girl presented with short stature, hepatomegaly, and liver cirrhosis. As there was no specific diagnosis made based on the laboratory data and liver biopsy results, targeted-gene sequencing (TGS) was performed to detect the molecular basis of the disease. It was confirmed that this patient carried a novel heterozygous variant in the PRKAG2 gene. The echocardiography was a normal.ConclusionA novel heterozygous variant c.592A > T (p.Met198Leu) expands the mutational spectrum of the PRKAG2 gene in this family. Also, liver damage in patients with PRKAG2 syndrome has never been reported, which deserves further discussion.

Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening.

OBJECTIVEAssess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSA total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.RESULTSThe prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).CONCLUSIONSModerate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.

A single-center experience: Liver biopsy results during a year.

Background and Aim:Liver biopsy is the gold standard method for the diagnosis and treatment of liver diseases. In this study, we aimed to evaluate the results of liver biopsies performed in a year in our clinic. In addition, we also aimed if these liver biopsies could reveal the etiology of liver disease in patients with elevations of transaminases or/and alkaline phosphatase levels or liver masses.Materials and Methods:Patients who had liver biopsies for persistently elevated transaminases or/and alkaline phosphatase levels, protocol biopsies after liver transplantation, or liver masses in our hepatology clinic between 2011 and 2012 were included in the study. Liver biopsy decisions were made by experts during the hepatology council. Liver biopsies were previously performed using classical percutaneous liver biopsy or ultrasonography-guided Sonocan® liver biopsy sets. The pathology results of liver biopsies and clinical data of the matching patients were obtained from the liver biopsy record archives and patient files, respectively.Results:Totally, 479 liver biopsy results (male=252, 52.6%, mean age 49±14.5 years) were evaluated in the study. Of these patients, 432 (male=228) underwent percutaneous liver biopsy and 47 (male=24) underwent Sonocan® needle biopsy. The most common histopathologic diagnoses in the percutaneous liver biopsy group were chronic hepatitis B (n=127, 29.4%), normal histopathological findings (n=50, 11.6% and 32 of them were protocol biopsies after liver transplantation), and nonalcoholic steatohepatitis (NASH, n=41, 9.5%). The most common histopathologic diagnoses in the Sonocan® group were 25 liver metastasis out of 29 liver tumors (n=25, 53.2% of all) chronic hepatitis B (n=5, 10.6%), and NASH (n=3, 6.4%).Conclusion:In this study, diversity in liver biopsy results indicates the importance of histopathological evaluation. The most prevalent pathology in the liver biopsies was chronic hepatitis B, which is the most common chronic liver disease in Turkey. The metastatic liver tumor was the most common among the liver masses.