Liver Biopsy Results Research Articles

A Case of a 65-year-old woman with Vitiligo and Diabetes Presenting with Severe Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a chronic liver disease with diverse clinical presentations and significant global variation in prevalence. AIH predominantly affects females and commonly manifests with nonspecific symptoms such as fatigue and malaise, often accompanied by extrahepatic autoimmune disorders. Here, we present the case of a 65-year-old Hispanic woman with vitiligo, type II diabetes mellitus, and severe AIH. Despite extensive diagnostic workup, including serological testing, the cause of this patient’s hepatitis proved to be a challenge. Eventually, autoimmune testing revealed positive anti-smooth muscle antibodies and an elevated IgG, prompting percutaneous liver biopsy, which confirmed mild to moderate active hepatitis with mixed inflammatory infiltrate. Despite there not being a standardized diagnostic criterion for autoimmune hepatitis, the interdisciplinary hospital team agreed that the most likely diagnosis was autoimmune hepatitis, given her constellation of symptoms, serologic testing, and liver biopsy results. Treatment with prednisone was initiated, leading to clinical improvement. This case underscores the importance of a thorough diagnostic workup in suspected AIH cases, especially in patients with concomitant autoimmune conditions, to facilitate timely management and improve patient outcomes. It also highlights the need for a consensus among diagnostic criteria for autoimmune hepatitis.

Serum Autotaxin Levels Predict Liver-Related Events in Primary Biliary Cholangitis Patients: A Long-term Multicenter Observational Study

Background: A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. The present study investigated whether serum autotaxin (ATX) could predict liver-related events (LRE) in PBC patients. Methods: This retrospective multicenter investigation included 190 biopsy-proven untreated PBC patients. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation to ATX levels at the time of liver biopsy Results: During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥ 1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs. 3.6%, p < 0.00001). Notably, the predictive capability of ATX for LRE in PBC patients surpassed that of FIB-4, ALBI, APRI, and M2BPGi. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, p = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, p < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32). Conclusion: Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.

Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B.

The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent. Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests. Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively. Ultimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King's score, the model in the training cohort (AUC = 0.834, 95% CI 0.800-0.868, p < 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742-0.866, p < 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King's scores in all cohorts. This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.

FIB-4 Reliability in Patients With Severe Obesity: Lower Cutoffs Needed?

Liver biopsy is the gold standard to evaluate hepatic fibrosis; however, it has many drawbacks, especially in patients with severe obesity. Noninvasive testing such as the FIB-4 score is increasingly being used as the initial screening tool to identify patients at risk for advanced fibrosis. The broader applicability of FIB-4 and the precision of its cutoff values remain uncertain in metabolic dysfunction-associated steatotic liver disease and patients with severe obesity. Our study explored the correlation between FIB-4 scores and intraoperative liver biopsy in patients with severe obesity undergoing bariatric surgery. A total of 632 patients with severe obesity underwent preoperative vibration-controlled transient elastography and intraoperative liver biopsy during bariatric surgery from January 2020 to August 2021. Variables collected included patient demographics, laboratory values, abdominal ultrasound, vibration-controlled transient elastography, and liver biopsy results. ANOVA 1-way test, χ 2 tests, and Fisher exact tests were used for quantitative and qualitative variables, respectively. The 95% CIs for the mean FIB-4 scores were used to generate surrogate cutoff values. The proposed FIB-4 cutoffs for F0-1, F2, F3, and F4 were 0.62 (CI: 0.59, 0.64), 0.88 (0.74, 1.01), 1.24 (0.94, 1.54), and 1.53 (0.82, 2.24), respectively. Area under the curve (AUC) methods were used to compare traditional to proposed cutoff values. Applying the traditional FIB-4 cutoffs to approximate advanced fibrosis yielded an AUC of 0.5748. Use of the proposed FIB-4 cutoffs increased the AUC to 0.6899. The proposed FIB-4 cutoffs correctly identified 40 patients with biopsy-proven advanced fibrosis (F3-F4), all of which would have been missed using traditional cutoffs. Our study revealed that the use of the currently accepted FIB-4 cutoffs as the screening modality for identifying patients with advanced fibrosis due to metabolic dysfunction-associated steatotic liver disease is insufficient and will result in missing patients with histologically confirmed advanced fibrosis. Use of the revised FIB-4 scores should be considered to diagnose patients with severe obesity at high risk of liver disease progression.

Tirzepatide for Metabolic Dysfunction–Associated Steatohepatitis with Liver Fibrosis

BackgroundMetabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear.MethodsWe conducted a phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis. Participants were randomly assigned to receive once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. The primary end point was resolution of MASH without worsening of fibrosis at 52 weeks. A key secondary end point was an improvement (decrease) of at least one fibrosis stage without worsening of MASH.ResultsAmong 190 participants who had undergone randomization, 157 had liver-biopsy results at week 52 that could be evaluated, with missing values imputed under the assumption that they would follow the pattern of results in the placebo group. The percentage of participants who met the criteria for resolution of MASH without worsening of fibrosis was 10% in the placebo group, 44% in the 5-mg tirzepatide group (difference vs. placebo, 34 percentage points; 95% confidence interval [CI], 17 to 50), 56% in the 10-mg tirzepatide group (difference, 46 percentage points; 95% CI, 29 to 62), and 62% in the 15-mg tirzepatide group (difference, 53 percentage points; 95% CI, 37 to 69) (P<0.001 for all three comparisons). The percentage of participants who had an improvement of at least one fibrosis stage without worsening of MASH was 30% in the placebo group, 55% in the 5-mg tirzepatide group (difference vs. placebo, 25 percentage points; 95% CI, 5 to 46), 51% in the 10-mg tirzepatide group (difference, 22 percentage points; 95% CI, 1 to 42), and 51% in the 15-mg tirzepatide group (difference, 21 percentage points; 95% CI, 1 to 42). The most common adverse events in the tirzepatide groups were gastrointestinal events, and most were mild or moderate in severity.ConclusionsIn this phase 2 trial involving participants with MASH and moderate or severe fibrosis, treatment with tirzepatide for 52 weeks was more effective than placebo with respect to resolution of MASH without worsening of fibrosis. Larger and longer trials are needed to further assess the efficacy and safety of tirzepatide for the treatment of MASH. (Funded by Eli Lilly; SYNERGY-NASH ClinicalTrials.gov number, NCT04166773.)

Influence of dispersion slope on the diagnosis of liver fibrosis by the shear wave in metabolic dysfunction-associated steatotic liver disease.

Shear wave (SW) elastography is used to evaluate metabolic dysfunction-associated steatotic liver disease (MASLD) pathophysiology. Increased elasticity due to fibrosis and increased viscosity due to necrosis and inflammation affect SW. Assessing fibrosis, the most prognostically relevant pathology, is critical. Viscosity is evaluated using the dispersion slope (DS); however, cut-off values that affect SW values are unclear. We compared the ultrasound imaging parameters (SW for viscoelasticity; DS for viscosity) with pathological findings. Patients (n=159) who underwent liver biopsy and SW and DS assessments at our hospital were included. Fibrosis stage and inflammation grade cut-off values were calculated from SW, DS, and liver biopsy results using receiver operating characteristic curves. Cases in which liver biopsy results were inconsistent with SW results were used to determine the effect of viscosity on SW values. DS was examined in the Correct and Incorrect Diagnosis groups, which were categorized based on the concordance between SW and liver biopsy results. Dispersion slope cut-off values between the two groups were calculated. Fibrosis stage cut-off values by SW (m/s) were: ≥F2, 1.62; ≥F3, 1.74; and F4, 1.97. Inflammation grade cut-off values by DS (m/s/kHz) were: ≥A1, 11.6; ≥A2, 14.5; and A3, 16.1. The Correct/Incorrect Diagnosis groups had 25/70 patients. The DS cut-off value for both groups was 13.2m/s/kHz. Shear wave and DS are useful for evaluating liver fibrosis and inflammation in MASLD. For DS>13.2m/s/kHz, SW may be affected by the increased viscosity owing to inflammation. In such patients, caution should be used when determining/interpreting values.

Assessment of transient elastography in diagnosing MAFLD and the early effects of sleeve gastrectomy on MAFLD among the Chinese population.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease among patients with obesity. Bariatric surgery, such as sleeve gastrectomy (SG), shows promise in improving the unfavorable condition of MAFLD. Transient elastography (TE) can be utilized to assess the extent of steatosis and liver fibrosis, providing a noninvasive method for preoperative prediction and postoperative evaluation of MAFLD. This study aims to investigate the effectiveness of TE in diagnosing MAFLD by evaluating liver steatosis and tissue stiffness, as well as assessing the early impact of SG in the treatment of obesity-associated MAFLD. In this study, the authors collected preoperative and 6-month postoperative data from patients with obesity who were diagnosed with MAFLD by intraoperative liver biopsy. The patients underwent SG at our hospital between August 2021 and April 2023. The authors estimated the diagnostic accuracy for the steatosis and fibrosis categories using the area under the receiver operating characteristic curve (AUROC). The authors also evaluated the influence of disease prevalence on the positive predictive value and negative predictive value. MAFLD diagnosis was based on the liver steatosis activity and fibrosis scoring system. The authors used univariate and multivariate logistic regression analyses to identify factors contributing to severe MAFLD. To visualize the results, the authors created a nomogram and enhanced it with bootstrap resampling for internal validation. Additionally, the authors plotted receiver operating characteristic and calibration curves. The authors compared preoperative and postoperative data, including general information, laboratory tests, and TE results, to assess the early impact of SG in the treatment of obesity-associated MAFLD. Based on the results of liver biopsy, the AUROC for controlled attenuation parameter (CAP) in identifying steatosis was found to be 0.843 (95% CI: 0.729-0.957) for S≥S1, 0.863 (95% CI: 0.786-0.940) for S≥S2, and 0.872 (95% CI: 0.810-0.934) for S=S3. The Youden limits for S≥S1, S≥S2, and S≥S3 were determined to be 271 dB/m, 292 dB/m, and 301 dB/m, respectively. Similarly, the AUROC for liver stiffness measurement (LSM)/E in detecting liver fibrosis was 0.927 (95% CI: 0.869-0.984) for F≥F2, 0.919 (95% CI: 0.824-0.979) for F≥F3, and 0.949 (95% CI: 0.861-0.982) for F=F4, with Youden cutoff values of 7.5kPa, 8.3kPa, and 10.4kPa, respectively. Patients with A≥3 and/or F≥3 were classified as having severe MAFLD. Multivariate logistic regression analysis identified CAP, E, LDL, and AST as the best diagnostic factors for severe MAFLD, and a nomogram was constructed based on these factors. The AUROC of the nomogram for the assessment of severe MAFLD was 0.824 (95% CI: 0.761-0.887), which was further validated by 1000 bootstrap resamplings with a bootstrap model area under curve of 0.823. Finally, after a 6-month follow-up period, the steatosis grade and fibrosis stage of the patients were graded based on the optimal cutoff values for CAP and LSM. Significant reductions in BMI, waist circumference, HbA1c, fasting glycemia, triglycerides, high density lipoprotein (HDL), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), gamma glutamyl transpeptidase (GGT), CAP, LSM, steatosis grade, and fibrosis stage were observed compared to the preoperative values. In this prospective study, the authors investigated the use of CAP and LSM as alternatives to liver biopsy for evaluating hepatic steatosis and fibrosis in patients with obesity combined with MAFLD. Furthermore, the authors examined the impact of SG on metabolic indicators and the progression of fatty liver disease during the early postoperative period, and observed significant improvements in both aspects.

Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations

ObjectiveTo describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA’s surveillance database.MethodsHepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020.ResultsAmong DILIN’s 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause.Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes.ConclusionAmiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.

МОРФОЛОГИЧЕСКИЕ И УЛЬТРАСТРУКТУРНЫЕ ИЗМЕНЕНИЯ ТКАНИ ПЕЧЕНИ ПРИ БИЛИАРНОЙ ОККЛЮЗИИ РАЗЛИЧНОЙ ДЛИТЕЛЬНОСТИ

An analysis of the morphological state of the liver was carried out in 160 patients with obstructive jaundice of non-tumor etiology who received treatment in the Novgorod Regional Clinical Hospital and Central City Clinical Hospital. The results of liver biopsy during surgery were studied. Pronounced structural and functional changes in liver tissue were revealed, which were further aggravated due to an increase in the duration of occlusion. In cases with long-term chronic jaundice, after decompression of the bile ducts, sclerotic changes, histiolymphocytic infiltration and proliferating biliary epithelium, fibrosis and foci of hepatocyte necrosis remain in the portal tracts. Ultrastructure analysis revealed changes in the cell membrane, cytoplasmic structures, destruction of mitochondrial membranes, formation of secondary lysosomes, disruption of the integrity of the nuclear membrane and signs of karyolysis. The study of puncture and surgical biopsies for obstructive jaundice makes it possible to establish the form and severity of cholestasis and, along with other diagnostic indicators, affects disease prognosis and the tactics of surgical treatment. Taking the different timing and severity of cholestasis into account, it is necessary to use therapeutic technologies in advance that lead to an improvement in liver morphology.

A Case of Wilson's Disease Suspected to Involve a Novel Genetic Mutation of ATP7B Gene, Requiring a Differential Diagnosis with Non-alcoholic Steatohepatitis.

A 19-year-old Japanese man was referred for a further evaluation of liver dysfunction. Despite the absence of symptoms or obesity, the liver biopsy results were consistent with non-alcoholic steatohepatitis. Subsequent investigations revealed low serum ceruloplasmin, increased urinary copper excretion, and a known mutation c.3809A>G (p.Asn1270Ser) in the copper-transporting enzyme P-type ATPase (ATP7B) gene, leading to a diagnosis of Wilson's disease. A previously unreported variant, i.e., c.3866A>T (p.Asp1289Val) was detected on the patient's other allele and was considered a novel mutation, classified as 'likely pathogenic' according to the American College of Medical Genetics guidelines.

How Successful Are APRI and FIB-4 Scores in Predicting Liver Fibrosis in Chronic Hepatitis B Patients?

We aimed to evaluate the correlation of fibrosis severity in liver biopsies, the gold standard for the diagnosis of patients with chronic hepatitis B (CHB), using noninvasive methods such as the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The study included patients who were followed and treated for CHB in 2018-2023. Biochemical markers and liver biopsy findings of the cases were retrospectively, and their correlations with APRI and FIB-4, which are noninvasive scores, were compared. The study included 202 patients. The biochemical markers and liver biopsy findings of the cases were examined retrospectively, and their correlations with the noninvasive scores APRI and FIB-4 were compared. According to liver biopsy results, 109 (54.0%) cases had no fibrosis (stage 0.1), 85 (42.1%) cases had mild fibrosis (stage 2, 3), and 8 (4%) cases had severe fibrosis (stage 4, 5, 6). The median FIB-4 score was 0.79 (0.25 -11.74), and the median APRI score was 0.29 (0.10-29.40). When the predictive power of the APRI score to discriminate between "without fibrosis" and "with fibrosis (mild and severe)" was evaluated by receiver operating characteristic (ROC) curve analysis, for the APRI score >0.408 as the ideal cut-off point, the sensitivity and specificity were found to be 34% and 79%, respectively. When the cut-off point for the FIB-4 score was >0.701, the sensitivity and specificity were 71% and 46%, respectively. Although the area under the curve (AUC) ratios ranged between 52% and 64% in the ROC analyses, the sensitivity ratios of the cut-off points calculated for FIB-4 were higher. The likelihood ratios of the cut-off point we found for the APRI score (1.61 and 1.75, respectively) were relatively better than those for FIB-4 (1.31 and 1.41, respectively). Noninvasive tests used to detect liver fibrosis in individuals with CHB do not eliminate the need for liver biopsy but may provide insight into the fibrosis status of patients.

Shear wave elastography as a non-invasive tool for staging liver fibrosis in children: A study in Algerian pediatric patients.

Traditionally, liver biopsy has been the gold standard for fibrosis staging. However, it is an invasive, expensive and uncomfortable procedure that is associated with the risk of complications. Thus, non-invasive methods such as shear wave elastography (SWE) have been developed as potential alternatives to liver biopsy. The aim of this study is to evaluate the diagnostic performance of SWE in pediatric patients with liver fibrosis, specifically in a group of Algerian children and to determine whether this method can be a reliable alternative to liver biopsy. This prospective, descriptive, monocentric study evaluated the non-invasive diagnostic performance of 2D-SWE in assessing liver fibrosis in pediatric patients. The assessment was carried out using various statistical methods, including Spearman's correlation coefficient, Kappa concordance coefficients, regression analysis, as well as the calculation of area under the receiver operating characteristic (AUROC) values and corresponding cut-off points based on the receiver operating characteristic (ROC) curve. Our study found that 2D-SWE is strongly correlated with liver biopsy in estimating liver fibrosis in children, with a correlation coefficient greater than 0.8. Furthermore, the Kappa correlation coefficients exceeded 0.8, indicating a strong agreement between 2D-SWE and liver biopsy results. The AUROC value was not less than 0.9 for significant fibrosis and above (≥ F2), indicating that it has satisfactory diagnostic performance in detecting liver fibrosis in children. 2D-SWE shows promise as a non-invasive method for evaluating liver fibrosis in children, offering a potential alternative to liver biopsy. Larger studies are needed to substantiate the findings of this study and to confirm the accuracy and reliability of 2D-SWE for assessing liver fibrosis in children.

Abstract 13902: Using a Proteomics-Based Cardiovascular Risk Test to Identify Systemic Changes in a Clinical Trial of Nonalcoholic Fatty Liver Disease

Background: Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular outcomes. Assessment of the impact of NASH therapy on cardiovascular risk is an important element of NASH drug development but is challenging particularly in early phase trials. Aptamer-based proteomic profiles (Somalogic®) in serum have been used to develop and validate a risk score as a surrogate for cardiovascular (CV) risk. Hypothesis: Improvement in NASH histology will result in improved proteomic cardiovascular risk scores. Methods: A post-hoc analysis of proteomic profiles of serum samples, using the Somalogic® platform, from the Pioglitazone vs. Vitamin E vs. Placebo for Treatment of Nonalcoholic Fatty Liver Disease (PIVENS) trial was conducted. PIVENS was a 96-week trial of nondiabetic participants with (NASH). We applied the proteomic CV risk scores to samples from baseline, on therapy and end of treatment visits (n=7) visits and received liver histology results at baseline and 96 weeks on N = 209 (84.6%) study participants. Generalized linear and mixed models were used to assess the association between CV risk score, treatment arm and change in liver biopsy results. Results: Baseline scores were similar across groups (mean 0.19, SD 0.14). There was no association between treatment arms and changes in scores during therapy and end of treatment. However, improvement in histological markers of activity (lobular inflammation and NAFLD activity score) and fibrosis were associated with improved cv risk scores (Figure) (p&lt; 0.05 for all). Conclusions: Improvement in hepatic inflammation, NAFLD activity score and fibrosis were associated with improved proteomic CV risk scores regardless of treatment provided. Additional prospective validation of these findings is warranted. Proteomic profiling can potentially be used to track changes in cardiovascular risk profile changes in response to therapy in the short term NASH treatment trials.

A Malaysian Case of Glycogen Storage Disease Type Vl

Glycogen storage disease (GSD) type VI is one of the rare GSD variants characterised by PYGL mutation. It leads to liver phosphorylase deficiency, thus causing glycogenolysis disorder. Classic manifestations are mild hypoglycaemia, abdominal distension, growth retardation, hepatomegaly, elevated liver transaminases, hyperlipidaemia, and normal lactate and uric acid. This proband is a 14-year-old Malay girl who was the second child of non-consanguineous parents. At four years old, she was referred for the incidental finding of hepatomegaly with deranged liver enzymes. Clinically, there was hepatomegaly (4 cm below the right costal margin) without any growth retardation. Subsequently, at 11 and 13 years old, she experienced a twisted left ovarian cyst and acute colitis, respectively. Biochemically, there was significantly increased transaminases, hypertriglyceridaemia, and mild hypoglycaemia. The liver biopsy result was consistent with GSD. Next-gene sequence analysis test revealed compound heterozygous mutations identified on the PYGL gene: splice site c.772+2_772+3del and missense c.2071G&gt;C (p.Gly691Arg). Biochemical parameters were normalised except for persistent hypertriglyceridemia after treatment with uncooked corn starch four times daily. Family screening of mother and younger brother exhibits both are carriers of a missense mutation at c.2071G&gt;C(p.Gly691Arg). Genetic testing helps patients better understand their conditions and serve as a guide for future pregnancy planning.

Development, Validation, and Application of a Scoring Model for Non-alcoholic Steatohepatitis.

The aim of this study was to explore risk factors of NASH and then develop a non-invasive scoring model in Chinese patients with obesity. A scoring system was then applied to assess the effect of sleeve gastrectomy on NASH. A total of 243 patients with obesity were included and divided into NASH group and non-NASH group according to the pathological results of liver biopsy. Logistic regression was used to determine risk factors of NASH. A scoring model was derived by risk factors of NASH. Then, postoperative follow-up was performed in 70 patients. Among the 243 patients, 118 (48.56%) patients showed NASH. Multivariate logistic regression identified aspartate aminotransferase (AST) (>21.50 IU/L), high-density lipoprotein cholesterol (HDL-C) (<1.155mmol/L), and homeostasis model assessment (HOMA-IR) (>9.368) as independent risk factors of NASH. The model included above risk factors showed a negative predictive value (NPV) of 70.38% in the low-risk category and a positive predictive value (PPV) of 85.71% in the high-risk category, with the area under the receiver operator curve (AUROC) of 0.737. Bariatric surgery resulted in a sharp decline in AST and HOMA-IR and a significant increase of HDL-C. The points of scoring model were improved at 6 months after surgery. A non-invasive scoring model was derived by the risk factors of NASH included AST, HDL-C, and HOMA-IR and applied to the postoperative follow-up. After sleeve gastrectomy, the above risk factors and points of scoring model were significantly improved.

Hepatic Manifestations of Pediatric Hemophagocytic Lymphohistocytosis

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory disorder.it is caused by benign systemic overgrowth of macrophages in the reticulo-endothelial system, leading to cytokine storm. The main features of HLH are; fever, splenomegaly, bi/pancytopenia; hyperferritinemia, hyper-triglyceridemia and hypofibrinogenemia; which if not diagnosed and early treated progresses to disseminated intravascular coagulopathy (DIC), multi-organ dysfunction with dismal outcome. Hepatic manifestations are not well recognized primary presentation in pediatric patients with HLH. This presentation mandates high levels of suspicious for early diagnosis. Aim of the Work To study the hepatic involvement clinical, laboratory, and pathological in patients with Familial/primary (1ry) HLH and in patients with secondary (2ry) acquired HLH. Patients and Methods A 6 month retrospective cohort study included 35 patients with genetically confirmed HLH divided into familial HLH by its types, X linked lymphoproliferative syndrome, HLH with partial albinism and secondary HLH; following at pediatric hematology/oncology clinic, Ain Shams University. By detailed review of clinical and laboratory data that include hepatic transaminases and synthetic liver function done at the time of presentation, at week 2, 8 from treatment start and at time of reactivation; Liver biopsy results and genetic analysis were recorded. Biochemical liver involvement was considered when alanine aminotransferase was three folds the upper level of normal at presentation. Overall and reactivation free survival were analyzed according to liver involvement Results Thirty five patients with HLH were recruited with age range of 2-108 months, 20(57.1%) of patients with HLH were genetically confirmed and 12(34.3%) of them had MUNC13D mutations, 3(8.6%) had STXBP2 mutation and 5(14.3%) had RAB27A mutation while 4(11.4%) had secondary HLH. 29(82.9%) had liver enlargement at diagnosis with hepatic reactivation in 18(51.4%). 8(22.8%) of patients had biochemical liver involvement; there was no significant difference in their demographic data or their clinical presentation, their final outcome or the type of mutant gene according to liver involvement. Conclusion HLH is a frequently lethal disease with a high variability in clinical presentation .it must be considered a differential in patients presenting with clinical signs of hepatic dysfunction especially when it is accompanied by cytopenias. Significant biochemical liver involvement is an under recognized presentation of HLH. Hepatic involvement did not impact response to treatment and disease outcome.

RDW Predicts Fibrosis in Patients with Chronic Hepatitis B Having Persistently Normal ALT Levels.

There are studies on the determination of hepatic fibrosis with noninvasive markers but data about liver biopsy results and noninvasive markers in patients with chronic hepatitis B (CHB) are limited. The aim of this study is to determine the relationship between pathological findings and noninvasive markers, and to determine the marker that predicts fibrosis in patients with consistently normal serum alanine aminotransferase (ALT) levels, diagnosed with CHB and undergoing liver biopsy. A total of 122 patients with CHB, 29 of them with HbeAg (+), aged 30 years and older, HBV DNA > 2000 IU / ml, and serum ALT levels measured four times in the last year, were consistently normal, and 93 of them with HbeAg (-) were included in the study. Demographic characteristics of patients, laboratory parameters, histological activity index (HAI) and fibrosis values obtained in liver biopsy, and noninvasive markers (AP (age-platelet) index, APRI (AST/Platelet ratio) and FIB-4 score, neutrophil/lymphocyte ratio, mean platelet volume (MPV) and erythrocyte distribution width (RDW) were recorded. The relationship between RDW value and fibrosis was statistically significant in the HbeAg (+) group (p<0.001). The relationship between AP index, APRI and FIB-4 score, neutrophil/lymphocyte ratio and MPV with fibrosis was not statistically significant (>0.05 for each). It has been shown that the RDW value can be used to predict fibrosis in CHB patients with normal ALT and HbeAg (+), and the cut-off value for RDW is 12.

Wilson's Disease.

Wilson's disease (WD) can present with liver disease, neurological deficits, and psychiatric disorders. Results of genetic prevalence studies suggest that WD might be much more common than previously estimated. Early recognition of WD remains challenging because it is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment. In association with other clinical and biochemical tests, liver biopsy results and molecular genetic testing can also be used for diagnosing WD. Medical therapy is effective for most patients; liver transplant can rescue those with acute liver failure or those with advanced liver disease who fail to respond to or discontinue medical therapy. Although novel therapies, such as gene therapy, are on the horizon, screening and prevention of delayed diagnosis remains paramount.

Kronik hepatit C’li hastaların karaciğer fibrozisini göstermede APRI ve FIB-4 skorlamalarının değeri

Purpose: Infection with hepatitis C virus causes chronic liver damage, fibrosis and in later processes, cirrhosis and liver cancer. Currently, the use of biomarkers, instead of invasive procedures, is recommended to identify liver fibrosis. In this study, we aimed to evaluate the sensitivity and specificity of aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4) scoring for detection of "significant fibrosis" in chronic hepatitis C patients.&#x0D; Materials and Methods: Liver biopsy results and blood test results of 50 patients, infected with chronic hepatitis C, were analyzed. APRI and FIB-4 scores were calculated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency for APRI and FIB-4 scorings were calculated using a fourfold table. The values of APRI and FIB-4, providing the best specificity and sensitivity in the diagnosis of significant fibrosis, was determined by ROC (receiver operator characteristics curve) analysis.&#x0D; Results: The mean fibrosis stage of 30 patients with significant fibrosis was 2.83±0.74 and the mean patient age was 56.8±13. The sensitivity of APRI ≥ 1.5 to detect significant fibrosis was 16%, the specificity was 90%, PPV was 71% and NPV was 41%. A FIB-4 score of ≥3.25 had a sensitivity of 20%, a specificity of 95%, a PPV of 85% and a NPV of 44%. &#x0D; Conclusion: APRI and FIB-4 have high specificity and PPV in demonstrating significant fibrosis, but have low sensitivity and NPV. The sensitivity of FIB-4 was higher compared to the APRI scoring. More research on this subject is needed, as well as revision of fibrosis scores and development of new fibrosis scores.

Ultrasound-Guided Percutaneous Liver Biopsy: Diagnostic Value in Diffuse Liver Disease and Viral Hepatitis

In this study, it is aimed to present the efficiency, diagnostic contribution, complications, and histopathology results of percutaneous liver biopsies performed under ultrasonography (US) guidance. For this purpose, 266 patients who underwent diffuse liver biopsy in our interventional radiology unit between January 1, 2016 and March 31, 2023 were retrospectively analyzed. Demographic characteristics, laboratory records, and pathology results of the patients were recorded. Major and minor complications, diagnosis rate, biopsy indications were evaluated. 152 (57.1%) of the 266 patients included in the study were male and 114 (42.9%) were female, and the mean age of the patients was 34.4±12.2 years (min-max: 18-69). According to biopsy results, the most common pathological finding was chronic hepatitis B (n=249, 93.6%), followed by chronic hepatitis C (n=6, 2.3%). Minor complications occurred in 9.4% (n=25) of all patients, and the most common complication was pain at the biopsy site or right shoulder (n=22, 8.3%). No major complications or mortality were observed. According to the fibrosis score, 77.4% (n=206) of the cases were mild fibrosis, 18% (n=48) had moderate fibrosis, and 3.8% had severe fibrosis (n=10). In two (0.75%) patients, fibrosis scoring was not performed because the sample was insufficient. In conclusion, we suggest that percutaneous tru-cut liver biopsies performed under US guidance by experienced interventional radiologists are effective and safe. Also, this invasive procedure, which plays an important role especially in the diagnosis, staging and treatment plan of the diffuse liver diseases can be performed with very low complication and high accuracy rates by using correct and appropriate technique.