Hepatic Histological Features Research Articles

Dietary supplementation of lysozyme can improve growth rate, laying performance, blood biochemistry, and mRNA levels of some related genes in different plumage-colored quails

The impact of dietary lysozyme (LZ) supplementation on the growth and laying performance was investigated over 4 weeks of growing and 6 weeks of laying periods in two different plumage color (white and brown-feathered) Japanese quail varieties. For each variety, 240 birds were randomly assigned into four groups with four replicates for each group. The first group (control) was fed a basal non-supplemented diet (BD). Whereas the 2nd, 3rd, and 4th received the BD supplemented with commercial LZ (CLZ) at 100 mg/kg diet, and natural LZ (NLZ) at 100 and 200 mg/kg diet, respectively. The main findings included significant increases in body weights and gains in the white-feathered quails supplemented with NLZ1 compared to the control and NLZ2. However, there were no significant differences in the case of brown-feathered quails in all LZ supplementations. Moreover, the different dietary LZ lowered FI in both quails with the lowest intake observed in the brown-feathered quails. Accordingly, enhanced FCR was reported in the CLZ groups for both quail varieties and in NLZ1 and NLZ2 for the white-feathered and brown-feathered quails, respectively. In both quail varieties, the NLZ2 significantly lowered serum creatinine and urea and increased albumen and globulin levels compared with other groups. Histologically, the best hepatic histological features were found in both quail’ varieties fed the NLZ1-supplemented diet. Accompanying LZ-induced modulations in the expression levels of GHR, IGF-1, leptin, CCK, FAS, and ACC genes in both quail varieties were reported. Besides, both quail varieties in NLZ1& NLZ2 supplementation exhibited significant increases in hen day egg production, egg weight, egg mass, and hatchability percentages along with differences in external and internal egg qualities compared with LZ-free diet or CLZ. Therefore, NLZ could be used as an effective feed supplement to enhance the growth and egg performance of Japanese quail with caution being drawn to the supplementation dose about quail variety.

Clinicopathologic features and outcomes of hepatic inflammatory pseudotumour (IPT) and hepatic IPT-like lesions.

Hepatic inflammatory pseudotumours (IPTs) are nonneoplastic hepatic masses characterized by variably fibroblastic stroma and inflammatory infiltrate, hypothesized to arise as part of a response to infection or prior surgery. The aim of this study was to evaluate the clinicopathologic features and outcomes of biopsy-proven hepatic IPT as well as other cases with IPT-like histologic features. A database search at our institution identified cases with a pathologic diagnosis of hepatic IPT (n = 80) between 2000 and 2023. Histologic features (stromal quality, inflammatory cell components, granulomas, and necrosis) were evaluated. Past medical and surgical history, microbiologic studies, and outcomes were reviewed retrospectively. Patients frequently had a past medical history of malignancy (34%), biliary disease (15%), or prior intraabdominal surgery (24%), and often presented with multifocal hepatic lesions (36%). Variable inflammatory backgrounds were present, including histiocytic (36%), lymphoplasmacytic (34%), or neutrophilic (24%). Specific organisms were identified in 15% of cases, most commonly Klebsiella and Staphylococcus species. Most patients with available clinical follow-up demonstrated radiologic resolution and/or had repeat negative biopsy; a minority of patients (8%) were subsequently diagnosed with neoplastic hepatic lesions. No significant association was seen between histologic features and the subsequent clinical or pathologic diagnosis of hepatic neoplastic lesions. Hepatic IPT is a heterogeneous entity that can present in a variety of clinical scenarios and show a wide morphologic spectrum. These lesions often regress spontaneously or with antibiotics. A subset of cases with hepatic IPT-like histologic features were subsequently diagnosed with malignancy, emphasizing the need for continued follow-up and repeat biopsy depending on clinical and radiologic features.

Potential Hepatoprotective Effects of Chamaecyparis lawsoniana against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation.

Methotrexate (MTX) therapy encounters significant limitations due to the significant concern of drug-induced liver injury (DILI), which poses a significant challenge to its usage. To mitigate the deleterious effects of MTX on hepatic function, researchers have explored plant sources to discover potential hepatoprotective agents. This study investigated the hepatoprotective effects of the ethanolic extract derived from the aerial parts of Chamaecyparis lawsoniana (CLAE) against DILI, specifically focusing on MTX-induced hepatotoxicity. UPLC-ESI-MS/MS was used to identify 61 compounds in CLAE, with 31 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 195 potential DILI targets for the bioactive compounds, including TP53, IL6, TNF, HSP90AA1, EGFR, IL1B, BCL2, and CASP3 as top targets. In vivo experiments conducted on rats with acute MTX-hepatotoxicity revealed that administering CLAE orally at 200 and 400 mg/kg/day for ten days dose-dependently improved liver function, attenuated hepatic oxidative stress, inflammation, and apoptosis, and reversed the disarrayed hepatic histological features induced by MTX. In general, the findings of the present study provide evidence in favor of the hepatoprotective capabilities of CLAE in DILI, thereby justifying the need for additional preclinical and clinical investigations.

Comparison of cardiometabolic risk factors between obese and non-obese patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is closely associated with cardiometabolic abnormalities. This association could be partly influenced by weight, but not entirely. This study aimed to compare the cardiometabolic risk factors between obese and non-obese NAFLD patients, and explored the relationship between adiposity and severity of fatty liver. This cross-sectional study included 452 patients with Fibroscan-proven NAFLD. Anthropometric measurements, metabolic components and hepatic histological features were evaluated. The risk of metabolic syndrome in each body mass index (BMI) category was analyzed using logistic regression. The prevalence of metabolic syndrome was 10.2%, 27.7%, and 62.1% in normal-weight, overweight and obese participants. Regression analysis showed that the risk of metabolic syndrome in overweight and obese NAFLD patients was 3.74 and 4.85 times higher than in patients with normal weight, respectively. Waist circumference (β = 0.770, P < 0.001) and serum concentration of fasting blood glucose (β = 0.193, P = 0.002) and triglyceride (β = 0.432, P < 0.001) were the determinants of metabolic syndrome occurrence in NAFLD patients. Metabolic abnormalities were similar in obese and non-obese NAFLD patients, although, the increase in BMI was associated with an increased risk of metabolic syndrome in patients.

Antidiabetic Effect of Noni Fruit and Moringa Leaves Extract on Blood Glucose Level, Hepatic and Pancreatic Histological Features of Diabetic Mice

One of the chronic diseases with high blood glucose levels is a characteristic of Diabetes Mellitus. Utilization of herbal ingredients needs to be developed to reduce blood sugar levels in diabetes, and one of them is by using moringa leaf extract and noni fruit. This study aimed to analyze the effect of a combination of moringa leaf extract and noni fruit on blood glucose levels and tissue cytology in diabetic mice. The study was a randomized pretest-posttest control group design using 28 male mice divided into seven groups. The data analysis showed the lowest decrease in blood glucose levels in the group of diabetic mice given noni fruit and moringa leaf extract at a dose of 150mg/20g BW/oral/day for two weeks. The results of histological examination of liver and pancreas tissue showed no tissue is damaged.

A case report of hepatic angiomyolipoma, inflammatory subtype. Clinico-pathological characterization: a diagnostic challenge

BackgroundAngiomyolipoma is a benign mesenchymal neoplasm of a wide histological heterogeneity belonging to the PEComa “family.” The liver, after the kidney, is their second most frequent location. However, inflammatory hepatic AMLs constitute a rare entity, with only fourteen documented cases until 2020. These neoplasms can overlap morphological features of IgG4-related diseases, being of great diagnostic relevance to demonstrating myomelanocytic-lineage differentiation of the neoplastic cells. Case presentation: we present a new case of an inflammatory hepatic AML resembling an IgG4-related disease in a 35-year-old woman with a subcapsular 5 cm mass confined to segment VII of the right hepatic lobe. Although having reduced its size along the tumor’s natural evolution, complete tumor resection was decided due to its hypermetabolic behavior (max. SUV = 12,6) assessed by PET-CT scan. Finally, the patient underwent a right hepatectomy due to spontaneous rupture and bleeding of the lesion during the intervention. All the diagnostic and therapeutic procedures occurred in the last months of the COVID-19 pandemic. Conclusions: This review aims to describe inflammatory hepatic AML histological and immunohistochemical features. We further sought to establish a clinicopathological contextualization of this tumoral subtype.

Glycemic control predicts the risk of hepatic fibrosis in biopsy-proven NAFLD: a possible mediating role for leukemia inhibitory factor?

Background Despite the clear link between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus, little is understood about how glycemic control impacts histological severity. We aimed to investigate the deeper association between hemoglobin A1c (HbA1c) and the histologic severity of liver fibrosis. Methods A total of 568 adults with biopsy-proven NAFLD from the PERSONS cohort in Wenzhou were enrolled. The association between mean HbA1c and hepatic histological features was investigated with ordinal logistic regression. Generalized additive models were used to identify the non-linear relationship between HbA1c and increased fibrosis stage (stage F ​≥ ​3). Causal mediation analysis was performed to calculate the indirect effect of the relationship between HbA1c and hepatic fibrosis mediated by cytokines. Results Every 1% increase in mean HbA1c was associated with 16% higher odds of increased fibrosis stage (odds ratio 1.16, 95%CI 1.04–1.30), even after adjustment for confounding factors. There was a non-linear association between HbA1c and increased fibrosis stage (stage F ​≥ ​3), and the HbA1c inflection point was 9.2%. In particular, the ORs on the left and right sides of this inflection point were 2.1 (95%CI 1.4–3.3) and 0.1 (95%CI 0–4.8), respectively. 7% of the association (OR 1.07, 95%CI 1.01–1.12) between HbA1c and liver fibrosis was mediated by leukemia inhibitory factor. Conclusions Glycemic control predicts severity of hepatic fibrosis and leukemia inhibitory factor plays an intermediary role between them, and thus optimizing glycemic control may be a means of modifying the risk of fibrosis progression in NAFLD.

Major Dietary Patterns in Association with the Grades of Nonalcoholic Fatty Liver Disease in Newly Diagnosed Patients Living in North of Iran.

Background:Evidence suggests that dietary pattern is related to incidence and grades of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between major dietary patterns and hepatic histologic features of newly diagnosed patients with NAFLD.Methods:This cross-sectional study included 260 newly diagnosed NAFLD patients. Hepatic fibrosis and steatosis were diagnosed using Fibroscan. Dietary information was obtained using a validated 168-item semiquantitative food frequency questionnaire. The association between dietary patterns and odds ratio of the grade of fibrosis and steatosis was examined by multinomial logistic regression.Results:The mean ± SD age participant was 46.53 ± 11.71 years. Fifty-seven percent of the participants were women. Two major dietary patterns were recognized: “Western dietary pattern” and “Mediterranean dietary pattern.” After adjustment for various confounders, adherence to the two extracted dietary patterns was not associated with odds of fibrosis and steatosis (P > 0.05). However, P was not significant. Patients in the second quartile of the Mediterranean dietary pattern had a higher risk for being in the F1 grade compared to those in the reference group in the crude and adjusted model.Conclusions:The major dietary patterns of NAFLD patients living in Gilan were not related to the severity of their disease. More precise study design such as cohort or interventional studies is suggested to reveal the strength of this study findings.

A Novel Mouse Model of Nonalcoholic Steatohepatitis Suggests that Liver Fibrosis Initiates around Lipid-Laden Macrophages

While the interaction of cells such as macrophages and hepatic stellate cells is known to be involved in the generation of fibrosis in nonalcoholic steatohepatitis (NASH), the mechanism remains unclear. This study employed a high-fat/cholesterol/cholate (HFCC) diet to generate a model of NASH-related fibrosis to investigate the pathogenesis of fibrosis. Two mouse strains: C57BL/6J, the one susceptible to obesity, and A/J, the one relatively resistant to obesity, developed hepatic histologic features of NASH, including fat deposition, intralobular inflammation, hepatocyte ballooning, and fibrosis, after 9 weeks of HFCC diet. The severity of hepatic inflammation and fibrosis was greater in A/J mice than in the C57BL/6J mice. A/J mice fed HFCC diet exhibited characteristic CD204-positive lipid-laden macrophage aggregation in hepatic parenchyma. Polarized light was used to visualize the Maltese cross, cholesterol crystals within the aggregated macrophages. Fibrosis developed in a ring shape from the periphery of the aggregated macrophages such that the starting point of fibrosis could be visualized histologically. Matrix-assisted laser desorption/ionization mass spectrometry imaging analysis detected a molecule at m/z 772.462, which corresponds to the protonated ion of phosphatidylcholine [P-18:1 (11Z)/18:0] and phosphatidylethanolamine [18:0/20:2 (11Z, 14Z)], in aggregated macrophages adjacent to the fibrotic lesions. In conclusion, the HFCC diet-fed A/J model provides an ideal tool to study fibrogenesis and enables novel insights into the pathophysiology of NASH-related fibrosis.

PPARGC1A rs8192678 G>A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease.

BACKGROUNDThe association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease (NAFLD) requires further confirmation. In addition, it is still unknown whether PPARGC1A rs8192678 is associated with hepatic histological features in NAFLD in the Chinese population. AIMTo investigate the interaction between PPARGC1A rs8192678 and nonalcoholic steatohepatitis (NASH), and whether this polymorphism is associated with hepatic histological features. METHODSFifty-nine patients with liver biopsy-proven NAFLD and 93 healthy controls were recruited to a cohort representing the Chinese Han population. The SAF (steatosis, activity, and fibrosis) scoring system was used for hepatic histopathological evaluation. The polymorphisms of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 were genotyped. The intrahepatic mRNA expression of PPARGC1A was evaluated by real-time polymerase chain reaction.RESULTSThirty-seven patients with NAFLD had NASH, of which 12 were nonobese. The PPARGC1A rs8192678 risk A allele (carrying GA and AA genotypes) had the lowest P value in the dominant model; the odds ratio (OR) for NAFLD was 2.321 [95% confidence interval (CI): 1.121-4.806]. After adjusting for age, sex, and the PNPLA3 rs738409 risk G allele, the PPARGC1A rs8192678 A allele was a risk factor for NAFLD (OR 2.202, 95%CI: 1.030-4.705, P = 0.042). The genetic analysis showed that patients with NAFLD, moderate-to-severe steatosis (S2-3), and Activity 2-4 (A ≥ 2) were more likely to carry A in PPARGC1A rs8192678 (OR 5.000, 95%CI: 1.343-18.620, P = 0.012; and OR 4.071, 95%CI: 1.076-15.402, P = 0.031). The multivariate logistic regression analysis showed that PPARGC1A rs8192678 risk A allele was also independently associated with S2-3, A ≥ 2, and NASH (OR 6.190, 95%CI: 1.508-25.410, P = 0.011; OR 4.506, 95%CI 1.070-18.978, P = 0.040; and OR 6.337, 95%CI: 1.135-35.392, P = 0.035, respectively) after adjusting for age, sex, body mass index, and PNPLA3 rs738409 risk G allele. The results also showed that this polymorphism was associated with nonobese NASH (OR 22.000, 95%CI: 1.540-314.292, P = 0.021). The intrahepatic expression of PPARGC1A mRNA was significantly lower in the group of patients who carried the risk A allele (P = 0.014). CONCLUSIONThe PPARGC1A rs8192678 risk A allele is associated with NAFLD, and with S2-3, A ≥ 2 and NASH in NAFLD patients, independent of PNPLA3 rs738409, and may be associated with nonobese NASH.

Protective Effect of Procyanidin B2 on Acute Liver Injury Induced by Aflatoxin B1 in Rats

ObjectiveThis study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B1 (AFB1) in rats. MethodsForty Sprague Dawley rats were randomly divided into control, AFB1, AFB1 + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB1 groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB1 and AFB1 + PCB2 groups were intraperitoneally injected with AFB1 (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2′-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. ResultsAFB1 significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB1. ConclusionOur findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB1.

The Role of Histone Deacetylase 9 in the Therapeutic Effects of Astaxanthin on Non-Alcoholic Steatohepatitis

Abstract Objectives The objectives of this study were to determine the role of histone deacetylase 9 (HDAC9) in the development of non-alcoholic steatohepatitis (NASH); and to evaluate the therapeutic effects of astaxanthin (ASTX), a xanthophyll carotenoid, on NASH via the modulation of HDAC9 in vivo. Methods Eight-week-old male and female wild-type (WT) and global Hdac9 knockout (KO) mice (n = 30/sex/genotype) were fed a high-fat/high-sucrose/high-cholesterol (HFHSHC) diet for 20 weeks to induce NASH. Subsequently, subsets of WT (n = 10/sex) and KO (n = 10/sex) mice were sacrificed to examine NASH features and served as baseline controls. The rest of the mice were randomly assigned into two diet groups for another 10 weeks: One continued on the HFHSHC diet, while the other group was fed an HFHSHC containing 0.03% ASTX (w/w). Results After 20 weeks on the HFHSHC diet, male KO mice had lower liver weights and triglycerides than WT, but no genotypic differences were observed in the female. Male KO mice showed less liver steatosis and fibrosis with significant decreases in the hepatic expression of lipogenic genes than male WT mice, but Hdac9 deletion did not inhibit NASH development in female mice. Compared with male KO baseline controls, consumption of control diet for an additional 10 week increased hepatic expression of lipogenic and pro-inflammatory genes in male KO mice, losing the beneficial effect of Hdac9 deletion shown at week 20 on the HFHSHC diet. However, the ASTX diet abrogated the induction. There were no significant differences in hepatic lipid contents and histological features of NASH between any genotypes regardless of ASTX supplementation. Also, additional control diet feeding did not induce any changes in hepatic gene expression in female mice, compared with those on the ASTX diet. Conclusions Hdac9 deletion protected male, but not female, mice from diet-induced hepatic steatosis and fibrosis, which may be attributable to decreased lipogenesis in the liver. However, the protection did not exist when liver damages progressed. Hdac9 deletion or ASTX alone did not alleviate the liver damage progression, but they together inhibited the induction of lipogenic and pro-inflammatory genes in the liver of male mice, indicating that they may have synergistic effects on ameliorating NASH progression. Funding Sources The study was supported by National Institutes of Health.

Induced sepsis by cecal ligation and puncture in a rat model: hepatic and renal histological features

Animal models have been developed in an attempt to test potential therapeutic agents. The study aims to determine the hepatic and renal histological features induced by sepsis following cecal ligation and puncture (CLP) in a rat model. Regarding the material, we used 20 adult-male Wistar rats (control group 1, n=10, and group 2, n=10, that underwent CLP protocol). The experimental protocol was approved by the National Sanitary Veterinary and Food Authority, Cluj (Romania), project number 116/11.05.2018. The endpoint of the experiment was pre-set to 10 hours post-surgery. A complete necropsy survey was performed. The main renal lesions detected histologically were: glomerular congestion and edema, hyalinization of glomerular mesangium, presence of hyaline in the urinary space with associated compression atrophy of vascular glomerular tuft, granules of hyaline in the lumen of cortical tubules, and reduction of the urinary space. The hepatic lesion identified histologically was represented by isolated miliary necrotic foci.

Mechanistic evaluation of AMPK/SIRT1/FXR signaling axis, inflammation, and redox status in thioacetamide-induced liver cirrhosis: The role of Cichorium intybus linn (chicory)-supplemented diet.

Liver cirrhosis is a scene profitable to the advance of hepatocellular carcinoma (HCC). The current work was engrossed to weigh the potential role of Cichorium intybus linn against thioacetamide (TAA)-induced liver cirrhosis and their probable underlying biochemical and molecular mechanisms. farnesoid-X-receptor (FXR) expression, proliferating cell nuclear antigen (PCNA) immunoreactivity, and activated AMP protein kinase (pAMPK), sirtuin-1 (SIRT1), and interleukin-6 (IL6) levels were estimated in hepatic tissue by real-time PCR, immunohistochemistry, and immunoassay, respectively. C. intybus linn supplementation caused a significant improvement in serum liver enzymes, albumin, bilirubin levels, tissues redox status and hepatic histological features in addition to decreased IL6 level, hydroxylproline content, and PCNA immunoreactivity. On contrary, increased pAMPK/SIRT1 levels and upregulated FXR gene expression were observed. C. intybus linn could feasibly protect against TAA-induced hepatic damage, fibrosis, and cirrhosis by relieving oxidative stress and by interruption of the inflammatory pathway via AMPK/SIRT1/FXR signaling. PRACTICAL APPLICATIONS: No specific therapies are available until now to target the underlying mechanisms for protection against liver diseases. Herbal protection is widely available and cheap with no side effect. Cichorium intybus linn, a natural supplement, is proved in this current work to have the potential of being hepatoprotectant, antioxidant, and anti-inflammatory agents, thus reducing the risk of hepatic cirrhosis.

Differences in the genetic backgrounds of patients with alcoholic liver disease and non-alcoholic fatty liver disease.

Background and AimAlcoholic liver disease (ALD) and non‐alcoholic fatty liver disease (NAFLD) have common hepatic histological features, but few studies have compared the genomic backgrounds of these two diseases. Here, we compared the genetic differences between ALD and NAFLD.MethodsThis study enrolled 318 Japanese patients with ALD (n = 118; male, 86%; median age, 62 years; liver cirrhosis, 58%; hepatocellular carcinoma [HCC], 31%) and NAFLD (n = 200; male, 55%; age, 61 years; cirrhosis, 19%; HCC, 12%). The genotype frequencies of 10 single nucleotide polymorphisms (SNPs) were analyzed.ResultsThe ADH1B genotype GG and ALDH2 genotype GG were observed more frequently, and the percentage of patients with the MTP genotype GG was lower in ALD compared with NAFLD patients (ADH1B, 16 vs 4%; ALDH2 84 vs 44%; MTP 62 vs 72%, respectively; all P < 0.01). Comparing noncirrhosis to cirrhosis, the frequency of the potassium voltage‐gated channel subfamily Q member 1 (KCNQ1) genotype TT and adrenoceptor beta 3 (ADRB3) genotype TT was increased significantly in ALD‐related cirrhosis. In contrast, the patatin‐like phospholipase 3 (PNPLA3) genotype CC was decreased significantly in NAFLD‐related cirrhosis. A comparison of patients with and without HCC demonstrated that the KCNQ1 genotype TT was increased significantly in both HCC groups. In addition, associations between the KCNJ15 genotype GG and ALD‐HCC and the G allele of PNPLA3 and NAFLD‐HCC were identified.ConclusionsSNPs in genes related to ethanol and lipid metabolism clearly differed between patients with ALD and NAFLD. KCNQ1 might affect the progression and hepatocarcinogenesis in both ALD and NAFLD.

Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults. This study examined the relationship between hepatic nuclear receptor (NR) expression and histologic features of NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis (NASH) are in clinical trials. Liver messenger RNA was isolated from 40 children (10‐19 years) undergoing end‐of‐treatment biopsy in the Treatment of NAFLD in Children (TONIC) trial. High‐throughput quantitative polymerase chain reaction assayed NR messenger RNA. Cluster analysis was used to group 36 NRs, and NR levels were related to histologic measures of specific NAFLD features. Cluster analysis determined five groupings of NRs. Significant (P < 0.05) differential expressions of specific NRs associated with histologic measures include farnesoid X receptor alpha and retinoic acid receptor (RARβ and RARβ) for steatosis; estrogen receptor alpha (ERα) and peroxisome proliferator‐activated receptor gamma 3 (PPARγ3) for hepatocellular ballooning; ER and PPARγ2 for lobular inflammation; PPARα/δ/γ1/γ2, ERα, constitutive androstane receptor, chicken ovalbumin upstream promoter transcription factor 1, RARα, RARβ1, retinoid X receptor, pregnane X receptor, thyroid hormone receptors α and β, and nuclear receptor related‐1 for fibrosis; and ERα and RARβ/β1/α for diagnosis of NASH. Conclusion: Differential expression of specific NRs correlates with histologic severity of specific NAFLD features. These NRs are pleiotropic transactivators regulating basal metabolic functions and inflammatory responses. Derangement of activity of these receptors in NAFLD provides a rationale for exploiting their ability with receptor‐specific ligands to ameliorate NASH and its consequences.

Histopathological changes and lipid metabolism in the liver of Bufo gargarizans tadpoles exposed to Triclosan

In the current study, the adverse effects of TCS on liver health of B. gargarizans tadpoles were assessed. B. gargarizans larvae were exposed to TCS at 0, 10, 30, 60, and 150 μg L−1 from Gosner stage 3 until metamorphic climax. The hepatosomatic index (HSI), hepatic histological and ultrastructural features, and transcript levels of genes associated with detoxification and oxidative stress as well as lipid metabolism in the livers were determined. Exposure to 150 μg L−1 TCS resulted in increased HSI of tadpoles at metamorphic climax. Histological changes characterized by an increase in the number of melanomacrophage, nucleus pyknosis, and deposition of collagen fibers were observed in liver at 60 and 150 μg L−1 TCS. Moreover, marked ultrastructural alterations including high electron dense in mitochondrial matrix and lipid accumulation were also observed. In addition, abundances of transcripts of Cu/Zn superoxide dismutase (SOD), phospholipid hydroperoxide glutathione peroxidase (PHGPx), and heat shock protein 90 (HSP90) were decreased in larvae exposed to 60 and 150 μg L−1 TCS, while transcript level of HSP90 was increased at 30 μg L−1 TCS. Also, abundances of transcripts of acetyl-CoA carboxylase (ACC), carnitine palmitoyltransferase 2 (CPT2), peroxisome proliferator-activated receptor alpha (PPARa), fatty acid elongase 1 (FAE), sterol carrier protein 2 (SCP) were significantly lesser in larvae exposed to 60 and 150 μg L−1 TCS. Overall, TCS at high levels induced histopathological changes in the liver of B. gargarizans tadpoles. This might have been due to the alteration of oxidative stress–related genes and lipid metabolism-related genes expression levels.

Association between plasminogen activator inhibitor-1 and severity of liver injury and cardiovascular risk in children with non-alcoholic fatty liver disease.

Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of the endogenous fibrinolytic system and is known to be increased in obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). We previously demonstrated that PAI-1 levels were closely related to the amount of hepatic steatosis in children. The aim of this study was to characterize plasma PAI-1 in relationship to severity of inflammation and fibrosis, as well as to plasma lipids in children with NAFLD. In 44 children with NAFLD, plasma PAI-1 levels and lipids were measured at the time of a liver biopsy. Hepatic histological features were systematically scored. Trend analysis was applied to determine the correlation of plasma PAI-1 levels with lipid markers for cardiovascular disease and with the staging of histological features in the liver. We found that plasma PAI-1 levels were significantly increased in children with increased severity of steatosis, lobular inflammation, ballooning and fibrosis. Furthermore, PAI-1 was strongly correlated with plasma lipids and insulin resistance indices. PAI-1 appears to be tightly related to both histologic severity of NAFLD as well as systemic features of the disease including insulin resistance and dyslipidemia. PAI-1 may be a mediator of disease progression and future cardiovascular complications in children with NAFLD.

Autophagy and nonalcoholic fatty liver disease

Autophagy is a lysosomal degradation pathway that functions to promote cell survival and maintain homeostasis by removing damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome whose hepatic histological features are similar to alcoholic liver disease (ALD), yet without excessive alcohol intake. Recent studies have revealed the close relationship of autophagy with development, progression, and outcome of NAFLD. Autophagy is capable of modulating lipid metabolism, improving insulin resistance, reducing oxidative stress, alleviating hepatocyte damage, etc., through multiple pathways. To induce hepatocyte autophagy pharmaceutically may be a novel therapeutic strategy for NAFLD. This review focuses on the mechanisms as well as the therapeutic targets of autophagy in NAFLD.

Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis.

The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m2) with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. LRYGB surgery was associated with significant weight loss (median BMI loss −13.7 [−16.4; −9.5] kg/m2), improved hepatic steatosis in all patients (55.5% with total resolution), and resolution of hepatic inflammation and hepatocyte ballooning in 100 and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase-3 levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death.