Hyperechogenicity and histopathological features of focal liver lesions.

The identification and accurate diagnosis of focal liver lesions are important in modern medicine, where diagnostic radiology plays an essential role. This review aimed to examine the hyperechogenicity and histopathological features of focal liver lesions. Hyperechogenic liver lesions can be either benign or malignant. Evidence shows that hyperechogenicity is caused by factors such as fat deposition, sinusoidal dilation, peliotic changes, and pseudoglandular patterns. Fat deposition is a common cause of increased echogenicity in hepatocellular carcinoma (HCC). Meanwhile, sinusoidal dilation and peliotic changes are more frequently observed in larger HCC nodules. Pseudoglandular patterns, characterized by the reflection of ultrasound waves at the walls of numerous acini, are associated with hyperechogenicity in well-to-moderately differentiated HCCs. Moreover, this review comprehensively examined the histological features that may cause hyperechogenic internal echoes in not only HCCs but also localized liver lesions (metastases of adenocarcinoma and neuroendocrine neoplasm, intrahepatic cholangiocarcinoma, cavernous hemangioma, focal nodular hyperplasia, and angiomyolipoma). To make an accurate diagnosis and provide appropriate management, it is important to understand the histopathological basis for hyperechogenicity in focal liver lesions. By maximizing the accuracy of imaging studies and enhancing the radiology-pathology correlation, unnecessary biopsies can be avoided, thereby reducing potential complications and mortality. This review can help facilitate the effective management of patients with focal liver lesions, thereby resulting in timely and appropriate treatment decision-making.

Intra-pancreatic fat is associated with continuous glucose monitoring metrics.

AIM: To investigate the relationship of fat in the pancreas with time spent in different glycaemic ranges. METHODS: Abdominal magnetic resonance imaging at 3.0 Tesla was used to quantify fat in the pancreas as both continuous [i.e. intra-pancreatic fat deposition (IPFD)] and binary (i.e. fatty change of the pancreas vs. normal pancreas) variables. Dexcom G6 devices were used to collect continuous glucose monitoring data every 5 min over a continuous 7-day period. Time above range (TAR), time in range (TIR) and time below range were computed. Statistical models were built to adjust for age, sex, body composition, and other covariates in linear regression analysis and analysis of covariance. RESULTS: In total, 38 individuals were studied. IPFD was significantly associated with TAR (p = .036) and TIR (p = .042) after adjustment for covariates. For every 1% increase in IPFD, there was a 0.3 unit increase in TAR and a decrease in TIR. Individuals with fatty change of the pancreas, when compared with those with normal pancreas, had significantly higher TAR (p = .034) and lower TIR (p = .047) after adjustment for covariates. Neither IPFD (p = .805) nor fatty change of the pancreas (p = .555) was associated with time below range after adjustment for covariates. CONCLUSION: Increased fat in the pancreas is associated with excessive glycaemic variability. Fatty change of the pancreas may contribute to heightening the risk of cardiovascular diseases.

Comprehensive analysis of dyslipidemia states associated with fat in the pancreas.

BACKGROUND: The global burden of cardiovascular diseases continues to rise, and it is increasingly acknowledged that guidelines based on traditional risk factors fail to identify a substantial fraction of people who develop cardiovascular diseases. Fat in the pancreas could be one of the unappreciated risk factors. This study aimed to investigate the associations of dyslipidemia states with fat in the pancreas. METHODS: All participants underwent magnetic resonance imaging on the same 3.0 T scanner for quantification of fat in the pancreas, analyzed as both binary (i.e., fatty change of the pancreas) and continuous (i.e., intra-pancreatic fat deposition) variables. Statistical analyses were adjusted for body mass index, glycated hemoglobin, fasting insulin, ethnicity, age, and sex. RESULTS: There were 346 participants studied. On most adjusted analyses, high-density lipoprotein cholesterol dyslipidemia was significantly associated with both fatty change of the pancreas (p = 0.010) and intra-pancreatic fat deposition (p = 0.008). Neither low-density lipoprotein cholesterol dyslipidemia nor triglyceride dyslipidemia were significantly associated with fatty change of the pancreas and intra-pancreatic fat deposition. The absence of any dyslipidemia was inversely associated with both fatty change of the pancreas (p = 0.016) and intra-pancreatic fat deposition (p < 0.001). CONCLUSIONS: Dyslipidemias are uncoupled when it comes to the relationship with fat in the pancreas, with only high-density lipoprotein cholesterol dyslipidemia having a consistent and strong link with it. The residual cardiovascular diseases risk may be attributed to fatty change of the pancreas.

Lipid Droplet-Associated Proteins Perilipin 1 and 2: Molecular Markers of Steatosis and Microvesicular Steatotic Foci in Chronic Hepatitis C.

Chronic infection with hepatitis C (HCV) is a major risk factor in the development of cirrhosis and hepatocellular carcinoma. Lipid metabolism plays a major role in the replication and deposition of HCV at lipid droplets (LDs). We have demonstrated the importance of LD-associated proteins of the perilipin family in steatotic liver diseases. Using a large collection of 231 human liver biopsies with HCV, perilipins 1 and 2 have been localized to LDs of hepatocytes that correlate with the degree of steatosis and specific HCV genotypes, but not significantly with the HCV viral load. Perilipin 1- and 2-positive microvesicular steatotic foci were observed in 36% of HCV liver biopsies, and also in chronic hepatitis B, autoimmune hepatitis and mildly steatotic or normal livers, but less or none were observed in normal livers of younger patients. Microvesicular steatotic foci did not frequently overlap with glycogenotic/clear cell foci as determined by PAS stain in serial sections. Steatotic foci were detected in all liver zones with slight architectural disarrays, as demonstrated by immunohistochemical glutamine synthetase staining of zone three, but without elevated Ki67-proliferation rates. In conclusion, microvesicular steatotic foci are frequently found in chronic viral hepatitis, but the clinical significance of these foci is so far not clear.

Unveiling the unreal: Comprehensive imaging review of hepatic pseudolesions.

Hepatic pseudolesions are defined as non-neoplastic focal abnormalities of the liver which can mimic or conceal true liver lesions. It is particularly common in liver due to its unique dual blood supply and the existence of multilevel anastomosis between them. Because of the recent advances in CT and MRI technology, they are being increasingly encountered in daily practice. Broadly they can be categorised in to (1) Focal parenchymal abnormalities like focal fatty change, focal fat sparing, focal confluent fibrosis, segmental hypertrophy and regenerative nodules, (2) Perfusion abnormalities which include transient hepatic parenchymal enhancement in portal vein obstruction, third inflow, intrahepatic shunts, hepatic arterial occlusion and hepatic venous obstruction, (3) Imaging pitfalls like parenchymal compression, unenhanced vessels and pseudolipoma. It is essential for the radiologists to be familiar with the typical and atypical imaging features of pseudolesions to avoid mistaking them for sinister pathologies and also to avoid overlooking underlying hidden pathologies.

Association Between the Normal-Density Psoas Muscle Index and Handgrip Strength or Gait Speed in Maintenance Hemodialysis Patients.

Introduction: This study aimed to evaluate the association between the psoas muscle (PM) index with or without fatty infiltration and various indices associated with muscle mass in hemodialysis (HD) patients. Methods: We included stable HD patients (n = 83). The collected data included subjective global assessment (SGA) score, ASM/Ht2 (appendicular skeletal muscle mass divided by the squared height in meters), gait speed (GS; m/s), and handgrip strength (HGS; kg). The abdominal computed tomography (CT) image was obtained using a CT scanner. The PM and normal-density PM (NPM) indices (mm2/m2) were calculated using the whole PM area or the area with an attenuation range of 35-100 HU divided by the squared height in meters. Results: Correlation coefficients for the SGA score, ASM/Ht2, HGS, and GS were greater for the NPM index than for the PM index. The linear regression analysis showed that, on multivariate analysis, the NPM index was significantly associated with the SGA score, ASM/Ht2, and GS. However, the PM index was significantly associated with the SGA score and ASM/Ht2 but not with HGS or GS. For calculating the low GS, the area under the receiver operating characteristic curve area was significantly greater for the NPM index than for the PM index (P = 0.012). Conclusion: The present study suggested that the NPM index excluding fatty infiltration may be an early and useful indicator for detecting muscle strength and physical performance among HD patients.

Chronic exposure of industrial grade calcium carbide and ethylene glycol alter histological architecture of systemic organs by disrupting redox balance in rat.

OBJECTIVES: The threat to human health or the surroundings by the use of artificial fruit ripening agents has become a global concern. Calcium carbide (CaC2) and ethylene glycol (EG) are the two widely using ripening agents. The present study evaluates the toxic effect of chronic exposures of CaC2 and EG in rats. METHODS: CaC2 and EG were administered to the rats for 180 days orally. The alterations in oxido-reduction status, haematological, biochemical and histopathological parameters were analysed. Arsenic content in CaC2 and animal samples were detected by atomic absorption spectrometer and phosphorus by molybdate-UV method. RESULTS: At chronic doses, there were no significant alterations in haematological and biochemical parameters except in creatinine level especially by EG. However, histological details revealed microvesicular fatty change in liver, corpuscles degeneration in kidney and lymphocytes infiltration in various tissues. In intestine, the mucosal lesion scoring was found high (p<0.01). SOD and CAT activities and GSH level was reduced significantly by CaC2 administration (p<0.01). Arsenic and phosphorus detected is above the toxic level: 7.222 and 13.91 mg/dL in CaC2, 1.634 and 6.22 mg/dL in blood and 0.563 and 6.99 mg/dL in liver, respectively. CONCLUSIONS: The study suggests that the industrial grade CaC2 and EG induce systemic toxicity to rats and the liver is the most susceptible organ. The CaC2 and EG toxicity is mediated through the upset of redox balance and subsequent inflammatory responses. This could be due to the presence of arsenic and phosphorus contents that detected above the normal level in the industrial grade CaC2.

Latent, sex-specific metabolic health effects in CD-1 mouse offspring exposed to PFOA or HFPO-DA (GenX) during gestation.

BACKGROUND: Perfluorooctanoic acid (PFOA) is an environmental contaminant associated with adverse metabolic outcomes in developmentally exposed human populations and mouse models. Hexafluoropropylene oxide-dimer acid (HFPO-DA, commonly called GenX) has replaced PFOA in many industrial applications in the U.S. and Europe and has been measured in global water systems from <1 to 9350 ng/L HFPO-DA. Health effects data for GenX are lacking. OBJECTIVE: Determine the effects of gestational exposure to GenX on offspring weight gain trajectory, adult metabolic health, liver pathology and key adipose gene pathways in male and female CD-1 mice. METHODS: Daily oral doses of GenX (0.2, 1.0, 2.0 mg/kg), PFOA (0.1, 1.0 mg/kg), or vehicle control were administered to pregnant mice (gestation days 1.5-17.5). Offspring were fed a high- or low-fat diet (HFD or LFD) at weaning until necropsy at 6 or 18 weeks, and metabolic endpoints were measured over time. PFOA and GenX serum and urine concentrations, weight gain, serum lipid parameters, body mass composition, glucose tolerance, white adipose tissue gene expression, and liver histopathology were evaluated. RESULTS: Prenatal exposure to GenX led to its accumulation in the serum and urine of 5-day old pups (P = 0.007, P < 0.001), which was undetectable by weaning. By 18 weeks of age, male mice fed LFD in the 2.0 mg/kg GenX group displayed increased weight gain (P < 0.05), fat mass (P = 0.016), hepatocellular microvesicular fatty change (P = 0.015), and insulin sensitivity (P = 0.014) in comparison to control males fed LFD. Female mice fed HFD had a significant increase in hepatocyte single cell necrosis in 1.0 mg/kg GenX group (P = 0.022) and 1.0 mg/kg PFOA group (P = 0.003) compared to control HFD females. Both sexes were affected by gestational GenX exposure; however, the observed phenotype varied between sex with males displaying more characteristics of metabolic disease and females exhibiting liver damage in response to the gestational exposure. CONCLUSIONS: Prenatal exposure to 1 mg/kg GenX and 1 mg/kg PFOA induces adverse metabolic outcomes in adult mice that are diet- and sex-dependent. GenX also accumulated in pup serum, suggesting that placental and potentially lactational transfer are important exposure routes for GenX.

Clinicopathological features of hepatocellular carcinoma with fatty change: Tumors with macrovesicular steatosis have better prognosis and aberrant expression patterns of perilipin and adipophilin.

The clinicopathological characteristics of steatosis in hepatocellular carcinoma (HCC) remain unclear. Here, we elucidate the features of macrovesicular steatosis (MaS) and microvesicular steatosis (MiS) in HCC and their relationships with background liver steatosis. A total of 165 HCC lesions were classified as MaS-HCC, MiS-HCC, or conventional HCC (cHCC) according to the cutoff value of 30% MaS or MiS in tumor cells. We analyzed the clinicopathological differences among these groups. MaS-HCC had less portal vein invasion, a higher proportion of HCC with intratumoral fibrosis, and a lower cumulative risk of recurrence than MiS-HCC or cHCC. Moreover, both MaS-HCC and MiS-HCC had lower incidences of hepatitis virus infection and higher levels of HbA1c than cHCC. Background liver steatosis was also higher in MaS-HCC than in cHCC. Immunohistochemical expression of perilipin (Plin1) and adipophilin (ADRP), major proteins expressed on lipid droplet membranes, revealed that almost all lipid droplets in HCC were Plin1 negative, whereas those in background liver were positive. In contrast, ADRP was expressed on lipid droplets in both HCC and background liver. We concluded that MaS-HCC and MiS-HCC were associated with metabolic abnormalities but exhibited different biologic behaviors. Furthermore, lipid droplets in HCC were pathophysiologically different from those in background liver.

Thai Perilla frutescens fruit oil alleviates carbon tetrachloride-induced hepatotoxicities in rats

Objective: To study the effect of perilla fruit oil against carbon tetrachloride (CCl4)-induced liver damage in rats. Methods: Perilla fruit oil was analyzed in terms of fatty acids, tocopherols and tocotrienols using chromatography. Sub-chronic toxicity of perilla fruit oil was investigated in rats for 90 d followed by a 28 d recovery period. Hematological, biochemical and pathological parameters were determined. To evaluate hepatoprotection, rats were divided into five groups and orally administered with Tween 80 for 10 d; Tween 80, silymarin, perilla fruit oil (0.1 mL/200 g) and perilla fruit oil (1 mL/200 g) for 10 d together with subcutaneous injection of CCl4 (2 mL/200 g) on days 9 and 10. Liver enzymes and pathological parameters were determined. Results: Perilla fruit oil contained α-linolenic acid (56.55％ of total fatty acid), β-tocopherol (49.50 mg/kg) and γ-tocotrienol (43.65 mg/kg). Rats showed significant changes in the percentage of monocytes and platelet indices following perilla fruit oil consumption for 90 d; in the percentage of neutrophils and lymphocytes, and RBC indices in the recovery period when compared with the deionized water group. Total protein and creatinine levels were increased while alkaline phosphatase and aspartate aminotransferase levels were decreased (P < 0.05). Organ weight index and pathological indicators did not change significantly. The liver of CCl4-induced rats showed remarkable centrilobular fatty changes, which was ameliorated by perilla fruit oil pretreatment. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase levels were decreased (P < 0.05) in rats given perilla fruit oil. Conclusions: Perilla fruit oil is rich in α-linolenic acid, β-tocopherol and γ-tocotrienol and improves blood biomarker levels and protects against CCl4-induced hepatotoxicity. Further studies are required before supporting its use for the treatment of hepatitis.

Acute pancreatitis-onset carcinoma in situ of the pancreas with focal fat replacement diagnosed using serial pancreatic-juice aspiration cytologic examination (SPACE).

A 59-year-old woman was admitted for acute pancreatitis. Abdominal computed tomography and magnetic resonance imaging revealed a swollen pancreatic parenchyma with dilatation of the main pancreatic duct (MPD) of the pancreas tail, which was separated from the normal pancreas body side by a locally atrophic part of the pancreas. Magnetic resonance cholangiopancreatography showed MPD stricture in the pancreas tail with dilatation of the upstream MPD. Endoscopic ultrasonography revealed that the MPD stricture of the pancreas tail was surrounded by a blurred and hypoechoic area. Endoscopic retrograde cholangiopancreatography was performed for serial pancreatic-juice aspiration cytologic examination (SPACE). The result indicated adenocarcinoma. Distal pancreatectomy was performed, and the histopathological examination showed high-grade PanIN (carcinoma in situ of the pancreatic duct) of the pancreas tail with atrophy and fibrosis of the pancreatic parenchyma, and local fat replacement adjacent to the lesion. The final histopathological diagnosis was carcinoma in situ of the pancreatic duct of the pancreas tail. Acute pancreatitis and local fatty change of the pancreatic parenchyma with MPD stricture are important clinical manifestations of pancreatic carcinoma in situ (PCIS) and performing SPACE in cases of MPD stricture without a recognizable mass is preferable for a diagnosis of PCIS.

Hepatocellular adenoma with severe fatty change in a male Spontaneously Diabetic Torii rat.

The Spontaneously Diabetic Torii (SDT) rat is a rat model of nonobese type 2 diabetes mellitus, and hepatocellular adenomas have not been reported in this model. We report a hepatocellular adenoma with severe fatty change in a male 42-week-old SDT rat fed a high-fat diet. At necropsy, the animal had a whitish nodular mass of approximately 2 cm in diameter in the right medial lobe. Histologically, the mass was well demarcated from the surrounding tissues, slightly compressing the adjacent hepatic parenchyma and widely compartmented by fibrous connective tissues. The mass consisted of vacuolated tumor cells resembling hepatocytes with a solid and occasionally trabecular growth pattern. Abundant neutral lipids, which were positive for fat with Oil Red O stain and which ultrastructurally had moderately dense material, were contained within the vacuoles of the tumor cells. Immunohistochemically, the tumor cells showed an increase in immunoreactivity or number for Cytokeratin 8/18 and proliferating cell nuclear antigen but were negative for mesenchymal markers. From these findings, the mass could be distinguished from hepatocellular hyperplasia and was diagnosed as hepatocellular adenoma. In rats, hepatocellular adenoma accompanied by severe fatty change is rare, and this is the first report of a hepatocellular tumor with severe fatty change in a SDT rat.

Rho-Kinase Inhibition During Early Cardiac Development Causes Arrhythmogenic Right Ventricular Cardiomyopathy in Mice.

OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty changes of the right ventricle, ventricular arrhythmias, and sudden death. Though ARVC is currently regarded as a disease of the desmosome, desmosomal gene mutations have been identified only in half of ARVC patients, suggesting the involvement of other associated mechanisms. Rho-kinase signaling is involved in the regulation of intracellular transport and organizes cytoskeletal filaments, which supports desmosomal protein complex at the myocardial cell-cell junctions. Here, we explored whether inhibition of Rho-kinase signaling is involved in the pathogenesis of ARVC. APPROACH AND RESULTS: Using 2 novel mouse models with SM22α- or αMHC-restricted overexpression of dominant-negative Rho-kinase, we show that mice with Rho-kinase inhibition in the developing heart (SM22α-restricted) spontaneously develop cardiac dilatation and dysfunction, myocardial fibrofatty changes, and ventricular arrhythmias, resulting in premature sudden death, phenotypes fulfilling the criteria of ARVC in humans. Rho-kinase inhibition in the developing heart results in the development of ARVC phenotypes in dominant-negative Rho-kinase mice through 3 mechanisms: (1) reduction of cardiac cell proliferation and ventricular wall thickness, (2) stimulation of the expression of the proadipogenic noncanonical Wnt ligand, Wnt5b, and the major adipogenic transcription factor, PPARγ (peroxisome proliferator activated receptor-γ), and inhibition of Wnt/ß-catenin signaling, and (3) development of desmosomal abnormalities. These mechanisms lead to the development of cardiac dilatation and dysfunction, myocardial fibrofatty changes, and ventricular arrhythmias, ultimately resulting in sudden premature death in this ARVC mouse model. CONCLUSIONS: This study demonstrates a novel crucial role of Rho-kinase inhibition during cardiac development in the pathogenesis of ARVC in mice.

Ginkgo biloba effects on mice fetal liver / Efectos de la ginkgo biloba en el hígado fetal de ratón

Ginkgo biloba is considered to be an alternative drug for various indications; unfortunately very few studies are available on its side effects. This present study describes the harmful effects of Ginkgo biloba on developing fetal liver. Two experimental groups of six pregnant female mice each were given Ginkgo biloba at human therapeutic dose (A) and a higher dose (B) throughout the gestation period. A third group (C) was taken as a control and given distilled water only. Fetal livers were examined and the effects of the drug observed. There were signs of congestion and fatty change along with dilatation of sinusoids in a dose dependent manner concluding that Ginkgo biloba affects fetal liver.

La Ginkgo biloba es considerada, en varias indicaciones, como un medicamento alternativo; sin embargo, existen pocos reportes disponibles sobre sus efectos secundarios. Este estudio describe los efectos nocivos de Ginkgo biloba en el desarrollo del hígado fetal. Dos grupos experimentales de 6 ratones hembras preñadas recibieron Ginkgo biloba en la dosis terapéutica humana (A) y una dosis más alta (B) por el período de gestación. Un tercer grupo control (C) recibió agua destilada. Los hígados fetales fueron examinados y observados los efectos de la droga. Hubo signos de congestión y degeneración grasa, junto con la dilatación de sinusoides en función de la dosis. Como conclusión la Ginkgo biloba afecta el hígado fetal.

Intratumoral Fat in Neurofibroma and Coexistence of Eccrine Hidrocystoma

We report a case of intratumoral fat in neurofibroma and coexistance of eccrine hidrocystoma on the occipital area of the scalp for one year duration. There are several diseases showing fatty change histopathologically. Among them, few cases of neurofibroma showing fatty change had been reported. The mechanism of fatty change is unclear, but several hypotheses are proposed. Here we report a case of neurofibroma showing fatty change and coexistence of eccrine hidrocystoma, and discuss the pathomechanism of fatty change and its relationship with disease.

Fatty Liver / 대한간학회지

No abstract available.

Inflammatory Pseud0tumor of the Liver: A case report

Inflammatory pseudotumor of the liver is a relatively rare entity, and frequently misdiagnosed as a malignant tumor. We report a case of inflammatory pseudotumor involving the liver in a 53year-old man. The liver function test and serum alpha-fetoprotein level were within normal range. His preoperative diagnosis was as hepatocellular carcinoma by radiologic studies, and ultrasonography guided fine needle aspiration cytology and biopsy were done but confirmative diagnosis of malignancy or pseudotumor was not given. Grossly a relatively well marginated reddish brown soft mass with focal hemorrhage, measuring 5.0 cm in the largest diameter, was noted in the left lobe of liver. Surrounding hepatic parenchyma was yellowish brown in color without cirrhosis. Microscopically the mass showed typical findings of inflammatory pseudotumor and the ing liver tissue revealed diffuse fatty change and moderate chronic inflammatory cell on in the portal areas.

Focal Fatty Change of the Liver

Focal fatty change of the liver is a nodular lesion which is a rarely described and poorly characterized entity. The hepatic nodule measured 1.4cm at its maximum diameter, was subcapsular in location and occurred adjacent to the falciform ligament. Microscopically it was composed of hepatic tissue with a preserved lobular architecture. The central venous structures and portal tracts with their triads were regularly placed. The cytoplasm of almost all of the hepatocytes within the nodule was replaced by macrovesicular fat vacuoles with the nuclei displaced. Several large abnormal vessels were found at the margin of the nodule. The nodule was discovered incidentally on postmortem examination of a female infant who proved, at autopsy, to have multiple cardiac anomalies and bronchopneumonia. The possible inadequate local tissue perfusion due to abnormal intrahepatic vessels at this particular location could be augmented by multiple cardiac anomalies culminating in focal ischemia and focal fatty change. When encountered in surgery or on gross examination, it could be confused with other space occupying lesions such as liver cell adenoma, abscess and metastatic lesions.