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Annals of Translational Medicine Sep 2021The goal of the present work is to provide an overview of the differential diagnosis of Wilson disease. (Review)
Review
OBJECTIVE
The goal of the present work is to provide an overview of the differential diagnosis of Wilson disease.
BACKGROUND
Wilson disease is a rare condition due to copper accumulation primarily in the liver and brain. Although there is no definitive cure, current anti-copper treatments are associated with better outcomes if initiated early and if the diagnosis is made promptly. However, diagnostic delays are frequent and often Wilson disease represents a diagnostic challenge. The diagnosis ultimately relies on a combination of clinical, laboratory and genetic findings, and it is crucial that clinicians list Wilson disease in their differential diagnosis, especially in patients presenting with a hepatocellular pattern of liver injury. Some biochemical and liver histological features of Wilson disease overlap with those of more common conditions including nonalcoholic fatty liver disease, alcohol-associated liver disease, and autoimmune hepatitis. In particular, hepatic steatosis, hepatocyte glycogenated nuclei, ballooning degeneration, and Mallory-Denk bodies are often identified in Wilson disease as well as more common liver diseases. In addition, the natural history of liver damage in Wilson disease and the risk of developing liver cancer are largely understudied.
METHODS
We conducted an enlarged review of published papers on Wilson disease focusing on its diagnosis and distinctive clinical and liver pathology features in relation to common non-cholestatic liver diseases with the final goal in aiding clinicians in the diagnostic process of this rare but treatable condition.
CONCLUSIONS
Aside from markedly altered copper metabolism, Wilson disease has essentially no pathognomonic features that can distinguish it from more common liver diseases. Clinicians should be aware of this challenge and consider Wilson disease in patients presenting with a hepatocellular pattern of liver injury.
PubMed: 34733946
DOI: 10.21037/atm-21-2264 -
International Journal of Surgical... May 2022Short telomere syndrome (STS) encompasses a broad family of genetically inherited conditions caused by various mutations in telomerase and other telomere maintenance... (Review)
Review
Short telomere syndrome (STS) encompasses a broad family of genetically inherited conditions caused by various mutations in telomerase and other telomere maintenance genes, resulting in premature telomere shortening. STS involves a variety of clinical manifestations, including dyskeratosis congenita, premature achromotrichia, bone marrow failure, immunodeficiency, pulmonary fibrosis and liver disease. Liver histopathologic features in STS patients have not been well characterized. We report a 46-year-old male patient who presented for dyspnea. The patient had a complicated medical history significant for immune thrombocytopenic purpura and splenectomy, recurrent respiratory tract infections, pneumonia, primary immunodeficiency, and severe hepatopulmonary syndrome. He and his brother both developed gray hair by their late 20s. He had a long history of intermittently elevated liver enzymes starting at age 33. These clinical manifestations prompted an evaluation for a possible telomere biology disorder, which revealed the telomere length was critically short and fell at or below the first percentile for age, supporting the diagnosis. The liver biopsy showed marked portal inflammation with interface hepatitis, ductular reaction and frequent foci of lobular inflammation with focal hepatocyte dropout. Hepatocytes around the portal tracts demonstrated ballooning degeneration and occasional Mallory-Denk bodies. A trichrome stain highlighted bridging fibrosis. A literature review shows liver histology is available in only a small number of STS patients, demonstrating a variety of morphologic features. Our case and others suggest liver disease associated with STS exhibits a spectrum of histopathology. Being aware of these features is important for establishing the correct diagnosis of STS which is under recognized.
Topics: Adult; Dyskeratosis Congenita; Growth Disorders; Humans; Hypercalcemia; Inflammation; Liver Diseases; Male; Metabolic Diseases; Middle Aged; Mutation; Nephrocalcinosis; Telomere
PubMed: 34714693
DOI: 10.1177/10668969211054102 -
Archives of Pathology & Laboratory... Jul 2022The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully...
CONTEXT.—
The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully established.
OBJECTIVE.—
To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on core-needle liver biopsies.
DESIGN.—
Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory-Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of <.05 was considered significant.
RESULTS.—
In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P < .001), dense lobular inflammation (P = .03), cholestasis (P < .001), ductular reaction (P = .001), hepatocyte degeneration (P < .001), and absence of advanced fibrosis stages (P < .001) were identified significantly more othen in ACLF patients than in disease controls on univariate analysis. On multivariate Cox regression analysis, the absence of advanced Ishak histologic activity index fibrosis stages (P = .02) and the presence of dense lobular inflammation (P = .04) were associated with increased 28-day mortality in ACLF patients. After adjusting the clinical causes of acute decompensation, only dense lobular inflammation was found as an independent predictor of short-term mortality (P = .04) in ACLF patients.
CONCLUSIONS.—
Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF.
Topics: Acute-On-Chronic Liver Failure; Biopsy; Cholestasis; Humans; Inflammation; Liver Cirrhosis; Necrosis; Prognosis
PubMed: 34705032
DOI: 10.5858/arpa.2021-0103-OA -
American Journal of Clinical Pathology Mar 2022Amiodarone-induced liver injury (AILI) is histopathologically similar to alcoholic steatohepatitis (ASH). We sought to elucidate their histologic differences and develop...
OBJECTIVES
Amiodarone-induced liver injury (AILI) is histopathologically similar to alcoholic steatohepatitis (ASH). We sought to elucidate their histologic differences and develop a scoring system to differentiate these two entities.
METHODS
A cohort of 17 AILI and 17 ASH cases was included in the initial study. Cases from three different institutions were included for further validation.
RESULTS
Macrovesicular steatosis was usually below 10% of the liver parenchyma in AILI. Hepatocyte ballooning degeneration was more common in ASH than in AILI. "Balloon-like" hepatocyte was more common in AILI than in ASH. Lobular neutrophilic inflammation, satellitosis, and cholestasis were more common in ASH. Mallory-Denk bodies and pericellular fibrosis in AILI were mainly located in zone 1 compared with a panacinar or zone 3 distribution in ASH. A scoring system was developed in which points were assigned to different histologic features; a total sum of less than 5 suggests AILI, more than 5 is ASH, and 5 is equivocal. This scoring system was then evaluated on a test cohort comprising 14 AILI cases, in which 13 cases were correctly assigned with a score less than 5. The sensitivity, specificity, and accuracy for diagnosing AILI in the test cohort were 92.9%, 91.7%, and 92.3%, respectively.
CONCLUSIONS
This scoring system can aid pathologists to differentiate AILI from ASH.
Topics: Amiodarone; Chemical and Drug Induced Liver Injury, Chronic; Fatty Liver; Fatty Liver, Alcoholic; Humans; Liver
PubMed: 34596220
DOI: 10.1093/ajcp/aqab142 -
Histochemistry and Cell Biology Jan 2022Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The...
Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression.
Topics: Hepatocytes; Humans; Inflammation; Liver; Necrosis; Non-alcoholic Fatty Liver Disease
PubMed: 34524512
DOI: 10.1007/s00418-021-02030-8 -
Current Biology : CB Sep 2021Each winter, the North Atlantic Ocean is the stage for numerous cyclones, the most severe ones leading to seabird mass-mortality events called "winter wrecks." During...
Each winter, the North Atlantic Ocean is the stage for numerous cyclones, the most severe ones leading to seabird mass-mortality events called "winter wrecks." During these, thousands of emaciated seabird carcasses are washed ashore along European and North American coasts. Winter cyclones can therefore shape seabird population dynamics by affecting survival rates as well as the body condition of surviving individuals and thus their future reproduction. However, most often the geographic origins of impacted seabirds and the causes of their deaths remain unclear. We performed the first ocean-basin scale assessment of cyclone exposure in a seabird community by coupling winter tracking data for ∼1,500 individuals of five key North Atlantic seabird species (Alle alle, Fratercula arctica, Uria aalge, Uria lomvia, and Rissa tridactyla) and cyclone locations. We then explored the energetic consequences of different cyclonic conditions using a mechanistic bioenergetics model and tested the hypothesis that cyclones dramatically increase seabird energy requirements. We demonstrated that cyclones of high intensity impacted birds from all studied species and breeding colonies during winter but especially those aggregating in the Labrador Sea, the Davis Strait, the surroundings of Iceland, and the Barents Sea. Our broad-scale analyses suggested that cyclonic conditions do not increase seabird energy requirements, implying that they die because of the unavailability of their prey and/or their inability to feed during cyclones. Our study provides essential information on seabird cyclone exposure in a context of marked cyclone regime changes due to global warming..
Topics: Animals; Atlantic Ocean; Birds; Charadriiformes; Cyclonic Storms; Humans; Seasons
PubMed: 34520704
DOI: 10.1016/j.cub.2021.06.059 -
Journal of Clinical and Experimental... 2021The presence of macrovesicular steatosis on liver biopsy is the commonest histopathological finding. Nonalcoholic fatty liver disease (NAFLD) is the presence of ≥5%...
BACKGROUND
The presence of macrovesicular steatosis on liver biopsy is the commonest histopathological finding. Nonalcoholic fatty liver disease (NAFLD) is the presence of ≥5% macrovesicular steatosis without significant alcohol use. It is subdivided into primary and secondary NAFLD; information on their differences is limited.
AIM
To determine the histopathological differences between primary and secondary NAFLD and establish whether the prevalence of advanced fibrosis varies between the two types.
METHODOLOGY
Three years of retrospective study of 90 liver biopsies with ≥5% macrovesicular steatosis. Age, gender, clinical history, serum transaminase levels were noted. The biopsy was reviewed for steatosis, inflammation, and fibrosis. Differences between primary and secondary NAFLD for age, gender, AST/ALT ratio, histopathological features were determined. Descriptive statistical analysis, 2-tailed Student's test, Chi-square test, Fisher's exact test were used, where p < was considered significant.
RESULT
Primary and secondary NAFLD were 42 (46.7%) and 48 (53.3%), respectively. Inflammation was noted in 50 (55.5%) and fibrosis in 31 (34.4%). The prevalence of advanced fibrosis was 24.4%. Primary and secondary NAFLD differed significantly on ballooning degeneration, Mallory Denk bodies (MDBs), glycogenated nuclei, and fibrosis stage (p < 0.05). There were no significant differences among AST/ALT ratio, steatosis, and inflammation grade.
CONCLUSION
Primary NAFLD is a more severe type of liver disease. On histopathology, ballooning degeneration, MDBs, glycogenated nuclei, and advanced fibrosis was more prevalent in primary than secondary NAFLD.
PubMed: 34511816
DOI: 10.1016/j.jceh.2020.12.009 -
Antioxidants (Basel, Switzerland) Jul 2021Tartary buckwheat is used as an ingredient in flour and tea, as well as in traditional Chinese medicine for its antioxidant effects. Here, we found that an ethanol...
Tartary buckwheat is used as an ingredient in flour and tea, as well as in traditional Chinese medicine for its antioxidant effects. Here, we found that an ethanol extract of tartary buckwheat (TBE) potently induced autophagy flux in HeLa cells by suppressing mTORC1 activity, as revealed by dephosphorylation of the mTORC1 substrates Ulk1, S6K, and 4EBP, as well as by the nuclear translocation of transcriptional factor EB. In addition to non-selective bulk autophagy, TBE also induced aggrephagy, which is defined as autophagy against aggregated proteins. Quercetin is a flavonol found at high levels in TBE. We showed that quercetin induced both non-selective bulk autophagy and aggrephagy. These effects were also observed in Huh-7 cells derived from hepatocytes. Thus, aggrephagy induction by TBE and quercetin may relieve alcoholic hepatitis, which is closely linked to the accumulation of protein aggregations called Mallory-Denk bodies.
PubMed: 34439466
DOI: 10.3390/antiox10081217 -
Scientific Reports Aug 2021A well-documented phenomenon among social insects is that brain changes occur prior to or at the onset of certain experiences, potentially serving to prime the brain for...
A well-documented phenomenon among social insects is that brain changes occur prior to or at the onset of certain experiences, potentially serving to prime the brain for specific tasks. This insight comes almost exclusively from studies considering developmental maturation in females. As a result, it is unclear whether age-related brain plasticity is consistent across sexes, and to what extent developmental patterns differ. Using confocal microscopy and volumetric analyses, we investigated age-related brain changes coinciding with sexual maturation in the males of the facultatively eusocial sweat bee, Megalopta genalis, and the obligately eusocial bumble bee, Bombus impatiens. We compared volumetric measurements between newly eclosed and reproductively mature males kept isolated in the lab. We found expansion of the mushroom bodies-brain regions associated with learning and memory-with maturation, which were consistent across both species. This age-related plasticity may, therefore, play a functionally-relevant role in preparing male bees for mating, and suggests that developmentally-driven neural restructuring can occur in males, even in species where it is absent in females.
Topics: Aging; Animals; Bees; Female; Male; Mushroom Bodies; Sweat
PubMed: 34426595
DOI: 10.1038/s41598-021-96268-w -
Journal of Molecular Histology Oct 2021The metabolic syndrome (MetS) and pathologies associated with metabolic dysregulations a worldwide growing problem. Our previous study demonstrated that pioglitazone...
The metabolic syndrome (MetS) and pathologies associated with metabolic dysregulations a worldwide growing problem. Our previous study demonstrated that pioglitazone (PGZ) has beneficial effects on metabolic syndrome associated disturbances in the heart. However, mechanism mediating the molecular alterations of Ubiquitin proteasome system (UPS) and autophagy has not been investigated in rat pancreas with metabolic syndrome. For this reason, we first aimed to detect whether MetS effects on the expression of UPS (p97/VCP, SVIP, Ubiquitin) and autophagic (p62, LC3) proteins in rat pancreas. The second aim of the study was to find impact of pioglitazone on the expression of UPS and autophagic proteins in MetS rat pancreas. To answer these questions, metabolic syndrome induced rats were used as a model and treated with pioglitazone for 2 weeks. Pancreatic tissue injuries, fibrosis and lipid accumulation were evaluated histopathologically in control, MetS and MetS-PGZ groups. Apoptosis and cell proliferation of pancreatic islet cells were assessed in all groups. UPS and autophagic protein expressions of pancreas in all groups were detected by using immunohistochemistry, double-immunfluorescence and Western blotting. Compared with the controls, the rat fed with high sucrose exhibited signs of metabolic syndrome, such as higher body weight, insulin resistance, higher triglyceride level and hyperglycaemia. MetS rats showed pancreatic tissue degeneration, fibrosis and lipid accumulation when their pancreas were examined with Hematoxilen-eozin and Mallory trichrome staining. Metabolic, histopathologic parameters and cell proliferation showed greater improvement in MetS-PGZ rats and pioglitazone decreased apoptosis of islet cells. Moreover, SVIP, ubiquitin, LC3 and p62 expressions were significantly increased while only p97/VCP expression was significantly decreased in MetS-rat pancreas compared to control. PGZ treatment significantly decreased the MetS-induced increases in autophagy markers. Additionally, UPS and autophagy markers were found to colocalizated with insulin and glucagon. Colocalization ratio of UPS markers with insulin showed significant decrease in MetS rats and PGZ increased this ratio, whereas LC3-insulin colocalization displayed significant increase in MetS rats and PGZ reversed this effect. In conclusion, PGZ improved the pancreatic tissue degeneration by increasing the level of p97/VCP and decreasing autophagic proteins, SVIP and ubiquitin expressions in MetS-rats. Moreover, PGZ has an effect on the colocalization ratio of UPS and autophagy markers with insulin.
Topics: Animals; Apoptosis; Autophagy; Autophagy-Related Proteins; Cell Proliferation; Glucagon; Insulin; Male; Metabolic Syndrome; Microtubule-Associated Proteins; Pancreas; Pioglitazone; Proteasome Endopeptidase Complex; Rats, Wistar; Ubiquitin; Rats
PubMed: 34410563
DOI: 10.1007/s10735-021-10013-1