-
Medicine Mar 2023Hepatic arteriovenous malformations (HAVMs) are a rare disorder reported in association with hereditary hemorrhagic telangiectasia (HHT), known as Rendu-Osler-Weber...
RATIONALE
Hepatic arteriovenous malformations (HAVMs) are a rare disorder reported in association with hereditary hemorrhagic telangiectasia (HHT), known as Rendu-Osler-Weber syndrome. HAVMs are usually detected in adulthood.
PATIENT CONCERNS
A 29-year-old pregnant woman underwent a routine prenatal examination at 37 weeks of pregnancy.
DIAGNOSIS AND INTERVENTIONS
There were fetal liver anomalies detected by prenatal ultrasonography and were managed. Furthermore, a hepatic mass was detected and was subsequently analyzed by fetal magnetic resonance imaging. There were no typical imaging findings in this case which was once misdiagnosed as a hepatoblastoma.
OUTCOMES
Considering the massive hepatic lesion, labor induction was performed on a pregnant woman to avoid adverse maternal and fetal outcomes. Histopathological examination confirmed the diagnosis of HAVMs. Lesions detected by imaging were determined to be hemorrhagic and necrotic.
LESSONS
Prenatal hepatic hemorrhage and necrosis due to an arteriovenous malformation are rare. The authors describe their observations and results.
Topics: Female; Humans; Adult; Arteriovenous Malformations; Telangiectasia, Hereditary Hemorrhagic; Liver Diseases; Magnetic Resonance Imaging; Hemorrhage; Necrosis; Fetus
PubMed: 36961151
DOI: 10.1097/MD.0000000000033380 -
Biochemical Pharmacology Sep 2015Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of-concept study...
Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of-concept study to assess the therapeutic potential of WA in a mouse model that mimics APAP-induced liver injury (AILI) in humans. Overnight fasted C57BL/6NTac (5-6 wk. old) male mice received 200 mg/kg APAP intraperitoneally (i.p.). After 1 h mice were treated with 40 mg/kg WA or vehicle i.p., and euthanized 4 and 16 h later; their livers were harvested and serum collected for analysis. At 4 h, compared to vehicle-treated mice, WA-treated mice had reduced serum ALT levels, hepatocyte necrosis and intrahepatic hemorrhage. All APAP-treated mice had reduced hepatic glutathione (GSH) levels however, reduction in GSH was lower in WA-treated when compared to vehicle-treated mice. Compared to vehicle-treated mice, livers from WA-treated mice had reduced APAP-induced JNK activation, mitochondrial Bax translocation, and nitrotyrosine generation. Compared to vehicle-treated mice, WA-treated mice had increased hepatic up-regulation of Nrf2, Gclc and Nqo1, and down-regulation of Il-6 and Il-1β. The hepatoprotective effect of WA persisted at 16 h. Compared to vehicle-treated mice, WA-treated mice had reduced hepatocyte necrosis and hepatic expression of Il-6, Tnf-α and Il-1β, increased hepatic Gclc and Nqo1 expression and GSH levels, and reduced lipid peroxidation. Finally, in AML12 hepatocytes, WA reduced H₂O₂-induced oxidative stress and necrosis by preventing GSH depletion. Collectively, these data show mechanisms whereby WA reduces necrotic hepatocyte injury, and demonstrate that WA has therapeutic potential in AILI.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Antioxidants; Cell Line; Cell Survival; Chemical and Drug Induced Liver Injury; Crosses, Genetic; Glutathione; Hemorrhage; Inflammation Mediators; Injections, Intraperitoneal; Lipid Peroxidation; Liver; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Necrosis; Oxidative Stress; Random Allocation; Specific Pathogen-Free Organisms; Withanolides
PubMed: 26212553
DOI: 10.1016/j.bcp.2015.07.024 -
Ecotoxicology and Environmental Safety Jun 2021Hepatopancreatic Necrosis Syndrome (HPNS) severely impacts the Chinese mitten crab (Eriocheir sinensis) industry. However, little knowledge of the aetiology and...
Hepatopancreatic Necrosis Syndrome (HPNS) severely impacts the Chinese mitten crab (Eriocheir sinensis) industry. However, little knowledge of the aetiology and pathogenesis of the disease causes significant difficulties in its prevention and control. In this study, we conducted a pathological analysis of HPNS through time-integrated large-volume sampling, to clarify the disease characteristics and mechanism of HPNS-afflicted crabs; besides, animal models were constructed to verify the pathological diagnosis. The results showed that the hepatopancreas was the principal target organ of HPNS; multiple correspondence analysis revealed that the main histopathological characteristics included non-interstitial atrophic hepatopathy diseases such as hepatic tubule atrophy, dilated hepatic tubules, and hepatic tubule necrosis. Additionally, the muscles also showed signs of disease, including myofibre atrophy, necrosis, and inflammation. Ultrastructural studies showed prominent apoptosis and autophagy-like alterations in the hepatopancreas of HPNS-afflicted crabs. Further, the establishment of animal models revealed that the double variate stimulation of environmental variables such as abamectin/sewage with nutrition deficiency could result in HPNS-similar lesions. Based on these studies, we concluded that HPNS is a chronic hepatopancreas-initiated energy-consumed disease with a low likelihood of pathogen but a high probability of environment and nutrition.
Topics: Animals; Apoptosis; Brachyura; China; Hepatopancreas; Inflammation; Necrosis; Seafood
PubMed: 33773151
DOI: 10.1016/j.ecoenv.2021.112157 -
Biochimica Et Biophysica Acta.... Mar 2020Lipotoxicity causes hepatic cell death and therefore plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metformin, a first-line...
Lipotoxicity causes hepatic cell death and therefore plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metformin, a first-line anti-diabetic drug, has shown a potential protective effect against NAFLD. However, the underlying mechanism is still not clear. In this study, we aim to understand the molecular mechanism of the protective effect of metformin in NAFLD, focusing on lipotoxicity. Cell death was studied in HepG2 cells and primary rat hepatocytes exposed to palmitate and metformin. Metformin ameliorated palmitate-induced necrosis and apoptosis (decreased caspase-3/7 activity by 52% and 57% respectively) in HepG2 cells. Metformin also reduced palmitate-induced necrosis in primary rat hepatocytes (P < 0.05). The protective effect of metformin is not due to reducing intracellular lipid content or activation of AMPK signaling pathways. Metformin and a low concentration (0.1 μmol/L) of rotenone showed moderate inhibition on mitochondrial respiration indicated by reduced basal and maximal mitochondrial respiration and proton leak in HepG2 cells. Moreover, metformin and rotenone (0.1 μmol/L) preserved mitochondrial membrane potential in both HepG2 cells and primary rat hepatocytes. In addition, metformin and rotenone (0.1 μmol/L) also reduces reactive oxygen species (ROS) production and increase superoxide dismutase 2 (SOD2) expression. Our results establish that metformin AMPK-independently protects against palmitate-induced hepatic cell death by moderate inhibition of the mitochondrial respiratory chain, recovering mitochondrial function, decreasing cellular ROS production, and inducing SOD2 expression, indicating that metformin may have beneficial actions beyond its glucose-lowering effect and also suggests that mitochondrial complex І may be a therapeutic target in NAFLD.
Topics: Animals; Apoptosis; Cell Death; Cell Line, Tumor; Hep G2 Cells; Hepatocytes; Humans; Lipid Metabolism; Liver; Male; Metformin; Mitochondria; Necrosis; Non-alcoholic Fatty Liver Disease; Palmitates; Protective Agents; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase
PubMed: 31786336
DOI: 10.1016/j.bbadis.2019.165621 -
Medicine Nov 2022Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a major complication of methotrexate (MTX) therapy that can develop in patients with rheumatoid...
Primary hepatic methotrexate-associated lymphoproliferative disorder associated with Epstein-Barr virus reactivation and accompanied by spontaneous necrosis: A case report.
RATIONALE
Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a major complication of methotrexate (MTX) therapy that can develop in patients with rheumatoid arthritis (RA), although primary hepatic MTX-LPD is extremely rare. Discontinuation of MTX results in remission in half of the patients with MTX-LPDs and is one treatment approach.
PATIENT CONCERN
A 64-year-old Japanese woman suffering from rheumatoid arthritis treated with MTX presented with upper abdominal pain.
DIAGNOSIS
Pathological evaluation showed that the tumor contained geographic necrosis and proliferation of large atypical lymphocytes strongly positive for cluster of differentiation 20 (CD20) antigen with immunohistochemical staining and Epstein-Barr Virus-encoded RNA transcript by in situ hybridization. The tumor was finally diagnosed as a primary hepatic MTX-associated Epstein-Barr Virus positive B-cell LPD.
INTERVENTIONS
Left hepatic lobectomy was performed for diagnosis and therapy.
OUTCOMES
No sighs of recurrence were observed for 2 years.
LESSONS
This patient demonstrated that MTX-LPD could arise in the liver, although it is rare. If liver tumors arise in patients taking MTX, examination of sIL-2R, Epstein-Barr virus-VCA IgG and EBNA might support the diagnosis of MTX-LPD. In this case, the primary hepatic MTX-LPD became necrotic without discontinuation of MTX. It is generally believed that withdrawal of MTX restores antitumor immunity resulting in tumor necrosis. This case indicates that spontaneous regression might occur without any treatment in some patients treated for RA with MTX-LPD. The relationship between MTX-LPD and spontaneous necrosis is unclear and further data is required to characterize the types of patients that will develop spontaneous regression without intervention.
Topics: Female; Humans; Middle Aged; Methotrexate; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Lymphoproliferative Disorders; Necrosis; Liver; Arthritis, Rheumatoid; Antigens, CD
PubMed: 36451467
DOI: 10.1097/MD.0000000000031993 -
Annals of Hepatology 2009Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent... (Review)
Review
Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent retransplantation. Two main forms of HAT are recognized as early and late HAT (diagnosis within or after 30 days following LT). Early HAT typically results in graft failure. Late HAT features biliary obstruction, cholangitis, and hepatic abscess formation. We report here the case of a patient of Wilson's disease who presented twelve years post-liver transplant symptoms typical of acute HAT and hepatic infarction. On diagnostic imaging, celiac axis and hepatic artery were thrombosed, resulting in ischemic necrosis of the left hepatic lobe. The resulting sepsis and transient hepatic insufficiency were managed conservatively, and repeat OLT was avoided. The patient remains stable more than one year later. To the best of our knowledge this case report is unique in the literature for the unusually long interval between OLT and late acute HAT, as well as celiac and portal vein occlusion. The acute presentation of sub massive hepatic necrosis is also uncharacteristic of late HAT and more typical of acute HAT. This report describes our experience in managing this and a literature review of the topic.
Topics: Adult; Celiac Artery; Hepatic Artery; Humans; Infarction; Liver; Liver Transplantation; Male; Portal Vein; Thrombosis; Tomography, X-Ray Computed
PubMed: 20009144
DOI: No ID Found -
Oxidative Medicine and Cellular... 2016Hepatic diseases are a major concern worldwide. Increased specific plasma enzyme activities are considered diagnostic features for liver diseases, since enzymes are... (Review)
Review
Hepatic diseases are a major concern worldwide. Increased specific plasma enzyme activities are considered diagnostic features for liver diseases, since enzymes are released into the blood compartment following the deterioration of the organ. Release of liver mitochondrial enzymes is considered strong evidence for hepatic necrosis, which is associated with an increased production of ROS, often leading to greater hepatic lipid peroxidation. Lipotoxic mediators and intracellular signals activated Kupffer cells, which provides evidence strongly suggesting the participation of oxidant stress in acute liver damage, inducing the progression of liver injury to chronic liver damage. Elevated transaminase activities are considered as an index marker of hepatotoxicity, linked to oxidant stress. However, a drastic increase of serum activities of liver enzyme markers ought not necessarily to reflect liver cell death. In fact, increased serum levels of cytoplasmic enzymes have readily been observed after partial hepatectomy (PH) in the regenerating liver of rats. In this regard, we are now showing that in vitro modifications of the oxidant status affect differentially the release of liver enzymes, indicating that this release is a strictly controlled event and not directly related to the onset of oxidant stress of the liver.
Topics: Animals; Antioxidants; Enzymes; Humans; Liver; Necrosis; Oxidants; Oxidative Stress; Vitamins
PubMed: 26798419
DOI: 10.1155/2016/3529149 -
Proceedings of the National Academy of... Jan 2024The presence of bacteria in the bloodstream is associated with severe clinical outcomes. In mice, intravenous inoculation of can lead to the formation of macroscopic...
The presence of bacteria in the bloodstream is associated with severe clinical outcomes. In mice, intravenous inoculation of can lead to the formation of macroscopic abscesses in the liver. Abscesses are regions of severe necrosis and consist of millions of bacteria surrounded by inflammatory immune cells. Liver abscess susceptibility varies widely across strains of mice, but the host factors governing this variation are unknown. Here, we profiled hepatic transcriptomes in mice with varying susceptibility to liver abscess formation. We found that transcripts from endogenous retroviruses (ERVs) are robustly induced in the liver by infection and ERV expression positively correlates with the frequency of abscess formation. Hypothesizing that ERV-encoded reverse transcriptase may generate cytoplasmic DNA and heighten inflammatory responses, we tested whether nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) influence abscess formation. Strikingly, a single NRTI dose administered immediately following inoculation prevented abscess formation, leading to a concomitant 100,000-fold reduction in bacterial burden. We provide evidence that NRTIs inhibit abscess formation by preventing the tissue necrosis that facilitates bacterial replication. Together, our findings suggest that endogenous reverse transcriptases drive inflammatory responses during bacterial bloodstream infection to drive abscess formation. The high efficacy of NRTIs in preventing abscess formation suggests that the consequences of reverse transcription on inflammation should be further examined, particularly in infectious diseases where inflammation drives negative clinical outcomes, such as sepsis.
Topics: Animals; Mice; Reverse Transcriptase Inhibitors; Escherichia coli; Escherichia coli Infections; Liver Abscess; Bacterial Infections; Endogenous Retroviruses; Nucleotides; Sepsis; Necrosis
PubMed: 38227662
DOI: 10.1073/pnas.2319162121 -
Journal of Orthopaedic Science :... Jul 2016Steroid (glucocorticoid)-induced osteonecrosis of the femoral head (ONFH) in young adults has been a challenging disorder due to frequent incidence of collapse of the... (Review)
Review
BACKGROUND
Steroid (glucocorticoid)-induced osteonecrosis of the femoral head (ONFH) in young adults has been a challenging disorder due to frequent incidence of collapse of the femoral head and resulting dysfunction of the hip joint and impairing quality of life. In Japan, the working group on ONFH in the Specific Disease Investigation Committee under auspices of the Japanese Ministry of Health, Labor and Welfare was founded in 1975, clinical and related basic research on ONFH have been continued for more than 40 years.
EPIDEMIOLOGY AND CLINICAL COURSE
A national epidemiologic survey in 2004 estimated that 2200 new patients per year would be diagnosed with ONFH in Japan. ONFH was associated with steroid intake (51%), heavy alcohol intake (31%), both (3%), and neither (15%). The male-to-female ratio was 5:4, and the peak decades of age at definitive diagnosis were the 40s in male patients and the 30s in females. MRI studies revealed that ONFH would have occurred in early phase after start of steroid administration and no expansion of necrotic lesion within the femoral head in spite of continued steroid use. To standardize ONFH diagnosis and treatment strategy, the Committee established validated diagnostic criteria, a radiological staging system, and type categorization.
TREATMENT OPTIONS
Most symptomatic patients with collapse of the femoral head require various surgical procedures. Joint preserving surgery, such as transtrochanteric rotational osteotomy and curved varus osteotomy, should be the treatment choice for young patients with healthy areas without severe collapse of the femoral head.
CLINICAL AND RELATED BASIC RESEARCH
Clinical and basic research has been performed to determine the pathogenesis of steroid-induced ONFH. Low hepatic CYP3A activity has been reported to significantly contribute to the risk of steroid-induced ONFH. Several gene polymorphisms related to steroid metabolism were shown to be associated with the occurrence of ONFH.
Topics: Femur Head Necrosis; Glucocorticoids; Humans; Japan; Research
PubMed: 27062553
DOI: 10.1016/j.jos.2016.03.008 -
Toxicologic Pathology Feb 2009Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels...
Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) to induce expression of genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPARalpha-mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation, increased catalase expression, and hepatocellular hypertrophy and hyperplasia. Female mice fed 0.5% phytol and male and female mice fed 1% phytol exhibited midzonal hepatocellular necrosis, periportal hepatocellular fatty vacuolation, and corresponding increases in liver levels of the phytol metabolites phytanic acid and pristanic acid. Hepatic expression of sterol carrier protein-x (SCP-x) was five- to twelve-fold lower in female mice than in male mice. These results suggest that phytol may cause selective midzonal hepatocellular necrosis in mice, an uncommon pattern of hepatotoxic injury, and that the greater susceptibility of female mice may reflect a lower capacity to oxidize phytanic acid because of their intrinsically lower hepatic expression of SCP-x.
Topics: Animals; Apoptosis; Body Weight; Carrier Proteins; Cell Death; Dose-Response Relationship, Drug; Fatty Acids; Female; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Necrosis; Organ Size; PPAR alpha; Peroxisomes; Phytanic Acid; Phytol; Reference Standards; Sex Factors; Time Factors
PubMed: 19188468
DOI: 10.1177/0192623308330789