Increased Liver Size Research Articles

Increased Liver Size and Dysfunction, Ionoregulatory Disturbance and Opportunistic Infections in Atlantic Salmon (Salmo salar) at Low Temperatures: A Case Study

ABSTRACTIn recent lab‐based experiments, some post‐smolt Atlantic salmon (Salmo salar) held at 3°C for 5 weeks exhibited a range of clinical signs. They became lethargic and swam at the water's surface, developed ulcers to the head and jaw (clinical signs similar to tenacibaculosis in Norwegian salmon aquaculture) and had fin erosion, and this was associated with significant mortalities. In addition, when fish with ‘early’ and ‘advanced’ stages of these different clinical signs were further examined, their livers were found to be large, pale and friable. Fish with this aetiology also had elevated aspartate aminotransferase levels (indicative of liver damage), elevated plasma [Na+], [Cl−] and osmolality (indicating osmoregulatory impairment), low glucose levels (likely limiting metabolic responses to maintain homeostasis) and high circulating cortisol levels (∼100 ng/mL). This suite of physiological disturbances is very similar to that observed in a condition referred to as ‘Winter Syndrome’ or ‘Winter Disease’ (WS/WD) in cultured gilthead sea bream (Sparus aurata) and other fish species. Thus, it appears that WS/WD described here for the first time in Atlantic salmon, alone or in combination with opportunistic infections, results in lipid deposition in the liver, compromising liver function and osmoregulatory capacity, and metabolic collapse that ultimately results in significant losses.

Evaluating Silvering Stages in European Eels: A Study on Biological and Morphometric Variations in the Asi River, Türkiye

The European eel (Anguilla anguilla) undergoes significant morphological and physiological changes during its transition from the yellow to the silver stage, which are critical for its long-distance spawning migration. This study aimed to investigate these changes in European eels from the Asi River, located in Hatay, Türkiye, during their silvering process. A total of 96 eels were sampled in February 2019, and various morphometric measurements, including total length, body weight, eye dimensions and height, and pectoral fin lengths, were taken. Liver and gonad weights were also measured to assess the hepatosomatic index (HSI). The length–weight relationship for silver eels was described by the equation, W = 0.0072 × L2.732, with silver-stage eels showing a higher growth rate compared to yellow-stage eels, which had a relationship of W = 0.0184 × L2.397. The average total length of silver eels (431.2 ± 16.7 mm) was significantly greater than that of yellow eels (382.4 ± 11.9 mm). Additionally, pectoral fin length was significantly longer in silver eels (20.8 ± 1.1 mm) compared to yellow eels (14.8 ± 0.9 mm). The hepatosomatic index (HSI) for silver eels was also found to be higher than for yellow eels, indicating increased liver size as an adaptation for energy storage during migration. Eye height, a key indicator of silvering, showed a substantial increase during the transition, with silver-stage eels having an average eye height of 5.3 ± 0.2 mm compared to 4.2 ± 0.1 mm in yellow-stage eels.

Intestinal human carboxylesterase 2 (CES2) expression rescues drug metabolism and most metabolic syndrome phenotypes in global Ces2 cluster knockout mice.

Carboxylesterase 2 (CES2) is expressed mainly in liver and intestine, but most abundantly in intestine. It hydrolyzes carboxylester, thioester, and amide bonds in many exogenous and endogenous compounds, including lipids. CES2 therefore not only plays an important role in the metabolism of many (pro-)drugs, toxins and pesticides, directly influencing pharmacology and toxicology in humans, but it is also involved in energy homeostasis, affecting lipid and glucose metabolism. In this study we investigated the pharmacological and physiological functions of CES2. We constructed Ces2 cluster knockout mice lacking all eight Ces2 genes (Ces2-/- strain) as well as humanized hepatic or intestinal CES2 transgenic strains in this Ces2-/- background. We showed that oral availability and tissue disposition of capecitabine were drastically increased in Ces2-/- mice, and tissue-specifically decreased by intestinal and hepatic human CES2 (hCES2) activity. The metabolism of the chemotherapeutic agent vinorelbine was strongly reduced in Ces2-/- mice, but only marginally rescued by hCES2 expression. On the other hand, Ces2-/- mice exhibited fatty liver, adipositis, hypercholesterolemia and diminished glucose tolerance and insulin sensitivity, but without body mass changes. Paradoxically, hepatic hCES2 expression rescued these metabolic phenotypes but increased liver size, adipose tissue mass and overall body weight, suggesting a "healthy" obesity phenotype. In contrast, intestinal hCES2 expression efficiently rescued all phenotypes, and even improved some parameters, including body weight, relative to the wild-type baseline values. Our results suggest that the induction of intestinal hCES2 may combat most, if not all, of the adverse effects of metabolic syndrome. These CES2 mouse models will provide powerful preclinical tools to enhance drug development, increase physiological insights, and explore potential solutions for metabolic syndrome-associated disorders.

Sex-Linked Changes in Biotransformation of Phenol in Brook Trout (Salvelinus fontinalis) over an Annual Reproductive Cycle

The microsomal metabolism of phenol (11 °C) over an annual reproductive cycle from June to December was studied using fall spawning adult brook trout (Salvelinus fontinalis). Hepatic microsomes were isolated from three male and three female fish each month. Incubations were optimized for time, cofactor concentration, pH, and microsomal protein concentration. The formation of phase I ring-hydroxylation metabolites, i.e., hydroquinone (HQ) and catechol (CAT), was quantified by HPLC with dual-channel electrochemical detection. Sample preparation and chromatographic conditions were optimized to achieve the separation and sensitivity required for the analysis of these labile products. Biotransformation of phenol over a range of substrate concentrations (1 to 150 mM) was quantified for the calculation of Michaelis–Menten constants (Km and Vmax) for each month. Results indicate a nearly equal production of HQ and CAT among males and females in late June. At the peak of maturity in October, there was an approximate ten-fold greater production of ring-hydroxylation metabolites noted in females in comparison with males on a total liver basis. In vitro phase II biotransformation of phenol glucuronidation was assessed by determining the Michaelis–Menten constants (Km, Vmax) using brook trout hepatic microsomes over a range of substrate concentrations (1 to 60 mM). Initially, there were no significant differences in the glucuronide rate of formation (pmol/min/mg protein) or total capacity (nmol/min/liver) between females and males. At the peak of maturation, the maximum rate of glucuronide formation was 4-fold less in females; however, the total capacity was 2-fold less in females due to the increased liver size in the females. The alterations in biotransformation coincided with increases in the hepatic and gonadal somatic indices and with changes in plasma hormone concentrations. These experiments provide insight into the metabolic deactivation of xenobiotics and to provide data for the prediction of altered hepatic biotransformation rates and pathways during the reproductive cycle.

MASLD does not affect fertility and senolytics fail to prevent MASLD progression in male mice

Senescent cells have been linked to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effectiveness of senolytic drugs in reducing liver damage in mice with MASLD is not clear. Additionally, MASLD has been reported to adversely affect male reproductive function. Therefore, this study aimed to evaluate the protective effect of senolytic drugs on liver damage and fertility in male mice with MASLD. Three-month-old male mice were fed a standard diet (SD) or a choline-deficient western diet (WD) until 9 months of age. At 6 months of age mice were randomized within dietary treatment groups into senolytic (dasatinib + quercetin [D + Q]; fisetin [FIS]) or vehicle control treatment groups. We found that mice fed choline-deficient WD had liver damage characteristic of MASLD, with increased liver size, triglycerides accumulation, fibrosis, along increased liver cellular senescence and liver and systemic inflammation. Senolytics were not able to reduce liver damage, senescence and systemic inflammation, suggesting limited efficacy in controlling WD-induced liver damage. Sperm quality and fertility remained unchanged in mice developing MASLD or receiving senolytics. Our data suggest that liver damage and senescence in mice developing MASLD is not reversible by the use of senolytics. Additionally, neither MASLD nor senolytics affected fertility in male mice.

Ultrasound criteria for assessing the correction of metabolic-associated fatty liver disease and liver blood flow disorders using arginine in patients with coronary artery disease in combination with COVID-19

Background. Coronavirus disease 2019 (COVID-19) remains one of the most urgent global health problems today. In the conditions of its spread around the world, the global scientific community is trying to study not only respiratory, but also extrapulmonary manifestations of this infection. It is known that with COVID-19, the endothelium, the hemostasis system, and the liver are affected with the occurrence of such a complication as metabolic dysfunction-associated steatotic liver disease (MASLD). The most vulnerable group of patients in terms of coronavirus disease and its complications (including MASLD) are those with coronary heart disease (CAD), therefore the search for effective drugs and optimal ultrasound criteria to evaluate liver steatosis in the dynamics of treatment is the main task of modern medicine. Goal: to determine the ultrasound criteria for assessing the correction of MASLD and liver blood flow disorders using arginine in patients with CAD associated with COVID-19. Materials and methods. A prospective study was conducted in 52 patients with CAD combined with PCR-positive COVID-19. The study was carried out upon admission to the hospital and 6 months after discharge. Group I (n = 27) consisted of CAD + COVID-19 patients who, in addition to standard therapy for MASLD, received arginine for 6 months after discharge from the hospital; group II (comparison group, n = 25) included participants who received standard therapy wi­thout arginine. Results. Splanchnic artery duplex scanning at baseline showed that 21 (78.0 %) patients in group I and 19 (76.0 %) in group II had a decrease in peak systolic velocity (PSV) in the proper hepatic artery (PHA), an increase in portal vein blood flow at the beginning of treatment, as well as increased liver size in 20 (74.0 %) patients in group I and 17 (68.0 %) in group II. An increase in the attenuation coefficient was detected in all patients of groups I and II. There were no differences between the groups at the time of inclusion in the study in terms of splanchnic blood flow and atte­nuation coefficient. After 6 months of arginine treatment, an improvement in the portal vein blood flow and a decrease in blood flow velocity in the PHA, a decrease in the diameter of the portal vein, a decrease in the size of the right and left liver lobes were found in group I, with no improvement in group II. A repeated study revealed a decrease in the attenuation coefficient in group I and no changes in group II. At the beginning of the study, a direct correlation was found between fibrinogen and the attenuation coefficient in group I (r = 0.54; p < 0.05), as well as in group II (r = 0.51; p < 0.05). After 6 months, C-reactive protein decreased in both groups. Conclusions. In patients with CAD combined with COVID-19 in the presence of MASLD, a decrease in the portal vein blood flow and an increase in PSV in the PHA were found. When arginine was used for 6 months in combination with standard therapy, according to the European Society of Cardiology protocols, there was a significant decrease in the attenuation coefficient, PSV in the PHA, and an increase in the portal vein blood flow. This indicates the possibility of using the attenuation coefficient as the main marker, and PSV in the PHA and the portal vein blood flow as additional criteria for ultrasound assessment of MASLD correction with arginine in patients with CAD combined with COVID-19.

In Vitro to In Vivo Scalars for Drug Clearance in Nonalcoholic Fatty Liver and Steatohepatitis.

In vitro-in vivo extrapolation (IVIVE) allows prediction of clinical outcomes across populations from in vitro data using specific scalars tailored to the biologic characteristics of each population. This study experimentally determined scalars for patients with varying degrees of nonalcoholic fatty liver disease (NAFLD), ranging from fatty liver to nonalcoholic steatohepatitis (NASH) and cirrhosis. Microsomal, S9, and cytosol fractions were extracted from 36 histologically normal and 66 NAFLD livers (27 nonalcoholic fatty liver [NAFL], 13 NASH, and 26 NASH with cirrhosis). Corrected microsomal protein per gram liver (MPPGL) progressively decreased with disease severity (26.8, 27.4, and 24.3 mg/g in NAFL, NASH, and NASH/cirrhosis, respectively, compared with 35.6 mg/g in normal livers; ANOVA, P < 0.001). Homogenate, S9, and cytosolic protein showed a consistent trend of decline in NASH/cirrhosis relative to normal control (post-hoc t test, P < 0.05). No differences across the groups were observed in homogenate, S9, cytosolic, and microsomal protein content in matched kidney samples. MPPGL-based scalars that combine protein content with liver size revealed that the reduction in MPPGL in NAFL and NASH was compensated by the reported increase in liver size (relative scalar ratios of 0.96 and 0.99, respectively), which was not the case with NASH/cirrhosis (ratio of 0.63), compared with healthy control. Physiologically based pharmacokinetics-informed global sensitivity analysis of the relative contribution of IVIVE scalars (hepatic CYP3A4 abundance, MPPGL, and liver size) to variability in exposure (area under the curve) to three CYP3A substrates (alprazolam, midazolam, and ibrutinib) revealed enzyme abundance as the most significant parameter, followed by MPPGL, whereas liver volume was the least impactful factor. SIGNIFICANCE STATEMENT: Nonalcoholic fatty liver disease-specific scalars necessary for extrapolation from in vitro systems to liver tissue are lacking. These are required in clearance prediction and dose selection in nonalcoholic fatty liver and steatohepatitis populations. Previously reported disease-driven changes have focused on cirrhosis, with no data on the initial stages of liver disease. The authors obtained experimental values for microsomal, cytosolic, and S9 fractions and assessed the relative impact of microsomal scalars on predicted exposure to substrate drugs using physiologically based pharmacokinetics.

DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.

Coordinating epigenomic inheritance and cell cycle progression is essential for organogenesis. UHRF1 connects these functions during development by facilitating maintenance of DNA methylation and cell cycle progression. Here, we provide evidence resolving the paradoxical phenotype of uhrf1 mutant zebrafish embryos which have activation of pro-proliferative genes and increased number of hepatocytes in S-phase, but the liver fails to grow. We uncover decreased Cdkn2a/b and persistent Cdk4/6 activation as the mechanism driving uhrf1 mutant hepatocytes into S-phase. This induces replication stress, DNA damage and Atr activation. Palbociclib treatment of uhrf1 mutants prevented aberrant S-phase entry, reduced DNA damage, and rescued most cellular and developmental phenotypes, but it did not rescue DNA hypomethylation, transposon expression or the interferon response. Inhibiting Atr reduced DNA replication and increased liver size in uhrf1 mutants, suggesting that Atr activation leads to dormant origin firing and prevents hepatocyte proliferation. Cdkn2a/b was downregulated pro-proliferative genes were also induced in a Cdk4/6 dependent fashion in the liver of dnmt1 mutants, suggesting DNA hypomethylation as a mechanism of Cdk4/6 activation during development. This shows that the developmental defects caused by DNA hypomethylation are attributed to persistent Cdk4/6 activation, DNA replication stress, dormant origin firing and cell cycle inhibition.

(068) Perfluorooctane Sulfonate (pfos) And Perfluorooctanic Acid (pfoa) Sub-chronic Exposure has Minimal Impact on Erectile Function in Sprague-dawley Ratsa

Abstract Introduction Per and polyfluoroalkyl substances (PFAS) are commonly used in industrial and consumer products and are environmental and health contaminants. The most common PFAS chemicals, perfluorooctane sulfonate (PFOS) and perfluorooctanic acid (PFOA), are used in firefighting foam, nonstick bakeware, water-resistant fabrics, grease-resistant paper and fire-resistant materials. PFAS is a known endocrine disruptor and can reduce testosterone and lower semen quality. The impact of PFAS exposure on erectile physiology is unknown. Objective Our study will assess the effect of PFOS and PFOA on erectile function in Sprague-Dawley rats. We hypothesize that PFOS and PFOA will decrease erectile function. Methods Adult male Sprague-Dawley rats were divided into three groups (n=10/group): 1) Control; 2) PFOS (10mg/kg/day); and 3) PFOA (10mg/kg/day). PFOS/PFOA was dissolved in 0.05% Tween 20 and administered in drinking water for 28 days. Controls received 0.05% Tween 20 in drinking water. The study was carried out in two different cohorts of rats (n=4 and n=6/group). Following 28 days of PFOS/PFOA exposure, rats were placed on regular drinking water for 2 weeks. Body weights were collected weekly and terminal organ weights of liver, testes, spleen, heart, lungs, brain, seminal vesicles, kidneys, bladder, and thymus were recorded. Erectile function was assessed prior to PFAS exposure and every 2 weeks thereafter via apomorphine-induced behavioral erections and yawns. Nerve-stimulated intracavernosal pressure and mean arterial pressure (ICP/MAP) was measured 2 weeks after exposure stopped. Results Four weeks of PFOS exposure significantly decreased body weight while PFOA exposure did not impact body weight (Con: 588±63.5g; PFOS: 453±16.3g; PFOA: 535±29.9g, p&amp;lt;0.01). The PFOS dose in the second cohort was overtly toxic with 5/6 rats dying following 3-4 weeks of exposure. Two weeks following PFOS/PFOA exposure, livers were markedly enlarged (Con: 19.4±2.85g; PFOS: 25.4±0.16g; PFOA: 20.2±3.77g, p&amp;lt;0.01), spleens were smaller (Con: 0.93±0.12g; PFOS: 0.65±0.03g; PFOA: 0.88±0.12g, p&amp;lt;0.05), and testes were larger in PFOS rats (Con: 1.8±0.07g; PFOS: 2.0±0.06g; PFOA: 1.8±0.07). No other organ weights were different across exposure groups. PFOS/PFOA exposed animals had similar numbers of apomorphine-induced erections throughout the 6 week period. Two weeks post-exposure, ICP/MAP was unchanged between all groups (n=5-10/group). Ongoing studies will assess testosterone levels. Conclusions A sub-chronic PFOS exposure markedly decreased body weight, increased liver size, decreased spleen weight, and increased testes weight. PFOA exposure did not impact body or organ weights. Following PFOS or PFOA exposure, there was no change in apomorphine-induced behavioral erections or ICP/MAP. Additionally, the dose of PFOS assessed was quite toxic to the second cohort of animals. Future studies will assess if a more chronic exposure will impact erectile function. Disclosure No.

Condition, Reproductive Fitness, and Fluctuating Asymmetry in Brook Stickleback: Responses to Anthropogenic Runoff

Multiple indicators have been used to assess the degree of exposure of fish to anthropogenic chemicals in their stream habitats. We hypothesized that brook stickleback (Culaea inconstans) in a headwater stream receiving urban and agricultural runoff (South Fork Whitewater River, SFWR) would exhibit poorer condition, reduced reproductive fitness, and a greater left side to right side morphological asymmetry (i.e., fluctuating asymmetry or FA) than fish from a nearby headwater stream with a forested drainage basin (Garvin Brook). Male and female fish were collected from both streams just prior to spawning in 2013–2015. In 2013 and 2014, fish were assessed for overall condition (Fulton’s K), internal measures of condition (hepatosomatic index, HSI) and reproductive fitness (gonadosomatic index [GSI], total oocyte count, and oocyte mass). In 2015, measurements of head length, jaw length, eye diameter, pectoral fin length, and pelvic fin length were made on both sides of each fish for assessing degree of FA. We observed declining condition with fish size, increased liver size, and reduced oocyte counts and oocyte size in female brook stickleback in SFWR relative to those from Garvin Brook. SFWR females had significantly higher FA than Garvin females for all structures assessed, except pelvic fin length. FA also was slightly higher for all structures in SFWR males compared to Garvin males, but differences were not significant. A composite FA index combining all measurements from an individual fish into a single value displayed highly significant differences for female fish (SFWR FA &gt;&gt; Garvin FA), but not for male fish (SFWR FA = Garvin FA). Exposure of brook stickleback to reduced water quality in SFWR during early development appears to increase morphological asymmetry in female (but not male) fish, and continuing exposure to compromised water quality throughout life impacts both general condition and reproductive fitness of stickleback, especially older female fish, in SFWR.

A rare case of primary hepatic poorly differentiated leiomyosarcoma in a goat

A 12-year-old Saanen goat presented with a history of hyporexia and sudden recumbency. Euthanasia was indicated due to suspicion of hepatic neoplasia associated with senility. Necropsy revealed generalized oedema and increased liver size and weight (33 × 38 × 17 cm and 10.6 kg, respectively), with a firm, multilobular mass. Fusiform to polygonal neoplastic cells, with marked pleomorphism, anisocytosis and anisokaryosis, were seen on histopathological examination of the hepatic mass. The neoplastic cells were immunohistochemically positive for alpha-smooth muscle actin and vimentin but immunonegative for pancytokeratin. The Ki-67 index was 18.8%. A poorly differentiated leiomyosarcoma was diagnosed on the basis of the gross, histopathological and immunohistochemical findings and should be included in the differential diagnosis of liver disease in goats.

Two Hippo signaling modules orchestrate liver size and tumorigenesis.

The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.

Lowering temperature to 1 °C results in physiological changes, stress and mortality in cultured Atlantic Salmon (Salmo salar)

Atlantic salmon (Salmo salar) reared in sea-cages in Atlantic Canada and Iceland can be exposed to temperatures as low as 0–1 °C during the winter months, and this can result in large-scale mortalities. Despite this threat to salmon aquaculture, most of our knowledge of this species' thermal biology is at temperatures above 10 °C. In this laboratory experiment, Atlantic salmon post-smolts (175 ± 24 g) were exposed to a temperature decline of 1 °C/week (from 8 to 1 °C) with an additional week at 1 °C (to simulate temperature changes in sea-cages in Atlantic Canada during the winter months), or a constant temperature of 8 °C (control), and sampled weekly. Growth was reduced by 58% in the cold-exposed group and was associated with a decrease in appetite beginning at 6 °C. Starting at 4–5 °C, an osmoregulatory disturbance ensued characterized by higher plasma [Cl−], lower plasma [K+] and increased osmolality. Hsp70 and hsp90 transcript expression also increased as temperature was reduced from 5 to 1 °C. However, plasma cortisol levels did not increase (to ∼18 ng/ml) until the fish reached 1 °C, and serpinh1 and cirbp expression were not good biomarkers of decreasing temperature. Symptoms suggestive of liver dysfunction (changes in plasma [aspartate aminotransferase] and an increase in liver size) were also evident at 1 °C. Finally, at 1 °C, 5% of the fish died, and these mortalities were typically associated with snout ulceration/erosion and fin rot. In summary, Atlantic salmon held at temperatures <5 °C suffer from decreased growth performance, osmoregulatory disturbance, liver dysfunction, stress, opportunistic infections, and increased mortality.

P181 Mucor in the land of the liver: a case report

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Introduction and ObjectivesMucormycosis is a rare, highly lethal opportunistic fungal infection affecting immune-compromised patients. It accounts for about 2% of invasive fungal infections occurring within 1 year after solid organ transplantation. Among renal recipients, Rhinocerebral is the commonest manifestation and Rhizopus species is the most frequent pathogen.The objectives are:To report a case of Hepatic mucormycosis in a renal transplant recipient.To resolve the dilemma in identification of Mucorale species detected on microscopy but culture negative.MethodA 29-year-old male patient was admitted with severe abdominal pain on day 28 post-live related renal transplantation. Patient was hypertensive, on oral steroids for idiopathic thrombocytopenic purpura, chronic kidney disease with venous thromboembolism-presumed chronic interstitial nephritis, and maintained on hemodialysis for the last 1 year. Post-transplant he was on triple immunosuppressants.Initial ultrasound of abdomen and transplant doppler were normal. CT of abdomen in view of worsening hypotension and non-resolving abdominal pain, revealed hepatomegaly with multiple discrete, coalescing hypodense areas in both lobes of liver with minimal subcapsular extension. Initial cultures included interventional radiology-guided liver aspirate and blood culture. Patient was started on antibiotics and antifungals. Patient continued to deteriorate and a repeat abdominal CT revealed an increase in liver size and rupture of liver abscess. Sample collected on pigtail catheter insertion was also sent for culture.ResultsThe pus aspirate was received for bacterial and fungal culture. Aerobic bacterial culture yielded Klebsiella species. Examination with KOH Calcofluor revealed broad aseptate fungal hyphae. However, fungal culture did not yield any growth. Pain resistant (PDR) Klebsiella species was isolated from blood culture. Pigtail catheter sample also yielded the same. Aseptate fungal hyphae were observed in the pigtail catheter sample also. The team decided on conservative management and patient was started on intravenous amphotericin B deoxycholate(50 mg/day), tigecycline, and meropenem. Immunosuppressants were withheld. The clinical course worsened and the patient succumbed to illness after 18 days of antifungal therapy. The pus sample was then sent to the referral center PGIMER for PCR and sequencing where it was identified as Lichtheimia species.ConclusionMucormycosis is an increasingly emerging invasive fungal infection especially in immune-compromised patients, including solid organ transplant recipients. Though uncommon it is frequently a fatal mycosis in transplant patients. Hepatic mucormycosis in renal transplant recipients has been reported in three patients so far. None are due to Lichtheimia species. The diagnosis of hepatic mucormycosis was confirmed as microscopy was positive in two successive samples. Our patient also had bacteremia with PDR Klebsiella.Diagnosis is challenging and often delayed, as the clinical presentation is non-specific. Although mucormycosis in a renal transplant recipient is rare, a high index of suspicion and critical microscopic examination is warranted for early initiation of specific therapy which includes liposomal amphotericin B and surgery. Often cultures yield no growth and gene sequencing proves to be efficient and time-saving. This probably is the way ahead, especially for culture-negative samples to establish the etiological diagnosis.

Predictors of biliary intervention in patients hospitalized for COVID-19.

BackgroundGastrointestinal complications of coronavirus disease-2019 (COVID-19) include abnormal liver function and acalculous cholecystitis. Cholecystostomy performed during the COVID-19 pandemic reflected a shift toward non-surgical treatment of cholecystitis and increased number of critically ill patients suffering from acalculous cholecystitis.Purpose(1) To determine demographic, clinical, laboratory, and ultrasound features associated with cholecystostomy placement during hospitalization for COVID-19. (2) To develop multivariable logistic regression modeling for likelihood of biliary intervention.MethodsThis retrospective review received institutional review board approval. Informed consent was waived. Between March 2020 and June 2020, patients with confirmed SARS-CoV2 infection admitted to New York-Presbyterian Hospital (NYP)/Weill Cornell Medical Center, NYP/Lower Manhattan Hospital, and NYP/Queens were evaluated for inclusion in this study. Inclusion criteria were (1) patient age ≥ 18, (2) confirmed COVID-19 infection by polymerase chain reaction testing of a nasopharyngeal swab, and (3) abdominal ultrasound performed during hospitalization. Exclusion criteria were (1) history of cholecystectomy and (2) biliary intervention performed prior to abdominal ultrasound. Patients were stratified into two groups based on whether they received cholecystostomy during hospitalization. Differences in demographics, medical history, clinical status, medications, laboratory values, and ultrasound findings between the two groups were evaluated using Chi-square test or Fisher’s exact test for categorical variables and t test or Wilcoxon-rank sum test for continuous variables. Multivariable logistic regression was used to model likelihood of biliary intervention.ResultsNine patients underwent cholecystostomy placement and formed the “Intervention Group.” 203 patients formed the “No Intervention Group.” Liver size and diuretics use during hospitalization were the only variables which were significantly different between the two groups, with p-values of 0.02 and 0.046, respectively. After controlling for diuretics use, the odds of receiving cholecystostomy increased by 30% with every centimeter increase in liver size (p = 0.03). ICU admission approached significance (p = 0.16), as did mechanical ventilation (p = 0.09), septic shock (p = 0.08), serum alkaline phosphatase level (p = 0.16), and portal vein patency (0.14).ConclusionPatients requiring biliary intervention during hospital admission for COVID-19 were likely to harbor liver injury in the form of liver enlargement and require diuretics use.

Kaposiform hemangioendothelioma/Kasabach–Merritt syndrome. Сlinical and laboratory characteristics. Analysis of clinical cases

Kaposiform hemangioendothelioma (KHE) is a rare, usually congenital vascular tumor. It resembles Kaposi sarcoma histologically, but etiologically it is not associated with herpes simplex virus type 8. KHE refers to tumors of intermediate malignancy degree. The most severe complication is the addition of thrombocytopenia and consumption coagulopathy, i.e. development of the Kasabach–Merritt syndrome/phenomenon (KMS), which determines the high mortality rate (up to 30%) in this histological variant. The frequency of occurrence of KMS is unknown. Over Patients with KHE/KMS have clear clinical and laboratory characteristics, which in most cases allow make to diagnose without histological confirmation. Over 7-year follow-up period 32 patients with KHE were registered in our center; in 90.6% of cases it was complicated by the development of KMS. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. In the most of patients the tumor was detected from birth (84%), in half of the cases (52%) hematological complications were diagnosed simultaneously with the detection of the tumor. Сommon local complications include joint contractures, destruction of bone tissue, and invasion of neighboring organs. The half of the patients had changes in the heart function: from minor cardiac pathology to congenital defects. In addition, there were clinical and instrumental changes associated with volume overload: an increase in liver size, myocardial hypertrophy. Despite the presence of clear clinical and laboratory characteristics of KMS, some cases require differential diagnosis with other vascular anomalies accompanied by thrombocytopenia and consumption coagulopathy – with congenital hemangiomas (rapidly involuting congenital hemangioma), multifocal lymphangioendotheliomatosis with thrombocytopenia, kaposiform lymphangiomatosis, venous malformations. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.

Характеристика функціонального стану жовчного міхура та структурних змін печінки при неалкогольній жировій хворобі печінки в дітей

Протягом останнього десятиліття поширеність неалкогольної жирової хвороби печінки досягла масштабів епідемії, вона стала одним з найбільш поширених хронічних захворювань печінки в дитячій популяції. Мета: вивчити взаємозв’язок функціонального стану жовчного міхура зі структурними змінами печінки в дітей з неалкогольною жировою хворобою печінки. Матеріали й методи. Обстежені 34 дитини віком від 8 до 17 років. Визначення стеатозу печінки проводили з використанням апарата FibroScan® 502 touch з визначенням контрольованого параметра ультразвукового затухання (CAP). За даними еластометрії й УЗД органів черевної порожнини з дослідженням функції жовчного міхура пацієнти були розподілені на 4 групи: 1-ша група складалася з 7 пацієнтів зі стеатозом і гіпофункцією жовчного міхура (20,5 %), 2-га група — 6 пацієнтів зі стеатозом і нормокінезією жовчного міхура (17,65 %), 3-тя група — 11 пацієнтів без стеатозу печінки з гіпофункцією жовчного міхура (32,35 %), 4-та група — 10 пацієнтів без стеатозу печінки з нормофункцією жовчного міхура (29,4 %). Результати. Результати сонологічного обстеження продемонстрували, що в дітей 1-ї групи (стеатоз із гіпокінезією жовчного міхура) визначалися значно більші розміри часток печінки порівняно з 4-ю групою (діти без стеатозу з нормофункцією жовчного міхура). Крім того, показники жорсткості паренхіми печінки були максимальні у хворих зі стеатозом печінки й гіпокінезією жовчного міхура. Обговорення. Поєднання стеатозу печінки та гіпокінезії жовчного міхура в дітей супроводжується значним збільшенням розмірів печінки, підвищенням жорсткості паренхіми печінки зі збільшенням ступеня стеатозу. Отримані дані вказують на взаємозв’язок функції жовчного міхура та структурних змін печінки.

Liver-specific decrease in Tff3 gene expression in infant mice perinatally exposed to 2,3,7,8-tetrabromodibenzofuran or 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/DFs) are byproducts of brominated flame retardants and can cause adverse health effects. Although exposure to polychlorinated (PC) DD/DFs induces toxic effects, including liver injury and neurobehavioral disorder, little is known about toxicities associated with PBDD/DF exposure. Thus, we examined effects of perinatal exposure to brominated congener on the infant mouse. Gene expression in several organs, such as the liver and brain, was analyzed in mouse offspring born to dams administered 2,3,7,8-tetrabromodibenzofuran (TBDF; 9 or 45 μg/kg body weight) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 3 μg/kg body weight) on gestational day 12.5. An increase in liver size was observed in TBDF- or TCDD-exposed offspring in infancy. Gene microarray analysis revealed that 163 and 36 genes were markedly upregulated and downregulated, respectively, in the liver of TBDF-exposed mice compared with those in vehicle-treated mice on postnatal day (PND) 5. Significant increases in Cyp1a1, Cyp1a2, Fmo3, and Pnliprp1 and decreases in Tff3, Ocstamp, Kcnk16, and Lgals2 mRNA levels in TBDF-exposed offspring on PNDs 5 and 12 were confirmed by quantitative PCR. In particular, a significant reduction in Tff3 mRNA in the liver, but not in the brain, small intestine, colon, and kidney, was observed in offspring perinatally exposed to TBDF or TCDD. Ultrasonic calls of TBDF- or TCDD-exposed offspring on PNDs 3-5 were impaired. Taken together, perinatal exposure to polyhalogenated dioxin/furan congeners disrupts gene expression patterns in the liver and ultrasonic calling during infancy. These results suggest that liver injury may contribute to neurobehavioral disorder.

Emphysematous hepatic abscess and pyometra, both caused by Burkholderia cepacia, in a bitch

AbstractA thirteen‐year‐old female intact mixed dog was presented to the emergency service with a history of vomiting and apathy. The bitch was under treatment of prednisone for chronic cough. The patient was depressed and showed abdominal pain. Abdominal radiographs revealed an increased liver size, a rounded structure of gas opacity located within the liver and a soft tissue opacity mass in the caudal abdomen. The ultrasonographic findings of the abdomen were consistent with emphysematous hepatic abscess (HA), vacuolar hepatopathy, focal peritonitis and pyometra. Surgical drainage, lavage and omentalisation of the liver abscess were performed, followed by an ovariohysterectomy. Twelve hours after surgery, the patient died due to the suspected multiple organ failure. Culture of the abscess and uterine fluid revealed presence of Burkholderia cepacia. To the authors’ knowledge, this report represented the first description of HA presumably caused by the haematogeneous spread of Burkholderia cepacia from a uterine infection.

Ультразвукова діагностика характеру та давності травми живота

The purpose of the study was to study a complex of changes in ultrasound parameters of injured tissues of the liver, spleen, pancreas in mechanical trauma and their dependence on the nature and duration of injury. Materials and methods. Ultrasound examinations were performed in 60 injured patients (41 males and 19 females) aged 20 to 60 years old in the dynamics as for the 1st, 2nd, 3rd, 4th and 5th days after injury. Puncture, transverse and oblique scans from all possible accesses were used. The conditions of the liver, pancreas, spleen, kidneys were studied. Results and discussion. In the course of the studies, a high number of injuries to the abdominal and retroperitoneal organs was demonstrated; it was proved that isolated liver injuries were observed in 32%, in 68% the liver injury was combined with injuries of other abdominal organs. We observed isolated damage to the pancreas in 10%, in the remaining 90%, the injury to the pancreas was combined with damage to the liver, gallbladder and extrahepatic bile ducts, spleen, and intestines. Isolated injuries of the spleen were observed in 31% of patients; in other cases, the injury to the spleen was combined with injuries of other organs of the abdominal cavity. We observed isolated kidney damage in almost 15%. In 85% of cases, kidney damage was observed in combination with injuries of other parenchymal organs. It has been demonstrated that in the area of injured tissues of the liver, pancreas, spleen, and kidneys with blunt trauma to the abdomen in persons with no signs of alcohol intoxication, regular ultrasound changes are observed, which are in direct proportion to the time elapsed since the injury was caused. The main ultrasound signs of liver damage were ruptures of the parenchyma with the formation of intra-parenchymal or subcapsular hematomas. In general, for almost all the injured people the following sings were characteristic as an increase in liver size (often due to increased part of damage), heterogeneity of structure, blurred contours and their discontinuity, presence of hypo- and anechoic areas (hematomas) on the background of intact parenchyma. Characteristic ultrasound criteria of pancreatic damage in the first day are the lack of clear contours of the gland, their discontinuity, increase in the size of the gland, the presence of hypoechoic areas of different sizes. At ultrasound examination of the spleen, the main signs of its damage are the heterogeneity of the parenchyma and the presence of anechoic structure and free fluid in the abdominal cavity. In 69% of cases, the main sings were blurred and uneven contours of the spleen, as well as an increase in its size. Characteristic features of renal hematoma are an increase in their size, heterogeneity of structure with increasing echogenicity of the parenchyma, blurred contours and their discontinuity. Conclusion. It has been proven that it is advisable to use in a complex of changes in the parenchymal organs revealed by ultrasound examinations, both in cases of isolated organ trauma, and in cases of combined trauma of the abdominal cavity and retroperitoneal organs, to determine the time of causing damage, since it makes it possible to increase the objectivity of the results of establishing the duration of the injury