Liver Mass Research Articles

Mixed Neuroendocrine Non-Neuroendocrine Tumor (MINEN) of the Liver: Report of Two Cases and Review of the Literature.

To highlight two cases mixed neuroendocrine non-neuroendocrine tumors (MINEN) of the liver and to review the literature till date. To present two cases of MINEN of the liver diagnosed in our centre with clinical & diagnostic workup, the treatment modalities, and follow up. Extensive review of the literature and compilation of the presentation and treatment modalities used in those cases. Thirty-three cases of MINEN of the liver have been reported till date including ours. Our cases presented as incidental masses in liver during workup for other symptoms. AFP levels were normal in both cases but PIVKA (Protein induced by vitamin K absence) levels were increased. Resection was done in one of the cases while the other patient had to undergo transplantation. A diagnosis of MINEN was made on H&E, and confirmed on IHC. One patient was unfit for systemic chemotherapy whereas the other patient received cisplastin and etoposide based chemotherapy. Both patients developed metastasis on follow up but are still alive after 12-15 months. MINEN is an uncommon tumor of the liver with a poor prognosis as shown by the few studies available. Recurrence and distant metastases are often described even after complete resection and the course is fatal. The role of adjuvant chemotherapy following surgical resection is not fully elucidated. Mean survival in the cases reported ranged from 1 month to 33 months. However, no significant differences were seen in the clinicopathologic profile of the cases described so far. Further multiinstitutional studies and follow up will help to further characterize this subtype for appropriate treatment.

An unusual cause of liver neoplasm in an older female.

We presented a 66-year-old woman with T2DM who had a liver mass discovered incidentally during hospitalization. She was asymptomatic with a right upper abdominal mass that was smooth, mobile, and non-tender. Hepatitis virus markers and tumor markers were normal. The computed tomography (CT) images showed a 4.7×4.0 cm lesion in the left liver lobe with indistinct borders. Further magnetic resonance imaging (MRI) revealed low T1 and high T2 signal intensity with ring-shaped enhancement following contrast administration. Surgical resection was performed, and histology confirmed hepatic angioleiomyoma with thick-walled vessels and spindle cell proliferation. Immunohistochemistry was positive for SMA, desmin, caldesmon, CD31, and CD34. The patient had no recurrence during 5 years follow-up.

Alterations of Liver Morphology in Senescent Rats.

Age-related liver changes can have important implications for health and metabolic function. This study aimed to describe the morphoquantitative alterations of the liver in senescent rats compared to adult rats. Twelve male rats were used, divided into 6-month-old adults (group A) and 36-month-old senescent rats (group S). Morphometric and histopathological studies, quantification of collagen types I and III, and stereological analyses were performed to determine the volume density of mononucleated (VvhepM) and binucleated (VvhepB) hepatocyte nuclei, surface area density (SvhepM), and number density (NvhepM) of mononucleated hepatocyte nuclei. The findings reveal an alteration of the normal liver tissue architecture in senescent rats and the presence of inflammatory lesions and fibrosis. In addition, there was a decrease in body and liver mass and volume. Group S showed a significant reduction in VvhepM and NvhepM; however, SvhepM was significantly higher. No significant differences were noted in the percentage of binucleated hepatocytes between the two groups. This study reveals substantial morphological changes in the aging liver, with possible functional implications. More research is needed on the underlying mechanisms and their consequences at older ages.

Insulin-like growth factor-1 deficiency caused by hepatocellular adenoma leads to growth arrest, primary amenorrhea and metabolic syndrome: a case report and 4 years follow up

BackgroundHepatocellular adenoma (HCA) is a rare benign neoplasm, seldom ascribed as the cause of endocrine and metabolic derangement. We herein report a case of primary amenorrhea, growth arrest and metabolic syndrome. En bloc resection of the tumor normalized all the disturbances.Case presentationA 16-year-old girl complained of primary amenorrhea and growth arrest for the past 2 years. Her height and weight were at the 3rd percentile, whereas waist circumference was at the 90th percentile for chronological age. She was hypertensive on admission. Plasma cholesterol, triglyceride and uric acid were elevated. Evaluation of GH/IGF-1 axis showed extremely low IGF-1 concentration, which was unresponsive to hGH stimulation. Computer tomography identified a huge liver mass (18.2 cm×13.7 cm×21 cm). The patient underwent an uneventful open right hepatic lobectomy. The tumor was en bloc resected. Immunohistochemistry indicated an unclassified HCA, which was confirmed by genetic screening. IGF-1 concentration, blood pressure, lipid profile and ovarian function were all normalized after surgery, and the girl had reduction in waist circumference and gain in height during the follow up.ConclusionWe provide evidence that liver-derived IGF-1 has a direct effect on skeletal and pubertal development, blood pressure, visceral adiposity and dyslipidemia independent of insulin resistance and obesity in the circumstance of undernutrition. Though rare, we propose the need to look into HCA cases for the existence of IGF-1 deficiency and its impact on metabolic derangement.

Salidroside promotes liver regeneration after partial hepatectomy in mice by modulating NLRP3 inflammasome-mediated pyroptosis pathway

Insufficient residual liver tissue after partial hepatectomy (PH) may lead to serious complications such as hepatic failure and small-for-size syndrome. Salidroside (SAL) is obtained from Rhodiola rosea through modernized separation and extraction and has been validated for treating various liver diseases. It's yet unknown, nevertheless, how SAL affects liver regeneration after PH. This study aimed to determine whether SAL could promote liver regeneration after PH in mice. We demonstrated that SAL could attenuate liver injury after PH and promote hepatocyte proliferation and liver mass recovery. Mechanistically, SAL inhibited the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, attenuating pyroptosis. RNA-seq analysis indicated that SAL downregulated the transcription of NLRP3 and GSDMD genes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the NOD-like receptor signaling pathway was significantly enriched in down-regulated signaling pathways. Notably, SAL in combination with the NLRP3 inhibitor MCC950 did not further inhibit NLRP3 inflammasome and promote liver mass recovery. In summary, our findings proved that SAL could be a potential agent for improving liver function and promoting liver regeneration after PH.

Is a two-hour monitoring period sufficient and safe for patients undergoing ultrasound-guided percutaneous liver mass biopsy?: A prospective and multicenter experience.

To investigate whether patients undergoing percutaneous liver mass biopsy (PLMB) can be safely discharged following a two-hour monitoring period. A multi-center prospective analysis was conducted for 375 patients (196 males and 179 females), mean age 63 ± 12.45 years (range 37-89) who underwent PLMB between August 2023 and March 2024. Patients were monitored for 24 h, and complications were classified as minor or major. The timing of complications was categorized into three groups: within the first two hours, between the 2nd and 24th hours, and within 1 week after 24 hours. Minor complications occurred in 18.93% (71/375) and major complications in 2.13% (8/375). Most minor complications (80.2%, 57/71) appeared within the first two hours, 12.7% (9/71) between 2 and 24 h, and 7.1% (5/71) after 24 h. All major complications (62.5%, 5/8) except late-onset cases, occurred within the first two hours. No major complications occurred between 2 and 24 h. Late-onset major complications occurred in 37.5% (3/8) after 24 h. The two-hour monitoring period did not adversely impact patient management regarding minor complications and is safe for identifying all major complications except for late-onset ones. Extending the post-biopsy recovery period does not significantly improve patient care.

Tumor in the liver: Six inflammatory pseudotumor patient

Inflammatory pseudotumor (IPT) is a rare liver disease confused with liver tumors. It is a disease that should be known in the differential diagnosis for clinicians as the correct diagnosis of IPT will prevent unnecessary surgery. Demographic datas, diagnoses and imaging modalities of six patients with radiologically and/or histopathologically diagnosed hepatic IPT between 2016 and 2023 were retrospectively analyzed. Four out of six patients were female and median age was 57.5 (47-66). C-reactive protein was higher in four patients, and carbohydrate antigen 19.9 level was higher in one patient. We used magnetic resonance imaging (MRI) for diagnosis in five patients. Only in one patient computed tomography was enough for diagnosis. Tumor locations were segment 5 for two patients, segment 7-8 in two patients, segment 7 in one patient, and 8 in one patient. Liver biopsy was performed in five patients because it could not be distinguished from malignancy by imaging methods. Histopathological results of all these biopsies defined as IPT. Initial tumor median size was 31 (17-55) mm. Two patients were operated on. The first one underwent right hepatectomy due to a 2-fold increase in size within 11 months. The second one had a mass indistinguishable from hepatic adenoma by MRI and underwent nonanatomic resection. In one patient, IPT disappeared completely in the 18th month of follow-up period while it regressed in size in two patients. Two of our patients had a history of recurrent endoscopic retrograde cholangiopancreatography, which we noticed incidentally before IPT was diagnosed. IPTs are liver masses with low malignant potential and may shrink spontaneously during follow-up. We suspected that biliary tract interventions may be the cause of IPT.

Intra- and interobserver agreement in computed tomography localization of primary nonhematopoietic hepatic masses and comparison with surgical and histopathological outcomes in 21 cats.

Computed tomography (CT) is commonly used in the staging of hepatic masses and for liver lobectomy planning. Mass location is an important factor in determining the feasibility of resection, including surgical technique and the likelihood of surgical complications. The objectives of this retrospective descriptive cross-sectional, observer agreement, method comparison study were to assess the reliability of CT in correctly determining the hepatic division and lobar site of origin of feline primary nonhematopoietic hepatic masses, compared with surgically confirmed locations. Furthermore, it provides an overview of the types and locations of liver masses found in a cohort of cats. Pre- and postcontrast CT images of 21 cats were independently and simultaneously reviewed by two observers. Intra- and interobserver agreements and descriptive statistics on demographic and histological diagnoses were calculated. Based on surgical assessment, it was found that masses most frequently originated from the left hepatic division (13/24, 54%). The most frequent lobar origins were the left lateral (8/24, 33%), left medial (5/24, 21%), and right medial lobes (5/24, 21%). No masses were found originating from the right lateral lobe. CT correctly determined hepatic division and lobar origin in 76% of cases, with good-to-excellent intra- and interobserver agreement. The hepatic division had higher agreements overall for both observers. Most of the masses were benign (17/21, 81%), and the most prevalent histological diagnoses were biliary cystadenoma (11/21, 52%) and hepatocellular adenoma (6/21, 29%). Findings suggest that postcontrast CT is a reliable method for correctly determining hepatic mass division and lobar origin in cats.

Locoregional Treatments in Peritoneal Metastasis from Gastric Cancer

Background: Liver cancer is among the top five causes of cancer death globally. Hepatocellular Carcinoma (HCC) accounts for up to 90% of primary liver neoplasms in adults. The incidence of thyroid me-tastasis from HCC is rare and estimated from 0.8 to 12%. This report describes a 51-year-old man presenting with hypercalcemia and known metastatic HCC with new metastasis to the thyroid gland. Case Report: A 51-year-old male was admitted due to symptomatic hypercalcemia. His medical history included HCC with metastasis to the retroperitoneal lymph nodes diagnosed one year prior. Computed tomography revealed an enlarging liver mass, diffuse lymphadenopathy and many osseous lytic lesions. Ultrasound of the neck revealed abnormal right cervical lymph nodes and a heterogeneous mass replacing the right thyroid gland. Biopsy of the right cervical lymph node immunohistochemical stained positive for PAN-K, Glypican-3, HepPar1 and Anti-Arginase and negative for p40 and CEA-poly, supporting the diagnosis for metastatic HCC. His hospital course was complicated by dysphagia, spontaneous bacterial peritonitis and acute-on-chronic liver failure. Despite aggressive resuscitation, he continued to decline and ultimately pursued hospice care. Conclusion: This case illustrates the need to have a high index of suspicion for thyroid metastasis in HCC patients presenting with a new-onset cervical mass, dysphagia or hypercalcemia. Metastatic cancer to the thyroid gland is generally considered a poor prognostic factor, as seen in this case with the rapid decline. This case demonstrates an extremely rare presentation of HCC with metastasis to the thyroid gland.

Urachus carcinoma initially presenting only as a liver metastasis, a diagnostic and therapeutic challenge: First case in literature

Introduction: Urachal carcinomas are uncommon malignant neoplasms comprising only 0.01% of all adult cancers. Most patients were aged from 58 to 64 years at diagnosis with 60 years being the median. It usually metastasizes to the lungs (22%), bones (22%), and liver (16%). Presentation: We report a case of a 71-year-old female patient initially presented with two large liver masses and a small nodule on the anterior side of the bladder. The symptoms were non-specific with abdominal discomfort. The final diagnosis of Urachal Adenocarcinoma was finalized with a biopsy of the bladder mass. The patient initially received six doses of FOLFOX6 without improvement and then Gem-Carbo, showing improvement after six doses. Finally, the patient received two doses of FOLFIRI-B with no response and kept deteriorating and died after 19 months of treatment. Discussion: About 90% of patients are symptomatic and hematuria is the most typical presenting symptom at diagnosis. The low incidence and the histopathologic similarities to adenocarcinoma from various sources pose a difficulty in recognizing the tumor. Our study presents the only case of a urachal carcinoma first manifesting with abdominal mass resulting from liver metastasis with no prior symptoms of urological origins. Also, our study presents the first attempt of using FLOFIRI-B to treat metastatic UraC. Conclusion: This case highlights the necessity for clinicopathological correlation to make the correct diagnosis and the challenges in the treatment which urges the need for further research to identify more effective treatment strategies for this rare cancer.

Mixed hepatocellular carcinoma and high-grade neuroendocrine neoplasm with ambiguous histopathological features: a case report.

Well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC) are distinct entities with different biological behavior. However, difficult cases showing equivocal morphology have been reported in some organs. Herein, we report a case of primary hepatic neuroendocrine neoplasm (NEN) with ambiguous histopathological features admixed with conventional hepatocellular carcinoma (HCC). A 70-year-old man with untreated chronic hepatitis B underwent left medial sectionectomy because of two incidental liver masses. On pathological examination, one of the resected tumors had intermingling NEN and HCC components. The NEN component consisted of relatively uniform tumor cells proliferating in trabecular, cord-like, or solid patterns with peripheral nuclear palisading. The tumor cells were immunopositive for synaptophysin, chromogranin A, cluster of differentiation 56 (CD56), and focally hepatocyte paraffin 1. p53 showed wild-type expression. The Ki-67 labeling index was 27% at the hot spot. Eleven months after the surgery, he died of a cerebral hemorrhage without evidence of recurrent liver cancer. The intermediate degree of differentiation and the modest proliferative activity can challenge the distinction between NEC and NET G3. While the coexisting HCC indicates NEC rather than NET in a pathogenetic viewpoint, such ambiguous tumor may not be as aggressive as typical NECs.

Design, synthesis and structure-activity relationship of novel 2-pyrimidinylindole derivatives as orally available anti-obesity agents

Due to the emerging global epidemic of obesity, developing safe and effective agents for anti-obesity is urgently needed. Our previous study found that 2-pyrimidinylindole derivative Wd3d exhibited potential anti-obesity activity. Herein, to further optimize the potential moiety, structural modifications were proceeded for two rounds in this study. Firstly, we designed, synthesized, and evaluated 36 new derivatives of 2-pyrimidinylindole scaffold with different substituents on the indole ring and pyrimidine ring to investigate their structure-activity relationship (SAR). Then, analogs with potent activity had the aldehyde group replaced with the acylhydrazone group to reduce cytotoxicity and improve metabolic stability. Detailed SAR studies and animal evaluation experiments led to the discovery of the compound 9ga, which significantly reduced TG accumulation with an EC50 value of 0.07 μM and showed relatively low cytotoxicity with an IC50 value of around 24 μM. Oral administration of 9ga effectively prevented the excessive growth of body weight and lessened fat mass as well as liver mass, decreased lipid accumulation in the liver and blood, and improved the heart injury parameter in the diet-induced obesity mouse model significantly better than Wd3d. A mechanism study showed that 9ga regulated the lipid metabolism during early adipogenesis by inhibiting PPARγ pathway. In conclusion, our study further highlights the anti-obesity potential of 2-pyrimidinylindole derivatives in diet-induced obesity.

55 Influence of gender on immunosurveillance in a novel mouse model of clear cell renal cell carcinoma

Abstract Background Renal Cell Carcinoma (RCC) is a cancer that exhibits sex dimorphism. Males have twice the incidence rate of their female counterparts and more than twice the mortality rate. They frequently present with larger, higher-grade tumors, greater metastatic spread, and earlier diagnosis of disease. Many hormonal, genetic, and environmental reasons have been explored, however a considerable amount of uncertainty remains. Methods Here, we explored the immunologic differences using a novel syngeneic mouse model of ccRCC. Tumors were orthotopically implanted by sub-renal capsular injection in immunocompetent WT C57Bl/6 and immunodeficient mice NOD/Scid/Gamma (NSG) mice, and tumor growth was longitudinally monitored using ultrasound imaging. At necropsy, liver and lung metastases were quantified and immune populations in the tumor and peripheral blood were analyzed by flow cytometry. Results In the immune-competent model, female mice had lower tumor penetrance as well as delayed tumor growth compared to male mice. In contrast, in the immune-deficient model female mice had similar tumor penetrance and growth rates as males suggesting that the female immune system may be protective against tumor development. No metastases were seen in either sex in the immune-competent model, whereas both lung and liver masses were found in the immune-deficient model suggesting the immune system is critical for restricting metastatic development. Interestingly, increased lung metastases were observed in females compared with male counterparts in NSG mice, suggesting that perhaps hormonal or other non-adaptive immunity-mediated mechanisms can promote metastatic seeding into the lungs. Flow cytometry characterization revealed higher peripheral B- and T-cells in females, with a higher CD8/CD4 T-cell ratio. Tumors from females had more activated and cytotoxic CD8 T cells and were more frequently metastatic to the lung compared to male mice. Conclusions Our findings suggest sex-related immunologic differences in immunosurveillance and metastatic tropism that warrants further interrogation. DOD CDMRP Funding: yes

Cellular Plasticity in Gut and Liver Regeneration.

The intestine and liver share a unique regenerative property that sets them apart from other mammalian visceral organs. The intestinal epithelium exhibits rapid renewal, making it one of the fastest renewing tissues in humans. Under physiological conditions, intestinal stem cells within each intestinal crypt continuously differentiate into the different types of intestinal epithelial cells to maintain intestinal homeostasis. However, when exposed to tissue damage or stressful conditions such as inflammation, intestinal epithelial cells in the gastrointestinal tract exhibit plasticity, allowing fully differentiated cells to regain their stem cell properties. Likewise, hepatic epithelial cells possess a remarkable regenerative capacity to restore lost liver mass through proliferation-mediated liver regeneration. When the proliferation-mediated regenerative capacity is impaired, hepatocytes and biliary epithelial cells (BECs) can undergo plasticity-mediated regeneration and replenish each other. The transition of mammalian liver progenitor cells to hepatocytes/BECs can be observed under tightly controlled experimental conditions such as severe hepatocyte injury accompanied by the loss of regenerative capacity. In this review, we will discuss the mechanism by which cellular plasticity contributes to the regeneration process and the potential therapeutic implications of understanding and harnessing cellular plasticity in the gut and liver.

Heterogeneous Pathological Changes in Liver Lobes During Liver Disease: A Perspective Review.

Liver diseases have a global prevalence of 25%, accounting for 4% of all deaths worldwide, and are associated with a 36% increased risk of fatal and nonfatal cardiovascular events. Metabolic dysfunction-associated steatotic liver disease constitutes the liver expression of metabolic syndrome and represents the primary type of liver disease. Microscopical analysis of biopsies, which allows the evaluation of a small portion of tissue with inferences made to the entire organ, is considered the gold standard for determining the presence of liver diseases. However, potential sampling errors in liver biopsies are conceivable because the obtained tissue represents only a tiny fraction of the entire liver mass and may not accurately reflect the true pathological state. Studies have demonstrated the existence of sampling errors in liver biopsies, particularly concerning the severity of inflammation, degree of fibrosis, and the presence of cirrhosis. Also, clinical studies have shown that histopathological abnormalities are better detected in humans when liver samples are collected from both the right and the left lobes. However, a gap exists in clinical investigation to clarify the role of differences between these lobes in improving the diagnostic and prognostic for liver diseases. Building upon the heterogeneous nature of pathological alterations observed in liver lobes, this perspective review provided recommendations to enhance the precision of diagnosis and prognostic accuracy of liver diseases.

Female Mice Exposed to Pyriproxyfen Since Prepuberty Showed Reproductive Impairment During Sexual Maturity and Increased Fetal Death in Their Offspring.

Pyriproxyfen (PPF) is an insecticide used in agriculture, which is approved for use in drinking water tanks for human consumption. However, some studies indicate that it may act as an endocrine disruptor and affect nontarget organisms. This study aimed to evaluate the effects of PPF on reproduction and general health status in female mice exposed from pre-puberty to adulthood. In the first experiment, females were treated by gavage from postnatal day (PND) 23 to (PND) 75 and were distributed into three experimental groups: control (vehicle), PPF 0.1 mg/kg, and PPF 1 mg/kg. Female mice were assessed for the age of puberty onset, body mass, water and food consumption, and the estrous cycle. On PDN 75, a subgroup was euthanized, when vital and reproductive organs were collected and weighed. The thyroid, ovary, and uterus were evaluated for histomorphometry. The other subgroup was assessed in relation to reproductive performance and fetal parameters. In a second experiment, the uterotrophic assay was performed with juvenile females (PND 18) using doses of 0.01, 0.1, or 1 mg/kg of PPF. PPF treatment reduced thyroid mass and increased liver mass. Furthermore, there was an increase in ovarian interstitial tissue and, in the uterus, a decrease in the thickness of the endometrial stroma with reduced content of collagen fibers. There was also a reduction of 30% in pregnancy rate in the treated groups and an increase in the frequency of fetal death. This study suggests that, based on this experimental model, the insecticide may pose a reproductive risk for females chronically exposed to the substance from the pre-pubertal period until adulthood. These results raise concerns about prolonged exposure of women to the same compound.

AGE-DEPENDENCE OF BIOCHEMICAL MANIFESTATIONS OF HEPATOTOXICINJURY IN RAT EXPOSED TO XENOBIOTICS OF VARIOUS GENESIS

Currently, the problem of liver diseases against the backdrop of the toxic effects of medicinal and industrial (herbicides) xenobiotics on the body is becoming increasingly relevant. The activation of compensatory mechanisms in response to the action of toxic agents –acetaminophen and/or diquat is closely related to age-specific features. Heightened focus on acetaminophen-induced injury is linked to the widespread use of this medication as an analgesic and antipyretic during pandemics of infectious and inflammatory diseases, especially under the conditions of warfare in Ukraine. In return, the widespread use of the herbicide diquat is accompanied by an increase in the registration of cases of diquat -induced acute poisoning. The aim of study was to evaluation the biochemical parameters of the functional state of the liver of different-aged rats under conditions of acetaminophen-and diquat-induced toxic injury. Animals were divided into three age groups: adolescent (60 days), reproductive (150 days), and mature age rats (360 days). Acute toxic injury by acetaminophen was modeled by its oral administration through gastric intubation at a daily dose of 1250 mg/kg of the animal's body weight during the last 2 days of the experiment. Acute toxic damage by diquat was modeled by a single intragastric administration using a probe at a dose of 115.5 mg/kg of the animal's body weight. The functional state of the liver was assessed on an automatic biochemical analyzer NTI Biochem FC-120.Acetaminophen intoxication led to an increase in the absolute liver mass indicator, organ index, changes in the macroscopic structure of the organ, increased serum activities of ALT and AST, total LDH, and a decrease in the De Ritis ratio amidst increased activities of ALP, GGT, and levels of total and indirect bilirubin in all age groups compared to the control. The most significant changes were observed in mature age animals (increase in ALT activity by 76%, AST by 56%, ALP by 51%, GGT by 51%, and a decrease in the De Ritis ratio by 47%). Under conditionsof diquat-induced toxic injury, a slightly different trend and degree in manifestation of established changes are observed. A more pronounced hepatotoxic effect was registered in adolescent animals, manifested by the maximum increase in absolute liver mass by 26%, ALT activity by 71%, AST by 47%, ALP by 50%, Bili-T level by 69%. No statistically significant differences compared to the control and APAP-induced injury in the activity of total LDH and GGT upon administration of toxic doses of the herbicide diquat regardless of age category were observed.Based on the experimental results, an age-related multidirectionality in the adverse effects of the medicinal xenobiotic acetaminophen and the industrial xenobiotic diquat on indicators of the morpho-functional state of the liver is observed. The most sensitive age group of animals to toxic injury by acetaminophen are rats of 360 days of age, while for diquat –60 days of age

Role of point-of-care ultrasound (POCUS) in clinical hepatology.

Hospitalized patients with cirrhosis frequently require critical care management for sepsis, HE, respiratory failure, acute variceal bleeding, acute kidney injury (AKI), shock, and optimization for liver transplantation, while outpatients have unique care considerations. Point-of-care ultrasonography (POCUS) enhances bedside examination of the hepatobiliary system and relevant extrahepatic sites. POCUS includes cardiac US and is used to assess volume status and hemodynamic parameters like cardiac output, systemic vascular resistance, cardiac contractility, and pulmonary artery pressure, which aid in the early and accurate diagnosis of heart failure, cirrhotic cardiomyopathy, porto-pulmonary hypertension, hepatopulmonary syndrome, arrhythmia, and pulmonary embolism. This also helps in fluid management and vasopressor use in the resuscitation of patients with cirrhosis. Lung ultrasound (LUS) can help in differentiating pneumonia, effusion, and edema. Further, US guides interventions such as line placement, drainage of abdominal collections/abscesses, relief of tension pneumothorax, drainage of pleural and pericardial effusions, and biliary drainage in cholangitis. Additionally, its role is essential to assess liver masses foci of sepsis, for appropriate sites for paracentesis, and to assess for vascular disorders such as portal vein or hepatic vein thrombosis. Renal US can identify renal and postrenal causes of AKI and aid in diagnosis of prerenal AKI through volume assessment. In this review, we address the principles and methods of POCUS in hospitalized patients and in outpatients with cirrhosis and discuss the application of this diverse modality in clinical hepatology.

Transcriptomic Characterization of Key Factors and Signaling Pathways for the Regeneration of Partially Hepatectomized Liver in Zebrafish.

Liver regeneration induced by partial hepatectomy (PHx) has attracted intensive research interests due to the great significance for liver resection and transplantation. The zebrafish (Danio rerio) is an excellent model to study liver regeneration. In the fish subjected to PHx (the tip of the ventral lobe was resected), the lost liver mass could be fully regenerated in seven days. However, the regulatory mechanisms underlying the liver regeneration remain largely unknown. In this study, gene expression profiles during the regeneration of PHx-treated liver were explored by RNA sequencing (RNA-seq). The genes responsive to the injury of PHx treatment were identified and classified into different clusters based on the expression profiles. Representative gene ontology (GO) enrichments for the early responsive genes included hormone activity, ribosome biogenesis and rRNA processing, etc., while the late responsive genes were enriched in biological processes such as glutathione metabolic process, antioxidant activity and cellular detoxification. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were also identified for the differentially expressed genes (DEGs) between the time-series samples and the sham controls. The proteasome was overrepresented by the up-regulated genes at all of the sampling time points. Inhibiting proteasome activity by the application of MG132 to the fish enhanced the expression of Pcna (proliferating cell nuclear antigen), an indicator of hepatocyte proliferation after PHx. Our data provide novel insights into the molecular mechanisms underlying the regeneration of PHx-treated liver.

Hepatocyte-derived extracellular vesicles regulate liver regeneration after partial hepatectomy.

While significant progress has been made in understanding different aspects of liver regeneration, the molecular mechanisms responsible for the initiation and termination of cell proliferation in the liver after massive loss or injury of liver tissue remain unknown. The loss of liver mass affects tissue-specific mitogenic inhibitors in the blood, which in turn regulate the proliferation of remaining hepatocytes and liver regeneration. Although well described in a number of publications, which inhibitory substances or "sensor molecules" control the regeneration mechanisms to properly maintain liver size remain unknown. Extracellular vesicles (EVs) are nano-sized, membrane-limited structures secreted by cells into the extracellular space. Their proposed role is stable intercellular carriers of proteins and RNAs, mostly micro-RNA, from secreted to recipient cells. Taken up by the recipient cells, EVs can significantly modulate their biological functions. In the present study, using in vivo and in vitro models, we demonstrate that hepatocyte proliferation and liver regeneration are regulated by EVs secreted by hepatocytes into the bloodstream. This regulation is carried out through a negative feedback mechanism, which explains the very precise regeneration of liver tissue after massive damage. We also demonstrate that an essential component of this mechanism is RNA carried by hepatocyte-derived EVs. These findings open up a new and unexplored area of biology regarding the mechanisms involved in the homeostasis regulation of various constantly renewing tissues by maintaining the optimal size and correct ratio between differentiating and proliferating cells.