Regenerative Nodules Research Articles

Platelet counts to spleen diameter ratio: A promising noninvasive tool for predicting esophageal varices in cirrhosis patients.

Liver cirrhosis is the end stage of progressive liver fibrosis as a consequence of chronic liver inflammation, wherein the standard hepatic architecture is replaced by regenerative hepatic nodules, which eventually lead to liver failure. Cirrhosis without any symptoms is referred to as compensated cirrhosis. Complications such as ascites, variceal bleeding, and hepatic encephalopathy indicate the onset of decompensated cirrhosis. Gastroesophageal varices are the hallmark of clinically significant portal hypertension. To determine the accuracy of the platelet count-to-spleen diameter (PC/SD) ratio to evaluate esophageal varices (EV) in patients with cirrhosis. This retrospective observational study was conducted at Tikur Anbessa Specialized Hospital and Adera Medical Center from January 1, 2019, to December 30, 2023. Data were collected via chart review and direct patient interviews using structured questionnaires. The data were exported to the SPSS software version 26 for analysis and clearance. A receiver operating characteristic curve was plotted for splenic diameter, platelet count, and PC/SD ratio to obtain sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. Of the 140 participants, 67% were men. Hepatitis B (38%) was the most common cause of cirrhosis, followed by cryptogenic cirrhosis (28%) and hepatitis C (16%). Approximately 83.6% of the participants had endoscopic evidence of EV, whereas 51.1% had gastric varices. Decompensated cirrhosis and PC were associated with the presence of EV with adjusted odds ratios of 12.63 (95%CI: 3.16-67.58, P = 0.001) and 0.14 (95%CI: 0.037-0.52, P = 0.004), respectively. A PC/SD ratio < 1119 had a sensitivity of 86.32% and specificity of 70% with area under the curve of 0.835 (95%CI: 0.736-0.934, P < 0.001). A PC/SD ratio < 1119 predicts EV in patients with cirrhosis. It is a valuable, noninvasive tool for EV risk assessment in resource-limited settings.

Metastatic Melanoma of Unknown Primary with Plasmacytoid Morphology Presenting as Acute Liver Failure

Abstract Introduction/Objective Viral hepatitis, drug toxicity, and autoimmune disorders are common etiologies of acute liver failure (ALF). Very rarely, a cause like metastatic melanoma may present as a primary driver of ALF. Malignant melanoma is histologically diverse and plasmacytoid melanoma is an unusual variant that may present as a solitary tumor or metastatic disease. Methods/Case Report A 48-year-old female presented with 2 weeks of right upper quadrant pain, nausea, coffee ground emesis and bleeding per rectum. She had no history of liver disease or alcohol use. On presentation, AST was 83 U/L, ALT was 29U/L, ALP was 159U/L and total bilirubin was 12.7g/dl. Viral hepatitis panel, HIV and chronic liver disease workup was negative. Esophagogastroduodenoscopy and colonoscopy showed no sources of bleeding. She was diagnosed with decompensated cirrhosis, ALF, and acute kidney injury from hepatorenal syndrome. Cirrhosis and multifocal indeterminate T1 hyper/T2 hypo intense lesions (dysplastic or regenerative nodules) were seen on MRI. Liver biopsy revealed metastatic melanoma. Almost entire liver parenchyma on biopsy was replaced by a population of neoplastic cells with plasmacytoid features. Immunostaining was positive for MART-1, HMB45 and SOX-10. Staining for Pan Cytokeratin and CK-7 highlighted the bile ducts and negative staining was seen for CK20, CD3, CD20, PAX-8, GATA-3, CDX-2 and P63. No primary lesion was found. It was deemed unlikely that she would benefit from therapy before complications occur. She passed away in 16 days. Results (if a Case Study enter NA) NA Conclusion In most cases of ALF associated with malignant melanoma, the liver may have a seemingly normal appearance on imaging studies due to the distinctive histology of leukemoid tumor infiltration within the liver sinusoids, resulting in sinusoidal obstruction and subsequent hepatocellular dysfunction. The rapidity of liver failure in these cases is related to the replacement of liver parenchyma by malignant cells. The plasmacytoid morphology is seen in a variety of malignancies and to avoid a potential misdiagnosis of an aggressive malignant melanoma, it is imperative to perform a thorough histopathological evaluation aided with immunohistochemistry. It is important to keep in mind that the potential involvement of malignant tumor cell infiltration may cause ALF and early histological assessment with a liver biopsy may be of paramount significance and may possibly change the course of the disease.

Sarcopenia Prevalence in Liver Cirrhosis Patients Using MRI and Handgrip Strength Measurements

Background: Cirrhosis, a leading cause of mortality worldwide, is histologically represented as formation of regenerative nodules encircled by fibrous bands caused by chronic liver injury. Nutritional status in cirrhotic patients is challenging to assess due to fluid accumulation resulting from impaired protein synthesis. Factors such as reduced food intake, malabsorption, and altered macronutrient metabolism negatively impact the nutritional status, leading to sarcopenia. The development of sarcopenia is multifactorial and is linked to lower survival rates. Aim: To assess sarcopenia prevalence in liver cirrhosis patients using MRI and handgrip strength measurements. Discussion: Impaired food intake in liver cirrhosis results from a combination of factors including loss of appetite, hormonal changes, early satiety, ascites, nausea, taste disturbances, and functional dyspepsia. Malabsorption can also occur due to portosystemic shunting, reduced bile production, chronic pancreatitis, and small intestinal bacterial overgrowth, all of which contribute to sarcopenia. It also arises from complex interactions involving impaired glycogen synthesis, inadequate nutrition, disrupted skeletal muscle protein synthesis and underlying hypermetabolism. Conclusion: MRI-based assessments indicate there is a significant occurrence of sarcopenia in individuals with cirrhosis. Our findings reveal that handgrip strength, when correlated with MRI results, is a reliable predictor of sarcopenia in these patients.

8467 From Highly Suspected Hemochromatosis to Liver Metastasis Neuroendocrine Tumor

Abstract Disclosure: M.E. Chacon Cruz: None. M. Sanchez Cordero: None. G. Guerra Velazquez: None. K.C. Velez Rivera: None. A neuroendocrine cancer, often referred to as a neuroendocrine tumor (NET) or neuroendocrine neoplasm begins in the specialized cells of the body's neuroendocrine system. These cells have traits of both hormone-producing endocrine cells and nerve cells. The carcinoid is the most common neuroendocrine tumor causing liver metastases, especially when of midgut origin. However, although appendix is the most common location for midgut carcinoids it most unusually gives rise to hepatic spread. NETs are described as functional or non-functional, depending on the release of hormones. About 60% of NETs are non-functional. Case of a 66 year old male patient with medical history of ESRD on HD, PPM placement, hypertension, type 2 diabetes mellitus, and auditory impairment presents to ED of this institution after presenting with RUQ abdominal pain of one day of evolution. Patient's pain is associated with food intake or changes in diet. Laboratory work on admission patient found with leukocytosis in 16.69, anemia 10.5 and transaminitis ALT 180, AST 176 and ALP 589. Abdominal ultrasound shows Hepatomegaly with a slightly irregular surface contour. Correlate for chronic liver disease. Abdomino pelvic CT showed Hepatomegaly with a diffusely heterogeneous parenchyma and ill-defined nodular foci of hypoattenuation. During admission liver enzyme and alkaline phosphatase continue in increasing trend up to 1,172 IU/L. Ferritin in 12,203, Transferrin saturation in 23.71%. Hemochromathosis DNA not detected, Angiotensin convert enzyme in 73 U/L, tumor marker alpha-fetoprotein in 1.8 ng/ml, carcinoembryoninc antigen in 25.63 ng/ml, CA19-9 in 903 U/ml, Serotonin 23 ng/ml. MRCP was ordered and show Hepatomegaly with innumerable T2 hyperintense nodules replacing the hepatic parenchyma, may be related to cirrhosis including regenerative nodules. Interventional radiologist was consulted for liver biopsy and came back positive for Malignant Neuroendocrine Tumor, Favor Metastatic Tumor This case illustrates the challenges physicians face in quickly identifying and diagnosing pathologies as unusual as neuroendocrine tumor. Furthermore, it points out that primary care physicians should consider this disease in the differential diagnosis (DDx) in case of non-specific signs and symptoms such as abdominal pain and how the DDx can change depending on the patient's clinical symptoms and evolution. The case shows us how, with the physical examination that the patient presented, his skin was like that described in hemochromatosis, skin hyperpigmentation (Bronze Skin), weakness, diabetes mellitus, along with elevated levels of ferritin, transaminitis, alkaline phosphatase and the finding of iron deposit in the kidney using CT, our differential diagnosis was our first diagnosis, until the genetics for hemochromatosis came back negative and the liver biopsy was positive for neuroendocrine tumor. Presentation: 6/2/2024

Lactate, Unmeasured Anions and Chloride as Predictors to the Outcome of Critically Ill Patients with Liver Cirrhosis

Abstract Background Liver Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. Aim of the Work The aim of the present study is to asses effect of serum lactate, Unmeasured anions and Chloride as predictors to the outcome of critically ill patients with liver cirrhosis. Patients and Methods This study was conducted on 95 patients divided to 4 groups according type of metabolic acidosis (lactic acidosis group, unmeasured anions acidosis group, hyperchloremic acidosis group, indeterminate acidosis group). Results This present study showed strong significance between (lactic acidosis), (unmeasured anion acidosis) and mortality incidence when compared with APACHE II score on day 0 (admission day). Where as hyperchloremia (hyperchloremic acidosis) was independently related to outcome. Conclusion The main finding in this study was that lactic acidosis constitutes the most common type of metabolic acidosis at the admission of critically ill patients. lactate, unmeasured anions were independent predictors of outcome. Any elevation in the concentration of these anions was associated with increasing Mortality. While, hyperchloremia was negatively related to mortality.

Liver cirrhosis: molecular mechanisms and therapeutic interventions.

Liver cirrhosis is the end-stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long-term inflammation can cause continuous damage to liver tissues and hepatocytes, along with increased vascular tone and portal hypertension. Among them, fibrosis is the necessary stage and essential feature of liver cirrhosis, and effective antifibrosis strategies are commonly considered the key to treating liver cirrhosis. Although different therapeutic strategies aimed at reversing or preventing fibrosis have been developed, the effects have not be more satisfactory. In this review, we discussed abnormal changes in the liver microenvironment that contribute to the progression of liver cirrhosis and highlighted the importance of recent therapeutic strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, and gut remediation, that regulate liver fibrosis and liver cirrhosis. Meanwhile, therapeutic strategies for nanoparticles are discussed, as are their possible underlying broad application and prospects for ameliorating liver cirrhosis. Finally, we also reviewed the major challenges and opportunities of nanomedicine‒biological environment interactions. We hope this review will provide insights into the pathogenesis and molecular mechanisms of liver cirrhosis, thus facilitating new methods, drug discovery, and better treatment of liver cirrhosis.

Prevalence of peptic ulcers in cirrhotics at the Cocody and Angré University Hospitals in Côte d'Ivoire

Introduction: Cirrhosis, is the consequence of a chronic attack of the liver, is histologically defined as a diffuse process associating mutilating fibrosis (concentric), and regenerative hepatocyte nodules, it has formidable complications (hemorrhagic, cancerous and encephalopathies) essentially. Method: this was a retrospective descriptive study from June 01, 2021 to May 30, 2023, i.e. 2 years. Results: we identified 205 cases of cirrhosis, 36 of which had at least one gastric or duodenal ulcer, i.e. a prevalence of 17.56%. There were 12 women and 24 men, i.e. a sex ratio (M/F) = 2. The mean age was 47.22 years ± 14.7 years with extremes ranging from 28 to 81 years. The etiologies of cirrhosis are (HBV 72.22%, HCV 15%, HBV+HCV 8.33% and chronic alcoholism 5.6%). Civil servants, pensioners, shopkeepers and housewives occupy the first places of complications respectively (25%, 16.7%, 13.9%, 11.1%). Signs of portal hypertension are represented by esophageal varices grade III with a proportion of 61.11% and grade II of 27.8% with or without red signs and at the gastric level, 63.9% of patients had gastropathy of portal hypertension. Ulcerative lesions were single in 80.55%, double in 19.44%, and in order of frequency according to bulbar (44.4%), antral (36.1%), antrobulbar (11.1%) and fundic (8.3%) location. The prognosis was, CHILD C (50%), CHILD B (30.55%) and CHILD A (19.45%). Conclusion: the complications of cirrhosis are formidable, prevention through awareness raising on the avoidance of risky behaviour and universal vaccination against hepatitis B remain the preferred option. Keywords: cirrhosis, Peptic ulcer, Portal hypertension, Cocody University Hospital

Artificial intelligence for ultrasonographic detection and diagnosis of hepatocellular carcinoma and cholangiocarcinoma

The effectiveness of ultrasonography (USG) in liver cancer screening is partly constrained by the operator’s expertise. We aimed to develop and evaluate an AI-assisted system for detecting and classifying focal liver lesions (FLLs) from USG images. This retrospective study incorporated 26,288 USG images from 5444 patients to train YOLOv5 model for FLLs detection and classification of seven different types of FLLs, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), focal fatty infiltration, focal fatty sparing (FFS), cyst, hemangioma, and regenerative nodules. AI model performance was assessed for detection and diagnosis of the FLLs on a per-image and per-lesion basis. The AI achieved an overall FLLs detection rate of 84.8% (95%CI:83.3–86.4), with consistent performance for FLLs ≤ 1 cm and > 1 cm. It also exhibited sensitivity and specificity for distinguishing malignant FLLs from other benign FLLs at 97.0% (95%CI:95. 9–98.2) and 97.0% (95%CI:95.9–98.1), respectively. Among specific FLL types, CCA detection rate was at 92.2% (95%CI:88.0–96.4), followed by FFS at 89.7% (95%CI:87.1–92.3), and HCC at 82.3% (95%CI:77.1–87.5). The specificities and NPVs for regenerative nodules were 100% and 99.9% (95%CI:99.8–100.0), respectively. Our AI model can potentially assist physicians in FLLs detection and diagnosis during USG examinations. Further external validation is needed for clinical application.

Computed Tomographic Findings of Liver Cirrhosis in Dogs: Comparison between Compensated and Decompensated Cirrhosis.

This study aimed to describe computed tomography (CT) characteristics of histologically confirmed cirrhosis and to compare these CT characteristics between compensated and decompensated cirrhosis. Sixteen dogs who underwent contrast CT and histopathological examinations were included; eleven dogs were assigned to the compensated group, and five dogs were assigned to the decompensated group. Irregular hepatic contours with a diffuse nodular distribution and hepatic lymph node enlargement are common concomitant features of cirrhotic livers on CT images. The enhancement patterns of the regenerative nodules and hepatic parenchyma were not significantly different from each other. Hypoattenuating areas with delayed contrast enhancement indicating fibrotic tissue were confirmed in 56.3% of cases. Hypoattenuating wedge-shaped area or nodule with minor or no contrast enhancement (histopathologically confirmed as focal necrosis) were confirmed in 37.5% of cases. Among CT variables, only normalized liver volume and portal vein-to-aorta ratio were significantly lower (p = 0.038 and 0.003, respectively) in the decompensated group. In conclusion, this study presented the CT features of cirrhosis and identified CT features that can discriminate between compensated and decompensated cirrhosis. Specifically, lower normalized liver volume and the portal vein-to-aorta ratio might be useful indicators for the progression of cirrhosis to the decompensated phase.

Case Report : Hepatic Cirrhosis and Nephrolithiasis

Liver cirrhosis and nephrolithiasis are significant health problems with different pathophysiological mechanisms. Liver cirrhosis, the final stage of chronic liver disease, is characterized by fibrosis and regenerative nodules, leading to severe complications, including portal hypertension and liver failure. Nephrolithiasis, commonly known as kidney stones, is a common urological condition characterized by the formation of stones in the renal system. Although these conditions are distinct, metabolic and physiological changes in cirrhotic patients may predispose to nephrolithiasis. It was reported that a man came to the emergency room of RSUD Dr. Suhatman MARS with complaints of left-sided low back pain that had been felt for 1 week. The complaint was accompanied by shortness of breath which was getting worse over time. The patient also felt cough, headache, nausea, fatigue, urine slightly coloured like tea, weight loss. The patient has a history of untreated kidney stones. The patient has a history of hepatitis 31 years ago. The main objective of investigating the coexistence of liver cirrhosis and nephrolithiasis is to understand the relationship between these two conditions and to develop effective management strategies that can address their combined impact on patients.

The utility of next-generation sequencing in challenging liver FNA biopsies.

Fine-needle aspiration (FNA) biopsy is increasingly used for the diagnosis of hepatocellular masses. Because distinguishing well differentiated hepatocellular carcinoma (HCC) from other well differentiated hepatocellular lesions (e.g., large regenerative nodules or focal nodular hyperplasia) requires an assessment of architectural features, this may be challenging on FNA when intact tissue fragments are not sampled. Poorly differentiated HCC and intrahepatic cholangiocarcinoma (ICC) may exhibit overlapping pathologic features. Molecular testing can be helpful, because mutations in TERT promoter and CTNNB1 (β-catenin) are characteristic of HCC, whereas mutations in BAP1, IDH1/IDH2, and PBRM1 may favor ICC. The goal of this study was to assess the role of next-generation sequencing (NGS) in further subclassifying indeterminate liver lesions sampled by FNA. A retrospective review of liver cytology cases with NGS on cell block material was performed. Age, radiologic features, background hepatic disease and treatment, outcome, and NGS data were obtained from the electronic medical record. Twelve FNA biopsies that had cell blocks from clinically suspected primary hepatic masses were identified. The presence of a TERT promoter mutation supported a diagnosis of HCC for one well differentiated neoplasm. For three patients, the presence of mutations, such as IDH1, CDKN2A/CDKN2B, and BRAF, supported a diagnosis of ICC. Of the eight poorly differentiated carcinomas, NGS helped refine the diagnosis in six of eight cases, with one HCC, three ICCs, and two that had combined HCC-ICC, with two cases remaining unclassified. Molecular diagnostics can be helpful to distinguish HCC and ICC on FNA specimens, although a subset of primary hepatic tumors may remain unclassifiable.

Imaging and Pathological Feature Analysis of Idiopathic Portal Hypertension

Background: Idiopathic portal hypertension (IPH) is a rare clinical condition often misdiagnosed as cirrhosis. The management of IPH focuses on preventing and treating complications related to portal hypertension, such as bleeding from esophagogastric fundal varices. In contrast, the management of cirrhosis focuses on symptomatic treatment based on etiology, protecting hepatocyte function, and inhibiting hepatic inflammation and fibrosis. Therefore, it is crucial to correctly recognize both diseases and take appropriate therapeutic measures. Objectives: The aim of this study was to summarize and analyze the imaging, pathological, and serological features of idiopathic portal hypertension and cirrhosis to reduce misdiagnosis in clinical practice. Patients and Methods: Pathological, radiological parameters [computed tomography (CT)/magnetic resonance imaging (MRI)], and serological examinations were retrospectively evaluated for 14 patients with IPH and 30 patients with cirrhosis. We analyzed and compared their imaging manifestations in terms of spleen thickness and length, liver morphology, hepatic lobe atrophy, hyperplasia, portal vein thrombosis, arteriovenous phase liver perfusion, regenerative nodules, focal nodular hyperplasia-like lesions of the liver, portal vein morphology, splenorenal shunt, and hepatorenal shunt. The aim was to investigate the correlation between the imaging manifestations and the pathological manifestations. Results: There were significant differences between the IPH and cirrhosis groups in individual indicators of liver function, routine blood tests, and coagulation function (P &lt; 0.05). Significant differences in spleen thickness and length were also observed between the IPH and cirrhosis groups (P &lt; 0.05). Atrophy and hyperplasia of the hepatic lobe differed between the two groups. Changes in liver morphology and parenchyma were observed in both the IPH and cirrhosis groups, with diffuse regenerative nodules and focal nodular hyperplasia-like lesions being significant for distinguishing between IPH and cirrhosis. Focal nodular hyperplasia-like lesions were more common in patients with idiopathic portal hypertension, whereas diffuse regenerative nodules were more common in patients with cirrhosis. All 14 IPH patients had abnormalities in the portal vein system, including main portal vein dilation, stiffness, straightening, and distal branch vein stenosis or occlusion, while 9 cirrhosis patients had portal vein abnormalities, primarily thinning of the portal vein. Pathology revealed that patients in the cirrhosis group had varying degrees of cell necrosis and edema, and pseudolobule formation was observed in all patients. Patients with IPH showed varying degrees of fibrosis in the portal and confluent areas, but lobular inflammation was not evident. Some IPH patients experienced portal vein occlusion and stenosis. Conclusion: Idiopathic portal hypertension is relatively rare in clinical practice and is characterized by mostly normal liver function and hypersplenism, which may lead to a decrease in platelets, red blood cells, and white blood cells. If a giant spleen is found on imaging and the liver surface is smooth, IPH should be considered. Additionally, fibrosis, stenosis, and occlusion of the portal venous system, as well as focal nodular hyperplasia-like lesions, are suggestive of idiopathic portal hypertension. In contrast, diffuse regenerative nodules and pseudolobule formation are often indicative of cirrhosis. Furthermore, atrophy and hyperplasia of the liver are significant in differentiating the two diseases.

Guidelines for oncologic surveillance in a patient with established cirrhosis

Cirrhosis is a chronic, diffuse disease process characterized by fibrosis and remodeling of the organ's normal architectonics into regenerative nodules. It is also one of the risk factors for cancers of the organ. One of the most common is hepatocellular carcinoma (HCC). The etiologic agent of HCC, which usually also causes cirrhosis, can be determined in more than 90% of patients. The annual risk of developing HCC ranges from 1% to 8%. It is estimated that about 1/3 of cirrhotic patients will develop HCC. By preventing cirrhosis and controlling its course, we reduce the risk of hepatocellular carcinoma [1].

A Impact Of Potentially Hepatotoxic Drug Use On Clinical Outcomes In Patients With Liver Cirrhosis

Liver cirrhosis is a pathological liver disease characterized by the formation of fibrous tissue and regenerative nodules in liver cells. The potential for hepatotoxicity due to the use of hepatotoxic drugs leads to worsening of the liver disease suffered by these patients. This study aims to assess the impact of using potentially hepatotoxic drugs on patients' clinical outcomes. This study was an observational study with a cross-sectional design. Data were collected retrospectively through the medical records of patients with liver cirrhosis hospitalized in 2021. The clinical outcomes studied were SGOT, SGPT, albumin, total bilirubin and length of hospitalization. The results obtained were tested using the Kruskal-Wallis statistical test. A total of 62 patients with liver cirrhosis met the inclusion criteria as the study sample. The number of potentially hepatotoxic drug prescriptions received by patients based on Likelihood scores with categories A, B, C, D and E was 368 drugs out of 776 total drug prescriptions (47.4%). The most commonly prescribed potentially hepatotoxic drugs were paracetamol, ceftriaxon, and levofloxacin. It can be concluded that potentially hepatotoxic drugs are still prescribed to patients with liver cirrhosis. Age, gender, child pugh-score, number of drugs, and number of potentially hepatotoxic drugs had no significant effect (p&gt;0.1) on SGOT, SGPT, albumin and total bilirubin. However, patients who received more drugs would have a higher.

Aberrant differentiation and proliferation of hepatocytes in chronic liver injury and liver tumors.

Chronic liver injury induces liver cirrhosis and facilitates hepatocarcinogenesis. However, the effects of this condition on hepatocyte proliferation and differentiation are unclear. We showed that rodent hepatocytes display a ductular phenotype when they are cultured within a collagenous matrix. This process involves transdifferentiation without the emergence of hepatoblastic features and is at least partially reversible. During the ductular reaction in chronic liver diseases with progressive fibrosis, some hepatocytes, especially those adjacent to ectopic ductules, demonstrate ductular transdifferentiation, but the majority of increased ductules originate from the existing bile ductular system that undergoes extensive remodeling. In chronic injury, hepatocyte proliferation is weak but sustained, and most regenerative nodules in liver cirrhosis are composed of clonally proliferating hepatocytes, suggesting that a small fraction of hepatocytes maintain their proliferative capacity in chronic injury. In mouse hepatocarcinogenesis models, hepatocytes activate the expression of various fetal/neonatal genes, indicating that these cells undergo dedifferentiation. Hepatocyte-specific somatic integration of various oncogenes in mice demonstrated that hepatocytes may be the cells of origin for a broad spectrum of liver tumors through transdifferentiation and dedifferentiation. In conclusion, the phenotypic plasticity and heterogeneity of mature hepatocytes are important for understanding the pathogenesis of chronic liver diseases and liver tumors.

Infarction of regenerative nodules in liver cirrhosis after implantation of TIPS and the role of CEUS.

Infarction of regenerative nodules in liver cirrhosis after implantation of TIPS and the role of CEUS.

Interventional Radiology Management of Pediatric Liver Tumors

AbstractPediatric liver tumors are not only rare, they are also different from the adult liver tumors. Hepatoblastomas and hepatocellular carcinomas (HCCs) are the most common primary malignant tumors seen in children. Fibrolamellar HCC, sarcomas, cholangiocarcinoma, germ cell tumor, and rhabdoid tumor and metastatic tumors comprise the remainder of liver malignancies. Hepatic infantile hemangiomas, mesenchymal hamartoma, regenerative nodules, adenomas, and focal nodular hyperplasia are the common benign liver tumors of childhood. The Pediatric Hepatic International Tumour Trial (PHITT) is an international trial with the goal of evaluating new and existing treatments for pediatric liver tumors. Chemotherapy, surgery, and liver transplantation are well-established in the management of pediatric liver tumors. In the background of increasing incidence of pediatric tumors, and availability of newer, less invasive modalities to treat tumors, it is vital to understand the role of interventional radiology in the management of pediatric liver tumors.

Hepatitis B and C Viruses: Prevalence and co-factors among patients with liver cirrhosis

Liver cirrhosis is the final pathway of multiple chronic liver diseases and is a pathological entity defined as diffuse hepatic fibrosis and regenerative nodule formation. The objective of this study was to investigate the prevalence and co-factors of hepatitis B and C viruses among patients with liver cirrhosis. A total of 79 patients were registered from 2018 to 2022. The prevalence of liver cirrhosis in 2018, 2019, and 2020. 2021 and 2022 were 21.7%, 13.0%, 19.1%, 6.1% and 8.7%, respectively. The incidence of cirrhosis was significantly (P = 0.01) greater in rural areas than in urban areas. In addition, according to age, the incidence of cirrhosis was significantly (P = 0.001) greater in those &gt;52 years old than in those 18-40 and 41-52 years old. Moreover, the incidence of cirrhosis was greater in females than in males, but the difference was not significant. Without that, the causes of cirrhosis for HBV, HCV and Non-B and Non-C patients were 13% and 40%, 15.7%, respectively. The results showed that causes of cirrhosis were significantly associated with HCV incidence, and the prevalence of underweight, normal, overweight, and obese individuals was 13%, 15.7%, 26.1% and 18.9%, respectively. Prevalence according to BMI categories did significantly differ among the categories. Furthermore, the incidences of diabetes mellitus for patients with HBV and HCV and for non-B and non-C individuals were 21.7%, 47% and 31.3%, respectively, but the incidence of diabetes mellitus was significantly associated with the incidence of HCV. In addition, the incidences of encephalopathy for HBV, HCV and non-B and non-C patients were 20.9%, 47.8%, and 31.3%, respectively, and for Ascites, they were 24.3%, 44.3%, and 31.4%, respectively. Finally, the incidence of cirrhosis was significantly (P = 0.001) greater in smoking patients than in nonsmokers.

Diabetes Accelerates Steatohepatitis in Mice: Liver Pathology and Single-Cell Gene Expression Signatures

Glucose lowering independently reduces liver fibrosis in human NAFLD. We investigated the impact of diabetes on steatohepatitis and established a novel mouse model for diabetic steatohepatitis.Male C57BL/6J mice were fed a 60% high-fat diet (HFD) and injected with carbon tetrachloride (CCl4) and streptozotocin (STZ) to induce diabetes. The HFD+CCl4+STZ group displayed more severe liver steatosis, hepatocyte ballooning, and regenerative nodules compared to other groups. Diabetes upregulated inflammatory cytokine-associated genes and elevated the M1/M2 macrophage ratios in the liver. Single-cell RNA sequencing (scRNAseq) analysis of non-parenchymal cells in the liver showed that diabetes reduced the Kupffer cells and increased bone marrow-derived recruited inflammatory macrophages, such as Ly6Chi-RM. Diabetes globally reduced liver sinusoidal endothelial cells (LSECs). Furthermore, the upregulation of genes related to the receptor for advanced glycation end products (RAGE)/toll-like receptor 4 (TLR4) was observed in Ly6Chi-RM and LSECs under diabetes, suggesting a possible role of the RAGE/TLR4 signaling in the interaction between inflammatory macrophages and LSECs.The study established a novel diabetic steatohepatitis model using a combination of HFD, CCl4, and STZ. Diabetes exacerbates steatosis, hepatocyte ballooning, fibrosis, regenerative nodule formation, and the macrophage M1/M2 ratios triggered by HFD and CCl4. scRNAseq analysis indicates that diabetes activates inflammatory macrophages and impairs LSECs through the RAGE/TLR4 signaling pathway. These findings open avenues for discovering novel therapeutic targets for diabetic steatohepatitis.

A rare case of liver regenerative and non-neoplastic lesion resembling a well-differentiated hepatocellular carcinoma

BackgroundNodular regenerative hyperplasia (NRH) is a rare disease that presents pathologically as diffuse hepatic nodules without fibrous septa. It is believed to be caused by vasculopathy against a background of various systemic diseases, such as hematologic, autoimmune, and drug-induced diseases, with various symptoms. In spite of the recent imaging advances, various atypical cases of nodular lesions are observed in daily clinical practice. Cases that do not completely meet these criteria are referred to as -like or -similar lesions in clinical situations, making it difficult to understand their pathogenesis. We present a case in which two hepatic nodular lesions were noted and difficult to differentiate from malignancy preoperatively. The lesions were laparoscopically resected and a pathological diagnosis with non-neoplastic liver regenerative nodules resembling NRH was made.Case presentationA 49-year-old man with no alcohol or drug intake and no past medical history was identified as having liver tumors on screening examination without any symptoms. Contrast-enhanced computed tomography (CT) showed two hepatic tumors; approximately 2-cm tumors at S7 and S8. Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed fat inclusions in their contents. Ethoxybenzyl (EOB) uptake was also observed during the hepatobiliary phase. Based on preoperative examinations, we suspected well-differentiated hepatocellular carcinoma (HCC) and performed laparoscopic S7/8 partial resection for these lesions. Macroscopically, the resected specimens showed a non-cirrhotic yellowish-cut surface containing brownish, ill-defined lesions with irregular borders. Microscopically, these lesions showed zonal necrosis, congestion, and aggregation of hemosiderin-laden macrophages around the central vein. In these areas, the fatty deposition of hepatocytes was lower than that in the surrounding background hepatocytes. Histopathologically, neither neoplastic nor hyperplastic lesions were observed, and he was diagnosed as regenerative hepatic change with centrilobular necrosis.ConclusionsConsidering the pathological results, these lesions were thought to be a type of NRH-like lesion with possible hepatic vessel disorder. However, the lesion’s cause and classification was difficult to determine. The accumulation of these regenerative changes accompanying fatty liver is needed to clarify the mechanism and its clinical significance.