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1.
Diagnostics (Basel) ; 14(14)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39061609

RESUMO

Androgens have long been recognized as oncogenic agents. They can induce both benign and malignant hepatocellular neoplasms, including hepatocellular adenoma (HCA) and hepatocellular carcinoma, though the underlying mechanisms remain unclear. Androgen-induced liver tumors are most often solitary and clinically silent. Herein, we reported an androgen-induced HCA complicated by spontaneous rupture. The patient was a 24-year-old male presenting with fatigue, diminished libido, radiology-diagnosed hepatocellular adenomatosis for 3 years, and sudden-onset, severe, sharp, constant abdominal pain for one day. He used Aveed (testosterone undecanoate injection) from age 17 and completely stopped one year before his presentation. A physical exam showed touch pain and voluntary guarding in the right upper quadrant of the abdomen. An abdominal CT angiogram demonstrated multiple probable HCAs, with active hemorrhage of the largest one (6.6 × 6.2 × 5.1 cm) accompanied by large-volume hemoperitoneum. After being stabilized by a massive transfusion protocol and interventional embolization, he underwent a percutaneous liver core biopsy. The biopsy specimen displayed atypical hepatocytes forming dense cords and pseudoglands. The lesional cells diffusely stained ß-catenin in nuclei and glutamine synthetase in cytoplasm. Compared to normal hepatocytes from control tissue, the tumor cells were positive for nuclear AR (androgen receptor) expression but had no increased EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit) protein expression. The case indicated that androgen-induced hepatocellular neoplasms should be included in the differential diagnosis of acute abdomen.

2.
Cancers (Basel) ; 14(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35954333

RESUMO

Hepatocellular carcinoma (HCC), a major global contributor of cancer death, usually arises in a background of chronic liver disease, as a result of molecular changes that deregulate important signal transduction pathways. Recent studies have shown that certain molecular changes of hepatocarcinogenesis are associated with clinicopathologic features and prognosis, suggesting that subclassification of HCC is practically useful. On the other hand, subclassification of hepatocellular adenomas (HCAs), a heterogenous group of neoplasms, has been well established on the basis of genotype-phenotype correlations. Histologic examination, aided by immunohistochemistry, is the gold standard for the diagnosis and subclassification of HCA and HCC, while clinicopathologic correlation is essential for best patient management. Advances in clinico-radio-pathologic correlation have introduced a new approach for the diagnostic assessment of lesions arising in advanced chronic liver disease by imaging (LI-RADS). The rapid expansion of knowledge concerning the molecular pathogenesis of HCC is now starting to produce new therapeutic approaches through precision oncology. This review summarizes the etiology and pathogenesis of HCA and HCC, provides practical information for their histologic diagnosis (including an algorithmic approach), and addresses a variety of frequently asked questions regarding the diagnosis and practical implications of these neoplasms.

3.
Radiographics ; 41(6): 1611-1631, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34597222

RESUMO

Hepatocellular carcinoma (HCC) is a malignancy with variable biologic aggressiveness based on the tumor grade, presence or absence of vascular invasion, and pathologic and molecular classification. Knowledge and understanding of the prognostic implications of different pathologic and molecular phenotypes of HCC are emerging, with therapeutics that promise to provide improved outcomes in what otherwise remains a lethal cancer. Imaging has a central role in diagnosis of HCC. However, to date, the imaging algorithms do not incorporate prognostic features or subclassification of HCC according to its biologic aggressiveness. Emerging data suggest that some imaging features and further radiologic, pathologic, or radiologic-molecular phenotypes may allow prediction of the prognosis of patients with HCC. An invited commentary by Bashir is available online. Online supplemental material is available for this article. ©RSNA, 2021.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Prognóstico , Estudos Retrospectivos
4.
Magn Reson Imaging Clin N Am ; 29(3): 359-374, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34243923

RESUMO

In the background of chronic liver disease, hepatocellular carcinoma develops via a complex, multistep process called hepatocarcinogenesis. This article reviews the causes contributing to the process. Emphasis is made on the imaging manifestations of the pathologic changes seen at many stages of hepatocarcinogenesis, from regenerative nodules to dysplastic nodules and then to hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiologia , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Radiografia
5.
Am J Gastroenterol ; 116(7): 1414-1425, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33993134

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.


Assuntos
COVID-19/complicações , Colangite Esclerosante/epidemiologia , Doença Hepática Terminal/epidemiologia , Icterícia/epidemiologia , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/imunologia , Ductos Biliares/patologia , Biópsia , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/imunologia , Colangite Esclerosante/terapia , Progressão da Doença , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Icterícia/diagnóstico , Icterícia/imunologia , Icterícia/terapia , Testes de Função Hepática , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
6.
Case Rep Gastroenterol ; 15(1): 408-417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976619

RESUMO

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.

7.
Commun Biol ; 4(1): 436, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790388

RESUMO

Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs. Fibrous coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently validated fluid flow through human fibrous tissues, though whether these interstitial spaces are continuous through the body or discontinuous, confined within individual organs, remains unclear. Here we show evidence for continuity of interstitial spaces using two approaches. Non-biological particles (tattoo pigment, colloidal silver) were tracked within colon and skin interstitial spaces and into adjacent fascia. Hyaluronic acid, a macromolecular component of interstitial spaces, was also visualized. Both techniques demonstrate interstitial continuity within and between organs including within perineurium and vascular adventitia traversing organs and the spaces between them. We suggest that there is a body-wide network of fluid-filled interstitial spaces that has significant implications for molecular signaling, cell trafficking, and the spread of malignant and infectious disease.


Assuntos
Espaço Extracelular/metabolismo , Matriz Extracelular/metabolismo , Humanos
8.
J Histotechnol ; 43(4): 163-173, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32998669

RESUMO

Multiplexed immunohistochemical techniques give insight into contextual cellular relationships by offering the ability to collect cell-specific data with spatial information from formalin-fixed, paraffin-embedded tissue sections. We established an automated sequential elution-stripping multiplex immunohistochemical assay to address two controversial scientific questions in the field of hepatopathology: 1) whether epithelial-to-mesenchymal transition or mesenchymal-to-epithelial transition occurs during liver injury and repair of a chronic liver disease and 2) if there is a stromal:epithelial relationship along the canals of Hering that would support the concept of this biliary structure being a stem/progenitor cell niche. Our 4-plex assay includes both epithelial and mesenchymal clinical immunohistochemical markers and was performed on clinical human liver specimens in patients with primary biliary cholangitis. The assay demonstrated that in each specimen, co-expression of epithelial and mesenchymal markers was observed in extraportal cholangiocytes. In regard to possible mesenchymal components in a stem cell niche, 82.3% ± 5.5% of extraportal cholangiocytes were intimately associated with a vimentin-positive cell. Co-expression of epithelial and mesenchymal markers by extraportal cholangiocytes is evidence for epithelial to mesenchymal transition in primary biliary cholangitis. Vimentin-positive stromal cells are frequently juxtaposed to extraportal cholangiocytes, supporting an epithelial:mesenchymal relationship within the hepatobiliary stem cell niche. Our automated sequential elution-stripping multiplex immunohistochemical assay is a cost-effective multiplexing technique that can be readily applied to a small series of clinical pathology samples in order to answer scientific questions involving cell:cell relationships and cellular antibody expression.


Assuntos
Células Epiteliais/metabolismo , Queratina-19/metabolismo , Cirrose Hepática Biliar/imunologia , Nicho de Células-Tronco/fisiologia , Sistema Biliar/metabolismo , Biomarcadores/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Imuno-Histoquímica/métodos , Fígado/citologia , Vimentina/metabolismo
9.
Am J Physiol Gastrointest Liver Physiol ; 319(1): G11-G22, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32463334

RESUMO

Hepatocellular carcinoma (HCC) is the fourth-leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and stiffness is a significant risk factor, HCC can also arise in noncirrhotic livers in the setting of nonalcoholic fatty liver disease (NAFLD). We hypothesized that lipid droplets in NAFLD might apply mechanical forces to the nucleus, functioning as mechanical stressors akin to stiffness. We investigated the effect of lipid droplets on cellular mechanosensing and found that primary human hepatocytes loaded with the fatty acids oleate and linoleate exhibited decreased stiffness-induced cell spreading and disrupted focal adhesions and stress fibers. The presence of large lipid droplets in hepatocytes resulted in increased nuclear localization of the mechano-sensor Yes-associated protein (YAP). In cirrhotic livers from patients with NAFLD, hepatocytes filled with large lipid droplets showed significantly higher nuclear localization of YAP as compared with cells with small lipid droplets. This work suggests that lipid droplets induce a mechanical signal that disrupts the ability of the hepatocyte to sense its underlying matrix stiffness and that the presence of lipid droplets can induce intracellular mechanical stresses.NEW & NOTEWORTHY This work examines the impact of lipid loading on mechanosensing by human hepatocytes. In cirrhotic livers, the presence of large (although not small) lipid droplets increased nuclear localization of the mechanotransducer YAP. In primary hepatocytes in culture, lipid droplets led to decreased stiffness-induced cell spreading and disrupted focal adhesions and stress fibers; the presence of large lipid droplets resulted in increased YAP nuclear localization. Collectively, the data suggest that lipid droplets induce intracellular mechanical stress.


Assuntos
Carcinoma Hepatocelular/metabolismo , Hepatócitos/metabolismo , Gotículas Lipídicas/metabolismo , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/patologia , Núcleo Celular/metabolismo , Humanos , Metabolismo dos Lipídeos/fisiologia , Lipídeos , Fígado/metabolismo , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia
10.
Med Hypotheses ; 140: 109680, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32240960

RESUMO

The origin and initiating features of PBC remain obscure despite decades of study. However, recent papers have demonstrated loss of canals of Hering (CoH) to be the earliest histologic change in liver biopsy specimens from patients with primary biliary cholangitis (PBC). We posit that CoH loss prior to significant inflammation or evidence of bile duct injury might be a very early, perhaps even an initiating lesion of PBC. As a potential target of inflammatory or toxic injury, CoH loss may initiate rather than follow the cascade of events leading to duct injury and loss and their sequelae. Toxins may be exogenous in origin, such as environmental toxins or drug exposures, or endogenous, resulting from genetic or epigenetic alterations in canalicular bile transporters upstream from the CoH. In turn, this hypothesis suggests that loss of CoH would lead to altered bile flow and composition injurious to downstream bile ducts, because bile composition has not been modulated by normal CoH physiologic functions or because, in the absence of CoH, canalicular fluid flow into the biliary tree is disrupted interfering with soluble trophic factors important for bile duct integrity. Regardless of the pathogenic mechanism causing CoH loss, only following such loss would the characteristic diagnostic findings of PBC become evident: damage to downstream interlobular and sub-lobular bile ducts. To the extent that the causal mechanisms for CoH loss can be identified, clinical identification (as through early identification of CoH loss) and intervention (depending on the inciting cause) may offer promise for treatment of this enigmatic disease.

11.
J Hepatol ; 72(1): 135-145, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31562906

RESUMO

BACKGROUND & AIMS: The extrahepatic bile duct is the primary tissue initially affected by biliary atresia. Biliary atresia is a cholangiopathy which exclusively affects neonates. Current animal models suggest that the developing bile duct is uniquely susceptible to damage. In this study, we aimed to define the anatomical and functional differences between the neonatal and adult mouse extrahepatic bile ducts. METHODS: We studied mouse passaged cholangiocytes, mouse BALB/c neonatal and adult primary cholangiocytes, as well as isolated extrahepatic bile ducts, and a collagen reporter mouse. The methods used included transmission electron microscopy, lectin staining, immunostaining, rhodamine uptake assays, bile acid toxicity assays, and in vitro modeling of the matrix. RESULTS: The cholangiocyte monolayer of the neonatal extrahepatic bile duct was immature, lacking the uniform apical glycocalyx and mature cell-cell junctions typical of adult cholangiocytes. Functional studies showed that the glycocalyx protected against bile acid injury and that neonatal cholangiocyte monolayers were more permeable than adult monolayers. In adult ducts, the submucosal space was filled with collagen I, elastin, hyaluronic acid, and proteoglycans. In contrast, the neonatal submucosa had little collagen I and elastin, although both increased rapidly after birth. In vitro modeling of the matrix suggested that the composition of the neonatal submucosa relative to the adult submucosa led to increased diffusion of bile. A Col-GFP reporter mouse showed that cells in the neonatal but not adult submucosa were actively producing collagen. CONCLUSION: We identified 4 key differences between the neonatal and adult extrahepatic bile duct. We showed that these features may have functional implications, suggesting the neonatal extrahepatic bile ducts are particularly susceptible to injury and fibrosis. LAY SUMMARY: Biliary atresia is a disease that affects newborns and is characterized by extrahepatic bile duct injury and obstruction, resulting in liver injury. We identify 4 key differences between the epithelial and submucosal layers of the neonatal and adult extrahepatic bile duct and show that these may render the neonatal duct particularly susceptible to injury.


Assuntos
Ductos Biliares Extra-Hepáticos/embriologia , Ductos Biliares Extra-Hepáticos/crescimento & desenvolvimento , Células Epiteliais/metabolismo , Mucosa/metabolismo , Animais , Animais Recém-Nascidos , Ductos Biliares Extra-Hepáticos/citologia , Ductos Biliares Extra-Hepáticos/diagnóstico por imagem , Atresia Biliar , Sobrevivência Celular , Células Cultivadas , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Modelos Animais de Doenças , Elastina/metabolismo , Feminino , Proteínas de Fluorescência Verde/metabolismo , Humanos , Ácido Hialurônico/metabolismo , Imuno-Histoquímica , Junções Intercelulares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Proteoglicanas/metabolismo
13.
Histopathology ; 74(2): 219-226, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30129657

RESUMO

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.


Assuntos
Hipertensão Portal/patologia , Fígado/patologia , Humanos
14.
Expert Rev Gastroenterol Hepatol ; 12(6): 565-573, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29806950

RESUMO

INTRODUCTION: 'Acute-on-Chronic-Liver Failure (ACLF)' entered hepatology practice by the end of the 20th century. Although we lack precise and universally agreed definitions, acute decompensation of chronic liver disease with jaundice and deranged clotting, multi-organ failure and high, short-term mortality are hallmarks of the syndrome. Timely recognition and and treatment, including urgent liver transplantation, may save the life of certain patients. The diagnosis and management are mostly based on clinical features, but some have suggested to incorporate histopathology (liver biopsy). This may add to the differentiation between acute and chronic disease, primary and concomitant etiologies, and identify prognostic determinants. Areas covered: A review of the literature on ACLF and the outcome of the discussions at a topical international meeting on specific histopathological aspects of diagnosis and prognosis of the syndrome. Expert commentary: There is a lack of standardized descriptions of histopathological features and there is limited prospective experience with the role of pathology of ACLF. It is important for the clinical hepatologist to understand the potential and limitations of (transjugular) liver biopsy in ACLF and for the pathologist to help address the clinical question and recognise the histopathological features that help to characterize ACLF, both in terms of diagnosis and prognosis.


Assuntos
Insuficiência Hepática Crônica Agudizada/patologia , Biópsia , Fígado/patologia , Insuficiência Hepática Crônica Agudizada/complicações , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/terapia , Diagnóstico Diferencial , Diagnóstico Precoce , Humanos , Transplante de Fígado , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
15.
Mod Pathol ; 31(8): 1191-1200, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29700417

RESUMO

In this new era of successful long term suppression of hepatitis B viral replication and consistent eradication of hepatitis C virus the necessity for routine pre-treatment biopsies has often been eliminated. Thus, whether there is utility to perform liver biopsy in chronic viral hepatitis is undergoing re-examination. In response to these changing needs, we have developed a new staging system, the Beijing Classification, for assessment of biopsy specimens from patients with chronic viral hepatitis. The most important novelty of the Beijing Classification is that it includes not only extent (stage) of fibrosis, but the quality of fibrosis, namely if the specimen shows predominantly regressive vs. progressive features (or is indeterminantly balanced between the two), the P-I-R score. This histologic distinction between regressive and progressive fibrosis, while invoked in this particular setting of chronic viral hepatitis, may have applicability to all forms of chronic liver disease. Thus, the review contains a description of the concepts of regression and progression with the aim of empowering pathologists to apply them in histopathologic-clinical correlation research as well as in the specific clinical setting for which it was developed. Also, in light of changing clinical needs, grading of necroinflammatory activity and staging of fibrosis are simplified into three point scales. These simplifications should aid the general diagnostic pathologist in being comfortable and confident in assessing biopsy specimens as the criteria for their distinction are far more precise, with significantly reduced "gray zones" of prior grading/staging systems.


Assuntos
Hepatite B Crônica/patologia , Hepatite C Crônica/patologia , Cirrose Hepática/classificação , Cirrose Hepática/patologia , Progressão da Doença , Humanos , Cirrose Hepática/virologia
16.
Sci Rep ; 8(1): 4947, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29588511

RESUMO

Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of human tissues at a depth of 60-70 µm during endoscopy. pCLE of the extrahepatic bile duct after fluorescein injection demonstrated a reticular pattern within fluorescein-filled sinuses that had no known anatomical correlate. Freezing biopsy tissue before fixation preserved the anatomy of this structure, demonstrating that it is part of the submucosa and a previously unappreciated fluid-filled interstitial space, draining to lymph nodes and supported by a complex network of thick collagen bundles. These bundles are intermittently lined on one side by fibroblast-like cells that stain with endothelial markers and vimentin, although there is a highly unusual and extensive unlined interface between the matrix proteins of the bundles and the surrounding fluid. We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia. These anatomic structures may be important in cancer metastasis, edema, fibrosis, and mechanical functioning of many or all tissues and organs. In sum, we describe the anatomy and histology of a previously unrecognized, though widespread, macroscopic, fluid-filled space within and between tissues, a novel expansion and specification of the concept of the human interstitium.


Assuntos
Fáscia/ultraestrutura , Sistema Linfático/ultraestrutura , Mucosa/ultraestrutura , Ductos Biliares/ultraestrutura , Colágeno/análise , Endoscopia , Fluoresceína/análise , Humanos , Linfa/química , Microscopia Confocal , Pele/ultraestrutura , Bexiga Urinária/ultraestrutura
17.
Virchows Arch ; 473(1): 15-22, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29589101

RESUMO

Cirrhosis has been traditionally viewed as an irreversible, end-stage condition. Eighteen years ago, Wanless, Nakashima, and Sherman published a study that was based on the concept that hepatic architecture is under constant remodeling in the course of chronic liver diseases, even during their most advanced stages; depending on the balance between injury and repair, the histologic changes might be progressing or regressing. These authors described in detail the morphologic features of regressing cirrhosis, identified a set of histologic features of regression that they called the "hepatic repair complex," and provided convincing morphologic evidence that incomplete septal cirrhosis represents regressed cirrhosis. In the years that followed publication of this pioneering article, a number of clinical studies with performance of pre- and post-treatment liver biopsies provided abundant evidence that cirrhosis can regress after successful therapy of chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis, and genetic hemochromatosis. Evidence for other chronic liver diseases may also be provided in the future, pending ongoing studies. Successful therapy allows resorption of fibrous septa, which can be followed by loss of nodularity and architectural improvement; however, many vascular lesions of cirrhotic livers are not thought to regress. Cases of cirrhosis that are considered more likely to improve than others include those of recent onset, with relatively thin fibrous septa and mild vascular changes. Histologic examination of liver biopsy specimens from patients with chronic liver diseases provides the opportunity to appreciate the features of the hepatic repair complex on a routine diagnostic basis; however, interpretation is often difficult, and can be aided by immunohistochemical stains. Clinicopathologic correlation is essential for a meaningful assessment of such cases. For many patients, cirrhosis is not an end-stage condition anymore; therefore, use of the term "cirrhosis" has been challenged, almost 200 years after its invention. However, regression of cirrhosis does not imply regression of molecular changes involved in hepatocarcinogenesis; therefore, surveillance for hepatocellular carcinoma should be continued in these patients.


Assuntos
Fibrose/patologia , Hepatite/patologia , Cirrose Hepática/patologia , Fígado/patologia , Biópsia , Doença Crônica , Fibrose/diagnóstico , Hepatite/diagnóstico , Humanos
18.
Sci Rep ; 8(1): 2989, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29445243

RESUMO

Current widely used semiquantitative histological assessment methods are insensitive to identify subtle changes of liver fibrosis. Therefore, to precisely assess therapeutic efficacy on chronic hepatitis B (CHB), we explored the utility of qFibrosis (a fully-quantitative morphometric method employing second harmonic generation/two photon excitation fluorescence) in liver fibrosis evaluation. Fibrosis changes were evaluated by Ishak fibrosis scoring and qFibrosis in CHB patients with paired liver biopsies before and after 78 weeks' antiviral therapy. A total of 162 patients with qualified paired biopsies were enrolled. Ishak fibrosis scoring revealed that 42.6% (69/162) of the patients achieved fibrosis regression (≥1-point decrease), 51.9% (84/162) remained stable, and 5.5% (9/162) showed progression (≥1-point increase). qFibrosis showed similar trends in the groups of regression and progression patients as evaluated by Ishak. However, in Ishak stable patients, qFibrosis revealed hitherto undetected changes, allowing for further subcategorization into regression ("Regression by qFibrosis"; 40/84, 47.6%), stable (29/84, 34.5%), and progression ("Progression by qFibrosis"; 15/84, 17.9%) groups. These newly fine-tuned categories were supported by changes of morphological parameters of fibrosis, collagen percentage area, and liver stiffness measurements. In conclusion, qFibrosis can be used to quantitatively identify subtle changes of liver fibrosis in CHB patients after antiviral therapy.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite B Crônica/diagnóstico , Fígado/patologia , Adulto , Antivirais/uso terapêutico , Biópsia , Colágeno/metabolismo , Progressão da Doença , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Humanos , Fígado/metabolismo , Cirrose Hepática , Masculino , Avaliação de Resultados da Assistência ao Paciente , Resultado do Tratamento
19.
Am J Clin Pathol ; 148(6): 502-512, 2017 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-29165568

RESUMO

OBJECTIVES: Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). METHODS: SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. RESULTS: Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. CONCLUSIONS: SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods.


Assuntos
Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Adolescente , Adulto , Fatores Etários , Biópsia/métodos , Criança , Progressão da Doença , Feminino , Fibrose , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto Jovem
20.
Liver Int ; 37(9): 1260-1271, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28135758

RESUMO

The liver is a unique organ for homoeostasis with regenerative capacities. Hepatocytes possess a remarkable capacity to proliferate upon injury; however, in more severe scenarios liver regeneration is believed to arise from at least one, if not several facultative hepatic progenitor cell compartments. Newly identified pericentral stem/progenitor cells residing around the central vein is responsible for maintaining hepatocyte homoeostasis in the uninjured liver. In addition, hepatic progenitor cells have been reported to contribute to liver fibrosis and cancers. What drives liver homoeostasis, regeneration and diseases is determined by the physiological and pathological conditions, and especially the hepatic progenitor cell niches which influence the fate of hepatic progenitor cells. The hepatic progenitor cell niches are special microenvironments consisting of different cell types, releasing growth factors and cytokines and receiving signals, as well as the extracellular matrix (ECM) scaffold. The hepatic progenitor cell niches maintain and regulate stem cells to ensure organ homoeostasis and regeneration. In recent studies, more evidence has been shown that hepatic cells such as hepatocytes, cholangiocytes or myofibroblasts can be induced to be oval cell-like state through transitions under some circumstance, those transitional cell types as potential liver-resident progenitor cells play important roles in liver pathophysiology. In this review, we describe and update recent advances in the diversity and plasticity of hepatic progenitor cell and their niches and discuss evidence supporting their roles in liver homoeostasis, regeneration, fibrosis and cancers.


Assuntos
Regeneração Hepática , Fígado/citologia , Células-Tronco/citologia , Animais , Comunicação Celular , Proliferação de Células , Hematopoese , Hepatócitos/citologia , Homeostase , Humanos , Fígado/patologia , Modelos Biológicos , Transdução de Sinais
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