Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steatohepatitis has recently been increasing as a cofactor influencing the progression of fibrosis, cirrhosis, adenoma and carcinoma in liver; however, the mechanisms by which it contributes to liver injury remain uncertain. We induced steatohepatitis in zebrafish embryos using thioacetamide (TAA). TUNEL assay revealed significant increasing of apoptosis in liver after 5 days post fertilization and the increasing of apoptosis was observed to be associated with the up-regulation of apoptotic genes such as, bad, bax, P-38a, caspase-3 and 8, and JNK-1. Histological sections by oil red O stain showed the accumulation of fatty droplets which causes the pushing of the nucleus towards one side. Up-regulation of steatosis markers such as, ACC, adiponectin, PTL, CEBP- alpha and beta, SREBP-1 was also observed. Furthermore, the elevation of glutathione peroxidase in TAA treated embryos indicated that TAA induces lipid peroxidation which leads to causes liver damage. Zebrafish has already been considered as a good human disease model and in this context; TAA-treated zebrafish may serve as a good animal model to study the molecular pathogenesis of steatohepatitis. Moreover, non-availability of specific drugs to prevent steatohepatitis, this animal model may serve as a powerful preclinical platform to study the therapeutic strategies and for evaluating chemoprevention strategies for this disease.
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PMID:Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis. 1645 12

Diffusion-weighted (Dw) imaging has for a number of years been a diagnostic tool in the field of neuroradiology, yet only since the end of the 1990s, with the introduction of echoplanar imaging (EPI) and the use of sequences capable of performing diffusion studies during a single breath hold, has it found diagnostic applications at the level of the abdomen. The inherent sensitivity to motion and the magnetic susceptibility of Dw sequences nonetheless still create problems in the study of the abdomen due to artefacts caused by the heartbeat and intestinal peristalsis, as well as the presence of various parenchymal-gas interfaces. With regard to focal liver lesions, a review of the literature reveals that Dw imaging is able to differentiate lesions with high water content (cysts and angiomas) from solid lesions. With regard to the latter, although there are differences between benign forms [focal nodular hyperplasia (FNH), adenoma] and malignant forms [metastasis, hepatocellular carcinoma (HCC)] in their apparent diffusion coefficient (ADC) in the average values for histological type, there is a significant overlap in values when lesions are assessed individually, with the consequent problem of their correct identification. One promising aspect is the possibility of quantifying the degree of fibrosis in patients with chronic liver disease and cirrhosis given that the deposit of collagen fibres "restricts" the motion of water molecules and therefore reduces ADC values. However, even in this field, studies can only be considered preliminary and far from real clinical applications. The retroperitoneum is less affected by motion artefacts and similarly deserves the attention of Dw imaging. Here it is possible to differentiate mucin-producing tumours of the pancreas from pseudocystic forms on the basis of ADC values even though the limited spatial resolution of Dw imaging does not enable the identification of small lesions. Dw imaging may be applied to the study of the kidney to differentiate hydronephrosis from pyonephrosis and with regard to tumours, solid from pseudocystic forms. In addition, given that renal parenchyma has significantly variable ADC values on the basis of the anatomic section and physiological conditions, the possibility of assessing functional alterations is currently being studied. Indeed, a good correlation has been found between ADC values and glomerular filtration rate. With regard to musculoskeletal applications, the absence of motion artefacts in the regions studied has enabled the development of sequences less sensitive to magnetic susceptibility and with greater spatial resolution than EPI. Attempts have therefore been made to use Dw imaging in the characterization of soft-tissue tumours although the findings so far have been disputed. Greater agreement has been found regarding sensitivity of the technique in assessing response of these tumours to chemotherapy: tumour necrosis is thought to increase ADC whereas the persistence of vital neoplastic tissue tends to lower it. One of the most promising applications of Dw imaging is without doubt the assessment of vertebral collapse where a high ADC has been shown to be associated with an osteoporotic cause and a low ADC with a neoplastic cause. Nonetheless, even here, a moderate overlap between ADC values of the two types has been encountered. Dw imaging has also been used in the assessment of bone marrow cellularity: areas of tightly packed cells show a higher ADC value than hypocellular areas. In particular, no significant difference in ADC is noted between normal hypercellular bone marrow and hypercellular bone marrow secondary to lymphomatous infiltration whereas this difference is significant between hypocellular, normocellular and haematopoietic hypercellular bone marrow. With regard to the study of joints, the limited structure dimensions, particularly cartilage, creates technical difficulties related to spatial resolution and an adequate signal-to-noise ratio, problems that can only be solved by further technological developments. Lastly, a significant difference in ADC values between degenerative and inflammatory effusion has been found, a fact that may be explained as the result of the activity of hyaluronidase present in inflammatory forms, which causes a reduction in the concentration of hyaluronic acid with a consequent decrease in viscosity.
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PMID:Magnetic resonance diffusion-weighted imaging: extraneurological applications. 1668 86

The incidence of hepatocellular carcinoma (HCC) will continue to increase for the next decade due to a latency of about 30 years due to cirrhosis caused by chronic hepatitis C. The diagnosis of an underlying cirrhosis is of diagnostic importance. According to WHO guidelines, HCC encompasses the following: trabecular, pseudoglandular, acinar, compact, scirrhous and fibrolamellar subtypes. Cytological appearance includes hepatocellular pleomorphic, clear cell and sarcomatous subtypes. Tumor cells in hepatocellular carcinoma may display intracytoplasmic inclusions that are helpful for establishing the diagnosis. Differential diagnosis has to be considered for such hepatic tumors as adenoma and precancerous lesions such as dysplastic nodules or mesenchymal tumors. Metastases in the liver may be difficult to differentiate, especially for primary tumors from the gastrointestinal tract which may be similar to glandular or scirrhous type of HCC. The existence of underlying cirrhosis is helpful for the diagnosis and an ample spectrum of antibodies against liver antigens and adenocarcinomas are commercially available to confirm the correct diagnosis.
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PMID:[Diagnosis and differential diagnosis of hepatocellular carcinoma]. 1676 25

Nodular regenerative hyperplasia (NRH) is characterized by a non-cirrhotic micronodular transformation of the liver parenchyma. It is based on the obliteration of small portal veins. Macroregenerative nodules (MRN) develop in areas of favourable blood flow in otherwise hypoperfused liver tissue. Hypoperfusion is caused by obliteration of liver veins and/or large portal veins with the subsequent atrophy or extinction of parenchyma. The hyperperfused and sometimes rapidly growing MRN might simulate a malignant tumor in CT and MRT. Morphologically, MRN resemble FNH. In contrast to hepatocellular adenoma, they show a more or less nodular architecture with fibrous septa and ductular structures. NRH and cases of MRN without cirrhosis can indicate an extrahepatic/systemic disease causing altered liver perfusion. MRN in liver cirrhosis must be differentiated from dysplastic nodules and highly differentiated hepatocellular carcinoma by cytological and microarchitectural criteria. Focal nodular hyperplasia (FNH) can imitate liver cirrhosis, steatohepatitis, cholangitis or chronic hepatitis, if biopsy material does not include normal perilesional liver tissue. Telangiectatic FNH might resemble classic hepatocellular adenoma. Neoductular structures and septation argue for this rare subtype of FNH. Neoductular transformation of hypoperfused liver parenchyma might imitate cholangioma or cholangiocarcinoma.
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PMID:[Nodular lesions of liver parenchyma caused by pathological vascularisation/perfusion]. 1677 11

The liver is morphologically and functionally modulated by sex hormones. Long-term use of oral contraceptives (OCs) and anabolic androgenic steroids (AASs) can induce both benign (hemangioma, adenoma, and focal nodular hyperplasia [FNH]) and malignant (hepatocellular carcinoma [HCC]) hepatocellular tumors. Hepatic adenomas (HAs) are rare, benign neoplasms usually occurring in young women, the development and the complications of which have been related to the strength of OCs and the duration of their use. HA incidence has fallen since the introduction of pills containing smaller amounts of estrogens. FNH is a benign lesion, most commonly seen in young women, which is thought to represent a local hyperplastic response of hepatocytes to a vascular abnormality. Because of the female predominance and the young age at onset, a role of female hormones has been suggested. Furthermore, a large proportion of women with FNH (50-75%) are OC users. Liver hemangiomas (LHs) are the most common benign liver tumors and are seen more commonly in young adult females. The female predilection and clinical observations of LH growth under conditions of estrogenic exposure suggest a possible role for estrogen in the pathogenesis of LHs. HCC has become one of the most widespread tumors in the world in recent years, representing the sixth leading cancer and the third most common cause of death from cancer. Apart from liver cirrhosis, numerous other factors responsible for its onset have been proposed: hepatitis infections from virus B (HBV) and C (HCV), alcohol, smoking, and aflatoxin. However, regardless of etiology, chronic liver diseases progress at unequal rates in the two sexes, with the major sequelae, such as cirrhosis and HCC, being more frequent in men than in women. These epidemiological data have prompted researchers to investigate the relationship between sex hormones and liver tumors. The human liver expresses estrogen and androgen receptors and experimentally both androgens and estrogens have been implicated in stimulating hepatocyte proliferation and may act as liver tumor inducers or promoters.
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PMID:Sex hormones and risk of liver tumor. 1726 70

Primary neoplasms of the liver are composed of cells that resemble the normal constituent cells of the liver. Hepatocellular carcinoma, in which the tumor cells resemble hepatocytes, is the most frequent primary liver tumor, and is highly associated with chronic viral hepatitis and cirrhosis of any cause. Benign tumors, such as hepatocellular adenoma in a noncirrhotic liver or a large, dysplastic nodule in a cirrhotic liver, must be distinguished from well-differentiated hepatocellular carcinoma. Cholangiocarcinoma, a primary adenocarcinoma that arises from a bile duct, is second in frequency. It is associated with inflammatory disorders and malformations of the ducts, but most cases are of unknown etiology. Cholangiocarcinoma resembles adenocarcinomas arising in other tissues, so a definitive diagnosis relies on the exclusion of an extrahepatic primary and distinction from benign biliary lesions.
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PMID:Neoplasms of the liver. 1748 52

Of hepatocellular carcinomas (HCC), 15-20% occur in the non-cirrhotic liver. All factors which cause HCC when liver cirrhosis (LC) is present, can also lead to HCC without LC. On the basis of the relative frequency, HCC can be roughly differentiated into 3 groups: 1) HCC, rarely occurring without cirrhosis (e.g. virus hepatitis, alcohol abuse). 2) HCC, frequently occurring without LC (alpha1-antitrypsin deficiency, hemochromatosis, non-alcoholic fatty liver disease). 3) HCC, consistently occurring without LC (glycogen storage disease type 1, consumption of oral contraceptives/anabolic steroids). In groups 1 and 2 the level of hepatocellular toxicity necessary to reach LC is not yet achieved but the carcinogenic effect is already strong enough to induce HCC, possibly owing to the influence of additional carcinogens or host factors. In group 3, the carcinogenic effect is mediated by a long-standing alteration of the hepatocellular metabolism that is of low toxic effect and does not lead to cell death, but is nevertheless carcinogenic. In these cases, the initial formation of hepatocellular adenomas that subsequently transform into HCC is a common finding (adenoma-carcinoma sequence).
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PMID:[Hepatocellular carcinoma in the non-cirrhotic liver]. 1805 36

Sinusoidal alterations unrelated to primary hepatocellular damage present without characteristic clinical findings and in these cases the liver biopsy is particularly important. Capillarization of sinusoids is characterized by closing of fenestration, formation of a basal membrane and by the expression of CD34 and is typical for active cirrhosis. In nodular regeneratory hyperplasia, capillarization indicates a local or general disturbance of perfusion. In large regenerative nodules, focal nodular hyperplasia and liver cell adenoma CD34-positive capillaries reflect afferent parts and CD34-negative sinusoids the efferent parts of the parenchymal vascular bed. HCC generally have a completely capillarized CD34-positive vascular bed. Hepatic angiosarcomas and epithelioid hemangioendotheliomas can be easily overseen in liver biopsies, if they spread along the sinusoids without detoriation of the acinar architecture and without significant alteration of the surrounding liver cell plates. Toxic damage of endothelial cells, post-sinusoidal stasis and sinusoidal hyperperfusion are the underlying pathogenetic principles of sinusoidal injury. Rupture and loss of the perisinusoidal reticulin fibres lead to peliosis hepatis. In these cases liver biopsy might disclose occlusion of the terminal liver veins (VOD). Perisinusoidal fibrosis can be caused by intrasinusoidal accumulation of pathologic cells, advanced intrasinusoidal macrophagocytic storage diseases and by activation of the vitamin A-storing hepatic stellate cells. Perisinusoidal amyloidosis can be the first sign of an underlying B-cell neoplasia.
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PMID:[Pathology along the liver sinusoids: endothelial and perisinusoidal findings]. 1821 Jan 8

Magnetic resonance imaging is routinely used for the workup of patients with focal or diffuse liver disease, including primary hepatocellular lesions, storage diseases, metastatic liver disease, and diseases of the hepatobiliary tree. The most important magnetic resonance imaging sequences used for diagnostic imaging of the liver consist of T1-weighted sequences, T2-weighted sequences, and at least the arterial and delayed phases of dynamic gadolinium-enhanced imaging. This article provides an overview of magnetic resonance imaging of primary hepatocellular lesions and will describe the following: (1) the classification and etiology of primary hepatocellular lesions, including focal nodular hyperplasia, hepatocellular adenoma, and hepatocellular carcinoma; (2) the stepwise carcinogenesis of hepatocellular carcinoma in cirrhosis on magnetic resonance imaging; and (3) the typical imaging findings of primary hepatocellular lesions on magnetic resonance imaging, with differential diagnoses.
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PMID:Primary hepatocellular lesions: imaging findings on state-of-the-art magnetic resonance imaging, with pathologic correlation. 1843 10

Glypican-3 is a heparin sulfate proteoglycan normally expressed in fetal liver and placenta, but not in normal adult liver. Preliminary studies have shown that glypican-3 can be useful for the diagnosis of hepatocellular carcinoma. We performed immunohistochemistry for glypican-3 on 80 resection cases of hepatocellular lesions to examine the utility of glypican-3 immunohistochemistry in hepatocellular carcinoma at two ends of the differentiation spectrum. Staining was compared to Hep Par 1 in poorly differentiated cases. Glypican-3 was expressed in 46 (79%) hepatocellular carcinomas (56, 83 and 89% of well, moderately and poorly differentiated respectively) and seven (64%) fibrolamellar carcinomas. Of the 16 well differentiated cases, 10 closely resembled adenoma and were diagnosed due to focal abnormalities and/or loss of reticulin. Glypican-3 expression was seen in 50% in this group. Hepatocellular carcinomas arising in cirrhotic liver were more likely to be glypican-3 positive (91 vs 57%, P=0.004). All hepatic adenomas and macroregenerative nodules were negative, and three (43%) high grade dysplastic nodules were positive. Focal staining was seen in regenerative nodules in four (11%) cirrhosis cases. Glypican-3 was significantly more sensitive than Hep Par 1 for diagnosis of poorly differentiated hepatocellular carcinomas (89 vs 63%, P=0.02). The difference was more significant when only cases with diffuse positive staining were considered (83 vs 21%, P<0.001). In conclusion, glypican-3 has high sensitivity for the diagnosis of hepatocellular carcinoma, but is less sensitive in the extremely well differentiated hepatocellular carcinoma and fibrolamellar variant of hepatocellular carcinoma. Caution should be exercised in using glypican-3 in biopsy specimens as cirrhotic nodules can show strong expression. Glypican-3 can be especially useful in the identification of poorly differentiated hepatocellular carcinoma as it has higher sensitivity compared to Hep Par 1.
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PMID:Utility and limitations of glypican-3 expression for the diagnosis of hepatocellular carcinoma at both ends of the differentiation spectrum. 1853 57


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