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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In explant livers with chronic hepatitis C (HCV-C) we have noted a distinctive histologic variant that we have termed steatohepatitic hepatocellular carcinoma (SH-HCC) with features resembling non-neoplastic steatohepatitis, including large droplet steatosis, ballooning of malignant hepatocytes, Mallory-Denk bodies, inflammation, and pericellular fibrosis. This study was undertaken to further describe the characteristics and prevalence of this histologic variant in HCV-C and any possible association with underlying risk factors for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We selected two 2-year periods (mid-2003 to mid-2005 and 2007 to 2008), from which selected explant livers with HCV-C and HCC were examined to determine the characteristics and frequency of SH-HCC. The underlying cirrhotic liver was also reassessed for steatosis and evidence of steatohepatitis. Clinical records were consulted for concomitant NAFLD and NASH risk factors. The SH-HCC variant was found in a total of 22 of 62 HCC cases (35.5%). Fourteen of the 22 patients with SH-HCC (63.6%) had at least one known risk factor for NAFLD/NASH including diabetes (6 of 22, 27.3%), obesity (6 of 22, 27.3%), hypertension (11 of 22, 50%), and hyperlipidemia (5 of 22, 27.8%). In 14 of the 22 cases (63.6%) of SH-HCC, the non-neoplastic liver showed changes of NAFLD/NASH superimposed on otherwise typical features of HCV-C. In conclusion, in our series of HCV-C explants, approximately one-third of HCCs show a distinctive histological variant termed SH-HCC. Underlying risk factors for NAFLD and for NASH were identified in 63.6% of our cases. Moreover, non-neoplastic tissue in HCV-C explants showed changes of NAFLD/NASH in 63.6% of cases. These results suggest a possible NAFLD/NASH pathway leading to SH-HCC in the setting of HCV-C which requires further investigation in the future.
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PMID:Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. 2097 41

Older patients with hemophilia face many challenges related not only to hemophilia but also to general comorbidity associated with aging. Patients with hemophilia often have known risk factors for cardiovascular disease, such as hypertension and hepatitis C virus (HCV) infection, which may counteract any protective effects bestowed by the hypocoagulable state. Arthritis and joint disease are common and contribute to disability and pain. The high prevalence of chronic HCV infection has led to an increased risk for liver failure and hepatocellular carcinoma. Renal function and urological disorders are a concern in these patients, and issues related to sexuality are an important but often-overlooked issue. The use of routine procedures for general health maintenance in the elderly (e.g. colonoscopy) can be more complex in patients with hemophilia due to the inherent risk of bleeding, and serious disorders such as malignancy can be overlooked if signs of abnormal bleeding are attributed to hemophilia, rather than to cancer. Prospective studies are needed to address these challenges so that evidence-based guidance can be given to clinicians who treat older patients with hemophilia.
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PMID:Clinical challenges within the aging hemophilia population. 2105 1

Obesity has become a pandemic disease causing a variety of lifestyle-related diseases, such as hypertension, dyslipidemia, diabetes mellitus, liver cirrhosis and hepatocellular carcinoma; therefore obesity has become an important health issue all over the world. Obesity was suggested to cause a chronic liver disease called nonalcoholic steatohepatitis (NASH) and to promote the progression of NASH to liver cirrhosis and hepatocellular carcinoma 30 years ago and this was proven 20 years ago. Today, 1% of the Japanese population is suffering from NASH. Twenty percent of NASH patients, 0.2 million patients, are suggested to develop liver cirrhosis latently in the next decade, and are at a serious risk of developing hepatocellular carcinoma. Indeed, diabetes mellitus has become prevalent among the Japanese population and 10% die from chronic liver disease, but few doctors are able to recognize liver cirrhosis and hepatocellular carcinoma in patients with diabetes mellitus. It is a serious health issue to ignore such risk factors that threaten life in Japan. There are many chronic liver diseases with fatty liver, and nonalcoholic fatty liver disease (NAFLD), a chronic liver disease of unknown etiology, affects 14% of the Japanese population today. As NASH is the most progressive form of this disease, it has become a very important health issue to let doctors know how to recognize patients with NAFLD. In this paper, we discuss how to recognize NAFLD, including NASH, in our outpatient clinic.
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PMID:[Chronic liver disease related to impaired glucose tolerance]. 2107 92

The introduction of novel targeted therapies into the clinic in recent years has had a considerable impact on the management of several neoplastic diseases--such as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell carcinomas--considered until recently refractory to systemic therapies. We describe here two such novel biological agents, sunitinib and sorafenib, as a paradigm of the successful clinical application of new concepts. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, C-Kit and others. Both agents are administered orally; sunitinib is tyically given in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given continually. Side effects occur in most patients, similar for both agents; they may affect several systems and organs but are mostly mild and easily manageable, rarely requiring discontinuation of the drug. However, these toxicities mandate prompt attention and intervention. The most frequently observed effects are hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac abnormalities may include congestive failure. Sunitinib, and markedly less frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism. Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for sunitinib as first-line treatment and for sorafenib in previously treated patients as second-line. Sunitinib is now approved as second-line therapy for patients with GIST refractory to imatinib; sorafenib has resulted in a significant prolongation in median survival in patients with hepatocellular carcinoma. Ongoing clinical trials will further define the spectrum of these agents' antitumor activity, their role in combination with other drugs, as well as their optimal dose and schedule of administration.
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PMID:Novel multitargeted anticancer oral therapies: sunitinib and sorafenib as a paradigm. 2109 May 21

The metabolic syndrome is a common complex entity that has emerged as a worldwide epidemic and major public health care concern with a prevalence of approximately 25% in the United States. There have been a number of different definitions of the metabolic syndrome but all center around the metabolic abnormalities of central obesity, hypertension, decreased high-density lipoproteins and elevated triglycerides with insulin resistance as the uniting physiologic factor. The importance of the metabolic syndrome is not just related to its high prevalence rate but also because it predicts the development of diabetes and cardiovascular disease. Nonalcoholic fatty liver disease is now recognized to be the hepatic component of the metabolic syndrome, which along with its individual components - particularly diabetes and elevated triglycerides, are the major risk factors for the development of nonalcoholic steatohepatitis (NASH); the most severe form of nonalcoholic fatty liver disease. NASH may progress to cirrhosis, hepatocellular carcinoma, and liver failure. It is currently the third most common cause for liver transplantation and is projected to be the leading cause for liver transplantation in 2020. Weight loss (via diet or bariatric surgery) and vitamin E have recently been demonstrated to be effective treatments of NASH. Although these and other agents may prove to be effective treatments for NASH, the most effective therapeutic strategy would be early screening and intervention to prevent the development of insulin resistance and oxidative stress at a societal level.
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PMID:Epidemiology of the metabolic syndrome in the USA. 2109 31

Antrodia cinnamomea (Ac) is a medicinal mushroom widely used for the treatment of abdominal pain, hypertension and hepatocellular carcinoma, but subchronic toxicity of this material has not yet been investigated. This present study was conducted to assess the 90-day oral toxicity of A. cinnamomea from submerged culture in male and female Sprague-Dawley (SD) rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. Test articles were administered by oral gavage to rats at 3000, 2200 and 1500 mg/kg BW/day for 90 consecutive days and reverse osmosis water was used as control. All animals survived to the end of the study. During the experiment period, no abnormal changes were observed in clinical signs, body weight and ophthalmological examinations. No significant differences were found in urinalysis, hematology and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. According to the above results, the no-observed-adverse-effect level (NOAEL) of Antrodia cinnamomea is identified to be greater than 3000 mg/kg BW/day in Sprague-Dawley rats.
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PMID:A 90-day subchronic toxicological assessment of Antrodia cinnamomea in Sprague-Dawley rats. 2109 23

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries, and accumulating evidence suggests it as the hepatic manifestation of the metabolic syndrome (MS). Although the published prevalence of hepatocellular carcinoma (HCC) is low in NAFLD/NASH patients, most of these data have been derived from areas endemic for viral hepatitis. We recruited 162 adults with HCC between February 2007 and March 2008, investigated the underlying etiologies and determined the prevalence of the MS and related features within each group. Patients with NAFLD/NASH-associated HCC exhibited a higher prevalence of metabolic features (Type 2 diabetes mellitus, hypertension, dyslipidemia, coronary artery disease) compared to non-NAFLD/NASH-HCC. Intriguingly, a significant number (41.7%; p < 0.005) of individuals with NAFLD/NASH-HCC had no evidence of cirrhosis. Patients with alcohol-induced liver disease also displayed many features (14/19, 73.7%) of the MS, although, in contrast to NAFLD/NASH-HCC, alcohol-associated HCC was highly associated with cirrhosis (95.0%; p = 0.064). NAFLD/NASH as the hepatic entity of the MS may itself pose a risk factor for HCC, even in the absence of cirrhosis. The MS may also promote development of HCC among those with alcoholic liver disease. Increased awareness of liver manifestations in the MS may instigate early interventions against developing HCC.
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PMID:Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. 2112 45

We analyzed the treatment outcome and effect of sorafenib in advanced hepatocellular carcinoma. Nine patients were received the therapy of sorafenib between June 2009 and October 2009. The overall incidence of treatment-related adverse events was 87.5%. Grade 3 drug-related adverse events included a hand-foot skin reaction (two patients) and fatigue (one patient). Grade 2 hypertension (three patients), grade 1 diarrhea (two patients) and anorexia (four patients) occurred at this study. The response rate was 0% (CR/PR 0, SD 2, PD 6) and median overall survival length was 101 days. Now there are two patients undergoing the therapy of sorafenib. Effect of sorafenib in advanced hepatocellular carcinoma was not good in this study, and drug-related adverse events had a high rate. However, the continuous treatment was possible with dose modified chemotherapy.
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PMID:[The outcome of chemotherapy by sorafenib in advanced hepatocellular carcinoma]. 2122 77

Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC). As the clinical use of sorafenib increases, many adverse effects have been reported, such as hand-foot skin reaction, diarrhea, anorexia, asthenia, alopecia, weight loss, hypertension and arterial thromboembolism. However, there are no prior reports of splenic infarction as an adverse effect of sorafenib. Here, a case of splenic infarction in a patient with HCC who was treated with sorafenib is reported. The patient had no other predisposing factors to explain the splenic infarction except for the administration of sorafenib. The splenic infarction improved after sorafenib was discontinued; however, the HCC progressed.
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PMID:Splenic infarction associated with sorafenib use in a hepatocellular carcinoma patient. 2124 3

Non-alcoholic steatohepatitis (NASH) as one entity of non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and accompanies the rise in the prevalence of obesity, diabetes mellitus, hypertension and hyperlipidemia in the western world. It is not known why some patients progress in the disease and develop inflammation in the liver, whereas others remain in the stage of simple steatosis, which generally has a benign course. However, NASH can progress to fibrosis and cirrhosis as well as hepatocellular carcinoma. Therefore, it is important to determine the stage of the disease in patients presenting with the metabolic syndrome and abnormal liver function tests, suggesting NAFLD. Liver biopsy is the only tool that allows for reliable detection, grading and staging of liver disease. The main strategies in the treatment of NASH are correction of risk factors (lifestyle modifications, insuline sensitizer) and anti-oxidants (ursodeoxycholic acid, vitamin E) which both have been shown to improve liver histology as well as liver enzymes. Patients wih alcoholic fatty liver disease (AFLD) present the same liver histology and often also metabolic alterations similar to metabolic syndrome. Therefore, MAFLD (metabolic syndrome-associated fatty liver disease) might describe both patient populations more accurately and also describes the pathophysiological characteristics.
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PMID:[Non-alcoholic steatohepatitis - from NAFLD to MAFLD]. 2145 38


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