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)

Shosaikoto, a Kampo medicine used clinically to treat patients with chronic hepatitis or cirrhosis in Japan, displays immunoregulatory effects, especially on macrophage functions. Oral administration of shosaikoto influences the synthesis of humoral factors such as the interleukins, nitric oxide and prostaglandins in macrophages. In addition, phagocytic activity is enhanced by treatment with shosaikoto, resulting in an antigen that is effectively presented to T lymphocytes to produce more antibodies. The role of macrophages in the pathogenesis of atherosclerosis is well recognized, although a therapeutic agent targeted at macrophages has not yet been developed. When shosaikoto was administered to atherosclerotic rabbits, it did not exhibit antihyperlipidemic effects but did reduce the formation of atherosclerotic lesions. In addition, treatment with shosaikoto suppressed intimal hyperplasia in apoE-deficient mice fed a cholesterol-enriched diet for nine weeks. Biochemical studies demonstrated that the mechanism of the antiatherosclerotic effect was partly due to the increase of oxidized low-density lipoprotein (oxLDL) elimination by macrophages, resulting from stimulation of oxLDL uptake through scavenger receptors, activation of acyl-CoA:cholesterol acyltransferase and neutral cholesteryl ester hydrolase, and increase of cholesterol elimination by high-density lipoprotein. Furthermore, shosaikoto is able to reverse the depression of macrophage functions caused by hyperlipidemia. These results indicate the potential of this medicine as a new type of preventive or therapeutic agent for atherosclerosis.
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PMID:Shosaikoto as a potential antiatherosclerotic agent. 1293 13

Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition.
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PMID:De novo non-alcoholic fatty liver disease following orthotopic liver transplantation. 1452 3

Nonalcoholic fatty liver disease (NAFLD) is very common in the United States, and in some patients it may lead to cirrhosis, liver failure, and liver cancer. NAFLD encompasses a spectrum of liver injury, ranging from steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Nonalcoholic steatohepatitis (NASH), an advanced form of NAFLD, histologically comprises steatosis, balloon degeneration, inflammation, and fibrosis in varying degrees. It is generally believed that simple steatosis is benign with minimal risk of progression, whereas NASH is progressive and can lead to cirrhosis. The commonly associated risk factors for NAFLD include obesity, hyperlipidemia, and diabetes mellitus. The pathogenesis of NAFLD and NASH is not fully known; however, current evidence suggests that insulin resistance and lipid peroxidation play a role in the pathogenesis of this condition. Currently, there are no proven effective therapies available for the treatment of NASH. Although there are numerous studies that have explored various treatments for NASH, these generally consist of small numbers of patients with suboptimal endpoints. Treatment strategies for NAFLD and NASH can be broadly divided into 1) treatment or control of underlying risk factors such as hyperlipidemia, diabetes mellitus, and obesity; and 2) specific pharmacologic therapy such as insulin sensitizers, antioxidants, or cytoprotective agents. Newer thiazolidinediones, such as rosiglitazone and pioglitazone, have shown promise in the treatment of NASH in pilot studies. However, these agents should not be used in clinical practice until their efficacy and safety are firmly established in larger studies. Despite encouraging initial studies, the recently completed multicenter, randomized, controlled trial failed to show any efficacy for ursodeoxycholic acid in the treatment of NASH. Other agents, such as vitamin E, betaine, probucol, and atorvastatin, have been explored as therapeutic agents for NASH. However, none of these studies have shown convincingly their utility in the treatment of NASH. Attempts to identify optimal therapy for patients with NASH are being vigorously pursued by the research community and important advances are expected within next several years. Until then, subjects should be advised to avoid alcohol, lose weight, and exercise regularly, and meticulous attention should be paid to the control of their risk factors such as diabetes and hyperlipidemia.
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PMID:Treatment of Nonalcoholic Fatty Liver Disease. 1458 34

Although histological hepatitis occurs in the majority of hepatitis C virus (HCV)-infected liver transplant recipients, the natural history is highly variable. Whereas progression to cirrhosis occurs in up to 30% after 3 to 7 years, the disease remains stable in another third of patients, in whom protocol liver biopsies might be avoided. However, there is recent concern that with prolonged follow-up, some patients with initial benign recurrence may develop a late-onset aggressive course. Aims of the study are to determine the incidence and factors associated with this event. Based on yearly protocol biopsies (median, five biopsies; range, three to seven biopsies), we evaluated the histological outcome of 57 HCV type 1b-infected transplant recipients with initial benign recurrence, defined as stable histological state (fibrosis stage F0 or F1) during the first 3 years posttransplantation. Severe late-onset liver damage is defined as progression to F3 or F4 in patients with previous benign recurrence. Potential predictors of this event include demographics, donor-related factors, liver enzyme levels at 1 and 3 (or baseline) years posttransplantation, activity grade and fibrosis stage at 1 and 3 years posttransplantation, nonalcoholic steatohepatitis-related variables occurring within the first 3 years posttransplantation (diabetes, hyperlipidemia, obesity), use of some drugs (renin-angiotensin inhibitors, ursodeoxycholic acid), and the advent of any unusual event. The incidence of severe late-onset liver damage was 35% (n = 20). Twelve transplant recipients progressed to F3, whereas 8 transplant recipients progressed to F4. Sudden histological deterioration was observed on postoperative biopsy 5 in 12 patients; biopsy 6 or 7, in 7 patients; and biopsy 4, in 1 patient. Variables associated with this event in univariate analysis were fibrosis stage and activity grade (and its components) at baseline (P <.0001), recipient female gender (P =.04), alanine aminotransferase (ALT) level at 1 year posttransplantation (P =.02), and aspartate aminotransferase (AST) and ALT levels at baseline (P =.008 and P =.005, respectively). By multivariate analysis, only one variable was retained in the model: fibrosis stage at baseline (relative risk, 11; 95% confidence interval, 3 to 41; P =.0007), whereas AST level almost reached statistical significance (P =.07). In conclusion, delayed HCV-related severe liver damage is not infrequent in transplant recipients with initial benign recurrence, occurring in approximately one third of them. The presence of some degree of fibrosis at baseline appears to predict this sudden change in the natural history of recurrent hepatitis C. Based on these findings, we recommend continuing protocol biopsies and evaluating potential antiviral therapy in transplant recipients with evidence of some fibrosis (even if it is only portal).
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PMID:Delayed onset of severe hepatitis C-related liver damage following liver transplantation: a matter of concern? 1458 75

A 56-year old Japanese female was admitted to our hospital because of the increased levels of serum AST, ALT, and gamma-GTP. She was diagnosed with systemic lupus erythematosus in September, 1996 and had been on a regular glucocorticoid therapy since then. Abdominal ultrasonography showed the mild fatty liver, and hepatic histopathology revealed a typical and remarkable steatohepatitis, a remarkable neutrophil infiltration, and Mallory bodies. Because she had no history of alcohol-drinking, diagnosis of non-alcoholic steatohepatitis (NASH) was made. Treatment was started with a low-calorie diet, bed-rest, and an oral administration of alpha-tocopherol and bezafibrate with favorable effects on her serum levels of AST, ALT, gamma-GTP, and LDH. When a patient on a glucocorticoid therapy shows signs of fatty liver, diabetes mellitus, hyperlipidemia, an insulin resistance, NASH should be considered as one of the differential diagnosis. This is particularly important since proper therapy with a low-calorie diet and drugs with anti-oxidant activities improve this potentially progressive disease before resulting in liver cirrhosis and hepatic carcinoma.
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PMID:[Systemic lupus erythematosus with steroid induced non-alcoholic steatohepatitis: a case report]. 1459 60

Obesity, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are becoming increasingly common medical problems in the developed world, often in the setting of the metabolic or insulin resistance syndrome (IRS). It is predicted that by the year 2025 > 25 million Americans may have NASH-related liver disease. NASH and NAFLD also affect the donor population. The use of steatotic donor livers for liver transplantation (LT) is associated with an increased risk of primary nonfunction (PNF) in the allograft. There is particular reluctance to use steatotic livers for living donor LT. There is indirect evidence to suggest that patients undergoing LT for cirrhosis resulting from NASH may have poorer outcome, despite careful selection of LT candidates. Indeed it is likely that many potential LT candidates with NASH are excluded from LT due to co-morbid conditions related to IRS. The post-LT patient is at risk of several components of IRS, such as diabetes mellitus, hypertension, hyperlipidaemia and obesity and there is increasing recognition of de novo and recurrent NAFLD and NASH after LT. Thus NAFLD and NASH affect all aspects of LT including donors, patients in evaluation and the LT recipient.
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PMID:Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and orthotopic liver transplantation. 1508 61

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as a common liver disorder that represents the hepatic manifestation of the metabolic syndrome, a variably defined aggregate of disorders related to obesity, insulin resistance, type II diabetes, hypertension and hyperlipidemia. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury that carries a risk for progressive fibrosis, cirrhosis, and end-stage liver disease. Hepatocellular carcinoma (HCC) is a documented complication in an as yet unknown percentage of cases of NASH cirrhosis. The diagnosis of nonalcoholic steatohepatitis requires histopathologic evaluation because the lesions of parenchymal injury and fibrosis cannot be detected by imaging studies or laboratory tests. This article will briefly discuss prevalence studies and the pathophysiology of NAFLD and focus on current discussions related to the specific lesions in the pathology of NASH, including the challenges of pediatric NASH and NASH-related cirrhosis.
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PMID:Nonalcoholic steatohepatitis. 1508 83

Non alcoholic fatty liver disease is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of insulin resistance. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification fatty liver disease in obese patients, is very important in order to prevent complications such as steathohepatitis and cirrhosis. The pathogenesis of non alcoholic fatty liver disease is very complex, there are mitochondrial morphologic and functional alterations, as well as, high sensitivity to injurious stimulus, an increased inflammatory activity, and modifications in cellular metabolism at post-receptor level. Weight reduction is one of the first steps in the treatment of patients with non alcoholic fatty liver disease, as well as the management of associated conditions such as obesity, diabetes mellitus and hyperlipidaemia. Antioxidants, and others drugs such as ursodeoxycholic acid may be beneficial in the treatment of non alcoholic fatty liver disease. These medications, however, need first to be tested in well-controlled trials with clinically relevant end-points and extended follow-up. In this review, we analyze the new concepts in epidemiology, pathophysiology and treatment of this disease.
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PMID:[An update on non-alcoholic fatty liver disease]. 1514 45

Non-alcoholic steatohepatitis (NASH) is emerging as an important cause of cryptogenic cirrhosis. Obesity, diabetes mellitus and hyperlipidaemia are important risk factors for NASH. The presence of these risk factors in patients with cryptogenic cirrhosis may suggest NASH as an aetiology of cirrhosis in them. Twenty-five patients of cryptogenic cirrhosis were compared with 18 patients of hepatitis B virus and hepatitis C virus related cirrhosis and primary biliary cirrhosis for the presence of obesity, diabetes mellitus and hyperlipidaemia. Patients with cryptogenic cirrhosis were found to have a significantly higher body - mass index increased prevalence of diabetes mellitus and lower high-density lipoprotein compared to the controls. Increased body weight and diabetes mellitus may play a role in the causation of cirrhosis in patients with cryptogenic cirrhosis.
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PMID:Prevalence of obesity, diabetes mellitus and hyperlipidaemia in patients with cryptogenic liver cirrhosis. 1530 64

Nonalcoholic steatohepatitis may cause severe fibrosis, cirrhosis, and hepatocellular carcinoma, but supporting evidence is based on indirect data. Few publications have examined the results of repeat liver biopsies to evaluate progression of fibrosis. The aims of this study were to assess rate of fibrosis progression in untreated patients with nonalcoholic steatohepatitis and to identify associated variables. Among 106 patients, a second liver biopsy was proposed to those who had undergone their first liver biopsy at least 3 years before. None of them had been given pharmacological therapy. Liver biopsy samples were evaluated blindly. Variables were compared between patients with (group P) and without (group NP) fibrosis progression, using a Wilcoxon rank-sum test for numerical variables and a difference of two binomial proportions for categorical ones. Twenty-two patients (median age, 45 years; age range, 20-69 years; 13 women; diabetes in 8 patients, obesity in 10 patients) underwent a second liver biopsy 4.3 years (range, 3.0-14.3 years) after the first. Fibrosis progression was found in 7 patients in group P (31.8%), no progression was found in 15 patients in group NP. There were no differences between both groups regarding age, gender, diabetes, hyperlipidemia, ALT levels, AST-to-ALT ratio levels, albumin levels, prothrombin activity, steatosis, or inflammation. Obesity was significantly more prevalent in group P (86%) than in group NP (27%; P =.01). Basal body mass index was higher in group P (median, 33.2; range, 29.1-38.2) than in group NP (median, 29.0; range, 24.0-38.1; P =.024). Time between biopsies was not different between groups. In conclusion, progression of liver fibrosis was found in a third of nonalcoholic steatohepatitis patients 4.3 years after the first liver biopsy, and obesity and body mass index were the only associated factors with such progression.
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PMID:Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. 1538 71


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