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)

Females have a greater susceptibility to ethanol-induced liver injury than males. Females who drink ethanol regularly and have been overweight for 10 years or more are at greater risk for both hepatitis and cirrhosis than males, and females develop ethanol-induced liver injury more rapidly and with less ethanol than males. Female rats on an enteral ethanol protocol exhibit injury more quickly than males and have widespread fatty changes over a larger portion of the liver lobule. Moreover, levels of plasma endotoxin, intracellular adhesion molecule-1, free radical adducts, infiltrating neutrophils and nuclear factor kappa B are doubled in female rat livers compared with male rat livers after enteral ethanol treatment. Additionally, estrogen treatment in vivo increases the sensitivity of hepatic macrophages or Kupffer cells to endotoxin. Evidence has been presented that Kupffer cells are pivotal in the development of ethanol-induced liver injury. Destroying Kupffer cells with gadolinium chloride or decreasing bacterial endotoxin by sterilizing the gut with antibiotics inhibits early inflammation due to ethanol. Similar results have been obtained with anti-tumour necrosis factor-alpha antibody. These data pointed to the hypothesis that ethanol-induced liver injury involves elevations in circulating endotoxin concentrations leading to activation of Kupffer cells, which causes a hypoxia-reoxygenation injury. This theory has been tested using pimonidazole, a 2-nitroimidazole marker, to quantify hypoxia in downstream, pericentral regions of the hepatic lobule. After chronic enteral ethanol treatment, pimonidazole binding doubles. Enteral ethanol also increases free radicals detected with electron spin resonance. Radical adducts, with coupling constants such as alpha-hydroxyethyl radical, have been shown to arise from ethanol. Importantly, hypoxia and radical production detected in bile are also decreased by the destruction of Kupffer cells with gadolinium chloride. These data support the hypothesis that Kupffer cells contribute to the vital sex differences in liver injury caused by ethanol.
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PMID:Sex-related liver injury due to alcohol involves activation of Kupffer cells by endotoxin. 1111 Jun 25

Studies assessing morbidity and mortality in obese patients undergoing orthotopic liver transplantation (OLT) have produced conflicting results, mainly because of the small sample size. The objective of our study was to determine graft and patient survival in obese adults receiving OLT in the U.S. between 1988 through 1996 using the United Network for Organ Sharing (UNOS) database. Among the 23,675 transplantations performed during the 9-year study period, 18,172 (75%) patients fulfilled the inclusion criteria. Of these, 8,382 (46%) were nonobese (body mass index [BMI] < 25 kg/m(2)), 5,913 (33%) were overweight (BMI, 25.1-30 kg/m(2)), 2,611 (14%) were obese (BMI, 30.1-35 kg/m(2)), 911 (5%) were severely obese (BMI, 35.1-40 kg/m(2)), and 355 (2%) were morbidly obese (BMI, 40.1-50 kg/m(2)). The outcome measures assessed were immediate (30-day), 1-, 2-, and 5-year patient survival. Obese groups had a higher proportion of women, a greater prevalence of cryptogenic cirrhosis (P <.05) and diabetes (P <.05), and a higher serum creatinine. Primary graft nonfunction, and immediate, 1-year, and 2-year mortality were significantly higher in the morbidly obese group (P <.05). Five-year mortality was significantly higher both in the severely and morbidly obese subjects (P <.05), mostly as a result of adverse cardiovascular events. Kaplan-Meier survival was significantly lower in morbidly obese patients, and morbid obesity was an independent predictor of mortality. Obesity is associated with a significant increase in long-term mortality, mostly as a result of cardiovascular events. Weight loss should be recommended for all patients awaiting a liver transplantation, especially if their BMI is more than 35 kg/m(2).
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PMID:Obesity and its effect on survival in patients undergoing orthotopic liver transplantation in the United States. 1248 Nov 72

Despite the rising incidence of obesity and diabetes, there is little emphasis on morbidity and mortality from obesity-related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity-related cryptogenic cirrhosis compared with cirrhosis of other origins. We analyzed retrospectively 27 overweight patients with cryptogenic cirrhosis (CC-O), 10 lean patients with cryptogenic cirrhosis (CC-L) and 391 patients with hepatitis C virus-related cirrhosis (C-HCV). In CC-O patients, cirrhosis was detected later in life than in C-HCV and CC-L patients. Severe liver disease was as frequent in CC-O as in C-HCV patients as indicated by the proportion of Child B or C or of episodes of hepatic decompensation. Survival of CC-O patients was lower than that of untreated, age- and sex-matched C-HCV controls (P <.02 at 30 months), with a higher mortality of Child B or C patients. Hepatocellular carcinoma was detected in 8 of 27 (27%) CC-O patients versus 21% of matched C-HCV controls with a similar age cumulated incidence, suggesting a comparable carcinogenic potential. In conclusion, obesity-related cirrhosis should now be recognized as a distinct entity that can cause severe liver disease and death. Increased awareness of and better diagnostic strategies for nonalcoholic steatohepatitis in overweight patients are urgently needed.
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PMID:Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. 1202 34

Non-alcoholic steatohepatitis (NASH), is a critical link in the chain of metabolic fatty liver disorders that spans steatosis to cryptogenic cirrhosis. It is the hepatic manifestation of the insulin resistance (or metabolic) syndrome, and provides a clue to understanding fibrotic progression of other chronic liver diseases, particularly hepatitis C. Non-alcoholic steatohepatitis is often the first clinical indication of insulin resistance, with its complications of high blood pressure, coronary heart disease and type 2 diabetes. Among those with risk factors, NASH is common: present in at least 20% of obese adults or children with or without type 2 diabetes, and at least 5% of those overweight. With emerging urbanization, increasing affluence and behavioral changes of physical inactivity and high fat/energy-excessive diet, type 2 diabetes has become common in Asia and the western Pacific rim. The rates range from 7-40%, which in countries like Japan represents a 3-20-fold increase (depending on age) over the last 20 years. The increase is associated with central adiposity, insulin resistance, hepatic steatosis and NASH. After cancer, cirrhosis from NASH is now the second most common age-related cause of death in type 2 diabetes. Reversing these trends must become a public health priority; the first awakenings were evident in Taiwan at the time of this meeting. In order to stimulate clinicians to think more about the importance of metabolic liver disease for development of cirrhosis, this review will cover clinical and laboratory features, natural history and an approach to diagnosis and management of NASH. Some emerging concepts on pathogenesis will be mentioned briefly, but the emphasis will be on the potency of lifestyle adjustments (physical activity and diet) to prevent or reverse fatty liver disorders.
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PMID:Non-alcoholic steatohepatitis: what is it, and why is it important in the Asia-Pacific region? 1254 95

The Hepatitis C virus has emerged over the last two decades as the cause of the second greatest viral infection epidemic after the human immunodeficiency virus (HIV). A significant characteristic of the infection with the Hepatitis C virus is the variable course of its natural history. About 80% of the people who acquire this agent develop a chronic infection, with varying degree of liver damage, including cirrhosis and even hepatocelular carcinoma. However, only a minority progresses towards more severe forms. Several factors associated with the host seem to influence the progression of Hepatitis C into cirrhosis. The most important are alcohol abuse, the age in which the infection is acquired, duration of the infection, overweight, male sex and coinfection with Hepatitis A or B or HIV. Evidence of the role of iron levels in the liver, tobacco or the source of infection are less clear. The factors associated with the agent do not seem to play any role in the progression of the disease. Additional studies with adequate control groups are required to confirm the participation of the above mentioned host factors and to identify others which could influence the natural history of the Hepatitis C infection. A reduction in the ingestion of alcohol, overweight and tobacco consumption could contribute to the treatment of HVC chronic infection, as well as vaccination against Hepatitis A and B.
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PMID:[Risk factors for the progression of chronic hepatitis C virus infection]. 1285 89

Nonalcoholic fatty liver disease is a condition gaining increasing recognition as a cause of cirrhosis and end-stage liver disease. The condition appears identical to alcoholic liver disease histologically, yet occurs in patients with negligible alcohol intake. Nonalcoholic fatty liver disease covers a spectrum of diseases ranging from simple fatty deposition in the liver to fat and inflammation and finally to fibrosis and cirrhosis. Conditions most frequently found in association with nonalcoholic fatty liver disease include obesity, Type 2 diabetes, and hyperlipidemia. Although the exact etiology of nonalcoholic fatty liver disease is not clear, insulin resistance is thought to play an important factor. Patients typically present with asymptomatic serum aminotransferase elevations of 2-3 times normal. Symptoms may include fatigue and abdominal pain. The clinical course is difficult to predict due to a lack of research in the natural history of the disease. It is known a percentage of patients progress to end-stage liver disease and may require liver transplantation. No medical treatment has been found to be totally effective. Patients who are overweight or obese should be encouraged in gradual weight reduction that has been associated with improvement in liver test abnormalities.
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PMID:Nonalcoholic Fatty liver disease. 1292 Apr 29

The aim of this study was to determine if body mass index (BMI) was an independent predictor of response to antiviral treatment in patients with chronic hepatitis C. A retrospective review was performed of all patients at a single center with chronic hepatitis C treated with antiviral medication from 1989 to 2000. A sustained response was defined as either negative hepatitis C virus (HCV) RNA by polymerase chain reaction and/or normal alanine aminotransferase (ALT) level (only in those treated before availability of HCV RNA testing) 6 months following completion of therapy. All patients were classified into one of 3 groups according to BMI (normal, <25 kg/m(2); overweight, 25-30 kg/m(2); obese, >30 kg/m(2)). A total of 253 patients were treated with either interferon (IFN) monotherapy or IFN in combination with ribavirin. Patients were excluded if predetermined clinical characteristics were unavailable. Using logistic regression, and after adjusting for the examined variables (age, sex, history of alcohol consumption >50 g/d, cirrhosis on pretreatment biopsy, and BMI), likelihood ratio tests showed significant differences in response to treatment according to BMI group (P =.01), genotype (P <.01), and cirrhosis (P <.01). Those with genotypes 2 or 3 had an odds ratio (OR) for success of 11.7 compared with those with genotype 1, cirrhotic patients had an OR of 0.15 compared with noncirrhotic patients, and obese patients had an OR of 0.23 compared with normal and overweight patients. Hepatic steatosis was not an independent risk factor for response to antiviral treatment. In conclusion, obesity, only when defined as a BMI greater than 30 kg/m(2), is an independent (of genotype and cirrhosis) negative predictor of response to hepatitis C treatment.
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PMID:High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. 1293 81

The spectrum of pathological lesions observed in non-alcoholic fatty liver disease (NAFLD) is wide and strongly resembles that of alcohol-induced liver disease. It ranges from fatty liver to steatohepatitis, progressive fibrosis and cirrhosis. Hepatocellular carcinoma is a possible complication of NAFLD, but whether it is related to frequently associated metabolic disorders (e.g., overweight, diabetes) or to underlying cirrhosis is unclear. This disease is the result of a multi-factorial process in which insulin resistance seems to play a major role in the initial accumulation of fat in the liver, whereas multiple causes of mitochondrial dysfunction and oxidative stress can induce the secondary occurrence of necroinflammatory lesions and fibrosis. Genetic factors might explain why only some patients with simple steatosis will develop steatohepatitis and fibrosis. Due to the increasing prevalence of obesity in Western countries, NAFLD will possibly be a public health problem and the liver disease of the future.
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PMID:Non-alcoholic fatty liver disease: an emerging pathological spectrum. 1468 53

Multicenter randomized trials have shown that once-weekly pegylated interferon (peginterferon) alfa-2a is more efficacious than conventional interferon alfa-2a (IFN) in patients with chronic hepatitis C. We performed a meta-analysis of 1,013 previously untreated patients (from 3 randomized trials) with pretreatment and post-treatment liver biopsies to assess the differences between peginterferon alfa-2a and IFN in terms of their effects on liver histology. Reported values were standardized mean differences (SMD) between patients receiving peginterferon alfa-2a and those receiving IFN (post-treatment value minus baseline value for each group). We used a random-effects model to quantify the average effect of peginterferon alfa-2a on liver histology. Peginterferon alfa-2a significantly reduced fibrosis compared with IFN (SMD, -0.14; 95% CI: -0.27, -0.01; P =.04). A reduction in fibrosis was observed among sustained virologic responders (SMD, -0.59; 95% CI: -0.89, -0.30; P <.0001) and patients with recurrent disease (SMD, -0.34; 95% CI: -0.54, -0.14; P =.0007), whereas no significant reduction was observed among nonresponders (SMD, -0.13; 95% CI: -0.32, 0.05; P =.15). Logistic regression analysis indicated that patients with sustained virologic responses (SVRs) had an odds ratio (OR) of 1.61 (95% CI: 1.14, 2.29) for reduction in fibrosis compared with patients without SVRs, whereas obese patients (body mass index [BMI] > 30 kg/m(2)) had an OR of 0.56 (95% CI: 0.35, 0.90) compared with normal-weight (BMI < 25 kg/m(2)) and overweight patients (BMI, 25-30 kg/m(2)). In conclusion, in patients with chronic hepatitis C with or without cirrhosis, peginterferon alfa-2a (relative to IFN) significantly reduced fibrosis. The beneficial effects of peginterferon on liver histology are closely related to virologic response.
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PMID:Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data. 1476 86

Nonalcoholic fatty liver disease (NAFLD) is defined as fatty infiltration of the liver exceeding 5% to 10% by weight. It is a spectrum of disorders ranging from simple fatty liver (steatosis without liver injury), nonalcoholic steatohepatitis (steatosis with inflammation), and fibrosis/cirrhosis that resembles alcohol-induced liver disease but which develops in individuals who are not heavy drinkers. NAFLD is likely the most common cause of chronic liver disease in many countries. NAFLD may also potentiate liver damage induced by other agents, such as alcohol, industrial toxins and hepatatrophic viruses. The lack of specific and sensitive noninvasive tests for NAFLD limits reliable detection of the disease. It is often diagnosed on a presumptive basis when liver enzyme elevations are noted in overweight or obese individuals without identifiable etiology for liver disease, or when imaging studies suggest hepatic steatosis. NAFLD is now considered to be a component of the insulin resistance syndrome (metabolic syndrome X). Controversy exists relative to optimal recognition, diagnosis and management of these conditions, and treatment recommendations are evolving.
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PMID:Nonalcoholic fatty liver disease (NAFLD): a comprehensive review. 1510 27


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