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)

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB01*03 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease.
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PMID:The immunobiology of primary sclerosing cholangitis. 1946 33

The growing numbers of potential transplant recipients on waiting lists is increasingly disproportionate to the supply of cadaveric donor organs. The hope for the next 20 years is that supply will satisfy demand. This requires both a reduction in indications for the procedure and an increase in the transplants performed. A multi-pronged approach is needed to increase cadaveric organ donation, generating enthusiasm for donation among both the general public and hospital staff. Accurate assessment of marginal grafts with stringent criteria known to predict graft function will diminish wastage of organs. Methods of rehabilitating marginal grafts during extracorporeal perfusion will increase organ availability. Supply of non-heart beating donors can be greatly expanded and protocols developed with ethical consent to optimize their initial function despite warm ischemia. Splitting livers that fulfill selection criteria, thus providing for two recipients, should be universally applied with acceptable incentives to those units who do not directly benefit. A proportion of recipients, though not those transplanted for autoimmune disease, will be spared the side-effects of immunosuppression thanks to immune tolerance. Protocols for close monitoring of those patients for rejection during treatment withdrawal must be carefully observed. In addition to gene therapy, it is highly likely that hepatocyte transplantation will replace orthotopic grafting in patients without cirrhosis, especially for inherited metabolic diseases. It is much more difficult to envisage that heterologous stem cell transplantation or xenotransplantation will have clinical impact in the next 20 years, although research in those areas has obvious long-term potential.
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PMID:Liver transplantation: Issues for the next 20 years. 1979 90

An increasing demand for transplant donor organs has made optimal allocation of resources a priority. Our objective was to evaluate outcomes for orthotopic liver transplantation (OLT) performed in the United States. A query of the United Network for Organ Sharing registry between 1988 and 2007 was performed for patients who underwent OLT for all etiologies. Patients were stratified by pathology necessitating OLT and clinical and pathologic factors were compared. Multivariate Cox-regression analysis was used to assess the association of pathology with survival. Of 61,823 patients, 33 per cent (n = 20,305) of OLTs were secondary to hepatitis C virus, 21 per cent autoimmune disease, 17 per cent alcohol-induced injury, 11 per cent cryptogenic cirrhosis, 8 per cent hepatocellular carcinoma (HCC), 6 per cent hepatitis B virus, and 4 per cent metabolic disease. Patients with autoimmune disease and HCC demonstrated the best and worst survival, respectively, after OLT (median survival 16.0 vs 6.4 yrs, respectively, P < 0.001). By multivariate analysis, OLT for HCC was significantly associated with poorer overall survival (hazard ratio [HR] 2.19, 95% confidence interval [CI]: 2.02-2.37, P < 0.001). Our results indicate that outcomes for liver transplantation vary by primary hepatic pathology with HCC patients having the poorest overall survival. To optimize organ allocation for all patients with end-stage liver disease, a better understanding of poor survival for HCC is necessary.
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PMID:A disease-based comparison of liver transplantation outcomes. 1988 31

Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that mainly targets the cholangiocytes of the interlobular bile ducts in the liver. The condition primarily affects middle-aged women. Without treatment, PBC generally progresses to cirrhosis and eventually liver failure over a period of 10-20 years. PBC is a rare disease with prevalence of less than 1/2000. PBC is thought to result from a combination of multiple genetic factors and superimposed environmental triggers. The contribution of the genetic predisposition is evidenced by the familial clustering. Several risk factors, including exposure to infectious agents and chemical xenobiotics, have been suggested. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at doses of 13-15 mg/kg/day, a majority of patients with PBC have a normal life expectancy without additional therapeutic measures. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarises current knowledge on the epidemiology, ethiopathogenesis, clinical, and therapeutic aspects of PBC.
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PMID:Primary biliary cirrhosis: a 2010 update. 2034 76

Adiponectin, which plays a pivotal role in metabolic liver diseases, is reduced in concentration in patients with NASH (non-alcoholic steatohepatitis). The aim of the present study was to determine adiponectin concentrations in patients with different forms and stages of chronic liver diseases. Serum adiponectin concentrations were measured in 232 fasting patients with chronic liver disease: 64 with NAFLD (non-alcoholic fatty liver disease), 123 with other chronic liver disease (e.g. viral hepatitis, n=71; autoimmune disease, n=18; alcohol-induced liver disease, n=3; or elevated liver enzymes of unknown origin, n=31) and 45 with cirrhosis. Circulating adiponectin levels were significantly lower in patients with NAFLD in comparison with patients with other chronic liver disease (4.8+/-3.5 compared with 10.4+/-6.3 microg/ml respectively; P<0.0001). Circulating adiponectin levels were significantly higher in patients with cirrhosis in comparison with patients without cirrhosis (18.6+/-14.5 compared with 8.4+/-6.1 microg/ml respectively; P<0.0001). Adiponectin concentrations correlated negatively with body weight (P<0.001), serum triacylglycerols (triglycerides) (P<0.001) and, in women, with BMI (body mass index) (P<0.001). Adiponectin concentrations correlated positively with serum bile acids (P<0.001), serum hyaluronic acid (P<0.001) and elastography values (P<0.001). Adiponectin levels were decreased in patients with NAFLD. In conclusion, adiponectin levels correlate positively with surrogate markers of hepatic fibrosis (transient elastography, fasting serum bile acids and hyaluronate) and are significantly elevated in cases of cirrhosis.
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PMID:Significance of serum adiponectin levels in patients with chronic liver disease. 2052 36

Nodular lymphoid hyperplasia, also known as pseudolymphoma of the liver, has been little reported in the current literature (37 cases) and requires differential diagnosis with other focal lesions of the liver. The development of this entity has been associated with other extrahepatic tumors, chronic liver disease, autoimmune disease, and other chronic inflammatory processes. Because pseudolymphoma of the liver usually shows hypervascularity on dynamic studies, it must be differentiated from other lesions-mainly metastatic lesions and hepatocarcinomas-in imaging studies, in which these lesions are usually an incidental finding. We report two cases of pseudolymphoma of the liver, studied with double-contrast (gadolinium + iron oxide) magnetic resonance imaging in two women aged 58 and 59 years old with a history of advanced primary biliary cirrhosis and advanced liver cirrhosis, respectively.
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PMID:[Pseudolymphoma of the liver. Contribution of double-contrast magnetic resonance imaging]. 2059 76

Autoimmune hepatitis is a chronic inflammatory disease of the liver with a dismal prognosis when left untreated. Key for the improvement of prognosis is a timely diagnosis before cirrhosis has developed. This is reached by the exclusion of other causes of hepatitis, elevated immunoglobulin G, autoantibody profile and histological assessment. Treatment achieves remission rates in 80% of individuals and consists of immunosuppression with corticosteroids and azathioprine. A recent randomised controlled multicenter trial has added budesonide to the effective treatment options in non-cirrhotic patients and leads to a reduction of unwanted steroid side effects. Autoimmune hepatitis is an autoimmune disease of unknown aetiology. Association studies of major histocompatibility complex and other genes demonstrate an influence of immunogenetics. However, apart from the autoimmune polyglandular syndrome type 1, in which 10% of patients suffer from an autoantibody-positive autoimmune hepatitis linked to mutations of the autoimmune regulator gene, there is no clear evidence for a hereditary aetiology of this disease.
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PMID:Autoimmune hepatitis. 2095 69

Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease characterized by the destruction of medium- to large-sized bile ducts and intense concentric fibrosis. Complications from PSC include bacterial cholangitis, cirrhosis, and cholangiocarcinoma and a therapy that might alter the natural history of the disease remains lacking. Our understanding of the pathogenesis of PSC also remains rudimentary but the strong association between PSC and inflammatory bowel disease suggest causal links between the diseases. The male predominance in PSC, lack of a defined, pathogenic auto-antigen, and the potential role of the innate immune system suggest that PSC may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC shares several genetic susceptibility loci with other autoimmune diseases including the human leukocyte antigen DRB01*03 haplotype. The precise immune response of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Progress in our basic understanding of PSC is desperately needed in order to rationally design new therapeutic approaches to this disease.
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PMID:Cutting edge issues in primary sclerosing cholangitis. 2117 Jun 5

Anti-mitochondrial autoantibodies (AMA) are specific markers of primary biliary liver cirrhosis (PBC), a cholestatic autoimmune disease which is characterised by a progressive destruction of the biliary epithelial cells followed by fibrosis, cirrhosis and liver failure. The prevalence of AMA in PBC is more than 90% and they can precede long before the clinical symptoms. AMA are conventionally detected by indirect immunofluorescence (IIF) using rodent liver, kidney, and stomach sections as substrates. Additionally, different PBC-specific anti-nuclear autoantibodies (ANA) can be observed in 30% of patients presenting with multiple nuclear dot or nuclear membrane staining patterns, which preferentially are identified using HEp-2 cells as substrate. The identification of the major PBC-specific mitochondrial and nuclear targets has allowed the generation of monospecific antigenic targets which are increasingly used in solid-phase assays for routine detection of AMA and ANA in mono- or multiparametric screen test systems. In the present paper, we give an overview of the diagnostic significance of autoantibodies in PBC, discuss the competencies of different techniques used for their determination and propose an effective diagnostic strategy.
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PMID:Disease-specific autoantibodies in primary biliary cirrhosis. 2118 72

Primary biliary cirrhosis (PBC) is an autoimmune disease of unclear etiology. It is a chronic, progressive condition that causes intrahepatic ductal destruction ultimately leading to symptoms of cholestasis, cirrhosis and liver failure. The disease predominantly affects middle aged Caucasian women. It has a predilection to certain regions and is found in higher incidences in North America and Northern Europe. It also has a genetic predisposition with a concordance rate of 60% among monozygotic twins. Combinations of genetic and environmental factors are proposed in the pathogenesis of this disease with a compelling body of evidence that suggests a role for both these factors. This review will elucidate data on the proposed environmental agents involved the disease's pathogenesis including xenobiotic and microbial exposure and present some of the supporting epidemiologic data.
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PMID:Primary biliary cirrhosis: environmental risk factors. 2129 51


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