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)

We investigated lymphocyte suppressor cell activity in 53 patients with acute and chronic liver diseases. Suppressor cells were generated by preincubation of peripheral blood mononuclear cells (PBM) with concanavalin A (Con A) for 48 hr. Suppressor cell activity was evaluated by inhibition of Con A-stimulated blast transformation and by inhibition of pokeweed mitogen-induced immunoglobulin (Ig) synthesis of fresh allogeneic normal PBM in the second-set cultures. Of 29 patients with chronic active liver diseases (CALD), defective suppressor cell activities were observed in eight cases (28%) for Ig synthesis and 16 cases (55%) for blast transformation study. The suppressor cell activities were decreased in two (22%) of nine cases with chronic persistent hepatitis and one (17%) of six cases with inactive cirrhosis for both Ig synthesis and blast transformation. In contrast, suppressor activities were inducible in all nine patients with acute viral hepatitis. The histocompatibility antigen DR4 was significantly increased in CALD patients, but there was no correlation between this antigen and suppressor cell activity. These findings suggest that altered lymphocyte suppressor cells in patients with CALD may contribute to the continuing liver cell injury in this disease.
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PMID:Lymphocyte suppressor cell activity in acute and chronic liver disease. 645 94

Two female and two male patients aged of 26, 27, 36 and 46 years with HBsAg-positive chronic active hepatitis (CAH) are presented. The liver disease showed a marked progression with transition to cirrhosis in spite of seroconversion from HbeAg to Anti HBe in three cases. All four patients developed serological markers recognized as typical for the autoimmune type of CAH, such as hypergammaglobulinemia with appreciable elevation of IgG concentrations, antinuclear antibodies and liver membrane antibodies. Furthermore all four patients were positive for the histocompatibility antigen B8. These cases indicate that in genetically predisposed individuals hepatitis B viruses can induce autoimmune processes responsible for the progression of hepatic inflammation. In view of the therapeutic implications it is important to recognize patients with liver disease taking such a course.
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PMID:[Development of chronic active hepatitis of the autoimmune type following hepatitis B virus infection with HBSAg-persistence. 4 case reports]. 671 67

Pigs usually reject MHC incompatible liver allografts less aggressively than skin or kidney allografts. Orthotopic liver allografts can survive undefinitely without any immunosuppression. The liver is considered to be an immunologically privileged organ. Despite this phenomenon, morphological changes and deranged liver function due to rejection reaction are regularly seen; their intensity depends on the histocompatibility antigen disparity between donor and recipient. In long-term survivors the continuous exposure of the recipient's immune system to the liver allograft results in an increasing fibrosis which can turn into liver cirrhosis being considered as the result of chronic rejection. The cholestasis represents a remarkable feature, which is mainly due to perfusion, infection and immunological reaction.
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PMID:[The allogeneic liver transplantation. I. Morphological and functional patterns in pig liver allografts (author's transl)]. 701 36

Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena.
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PMID:HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease. 740 Mar 47

The estimation of patients who are at risk for infection, sepsis, and organ dysfunction/failure is crucial not only for inclusion in treatment algorithms but also for entry into appropriate clinical trials of prophylaxis and therapy. Patients on the surgical service who have sustained major trauma or who have undergone transplantation are clearly at the greatest risk. Other immunosuppressed patients at risk for sepsis include those receiving myelosuppressive chemotherapy, those with overwhelming malignancy, and those who suffer from cirrhosis, diabetes mellitus, and severe malnutrition. We have focused on the trauma patient, in whom infection and organ failure are the leading causes of late death, major morbidity, and prolonged hospital stay. Over a 10 yr period, we have surveyed a number of host defense parameters that pertain to an adequate immune response and found a suppressed response shortly after injury in many. All were anergic to a standard skin test panel, and the duration of anergy varied with the clinical course of infection. Immunoglobulin levels were low after major injury as well as specific antibodies to both Gram-positive and Gram-negative organisms. The ability of serum from the trauma patient to opsonize heat-killed bacteria was markedly depressed 24 h after injury in those patients who subsequently died of infection. Class II major histocompatibility antigen expression on peripheral blood monocytes correlated closely with clinical outcome and led to the development of an Outcome Predictive Score. This score can identify patients within hours of hospitalization who are at risk of subsequently developing overt clinical infection and sepsis. Intervention then can be applied to such at-risk populations prior to the onset of sepsis and to evaluate the efficacy of prophylaxis. Patients in whom prophylaxis fails could be eligible for trials of therapeutic intervention as well.
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PMID:Sepsis and septic complications in the surgical patient: who is at risk? 882 91

Genetic hemochromatosis is one of the most common inherited disorders in Caucasian populations. The disease frequency in Caucasian populations in Australia, Europe, and the United States is 1:300-400. The basic genetic defect remains unknown, although the hemochromatosis gene is closely linked to histocompatibility antigen (HLA) A, thus allowing early diagnosis in members of affected families. Many factors-environmental, genetic, and nongenetic in nature-influence the degree of iron loading in affected individuals. In particular, pathologic and physiologic blood loss and blood donation influence iron stores in hemochromatosis. The iron concentration in the liver is an important determinant of survival because a hepatic iron concentration in excess of 400 mumol/g dry weight is usually associated with cirrhosis. Patients with cirrhosis secondary to hemochromatosis are at risk of heptocellular carcinoma and complications of portal hypertension. The combination of improved awareness of the condition and the use of HLA typing to identify affected family members has led to earlier diagnosis and therapy, and to an improvement in overall survival.
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PMID:Factors influencing disease expression in hemochromatosis. 883 23

Persistent hepatitis B virus (HBV) infection often leads to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. There is a need to develop new antiviral approaches for the treatment of this disease. We have explored various nucleic acid-based strategies designed to inhibit HBV replication including: the use of antisense RNA and DNA constructs, DNA-based immunization techniques to stimulate broad-based cellular immune responses with particular emphasis on the generation of cytotoxic lymphocyte (CTL) activity to viral structural proteins, hammerhead ribozymes to cleave HBV pregenomic RNA in vitro and dominant negative HBV core mutant proteins as inhibitors of nucleocapsid formation within cells. In order to optimize these antiviral effects, various novel expression vectors have been developed to deliver such DNA constructs to cells. For example, adenoviral vectors carrying genes that encode for dominant negative proteins have been employed to transfect hepatocytes in vitro and in vivo. In addition, plasmid vectors have been produced to promote expression of HBV structural genes following injection into muscle cells as a means to stimulate the host's cellular and humoral immune response in the context of histocompatibility antigen (HLA) class I and II antigen presentation. These experimental approaches may have important implications for the generation of efficient antiviral effects during chronic HBV infection.
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PMID:Nucleic acid-based antiviral and gene therapy of chronic hepatitis B infection. 940 58

Autoimmune hepatitis is a chronic, progressive liver disease that responds well to immunosuppressive therapy, but has a poor prognosis if untreated. Possible triggering factors include viruses, other autoimmune disorders and drugs. The molecular mechanisms contributing to the pathogenesis include: reactions of autoantibodies against their corresponding autoantigens; aberrant expression of histocompatibility antigen class I and II molecules, cell adhesion molecules and cytokines; increased oxidative stress; and the occurrence of angiogenesis. The prevalence of the disease is highest in Caucasians, Europeans and women. The natural history of autoimmune hepatitis shows a poor prognosis, with frequent progression to cirrhosis and hepatic insufficiency in untreated patients. The occurrence of hepatocellular carcinoma is rare and is found only in long-standing cirrhosis. Corticosteroids as monotherapy or in combination with azathioprine are the treatments of choice; different therapeutic schedules and particularities of treatment for pregnant women and children have been established. To avoid treatment-associated adverse effects, alternative therapies have been proposed, including ciclosporin, budesonide, tacrolimus, mycophenolate mofetil, ursodeoxycholic acid, methotrexate, cyclophosphamide, mercaptopurine and free radical scavengers. Liver transplantation is indicated for patients refractory to or intolerant of immunosuppressive therapy.
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PMID:Review article: immunopathogenetic and therapeutic aspects of autoimmune hepatitis. 1249 28