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 the production of tumor necrosis factor alpha by peripheral blood mononuclear cells of patients with chronic liver disease and its association with hepatitis activity. Tumor necrosis factor alpha production was measured with an enzyme-linked immunosorbent assay. Tumor necrosis factor alpha production by peripheral blood mononuclear cells stimulated with recombinant gamma-interferon of patients with chronic active hepatitis (5.8 +/- 4.0 units per ml, p less than 0.05) and patients with cirrhosis (4.1 +/- 2.1 units per ml, p less than 0.05) was significantly increased when compared with controls (2.5 +/- 1.6 units per ml). Tumor necrosis factor alpha production by peripheral blood mononuclear cells stimulated with a combination of recombinant gamma-interferon and recombinant interleukin 2 of patients with chronic persistent hepatitis (5.8 +/- 3.8 units per ml, p less than 0.05), patients with chronic active hepatitis (8.9 +/- 3.0 units per ml, p less than 0.001) and patients with cirrhosis (6.7 +/- 3.2 units per ml, p less than 0.05) was significantly increased in comparison with controls (3.3 +/- 1.8 units per ml). Tumor necrosis factor alpha production of patients with chronic active hepatitis was significantly higher than that of patients with chronic persistent hepatitis (p less than 0.05). There was a significant correlation (r = 0.5699, p less than 0.005) between tumor necrosis factor alpha production and histologic activity index in patients with chronic persistent hepatitis or chronic active hepatitis. These findings show that tumor necrosis factor alpha production is increased in chronic liver disease and that the increased tumor necrosis factor alpha production is related to hepatitis activity.
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PMID:Tumor necrosis factor alpha production by peripheral blood mononuclear cells of patients with chronic liver disease. 255 75

Therapy for chronic hepatitis B virus (HBV) infection is primarily directed at those patients with evidence of replicative infection because they are most at risk for developing chronic hepatitis, cirrhosis, and possibly hepatocellular carcinoma (HCC). Although a number of agents or therapeutic approaches have been tested against HBV infection, only a few have been subjected to controlled clinical trial. Corticosteroid therapy, particularly if prolonged, may be harmful and should be avoided. Adenine arabinoside monophosphate (Ara-AMP) has potent inhibitory effects on HBV replication, but its use is limited by severe neurotoxicity. At present, prolonged treatment with alpha interferon offers the most promise as a beneficial therapy for chronic type B hepatitis. Alpha interferon consistently induces permanent clearance of hepatitis B e antigen (HBeAg) and HBV DNA from serum more often than in untreated patients. Present efforts are directed at determining the factors predictive of a favorable response to interferon, and attempting to increase the response rate by using alpha interferon in combination with other antiviral or immunomodulatory agents.
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PMID:Treatment of chronic type B hepatitis. 262 Mar 10

Cirrhosis is a histologic term that requires liver biopsy for definitive diagnosis. Although we may usefully classify cirrhosis by cause, such as alcoholic cirrhosis, the morphologic diagnosis is confined to only a few descriptive terms. Cirrhosis is the end result of hepatocellular necrosis that initiates the inflammatory process. Hepatocellular necrosis induced by the hepatoviruses is caused by the host response to the parasitized cells rather than by the viruses themselves. Inflammatory cells, apparently by diverse mechanisms that include the immune system, stimulate the deposition of collagen around hepatocytes and in sinusoidal membranes, causing profound alteration in hepatocyte function and hepatic blood flow. Fully developed cirrhosis cannot be reversed with therapy presently available. Efforts to change morbidity and mortality of this common disease include preventive measures, attempts to manipulate the immune response, efforts to influence the biologic process of fibrosis, and, finally, attempts to induce resorption of established collagen. No acceptable therapy to prevent cirrhosis currently exists, but there is reason to believe that one can and will be developed in the future, probably through the discovery of better methods of eliminating the persistent infection by hepatoviruses. The most encouraging results to date come from experiments using prednisone followed by interferon, and from very preliminary results with methotrexate in specific circumstances. In the meantime, the clinician will continue to support the existing physiology, minimize and treat the complications, and offer support to the patient and family.
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PMID:Cirrhosis of the liver: new concepts. 264 80

Chronic liver disease associated with hepatitis B virus infection is both common and serious; no satisfactory treatment currently exists. Orthotopic liver transplantation is an option for patients with end-stage liver disease associated with hepatitis B virus infection despite the risk of allograft reinfection. Passive immunoprophylaxis has been attempted perioperatively to prevent graft infection but has not been beneficial. Some patients with chronic type B hepatitis have benefited clinically from antiviral therapy and, in particular, interferon, but its use has not previously been reported as an approach to prevent allograft infection. We administered recombinant leukocyte A interferon perioperatively to a patient who underwent liver transplantation for type B chronic active hepatitis and cirrhosis. Circulating hepatitis B virus DNA was found postoperatively while the patient was receiving interferon, and stainable viral antigen subsequently reappeared in the transplanted liver. Thus, the drug failed to prevent viral replication and allograft infection. Thus far, no evidence of progression of the chronic hepatitis has been noted.
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PMID:Failure of interferon to prevent recurrent hepatitis B infection in hepatic allograft. 265 99

Over the 12 years since the first introduction of interferon for the treatment of chronic hepatitis B, progress has apparently been slow. Nevertheless, it now appears that at least one third of chronic hepatitis virus carriers, particularly those with more severe disease, and a similar, perhaps greater, proportion of those with chronic parenteral non-A, non-B hepatitis, can be successfully treated with alpha-interferon. In the not too distant future, controlled trials of alpha-interferons in these situations will be complete and they will be a yardstick by which other future therapies can be judged. Already a number of trials are in progress to determine which agents might, in addition to interferon, augment the response rates. The situation clinically is analogous to that for tuberculosis in the 1950s and for cancer chemotherapy only a decade or so ago. The prospects of prevention of the progression to cirrhosis, and perhaps in the long term reduction in the incidence of hepatocellular carcinoma, are exciting, and with the introduction of a number of new cytokines available through recombinant technology, each with novel antiviral activities, the future prospects are exciting indeed.
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PMID:Treatment of acute and chronic viral hepatitis. 265 45

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.
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PMID:Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a 10-month follow-up study. 268 91

Monocytes play an important role in the initiation and regulation of the antiviral immune response. These cells have a dense framework of intermediate filaments composed of vimentin monomers. In 35 patients with chronic hepatitis B, 26 healthy controls, seven patients with acute liver damage and eight patients with inactive HBsAg-negative cirrhosis, we investigated the expression of vimentin filaments, C3b and IgGFc receptors, HLA-DR molecules and the phagocytic activity in monocytes purified from venous blood. In the same subjects, we also studied the display of CD2, CD3 and CD5 on lymphocytes. In patients with chronic hepatitis B manifesting viral replication (n = 21; Group 1), the expression of vimentin filaments and the other functional monocyte parameters were decreased, whereas in patients in the nonreplicative phase of the disease (n = 14; Group 2) and in control cases with various forms of acute liver damage or inactive HBsAg-negative cirrhosis, they were similar to those found in healthy subjects. In Group 1, there was also a selective defect in the display of CD3 on lymphocytes. The expression of this molecule correlated with the functional state of monocytes. In three patients with chronic hepatitis B that changed from the replicative to the nonreplicative phase of the disease, the expression of vimentin filaments in monocytes and of CD3 on lymphocytes increased to normal levels. On the other hand, the incubation of patients' monocytes with gamma-interferon corrected the diminished expression of vimentin filaments and the other decreased functional parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytoskeletal organization and functional changes in monocytes from patients with chronic hepatitis B: relationship with viral replication. 270 39

Immunohistochemical examinations were carried out for the study of cytochrome P-450 implication in the human hepatic disorders. An isozyme of human hepatic P-450 (P-450-HM1) with the m.w. of 51,000 was purified from human autopsied liver. Antibody against P-450-HM1 was prepared in rabbits, of which specificity was confirmed by Western blot. Eighty-three livers (27 autopsies and 56 biopsies, M:F = 63:20), which were either normal or of various hepatic disorders such as acute or chronic hepatitis, cirrhosis and hepatocellular carcinomas, were examined by the method of avidin-biotin-complex technique. It was revealed that immunoreactive hepatocytes were diffused throughout the lobule of the fetal liver. In the normal livers as well as those of acute and chronic hepatitis, positive hepatocytes were found in the centrilobular zone. Three of the 4 cases treated with beta-interferon showed faint staining; and the presence of positive individual hepatocytes was considered to be induced by steroid therapy. In the livers with chronic hepatitis and cirrhosis, hepatocytes near the perifibrous region and those trapped in the portal triad by thin fibrous connective tissue, as well as in the regenerating nodules, were strongly stained, which indicate that P-450-HM1 is expressed in the regenerating hepatocytes. Hepatocellular carcinomas, however, were devoid of immunohistochemistry. From these results, the antibody might be a useful tool for differentiating regenerating nodule from hepatocellular carcinoma.
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PMID:[Clinico-pathological studies of cytochrome P-450 on human hepatic disorders]. 276 18

In Southeast Asia, 15 to 20 percent of the population are hepatitis B surface antigen carriers. The majority of these carriers have chronic hepatitis and would progress to cirrhosis or hepatocellular carcinoma at an annual incidence of 2 percent and 1 percent, respectively. Previous studies from Southeast Asia suggested that immunosuppressive therapy could be harmful, or at best of no value, and antiviral treatment with vidarabine, picibanil, or even interferon was also unsatisfactory. Currently, a randomized controlled trial of human lymphoblastoid interferon, with or without prednisolone pretreatment, versus placebo in patients with hepatitis B core antigen in the liver and hepatitis B e antigen in the serum is being conducted. Forty-five patients (29 receiving interferon, 16 receiving placebo) have been entered in the trial for at least two months. Actuarial analysis shows that the response to interferon therapy was better than that to placebo. Although flu-like symptoms, hair loss, and body weight loss were seen, no side effect requiring specific treatment has been encountered. These preliminary results suggest that human lymphoblastoid interferon is effective and safe in Oriental patients.
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PMID:Treatment of chronic type B hepatitis in Southeast Asia. 304 79

For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in more than 40 percent of patients treated with combination therapy, 30 percent with interferon therapy, 18 percent with acyclovir, and 0 percent with no treatment. HBe reactivation occurred in two patients with cirrhosis. Hepatitis B surface seroconversion followed HBe seroconversion in 11 to 30 percent of treated patients. HBe seroconversion was significantly related to initial low levels of viral replication and to transient aminotransferase elevation during the second half of the interferon treatment of 16 weeks. Clinical improvement and persistent normalization of aspartate aminotransferase was observed in all patients with HBe seroconversion. Conversion to a state of virus latency (HBe negative) mostly occurred after therapy, suggesting that the specific immunologic host response had been brought about by the suppression of virus replication through antiviral agents. Recommendations for selection of patients for antiviral combination therapy are made on the basis of these long-term results.
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PMID:Long-term follow-up of antiviral combination therapy in chronic hepatitis B. 304 80


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