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)

A 44-year-old man with chronic hepatitis B virus infection and cirrhosis was treated with recombinant human interferon alfa for 67 days immediately before orthotopic liver transplantation and immunoprophylaxis with hyperimmune globulin to hepatitis B virus in the peritransplant period. Dot blots for hepatitis B virus DNA demonstrated marked reduction in viremia after 41 days of interferon alfa treatment. Southern analysis for hepatitis B virus in liver showed a pronounced decrement in actively replicating forms in the explant, although hepatic infection was still detectable. After liver transplantation, tests for serum hepatitis B virus DNA and hepatitis B surface antigen remained negative. The patient died 32 days after transplantation of causes unrelated to hepatitis B virus. DNA isolated from liver and other visceral organs at autopsy showed infection of the engrafted liver and the persistence of monomeric relaxed circular forms of hepatitis B virus DNA in pancreas, kidney, and spleen. Thus, graft reinfection occurred despite aggressive antiviral therapy and immunoprophylaxis combined with liver transplantation. Existing viral serological markers appear insufficiently sensitive to assess residual infectivity.
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PMID:Persistent hepatitis B virus following interferon alfa therapy and liver transplantation. 198 31

The Hepatitis Delta Virus (HDV) is a small RNA virus which replicates only in patients who are concurrently infected with hepatitis B virus (HBV). Delta hepatitis is endemic particularly in countries in the Mediterranean basin. In other parts of the world, HDV infection occurs among intravenous drug addicts and persons who receive multiple blood transfusion. HDV superinfection in a chronic HBV carrier often leads to severe chronic hepatitis and cirrhosis, whereas acute HDV and HBV co-infection is frequently associated with fulminant hepatitis. Diagnosis is usually based on the detection of HDV antigen in liver tissue and antibody to HDV (anti-HD) in serum. Nowadays, HDV antigen can also be detected in serum using immunoblot assay. The presence of HDV-RNA can now be confirmed by molecular biology techniques including polymerase chain reaction (PCR). Interestingly, up to 50% of patients with chronic HDV infection have in the serum autoantibodies against microsomal antigens of the human liver and kidney (LKM) and antibodies against the basal cell layer of the rat forestomach. Therapeutic approaches including interferon therapy and liver transplantation are still under discussion. This review discusses in detail some of the main features of chronic HDV infection.
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PMID:Chronic hepatitis delta virus (HDV) infection. 202 85

Variants of chronic hepatitis delta (CHD) course were studied in 94 patients. Slow progress (for decades) occurred most frequently, while rapid progress to hepatic cirrhosis (for 1-2 years) or benign course presenting as greater than 3-year remission were rare findings. In addition to routine therapeutic modalities, except corticosteroids, 43 CHD patients received recombinant alpha 2-interferon (reaferon). Follow-up results evaluated separately for hepatic cirrhosis and free of it CHD patients support clinical promise of Soviet recombinant alpha 2-interferon against CHD.
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PMID:[Chronic hepatitis delta--the course and approaches to therapy]. 206 48

After 15 years of unsuccessful efforts, the most frequent of hepatitis non-A non-B viruses has just been identified and called hepatitis C virus (HCV). The viral genome had been sequenced by an original and direct molecular biology method before the agent could be detected serologically or at electron microscopy. HCV is a small, encapsulated RNA virus, perhaps loosely related to flaviviruses. A non-structural protein, corresponding to the virus replication enzyme, is the specific component as target for ELISA tests to detect specific anti-HCV antibodies. This serology has enabled us to confirm that HCV is the most common of NANB viruses, being responsible for 60 to 80 p. 100 of all cases of post-transfusion hepatitis. The antibodies appear belatedly: in 40 p. 100 of patients they do so during convalescence, 2 to 12 months after the serum transaminase peak of primary infection. 60 to 80 p. 100 of patients with presumed NANB hepatitis are positive for anti-HCV antibodies. The same applies to cirrhosis and cancer which, in 40 p. 100 of the cases, complicates post-NB hepatitis cirrhosis. Since March 1, 1990, screening for anti-HCV antibodies has become compulsory for all blood donors in France. The prevalence of these antibodies is 0.68. Among groups of patients at risk, prevalences are 70 p. 100 in haemophiliacs, 50-75 p. 100 in drug addicts and more than 30 p. 100 in patients under haemodialysis. Sexual transmission seems to be weak but possible; 5 p. 100 of homosexuals carry anti-HCV antibodies, and this percentage is higher in HIV positive subjects. The discovery of the hepatitis C virus coincides with the finding that interferon is effective in the treatment of NANB hepatitis, and this exceptional opportunity in the field of public health should engender specific programmes. It may now be hoped that prevention by vaccine will be available in a not too distant future.
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PMID:[Hepatitis virus C: from discovery to applications in public health]. 211

The purpose of this study was to determine whether the response of serum alanine aminotransferase (ALT) to recombinant alpha-interferon was related to the presence or absence of antibodies to hepatitis C virus (anti-HCV) in patients with chronic non-A,non-B hepatitis. A group of 65 patients with chronic non-A, non-B hepatitis was studied. The source of contamination was blood transfusion or administration of blood products in 32, intravenous drug addiction in 14 and unknown in 19. The patients received 1, 3 or 5 MU of recombinant alpha-interferon, three times a week, for 6 months. A complete response was defined as normal ALT by the end of recombinant alpha-interferon treatment. Sera collected before treatment were tested for anti-HCV with an enzyme immunoassay. The overall percentage of anti-HCV positive patients in the study group was 75%. There was no difference between the anti-HCV positive and the anti-HCV negative patients before the treatment with respect to age, sex ratio, source of contamination, serum albumin, prothrombin, bilirubin, ALT or prevalence of cirrhosis. In the anti-HCV positive and the anti-HCV negative groups, there was no difference in the proportion of patients receiving the 1, 3 or 5 MU dosage. The percentage of patients with complete response was not different in anti-HCV positive patients (48%) and in anti-HCV negative patients (50%). There was also no difference in the kinetics of the decrease of mean serum ALT levels between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is the response to recombinant alpha interferon related to the presence of antibodies to hepatitis C virus in patients with chronic non-A, non-B hepatitis? 164 37

We investigated lipopolysaccharide-induced tumor necrosis factor production in vitro by peripheral blood monocytes from patients with various liver diseases. Tumor necrosis factor production was found to be significantly reduced in patients with chronic hepatitis B (n = 17; 135 +/- 30 pg tumor necrosis factor/ml; mean +/- S.E.M.) and patients with chronic non-A, non-B hepatitis (n = 15; 212 +/- 22 pg tumor necrosis factor/ml) compared with healthy control individuals (n = 47; 411 +/- 40 pg tumor necrosis factor/ml; p less than 0.0005 and p less than 0.01, respectively). This reduced tumor necrosis factor production was not only seen with an optimal stimulating concentration of lipopolysaccharide (100 ng/ml) but also with suboptimal concentrations (0.1 ng/ml). In contrast to patients with chronic viral hepatitis, monocytes from patients with alcohol-induced cirrhosis (n = 26; 444 +/- 49 pg tumor necrosis factor/ml), primary biliary cirrhosis (n = 7; 412 +/- 81 pg tumor necrosis factor/ml) and alcohol-induced fatty liver changes (n = 5; 401 +/- 62 pg tumor necrosis factor/ml) produced normal amounts of tumor necrosis factor when stimulated with an optimal concentration of lipopolysaccharide. Lipopolysaccharide (0.1 ng lipopolysaccharide/ml)-stimulated peripheral blood monocytes of patients with chronic hepatitis B (n = 15; 102 +/- 32 pg/ml) or non-A, non-B hepatitis (n = 13; 97+/- 16 pg/ml) could not be induced to produce more tumor necrosis factor either when prestimulated with gamma-interferon (170 +/- 45 pg/ml and 149 +/- 32 pg/ml, respectively), a lymphokine known to activate monocytes, or with the cyclooxygenase inhibitor indomethacin to reduce the suppressive effect of prostaglandin E2 (148 +/- 40 pg/ml and 153 +/- 45 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired lipopolysaccharide-inducible tumor necrosis factor production in vitro by peripheral blood monocytes of patients with viral hepatitis. 212 37

Alpha-interferon has emerged as the most effective agent for the treatment of chronic hepatitis when active replication of virus B, C, or D is present. Exogenous administration of human alpha-interferon, now possible through modern large-scale production methods, is associated with suppression of virus in blood. Amelioration of liver disease occurs in 35% of patients with hepatitis B virus and in 50% with hepatitis C virus with interferon doses of 30 and 10 MU per week, respectively, for 16-26 weeks; after therapy, persistent normalization of serum alanine aminotransferase is observed in 35% and 27%, respectively. Similar results have now also been reported for chronic hepatitis D. Enhanced response rates (greater than 50%) may be obtained by prolonged intermittent interferon therapy. Combination of interferon with another 'antiviral' agent (vidarabine, acyclovir, prednisone) has not increased therapeutic efficacy. Alpha-interferon induces side effects such as fatigue, flu-like syndrome, myalgia, and changes in mood and granulocytes. Patients with decompensated cirrhosis are particularly prone to bacterial infection and disease exacerbation and should receive lower doses. Interferon, when applied skillfully, induces the highly beneficial transition of active viral replication into viral latency, thereby greatly reducing infectivity, symptoms, and activity of the liver disease. Prevention of death from liver failure or hepatocellular carcinoma is to be expected.
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PMID:Treatment of chronic viral hepatitis anno 1990. 212 46

An economic evaluation to compare the costs of care and likely outcome for patients treated with alpha-interferon for chronic active hepatitis B and C was performed. As complete prospective data are not available, we have made comparisons between two cohorts of 100 hypothetical patients. Treatment of chronic hepatitis B would be with alpha-interferon at an average dose of 9 million units three times per week for 16 weeks. Chronic active hepatitis C treatment is based on a dose of 3 million units three times weekly for a total of 6 months. In untreated patients with chronic active hepatitis B or C, the risk of developing cirrhosis is considered to be 10-20% in a 10-year period. Patterns of good practice are costed using typical costs of patients in our institution. These costs are aggregated using the probabilities of morbidity and mortality, from therapeutic and epidemiological studies, for patients developing cirrhosis. A sensitivity analysis has been applied to the results. If we assume a latency period of 10 years, the costs of a successfully treated patient with both hepatitis B and C will be recouped. For hepatitis C, benefits are apparent when social costs are added, the price of alpha-interferon is reduced by 10% and the response rate raised by 20%. Nevertheless, if morbidity effects and costs to patients are included, the advantages of treatment are more apparent, with potential savings in both chronic hepatitis B and C. The model we have developed can be adapted as firmer evidence becomes available.
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PMID:An economic evaluation of the costs of alpha-interferon treatment of chronic active hepatitis due to hepatitis B or C virus. 212 84

Non-A, non-B (type C) hepatitis is a serious world problem which typically results in chronic hepatitis and may lead to cirrhosis and hepatocellular carcinoma. alpha-Interferon has recently been studied in a number of randomized controlled trials throughout the world. The results of those studies are reviewed here. ALT levels were normalized by 2-3 MU recombinant interferon alfa-2b, three times per week s.c. for 6 months (p less than 0.001 vs. control) in 36% of patients in five trials. Biopsy tests also demonstrated histological improvement in lobular and periportal inflammation. Unfortunately, relapse is a common problem in these studies, occurring in 49% of patients treated with 3 million units and 57% of those treated with 1 million units. Retreatment usually brings remission once again. In the future, long-term studies will further elucidate the natural history of the disease and documented guidelines for interferon dosage and duration of dosing in a wider range of patient subgroups will become available.
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PMID:Recombinant alpha-interferon treatment of non-A, and non-B (type C) hepatitis: review of studies and recommendations for treatment. 212 92

Of all the hepatotropic viruses, HBV is associated with the greatest worldwide morbidity and mortality. This is because of the ease of transmission and the potential for progression to a chronic infective carrier state, with the complications of cirrhosis and hepatocellular carcinoma. The use of PCR has shown that some of the earlier concepts concerning the interpretation of serological data were inaccurate. Many patients with anti-HBe and anti-HBs have viral DNA detectable by PCR, and some hepatocellular carcinoma patients have detectable HBV DNA in their livers in the absence of all serological markers of HBV disease. The clearance of HBV infected cells from the liver is dependent on the interplay between the interferon system and the cellular limb of the host immune response. The importance of the nucleocapsid proteins as targets for sensitized cytotoxic T cells has been established for chronic HBV infection. The importance of pre-S sequences as inducers and targets of the virus-neutralizing humoral immune response is becoming established, but their precise role must await the development of in vitro models of hepadnavirus infection and a greater understanding of the mechanisms of viral uptake. The epidemiology and clinical course of the disease can be modified by immunization, immune stimulation and antiviral chemotherapy. For the developing world, a programme of immunization at birth would be the most effective way of eliminating this disease, but at present the cost is prohibitive. For the developed world, immunization is realistic for the at-risk population, and anti-viral and immunostimulatory therapy available for those already infected. In adult acquired chronic HBV infection alpha-interferon produces HBe antigen clearance in 40-60% of cases and is followed by resolution of the hepatic inflammation. Results in neonatally acquired infection are less impressive and prednisolone priming followed by interferon may be needed. The presence of a mutation in the pre-core region of some virus isolates has recently been described. Hepatocytes infected with this virus cannot produce HBe antigen and the course of the liver disease is fairly rapid. Whether this mutant causes liver damage in the same way as the wild virus or is directly cytopathic remains unclear, and its relationship to fulminant hepatitis is under investigation.
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PMID:The hepatitis B virus. 214 22


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