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)

Interferon-alpha is used in antiviral therapy in humans, mainly for viral hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even in the absence of anti-viral response, which suggests that interferon directly inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica regularly develop diffuse septal fibrosis of the liver, which terminates in cirrhosis 40 days after inoculation. The aim of this study was to test the anti-fibrotic effect of interferon in this experimental model. Evaluation of fibrosis was made by three separate methods: semi-quantitative histology, computerized morphometry and hydroxyproline measurements. Treatment with interferon-alpha proved to inhibit the development of fibrosis in this model, especially when doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the anti-fibrotic potential of interferon-alpha on a non-viral new experimental model of hepatic fibrosis, a clear-cut dose-dependent effect was observed.
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PMID:Effect of interferon-alpha on experimental septal fibrosis of the liver - study with a new model. 1131 41

This report is the 5-year follow-up of those 25 UK patients with primary antibody deficiencies infected with hepatitis C virus (HCV), type 1a, from one batch of contaminated anti-HCV-screened intravenous immunoglobulin in 1993-1994. Of these patients, who were reported previously (1, 2), 2 cleared HCV spontaneously, 18 received early interferon-alpha (IFN) treatment for 6 months, and 5 declined treatment or treatment was contraindicated. The clinical course of this cohort was followed prospectively using serial standardized questionnaires. Seven patients (54% of those who had completed therapy) had a sustained response (normal transaminase levels, negative serum HCV RNA) for 5 years posttreatment. Eight patients died: 3 from decompensated cirrhosis, 2 from pneumonia but with evidence of liver failure, and 3 from unrelated causes. One further patient developed decompensated cirrhosis but was successfully transplanted. Seven patients remain chronically infected; only 1 patient is symptomatic but 1 further patient has evidence of progressive fibrosis on liver histology. In conclusion, within 5 years, rapid end-stage HCV liver disease has been seen in 6/25 (24%) patients. Seven patients, (54% of those fully treated) remain well after treatment, making 9/25 (36% of the cohort) clear of virus after 5 years. Those who completed early treatment with IFN had a relatively high sustained response rate compared to previous studies in both immunodeficient and immunocompetent patients.
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PMID:Five-year follow-up of patients with primary antibody deficiencies following an outbreak of acute hepatitis C. 1135 26

Chronic hepatitis B infection is frequently diagnosed within the genitourinary clinic setting with sexual transmission the commonest route of acquisition in the United Kingdom. Only 3--5% of adults who contract acute hepatitis B will progress to chronic infection, and these individuals can be identified by the presence of hepatitis B surface antigen (HBsAg) in the bloodstream 6 months after infection. Individuals at highest risk of long-term complications such as cirrhosis and hepatocellular carcinoma, carry HBeAg and have high levels of circulating hepatitis B virus (HBV) deoxyribonucleic acid (DNA). Therapy should be targeted towards this group of patients. Two forms of therapy are now licensed for use in chronic hepatitis B infection: interferon-alpha and lamivudine. Seroconversion occurs in 30--40% of patients treated with interferon and treatment is often limited by toxicity. Lamivudine is well tolerated with seroconversion rates of 15--20% at one year, rising with increasing duration of therapy. Long-term monotherapy is limited however by the development of resistance mutations and combination nucleoside therapy is likely to become the treatment of choice in the future. Patients with chronic hepatitis B should be counselled regarding transmission, partner vaccination and alcohol intake and co-infection with other hepatitis viruses should be excluded.
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PMID:The management of chronic hepatitis B infection. 1180 40

Background: Essential mixed cryoglobulinemia (EMC) is a systemic disease frequently associated with chronic viral hepatitis. This study was conducted in order to assess the prevalence of EMC in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. We also evaluated the possible associations of EMC with (1) the clinical, virological, and histological status of liver disease; (2) the presence of EMC-related symptoms; and (3) the response rate to interferon-alpha (IFN-alpha) treatment, in an attempt to address whether EMC is a major problem in hepatitis patients. Methodology: A total of 154 consecutive patients (104 with HBV and 50 with HCV infection) were investigated for the presence of rheumatoid factor (RF), cryoglobulins, and EMC-related manifestations. Sixty-two HBV patients were chronic carriers of hepatitis B surface antigen, 29 had chronic hepatitis B, and 13 HBV cirrhosis. Thirty-five HCV patients had chronic hepatitis C and 15 HCV cirrhosis. HCV genotyping was performed in 44 patients. Results: The prevalence of cryoglobulins was significantly higher (P<0.001) in HCV patients (46%) than in HBV patients (13.4%). EMC was associated with a high frequency of RF detection, older age, and longer duration of viral diseases. Weakness or malaise, arthralgias, and purpura were significantly more frequent in cryoglobulin-positive patients. These manifestations, however, were mild in most of the patients. The EMC-related symptoms were significantly associated with the presence of HCV infection, increased levels of cryoglobulins, and RF detection (P<0.01, P<0.05, and P<0.000005, respectively). Worse liver histology was unrelated to a higher prevalence or increased levels of cryoglobulins in both HBV and HCV infection. There was no relationship between EMC and a specific HCV genotype. IFN-alpha therapy led to the disappearance of cryoglobulins and EMC-related manifestations in most cases. The response rate to IFN-alpha was similar in both groups of patients (with and without EMC). Conclusions: A higher prevalence of EMC was observed in HCV patients than in HBV patients. However, this finding was unrelated to overt clinical manifestations of EMC, a specific HCV genotype, or worse liver histology. The latter suggests that EMC does not contribute to liver injury and vice versa, that EMC pathogenesis is rather unrelated to the degree of liver injury. From a clinical point of view, testing for cryoglobulins seems reasonable only for HCV patients with EMC-related manifestations, since this may have therapeutic consequences. RF detection could be used primarily as a surrogate marker for the existence of cryoglobulins.
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PMID:Cryoglobulinemia due to chronic viral hepatitis infections is not a major problem in clinical practice. 1155 30

Hepatitis C virus (HCV) infection is emerging as one of the most prevalent viral diseases of medical significance. It afflicts approximately 100 million people worldwide. Although HCV infections are mostly clinically inapparent during the acute stage, the majority of infected patients develop chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Mainly as a result of ongoing HCV epidemics, the incidence of hepatocellular carcinoma and demands for liver transplantation have increased at a rapid pace in many countries in the last couple of decades. The current therapeutic options for HCV are limited; interferon-alpha (IFN-alpha) alone or IFN plus ribavirin are the only available treatments. Unfortunately, these treatments are efficacious for only a limited number of patients. They are particularly ineffective against genotype 1 HCV, which is the most common genotype in developed countries, including most European countries, the USA and Japan. Therefore, the development of new therapeutic strategies is urgently needed, so that the progression of hepatic diseases in HCV-infected patients can be halted before serious late-stage illnesses manifest themselves. Otherwise, HCV may exact a huge toll on health care budgets and the wellbeing of societies in the ensuing decades.
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PMID:RNA polymerase as an antiviral target of hepatitis C virus. 1159 81

Despite the availability of an efficient vaccine, chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. The World Health Organization estimates that there are still 350 million chronic carriers of the virus who are at risk of developing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Antiviral therapy consists of the administration of either interferon-alpha (IFN alpha) or lamivudine. In the elderly, specific issues should be addressed. Because of the long duration of viral infection, screening for HCC is warranted in these patients, as new therapeutic options are being developed. Antiviral treatment for chronic hepatitis B is indicated in patients with elevated transaminases, the presence of HBV replication, and inflammatory activity on liver histology analysis, providing the patient has no other serious health problem impacting on life expectancy. Since IFN alpha therapy may cause many general adverse effects, lamivudine may be the best current treatment option in this patient population. The pharmacokinetics of lamivudine in the elderly are slightly different from those in younger adults but this does not require dose adjustment, except in the presence of renal function impairment. However, the beneficial effects of lamivudine therapy must be weighed against the selection of drug-resistant mutants. New therapeutic strategies are now under evaluation and may be available in the future for the elderly population. Besides mass HBV vaccination programmes, people sharing a house with patients infected with HBV should be vaccinated to prevent viral transmission.
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PMID:Current management strategies for hepatitis B in the elderly. 1173 20

The results of liver resection for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) are affected by persistent active hepatitis and/or hepatic fibrosis including cirrhosis. In patients infected with HCV, interferon therapy prevents the development of HCC by eradication of HCV and/or the remission of active hepatitis. Although HCCs are found even in some patients treated with interferon, the results of liver resection for such HCCs were satisfactory, especially in patients successfully treated with interferon. Postoperative interferon-alpha therapy decreased recurrence after resection of HCV-related HCC in a randomized controlled trial. Strategies for viral infection as well as the carcinoma can improve the outcome after treatment of HCV-related HCC. Interferon therapy is useful to improve the outcome after treatments for HCV-related HCC.
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PMID:[Clinical significance of interferon therapy in treatments for hepatitis C virus-related hepatocellular carcinoma]. 1179 77

Viral hepatotropic infections may lead to diagnostic and therapeutic problems in hemodialysis patients and kidney recipients. The parenteral and community-acquired routes of contamination of hepatitis B and C viruses explain their high frequency in this population. Their impact, because the immunosuppressive treatments, is harmful with a decrease in patients and allografts survival; cirrhosis is a contra-indication for renal transplantation since associated with a bad short-term prognosis and may require a combined kidney-liver transplantation. Thus, a liver biopsy is recommended in order to evaluate the histopathological severity of the liver disease (stage and grade) and to precise if an antiviral treatment appears necessary, especially because interferon-alpha, the main treatment of hepatitis B and C infections, is contra-indicated in kidney recipients because of the risk of graft rejection. In summary, the diagnosis of viral hepatotropic infections has to be early undergone and its pathological impact has to be evaluated by a liver biopsy. The best treatment has to be prophylactic (vaccination against hepatitis B virus and the respect of universal hygiene rules for hepatitis C virus).
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PMID:[Prevention and treatment of viral hepatitis in renal insufficiency conditions]. 1181 11

At present standard treatment of patients with chronic hepatitis C is combined therapy with interferon-alpha and ribavirin which so far gives the best results. It is recommended in patients with resistance to interferon or a relapse after termination of treatment by interferon alone as well as in hitherto untreated patients. Combined treatment produces, however, not only common side-effects which are caused by interferon as well as ribavirin but rarely also serious side-effects produced by combined treatment which call for premature termination of therapy. The authors present an account on two patients who had serious side-effects during combined treatment: the first one was an intravenous drug addict who developed psychosis during combined treatment, the second one a female patient with cirrhosis and incipient portal hypertension who developed after nine months of combined treatment a severe biochemical relapse with jaundice, and treatment was also terminated. Both serious complications after treatment receded and in the first patient a sustained response to antiviral therapy persists for more than one year.
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PMID:[Serious side-effects of interferon alfa and ribavirin combination therapy in patients with chronic hepatitis C]. 1185 90

Until recently, interferon monotherapy has been the only available therapeutic option for patients with chronic hepatitis B and hepatitis C. Lamivudine has emerged as another effective first-line therapy for chronic hepatitis B as well as a beneficial treatment option for patients with decompensated hepatitis B cirrhosis. Viral resistance with long-term lamivudine therapy remains a major concern but new data continue to show benefits despite the development of YMDD mutations. Combination therapy with ribavirin and pegylated interferon-alpha has revolutionized the treatment of chronic hepatitis C. The rate of sustained virological response can now be expected to be as high as nearly 50% for genotype 1 and 80% for non-1 genotypes of hepatitis C.
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PMID:Therapeutic advances in the management of hepatitis B and hepatitis C. 1196 81


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