Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this retrospective trial we report the immediate and long-term effects of rIFN-alpha therapy on serum aminotransferases, especially on their behaviour in relation to the disappearance of serum HCV-RNA at the end of the treatment and one year later. Eighty-eight subjects were eligible in our study. The diagnosis of hepatitis was based on clinical, serological and histological data in all patients. They showed ALT and AST levels at least twice the upper maximum normal value and detectable serum HCV-RNA before the study. These patients were treated with rIFN-alpha 3MU, 3 times a week, in 54 cases for 6 months and in 34 for 1 year. Patients were examined at monthly intervals. Serum HCV-RNA was assessed before and at the end of the treatment and every six months during the follow-up. A complete response was defined exclusively as a normalization of aminotransferases and disappearance of serum HCV-RNA. The two groups were homogeneous. During the treatment drop-outs were 5 (5.7%), and 7 patients (7.9%) stopped the therapy for side-effects. The treatment induced a complete response in 13 (25.4%) of 51 patients treated for 6 months, and in 8 (32%) of 25 cases treated for 12 months. The patients with normalization of aminotransferase levels but with still detectable HCV-RNA in serum were 20 (39.2%) of 51 treated for 6 months and 13 (41.9%) of 31 treated for 12 months. The cases with normalization of aminotransferases were followed up for one year after IFN withdrawal. Serum liver function tests and HCV-RNA were performed every 6 months in these patients. One year after IFN withdrawal the numbers with persistent normalization of liver enzymes and absence of serum HCV/RNA were 9 (69.2%) of 13 cases with complete response after a 6-month course, and 5 (62.5%) of 8 subjects with complete response after a 12-month course. The subjects with continuous normalization or liver enzymes but persistence of serum HCV-RNA at the end of the trial were 3 (15.7%) of 19 patients with normalization of liver enzymes and still detectable HCV-RNA after a 6-month course, and 2 (15.3%) of 13 cases with normalization of liver enzymes and still detectable HCV-RNA after a 12-month course. Overall at the end of our study the patients with normal aminotransferases were 19 (21.5%) of 88 cases studied. 14 of them (73.6%) being from the subjects with disappearance of serum HCV-RNA just after IFN treatment.
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PMID:Sustained remission and viraemia in chronic hepatitis C treated with recombinant alpha-interferon (rIFN-alpha). 883 15

The protective effects of recombinant IFN-alpha/beta on MHV-2cc-induced chronic and persistent hepatitis in athymic nude mice were examined. The mice intraperitoneally (ip) inoculated with MHV-2cc at day 0 of experiment were divided into 4 groups. Three of them were administered ip with recombinant IFN-alpha/beta at a daily dose of 1 x 10(3) IU from -1 (-1D-group), 0 (0D-group), and +1 day of experiment (+1D-group), respectively, for 3 consecutive weeks. The remaining one (control group) was given 0.1 ml/mouse of PBS from +1 day of the experiment in the same way. Three mice in each group were killed at 1, 2 and 3 weeks post inoculation (WPI) with MHV, respectively. The liver virus titer in the control group increased gradually and maintained high levels throughout the experimental period. In the IFN-groups, particularly in the -1D- and 0D-groups, the virus titers were significantly lower than that in control group. Histopathologically, focal hepatic lesions were observed at 1WPI and large irregular inflammatory lesions developed at 3WPI in the control group. Similar but somewhat less severe lesions were observed in the +1D-group. In the -1D- and 0D-groups, lesions were not observed at 1WPI and only small organized lesions with mononuclear cell infiltration were seen at 3WPI. In conclusion, it was clarified in the present study that the progression of MHV-2cc-induced chronic hepatitis in athymic nude mice was effectively prevented by extrinsic IFN-alpha/beta when administered from -1 day and 0 day of the virus infection.
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PMID:Protective effect of recombinant interferon (IFN)-alpha/beta on MHV-2cc-induced chronic hepatitis in athymic nude mice. 884 Jan 51

Hepatitis C virus (HCV) infection is associated with a variable disease course and response to therapy. Some infected patients may develop little or no disease for 30 to 40 years, whereas others will develop cirrhosis within 5 to 10 years. Both host and viral factors influence the rate of disease progression. The management of patients is determined by the severity of their disease assessed by liver biopsy. Those with mild hepatitis without fibrosis do not require treatment but should undergo liver biopsy every 3 years. Patients with mild hepatitis with fibrosis, or with moderate or severe hepatitis with or without fibrosis, should be offered treatment. Interferon-alpha (IFN alpha) is currently the only licensed treatment for HCV infection. Although initial response rates to IFN alpha are high, over half the patients relapse and a sustained response is achieved in only 10 to 35% of patients. Higher doses of IFN alpha and a longer treatment duration are associated with better response rates. Treatment options for those who fail to respond to IFN alpha include a second course of IFN alpha at a higher dose or IFN alpha in combination with ribavirin, phlebotomy or ursodeoxycholic acid. At present, however, there are insufficient data to routinely recommend any of these options.
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PMID:Pathophysiology and treatment of hepatitis C. 886 30

An association between hepatotropic viruses, chiefly hepatitis C virus (HCV), occasionally hepatitis B virus (HBV), and mixed cryoglobulinemia has been widely reported. Alpha-interferon (IFN-alpha) has usefully been employed in the treatment of mixed cryoglobulinemia, particularly for liver and renal involvement. IFN-alpha treatment may be associated with neurological complications, including peripheral neuropathy. We describe an HBV positive patient with mixed cryoglobulinemia with recurrent purpura, mild sensory peripheral neuropathy, and active hepatitis treated with IFN-alpha. Rapid improvement of the purpura, liver enzymes, and cryocrit, and disappearance of serum HBV DNA were observed after a 4 week treatment period. However, concomitant worsening of the neuropathy prompted us to discontinue IFN-alpha. Although in this case, a positive effect of IFN-alpha on the clinico-serological and virological variables was confirmed, due to the possible exacerbation of neurological manifestations, a careful patient evaluation is necessary before starting IFN-alpha in patients with mixed cryoglobulinemia.
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PMID:Exacerbation of peripheral neuropathy during alpha-interferon therapy in a patient with mixed cryoglobulinemia and hepatitis B virus infection. 941 68

The mechanisms underlying the chronic hepatic inflammatory process in hepatitis C virus (HCV) infection are not well understood. Some models of experimentally induced hepatitis point to a role of interferon-gamma (IFN-gamma) secreted by liver-infiltrating peripheral blood lymphocytes (PBMC) in mediating hepatocellular injury. In the present study, IFN-gamma gene expression was analysed in PBMC and in liver biopsy specimens from patients with chronic HCV infection using a quantitative reverse transcriptase polymerase chain reaction technique. IFN-gamma gene expression by PBMC from HCV-infected patients exhibiting elevated serum transaminase activities was found to be increased up to ninefold when compared with (1) healthy individuals, (2) HCV-infected patients exhibiting normal or only slightly elevated serum enzyme activities, or (3) patients with drug-induced elevated serum transaminase activity. A histo-pathological evaluation of liver biopsy sections revealed further that high IFN-gamma gene expression by PBMC was associated with a more pronounced degree of inflammatory activity. In individual patients, the expression of IFN-gamma by PBMC was shown to parallel closely serum transaminase activities during IFN-alpha 2a therapy. Moreover, liver biopsy material from patients chronically infected with HCV contained higher amounts of IFN-gamma transcripts than liver tissue from patients with liver disorders unrelated to HCV infection or without any liver disease. These data thus demonstrate a close association between the amount of IFN-gamma transcripts in PBMC and in liver tissue and the inflammatory activity in chronic HCV infection in man.
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PMID:High inflammatory activity is associated with an increased amount of IFN-gamma transcripts in peripheral blood cells of patients with chronic hepatitis C virus infection. 888 41

We have evaluated the efficacy of treatment with recombinant Interferon-2b (IFN-2b) in 12 children with cancer who developed chronic hepatitis-B infection. Seven of them had lymphoblastic leukaemia and others had solid tumours. Seven cases were male. Mean age was 10.5 years with a range of 5-16 years. Chronic Hepatitis B was diagnosed biochemically, serologically and histopathologically. They were HBsAg(+), HBV-DNA(+), and HCV(-), HIV(-). Seven cases were HBeAg(+) and two of them were anti-Delta IgG(+). Liver biopsy revealed chronic active hepatitis in six cases and persistent hepatitis in three cases. IFN was given at the dose of 5 MU/m2 three times a week, subcutaneously for 6 months. It was well tolerated. After IFN therapy, ALT levels returned to normal in seven cases. All cases were still HBsAg(+). Four of them seroconverted to anti-HBe antibody. Loss of serum HBV-DNA in three cases, but 11 cases showed a marked decrease after IFN. The control liver biopsies showed that histopathological activity index was diminished in five cases. Other 16 patients, serving as control, received no therapy. Five of them were leukaemia and others were solid tumours. Twelve cases were male. Mean age was 9.3 years with a range of 4-19 years. After 6 months, only one patient lost HBV-DNA and three of them seroconverted to anti-HBe with normalization of ALT values. In our study, IFN treatment favourably influenced the progress of chronic hepatitis B in children with cancer.
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PMID:alpha-Interferon-2b treatment for chronic hepatitis-B infection in children with cancer. 893 55

Liver transplantation for cirrhosis caused by hepatitis B virus (HBV) has a poor prognosis. This is primarily a consequence of the near universal reinfection of the allograft, subsequent accelerated hepatic disease while receiving immunosuppression, and a reduced long-term survival. Because interferon-alpha has been shown to have an antiviral effect on HBV, a study was initiated in 1986 to assess the effect of interferon-alpha therapy on the course of liver transplantation in HBV-positive recipients. Twenty-eight patients with decompensated endstage liver disease caused by HBV were treated with 5, 2.5 or 1.25 million units (MU) of human recombinant interferon-alpha 2b (r-IFN-alpha 2b) daily for a minimum of 14 days prior to transplantation and continuing for 42 days post-transplantation. HBV antigens, HBV antibodies, HBV DNA and serum transaminase levels were measured throughout the treatment and post-treatment period. HBV DNA was eliminated in 10 of 19 patients, who survived 3 months or more post-transplantation, and was associated with a significant flare of hepatitis as detected by symptoms and transaminase levels (P < 0.05). Patients who cleared HBV DNA had lower HBV DNA levels (P < 0.05) at entry compared with those who did not. While four of 10 patients with hepatitis B e antigen (HBeAg) converted to hepatitis B e antibody (HBeAb), no surviving patient cleared hepatitis B surface antigen (HBsAg) on a long-term basis. Nonetheless, post-transplant survival was significantly better (P < 0.0001, median follow-up 42 months) in the IFN-alpha treated patients as compared with historical controls, and was similar to that of patients transplanted for all causes of parenchymal liver disease other than HBV cancer. Hence IFN-alpha therapy in the perioperative liver transplantation period improves short-term survival but does not prevent HBV infection of the allograft.
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PMID:Interferon-alpha 2b improves short-term survival in patients transplanted for chronic liver failure caused by hepatitis B. 894 86

Infection with hepatitis C virus (HCV) may affect not only the liver but also various nonhepatic tissues and organs and may combine with many etiologically unrelated diseases and morbid conditions. Numerous nonhepatic manifestations in HCV infection have been previously reported. For some (eg, cryoglobulinemia), the association is well established. For others, such as sialadenitis and lichen planus, the association is probable (but not completely documented) and, for the remainder, the associations are weak. Extrahepatic manifestations may result from immunological mechanisms as well as virus invasion and replication in the affected extrahepatic tissues and organs. Thyroid abnormalities, primarily Hashimoto's disease, and isolated increases of anti-thyroid antibodies (ATPO) appear to be more frequent in chronic hepatitis C than B or D, with high ATPO titers clustering mainly among females. Interferon-alpha (IFN-alpha) therapy is associated with development of thyroid dysfunction in 5.5-12.9% of patients, usually exposing preexisting subclinical thyroid abnormalities. Mixed cryoglobulinemia (MC) is commonly found (36-45%) in patients with chronic HCV infection; however, only in a minority of cases does it become clinically manifested as systemic vasculitis with purpura, neuropathy, or Raynaud's phenomenon. In a number of patients, MC may terminate in non-Hodgkin's B-cell lymphoma. Treatment of these lymphoproliferative disorders with IFN-alpha is advocated. Idiopathic thrombocytopenia is now recognized more frequently in association with chronic HCV infection and is usually aggravated by IFN-alpha therapy. Patients with porphyria cutanea tarda (PCT) have demonstrated serological markers of HCV infection in 62-82% of cases. The usefulness of IFN-alpha in PCT remains to be demonstrated. Lichen planus has also been found in association with chronic HCV infection, particularly when severe or affecting the oral cavity. Other nonhepatic manifestations have also been reported in HCV infection such as diabetes, corneal ulceration, uveitis, and sialadenitis. These manifestations deserve further study and documentation. Finally, markers of autoimmunity occur with high frequency in chronic HCV infection; however, combination with the classical syndrome of autoimmune hepatitis is rare. In the presence of various autoantibodies, the clinical features of chronic hepatitis C do not appear to be modified and, contrary to general perception, IFN-alpha therapy within randomized controlled trials should not be withheld since the response rate to IFN-alpha does not appear to differ in the presence or absence of low titers of these markers.
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PMID:Nonhepatic manifestations and combined diseases in HCV infection. 901 79

This report presents the interferon alpha (IFN-alpha) treatment results for 75 patients with chronic hepatitis B virus (HBV) (51 cases) and hepatitis C virus (HCV) (24 cases) induced hepatitis in maximal 61 months follow-up. Among the group of 51 patients with chronic HBV hepatitis, 35 were treated orally with IFN-alpha in the form of lozenges in low daily doses (37.5-150 U). The treatment was completed in 32 cases. The remaining 16 patients with chronic HBV hepatitis completed the treatment with parenteral IFN-alpha (3 x 10(6) U, 3 times a week). Positive results measured by the use of seroconversion in the HBe-antigen system were obtained for 68.7% (5-61 months follow-up) and 56.2% (7-44 months follow-up) of the patients treated with oral and parenteral IFN-alpha, respectively. Among the group of 24 patients with chronic HCV hepatitis, the first 6 patients were initially treated with IFN-alpha in the form of lozenges, in low daily doses. Biochemical remission was not achieved in these patients; genotype 1b was documented in 4 of them. Both, the first 6 patients (after a break) and the remaining 18 were treated with IFN-alpha parenterally, as in HBV patients. Temporary clinical and biochemical remission was achieved in 62.5% of the cases during the treatment, however the durable remission observed during 6-29 months of follow-up was achieved in 20.4 of the cases only.
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PMID:Comparison of the long-term effects of treatment with oral and parenteral interferon alpha in chronic viral hepatitis patients. 901 52

To investigate whether interferon-alpha receptor (IFN-alpha Rc) expression was related to the effectiveness of interferon therapy in hepatitis C virus (HCV)-associated chronic liver disease (CLD). IFN-alpha Rc mRNA was investigated by reverse transcription polymerase chain reaction (RT-PCR) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 40 patients with HCV-associated CLD who subsequently received IFN-alpha therapy. IFN-alpha Rc mRNA in the liver was detected in 18 of 20 (90%) responders to IFN and in 5 of 20 (25%) non-responders (P < 0.01). In PBMCs, IFN-alpha Rc mRNA was detected in all patients regardless of response to IFN. Increased histological hepatitis activity and liver fibrosis were significantly related to the absence of IFN-alpha Rc mRNA. The HCV-RNA genotype showed no significant relationship to IFN-alpha Rc mRNA expression. Our results suggest that IFN-alpha Rc mRNA expression in the liver, but not in PBMCs, is closely associated with the effectiveness of IFN-alpha therapy in HCV-associated CLD.
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PMID:Expression of interferon-alpha receptor mRNA in the liver in chronic liver diseases associated with hepatitis C virus: relation to effectiveness of interferon therapy. 902 43


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