Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the efficacy of interferon-alpha 2a in chronic active hepatitis B, 238 patients were randomly divided, into four groups: three groups received either 2.5 MIU m-2, 5.0 MIU m-2 or 10.0 MIU m-2, three times weekly by intramuscular injection for 12-24 weeks; and a control group received no treatment. Patients were followed for up to 12 months after treatment was discontinued. There was a statistically significant difference in response [clearance of hepatitis B e antigen (HBeAg) and hepatitis B viral DNA (HBV-DNA)] between treated and untreated patients (37 vs 13%) but no statistically significant difference was seen between treatment groups (33%, 34% and 43% for the 2.5, 5.0 and 10.0 MIU m-2 groups, respectively). A transient rise in transaminases (seroconversion hepatitis) was seen in responders, but levels returned to within the normal range after response to treatment. In patients responding to interferon therapy there was a significant reduction in the severity of the hepatitis. Interferon-alpha 2a was generally well tolerated with respect to vital signs and laboratory parameters.
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PMID:Comparative study of three doses of interferon-alpha 2a in chronic active hepatitis B. The International Hepatitis Trial Group. 879 May 69

A meta-analysis of six randomized clinical trials involving 240 children with chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was performed. IFN-alpha treatment was effective in blocking viral replication. Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the end of the follow-up period, viral replication was still reduced in IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P = .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026). Regarding these virological and biochemical endpoints, we found that prolonged therapy (> 6 months) was associated with a better response, whereas high dosages of IFN-alpha were not. These findings could be biased by limited follow-up. Children with high ALT levels had a better response. However, these randomized clinical trials had some methodological flaws, including the lack of information on histologic response to IFN-alpha treatment by pediatric patients and the absence of "hard outcomes" (such as survival or development of cirrhosis or hepatocellular carcinoma).
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PMID:Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis. 881 42

The hepatitis B virus (HBV) is the world's most important chronic virus infection. The immunomodulator interferon-alpha (IFN alpha) is the only clinically applied drug available, despite its low response rate (approximately 30%) even in highly selected chronic carriers. Antiviral nucleoside analogues have proven to be potent inhibitors of viral replication in vitro, but their significant adverse effects which are, at least partially, due to their nonspecific body distribution, have forced the cessation of their clinical development in the past. For example, vidarabine causes severe neuromuscular toxicity, and fialuridine has caused fatal cases of liver and kidney failure in a recent clinical trial. Furthermore, the potential clinical application of (modified) antisense oligodeoxynucleotides, which are very specific inhibitors of viral replication, is hampered by their nonspecific body distribution, instability in serum and poor cell penetration. As infection and replication of HBV mainly occur in liver parenchymal cells, selective targeting of antiviral nucleoside analogues as well as antisense oligodeoxynucleotides to the liver would theoretically improve therapeutic efficacy. At present, conjugates of vidarabine and neoglycoproteins have entered clinical trials, and initial data suggest that therapeutic concentrations are achieved at lower dosages with minor adverse effects. These data have stimulated preclinical research on other liver-specific drug carriers for the selective delivery of HBV-active drugs such as glycosylated polymers and neolipoproteins: these approaches are outlined in this paper.
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PMID:Targeting hepatitis B therapy to the liver. Clinical pharmacokinetic considerations. 885 35

In recent years, interferon-alpha has become widely used for systemic therapy of tumours and infectious diseases. Well-known cutaneous side effects include dry skin, pruritus and hair loss. Since 1986, 17 patients with renal cell carcinoma, malignant melanoma, hepatitis B and C, carcinoid syndrome and hairy cell leukemia have been reported in whom psoriasis with or without psoratic B joint involvement was induced or exacerbated by systemic interferon-alpha therapy. In these patients, the drug was discontinued because of the severity of the psoriatic symptoms induced. The psoriatic lesions then resolved in nearly all patients within 2 weeks to 6 months, but in 10 of 22 patients treated with interferon-alpha specifically for psoriasis exacerbation was reported. We report three new cases of interferon-alpha-induced psoriasis. The patients were treated with the drug for HIV-associated Kaposi's sarcoma, renal cell carcinoma, and hepatitis C. We conclude that interferon-alpha can provoke psoriatic skin and joint symptoms, especially when additional precipitating factors are involved. In patients in whom such risks are present careful consideration of the benefit/risk ratio and concomitant antipsoriatic treatment are essential if interferon-alpha therapy is to be continued.
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PMID:[Interferon-alpha-induced psoriasis vulgaris]. 886 56

We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.
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PMID:Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study. 887 70

This open label study was initiated to assess the safety and efficacy of lymphoblastoid interferon-alpha (IFN-alpha) and thymosin alpha 1 (T alpha 1) in the treatment of 11 patients with chronic hepatitis B, who had failed to respond to standard IFN-alpha 2b therapy, and in four interferon naive patients. These fifteen hepatitis B surface antigen (HBsAg) positive and serum hepatitis B virus (HBV) DNA positive patients were given T alpha 1 (1 mg) subcutaneously (s.c.) on 4 consecutive days. Low-dose lymphoblastoid IFN-alpha (3 MU) was administered intramuscularly (i.m.) on the fourth day. Beginning with the second and for the subsequent 25 weeks, patients self-administered T alpha 1 twice weekly in the morning followed, 12 h later, by 3 million units (MU) lymphoblastoid IFN-alpha. Patients were followed-up for 12 months. Nine (60%) of the 15 patients, including six (55%) of the 11 patients previously treated with IFN-alpha 2b, responded by losing serum HBV DNA and normalizing alanine aminotransferase (ALT) values. Six of the nine responders seroconverted to HBsAg negativity. Significant improvements in the Knodell histological activity index were observed in the responders and no significant adverse effects were observed. Combination low-dose lymphoblastoid IFN-alpha and T alpha 1 treatment may provide a safe and potentially effective therapeutic approach in chronic hepatitis B. These results require confirmation in future randomized controlled studies.
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PMID:Combination low-dose lymphoblastoid interferon and thymosin alpha 1 therapy in the treatment of chronic hepatitis B. 887 80

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

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Several risk factors for HCC development have been identified, including cirrhosis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection. With regard to cirrhosis, multivariate analysis indicates that alcohol abuse, HBsAg positivity, and anti-HCV seropositivity are independent variables associated with an increased risk for HCC in the cirrhotic patient. A close relationship between chronic HBV infection and HCC has been established by epidemiological studies and laboratory investigations. Evidence indicates that HCV also plays a leading role in development of HCC. Most patients with HCV-related HCC develop the tumor as a consequence of long-standing infection accompanied by chronic and progressive liver damage. In our study of 290 consecutive patients with cirrhosis, patients with persistently elevated or fluctuating ALT levels had a significantly greater rate of HCC development. The mechanism of HCC development in HCV infection remains to be elucidated. The annual cumulative risk of developing HCC is approximately 1% in patients without cirrhosis at inclusion and 3-10% in those with cirrhosis, depending on the stage of cirrhosis and presence of etiological cofactors. Although some evidence suggests that patients infected with the HCV genotype 1b are at increased risk for development of more severe liver disease, including HCC, results of our prospective study do not support a difference between cirrhotic and noncirrhotic patients in terms of the natural course of cirrhosis and the rate of developing HCC based on genotype. Strategies to prevent HCV-related HCC include blood screening and treatment of chronic HCV infection with interferon-alpha. Recent studies suggest that interferon-alpha treatment may prevent the development of HCC in HCV infection. Further research is warranted.
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PMID:Risk factors and prevention of hepatocellular carcinoma in HCV infection. 901 76

A new member of the Flaviviridae family has recently been cloned and completely sequenced. The new virus, tentatively named hepatitis G virus (HGV) and known to be closely related to GB virus C (GBV-C), is transmitted by blood and blood products, intravenous drug use and other behaviour associated with a high risk of parenteral exposure to blood. The association of the virus with hepatitis is demonstrated by the presence of raised liver transaminase (alanine aminotransferase, ALT) levels in patients infected with HGV in the absence of other identifiable causes of hepatitis. No patient sera from groups exposed to blood and blood products were found to be positive when tested for the presence of GBV-A or GBV-B sequences, two other recently described flaviviruses. Forty-five per cent of the HGV-infected patients investigated had normal ALT suggesting the existence of a normal carrier state. Persistent infection of up to 13 years duration was observed. Co-infection with hepatitis B or hepatitis C viruses (HBV and HCV) was commonly seen presumably because of shared risk factors. None of five patients with fulminant hepatic failure was positive for HGV infection. The virus is sensitive to interferon-alpha, but sustained responses were not seen with the treatment regimens used for HBV and HCV. Viral titres increased during immunosuppression following liver transplantation and the higher levels of viraemia were in one case accompanied by elavated ALT. Whether HGV (GBV-C) replicates in the liver in some or all cases remains to be established. Preliminary data suggest that it is present within peripheral blood lymphocytes.
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PMID:Hepatitis G virus infection: clinical characteristics and response to interferon. 903 Oct 63

Eleven hepatitis B virus (HBV) carrier children, infected with genotypes A-D, were treated with interferon-alpha. Two children had a sustained loss of hepatitis B e-antigen and HBV DNA. They were infected with the non-Asian genotypes A and D, and had low HBV DNA and high ALT levels in serum before treatment. However, HBV DNA titres decreased during treatment also in children infected with the East-Asian genotypes B and C.
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PMID:Interferon-alpha 2b treatment in hepatitis B carriers. Effect on hepatitis B virus DNA levels in children infected with different genotypes. 905 80


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