Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analysed the time from the date CD4+ cell counts fell below 200 x 10(6) L-1, defined as ti, to the onset of clinical AIDS, according to the 1987 Centers for Disease Control and Prevention case definition, in 129 Japanese haemophilia patients infected with HIV-1. The cumulative onset of clinical AIDS was analysed by the Kaplan-Meier method and proportional hazard model. Incorporated covariates were age of each patient at time ti, as well as CD4+ and CD8+ cell counts, serum levels of IgG, IgA, IgM, GOT and GPT at ti. The time of antiretroviral treatment initiation was also considered. The 50% AIDS-free interval after ti was 3.00 years (95% confidence interval (CI), range 0.49-5.51) and 1.71 years (95% CI, range 0.66-2.76) for the patients at CDC stage II and stage III, respectively (significantly different, P = 0.0013). Among the patients at CDC stage II at ti, higher levels of IgA were tightly associated with a shorter period from ti to onset of clinical AIDS (P < 0.0001), and relative hazard was 1.35 (95% CI, 1.11-1.64) with increase of IgA level by 1.0 g L-1. Thus there is a broad distribution in the time to onset of clinical AIDS in Japanese haemophiliacs even after CD4+ cell counts fall below 200 x 10(6) L-1. This should be taken into consideration in deciding upon the therapy and care of HIV-1 infected people.
Haemophilia 1998 Jan
PMID:Analysis of clinical AIDS-free interval after CD4+ cell counts fall below 200 x 10(6) L-1 in Japanese haemophiliacs infected with HIV-1. 987 64

In 80% of children with haemophilia treated in our department, screening tests showed the presence of antibodies against the hepatitis C virus (HCV). HCV RNA was detected in serum in 41% of cases. In 20% of cases there were periodic increases in the level of alanine aminotransferase (ALT) activity, and in these cases liver biopsy was performed after factor concentrate replacement. No haemorrhagic complications or pain complaints were reported either during the biopsy or immediately afterwards. In all cases histopathological examination revealed chronic hepatitis type C - chronic mild hepatitis and chronic minimal hepatitis. Eight boys were treated with interferon (INF) alpha. In two cases this therapy was successful. No HCV RNA was detected in serum and transaminase activity was normal during the year following interferon treatment.
Haemophilia 1999 Nov
PMID:Incidence and treatment of hepatitis C virus infection in children with haemophilia in Poland. 1058 32

Individuals with Haemophilia are at risk from hepatitis A virus (HAV) infection through exposure to blood products. Havrix(R), an intramuscular hepatitis A vaccine, is currently recommended for the prevention of disease caused by hepatitis A virus. Because bleeding may complicate intramuscular injections in those with bleeding disorders, we conducted a randomized, Phase IV clinical trial to compare the safety and immunogenicity of Havrix(R) given by the subcutaneous (s.c) vs. intramuscular (i.m.) route. A total of 45 children with Haemophilia were vaccinated subcutaneously, while their 41 nonhaemophlic siblings were vaccinated intramuscularly, at a dose of 720 Elisa units (EL.U.) at time 0 and 6 months. All children were anti-HAV and anti-HIV negative at baseline, and the haemophilic group did not differ from their siblings in alanine aminotransferase (ALT; 25 IU L-1 vs. 22 IU L-1), or in age; 8.5 years vs. 8.7 years. The vaccine was well tolerated, with minor adverse events being similar between groups; 21 (47%) vs. 24 (58%), P > 0.05. Local symptoms included soreness in 39 (45%), erythema in 25 (29%), swelling in 21 (24%), and bruising in six (7%), with no differences between groups. The proportion seroconverting to anti-HAV IgG positive did not differ between groups; 98% vs. 97% at month 1; 82% vs. 93% at month 6; and 100% vs. 100% at month 8, respectively. The HAV geometric mean titre was lower in those with Haemophilia, 185 vs. 233 mIU mL-1 at month 1; 68 vs. 94 mIU mL-1 at month 6; and 584 vs. 1082 mIU mL-1 at month 8, respectively. We conclude that Havrix(R) is safe and immunogenic when administered s. c. in children with Haemophilia.
Haemophilia 2000 Mar
PMID:Safety and immunogenicity of subcutaneous hepatitis A vaccine in children with haemophilia. 1078 Nov 96

We performed a pilot study to evaluate the factors associated with response to interferon (IFN) therapy for chronic hepatitis C (CHC) with human immunodeficiency virus (HIV) coinfected haemophiliacs. Seven haemophiliacs, coinfected with HIV and hepatitis C virus (HCV), received 9 mega-units (MU) of natural IFN-alpha daily during the first 2 weeks and then three times a week for 22 weeks, all injected subcutaneously. Six patients were receiving zidovudine (AZT) 600 mg day-1 and didanosine (ddI) 200 mg day(-1) during IFN therapy. This treatment was safe and well tolerated. Four patients had no detectable serum HCV-RNA at the end of therapy, but long-term, none of the seven patients achieved a sustained response, i.e. undetectable serum HCV-RNA with persistently normal serum alanine aminotransferase (ALT) 6 months after therapy. IFN did not affect CD4-positive cell counts. Most of our patients had high HCV-RNA loads and/or low CD4 counts, both unfavourable markers for IFN therapy. In conclusion, IFN therapy did not eradicate HCV from haemophiliacs coinfected with HIV.
Haemophilia 2000 Nov
PMID:Poor response to interferon treatment for chronic hepatitis C in human immunodeficiency virus-infected haemophiliacs. 1112 95

In the seventh national voluntary cross-sectional survey (in 1999) of Finnish patients with haemophilia A or B, type 3 von Willebrand disease or factor XIII deficiency, a plasma sample was received from 193 patients (67%). The samples were tested for hepatitis B and C, human immunodeficiency virus (HIV) and human T-cell leukaemia virus (HTLV) antibodies. Fifty-one percent of the patients were hepatitis C antibody positive and 34% hepatitis B core antibody positive. None of the patients had antibodies against HIV or HTLV. Eighteen percent of the patients had an elevated alanine aminotransferase activity. Abnormal alanine aminotransferase was significantly associated with hepatitis C seropositivity. No new seroconversions were detected among the haemophiliacs or patients with type 3 von Willebrand disease when compared with the last two surveys in 1993 and 1996, and there was no seroconversion in sole users of solvent/detergent-treated factor products. Currently, 32% of the patients use prophylactic factor treatment as their principal mode of therapy, particularly the younger patients with severe forms of the bleeding diseases.
Haemophilia 2001 Jan
PMID:Viral markers and use of factor products among Finnish patients with bleeding disorders. 1113 80

The efficacy and viral safety of a pasteurized, immunoaffinity-purified procoagulant factor VIII protein (FVIII:C; Monoclate-P) was studied in two multicentre, prospective, open-label trials in 30 previously untreated patients, 18 with severe (< 1% FVIII:C activity), and 12 with moderate (1% to 5% FVIII:C activity) haemophilia A. Clinical assessments, performed at screening and regularly thereafter for 6 to > 24 months (maximum 34 months), showed that none of 24 assessable patients acquired illnesses consistent with monitored transfusion-transmissible diseases. No patients acquired hepatitis B surface antigen, or antibodies against hepatitis B core antigen, hepatitis C, or human immunodeficiency virus. Likewise, no patients acquired treatment-related hepatitis A antibodies or sustained elevations of alanine aminotransferase levels. The safety profile for Monoclate-P is brought about by a multi-step safety system that incorporates viral inactivation (through a combination of immunoaffinity chromatography and pasteurization) plus donor screening, plasma testing, and quality assurance. The inhibitor development rate (13% low titre, 10% high titre) was similar to that reported in the literature for other FVIII concentrates (24% to 52%). The most frequently reported adverse events were related to typical infant and childhood diseases. Monoclate-P was effective in all patients treated according to protocol, except in two, who developed inhibitors.
Haemophilia 2001 Mar
PMID:Viral safety of a pasteurized, monoclonal antibody-purified factor VIII concentrate in previously untreated haemophilia A patients. 1126 Feb 73

Coinfection with hepatitis C virus (HCV) and HIV-1 is common in patients with hemophilia and in intravenous drug users. Little, however, is known about the relation between HIV-1 and HCV coinfection and the effects on HCV clearance and pathogenesis. We examined data from 207 HIV-1-infected and 126 HIV-1-uninfected patients with hemophilia enrolled in the multicenter Hemophilia Growth and Development Study. Participants were observed during prospective follow-up for approximately 7 years with annual measurements of alanine aminotransferase (ALT), CD4+ cells, and HCV and HIV-1 RNA levels. Clearance of HCV was more likely to occur in those uninfected with HIV-1 (14.3 versus 2.5%; odds ratio [OR] 4.79; 95% confidence interval [CI], 1.63-14.08, p =.005) and was more common with decreasing age (OR, 1.23; 95% CI, 1.04-1.47; p =.017). HCV RNA levels were higher throughout the 7 years of follow-up in those HIV-1-infected (p <.001). In the HIV-1-infected participants, baseline CD4+ cells were inversely related to HCV RNA with every 100-cell increase associated with a 0.19 log10 copy/ml decrease in HCV RNA (p =.002), and HIV-1 and HCV RNA levels were directly related (p =.008). Increasing HCV RNA levels were also associated with significantly higher ALT levels regardless of HIV-1 infection status. These results demonstrate that HIV-1/HCV co-infection is associated with a reduced likelihood of HCV clearance and that higher levels of HCV RNA are associated with increased hepatic inflammation.
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PMID:Relation between HIV-1 and hepatitis C viral load in patients with hemophilia. 1139 Nov 67

In multiply coinfected human immunodeficiency virus (HIV)-positive patients, we investigated the effects of high-activity antiretroviral therapy (HAART) using HIV protease inhibitors on three other viruses: hepatitis C virus (HCV), hepatitis G virus (HGV), and TT virus (TTV). Viral concentrations were measured serially by polymerase chain reaction methods in five patients with quadruple infection (HIV, HCV, HGV, and TTV) and in two patients with triple infection (HIV, HCV, and HGV) before and during HAART. In addition, CD4+ cell counts and serum alanine aminotransferase (ALT) levels were measured serially. Generally we observed no difference in serum HCV RNA, HGV RNA, or TTV DNA concentrations between samples obtained before and after initiation of HAART, whereas HIV RNA concentration decreased and CD4 counts increased in most patients. However, two patients had markedly decreased concentrations of HCV RNA and HGV RNA, respectively, more than 12 months after beginning HAART. Normalization of serum ALT levels was observed in a patient with decline of HCV RNA concentrations. No interactions were observed among these four viruses. HAART had no apparent direct effects on HCV, HGV, or TTV. Further studies will be required to elucidate whether the restoration of immune status through suppression of HIV replication by HAART may affect HCV or HGV RNA concentrations.
Haemophilia 2001 Nov
PMID:Effects of HAART on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with haemophilia. 1185 56

Between January 1999 and December 2001, 33 HIV-negative haemophiliacs with interferon-nonresponsive chronic hepatitis C were treated with interferon (IFN) alpha2b (5 MU three times weekly) and ribavirin (1-1.2 g daily) for 12 months. Four patients (12.1%) dropped out of the study due to adverse effects. At the end of therapy, normalization of ALT occurred in 14/33 treated patients (42.4%) and HCV-RNA was cleared in 12 (36.4%). Eleven patients (33.3%) became sustained responders. Genotype 1 was the only factor associated with a poor response to therapy (P < 0.001). Our study shows that IFN and ribavirin combination therapy is effective in HIV-negative chronically HCV-infected haemophiliacs who do not respond to a previous IFN treatment.
Haemophilia 2002 Nov
PMID:Interferon and ribavirin in HIV-negative haemophiliacs with chronic hepatitis C who were nonresponders to a previous interferon treatment. 1241 Jun 49

Individuals with haemophilia are frequently infected with both human immunodeficiency virus (HIV) and hepatitis C virus (HCV); however, limited evidence is currently available regarding the efficacy of HCV treatment with pegylated interferon and ribavirin in this patient population. The aim of this study was to review HCV treatment outcomes in a cohort of patients with haemophilia and HIV/HCV co-infection. A retrospective, single centre review of 13 consecutive patients treated with pegylated interferon and ribavirin was performed. All patients were male with haemophilia A and a median age of 43 (range 27-62) at initiation of HCV therapy. Nine of 13 (69%) patients had genotype (gt1) 1 HCV (3 x gt3, 1 x gt4). Twelve of 13 (92%) were receiving ART, with a mean CD4+ count of 428 cells microL(-1) (range 175-928 cells microL(-1)) at initiation of HCV therapy. Six of 11 (55%) patients achieved EVR (3 x gt1, 2 x gt3, 1 x gt4) at 12 weeks, 4/13 (31%) had EOTR (2 x gt1, 2 x gt3) and 1/13 (8%) achieved sustained virological response (1 x gt1). Seven of 11 (64%) patients normalized ALT during therapy wherein mean ALT fell from 101 to 76 U L(-1). Only 1/13 (8%) patients discontinued therapy prematurely due to side effects. CD4+ cell counts and HIV viral load remained stable during HCV treatment, with a mean 437 cells microL(-1) and <50 copies mL(-1) at 48 weeks respectively. Patients in our cohort with haemophilia and HCV/HIV co-infection responded poorly to HCV treatment. Alternative HCV treatment strategies need to be considered in patients with haemophilia and HIV/HCV co-infection.
Haemophilia 2009 Mar
PMID:HCV treatment with pegylated interferon and ribavirin in patients with haemophilia and HIV/HCV co-infection. 1918 89


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