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)

People with haemophilia who received non-virucidally treated large-pool clotting factor before 1986 were infected with hepatitis C virus (HCV), previously referred to as non-A, non-B hepatitis. Approximately one-tenth of patients have been shown to clear infection naturally and shown persistently negative HCV PCR. Patients have been infected with genotypes 1, 2 and 3 reflecting the plasma donors in Northern Europe and the United States. Several studies have shown that HCV mono-infection has a very slow progression. Co-infection with human immunodeficiency virus (HIV), however, can hasten the progression to cirrhosis and liver failure. Genotype 1 and older age at first infection also increase the progression rate. Candidates with detectable HCV RNA are candidates for therapy. The combination of standard interferon-alpha and ribavirin doubles the effectiveness of interferon-alpha alone and is the current standard of care for the treatment of chronic hepatitis C. The duration of therapy depends on the genotype and level of viraemia. Patients with genotypes 2 or 3 should have 6 months' therapy while those with genotype 1 and > 2 million copies mL-1 should have 1 year of therapy. Pegylated interferon is an emerging therapy. Patients co-infected with HIV, in whom treatment has stabilized the HIV infection, may be able to tolerate therapy for HCV infection. Liver transplantation is indicated for patients with haemophilia who have decompensated hepatitis C infection.
Haemophilia 2002 May
PMID:The natural history and antiviral treatment of hepatitis C in haemophilia. 1201 Apr 29

The introduction of plasma-derived human factor VIII (FVIII) and later human recombinant FVIII (rFVIII) has potentially allowed patients suffering from hemophilia A to have a quality of life and life expectancy similar to the population at large. One of the major achievements in molecular biology over the past 15 years was the sequencing of the gene coding for FVIII, leading eventually to the ability to isolate the human gene for FVIII and transfect cells to produce human rFVIII. The first rFVIII products, which are native full-length FVIII molecules, have proved to have an excellent efficacy and safety profile in patients with hemophilia A. Initial concerns about a potential increased inhibitor formation have not been confirmed so far but long-term pharmacovigilance of inhibitor formation is still ongoing. To date, no transmission of hepatitis or human immunodeficiency virus (HIV) attributable to rFVIII products has been reported. However, a theoretical risk of transmission of infectious disease does exist as long as nonsynthetic proteins are used during the production process. The next-generation native rFVIII has been developed to minimize the exposure of patients to animal or human plasma-derived proteins. This has been achieved through major changes to the process of production of rFVIII from baby hamster kidney cells (BHK). This change has included the introduction of a solvent/detergent step and, of more importance, the introduction of a purification procedure without using albumin as a stabilizer. Finally, the rFVIII (BHK) is formulated using sucrose as the final stabilizer to produce the sucrose formulated rFVIII referred to as rFVIII-FS. This article summarizes the recently published pharmacokinetic, safety, and efficacy data for the native rFVIII-FS and compares its clinical profile with that of the first-generation rFVIII.
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PMID:First and next generation native rFVIII in the treatment of hemophilia A. What has been achieved? Can patients be switched safely? 1209 89

Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high-titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all-cause mortality among HIV-uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV-uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all-cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV-uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia.
Haemophilia 2002 Sep
PMID:Factors predictive of death among HIV-uninfected persons with haemophilia and other congenital coagulation disorders. 1219 76

Chronic hepatitis C is associated with more severe liver disease in patients coinfected with HIV, but the pathogenic mechanism of this more aggressive course is still unclear. The aim of this study was to assess the relationship of HCV genotype, viral load and epidemiological factors with the histological severity of chronic hepatitis in haemophilia patients with HCV/HIV coinfection, taking into consideration the immune status of the patients. Twenty-one HIV/HCV coinfected haemophilia patients, with mean age +/- SD 35.7 +/- 8.7 years, underwent transcutaneous liver biopsy 6-15 years (median 12 years) after HIV and 6-32 (median 21.5 years) years after HCV infection. Twelve patients were stage A (CDC), six stage B and three stage C. CD4 cells were < 50 microL(-1) in three patients (14.3%), 50-200 in 11(52.4%) and > 200 in 7(33.3%). Mean +/- SD log(10) HCV-RNA was 6.87 +/- 0.7 copies mL(-1) (range 5.4-7.9), and mean +/- SD log(10) HIV-RNA was 3.75 +/- 0.98 copies mL(-1) (range 2.7-6), at the time of liver biopsy. Minimal hepatitis was diagnosed in five patients (24%), mild in 10 (48%) and moderate in six (28%). Hepatitis stage 0-2 was found in seven cases (33%) and cirrhosis in six (29%). Statistical analysis showed a significant association of CD4 count < 50 with minimal hepatitis and of CD > 200 with mild and moderate hepatitis (P = 0.033). In addition, minimal hepatitis was found only in patients with stage C, while the majority of subjects with HIV stage A showed mild and moderate hepatitis (P = 0.003). Moreover genotype 1 was independently associated with advanced hepatitis stage (P = 0.04). No relationship was found between hepatitis severity, HIV or HCV RNA levels, patient's age and duration of HIV or HCV infection. Our results suggest that HCV/HIV coinfection may aggravate the course of hepatitis in the phase of immunocompetence, most probably through an immune mediated process. Genotype 1 seems to be associated with advanced liver disease.
Haemophilia 2002 Sep
PMID:Significance of immune status, genotype and viral load in the severity of chronic hepatitis C in HIV infected haemophilia patients. 1219 77

The hemophilias are a group of disorders associated with a chronic burden of morbidity and early mortality. Improvements in these adverse features have been achieved by the use of clotting factor concentrates within comprehensive centers of specialized care providing home infusion programs. Offsetting effects from transfusion-transmitted hepatitis and HIV infection are in recent decline. The net impact of these changes merits assessment. To test the a priori hypotheses that increasing severity of factor VIII deficiency would be associated with an increasing burden or morbidity and that hepatitis and HIV positivity would impair health status further, a cross-sectional study of a population-based cohort was undertaken in a regional hemophilia program in Ontario, Canada. A survey was made of mild, moderate, and severe hemophiliacs over 13 years of age who self-reported their health status using a standard 15-item questionnaire. The responses were converted to levels in the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems to form multi-element vectors from which single-attribute morbidity and overall health-related quality of life utility scores were determined. The burden of morbidity was greater in hemophiliacs than in the general population and correlated with the category of disease (mild < moderate < severe). Hepatitis and HIV positivity conferred additional burdens of morbidity, which were mainly in the attributes of mobility (HUI2), ambulation (HUI3), and pain (HUI2/3), all of these differences reaching levels of statistical significance. Despite demonstrable improvements in the safety, effectiveness, and utilization of clotting factor concentrates, hemophiliacs continue to experience an important burden of morbidity. Measurement of this burden, as reported here, provides a basis for future economic evaluation of the costs and consequences of health care interventions provided to this population.
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PMID:Health status and health-related quality of life associated with hemophilia. 1241 May 68

Blood-borne hepatitis is a well-known complication in patients with bleeding disorders. A recently discovered parentally transmitted virus, hepatitis G [GB virus C (GBV-C)] has an increased prevalence in patients with haemophilia. Clotting factor concentrates derived from pools of human plasma currently undergo viral inactivation techniques known to be effective against hepatitis B, C and HIV; however, the effectiveness of current purification and viral inactivation techniques against newly discovered viruses such as GBV-C is unknown. A total of 37 vials of clotting factor concentrates manufactured in the USA from 1981 to 1995 were tested for the presence of GBV-C virus. All samples that did not undergo a specific viral inactivation step were positive for GBV-C. Viral inactivation techniques that did not uniformly remove GBV-C included vapour heat treatment and dry heat treatments for less than 144 h. All samples treated by pasteurization, solvent detergent or dry heat for 144 h, were negative for the presence of GBV-C.
Haemophilia 2003 Jan
PMID:Hepatitis G virus in clotting factor concentrates. 1255 87

Comprehensive hemophilia treatment centers (HTCs) were first inaugurated more than 50 years ago. In 1976, a federally funded HTC network was created in the United States, making multidisciplinary care for patients with hemophilia and other inherited bleeding disorders available throughout the country for the first time. Education of the patient and healthcare professional in the management of bleeding became a mainstay of these programs. The HTCs began surveillance of the complications of treatment, such as hepatitis and HIV. The high rate of HIV infection in the hemophilia population from contaminated clotting factor concentrates forced an adaptation of HTCs to manage the medical and psychosocial consequences of these diseases. In addition, expanded surveillance for potential new therapy-associated complications became a legacy of these efforts. From the HIV era until the present, HTCs have undertaken expanded clinical research (drawing on a new scientific understanding regarding hemostasis and new knowledge regarding the management of quality of life) to study new methods to improve the well-being of patients with hemophilia. The further research has extended to phase 1 gene transfer trials for hemophilia A and B. Although the prospect for a complete cure for patients with hemophilia is some time away, HTCs in the 21st century continue to vigorously research a cure. In the interim, the HTC model continues to provide essential services that are being reassessed in light of new scientific information to prevent the complications that have defined the clinical picture of hemophilia.
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PMID:Comprehensive care for hemophilia and related inherited bleeding disorders: why it matters. 1293 11

Haemophilia is a group of inherited, congenital diseases present all through the life. Those disorders are associated with a chronic burden of morbidity punctuated by episodes of acute deterioration in health-related quality-of-life (HR-QL). The significances of assessing HR-QL in individuals with haemophilia as an important component of the clinical database have gained increasing recognition in recent years. To the best of our knowledge, reports on the HR-QL of Chinese patients with haemophilia are not available. The purpose of this paper was to assess the HR-QL of patients with haemophilia in China. In order to do this, 179 patients with haemophilia (age 16-70) were mailed China quality-of-life questionnaire, which was designed specially for this study taking into account the culture characters of Chinese. Compared with the normal male general population, individuals with haemophilia experienced significantly lower levels of HR-QL and within the subgroups of patients, there was a gradation of HR-QL from mild < moderate < severe haemophilia patients. Age, clinical severity, degree of arthropathy, hepatitis status, salary and mean annual expenditure for replacement therapy were predictors of HR-QL. Clinical severity of the disease manifestation rather than the severity of the disease based on molecular classification was a factor that negatively influenced the HR-QL of patients with haemophilia. Arthropathies of patients with haemophilia in China were more severe than that in western countries because of the poorer medical care and were associated with their lower income and therapy cost. A large number of patients never had hepatitis or HIV serological examination. The exact prevalence of hepatitis and HIV was difficult to obtain and the HR-QL of hepatitis and HIV positive patients required further study.
Haemophilia 2004 Jul
PMID:Assessing health-related quality-of-life in individuals with haemophilia in China. 1523 Sep 52

Hemophilia is an inherited bleeding disorder, which in its severe form is characterized by recurrent hemarthrosis and internal bleeding. In the absence of effective treatment the prognosis is poor, but the development of blood products in the last few decades has transformed the outlook, and patients can now live essentially normal lives. Treatment options vary around the world, with cryoprecipitate still the mainstay of therapy in many developing countries. Many patients were infected with hepatitis and/or HIV through the use of coagulation factor concentrates before the introduction of physical methods of viral inactivation in the mid-1980s. In more affluent countries, the debate in recent years has focused on the relative merits of plasma versus recombinant products. Coagulation factor concentrates are expensive, and cost-benefit and quality-of-life studies will assume an increasing importance in guiding the selection of products. Looking to the future, genetic engineering offers the potential to create coagulation factors with enhanced properties, such as reduced immunogenicity and prolonged half-life. Transgenic animals are a potential source of therapeutic materials. Several trials of gene therapy for hemophilia are already underway.
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PMID:Blood products for hemophilia: past, present and future. 1524

Hepatitis C is a major cause of morbidity and mortality in haemophiliacs who received clotting factor concentrates before the availability of virus-inactivated factors in the mid-1980s. Early studies gave conflicting indications as to the severity of hepatitis C (originally termed non-A non-B hepatitis), as mild, slowly progressive hepatitis was documented in several infants and young adults with haemophilia who were examined with repeat liver biopsies, whereas more progressive hepatitis and cirrhosis was documented in others. One major point of dispute was whether these discrepancies could in part be accounted for by epidemiological differences among studies, as hepatitis C acquired early in life may initially run a benign course and later worsen owing to spontaneous recrudescence of hepatitis or interference with such comorbidity factors as alcohol abuse or infection with the human immunodeficiency virus (HIV). In the mid 1990s, the latter infection overshadowed hepatitis C as a cause of death in this patient population. Because hepatocellular carcinoma is emerging as an important complication in haemophiliacs with long-standing hepatitis C virus (HCV) infection who survived HIV infection, and because of recent advances in treating HIV, morbidity and mortality associated with chronic hepatitis C have regained emphasis amongst haemophiliacs. The development of newer interferon-based therapies provides an opportunity for modifying the natural history of HCV infection in a substantial number of haemophilic patients.
Haemophilia 2004 Oct
PMID:Hepatitis C in haemophilia: lights and shadows. 1547


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