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Biomedical subjects

N N Zein

Publications and source records attributed to N N Zein.

At least 19 recordsLinked to original sources
PubMed2006

Hepatitis B virus (HBV) reactivation with immunosuppressive therapy in rheumatic diseases: assessment and preventive strategies.

Understanding of the natural history and basic biology of hepatitis B virus (HBV) has increased greatly in recent years. In view of this, the following are reviewed here: (a) recent advances in HBV biology pertinent to the rheumatic disease population; (b) the risks of HBV reactivation in patients with rheumatic disease undergoing immunosuppression; and (c) potential strategies to manage these risks.

Antirheumatic Agents↗
PubMed2002

Interleukin-2 liposomes for primary immune deficiency using the aerosol route.

This is the first report of aerosol interleukin 2 (IL-2) liposome administration to individuals with immune deficiency. Parenteral IL-2 therapy has shown beneficial effects in some patients with cancer, common variable immunodeficiency (CVID), and human immunodeficiency virus (HIV) but is problematic because of side effects including fever and malaise as well as local swelling (delayed type hypersensitivity like reaction) after each subcutaneous IL-2 injection. Provision of an IL-2:human albumin liposome formulation via the aerosol route had few side effects in a recent clinical trial in cancer patients. Details of good manufacturing practice (GMP) synthesis and analysis of IL-2 liposomes (N= 6 lots) made without albumin carrier protein and placebo liposomes (three lots) are presented. After centrifugation, IL-2 was closely associated with the liposome pellet (99%). Mean diameter of liposomes was 1.1 microm. Patient acceptance, safety, toxicity, and immune effects of IL-2 liposomes were studied in individuals with primary immune deficiency (N = 15) and subsequently, a larger cohort of patients with hepatitis C. Experience in the immune deficient patients is the subject of this report. Placebo liposomes (12 weeks) and IL-2 liposomes (12 weeks) were provided using a nebulizer. Aerosol placebo liposomes and IL-2 liposomes were well tolerated. No changes in chest X-ray or pulmonary function were seen. Since biologic activity of aerosol IL-2 liposomes has been seen in viral disease (hepatitis C), additional studies of aerosol IL-2 liposomes in individuals with hepatitis C and HIV are planned.

Administration, Inhalation↗
PubMed2001

Safety and efficacy of hepatitis A vaccination in liver transplantation recipients.

OBJECTIVE: Vaccination against hepatitis A (HAV) has been shown to be safe and effective in healthy subjects and in patients with chronic liver disease (CLD). The safety and efficacy of HAV vaccines in liver transplant (OLT) recipients have not been established. The objective of this study is to assess the safety and efficacy of inactivated hepatitis A vaccine in OLT recipients. METHODS: Thirty-seven HAV seronegative OLT recipients were enrolled. Patients received two doses of vaccine 6 months apart. Postvaccination IgG anti-HAV were determined at 1, 6, and 7 months after the first vaccine dose. Side effects were monitored for 3 days after each vaccination shot. An unvaccinated control group (45 patients) was followed for evidence of seroconversion. Seroconversion rate was also compared with those reported in healthy patients and in patients with chronic liver disease. RESULTS: Testing was available for all the cases at 1 month, and for 26 and 23 patients at 6 and 7 months, respectively. Only 3 of 37 patients (8%) had seroconversion at 1 month. At 6- and 7-month time points, 5 of 26 (19%) and 6 of the 23 (26%) patients had seroconversion, respectively. Vaccine responders had higher total white blood cell count and lymphocyte count and were further out from transplant compared with nonresponders. None of the unvaccinated patients had seroconversion over the follow-up time. Seroconversion rates in OLT recipients were significantly lower than that reported in healthy individuals (P=0.001) or in pre-OLT patients with CLD (P=0.001). All patients tolerated the vaccine well. CONCLUSIONS: HAV vaccination is safe in OLT recipient. Efficacy of HAV vaccination in OLT recipients, as measured by a commercially available enzyme immunoassay, is low and alternative strategies should be developed to improve response rate.

Adult↗
PubMed2001

Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease.

The aims of this study are to assess the efficacy of hepatitis B virus (HBV) vaccination using an accelerated schedule and double dose of recombinant vaccine in liver transplant recipients and identify factors associated with seroconversion and persistence of antibody to hepatitis B surface antigen (anti-HBs). Three hundred fifty-six patients were enrolled. Exclusion criteria were previous HBV infection, fulminant liver failure, or less than 2 years of follow-up after orthotopic liver transplantation (OLT). The vaccination schedule was 0, 2 weeks, 4 weeks, and 6 months using double-dose recombinant vaccine. Seroconversion was evaluated prospectively by measuring anti-HBs on the day of OLT and 1 and 2 years after OLT. Quantitative analyses of anti-HBs were performed retrospectively on stored sera. Geometric mean concentrations (GMCs) were calculated using a standard formula. All patients completed the full vaccination schedule, and 129 patients (36%) completed the schedule before OLT. The overall prevalence of anti-HBs was 128 of 356 pre-OLT samples (36%) compared with 41 of 353 (11.6%) and 26 of 325 post-OLT samples (8%) 1 and 2 years after OLT, respectively (both P =.001). The pre-OLT GMC was 86.7 compared with 0.32 and 0.33 at 1 and 2 years after OLT, respectively (P =.001). Patients with high titers of anti-HBs before OLT were more likely to have persistence of antibodies 1 or 2 years after OLT. Younger age (P =.02), low Child-Pugh score (P =.02), underlying chronic hepatitis C (P=.03), and specific host HLA subtypes were most strongly associated with seroconversion and/or persistence of anti-HBs. Thus, (1) seroconversion before or after OLT using double-dose accelerated-schedule vaccination against HBV is low, (2) there is a rapid, significant decrease in antibody titer after OLT, (3) pre-OLT anti-HBs titer potentially may be useful in predicting persistence of protective antibodies after OLT, and (4) several factors (age, genetic predisposition, severity of liver disease, and underlying liver disease) may have a role in poor vaccine responsiveness.

Adolescent↗
PubMed2001

Experimental and emerging therapies for chronic hepatitis C virus infection.

Hepatitis C virus infection is prevalent throughout the world and is associated with substantial morbidity, mortality and health economic burden. No effective preventative measure, including vaccination, is currently available. Incremental and substantial progress in the rate of viral eradication using interferon-based therapies has been made over the past decade. The most recent advance has been related to the development of a pegylated form of IFN-alpha by two independent pharmaceutical companies. Pegylation of IFN-alpha appears to prolong its half-life, allowing for less frequent dosing. Reports have suggested that pegylated interferons are also associated with better efficacy for viral eradication in patients with hepatitis C virus. Slower progress also has been made in developing non-interferon-based therapeutic agents against hepatitis C virus, including protease inhibitors, helicase inhibitors, ribozymes, antisense therapies, cytokine-based therapies and T-cell-based therapeutic vaccines.

Animals↗
PubMed2001

Clostridium difficile-associated diarrhea and colitis.

Clostridium difficile is a spore-forming toxigenic bacterium that causes diarrhea and colitis, typically after the use of broad-spectrum antibiotics. The clinical presentation ranges from self-limited diarrhea to fulminant colitis and toxic megacolon. The incidence of this disease is increasing, resulting in major medical and economic consequences. Although most cases respond quickly to medical treatment, C difficile colitis may be serious, especially if diagnosis and treatment are delayed. Recurrent disease represents a particularly challenging problem. Prevention is best accomplished by limiting the use of broad-spectrum antibiotics and following good hygienic techniques and universal precautions to limit the transmission of bacteria. A high index of suspicion results in early diagnosis and treatment and potentially reduces the incidence of complications.

Adult↗
PubMed2001

Advances in the molecular diagnosis of hepatitis C and their clinical implications.

Serologic assays for diagnosis of hepatitis C infection may yield indeterminate results despite improvements in sensitivity and specificity through second- and third-generation assays. Direct detection of hepatitis C virus (HCV) RNA based on qualitative reverse transcription-polymerase chain reaction or transcription-mediated amplification allows diagnosis in the early stages of acute infection and in patients unable to mount an antibody response. Quantitative HCV RNA assays are useful for selecting appropriate antiviral therapies, but until recently they have lacked comparability between tests. More sensitive qualitative assays should be used for determining duration of treatment or recognizing a sustained virologic response to therapy. Hepatitis C virus genotyping can be performed from a limited sequence analysis of the viral genome by using various techniques. Although newer genotyping methods are relatively practicable and are satisfactory for the discrimination of the majority of genotypes, discrimination between subtypes can be challenging. Serologic typing of HCV lacks sensitivity and specificity compared with molecular-based techniques. Recent advances in serologic assays and nucleic acid detection techniques allow physicians to make accurate diagnoses, and these assays serve as important tools in treatment planning.

DNA, Viral↗
PubMed2000

Hepatitis A antibodies in liver transplant recipients: evidence for loss of immunity posttransplantation.

Liver transplant recipients frequently have chronic liver diseases and should be considered for vaccination against hepatitis A virus (HAV). However, persistence of protective antibodies after orthotopic liver transplantation (OLT) has not been shown in this population, which may have implications for future vaccine recommendations. We evaluated the prevalence and epidemiological significance of immunoglobulin G (IgG) antibody to HAV (anti-HAV) in a nonvaccinated population before OLT (immunity from previous exposure) and determined the persistence of IgG anti-HAV at 1 and 2 years after OLT. One hundred consecutive patients were identified who underwent OLT and had at least 2 years of follow-up post-OLT. They were not vaccinated against HAV infection at any time. Clinical data were summarized from medical records, and stored sera were tested for IgG anti-HAV before OLT and at 1 and 2 years after OLT by a commercially available enzyme immunoassay. Of 100 patients, 24 had IgG anti-HAV before OLT. No epidemiological differences were noted between those with or without detectable IgG anti-HAV before OLT. Among patients with detectable IgG anti-HAV before OLT, 4 of 22 patients (18%) and 7 of 24 patients (29%) became negative for IgG anti-HAV at 1 and 2 years post-OLT, respectively. None of the patients with undetectable IgG anti-HAV before OLT became positive at any time. Most of our patients with end-stage liver disease had no serological evidence for immunity against HAV. A significant proportion of patients with detectable protective antibodies before OLT lost their antibodies at 2 years after OLT.

Adolescent↗
PubMed2000

What do we need to know about non-A-to-E viral hepatitis?

The list of potential hepatotrophic viruses continues to grow, with the recent discovery of the GB virus-C, the TT virus, and the SEN virus. Prevalence rates of the GB virus-C have ranged from 1.2% to 13% among healthy blood donors from all over the world. Higher prevalence rates have been reported among intravenous drug users. Similarly, the TT virus has a global distribution. However, in spite of numerous reports of the presence of both of these viruses in various kinds of liver diseases, definite evidence linking it to a specific disease or illness is lacking. The SEN virus is thought to be a novel viral agent that may be linked to cryptogenic chronic hepatitis, but data are awaited.

Hepatitis Viruses↗
PubMed2000

Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease.

BACKGROUND/AIMS: The aims were to study: 1) the prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic liver disease, 2) viral and host immunogenetic factors that may predispose to diabetes, and 3) liver transplantation outcome in patients with or without diabetes. METHODS: Fasting blood glucose values of patients who underwent liver transplantation because of hepatitis C-related cirrhosis (73 patients) were compared with those of patients with cirrhosis due to cholestatic (78 patients) or alcoholic liver disease (53 patients) and to a general population. Data on diabetes prevalence in a population without liver cirrhosis was based on the prevalence of diabetes in Olmsted County, Minnesota, residents. HLA was determined using serologic assays. Hepatitis C virus genotypes were determined with polymerase chain reaction amplification and direct sequencing. Hepatitis G RNA was detected with polymerase chain reaction. Liver transplantation outcome in patients with or without diabetes was determined with rejection, retransplantation, or death at 1 year after transplantation as end points. RESULTS: Of 64 patients with hepatitis C alone, 16 (25%) had diabetes before transplantation compared with 1 of 78 (1.3%) with cholestatic liver disease (p= 0.0001) and 10 of 53 (19%) with alcoholic liver disease (p=0.36). Nine patients had hepatitis C plus cholestatic liver disease; one of these (11%) had diabetes. The prevalence of diabetes in patients with cholestatic liver cirrhosis was not different from that of the general population. The frequency of hepatitis G virus coinfection, HLA-DR3, or HLA-DR4 in hepatitis C and diabetes was not different from that of hepatitis C alone. The distribution of hepatitis C virus genotype was similar in those with and those without diabetes. Diabetes was not associated with increased risk of rejection, retransplantation, or death at 1 year after transplantation, and had no impact on overall survival after transplantation. CONCLUSIONS: 1) The risk of diabetes is not increased in patients with liver cirrhosis due to cholestatic liver disease but is in patients with liver cirrhosis due to hepatitis C or alcoholic liver disease; 2) cofactors (age, sex, body mass index, hepatitis G virus coinfection, hepatitis C virus genotype, or HLA-DR3/DR4) did not explain the increased risk of diabetes in patients with hepatitis C; 3) diabetes before liver transplantation did not change the outcome at 1 year after transplantation or survival.

Adult↗
PubMed2000

Nature and behavior of serum cytokines in type 1 autoimmune hepatitis.

To assess the relationship between serum cytokine behavior and treatment outcome in type 1 autoimmune hepatitis, serum levels of interferon-gamma, interleukin-2, interleukin-4, and interleukin-10 were measured by enzyme immunoassay in 43 patients and 20 normal subjects. Serum samples were similarly tested in 38 patients after corticosteroid treatment. Serum levels of interleukin-2 and interleukin-4 were significantly lower in patients than in normal subjects. Interleukin-2 was the least common cytokine detected before (3%), during (0%), or after treatment (0%). Serum levels of interleukin-10 at presentation did not differ from those of normal subjects but they did decrease during therapy, especially in patients who entered remission. Changes in these levels, however, did not always parallel treatment outcome or histological activity. We conclude that serum levels of interleukin-2 and interleukin-4 are lower than normal in type 1 autoimmune hepatitis. Serum concentrations of interleukin-10 diminish during corticosteroid therapy but changes do not closely reflect outcome. The rarity of interleukin-2 in serum may be a distinguishing feature.

Adolescent↗
PubMed2000

Prevalence of TT virus infection in blood donors with elevated ALT in the absence of known hepatitis markers.

OBJECTIVE: Recently a novel DNA virus (TT virus) has been identified in Japan and shown to be associated with elevated aminotransferase levels after blood transfusion. The exact role of TTV in the pathogenesis of liver disease is yet to be established. Our aim was to determine the prevalence and role of TTV in the pathogenesis of elevated transaminases in healthy blood donors in the absence of markers for viral hepatitis A-C. METHODS: Stored sera were collected from 99 healthy blood donors with elevated alanine amino transferase (ALT) values that were discovered at the time of blood donation. A total of 146 samples were obtained from healthy donors with normal ALT values who were used as controls. None of the patients or controls had a history of blood transfusion or had clinical signs of acute or chronic hepatitis. Serological markers for hepatitis A, hepatitis B, and hepatitis C viruses were negative. TTV DNA was amplified and detected using polymerase chain reaction followed by gel electrophoresis. RESULTS: Five of 99 (5%) samples obtained from donors with elevated ALT had TTV DNA detected by PCR, as compared to one of 146 (0.7%) of those with normal ALT (p = 0.006). Among those with elevated ALT, mean ALT values in patients with TTV (296 +/- 305 U/L) were higher than in patients without TTV (95 +/- 37 U/L), but the difference was not statistically significant (p = 0.08). The two samples with highest ALT values (both >450 U/L) were among the five samples with detectable TTV DNA in serum. CONCLUSIONS: Although TTV is not likely to explain the majority of elevated ALT cases in otherwise healthy blood donors, TTV infection may potentially be associated with some cases. Based on these findings, we propose that the role of TTV in the pathogenesis of acute and chronic liver diseases merits further investigation.

Alanine Transaminase↗
PubMed2000

Clinical significance of hepatitis C virus genotypes.

On the basis of phylogenetic analysis of nucleotide sequences, multiple genotypes and subtypes of hepatitis C virus (HCV) have been identified. Characterization of these genetic groups is likely to facilitate and contribute to the development of an effective vaccine against infection with HCV. Differences among HCV genotypes in geographic distributions have provided investigators with an epidemiologic marker that can be used to trace the source of HCV infection in a given population. HCV genotype 1 may represent a more aggressive strain and one that is less likely to respond to interferon treatment than HCV genotype 2 or 3. However, these observations require confirmation before HCV genotyping can be used in clinical settings.

Antiviral Agents↗