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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
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↗
PubMed1999

No evidence of hepatitis G virus in fulminant hepatic failure in children.

BACKGROUND: The cause of fulminant hepatic failure in children remains unknown, but a viral origin has been suspected in most cases. The recently discovered blood-borne virus, hepatitis G, has been suggested as a possible causative agent. METHOD: Six consecutive children who underwent liver transplantation for fulminant hepatic failure were studied. The children were tested for hepatitis G virus antibodies and hepatitis G virus RNA by polymerase chain reaction after excluding other causes of fulminant hepatic failure. RESULTS: No evidence of hepatitis G virus infection was found in these patients. CONCLUSION: Hepatitis G virus is unlikely to be a common cause of fulminant hepatic failure in pediatric patients from the upper midwestern United States.

Adolescent↗
PubMed1999

Clinical significance of TT virus infection in patients with chronic hepatitis C.

OBJECTIVE: The TT virus (TTV) is a novel DNA virus that has recently been identified. The clinical significance of TTV infection in patients with chronic hepatitis C has not been determined. The aim of this study was to determine the prevalence and possible role of TTV in a well characterized population with chronic hepatitis C infection. METHODS: Ninety patients with chronic HCV and known time of HCV acquisition were selected from approximately 250 patients followed at our institution. Characteristics including age, sex, histology, and length of disease were recorded. Direct sequencing of the NS5 region was used for HCV genotyping. TTV DNA detection was based on PCR. RESULTS: TTV infection was present in 24 of 90 (27%) HCV patients. Patients were divided into four groups based on stage of disease; chronic hepatitis (CH, 29 patients), compensated cirrhosis (CC, 17 patients), decompensated cirrhosis (DC, 28 patients), and hepatocellular carcinoma (HCC, 16 patients). TTV was present in 2/29 (7%), 2/17 (12%), 11/28 (39%), and 9/16 (56%) in those with CAH, CC, DC, and HCC respectively. TTV was significantly more prevalent among those with advanced disease (DC and HCC) compared to those with stable disease (CH and CC; p = 0.001). Mean age, sex, and the time from exposure to HCV to development of complications were similar in TTV-positive and -negative patients. TTV infection was more common in patients infected with HCV genotype 1b. Univariate analysis showed that length of HCV infection, HCV genotype 1b, and TTV infection were important in predicting the stage of liver disease in HCV patients. However, after adjusting for length of HCV infection, TTV but not HCV genotype was important in predicting the stage of liver disease. CONCLUSIONS: We conclude that 1) TTV infection is common in patients with chronic HCV; 2) TTV infection is more prevalent among patients with advanced HCV-associated liver disease (DC and HCC) than in those with stable disease (CH and CC); and 3) TTV infection is more common in patients with HCV genotype 1b but is independent from genotype in predicting the stage of HCV-associated liver disease.

Base Sequence↗
PubMed1999

Viral genotypes as determinants of autoimmune expression in chronic hepatitis C.

OBJECTIVE: To correlate viral genotypes with the immune manifestations of chronic hepatitis C and evaluate the effect of immune features on disease expression and response to antiviral treatment. DESIGN: We undertook a retrospective analysis of 67 patients with chronic hepatitis C. MATERIAL AND METHODS: Patients were selected for study if they had been screened for autoantibodies and concurrent immune diseases and if viral genotyping had been performed or was possible. Concurrent immune manifestations and responses to interferon therapy were determined. RESULTS: Of the 67 patients, 18 (27%) had one or more immune features. Immune manifestations occurred as commonly in patients with genotype 1 as in those with other genotypes (30% versus 14%; P = 0.3). Concurrent immune features did not distinguish patients, and responses to interferon therapy were similar between patients with and those without immune manifestations. None of the 14 patients with concurrent immune diseases or high-titer autoantibodies (serum titers, 1:320 or more) entered remission during interferon treatment. In contrast, 6 of 53 patients without concurrent immune diseases and no or low-titer autoantibodies had treatment-related remission. These differences, however, were not statistically significant (0% versus 11%; P = 0.3). CONCLUSION: Autoantibodies and concurrent immune diseases are not associated with a particular viral genotype, clinical profile, or treatment outcome. Larger studies are necessary for complete assessment of the influence of prominent immune manifestations on treatment response.

Adult↗
PubMed1998

Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.

Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in bone mass during adult life. Despite the rarity of HCAO, understanding the mediator(s) of the skeletal disease is of great interest. The IGFs-I and -II have potent anabolic effects on bone, and alterations in the IGFs and/or IGF-binding proteins (IGFBPs) could be responsible for the increase in bone formation in this disorder. Thus, we assayed sera from seven cases of HCAO for IGF-I, IGF-II, IGF-IIE (an IGF-II precursor), and IGFBPs. The distribution of the serum IGFs and IGFBPs between their ternary ( approximately 150 kD) and binary (approximately 50 kD) complexes was also determined to assess IGF bioavailability. HCAO patients had normal serum levels of IGF-I and -II, but had markedly elevated levels of IGF-IIE. Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients. IGF-I and -II in sera from patients with HCAO were carried, as in the case of sera from control subjects, bound to IGFBP-3 in the approximately 150-kD complex, which is retained in the circulation. However, IGF-IIE was predominantly in the approximately 50-kD complex in association with IGFBP-2; this complex can cross the capillary barrier and access target tissues. In vitro, we found that IGF-II enhanced by over threefold IGFBP-2 binding to extracellular matrix produced by human osteoblasts and that in an extracellular matrix-rich environment, the IGF-II/IGFBP-2 complex was as effective as IGF-II alone in stimulating human osteoblast proliferation. Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function. Our findings in HCAO suggest a possible means to increase bone mass in patients with osteoporosis.

Alkaline Phosphatase↗
PubMed1998

Gastroesophageal reflux in infants and children.

Gastroesophageal reflux is a common pediatric complaint and a frequent reason for pediatric patients to be referred to a gastroenterologist. The pathophysiology and clinical manifestations of this disorder differ according to patient age. The diagnosis is suggested by the history and can be confirmed by a pH probe. In the appropriate clinical setting, anatomic obstruction may need to be ruled out by contrast study. Endoscopy is used to assess associated complications, including esophagitis, esophageal strictures, Barrett's transformation, and failure to thrive. Other complications are controversial, including pulmonary disease, apnea, and sudden infant death syndrome. Treatment depends on the severity of disease. Conservative therapy includes behavorial modifications, prokinetic agents, and H2 antagonists. Proton pump inhibitors are generally reserved for refractory esophagitis. Surgical treatment may be necessary for gastroesophageal reflux resistant to medical management or for severe complications. Gastroesophageal reflux beyond infancy tends to be chronic; therefore, lifelong behavioral modifications or repeated courses of medical therapy may be necessary. An algorithm for the suggested diagnostic approach to gastroesophageal reflux is presented herein.

Algorithms↗
PubMed1998

GB virus-C infection in type 1 autoimmune hepatitis.

OBJECTIVE: To assess the frequency and significance of GB virus-C infection in type 1 autoimmune hepatitis. MATERIAL AND METHODS: Serum specimens from 94 patients with type 1 autoimmune hepatitis were tested for GB virus-C RNA by reverse transcription and polymerase chain reaction. Serum samples from 50 normal subjects were also assessed. RESULTS: Three of the 94 specimens from patients with autoimmune hepatitis were positive for GB virus-C RNA in comparison with none of the 50 control samples (3% versus 0%; P = 0.5). Two patients were seropositive after variceal hemorrhage and blood transfusion, including one patient who clearly acquired the infection in this fashion. One patient had no epidemiologic basis for his seropositivity. Viremia was prolonged in all infected patients (mean duration, 69 +/- 23 months; range, 36 to 113); however, no clinical features suggested a concurrent viral infection, and mortality was similar to that among the uninfected counterparts (33% versus 8%; P = 0.2). Liver transplantation was more common in the infected patients (67% versus 9%; P = 0.03), but the duration of disease was also longer in these patients (277 +/- 29 months versus 106 +/- 9 months; P = 0.0008). Clinical features and immediate responses to corticosteroid therapy were similar in both groups. CONCLUSION: GB virus-C RNA is found infrequently in type 1 autoimmune hepatitis, and GB virus-C is unlikely to be an important etiologic agent or prognostic determinant.

Biopsy, Needle↗