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S Hadziyannis

Publications and source records attributed to S Hadziyannis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP)

OBJECTIVE: The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B. METHODS: This was a retrospective cohort study of 309 consecutive white patients with biopsy-proved compensated cirrhosis type B. RESULTS: During a mean follow-up of 68 months, HBsAg loss occurred in 32 patients, including 16 (8%) of 196 untreated patients (mean annual incidence 0.8%), 8 (10%) of 82 interferon (IFN) alpha-treated patients and eight patients who had been treated with other antivirals or steroids. The 5-yr probability of HBsAg loss was 4% and 16% for untreated and IFN-treated patients, respectively (p = 0.0001). Cox's regression analysis identified hepatitis B e antigen-positivity at entry as the sole independent prognostic factor for HBsAg loss. Of the 32 patients who lost HBsAg, one (3%) subsequently developed hepatocellular carcinoma (HCC) and died, whereas, among the patients who remained HBsAg-positive, 11% developed HCC and 20% had died. The probability of HCC appearance was lower (p = 0.0137) and survival was longer (p = 0.0006) in patients who cleared HBsAg compared with patients with HBsAg persistence. CONCLUSION: The incidence of HBsAg loss is about 0.8% in cirrhosis type B. Prognostic factors for clearance of HBsAg are initial HBeAg positivity and therapy with alpha interferon. Patients with cirrhosis type B, who lose HBsAg, have a low risk for liver cancer or liver-related death.

Adult↗
PubMed1997

Geographic distribution and genetic variability of hepatitis delta virus genotype I.

Three genotypes of hepatitis delta virus (HDV) have been identified, each with different geographic distributions and disease associations. To better define the geographic distribution and genetic variability of HDV genotype I, and to evaluate the extent of genome variability in populations with different patterns of HDV infection, we have analyzed the sequence of HDV RNA in the sera of 72 patients from different areas. Patients were primarily residents of the United States and areas in and around Greece, including Archangelos, Rhodes. All sequences obtained belonged to HDV genotype I, confirming the wide geographic distribution of this genotype and its predominance in Europe and the United States. In contrast to previous studies, phylogenetic analysis of this large and diverse group of sequences, along with all available previously published HDV sequences, showed no well-defined subtypes within genotype I. Low sequence diversity was found for isolates from the United States, Archangelos, Turkey, and Albania, suggesting that HDV was introduced more recently and/or from fewer sources into these areas as compared to mainland Greece, Italy, and north Africa, where sequence diversity is much greater. The low sequence diversity among isolates from Archangelos is particularly interesting in light of the unusually mild pattern of HDV disease found in this community. Comparison of nucleic acid and amino acid sequences within and among genotypes indicated both highly conserved regions as well as genotype-specific sequences that could be related to functional differences. The most distinctive of the latter was that corresponding to the C-terminal 19-20 amino acids of the long form of hepatitis delta antigen, which is highly conserved within each genotype but considerably diverged among them.

Amino Acid Sequence↗
PubMed1997

Thyroid abnormalities in chronic viral hepatitis and their relationship to interferon alfa therapy.

The prevalence of antithyroid peroxidase antibodies (ATPO) and/or of thyroid dysfunction was studied in 422 patients with chronic viral hepatitis C, B, and D. Baseline results were compared with those during and 6 months after interferon alfa (IFN-alpha) therapy. The overall prevalence of ATPO among untreated patients was 14.1%, with no significant differences between chronic hepatitis C, B, or D, as well as between males and females. However, high ATPO titers (> or = 18 IU/mL) clustered significantly among females (8.7% vs. 3.4%; P = .022), especially those with chronic hepatitis C (11.2% vs. 3.6%; P = .036). Before treatment, 3.7% of the patients had thyroid dysfunction, mostly hypothyroidism (3.5%), the latter increasing to 14.3% among patients with ATPO titers > or = 18 IU/mL. IFN-alpha treatment significantly increased overall thyroid dysfunction (9.7%; P = .001) and hypothyroidism (7.8%; P = .01), particularly among patients with high baseline ATPO (38.5%; P = .0002). Six months after stopping IFN-alpha treatment, the prevalence of thyroid dysfunction was 8.0%, still significantly higher than at baseline. By multivariate analysis, the only predictor positively associated with pre- or on-treatment hypothyroidism was the baseline titer of the ATPO antibodies (relative risk [RR], 3.0 and 3.8 per each log titer increase, respectively). In conclusion, patients with chronic viral hepatitis on IFN-alpha treatment exhibit an almost threefold increase of baseline thyroid dysfunction, persisting long after the end of therapy. High ATPO titers, clustering among females, particularly those with hepatitis C, represent the only predictor of pre- and on-treatment hypothyroidism by multivariate analysis. Patients with chronic viral hepatitis, especially females, should be tested for ATPO and thyroid function and monitored during and posttreatment for free thyroxin (FT4) and thyroid-stimulating hormone (TSH) levels.

Adolescent↗
PubMed1997

Hepatitis B virus core protein mutations are concentrated in B cell epitopes in progressive disease and in T helper cell epitopes during clinical remission.

The distribution and temporal and clinical features of amino acid substitutions of the core protein of hepatitis B (HB) virus were analyzed, using at least 2 sequential samples from 27 patients. Six patients seroconverted from HBe antigen (HBeAg)-positive to anti-HBe-positive (3 went into remission), and 21 were continuously anti-HBe positive with progressive hepatitis. Precore mutations, which terminate HBeAg translation, all appeared by the second sample. Most core mutations occurred between the first and second samples; significantly fewer occurred after the second. In seroconverters who went into remission, mutations occurred in the T helper epitope from aa 50 to 69 (P = .00045); for anti-HBe-positive patients with ongoing disease, mutations occurred in B cell epitopes (P = .0007 for aa 74-83). An ineffective anti-HBc B cell response accounts for ongoing disease and selection of mutations after seroconversion. In those who remit, mutations in the major T helper epitope allow immune escape, thus minimizing immune-mediated hepatitis.

Adult↗
PubMed1996

Hepatitis C virus 1b is the dominant genotype in HCV-related carcinogenesis: a case-control study.

In an ongoing case-control study in Athens on the etiology of hepatocellular carcinoma (HCC), an analysis was made in order to assess whether HCV genotype 1b is associated with hepatocellular carcinoma (HCC). The HCV genotype was determined in 17 HCC patients, 87 patients with chronic hepatitis C (CHC) without cirrhosis (NC-CHC) and 23 patients with CHC and cirrhosis (C-CHC). HCV genotype 1b was detected in 14/17, 16/23 and 23/87 of HCC, C-CHC and NC-CHC respectively. The age- and gender-adjusted odds ratios contrasting HCC with NC-CHC and C-CHC with NC-CHC were 8.3 and 3.8 respectively. These data strongly support the hypothesis that HCV 1b is a stronger liver carcinogen than other HCV genotypes, probably through increased HCV replication and enhanced liver cytopathicity.

Adult↗
PubMed1996

Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent.

An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

Acute Disease↗
PubMed1995

A case-control study of hepatitis B and C virus infections in the etiology of hepatocellular carcinoma.

During a 16-month period in 1991-1992, blood samples and questionnaire data were obtained from 65 incident cases of hepatocellular carcinoma (HCC) as well as from 2 control groups of hospitalized patients matched on gender and age, which included 65 metastatic liver cancer (MLC) patients and 65 patients hospitalized for eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg and antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay. The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 18.8 (8.2-43.2) for the presence of HBsAg and 7.7 (1.7-35.1) for anti-HCV. In the present hospital-based case-control study anti-HCV testing was conducted on recently collected sera, using a second-generation enzyme immunoassay with confirmation by immunoblot assay. Comparisons with previous work in a similar population demonstrated that, when second-generation anti-HCV assays are applied to sera stored for 7-15 years, confirmatory assays or a higher diagnostic cut-off point may be necessary to ensure that the testing is specific.

Adult↗
PubMed1995

Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis.

To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of HCC appearance was 6% and the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35% at 5 years. Cox's regression analysis identified three variables that independently correlated with HCC: age, serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value for the development of HCC. In conclusion, a high proportion of patients with HBsAg-positive compensated cirrhosis do not experience worsening of their condition for several years, but once decompensation occurs life expectancy is poor. European, white patients with compensated cirrhosis type B are at consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of cirrhosis and support the hypothesis that development of a tumor could be the likely consequence of long-standing hepatic disease.

Aged↗
PubMed1995

Gastroscopic findings in Mediterranean Kaposi's sarcoma (non-AIDS).

The frequency and degree of gastrointestinal involvement in patients with Mediterranean Kaposi's sarcoma (non-AIDS), a newly recognized form of Kaposi's sarcoma, is unknown. Eighty-seven patients with Mediterranean Kaposi's sarcoma proven by skin and/or nodal biopsy underwent endoscopic study of the upper gastrointestinal tract. Of these, 71 (81.6%) had gastrointestinal lesions. All these patients had lesions in the stomach. Additional lesions were detected in the esophagus in 19 patients and in the proximal duodenum in 8 patients, whereas additional lesions in both the esophagus and duodenum were identified in 2 patients. The lesions were classified into 4 types according to their size, shape, and color. Most types of lesions showed characteristic discoloration, but lesions with the appearance and color of normal mucosa that histologically were shown to be Kaposi's sarcoma were also identified. The high prevalence of gastrointestinal involvement in patients with Mediterranean Kaposi's sarcoma (non-AIDS) suggests that an endoscopic examination of the upper gastrointestinal tract may be useful in non-AIDS-related forms of Kaposi's sarcoma.

Adult↗
PubMed1995

Hepatitis B e antigen negative chronic active hepatitis: hepatitis B virus core mutations occur predominantly in known antigenic determinants.

In chronic hepatitis B virus (HBV) infection seroconversion from hepatitis B e antigen (HBeAg) to hepatitis B e antibody (HBeAb) may be followed either by remission of the disease with low-level viraemia, or by continuing inflammation with high-level viraemia. In both situations the virus may acquire a mutation in the precore sequence which prevents it from encoding HBeAg. We now show that the number of amino acid substitutions in the HBV core is low in viral sequences from patients with HBeAg positive chronic liver disease and HBeAg negative HBeAb positive patients in remission, but the frequency of substitutions is high in HBeAg, negative HBeAb positive patients with active liver disease. Furthermore we show that these substitutions cluster in the promiscuous CD4+ T-helper-cell epitope and in HBV core/e antibody binding determinants, but are not found in regions recognized by major histocompatability complex (MHC) restricted cytotoxic T lymphocytes. Sequential viral sequences from patients before and after HBeAg/HbeAb seroconversion shows that core mutations arise either at the same time or after the precore stop mutation which prevents the virus from encoding HBeAg. These results are consistent with the hypothesis that after clearance of HBeAg, mutations in regions of the virus recognized by CD4+ helper T cells and B cells allow persistence of the HBe negative virus in HBeAb positive patients with viraemia and active hepatitis.

CD4-Positive T-Lymphocytes↗
PubMed1995

Fulminant hepatitis associated with hepatitis B virus e antigen-negative infection: importance of host factors.

The precore stop-codon variant of hepatitis B virus (HBV) has been implicated in fulminant hepatitis. The precore/core regions of such variants from two sets of patients with interpartner transmission resulting in fulminant hepatitis in the contact, were sequenced to establish whether further sequence variations in the core region are specifically associated with the fulminant disease. In both sets of patients, there was sequence diversity of the precore/core region from the wild type, leading to numerous amino acid substitutions in the core region. Between the infecting source and the contact, there was only one amino acid change in one set of patients and none in the other. In addition, in the second set of patients, serum samples from four different time points were investigated. Sequence data showed no variation in each patient at the nucleotide level in the core region, even in the case of the source, who was followed for 3 years. In this same pair of subjects, the remainder of the genome was sequenced and was identical at the nucleotide level. Therefore, it appears that, at least in some cases of fulminant hepatitis caused by infection with the precore variant, the nucleotide sequence of the patient with fulminant hepatitis is identical to that observed in the asymptomatic source of infection. These data indicate that the severity and outcome of infection in such cases are unrelated to any additional variation in the entire HBV genome, and that the changed clinical picture is dependent on host factors, possibly the HLA environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Optic tract neuropathy complicating low-dose interferon treatment.

Optic neuritis occurred in three of our patients receiving treatment with alpha interferon-2b (Intron-A; 3MU thrice weekly) for chronic hepatitis. The complication appeared within, 1, 9 1/2 and 10 months of treatment, respectively. In all cases, blurred vision was the initial complaint and subsequent electrophysiologic investigation confirmed the presence of optic tract neuropathy. The patients had no other neurologic signs. Computerized tomography and magnetic resonance image of the brain were not remarkable. Psychiatric symptoms, in the form of an interferon-associated depressive reaction, were present in two of them; in one case, it was severe enough to require immediate discontinuation of treatment. In two patients the visual symptoms resolved and the parameters of neurophysiologic testing returned to normal within 1 month after stopping interferon. In one case, however, residual optic tract impairment associated with a unilateral central scotoma and a substantial decrease of visual acuity was present 2 years later, despite a course of methylprednizolone. In this patient the interferon treatment was continued for 3 months despite the visual symptoms, and he later received two additional interferon courses because of relapses of hepatitis. We conclude that clinically evident optic tract neuropathy may complicate interferon administration. Candidates for interferon treatment may need routine examination of optic fields and visual evoked potentials, before and during administration of the drug to avoid possibly permanent visual sequelae.

Adult↗
PubMed1994

Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. The Investigators of the European Concerted Action on Viral Hepatitis (EUROHEP).

A multicenter longitudinal study was performed to assess the survival of hepatitis B surface antigen positive compensated cirrhosis, primarily in relation to hepatitis B virus replication and hepatitis delta virus infection, and to construct a prognostic index based on entry characteristics. This cohort study involved nine university medical centers in Europe. Three hundred and sixty-six Caucasian HBsAg positive patients with cirrhosis who had never had clinical manifestations of hepatic decompensation were enrolled and followed for a mean period of 72 months (6 to 202 months). Inclusion criteria were biopsy-proven cirrhosis, information on serum hepatitis B e antigen and antibody to hepatitis D virus at the time of diagnosis and absence of complications of cirrhosis. At entry 35% of the patients were HBeAg positive, 48% of the patients tested were HBV-DNA positive and 20% anti-HDV positive. Death occurred in 84 (23%) patients, mainly due to liver failure (45 cases) or hepatocellular carcinoma (23 cases). The cumulative probability of survival was 84% and 68% at 5 and 10 years, respectively. Cox's regression analysis identified six variables that independently correlated with survival: age, albumin, platelets, splenomegaly, bilirubin and HBeAg positivity at time of diagnosis. According to the contribution of each of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. No difference in survival of hepatitis D virus infected and uninfected patients was observed. Termination of hepatitis B virus replication and/or biochemical remission during follow up correlated with a highly significant better survival. These data show that in compensated cirrhosis B, hepatitis B virus replication, age and indirect indicators of poor hepatic reserve and established portal hypertension significantly worsen the clinical course of the disease, whereas hepatitis D virus infection does not influence the prognosis. The highly significant improvement in life expectancy following cessation of hepatitis B virus replication and biochemical remission favors antiviral therapy in those patients with a guarded prognosis, as estimated by a prognostic index.

Adult↗
PubMed1993

Viral hepatitis management. Standards for the future. Case studies.

These four case studies were presented by Professor Sheila Sherlock to a panel of four expert hepatologists and a mixed audience of specialists. The response of the audience to a number of questions was monitored using an interactive key pad system. This response is presented in the form of bar graphs and is accompanied by comments from the expert panel.

Adult↗
PubMed1992

Association between hepatitis C virus and hepatocellular carcinoma using assays based on structural and nonstructural hepatitis C virus peptides.

Stored sera from 181 Greek patients with hepatocellular carcinoma (HCC), 35 patients with metastatic liver cancer, and 416 hospital controls with diagnoses other than malignant neoplasm or liver disease were examined with first and second generation hepatitis C virus (HCV) enzyme immunoassays as well as with five HCV supplemental assays based on structural and nonstructural HCV peptides. Second generation HCV enzyme immunoassays were more sensitive than first generation assays. However, both assays had suboptimal specificity using the standard reactivity criterion (absorbance of sample to cutoff greater than or equal to 1.0). Specificity was improved by centrifugation and by using a sample's optical density to cutoff ratio greater than or equal to 3.0 or supplemental assays; in this instance the prevalence of antibodies to HCV was 13.3% (24 of 181), 0 (0 of 35), and 1.4% (6 of 416) in HCC, metastatic liver cancer, and hospital controls, respectively. A similar estimation of prevalence of antibody to HCV in HCC (12.5% or 4 of 32) was obtained when the recombinant immunoblot assay, second generation, was used to screen a random sample of HCC patients. The relative risk linking HCV to HCC was estimated as 10.4 (95% confidence interval, 4.2-26.0; P less than 0.0001). These data suggest that the prevalence of antibodies to HCV in HCC using stored sera has been previously overestimated even though the evidence of a causal association of HCV with HCC persists.

Carcinoma, Hepatocellular↗