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Biomedical subjects

S Hadziyannis

Publications and source records attributed to S Hadziyannis.

At least 19 recordsLinked to original sources
PubMed2006

Predicting response to peginterferon alpha-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B.

OBJECTIVE: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon alpha-2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated. METHODS: Multivariate analyses were performed using available data from 518 patients treated with peginterferon alpha-2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20,000 copies/ml. RESULTS: In logistic regression analyses across all treatment arms, peginterferon alpha-2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon alpha-2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon alpha-2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon alpha-2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon alpha-2a with or without lamivudine therapy. CONCLUSIONS: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon alpha-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alpha-2a with or without lamivudine.

Adult↗
PubMed2005

Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma.

To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the p53 oncoprotein in hepatitis B virus (HBV)/HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma (HCC). We studied needle liver biopsies from 107 patients with cirrhosis and no HCC (52 HBV, 55 HCV) who had been assessed for protocol studies, and 57 cirrhotic patients with HCC (40 HBV, 17 HCV). We evaluated small and large cell dysplastic changes along with the expression of Ki-67 and p53 by immunohistochemistry. The labelling index (LI) was defined as the proportion (%) of positive-stained nuclei of the 500 measured. Large and small cell dysplastic changes were observed in 12 and 9% of specimens respectively. Only small cell changes were associated with Ki-67 expression. Ki-67 LI was 5.50 +/- 5.7 in cirrhosis (13.90 +/- 3.84 in those with small cell dysplastic changes vs 4.64 +/- 4.98 in those without, P < 0.01), 10.2 +/- 5.95 in cirrhosis with HCC (P < 0.05) and 18.56 +/- 10 in HCC (P < 0.01). Neither the presence of small cell dysplastic changes nor the expression of Ki-67 was related to severity or aetiology of cirrhosis. Expression of p53 was observed in 30% of the non-tumorous and in 53% of the neoplastic tissue obtained from patients with HCC, with no differences between HCV and HBV. Ki-67 and p53 expression was associated with the tumour grade (P < 0.001). Our observations clearly demonstrate the association between the proliferation activity and the morphological changes in the cirrhotic liver from the non-dysplastic to dysplastic lesion to HCC. They also support the hypothesis that p53 alterations are a rather late event in carcinogenesis and related to HCC grade. And finally, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the chronic viral infection.

Adult↗
PubMed2003

Changing relative roles of hepatitis B and C viruses in the aetiology of hepatocellular carcinoma in Greece. Epidemiological and clinical observations.

Chronic infection with hepatitis B virus (HBV) has been reported in two-thirds of cases of hepatocellular carcinoma (HCC) in Greece from 1973 to 1995, while chronic hepatitis C virus (HCV) infection in 10% of them. We studied the roles of HBV and HCV in HCC in Greece between 1996 and 2000 compared with the past, and possible differences in clinical and laboratory characteristics of HBV- and HCV-related HCC. Complete clinical and laboratory data from 306 patients with HCC, diagnosed from January 1996 to December 2000, were analyzed. Chronic HBV and HCV infection were detected in 52.3 and 21.6% of the patients, respectively. The ratio of HBV- to HCV-related HCC was 2.42. Compared with the data prior to 1996, there was a 101.8% increase in the relative frequency of HCV (P < 0.0001) and an 11.8% decrease in that of HBV (P = 0.033), with a -56.3% change in the ratio of HBV- to HCV-related HCC cases. Statistically significant differences in the male/female ratio, median age and frequency of multifocal lesions were found in HBV- vs HCV-related HCC. Although HBV still represents the major aetiological factor of HCC in Greece, its role has significantly decreased in the last 5 years, while a more significant increase has occurred in HCV-related HCC. The two aetiological types of HCC differ in Greece in demographic, epidemiological and other features.

Carcinoma, Hepatocellular↗
PubMed2003

Characterization of secreted and intracellular forms of a truncated hepatitis C virus E2 protein expressed by a recombinant herpes simplex virus.

A replication-defective herpes simplex virus type 1 (HSV-1) recombinant lacking the glycoprotein H (gH)-encoding gene and expressing a truncated form of the hepatitis C (HCV) E2 glycoprotein (E2-661) was constructed and characterized. We show here that cells infected with the HSV/HCV recombinant virus efficiently express the HCV E2-661 protein. Most importantly, cellular and secreted E2-661 protein were both readily detected by the E2-conformational mAb H53 and despite the high expression levels, only limited amounts of misfolded aggregates were detected in either the cellular or secreted fractions. Furthermore, cell-associated and secreted E2-661 protein bound to the major extracellular loop (MEL) of CD81 in a concentration-dependent manner and both were highly reactive with sera from HCV-infected patients. Finally, BALB/c mice immunized intraperitoneally with the recombinant HSV/HCV virus induced high levels of anti-E2 antibodies. Analysis of the induced immunoglobulin G (IgG) isotypes showed high levels of IgG2a while the levels of the IgG1 isotype were significantly lower, suggesting a Th1-type of response. We conclude that the HSV-1 recombinant virus represents a promising tool for production of non-aggregated, immunologically active forms of the E2-661 protein and might have potential applications in vaccine development.

Adolescent↗
PubMed2002

Expression of immunoreactive forms of the hepatitis C NS5A protein in E. coli and their use for diagnostic assays.

In this study different forms of the hepatitis C virus (HCV) NS5A protein, including a nearly full-length, an amino-terminal and a carboxy-terminal truncated form were produced in E. coli as fusion proteins with the MBP or the GST protein. The chimeric proteins were tested for their reactivity with sera from HCV infected patients by immunoblot and ELISA assays. A panel of 110 sera specimens, including 39 HCV-positive sera, 27 sera from patients with non-HCV-associated liver disease and 44 healthy individuals were analyzed for the presence of antibodies to NS5A. Twenty four (61 %) out of the 39 HCV positive sera, showed reactivity against the nearly full length NS5A, 21 (54 %) against the amino-terminal part of NS5A and 20 (51 %) against the carboxy-terminal part of the NS5A protein in immunoblot assays, suggesting that immunoreactive epitopes are present both at the carboxy- and the amino- terminal part of the protein. None of the 71 HCV-negative serum samples showed any reactivity against the NS5A antigens. With the exception of one patient, similar data were obtained with an ELISA assay based on the use of the nearly full-length NS5A antigen. The data indicate that new forms of NS5A may be potentially valuable antigens for the development of serological assays for HCV.

Adolescent↗
PubMed2002

Post-infantile giant cell hepatitis associated with autoimmune hepatitis and polyarteritis nodosa.

We report the case of a patient with corticosteroid-responsive giant cell hepatitis associated with typical manifestations and changes of polyarteritis nodosa from the kidney and central nervous system. Initially, the patient presented with transient right hemiparesis, followed by spontaneous remission without any abnormalities on computed tomography scan, magnetic resonance imaging and cerebrospinal fluid examination. A few months later he was admitted to our clinic because of icterus, peripheral oedema and abdominal distension. He was found to have clinical signs of active cirrhosis. Serological tests for hepatitis B, C and HIV virus were negative. Serum ceruloplasmin. a1-AT and ferritin levels were within normal limits. Antinuclear antibodies were positive (1: 160). Liver biopsy showed micronodular cirrhosis with many eosinophils in the portal tracts and giant hepatocytes with multiple nucleoli in the lobule. Fulfilling the diagnostic criteria for autoimmune hepatitis, he was started on treatment with prednisolone and azathioprine, resulting in both clinical and biochemical responses. Four years later he presented with severe pain at the right costovertebral angle. Ultrasonography revealed a haematoma at the right kidney, and selective angiography of the abdominal aorta, renal arteries and hepatic artery documented microaneurysms in both kidney and liver arteries. Because of severe haemorrhage, right nephrectomy was performed. Histology of kidney specimen showed characteristic lesions of polyarteritis nodosa. Several months later, while on treatment with prednisolone and cyclophosphamide, the patient experienced a fatal episode of brain haemorrhage. An association between autoimmune hepatitis, polyarteritis nodosa and postinfantile giant cell hepatitis has not been reported previously.

Adult↗
PubMed2002

Assessment of depression in patients with chronic hepatitis: effect of interferon treatment.

INTRODUCTION/AIM: Chronic viral hepatitis and its treatment with interferon (IFN) have an impact on patients' quality of life. The purpose of this study was to evaluate the degree of depression in patients with chronic viral hepatitis before and during IFN therapy. PATIENTS/METHODS: Our study group comprised 132 patients, 38 with chronic hepatitis C (26 males, 12 females), 36 with chronic hepatitis B (29 males, 7 females), and 58 individuals with no chronic disease (24 males, 34 females). Depression was assessed using the Zung Self-Rating Depression Scale and the corresponding SDS index. RESULTS: At baseline, patients with viral hepatitis and healthy controls had similar SDS indexes. During treatment, a significant increase in the SDS index was observed in both HBV and HCV patients (p < 0.001), which returned to the baseline levels after treatment. During IFN therapy, the SDS indexes were higher in HCV compared to HBV patients and women compared to men (p = 0.001 and p = 0.008, respectively), and there was a >5- fold increased frequency to develop severe depression. CONCLUSIONS: IFN-induced depression occurs more frequently in HCV than HBV patients and in women than men. Monitoring during treatment is mandatory in order to maximize treatment adherence.

Adult↗
PubMed2001

Multiple myeloma in sickle cell syndromes.

Multiple myeloma (MM) is rare among patients with sickle cell syndromes (SCS). We describe six Greek sickle cell patients aged 56 to 65 years: five haemoglobin Sbeta+thalassaemia (HbSbeta+ (thal), one sickle cell anaemia (HbSS), who developed MM (three IgGkappa, one IgGlambda, one IgAkappa, and one IgGK-IgAK (biclonal). Our HbSbeta+thal cases, represent the first reported association of this entity with MM. Generalized bleeding diathesis, stroke, grand mal seizures, bone marrow necrosis and other clinical manifestations due to hyperviscosity aggravated by sickle cell vasoocclusion were treated by plasmaphereses and exchange blood transfusions. The increase of mean survival in SCS patients due to the current medical facilities may have an impact on the incidence of MM among them, if a pathogenetic link between the two conditions exists. All our patients carried a diagnosis of cholelithiasis which may predispose to MM; two of them progressed from a monoclonal gammopathy of undetermined significance (MGUS) to MM. Further studies are needed in order to understand the relationship between SCS and MM.

Adult↗
PubMed2000

Hepatitis B and C viruses in the etiology of hepatocellular carcinoma; a study in Greece using third-generation assays.

OBJECTIVES: The purpose of this study was to describe the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of hepatocellular carcinoma (HCC). METHODS: During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of HCC from Athens, Greece, as well as from patients in two control groups, also from Athens. Controls were 272 metastatic liver cancer (MLC) patients and 360 patients hospitalized for injuries or eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays. RESULTS: The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 48.8 (30.5-78.3) for the presence of HBsAg and 23.2 (11.4-47.3) for the presence of anti-HCV. The odds ratio for concurrent infection with HBV and HCV was 46.2 (9.9-216.6) compared to infection with neither virus. CONCLUSIONS: Although HBV and HCV are both important causes of HCC in this study population the data do not suggest, neither do they conclusively refute, a super-additive interaction between the two infections in the development of this malignancy. In this population, 58% of HCC cases can be attributed to HBV, 12% to HCV, and 3% to dual infection with these viruses.

Adult↗
PubMed2000

Interferon treatment with or without oral ganciclovir in HBeAg-negative chronic hepatitis B: a randomized study.

The treatment of HBeAg-negative chronic hepatitis B with alpha interferon alone is unsatisfactory. We evaluated the efficacy of combined administration of interferon-a2a (IFN) with oral ganciclovir, a nucleoside analogue. Forty patients with hepatitis B virus (HBV)-DNA-positive/HBeAg-negative chronic hepatitis B, were randomized to receive 4.5 MU IFN thrice weekly, subcutaneously, alone or in combination with 3 g ganciclovir per os daily for 26 weeks and followed for 12 months after treatment. Mean serum HBV-DNA levels decreased by 4.0 log10 in the combination group (from 5 x 106 to 4.8 x 102 copies/ml) and by 2.2 log10 in the interferon group (from 8 x 106 to 4.8 x 104 copies/ml) by quantitative polymerase chain reaction (PCR). HBV-DNA became undetectable in 11 of 20 (55%) and in three of 20 (15%) patients in the two groups, respectively (P=0.02). The alanine aminotransferase levels became normal in all patients receiving combination therapy, compared to 75% of those in the interferon group. After cessation of therapy, HBV-DNA increased or reappeared in all patients with 85% also relapsing biochemically. One year after treatment, three patients in each group (15%) remained in sustained biochemical remission with very low serum HBV-DNA levels (median 15 700 copies/ml). We conclude that, in HBeAg-negative chronic hepatitis B, 6-month combination therapy with oral ganciclovir and IFN is associated with complete biochemical remission in all treated patients and a 4 log10 decrease in serum HBV-DNA levels. The end of treatment efficacy of this combination scheme is far super- ior to that of IFN monotherapy but sustained responses are few. Further studies are warranted to evaluate the efficacy of prolonged combination schemes with nucleoside analogues and IFN, compared to IFN monotherapy.

Administration, Oral↗
PubMed2000

Comparison between three quantitative assays in patients with chronic hepatitis C and their relevance in the prediction of response to therapy.

To compare three quantitative assays measuring viral load in patients with chronic hepatitis C and to determine their value in predicting response to interferon (IFN) therapy, we analysed serum from 896 patients from eight European Centres using QUANTIPLEXtrade mark bDNA, MONITOR AMPLICORtrade mark and SUPERQUANTtrade mark assays. Analyses were performed on the same sample. Viral genotype was assessed using INNO-LiPA HCV II kits. Intercentre variations were observed that were related to the handling of specimens not processed and stored within 6 h of blood sampling. Among sera with optimal handling, a stronger correlation was observed between bDNA and SUPERQUANT (0.806) than between bDNA and MONITOR (0.677) and between MONITOR and SUPERQUANT (0.632). These discrepancies were greatest with genotype 2 (bDNA/SUPERQUANT= 0.772; bDNA/MONITOR=0. 456; SUPERQUANT/MONITOR= 0.299). This correlation was influenced by viraemia level and was better at lower viral loads. The proportion of sera with undetectable viral load was 15% with bDNA, 9.7% with MONITOR and 7.7% with SUPERQUANT. For the three measurements, the best cut-offs of sustained response to IFN treatment were located at their detection threshold. Among patients with viral load below the detection level, a sustained response was observed in 35% tested with bDNA, 38% with MONITOR and 80% with SUPERQUANT. Hence a stronger correlation was observed between bDNA and SUPERQUANT than between either of these assays and MONITOR. SUPERQUANT was the most sensitive assay and this greater sensitivity was associated with a better predictive value of treatment response.

Antiviral Agents↗
PubMed1999

Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP).

Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-alpha) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-alpha therapy (9 million units [MU] of IFN-alpha-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-alpha compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (chi2 = 4.66, P =.031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-alpha were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3. 3%; Fisher's exact test P =.09 ). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-alpha retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-alpha treatment; these were mild and reversible on IFN-alpha discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-alpha. Thus, retreatment with IFN-alpha may be considered a therapeutic option.

Adolescent↗
PubMed1999

Systemic AL amyloidosis in Gaucher disease. A case report and review of the literature.

Chronic Gaucher disease [GD] in association with systemic AL amyloidosis is extremely rare. We describe a 46-year-old Greek male with chronic GD confirmed by low glucocerebroside activity in fibroblasts and N370S/L444P mutations at the cerebrosidase gene, who also had systemic AL amyloidosis diagnosed by bone marrow diffuse plasmacytosis, serum monoclonal IgA-lambda, severe total proteinuria with monoclonal IgA-lambda, Bence-Jones-lambda and amyloid deposits in bone marrow, liver, spleen and kidney biopsy specimens. Treatment with melphalan and prednizolon has dramatically decreased both levels of serum M-IgA and proteinuria and also improved the clinical symptoms of amyloidosis. He died from restrictive cardiac disease 30 months after the diagnosis of amyloidosis. Previously reported cases of GD in association with AL amyloidosis are reviewed.

Amyloidosis↗
PubMed1999

Overlapping syndrome of autoimmune hepatitis and primary sclerosing cholangitis associated with pyoderma gangrenosum and ulcerative colitis.

We describe the case of a 18-year-old male patient who first presented with decompensated cirrhosis, fever and generalized lymphadenopathy. He had abnormal results for liver biochemical tests, with a hepatitic-like picture and high titre of antinuclear antibodies. According to the scoring system proposed by the International Autoimmune Hepatitis Group he had 'definite' autoimmune hepatitis and responded well to immunosuppressive treatment. One year later he developed pyoderma gangrenosum which was successfully treated with cyclosporine. Two years later he experienced bloody diarrhoea as a first presentation of ulcerative colitis. At that time both the cholestatic biochemical picture and the cholangiographic appearances of the biliary tree were consistent with primary sclerosing cholangitis. Despite the addition of azathioprine and ursodeoxycholic acid to his treatment regime he developed recurrent episodes of cholangitis and intractable pruritus for which he underwent successful liver transplantation.

Adolescent↗
PubMed1998

Neurovisual impairment: a frequent complication of alpha-interferon treatment in chronic viral hepatitis.

Following our earlier observation of clinically evident optic tract neuropathy in patients receiving low-dose interferon (IFN) therapy, we prospectively evaluated 53 consecutive patients treated for chronic hepatitis B or C with a median dose of 3 MU of IFN-a2b thrice weekly. Measurements included routine ophthalmologic evaluation and recordings of visual evoked responses (VER), electroretinograms (ERG), visual acuity, and visual fields, before, at the end of IFN treatment, and at follow-up visits. Baseline P100 latencies of VERs (base-VER) were abnormally prolonged in 24 patients (32 of 106 eyes, 30.2%); age was the only significant covariate associated with increased risk for an abnormal base-VER by multiple logistic regression (relative risk [RR] 5.3 per each 5-year increase in age). In 45 patients (74 eyes) with normal baseline P100 latencies, the end-of-treatment VERs (end-VER) were significantly prolonged compared with baseline, becoming abnormal in 11 (15 of 74 eyes, 20.3%) (138.8+/-8.7 vs. 117.7+/-5.2 ms, P < .001). This subgroup had older age (59.1+/-11.0 vs. 47.5+/-15.3, P=.007) and reduced visual sensitivity compared with their own pretreatment measurements (24.5+/-1.6 vs. 23.0+/-1.2db, P=.019). Changes of end-VERs by age had a sigmoid distribution with a steep increase of values beyond the 5th decade (R2=.326, P < .001). In a logistic regression model, significant predictors of abnormal end-VERs were, patients' age (RR 5.6 per each 5-year increase), presence of hepatitis B virus (HBV) infection (RR 15.1 compared with hepatitis C virus [HCV] infection) and serum cholesterol levels above 240 mg% (RR 7.1 compared with values < 240 mg%). Subconjunctival hemorrhages were seen in 2 cases and funduscopic examination revealed cotton wool spots in one other. ERG recordings and the P100 amplitude remained unchanged. After stopping IFN, the treatment-associated neurovisual abnormalities reversed to normal in 7 patients (10 of 15 eyes) and persisted in 5 (5 of 15 eyes, 33.3%) for up to 37 (median 7.3) months observation, all patients remaining clinically asymptomatic. In conclusion, subclinical neurovisual impairment is a frequent, largely unrecognized complication of low-dose IFN therapy, and patients with chronic hepatitis B and older age appear to be most susceptible. This apparently innocuous complication is long lasting, possibly irreversible in some patients, with yet undetermined consequences on visual function.

Adult↗
PubMed1998

Impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action.

BACKGROUND/AIMS: To investigate the impact of hepatitis B (HBV) and C (HCV) infections on hepatocellular carcinoma (HCC) in Europe. METHODS: Five hundred and three patients with HCC, from six liver centers, were included. All 503 sera and 80 liver samples were tested for HBV DNA and HCV RNA by polymerase chain reaction. GBV-C/HGV RNA was also tested in 57 sera. RESULTS: HBsAg and anti-HCV were detected in 19% and 40.1% of the patients, respectively. Serum and liver HBV DNA were detected in 82% and 91% of the HBsAg positive subjects. HBV DNA was also detected in the serum and liver of 33% and 47% of HBsAg negative patients. In this group, serum HBV DNA was more prevalent in anti-HBs and/or anti-HBc patients (47.9%), compared to those without any HBV marker (25.1%). HCV RNA was detected in 89% and 7% of anti-HCV positive and negative cases, respectively, HCV 1b being the most prevalent genotype (80%). Coinfection with HBV and HCV was shown in 20.4% of patients, while only 29% had neither HBV nor HCV GBV-C/HGV RNA was detected in only 4/57 sera. CONCLUSIONS: This study offers the first large analysis of HCC in Europe, based on both serology and molecular tests. It demonstrates the major impact of HBV and HCV, but not of GBV-C/HGV, in liver carcinogenesis in Northern as well as Southern Europe. It also stresses the need to use viral genome detection in epidemiological studies when serological tests are negative.

Aged↗