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G Ballardini

Publications and source records attributed to G Ballardini.

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

Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of hepatitis C virus etiology.

In this paper we show that in viral hepatitis most Kupffer cells (KCs) are activated and express high levels of CD80, CD40, and class-II MHC molecules, thus acquiring the phenotype of professional antigen presenting cells (APCs). Activated KCs display a close contact with CD4+ T lymphocytes and form KCs-T lymphocyte clusters. Clusters are found within the sinusoids, across the sinusoid wall, and within the liver parenchyma as well, as a consequence of transendothelial migration (TEM). The positivity of activated KCs for hepatitis C virus (HCV) antigens, which likely reflects phagocytosis of infected hepatocytes, suggests that KCs-T cell clusters represent the morphological expression of the functional interaction between KCs acting as professional APCs and antigen-experienced CD4+ T lymphocytes within the liver. These phenotypic and morphological changes are distinct features of livers in chronic hepatitis patients compared with controls.

Adult↗
PubMed1998

Methotrexate therapy in refractory pediatric onset systemic lupus erythematosus.

OBJECTIVE: To evaluate the efficacy, safety, and corticosteroid sparing potential of methotrexate (MTX) in patients with pediatric onset systemic lupus erythematosus (SLE). METHODS: The medical records of 11 patients with SLE with onset before age 16 years were reviewed. Details of clinical features, previous therapy, indications for MTX, efficacy, toxicity, and corticosteroid reduction during MTX therapy were recorded. RESULTS: At the start of MTX treatment, 7 patients had nephritis, 3 malar rash, 3 arthritis, 2 skin vasculitis, and 2 thrombocytopenia. All patients were given MTX (12.5-17.0 mg/m2/week) as the sole drug therapy along with prednisone. Although many patients showed initial improvement and/or were able to reduce the prednisone dose, after 7 to 23 months 8 patients had a flare of SLE requiring increased doses of prednisone, one patient had unchanged SLE activity, and 2 patients were permanently discontinued from MTX because of toxicity. Side effects were observed in 8 (73%) patients, but only 2 (18%) discontinued MTX due to toxicity. CONCLUSION: MTX given as the sole drug therapy along with prednisone did not show a major corticosteroid sparing potential in our patients with pediatric onset SLE.

Adolescent↗
PubMed1997

Anti-neutrophil cytoplasmic antibodies in type 1 and 2 autoimmune hepatitis.

Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) have been recently defined as the most sensitive autoantibody of type 1 autoimmune hepatitis (AIH-1). Their prevalence in type 2 autoimmune hepatitis (AIH-2) has not yet been evaluated. The aim of the present study was to verify the association of pANCA with AIH-1 in an Italian series and to investigate the prevalence of the antibodies in AIH-2 and in proper control groups represented by cases of chronic hepatitis C (CH-C) with similar autoimmune features. pANCA were found in 30 of 46 (65%) AIH-1 and in 4 of 30 (13%) ANA/smooth muscle antibody (SMA) positive CH-C (P = .0000006). Nineteen AIH-2, 29 liver kidney microsomal antibody type 1/liver cytosol antibody type 1 (LKM1/LC1) positive CH-C cases and 50 healthy controls were all negative. In AIH-1, pANCA were significantly (P = .009) more frequent in males (8 of 9, 89%) than in females (22 of 37, 59%). All pANCA positive sera showed SMA of the antiactin type. The present data confirm that pANCA, although less prevalent in our series than in other reports, do associate with AIH-1 also in the Mediterranean area and show that it can identify a small subgroup (13%) of ANA/SMA positive chronic hepatitis C, in which autoimmune reactions might play a more relevant role than viral infection. They also show the antibodies are absent in AIH-2. In conclusion, pANCA appear to be mutually exclusive of LKM1 positivity, either hepatitis C virus-related or not, thus representing a further valuable tool to differentiate the two types of autoimmune hepatitis.

Adolescent↗
PubMed1997

Quantitative liver parameters of HCV infection: relation to HCV genotypes, viremia and response to interferon treatment.

BACKGROUND/AIMS: This study aimed to evaluate the relation between the number of hepatocytes positive for HCV antigens and the amount of HCV RNA in the liver and to evaluate the relationship between the above parameters and viremia levels, HCV genotype and response to interferon treatment. METHODS: This was a retrospective study on 31 consecutive patients with chronic HCV-related liver disease, selected on the basis of the availability of frozen liver tissue for both liver HCV antigens detection and liver HCV RNA quantitation. HCV antigens (immunohistochemistry), liver and plasma HCV RNA (competitive RT-PCR), and HCV genotype (commercial kit) were studied. RESULTS: A significant correlation (p=0.0005) was found between the amount of liver HCV RNA (log 10 copy/microg of extracted RNA) and the number of HCV-infected hepatocytes (scored from 0 to 3). These parameters were not significantly correlated with viremia levels. The highest liver HCV RNA levels and HCV antigen scores were found in patients infected with genotype 1b. Liver HCV RNA (median 541 x 10(3) vs 118 x 10(3) copy number/microg, p=0.031) and liver HCV antigens (mean score 2.3 vs 1.3, p=0.018) but not plasma HCV RNA (median 14956 x 10(3) vs 2885 [correction of 2.885] x 10(3) copy number/ml, ns) were significantly higher in patients not responding to interferon treatment compared to responders. CONCLUSIONS: The tissue parameters tested in this study were significantly correlated, shared the same clinical implications and predicted short-term response to interferon treatment better than viremia levels. We suggest that these tests should be included in the study protocol of patients under evaluation for interferon treatment, basing the choice on local facilities.

Adult↗
PubMed1997

Ultrasound-detected abdominal lymphadenopathy in chronic hepatitis C: high frequency and relationship with viremia.

BACKGROUND/AIMS: This study aimed to investigate the prevalence and significance of ultrasound-detected deep abdominal lymphadenopathy in chronic hepatitis due to C virus. METHODS: One hundred and thirty-four consecutive patients with various liver disorders were examined with portable real-time equipment. RESULTS: In 25 (19%), the procedure failed because of excessive meteorism. Deep nodes, mainly located in the hepato-duodenal ligament, were detected in 62 of the remaining 109 patients (57%), reaching the highest prevalences in primary biliary cirrhosis (5/7, 71%), chronic hepatitis C (44/66, 67%) and autoimmune hepatitis type 1 (2/3, 67%). For all patients, including those with liver diseases with multiple etiology, lymphadenopathy was more frequent in anti-HCV positive (51/81, 63%) than in negative cases (11/28, 39% p=0.02). In chronic hepatitis C, serum HCV RNA was detected by nested polymerase chain reaction in all 31 patients with, but in only 75% (12/16) of those without nodes (p=0.018). No other distinct clinical or laboratory feature was found in association with lymphadenopathy; in particular, its incidence was similar in cases with and without liver cirrhosis. CONCLUSIONS: Enlarged deep abdominal lymph nodes are frequently detected by ultrasound in patients with chronic hepatitis C. This feature may be of diagnostic utility, especially in early cases, when liver cirrhosis has not yet developed and therefore no other ultrasound sign of the underlying disease can be detected. Lymphadenopathy may be of biological significance, marking hepatitis C virus infection in a replicative, viremic stage. These observations support the existence of a close interaction between hepatitis C virus and the lymphatic system.

Abdomen↗
PubMed1997

Clinical implications of GBV-C/HGV infection in patients with "HCV-related" chronic hepatitis.

BACKGROUND/AIMS: To evaluate the clinical, biochemical and histological implications of a concomitant HGV infection in "HCV-related" chronic liver disease. METHODS: Eighty-three HCV-RNA positive patients with chronic liver disease were tested for GBV-C/HGV coinfection by heminested PCR. RESULTS: Twenty-two (26.5%) patients were found to be positive for GBV-C/HGV RNA. GBV-C/HGV+ patients differed significantly from GBV-C/HGV- ones for younger age, higher frequency of history of drug addiction, which in turn might favor coinfection with interferon-sensitive HCV genotypes (3a), and increased probability of long-term response to interferon. GBV-C/HGV infection appears to have no responsibility for specific aspects of HCV infection such as biochemical or histological cholestatic features, lymphoid follicles, symptomatic cryoglobulinemia or presence of serum autoantibodies, including LKM1. It does not worsen the HCV-related disease (ALT levels and histological activity) and does not significantly interfere with HCV infection, as explored by the number of hepatocytes positive for HCV antigens. The amount of steatosis (mean score) was shown to be higher in GBV-C/HGV+ patients. A virological follow up was performed in 17 interferon-treated GBV-C/HGV+ patients On the whole, GBV-C/HGV seems to be as sensitive to IFN treatment as HCV, but recurrence after withdrawal is more frequent. In spite of this, ALT levels often remain normal after treatment withdrawal. CONCLUSIONS: The present data suggest that GBV-C/HGV infection, apart from more marked liver steatosis, does not modify the overall picture of chronic hepatitis due to HCV infection.

Adolescent↗
PubMed1997

Correlation between conventional disease activity measures in juvenile chronic arthritis.

OBJECTIVE: To estimate in a cross sectional analysis the degree of colinearity among the disease activity measures more commonly used in juvenile chronic arthritis (JCA). METHODS: This study assessed in a single clinical evaluation three subjective variables, three measures of functional capacity, eight articular indices, and two laboratory indicators of systemic inflammation in 55 consecutive children with JCA. The relation between the clinical measures of JCA activity was determined by Pearson correlation coefficients. An r value of 0.7 or greater was considered evidence of colinearity. RESULTS: Among the subjective variables, parent global assessment of overall well being and parent assessment of pain were correlated with each other; the physician assessment of disease activity did not show evidence of colinearity with any other variable. The functional status measures were correlated with each other, but not with the indices of articular inflammation. There was a high degree of colinearity among the articular variables, with the number of active joints and the overall severity score being correlated with each other as well as with all the single articular indices. The laboratory variables were correlated with each other, but not with any of the articular, functional or subjective variables. CONCLUSION: Our results show a high degree of colinearity among the disease activity measures belonging to the same category, whereas this is uncommon for variables that investigate different domains of disease activity. These data underline the need to include the evaluation of each domain in the assessment of JCA activity.

Adolescent↗
PubMed1996

Impact of international autoimmune hepatitis group scoring system in definition of autoimmune hepatitis. An Italian experience.

We have reclassified 110 patients with autoantibody-positive cryptogenic chronic hepatitis according tot he aggregate scoring system proposed by the International Autoimmune Hepatitis Group for signs of hepatitis C virus (HCV) infection and the newly proposed terminology of "unclassified" chronic hepatitis. Anti-HCV and HCV viremia were assessed by second-generation assays and reverse transcription-polymerase chain reaction. Immunomorphological and immunochemical characterizations of antinuclear, smooth, muscle, liver-kidney microsomal type 1, and liver cytosol type 1 autoantibodies were also performed. All 45 anti-HCV negative patients fulfilled the score criteria for the diagnosis of "definite" or "probable" autoimmune hepatitis (AIH). Eight anti-HCV-positive cases reached the score of "probable" AIH, whereas the remaining 57 cases were diagnosed as unclassified chronic hepatitis. The scoring system allows the correct identification of all autoimmune cases without HCV infection. Autoimmune hepatitis runs a more severe disease course than unclassified chronic hepatitis, whose clinical and histological features are similar to those of autoantibody-negative chronic hepatitis C.

Adolescent↗
PubMed1995

Specific reactivity of fluorescein isothiocyanate-conjugated separated IgG and IgA from celiac disease sera on human tissues.

Study of the reaction of celiac disease-related antibodies with human substrates has been hampered by the immunological cross-reactivity between fluorescein isothiocyanate-conjugated anti-human immunoglobulins and immunoglobulins normally present in human tissues. In order to overcome this problem we extracted IgG from 2 celiac disease sera (positive for specific IgG and IgA antibodies) using a genetically engineered recombinant form of streptococcal protein G covalently immobilized on 4% agarose beads. The separated IgG and IgA was conjugated with fluorescein isothiocyanate and used in direct immunofluorescence on 0 blood group human duodenum, liver, and myocardium. Staining of the lamina propria beneath the villous epithelium, the endomysium of smooth muscle layers in the duodenum, and the liver sinusoidal and pericellular myocardial matrix was observed. The reactivity of celiac disease-related antibodies with various human tissues indicates that these antibodies are the result of a systemic immune response directed against all tissues containing matrix proteins.

Animals↗
PubMed1995

Distribution of three major hepatitis C virus genotypes in Italy. A multicentre study of 495 patients with chronic hepatitis C.

Different genotypes of hepatitis C virus (HCV) have been shown to have distinct geographical distribution and to associate with variable clinical features. To evaluate their role in chronic hepatitis in Italian patients, we studied 495 consecutive cases with chronic hepatitis C seen in nine sentinel centres homogeneously distributed over Italy. HCV genotyping was carried out using a dot-blot hybridization assay with genotype-specific probes. Four hundred and eleven patients were viraemic and could be evaluated: 57% were found to be infected with HCV-1, 31% with HCV-2, 8% with HCV-3, 1% showed mixed infection and 3% were ascribed to HCV-2b or HCV-4 by direct sequencing. Geographical distribution showed discrete territorial variations. A history of drug addiction was commoner in patients infected with HCV-3. There were no significant differences in activity of liver disease among different HCV genotypes but the response to interferon therapy was reduced in patients infected with HCV-1 compared to HCV-2 or HCV-3.

Adult↗
PubMed1995

Liver cytosolic 1 antigen-antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection.

Within the multiform liver/kidney microsomal (LKM) family, a subgroup of sera that reacts with a liver cytosolic (LC) protein has been isolated and the new antigen-antibody system is called LC1. Unlike LKM antibody type 1 (anti-LKM1), anti-LC1 is said to be unrelated to hepatitis C virus (HCV) infection and has therefore been proposed as a marker of 'true' autoimmune hepatitis type 2. Altogether 100 LKM1 positive sera were tested by immunodiffusion (ID). Twenty five gave a precipitation line with human liver cytosol; 17 of the 25 also reacted with rat liver cytosol. Thirteen of the 25 sera were anti-HCV positive by second generation ELISA: anti-HCV positive patients were significantly older (p < 0.001) and tended to have less active disease. No difference in anti-LC1 titre or ID immunoreactivity was found between anti-LC1/anti-HCV positive and anti-LC1/anti-HCV negative cases. In Western blotting experiments, 14 of 24 ID positive sera recognised a 58 kD protein of the human cytosolic fraction and 11 gave a similar reactivity when tested with human microsomes, suggesting the presence of the LC1 target antigen also in the microsomal preparation. Western blotting reactivity was similar for both anti-HCV positive and negative sera. These data confirm the existence of the LC1 antigen-antibody system that partially overlaps with LKM1, and that it is an additional marker of juvenile autoimmune hepatitis type 2. It does not, however, discriminate between patients with and without HCV infection.

Adolescent↗
PubMed1995

Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C.

To obtain information on the mechanisms of hepatocellular damage and the determinants of response to interferon, hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C and intercellular adhesion-1 molecules, and the number of lobular T lymphocytes were studied in 38 anti-HCV-positive patients. 14 patients did not show a primary response to interferon treatment. HCV genotype 1b was detected in 11 of them. They displayed higher scores of HCV-positive hepatocytes, HLA-A,B,C, and ICAM-1 molecules expression than with the responders. HCV-infected hepatocytes maintained the capacity to express HLA-A,B,C and ICAM-1 molecules. CD8-positive T cells in contact with infected hepatocytes and Councilman-like bodies were observed. A significant correlation was found between the number of lobular CD8-positive T cells and alanine amino transferase levels. No differences were observed in clinical, biochemical, and histological features between patients with high and low number of hepatocytes containing HCV antigens. These data suggest a prominent role of T cell-mediated cytotoxicity in the genesis of hepatocellular damage. The high expression of interferon-inducible antigens like HLA-A,B,C molecules suggests the presence of strong activation of the interferon system possibly related to high HCV replication in nonresponder patients infected with genotype 1b.

Antigens, Viral↗
PubMed1995

Hepatocellular codistribution of c100, c33, c22, and NS5 hepatitis C virus antigens detected by using immunopurified polyclonal spontaneous human antibodies.

Hepatitis C virus (HCV) antigens in liver biopsy have been detected by immunohistochemistry using both spontaneous human IgG and murine monoclonal or rabbit polyclonal monospecific reagents. Conflicting results have been obtained in different studies. This was probably because of the incapacity of single experimental antibodies, raised against synthetic or recombinant peptides, to recognize native tissue antigens. To overcome this possibility, we immunopurified monospecific spontaneous polyclonal human Ig, therefore induced by native antigens, from the single antigen-containing bands of RIBA 3 strips. Antibodies to c100, c33, c22, and NS5 antigens were obtained from the serum of a patient affected by chronic hepatitis C. The IgG fraction of this serum had proved to stain tissue HCV antigens. Eight biopsies were selected on the basis of strong hepatocellular reactivity with the whole IgG fraction in a variable number (from 5% to 75%) of cells. The four antigens were detected in all biopsies; a clear cellular codistribution was observed on serial sections. These data demonstrate that the possibility to identify HCV antigens in liver biopsies is higher when using human antibodies induced by native antigens rather than experimental antibodies. The approach of immunopurification of human antibodies can be extended to other HCV-related epitopes to obtain reagents useful for the selection and optimization of monoclonal or polyclonal antibodies.

Antigens, Viral↗
PubMed1994

Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation.

The immunohistochemical determination of the accessory protein of DNA-polymerase delta (PCNA), a marker of an early S-phase of the cell cycle, was used to evaluate cell proliferation retrospectively in formalin-fixed, paraffin-embedded liver biopsy sections in a group of patients with cirrhosis of similar age and duration of follow up, and with no evidence of hepatocellular carcinoma (41), including 17 patients with and 24 without hepatocellular carcinoma appearance during follow up. Proliferation was expressed as total (PCNA-TOT) and strongly (PCNA-STRO) positive nuclei per 1000 hepatocytes. The presence of dysplasia was also recorded. Histological findings and biochemical data, at the time of liver biopsy, were compared in the two groups. While total PCNA positivities were not significantly different in the two groups, strong reactivity was significantly higher in patients who eventually developed hepato-cellular carcinoma (median 0.7 vs 2.6). Univariate analysis of histological and biochemical data at the time of biopsy, followed by a stepwise regression study, showed that the significant parameters for a time-dependent disease-free state were, in decreasing order: cholesterol, PCNA-STRO, PCNA-TOT and alpha foeto-protein. Other clinical, biochemical and histological parameters, including dysplasia, provided no further information. From these data, hepatocellular proliferation can be evaluated in patients with cirrhosis with a currently available technique. Patients with high cell proliferation are at increased risk of developing hepatocellular carcinoma and may require differentiated follow up.

Adult↗
PubMed1994

Interferon therapy in liver/kidney microsomal antibody type 1-positive patients with chronic hepatitis C.

The association between liver/kidney microsomal antibody type 1 and adult cases of hepatitis C virus-related chronic liver disease has been firmly established. In the presence of both markers, evidence of autoimmunity (liver/kidney microsomal antibody type 1) and actual viremia (serum HCV RNA), the therapeutic dilemma arises between steroids, which are beneficial to autoimmune but deleterious to viral diseases, and interferon-alpha, which may exacerbate an autoimmune disorder. Six patients with liver/kidney microsomal antibody type 1 and serum HCV RNA were given interferon-alpha: three showed a response pattern similar to that observed in autoantibody-negative chronic hepatitis C cases; the other three developed a sharp transaminase peak, which was not followed by HCV RNA clearance. Considering the brisk flare-up of liver cell necrosis, interferon-alpha treatment proved to be dangerous in the above three liver/kidney microsomal antibody type 1/HCV RNA positive cases. Subsequent steroid administration reduced alanine aminotransferase peaks, but may be harmful in viral infections. Therapeutic alternatives are needed: they will probably include pure antivirals (exerting no immunostimulatory effects) with or without immunosuppressive drugs.

Adolescent↗
PubMed1994

Analysis of the hepatitis C virus genome in patients with anti-LKM-1 autoantibodies.

Hepatitis C virus genotypes have been characterized in 22 patients with anti-LKM-1 positive chronic hepatitis C. Following the Simmonds classification, 77% of patients were infected by hepatitis C virus genotype 1, 18% by genotype 2 and 5% by genotype 3, thus excluding the association of the autoimmune reaction with a particular viral type. Prevalences of genotype 1 and 2 were significantly different from those obtained in 79 patients with chronic hepatitis C who were negative for anti-LKM-1, as these were more rarely infected by genotype 1 and more frequently by genotype 2. Clinical findings of anti-LKM-1 positive patients were similar in all three groups. Sequence analysis of the amplified 5'UTR provided identification of peculiar and identical nucleotide substitutions in two out of four patients with genotype 2. The analysis of the secondary structure of this region showed that the observed nucleotide mutations increased the stability of the stem formed in this position.

Adolescent↗
PubMed1994

Hepatocellular expression of HLA-A, B, C molecules predicts primary response to interferon in patients with chronic hepatitis C.

Primary response rate to alpha-interferon (IFN) is about 50% in patients with chronic hepatitis C. Criteria for predicting a positive primary response are lacking. HLA-A,B,C molecule expression is known to be stimulated by viral infections. In 36 consecutive interferon-treated anti-HCV positive patients with an available frozen liver biopsy sample, the predictive value of liver HLA-A,B,C expression, and of histologic, clinical, and biochemical parameters was evaluated. Response to treatment was defined by normalization of transaminases, and disappearance of serum HCV-RNA within 3 months. According to these criteria, 17 patients were classified as nonresponders and 19 were classified as responders. The pattern of HLA-A,B,C hepatocellular positivity varied from normal (negative or occasional faint staining of hepatocellular membranes) to diffuse, strong "honeycomb" positivity. The highest scores of positivity were found in nonresponder patients. The discriminant capacity of HLA-A,B,C scores of positivity was compared with clinical, biochemical and histologic parameters by discriminant analysis. HLA-A,B,C expression was found to be the main discriminant parameter, in addition to alkaline phosphate (ALP) and gamma-glutamyl-transpeptidase (GGT) which added little additional information. The higher hepatocellular expression of class I MHC molecules in nonresponder cases may reflect a different viral effect on hepatocytes, which is induced by different HCV genotypes or levels of viremia. From a clinical point of view, the pretreatment HLA-A,B,C pattern of positivity represents a powerful tool in the selection of patients for interferon treatment.

Adult↗