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F Rosina

Publications and source records attributed to F Rosina.

At least 37 records · Page 2Linked to original sources

The tumor necrosis factor-alpha promoter correlates with progression of primary biliary cirrhosis.

BACKGROUND/AIMS: There have been many studies attempting to identify genes that determine susceptibility to primary biliary cirrhosis (PBC), but few studies have attempted to define the genes that modulate the natural history of the disease. There is a biallelic polymorphism, coined TNF1 and TNF2, in the TNFalpha promoter region at -308. We investigated the relative frequency of the TNF1 and TNF2 alleles in patients with PBC, based on the hypothesis that a polymorphism of the TNFalpha promoter region may be associated with the rate of progression and prognosis of PBC. METHODS: Seventy-one Caucasoid patients with PBC and 133 healthy and unrelated Caucasoid individuals were studied. Genomic DNA was extracted from blood, and the mutation at position -308 of the TNFalpha gene analyzed by PCR and NcoI digestion. RESULTS: In 71 patients with PBC, 56/71 (78.9%) patients were TNF1/TNF1 homozygotes, 14/71 (19.7%) were TNF1/TNF2 heterozygotes and 1/71 (1.4%) were TNF2/TNF2 homozygotes. In 133 healthy individuals, 109/133 (80.5%) patients were TNF1/TNF1 homozygotes, 24/133 (18%) were TNF1/TNF2 heterozygotes. No control individuals were TNF2/TNF2 homozygotes. The difference between the two groups was not statistically significant (p = 0.3684). However, in patients with TNF1/TNF1 the Mayo score for disease severity was 4.596+/-0.157 (mean +/- SEM), compared to 5.637+/-0.420 for patients with TNF1/TNF2. This Mayo score was significantly higher in patients with the TNF1/TNF2 genotype than those with TNF1/TNF1 (p = 0.0140), with an odds ratio of 4.9. CONCLUSIONS: Our data demonstrate that the presence of the TNF2 allele may be associated with a higher Mayo score, and thus with patients in a more advanced clinical stage. These data have both theoretical and clinical implications.

Alleles↗

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations.

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.0, P<0.00001) and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes (RR=2.4, P<0.0001) were observed in all five patient groups. A total of 16% of the PSC patients were homozygous for the DRB1*03, DQA1*0501, DQB1*02 haplotype compared to 1% of the controls (RR=20, P<0.0001). The DRB1*04, DQA1*03, DQB1*0302 haplotype was significantly reduced in frequency(RR=0.4, P<0.00001). Among Norwegian, Swedish and British patients that did not carry neither the DRB1*03, DQA1*0501, DQB1*02 nor the DRB1*13, DQA1*0103, DQB1*0603 haplotype, an increased frequency of the DRB1*15, DQA1*0102, DQB1*0602 haplotype was observed (RR=2.0, P<0.0001). Thus, PSC was found to be positively associated to three different HLA class II haplotypes (i.e. the DRB1*03, DQA1*0501, DQB1*02, the DRB1*15, DQA1*0102, DQB1*0602 and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes) and negatively associated to one HLA class II haplotype (i.e. the DRB1*04, DQB1*0302 haplotype).

Adolescent↗

Long-term results with interferon therapy in chronic type B hepatitis: a prospective randomized trial.

OBJECTIVES: The aims of this long-term, prospective randomized study were to evaluate the clinical usefulness of alpha-interferon in treating chronic HBV infection and to establish whether clearance of viral replication markers and normalization of liver function tests induced by alpha-interferon were sustained. METHODS: Sixty-four patients with chronic wild type (HBeAg-positive) hepatitis B, enrolled between 1983 and 1987, were randomized into two groups. Thirty-three patients received alpha-interferon (5 MU/m2 three times weekly for 6 months; treated group), and 31 were not treated (controls). Treated and control patients were prospectively followed for a mean of 86.4 +/- 6.96 and 79.7 +/- 6.8 (p = NS) months, respectively. RESULTS: Clearance of the following viral markers was found in treated and control patients as follows: HBV-DNA, 26 (78.9%) and 18 (58.1%) (p = 0.106); HBeAg, 30 (90.9%) and 19 (61.2%) (p < 0.007); and HBsAg, 12 (36.4%) and three (9.8%) (p < 0.017). Persistent abnormal ALT levels were found in 11 (33.3%) treated and in 22 (70.9%) control patients (p < 0.025). Four control and three treated patients developed portal hypertension whereas two control and one treated patient developed hepatocellular carcinoma. Seven patients (five treated and two controls) were retrospectively found to have hepatitis C virus (HCV) coinfection before enrollment. To date, all coinfected patients remain positive for HCV-RNA. Also, all HCV coinfected patients, except one in the treated group, had persistent increased serum ALT levels. One of the coinfected patients developed portal hypertension. CONCLUSIONS: Chronic HBV hepatitis patients responding to interferon treatment had a faster, more complete, and sustained clearance of viral markers than controls; HCV coinfection does not seem to negatively affect the clearance of HBV replicative markers. However when coinfection occurs, hepatic disease persists despite HBV marker clearance.

Adolescent↗

Characterization of antimitochondrial antibodies in health adults.

The detection of antimitochondrial antibodies (AMAs) is an important criterion for the diagnosis of primary biliary cirrhosis (PBC). During the last decade, the mitochondrial autoantigens have been cloned, sequenced, and identified as members of the 2-oxo-acid dehydrogenase pathway, including the E2 subunits of pyruvate dehydrogenase (PDC-E2), branched-chain 2-oxo-acid dehydrogenase (BCOADC-E2), and 2-oxo-glutarate dehydrogenase (OGDC-E2). We have developed a rapid and sensitive diagnostic test for use in PBC based on a triple hybrid recombinant molecule (r-MIT3) that contains the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2. To help understand the frequency and antigen specificity of AMAs in an asymptomatic population and to identify patients with early disease, we investigated the prevalence of AMA, by enzyme-linked immunosorbent assay (ELISA), in a cohort of 1,530 people from northern Italy. Positive sera were further analyzed for immunoglobulin (Ig) isotypes, subclasses, and epitopes of AMA by a combination of ELISA and immunoblotting. In this cohort of 1,530 people, 9 (0.5%) reacted to r-MIT3 by ELISA. Of the 9 reactive sera, 2 recognized PDC-E2, 2 of 9 recognized BCOADC-E2, 1 of 9 recognized OGDC-E2, 2 of 9 recognized both PDC-E2 and BCOADC-E2, and 1 of 9 recognized PDC-E2 and OGDC-E2. AMA reactivity was primarily IgM and IgA. Epitope mapping revealed an AMA pattern of reactivity to PDC-E2 that differed from that found in patients with histologically proven PBC in most of the sera. However, 1 sera of a 72-year-old female with a normal alkaline phosphatase had an AMA profile identical to typical PBC. After a variable follow-up period (8-14 months), sera from 8 of 9 of these people were re-obtained for AMA and relative epitope mapping. Interestingly, the reactivity had a wider AMA pattern than before.

Adult↗

Serum immunoglobulin M antibody to hepatitis D as a surrogate marker of hepatitis D in interferon-treated patients and in patients who underwent liver transplantation.

The kinetics of the immunoglobulin (Ig) M type antibody to the hepatitis D virus (IgM anti-HD) were investigated in hepatitis B surface antigen (HBsAg) carriers with chronic hepatitis D treated with interferon (IFN) and in patients with terminal hepatitis delta virus (HDV) cirrhosis who underwent liver transplantation. The IgM antibody disappeared in each of 8 patients who responded to IFN therapy with the persistent normalization of aminotransferases and with the clearance of serum HBsAg and HDV-RNA. The IgM reactivity did not decline in the 45 treated patients who did not respond to the cytokine or who experienced a relapse after responding while on therapy. The antibody rapidly disappeared from serum post-transplantation in each of 10 examined patients with HDV who underwent transplantation. In 5 patients who underwent transplantation and who became reinfected with HDV, the antibody remained undetectable during the early reinfection phase, as marked by HDV replication and by the absence of liver damage; however, it rapidly raised to pre-transplantation levels with the recurrence of hepatitis D (HD) in the liver graft. Monomeric 7S IgM anti-HD predominated over pentameric 19S antibody in each of the two patients examined for IgM anti-HD molecular species. The IgM antibody to HDV raises in response to HDV-induced damage and represents a valid surrogate marker of liver damage which is immunopathologically related to HDV infection. Besides providing diagnostic information, it provides the best predictor of impending resolution of chronic HDV disease, whether spontaneous or IFN-induced.

Adult↗

Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis.

Primary biliary cirrhosis is an autoimmune disease characterized by high titer autoantibodies predominantly against mitochondrial antigens PDC-E2, BCOADC-E2 and OGDC-E2. Currently orthotopic liver transplant (OLT) is the major form of treatment for end-stage primary biliary cirrhosis (PBC), but it is still unclear whether the autoimmune response continues post-transplantation. In this study we took advantage of a well-defined collection of sera collected serially before and after liver transplantation. We assayed these sera for quantitative and isotype-specific titers of antibodies against a set of recombinant mitochondrial autoantigens. We also studied reactivity to gp210. Serum samples were taken before transplantation and at intervals of 6 months, 1, 2, and 3 years after OLT. Before OLT 24/35 patients were AMA-positive, including seven out of the 35 to PDC-E2 alone, eight to both PDC-E2 and OGDC-E2, six to both PDC-E2 and BCOADC-E2, two to BCOADC-E2 alone and one to OGDC-E2. Following OLT, the frequency of sera that responded to PDC-E2 alone increased from seven to 12/35. Similarly, reactivity to BCOADC-E2 slightly increased from two to four out of 35. However, there was an overall decrease in sera that responded to more than one antigen. Neither Ig isotype nor subclass of the autoimmune response changed following OLT. Findings with gp210 were similar, in that reactivity to gp210 was found in nine out of 35 patients pre-OLT; following OLT the frequency decreased to seven out of 35 patients. Overall, the titers of AMAs decline slightly during the first year post-OLT, but are equivalent to pre-OLT values by 6 months. Moreover, the antibody subclass/ isotype remained unchanged. These data suggest that the removal of a diseased PBC liver has little, if any, impact on the serological characteristics of PBC. Moreover, it provides information regarding the natural history of PBC, particularly on the long latency time for disease development.

Antibodies, Monoclonal↗

Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis: a comparison of the alkaline phosphatase and immunofluorescent techniques.

BACKGROUND: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. METHOD: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. PATIENTS: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. RESULTS: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. CONCLUSION: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient, related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.

Adult↗

Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles.

The T-cell-mediated immune response plays a crucial role in defense against hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides. However, very little is known about the role of specific T cells during hepatitis delta virus (HDV) infection in humans. In this study, the T-cell response to HDV in chronic hepatitis B virus (HBV) carriers with HDV superinfection was investigated at different levels. Analysis of peripheral blood mononuclear cell (PBMC) proliferation in response to a recombinant form of large hepatitis delta antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically responded to HDAg. By employing synthetic peptides spanning the entire HDAg sequence, we found that T-cell recognition was directed against different antigenic determinants, with patient-to-patient variation in the pattern of response to peptides. Interestingly, all responders had signs of inactive HDV-induced disease, while none of the patients with active disease and none of the control subjects showed any significant proliferation. More accurate information about the specific T-cell response was obtained at the clonal level. A panel of HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine-specificity analysis revealed that the clones tested individually recognized four epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106 to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells in association with multiple class II molecules. In addition, peptide 26 to 41 was efficiently generated after processing of HDAg through the endogenous processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell clones assayed were able to produce high levels of gamma interferon (IFN-gamma), belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were cytotoxic in a specific assay. This study provides the first evidence that detection of a specific T-cell response to HDAg in the peripheral blood of individuals with hepatitis delta is related to the decrease of HDV-induced disease activity. The HDAg epitopes identified here and particularly those recognized by CD4+ T cells in association with multiple major histocompatibility complex class II molecules may be potentially exploited for the preparation of a vaccine for prophylaxis and therapy of HDV infection.

CD4-Positive T-Lymphocytes↗

Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.

OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.

Adult↗

Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.

We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.

Adolescent↗

[The risk factors for hepatitis D viral infection in southern Italy].

The aims of this study were to evaluate the prevalence of hepatitis delta virus (HDV) infection and risk factors associated to it. Three hundred sixty-one HBsAg chronic carriers from southern Italy were studied and 13.8% of them resulted anti-delta positive. 80% of these subjects were less than 50 years old. When anti-delta positive subjects were compared with anti-delta negative ones, a lower number of healthy HDV carriers and a higher frequency of cirrhotics were noted among anti-delta positive. Of lower than 50 years, imprisonment, sexual contacts with drug abusers and male homosexuality were risk factors of HDV infection. No association was found with sex, household contacts with HBV or HDV carriers, number of family members and transfusion of blood products. These data confirm the high prevalence of HDV infection in southern Italy.

Adolescent↗

Effect of patient characteristics on hospital costs for cirrhosis: implications for the disease-related group (DRG) reimbursement system.

The Prospective Payment System uses Diagnosis-Related Groups (DRG) as a reimbursement system. DRG 202 is a disease-related group including liver cirrhosis as a whole. Patients referring to the inpatient unit complain of variable severity and complications of cirrhosis, possibly implying different expenditure of resources. Aim of the investigation was to identify factors affecting cost variability in patients with cirrhosis. A total of 73 consecutive, DRG 202-assigned, cirrhotic patients classified according to demographic and clinical variables were evaluated for length and costs of hospitalization calculated on a full-cost basis. Mean length of hospitalization was 10.2 +/- 7 days. Mean cost of hospitalization was Lit. 4.348.000 +/- 2.718.000. Medical, nursing, diagnostic, drug and general charges accounted for 13%, 29%, 37%, 5% and 16% of the cost, respectively. Child-Pugh score significantly correlated with drug consumption (p < 0.005), length (p < 0.01) and costs (p < 0.001) of hospitalization, but not with cost per day. Age, sex, admission status, referral reason, associated diseases and liver transplant susceptibility did not correlate with duration and costs of hospitalization. Disease severity significantly modifies costs of hospital admission in cirrhotic patients mostly on account of longer hospital stay. Surrogate indexes of disease severity, derived from ISTAT/DRG records, cannot identify patients consuming larger resources. In liver cirrhosis, the DRG system could be improved by introducing parameters, such as Child-Pugh score, directly taking into account disease severity.

Adolescent↗

Detection of hepatitis D virus RNA in serum by a reverse transcription, polymerase chain reaction-based assay.

We designed a reverse transcription, polymerase chain reaction-based assay for serum hepatitis D virus RNA. Amplified hepatitis D virus cDNA was revealed by ethidium bromide staining, followed by blotting onto a nylon membrane and hybridization with a 32phosphorus-labelled oligonucleotide, or by a DNA enzyme immunoassay (DEIA) using a double stranded DNA-specific monoclonal antibody. The absolute sensitivity was expressed as number of hepatitis D virus RNA molecules, using a serum of known viral RNA concentration. Three sets of primers were used, encompassing the base positions 66-686 (variable rod-stabilizing region), 701-962 (conserved, viroid-like domain) and 886-1,333 (portion of the open reading frame 5 encoding for the carboxyterminus of the hepatitis D antigen) of the viral genome. The lower detection limits, after amplification of the three RNA portions, as assessed by ethidium bromide staining, were 7.5 x 10(6), 7.5 x 10(4) and 7.5 x 10(2) molecules of hepatitis D virus RNA per assay, respectively. The region encompassing bases 886-1,333 was chosen for blotting and hybridization to a radiolabelled oligonucleotide probe or for a capture-based DNA enzyme immunoassay, where the microplate was coated with this same probe. The two procedures showed comparable sensitivity, i.e., about 10 molecules of viral RNA per assay. The specificity of the assay was further on a panel of both anti-hepatitis D-positive and -negative sera. Amplification of serum hepatitis D virus RNA by reverse transcription/polymerase chain reaction followed by detection of the amplified cDNA by DNA enzyme immunoassay is a promising and feasible routine assay for detecting low amounts of circulating virions.

Animals↗

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease: do they recognize different subsets of a heterogeneous disease?

OBJECTIVE: To evaluate the prevalence of anti-neutrophil cytoplasmic antibodies in a series of patients with inflammatory bowel disease, the discriminatory value of these antibodies in differentiating between ulcerative colitis and Crohn's disease, their antigen specificity and their correlation with epidemiological and clinical variables. METHODS: Serum anti-neutrophil cytoplasmic antibodies were evaluated by indirect immunofluorescence and immunoblotting using neutrophils isolated from peripheral blood and by enzyme-linked immunosorbent assays (ELISAs) using proteinase 3 and myeloperoxidase as antigens. RESULTS: Anti-neutrophil cytoplasmic antibodies were detected by immunofluorescence in 43 (39.8%) of 108 patients with ulcerative colitis, in 11 (11.9%) of 92 patients with Crohn's disease (P < 0.001) and 5 (6.8%) of 73 control patients. The predominant pattern was perinuclear staining around neutrophil nuclei (44 of 59, 75%); a homogeneous cytoplasmic staining was present in 15 (25%) of 59 sera, mainly among Crohn's disease and control patients. The ELISAs gave no positive results. Recognition of proteins of relative molecular masses 27,000 and 49,000 at immunoblotting was common to ulcerative colitis, Crohn's disease and control sera. The proteins of relative molecular masses 32,000 and 106,000 were recognized exclusively by 11% of anti-neutrophil-positive ulcerative colitis sera. No significant correlation was found between the presence of anti-neutrophil cytoplasmic antibodies and the demographic and clinical characteristics of the patients. CONCLUSION: Anti-neutrophil cytoplasmic antibodies are detectable in a large proportion of patients with ulcerative colitis, but their prevalence in a limited proportion of patients with Crohn's disease reduces their discriminatory capability. The persistence of anti-neutrophil cytoplasmic antibodies after total colectomy and the absence of a correlation between the activity of the disease and the presence or titre of these antibodies support the hypothesis that anti-neutrophil cytoplasmic antibodies are not simply an epiphenomenon of colonic inflammation.

Adult↗

Interferon in HDV infection.

Chronic hepatitis D is a usually severe and progressive liver disease due to infection with the hepatitis delta virus, a unique RNA virus requiring the hepatitis B virus helper function to exert its pathogenic potential. Alpha IFN is at present the treatment of choice for chronic viral hepatitis, but the results obtained in chronic hepatitis D are far from being satisfactory. Available data show that IFN is more likely to be effective if administered to patients with a recent infection (lasting less than 1 year) at high doses (9-10 MU thrice in a week) and for a prolonged length of time (at least 12 months). The optimal timing of IFN treatment remains to be addressed: apart from the clearance of HBsAg and seroconversion to anti-HBs (an event often occurring months to years after completion of a successful IFN treatment) no other early biochemical or virological events can predict a sustained response. Better therapeutic options are therefore needed. Unfortunately, antiviral agents, such as Ribavirin, active against HDV in cell cultures, have failed to confirm their attitude in the clinical setting. In vitro and in vivo evidence points to HBV as a possible target for antiviral therapy in chronic hepatitis D, providing the rationale for trying new deoxynucleotide analogues also in this severe form of hepatitis.

Age Factors↗