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Biomedical subjects

A Craxì

Publications and source records attributed to A Craxì.

At least 73 records · Page 4Linked to original sources

A performance evaluation of the expert system 'Jaundice' in comparison with that of three hepatologists.

The diagnostic performance of an Expert System (Jaundice) designed to discriminate between different causes of jaundice was evaluated in a test sample of 200 consecutive in-patients with serum bilirubin greater than or equal to 51 mumol/l. The average probability assigned to true diagnosis, the non-error rate and the overall accuracy were, respectively, 55%, 77% and 70%. The Expert System's discriminatory ability in probabilistic prediction, assessed by a method based on continuous functions of the diagnostic probabilities (Brier score) was good. We also compared the ability of our Expert System to that of three experienced hepatologists, who were required to give a diagnosis in 20 cases following the same protocol used by computer (i.e., by asking only clinical and laboratory items). Both the hepatologists and Jaundice achieved a correct diagnosis in 70% of 20 cases, but the Expert System asked a significantly higher average number of questions during each consultation. Analysis of the reasoning pathway made by an external referee showed a high agreement between the diagnostic strategies of the Expert System and the physicians. We conclude that Jaundice can be a useful tool to support a physician with insufficient clinical experience in this field to generate correct diagnostic hypotheses.

Diagnosis, Computer-Assisted↗

Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomised clinical trials.

We reviewed randomised clinical trials evaluating the effect of lymphoblastoid or recombinant alpha-interferon in non-A, non-B chronic hepatitis. The outcomes assessed were the rates of serum alanine aminotransferase normalization and relapse during and after stopping interferon. Data were pooled by meta-analysis and a 50% overall rate difference, favouring treated patients, was found. Results showed homogeneity in direction of treatment effect both after short-term (2-6 months, greater than or equal to 2 mega-units thrice weekly) and long-term (9-18 months, variable dose) interferon course. Moreover, results did not change when type of publication (abstracts vs. full reports) and treatment duration or schedule were accounted for. About 50% of patients originally responding to treatment relapsed within 6 months of either dose reduction or stopping interferon, thus suggesting that only in about one out of four patients is benefit from treatment sustained up to 1 year. We conclude that larger trials are needed to identify an optimal schedule of treatment and to evaluate predictors of interferon effectiveness in patients with non-A, non-B chronic hepatitis.

Alanine Transaminase↗

Is autoimmune chronic active hepatitis a HCV-related disease?

We evaluated the specificity and clinical relevance of anti-hepatitis C virus antibody positivity in 22 HBsAg-negative patients with autoimmune (anti-nuclear, anti-actin or anti-liver-kidney microsomal antibody positive) chronic active hepatitis. An ELISA anti-HCV test and a recombinant immunoblot assay (RIBA-HCV) were used. Thirteen patients (59%) were anti-HCV positive and five (23%) anti-HCV negative by both ELISA and RIBA-HCV tests. Four patients (18%) were borderline positive by ELISA (OD less than 1.0), and three of them (all with severe disease) were negative by RIBA. Histologic necroinflammation, AST/ALT and gamma-globulins levels were higher and response to prednisolone treatment was better in RIBA anti-HCV-negative than in anti-HCV-positive cases. We confirmed with both RIBA and ELISA tests the high prevalence of anti-HCV already reported by ELISA in anti-nuclear and anti-liver-kidney microsomal antibody positive chronic active hepatitis. False positive for anti-HCV (i.e., a positive ELISA test not confirmed by RIBA) occurred only among patients with severe disease. Since RIBA-negative subjects showed the best response to corticosteroid, they might represent the only subset of cases of 'true' autoimmune chronic active hepatitis.

Adrenal Cortex Hormones↗

Smouldering hepatitis B virus replication in patients with chronic liver disease and hepatitis delta virus superinfection.

Hepatitis B virus deoxyribonucleic acid (HBV-DNA) was studied by Southern blot analysis in liver biopsy specimens from 75 HBsAg-positive patients with chronic liver disease living in southern Italy. Twenty-seven of the patients were hepatitis delta virus (HDV) superinfected. Intrahepatic HBV-DNA was detected in 54 (72%) patients, 32 (59%) of them with replicative forms. The presence of replicative forms was directly related to liver HBcAg and inversely related to liver HDAg, as shown by multivariate analysis. However, 14 patients with intrahepatic HBV-DNA non-replicative pattern and about half of HDV-infected patients were liver HBcAg and/or serum HBV-DNA positive, mostly in low amounts. Histological inflammatory activity was strongly related to liver HBcAg expression regardless of HDV superinfection, as confirmed by multivariate analysis. Our results confirm previous studies about the concordance between intrahepatic HBV-DNA replicative pattern and liver HBcAg expression and about inhibition by HDV of high-level HBV replication. However, they suggest that low-level HBV replication may have an important role in causing liver damage also among HDV-infected patients, in a population where the spreading of HBV and HDV is a naturally occurring event.

Adolescent↗

Hepatitis-C virus infection in Italy: a multicentric sero-epidemiological study (a report from the HCV study group of the Italian Association for the Study of the Liver).

To assess possible geographical differences in the spread of hepatitis-C virus (HCV), the prevalence of antibodies against HCV (anti-C-100-3) was investigated in various adult population groups in 29 centres in Italy. Anti-HCV was positive in 375 out of 28,433 voluntary blood donors (1.3%): prevalence was higher in southern Italy (1.51%) than in the northern regions (1.28%), but the difference was not statistically significant. Anti-HCV prevalence was similar in the north and south in post-transfusion chronic hepatitis (91%), haemophiliacs (73%), intravenous drug users (70%), and haemodialysis patients (28%), where parenteral contacts are obvious, and in HBsAg carriers (14%), a group with evidence of previous parenteral contamination. In contrast, anti-HCV prevalences were found to be significantly higher in the south than in the north and central Italy among patients with hepatocellular carcinoma (HCC) (73 vs 59%), cryptogenic liver disease (67 vs 58%), autoimmune chronic hepatitis (72 vs 44%) and alcoholic liver disease (51 vs 34%). These results indicate a very high circulation of HCV in Italy, with maximum incidence in the south and in the islands. They suggest that its spread in the community can occur through inapparent parenteral routes as observed for hepatitis-B (HBV) and hepatitis-delta viruses (HDV) and possibly facilitated by poorer social-demographic and life-style factors.

Adult↗

Hepatitis B vaccination of relatives of hepatitis B virus DNA positive carriers: an experience with plasma-derived vaccine.

We assessed in a western population the efficacy of a plasma-derived hepatitis B vaccine in relatives of highly infectious hepatitis B virus (HBV) carriers. A consecutive group of 103 HbsAg, anti-HBs and anti-HBc negative household relatives of 45 HBV-DNA positive chronic carriers received a 5 micrograms dose of plasma-derived vaccine at 0, 1, 2 and 12 months. Protective levels of immunity developed in 101 subjects (97.8%) 3 months after boosting. Low responders to the vaccine were mostly found among parents and spouses of carriers, whilst offspring and siblings were usually high responders. The main discriminant in predicting a good response was age below 12 years. Hyporesponsiveness did not occur in family clusters. No major HBV events occurred among immunized relatives patients. Hepatitis B vaccine is safe and effective in immunizing relatives of HBV carriers while no genetic conditioning of the immune response is evident among them.

Adult↗

Interleukin-2, interleukin-2 receptor and gamma-interferon synthesis by peripheral blood mononuclear cells in chronic hepatitis delta virus infection.

The behaviour of the immune system during liver damage caused by chronic hepatitis delta virus (HDV) infection was evaluated by assessing, in 16 patients with HBsAg+ chronic liver disease and HDV superinfection (15 HBeAg-, 1 HBeAg+), phytohaemagglutinin (PHA)-induced interleukin-2 synthesis and interleukin-2 receptor expression, PHA and staphylococcal enterotoxin B (SEB)-induced gamma-interferon synthesis and, in some cases, the presence of hepatitis B virus DNA (HBV-DNA) within peripheral blood mononuclear cells (PBMC). The results were compared to those obtained in 13 patients without HBV replication (i.e., serum HBV-DNA and liver HBcAg-negative), in 15 with HBV replication (i.e., serum HBV-DNA and/or liver HBcAg-positive) with chronic liver disease without HDV superinfection, and in 15 HBsAg-negative healthy control subjects. The lymphokine pattern in HDV infection was comparable to that of healthy subjects and of HBV non-replicating patients without HDV superinfection. Interleukin-2 receptor expression and gamma-interferon synthesis were however significantly decreased in HDV-negative patients with active HBV replication. HBV-DNA was detected in PBMC from 8 of 23 patients, without any correlation with the lymphokine pattern. Our results suggest that in HDV-related chronic liver disease, immune system alterations are unlikely. HDV superinfection does not affect the occurrence of HBV-DNA sequences within the leukocytes. HBV-DNA in PBMC does not interfere with the interleukin-2 system nor with the gamma-interferon response in HBV- and HDV-related chronic liver disease.

Adult↗

IgM anti-HBc in acute and chronic hepatitis B virus (HBV) infection: diagnostic value and correlation with viral replication and disease activity.

IgM antibody to hepatitis B core antigen (IgM anti-HBc) was determined in 348 subjects with hepatitis B virus infection, in order to evaluate, in an area of high hepatitis D virus (HDV) endemicity, its usefulness in discriminating acute HBV hepatitis from HDV superinfection of HBsAg carriers, and to see whether in chronic HBV infection IgM anti-HBc can be related to viral replication, disease activity, or risk of neoplastic transformation. The positive predictive value (PV) of IgM anti-HBc for acute hepatitis was low at the standard 2.1 cut-off (35.2%), but a cut-off of 7 raised the positive PV, retaining a negative PV of above 90% and a sensitivity of 59.5%. No significant relationship was found in chronic infection between IgM anti-HBc, the level of HBV replication or the type of liver disease. Patients with HDV infection were mostly IgM anti-HBc negative. Hepatocellular carcinoma was not associated with a raised prevalence of IgM anti-HBc.

Acute Disease↗

Assessment of HBV replicative status by receptors for polymerized human albumin.

Receptors for polymerized human albumin (pHSA-r) are expressed on HBsAg in larger numbers during complete viral replication. We have evaluated the usefulness of pHSA-r as a marker of high-level infection by a comparison with serum HBeAg, liver HBcAg and serum HBV-DNA. One-hundred-and-fifty-seven patients with HBsAg positive chronic liver disease were tested for HBeAg and pHSA-r titre. In 73 of them liver HBcAg was tested by immunofluorescence, while in the remaining 84 serum HBV-DNA was determined. Seventy-three subjects were HBeAg positive, 20/73 were HBcAg positive, and 60/84 had circulating HBV-DNA. The best cut-off for pHSA-r was found at 1:204,800 (sensitivity of 67.6% and specificity of 95.7% in detecting viral replication). At this cut-off the concordance rate between pHSA-r and viral replication (as assessed by HBV-DNA or liver HBcAg) was 83%, a figure similar to that of HBeAg (88%). Three HBeAg negative subjects who were actually complete replicators were identified by the pHSA-r test.

Carrier State↗

Polyalbumin receptors, hepatitis B surface antigen (HBsAg), and HBsAg/IgM complexes in HBsAg positive patients with and without delta superinfection.

Receptors for polymerized human albumin are found at high titres during high-level hepatitis B virus (HBV) replication and in small amounts in chronic low-level infection. Complexes between hepatitis B surface antigen (HBsAg) and IgM without specificity for HbsAg are expressed in a pattern similar to that of receptors. Anti-albumin antibodies could be involved in their formation. Delta infection depresses the synthesis of gene products of HBV. To assess whether delta modifies the expression of receptors on HBsAg and the level of HBsAg/IgM complexes, and if anti-albumin antibodies are actually part of the complex, we tested sera from 86 subjects with acute and chronic HBV infection. Our findings show that the amounts of circulating receptors and HBsAg/IgM are proportional to the concentration of HBsAg and thus probably to the degree of viral replication. We did not find any correlation between circulating anti-albumin antibodies of the IgM class and HBsAg/IgM complexes. Delta infection depresses HBsAg synthesis and causes a related decrease in receptors and HBsAg/IgM titres if superimposed on the more active stage of HBV infection. When HBsAg, receptors, and HBsAg/IgM are at low levels, no further depression is caused by delta infection. HBsAg/IgM titre is not enhanced by presence of anti-delta antibodies, thus excluding a role of the latter in forming these complexes.

Acute Disease↗

The prognostic value of thyroid function tests in predominantly non-alcoholic cirrhotic patients: a prospective investigation.

The prognostic value of thyroid function parameters (T3, T4, rT3 and the rT3:T3 ratio) and common liver tests (serum bilirubin, albumin and prothrombin activity) was investigated on hospital admission in 100 consecutive patients with predominantly non-alcoholic liver cirrhosis. Twenty-nine out of 100 patients had a well compensated cirrhosis and their mean values of thyroid tests were similar to those of 40 healthy controls. A low T3 syndrome was found in the remaining 71 decompensated patients. In these thyroid function parameters were correlated with serum bilirubin and prothrombin activity. Moreover mean values of all thyroid and liver tests, except serum albumin, were significantly different between survivors and nonsurvivors at 3 months. To evaluate the best cut-off value which allowed to predict the outcome of patients, the Receiver Operating Characteristics (ROC) curves were generated for each test by plotting the values obtained in survivors at 3 months (true positives) vs nonsurvivors (false positives). By holding the false positive errors within 10%, the highest percentage of true positive results (i.e. patients dead at 3 months) was observed for the rT3:T3 ratio, rT3 and serum bilirubin at a cut-off point of 0.841, 55 ng/dl and 3.5 mg/dl, respectively. According to the above cut-offs the rT3:T3 ratio had the best positive predictive value (74%; 95% confidence limits 60-90%) in comparison to rT3 and bilirubin.

Adult↗

Delta agent infection in acute hepatitis and chronic HBsAg carriers with and without liver disease.

Hepatitis B virus (HBV) is a major cause of chronic liver disease in southern Italy. In the same area superinfection with the delta agent is endemic. To assess the prevalence of delta infection in a large population of patients with acute and chronic HBV related liver disease and to look for differential features among delta infected and uninfected subjects sera from 592 consecutive HBsAg positive patients were tested for the delta/anti-delta system by RIA. In no case was delta Ag found in serum. The prevalence of anti-delta was low in acute hepatitis (6.6%) and in asymptomatic carriers (6.4%) but raised in chronic active hepatitis with or without cirrhosis (52.3%). A decrease in frequency of anti-delta was seen in inactive cirrhosis (38.8%) and in hepatocellular carcinoma (11.9%). A younger mean age of delta-infected subjects was observed in each type of chronic liver disease. Our data confirm that delta agent superinfection is definitely associated with severe chronic active liver disease. The difference in age between anti-delta positive and negative patients suggests that delta infection accelerates the natural history of HBV related liver disease.

Acute Disease↗

Percutaneous blind biopsy versus laparoscopy with guided biopsy in diagnosis of cirrhosis. A prospective, randomized trial.

A prospective controlled study of the diagnostic accuracy of blind percutaneous liver biopsy in comparison to laparoscopy plus guided biopsy for the recognition or exclusion of cirrhosis has been performed. One hundred twenty-six patients with a clinical diagnosis of chronic, diffuse, well-compensated liver disease were randomized into two groups and submitted either to percutaneous blind liver biopsy (PB: 64 patients) or to laparoscopy with guided biopsy (LB: 62 patients), in order to assess the accuracy of either procedure in diagnosing cirrhosis. PB correctly recognized or ruled out cirrhosis in 52 patients (82%). Inconclusive results were mostly false negative, as demonstrated by the presence on endoscopy of esophageal varices or by subsequent LB. LB demonstrated presence or absence of cirrhosis in all patients. The difference between the rate of accurate results of the two procedures is statistically significant. It is concluded that in patients without esophageal varices, LB should be the investigation of choice for the assessment of liver structure since the presence of cirrhosis can be missed in up to 20% of cases by PB.

Adult↗