Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in chronic hepatitis C

AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in chronic hepatitis C virus (HCV) infection. METHODS: The model, based on the sequential combination of the Bonacini score (BS: ALT/AST ratio, platelet count and INR) and ultrasonography liver surface characteristics, was applied to 176 patients with chronic HCV infection. Assuming a pre-test probability of 35%, the model defined four levels of post-test probability of severe fibrosis/cirrhosis: <10% (low), 10-74% (not diagnostic), 75-90% (high) and >90% (almost absolute). The predicted probabilities were compared with the observed patients' distribution according to the histology (METAVIR). RESULTS: Severe fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated patients in three comparable groups: 34% with a very high (>90%) or low (<10%) probability of severe fibrosis, 33% with a probability ranging from 75% to 90%, and 33% with an uncertain diagnosis (i.e., a probability ranging from 10% to 74%). The observed frequency of severe fibrosis/ cirrhosis was within the predefined ranges. CONCLUSION: The model can correctly identify 67% of patients with a high (>75%) or low (<10%) probability of cirrhosis, leaving only 33% of the patients still requiring liver biopsy.     

Raloxifene lowers IGF-I levels in acromegalic women

BACKGROUND: IGF-I suppression in acromegaly obtained by tamoxifen, a selective estrogen receptor modulator (SERM), prompted us to evaluate the effects of the administration of a newer SERM, raloxifene (RAL), devoid of estrogenic activity at uterine level, on GH/IGF-I levels in patients with this disease. PATIENTS: Thirteen post-menopausal acromegalic women (aged 55-84 years) with active acromegaly entered a prospective open pilot study of RAL treatment at 60 mg/day. Nine of the patients, who were resistant to somatostatin analog and dopamine agonist treatment, were not undertaking therapy; the other four, who were partially sensitive to medical treatment, maintained treatment at the maximally effective dosages throughout the study. RESULTS: IGF-I levels fell significantly from 444 (median, interquartile 393-590) microg/l to 300 (216-608) microg/l (P=0.0192) after 1 month of RAL administration and this fall remained stable up to the final evaluation at 5+/-1 months from the start of RAL treatment (260 (187-410) microg/l). An IGF-I decrease greater than 30% of basal values was observed in 10 patients (mainly in patients with IGF-I levels lower than 600 microg/l) and normal values were reached in seven (54%). GH levels did not change (basal 6 (4.1-8) microg/l, final 5.5 (3.2-7.4) microg/l). The clinical picture improved in patients sensitive to RAL. RAL withdrawal was followed by the return of IGF-I levels to pretreatment values within 8 weeks in all patients. CONCLUSIONS: RAL decreases IGF-I levels in most acromegalic women with mild or intermediate disease (i.e. with values lower than 600 microg/l) and normalizes it in many. A prospective randomized study in patients resistant or partially sensitive to other medical treatments is warranted.     

Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests

Conventional coagulation tests might be inadequate to explore mechanisms regulating thrombin generation in neonates, because they do not allow full activation of the reduced levels of protein C. Therefore, they do not reflect the action of pro- and anti-coagulants as does the endogenous thrombin potential assessed in the presence of thrombomodulin. Endogenous thrombin potential measured without thrombomodulin was greater than the lower-limit of the adult reference interval in 30% of 109 full-term and 49% of 55 pre-term neonates, a finding consistent with the reduced levels of procoagulants in this setting. When the test was modified adding thrombomodulin, endogenous thrombin potential reverted into the adult reference interval in 97% and 100% full-term and pre-term neonates. In conclusion, the coagulation balance in neonates is restored by the concomitant reduction of pro- and anticoagulants. The restored balance can be shown in vitro by the endogenous thrombin potential test that includes thrombomodulin, but not by conventional coagulation tests.     

Direct-acting antiviral agents for hepatitis C virus-mixed cryoglobulinaemia: dissociated virological and haematological responses

The hepatitis C virus-positive (HCV+) mixed cryoglobulinaemia (MC) is associated with haematological alterations such as monoclonal B-cell lymphocytosis or non-Hodgkin lymphomas (NHLs). Antiviral therapy for MC, based on interferon and ribavirin, has been shown to be able to eliminate the viral replication as well as the B-cell monoclonal alterations. Many studies have reported the efficacy of direct-acting antivirals (DAAs) in the treatment of HCV+ MC. However, some authors noticed the persistence of haematological diseases despite HCV eradication. To verify the effects of DAAs on B-cell proliferation, we evaluated 67 patients with HCV+ MC. Six patients had an overt NHL and 30% had monoclonal B-lymphocytosis. In 20% of the patients, the mutation L265P of the myeloid differentiation factor 88 (MYD88) gene was detected in peripheral blood. All patients had negative HCV viraemia at week 12; one had a breakthrough, while two cases relapsed. A complete clinical response of vasculitis was seen in 60% of the patients. Among the six patients with NHL, one showed a complete response, whereas in the others there were no changes in the number and size of the nodes. Among the patients carrying a clonal population in peripheral blood, only 22% became negative. These data indicate that DAAs are not able to eliminate the clonal alterations induced by HCV in a large proportion of cases.     

Is there a practical way of predicting therapeutic success in type 2 diabetes on the basis of psychological features? Development and validation of the Psychological Predictors of Therapeutic success in Diabetes (PPTD) questionnaire

Many psychiatric disorders and symptoms have been associated with impaired metabolic control in type 2 diabetes; several studies focused on non-pathological psychological features. Aims of this observational, longitudinal study are: the assessment of the impact of a wide range of psychological factors on metabolic control in type 2 diabetes; and the development and validation of a simple questionnaire to assess the impact of psychological factors on therapeutic success. To identify psychological factors interfering with attainment of glycemic targets, a prospective 1-year study was performed on a sample of 250 patients with type 2 diabetes. The impact of identified factors on therapeutic outcome was then subsequently verified on a further, independent sample of 200 patients. The first phase of the study allowed the development of a 19-items questionnaire, the Psychological Predictors of Therapeutic success in Diabetes (PPTD) questionnaire. Validation analyses showed that the questionnaire was able to predict therapeutic success. Patients with HbA1c ≤7 % (53 mmol/mol) at follow-up showed higher test scores than those with HbA1c >7 % [31.0 (26.2; 35.0) vs 28.0 (23.0; 32.0); p = 0.016]. The attainment and maintenance of therapeutic goals in patients with type 2 diabetes depend on a wide range of factors. The PPTD is an attempt at condensing the complexity of psychological factors affecting glycemic control in a simple and easy-to-use self-reported questionnaire, which can be used in wide-scale research.