ABSTRACT
AIM: Hepatocellular carcinoma (HCC) develops with high incidence in patients with chronic liver disease (CLD), and particularly in those with cirrhosis. Currently, diagnosis and surveillance are mainly based on imaging methods. The aim of this study was to evaluate the diagnostic accuracy of highly sensitive measurement of α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxyprothrombin (DCP) alone and in combination, for HCC detection. In addition, a recently proposed statistical model, including these three biomarkers plus sex and age, the GALAD model, was applied. METHODS: In a total of 98 patients (44 CLD patients without HCC [23 men, 21 women; mean age, 53.2 ± 13.4 years] and 54 patients with HCC [45 men, nine women; 69.5 ± 9.8 years]), AFP, AFP-L3 and DCP levels were determined using a highly sensitive assay on an µTASWako i30 immuno-analyzer. Areas under the curve (AUC), sensitivity and specificity were calculated and compared to assess diagnostic performance of the HCC biomarkers and of the GALAD model. RESULTS: AFP, AFP-L3 and DCP serum levels were significantly elevated in HCC compared with CLD patients (P < 0.0001). AUC values were 0.891, 0.867 and 0.870, respectively. The combination of the three biomarkers resulted in an AUC of 0.947, whereas the GALAD model showed an AUC of 0.976 with a difference between AUC values of 0.029 (P = 0.028). CONCLUSION: The combination of AFP, AFP-L3 and DCP is superior to a single biomarker in HCC detection. Furthermore, GALAD model performance is significantly higher than simple combination of these three biomarkers.
ABSTRACT
BACKGROUND: In Europe, adverse drug reactions and drug interactions are the cause of considerable morbidity and mortality. In over 75s, hospital access due to adverse drug reactions can be as high as 1 in every 3. AIMS: To assess the quality of the prescribed polytherapies in the territory, in terms of the risk of drug interactions and of prescription appropriateness, in over 75s. METHODS: Randomly selected patients, over 75s, were analysed among the patients of 3 general practitioners. Their data were analysed with the INTERCheck® software. This software provided the list of drug interactions deriving from the chronic therapies. The program also provided the Beers criteria and the STOPP criteria related to the drugs, highlighting potentially inappropriate drugs. RESULTS: A total of 188 patients were included in the study. A total of 216 serious or very serious drug interactions have been identified. A total of 92 patients (48.9%) were at risk of at least one serious or very serious interaction. The cut-off of the correlation between the number of drugs taken and the risk of incurring a serious or very serious interaction was found to be 5 (AUC = 0.833, sensitivity = 87%, p < 0.001). Patients on ≥ 4 drugs were at risk of prescriptive inappropriateness with a sensitivity of 84% (AUC = 0.781, p < 0.0001). CONCLUSIONS: Focusing on patients with at least 4 drugs in therapy is the right strategy to reduce the risks associated with polypharmacy.
Subject(s)
Drug Interactions/physiology , Drug-Related Side Effects and Adverse Reactions/diagnosis , Inappropriate Prescribing/adverse effects , Aged , Aged, 80 and over , Female , Humans , Male , PolypharmacyABSTRACT
BACKGROUND: Data on the prevalence of hepatitis C virus (HCV) infection in Italy are outdated and usually derived from studying residents in small towns. METHODS: To assess prevalence of and risk factors for HCV infection among Italian residents in 5 metropolitan areas, subjects ≥20â¯years of age were randomly selected from the list of the general practitioners' registers in 2015. Anti-HCV was tested by a salivary test; HCV-RNA, HCV genotypes, and ALT were determined in positive individuals. Logistic regression analysis evaluated independent risk factors for HCV. RESULTS: Of the 4907 enrolled subjects, 112 (2.3%) tested anti-HCV positive. The prevalence of HCV increased with age, from 0.2% in subjects born after the year 1984, to 4.2% in those born before the year 1935 (Pâ¯<â¯0.01). The birth-cohort prevalence peaked (7.0%) in elderly. Serum HCV-RNA was detected in 1.7% of the whole population. Nearly 80% of anti-HCV subjects were aware of their status. Ageâ¯>â¯70â¯years, low education level, past use of glass syringes, blood transfusion, intravenous drug use, and cohabitation with an anti-HCV positive subject predicted the HCV positivity. INTERPRETATION: In metropolitan areas in Italy, HCV is prevalent in elderly, reflecting a cohort effect determined by modalities of viral transmission no longer operative. The impact of the infection will further diminish in the years to come due to the natural depletion of the reservoir of the virus. This age pattern and the high proportion of subjects aware of their status do not warrant a policy of screening.
Subject(s)
Health Knowledge, Attitudes, Practice , Hepatitis C Antibodies/blood , Hepatitis C/epidemiology , RNA, Viral/blood , Adult , Age Distribution , Aged , Aged, 80 and over , Female , Hepacivirus/genetics , Humans , Italy/epidemiology , Logistic Models , Male , Middle Aged , Prevalence , Risk Factors , Sex Distribution , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Reliable biomarkers for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis are lacking. We evaluated the use of miR-122, alpha-fetoprotein (AFP) and protein induced by vitamin k absence/antagonist II (PIVKA-II) for HCC risk prediction in patients with HBV-related cirrhosis under surveillance. METHODS: We first analyzed a group of 63 patients with HBV-related liver cirrhosis of whom 33 had HCC. Then we performed a retrospective analysis on another group of 13 cirrhotic patients who developed HCC during surveillance, of whom serial serum samples were available (at time of HCC diagnosis [T0], 6-9 months [T-1] and 12-18 months [T-2] before HCC detection). Serum miR-122 levels were assessed by quantitative real time-PCR, whereas AFP and PIVKA-II were measured by fully automated chemiluminescent enzyme immunoassay. RESULTS: Serum levels of miR-122, AFP and PIVKA-II were different between patients with cirrhosis and those with HCC (P=0.024, P<0.001 and P<0.001, respectively). Areas under the curve (AUC) were 0.675 for miR-122, 0.791 for AFP and 0.846 for PIVKA-II, while their combination improved the discrimination power between cirrhosis and HCC (AUC=0.918). In the longitudinal study, we found a significant variation overtime for the biomarkers combination (P=0.011) but not for each single biomarker (miR-122, P=0.163; AFP, P=0.170; PIVKA-II, P=0.447). Combined miR-122+AFP+PIVKA-II adjusted Hazard Ratio for HCC development was 10.63, 95% confidence interval 1.87-60.28 (P<0.001). CONCLUSIONS: In HBV-related cirrhosis, the combination of miR-122, AFP and PIVKA-II enables the identification of patients at higher risk of HCC development that could benefit from closer monitoring.
Subject(s)
Biomarkers/blood , Carcinoma, Hepatocellular/blood , Early Detection of Cancer/methods , Hepatitis B/blood , Liver Cirrhosis/blood , Liver Neoplasms/blood , MicroRNAs/blood , Protein Precursors/blood , alpha-Fetoproteins/metabolism , Area Under Curve , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Cross-Sectional Studies , Female , Hepatitis B/complications , Hepatitis B/diagnosis , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/virology , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Longitudinal Studies , Male , MicroRNAs/genetics , Middle Aged , Predictive Value of Tests , Prognosis , Prothrombin , ROC Curve , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk Factors , Time FactorsABSTRACT
BACKGROUND: Patients with inflammatory bowel diseases (IBD) frequently have extraintestinal manifestations including arthritis, sacroiliitis, and ankylosing spondylitis. While the treatment of these rheumatological conditions with traditional non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to lead to frequent IBD exacerbation, the safety of cyclooxygenase-2 (COX-2) inhibitors (Coxibs) remains unclear. OBJECTIVES: Our aim is to carry out a meta-analysis to verify if Coxibs, employed to treat rheumatological manifestations, are associated with an increased risk of exacerbation of IBD compared to placebo. STUDY DESIGN AND SETTING: A MEDLINE, SCOPUS, ISI-Web of Knowledge, and EMBASE search of all studies published in English from 1965 to April 15, 2015, was conducted. Articles on the safety of Coxibs in patients with IBD were identified using the terms "Coxibs or cyclooxygenase-2 inhibitors or COX-2 inhibitors AND inflammatory bowel disease." METHODS: The criteria of exclusion of the studies were NSAIDs administration within 2 weeks before starting Coxibs. For the "proportion" meta-analysis, the studies had to report the proportion of patients that had to discontinue the Coxibs therapy due to an exacerbation of IBD; for the "relative risk" meta-analysis, the studies had to be prospective with a comparison between patients taking Coxibs and patients taking placebo. Two authors independently reviewed titles and abstracts of references retrieved from the literature search and selected potentially relevant studies. Differences in opinion were resolved by discussion until consensus was reached. If an agreement failed to be reached, a third author was consulted. The quality of each study was assessed on a 5-point scale adapted from studies by the Quebec Task Force on Whiplash-Associated disorders and Jadad. RESULTS: The search identified 72 publications of which 7 studies reported the proportion of patients with IBD that had to stop the Coxibs therapy because of a worsening of the activity of IBD. The pooled proportion of flare up of IBD in patients that received Coxibs was 14.4% (95% CI: 6.7-24.4%). There was no statistically significant difference between patients that assumed Coxibs and those that assumed placebo (total fixed effect relative risk = 0.86, 95% CI: 0.39-1.88, P = 0.7). LIMITATIONS: A proportion of patients received maintenance therapy with azathioprine or 6-mercaptopurine and these co-interventions could have protected against a Coxib-induced flare; furthermore, the duration of Coxib assumption in the prospective studies is shorter compared to that of the medical practice. Three of the studies included in our meta-analysis had an insufficient quality but due to the higher number of recruited patients, the studies with a better quality had a higher weight in the final result. Moreover, to assess the relative risk of flare up of IBD only randomized controlled trials have been used in the second meta-analysis. CONCLUSIONS: This meta-analysis showed that Coxibs are safe in most patients with IBD. Controlled trials of Coxibs compared with NSAIDs would be useful, at least in patients suffering from rheumatic pain refractory to standard treatment.