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Biomedical subjects

Alfonso Mele

Publications and source records attributed to Alfonso Mele.

At least 19 recordsLinked to original sources

Acute hepatitis delta virus infection in Italy: incidence and risk factors after the introduction of the universal anti-hepatitis B vaccination campaign.

BACKGROUND: Updates on the incidence of and risk factors for acute hepatitis delta virus infection in Italy, as well as in other countries, are lacking, and the impact of the mandatory anti-hepatitis B vaccination has not been evaluated. METHODS: We performed a case-control study within a population-based surveillance for acute viral hepatitis. RESULTS: During 1993-2004, 344 cases of acute hepatitis delta virus infection were reported. After a peak in 1993 (2.8 cases per 1 million population), the incidence decreased from 1.7 to 0.5 cases per 1 million population. Coinfections were prevalent. The decrease in incidence particularly affected young adults, and it paralleled the decrease in incidence of acute hepatitis B. In 1993, being an injection drug user (adjusted odds ratio [OR(adj)], 67.9; 95% confidence interval [CI], 18.1-254.5) or being a member of a household with a carrier of hepatitis B surface antigen (OR(adj,) 14.8; 95% CI, 3.0-72.9) were the only independent predictors of infection. During 1994-2004, being an injection drug user (OR(adj), 36.8; 95% CI, 20.7-65.4), cohabitation with an injection drug user (OR(adj), 4.2, 95% CI, 1.7-12.3), hospitalization (OR(adj), 3.5; 95% CI, 1.9-6.6), receipt of dental therapy (OR(adj), 2.3; 95% CI, 1.4-3.6), promiscuous sexual activity (OR(adj), 2.2; 95% CI, 1.4-3.6), and receipt of beauty treatment (OR(adj), 2.0; 95% CI, 1.3-3.2) were independently associated with infection. CONCLUSIONS: Incidence of acute hepatitis delta infection is markedly decreasing in Italy. Undergoing invasive medical procedures, engaging in promiscuous sexual activity, and receiving beauty treatments are emerging, in addition to injection drug use, as important risk factors for infection. Further efforts are needed to increase vaccine coverage in high-risk groups and to implement the safety of invasive procedures performed both inside and outside health care facilities.

Adolescent↗

High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma.

In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.

Antibodies, Viral↗

An outbreak of hepatitis A virus infection with a high case-fatality rate among injecting drug users.

BACKGROUND/AIMS: In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. METHODS: We conducted an epidemiological investigation, including a case-control study, to identify the source and the modes of HAV transmission. Hepatitis B and C (HCV) viruses and human immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence analysis of the VP1/2A junction of the HAV isolates was also performed. RESULTS: Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was contact (not related to injecting practices) with a jaundiced person (odds ratio: 5.8; 95% confidence interval: 1.3-29.9). Of the cases, 58% were anti-HCV positive and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype IB (8 cases) and IIIA (7 cases) were detected. CONCLUSIONS: HAV was probably transmitted through the fecal-oral route, although parenteral transmission cannot be excluded. The high fatality rate was probably due to severe underlying liver damage. The occurrence of this outbreak highlights the need for routine HAV vaccination for IDUs.

Adolescent↗

Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection.

Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8+ T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8+ T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8(+ T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi-species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8+ T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage.

Adult↗

Prevalence and etiology of altered liver tests: a population-based survey in a Mediterranean town.

Serum biochemical liver tests (LTs) (ALT, AST, GGT) and platelet counts are often used to screen for chronic liver disease. Population-based data on abnormal LTs in Mediterranean areas are lacking. The prevalence and etiology of abnormal LTs were assessed from 2002 to 2003 in a 1 in 5 systematic random sample of the general population who were 12 years of age or older in Cittanova, a southern Italian town with 10,600 inhabitants. LTs, indices of metabolism, and markers of HBV and HCV infection were assayed and alcohol intake was recorded in the selected population. In virus-free individuals with abnormal LTs, LTs were retested, and upper abdominal echography and tests for other causes of liver damage were undertaken. Among the 1,645 individuals screened, the prevalence of anti-HCV was 6.5%; the prevalence was particularly high in individuals over 50 years of age. The corresponding prevalence for HBsAg was 0.8%. The overall prevalence of individuals with abnormal LTs was 12.7% (95% CI: 11.1-14.3). The probable cause of abnormal LTs was excessive alcohol in 45.6%, HCV in 18.6%, HBV in 1%, alcohol plus HCV and/or HBV in 8.8%, and rare diseases in 2%. In 24% of individuals with abnormal LTs, the probable cause was nonalcoholic fatty liver disease (NAFLD); in this subgroup, increased body weight, hypercholesterolemia, and hyperglycemia were common, and 63.3% of them had a bright liver at echography. In conclusion, in southern Italy, a Mediterranean area where dietary habits are different from those in industrialized areas, one eighth of the general population has abnormal LTs suggestive of possible liver damage; NAFLD appears to be emerging as a potentially important etiology of this presumed liver injury.

Adult↗

The importance of HCV on the burden of chronic liver disease in Italy: a multicenter prevalence study of 9,997 cases.

Knowledge of the current epidemiology of chronic liver disease in Italy is mostly obsolete and fragmentary for the lack of up-to-date consistent data. In 2001, a 6-month prevalence study was undertaken in 79 hospitals to assess the characteristics of chronic liver disease in Italy. Both prevalent and incident cases were enrolled. A total of 9,997 patients were recruited, of whom 939 (9.4%) had normal liver biochemistry, 6,210 (62.1%) had chronic hepatitis, 1,940 (19.4%) had liver cirrhosis, and 341 (3.4%) had hepatocellular carcinoma (HCC). In 567 patients (5.7%) the diagnosis was not established. Hepatitis C virus (HCV) was found in 69.9% of the patients and was the only etiological factor in 56.3% of all the patients. Hepatitis B surface antigen (HBsAg) was present in the serum of 13.4% of the cases (in 10% it was the only etiological factor). A history of alcohol abuse was found in 23% of the cases (9.4% without viral infection). The prevalence of HCV-related cases was significantly lower in incident than in prevalent cases (44.9% vs. 59.9%, P < 0.0001), while the proportion of patients with alcohol abuse was much higher in incident than in prevalent cases (18.1% vs. 6.6%, P < 0.0001). These findings indicate that nearly one quarter of patients with chronic liver diseases in Italy have a severe disease such as liver cirrhosis and HCC represents a not negligible burden for the national health system. Hepatitis B fell in importance as an etiological factor. Hepatitis C is the important pathogenic factor for chronic liver disease in Italy. However, a comparison between the prevalent and incident cases suggests that in future HCV infection will also play a progressively decreasing role, in part as a consequence of treatment.

Adult↗

Prevention of viral hepatitis in Italy.

The overall situation on viral hepatitis prevention and control in Italy was reviewed and evaluated at a Viral Hepatitis Prevention Board (VHPB) meeting in Catania, Sicily, on 7-8 November 2002. Several specific conclusions, drawn from the presentations and discussions, were considered to constitute an example of how to handle these issues in other European and industrialized countries.

Disease Notification↗

Role of beauty treatment in the spread of parenterally transmitted hepatitis viruses in Italy.

The aims of the study were to evaluate the role of beauty treatments in the spread of acute viral hepatitis B (HBV) and acute viral hepatitis C (HCV) in Italy. Data from the surveillance system for acute viral hepatitis (SEIEVA) during the period 1997-2002 were used. After exclusion of subjects <15 years or >55 years old and reporting intravenous drug use or blood transfusion, the association of acute HBV and HCV cases with beauty treatments (tattooing, piercing, manicure/chiropody, and barber shop shaving) was estimated comparing 2,964 hepatitis B and 598 hepatitis C cases with 7,221 hepatitis A cases, used as controls, by multiple logistic regression analysis. The population attributable risk (PAR) to beauty treatments was estimated according to Levin's formula. Beauty treatments were associated with acute HBV (OR = 1.8; CI 95% = 1.5-2.1) and acute HCV (OR = 1.7; CI 95% = 1.2-2.3). The strongest association was found with barber shop shaving for HBV (OR = 1.8; CI 95% = 1.5-2.2) and with tattooing for HCV cases (OR = 5.6; CI 95% = 2.8-11.0). The estimates of the population attributable risk (PAR) indicate that nearly 15% of all acute HBV (17.4% in males) and 11.5% of all acute HCV cases (16.4% in males) occurring in 15-55 year old subjects not exposed to intravenous drugs or blood transfusion in Italy are due to beauty treatments. It is concluded that certain beauty treatments play an important role in the spread of HBV and HCV infections in Italy.

Adolescent↗

Use of the minimum spanning tree model for molecular epidemiological investigation of a nosocomial outbreak of hepatitis C virus infection.

The minimum spanning tree (MST) model was applied to identify the history of transmission of hepatitis C virus (HCV) infection in an outbreak involving five children attending a pediatric oncology-hematology outpatient ward between 1992 and 2000. We collected blood samples from all children attending since 1992, all household contacts, and one health care worker positive for antibody to HCV (anti-HCV). HCV RNA detection was performed with these samples and with smears of routinely collected bone marrow samples. For all isolates, we performed sequence analysis and phylogenetic tree analysis of hypervariable region 1 of the E2 gene. The MST model was applied to clinical-epidemiological and molecular data. No additional cases were detected. All children, but not the health care worker, showed genotype 3a. On six occasions, all but one child had shared the medication room with another patient who later seroconverted. HCV RNA detection in bone marrow smears revealed, in some cases, a delay of several months in anti-HCV responses. Sequence analysis and phylogenetic tree analysis revealed a high identity among the isolates. The MST model applied to molecular data, together with the clinical-epidemiological data, allowed us to identify the source of the outbreak and the most probable patient-to-patient chain of transmission. The management of central venous catheters was suspected to be the probable route of transmission. In conclusion, the MST model, supported by an exhaustive clinical-epidemiological investigation, appears to be a useful tool in tracing the history of transmission in outbreaks of HCV infection.

Child↗

Prevalence of hepatitis C virus infection in lymphoproliferative diseases other than B-cell non-Hodgkin's lymphoma, and in myeloproliferative diseases: an Italian Multi-Center case-control study.

BACKGROUND AND OBJECTIVES: Infection with hepatitis C virus (HCV) is associated with type II mixed cryoglobulinemia (MC), a lymphoproliferative disorder which, in some patients, evolves into overt B-cell non-Hodgkin's lymphoma (B-NHL). Recently, also the association between HCV infection and B-NHL, which had long been controversial, was confirmed in a large case-control study. Little knowledge is, however, available on possible associations between HCV infection and other lymphoid or myeloid malignancies. The present study was set up in order to investigate this aspect. DESIGN AND METHODS: The study was conducted in hematology departments of ten hospitals in different Italian cities. The cases consisted of consecutive patients with a new diagnosis of T-NHL, Hodgkin's disease (HD), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), multiple myeloma (MM), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). The controls were patients in other departments of the same hospitals. HCV infection was investigated by testing for HCV antibodies and HCV-RNA in serum samples. RESULTS: The prevalence of HCV infection was not higher in patients with HD (3.2%, 5 out of 157 cases) or MM (4.7%, 5 out of 107) than in controls. On the other hand, it was consistently higher in T-NHL (13.8%, 4 out of 30), CLL (9.0%, 9 out of 100), ALL (7.6%, 5 out of 54), AML (7.9%, 11 out of 140), and CML (12.2%, 6 out of 49) patients. These patient groups were not, however, large enough to render statistically significant results. INTERPRETATION AND CONCLUSIONS: Our data suggest that HCV infection may be associated not only with B-NHL but also with some other lymphoid and myeloid malignancies.

Acute Disease↗

Survival of elderly patients with acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: The prognosis of elderly patients with acute myelogenous leukemia (AML) is usually dismal, while the true survival of older patients not included in clinical trials is not known. We retrospectively evaluated the impact on survival of an aggressive versus a non-aggressive approach in 1005 patients aged >60 years registered in the database of the GIMEMA cooperative group. DESIGN AND METHODS: Group A patients (n=621) received aggressive treatment, while group B patients (n=384) underwent non-aggressive therapy. The groups were different for risk factor distribution: the patients in group B had a higher median age, worse performance status (PS) and a higher proportion of previous myelodysplastic disease. RESULTS: The overall median survival was 7 and 5 months in groups A and B, respectively (p min of 0.0001). At multivariate analysis the following factors were associated with a significantly shorter survival: age >71 years (RR=1.27; 95% CI=1.07-1.50), PS=2-4 (RR=1.44; 95% CI=1.24-1.68), white cell count > 10,000 mL (RR=1.37; 95% CI=1.06-1.75), and heart dysfunction requiring treatment (RR=1.26; 95% CI=1.05-1.50). No difference in survival was associated with aggressive or non-aggressive treatment (RR=1.1; 95% CI=0.94-1.32). Patients aged min of 70 years, with no heart disease, but a white cell count > 10,000/mL showed a significantly better survival when treated aggressively (median survival 7 vs 3 months, p = 0.011). INTERPRETATION AND CONCLUSIONS: Despite an obvious selection of patients with a worse prognosis in group B, the difference in survival between the two groups was marginal. Multivariate analysis failed to demonstrate a significant survival benefit in aggressively treated patients. All these considerations indicate that elderly patients with AML are overall unlikely to benefit from aggressive treatment, so that this should be offered only to selected patients.

Acute Disease↗

Hepatitis C virus and B-cell non-Hodgkin lymphomas: an Italian multicenter case-control study.

The existence of an association between infection with hepatitis C virus (HCV) and B-cell non-Hodgkin lymphoma (B-NHL) remains controversial, largely because previous studies were based on prevalent case series or comparisons with less than optimal control groups. This hospital-based case-control study was conducted from January 1998 through February 2001 to evaluate the association between HCV infection and B-NHL of different types. Cases were consecutive patients with a new diagnosis of B-NHL; controls were patients from other departments of the same hospitals. Both groups were interviewed using a standardized questionnaire. The prevalence of HCV infection was calculated by histologic type of B-NHL and clinical behavior (indolent or aggressive). Adjusted odds ratio (OR) and HCV-attributable risk (AR) were estimated. HCV prevalence was 17.5% among the 400 lymphoma patients and 5.6% among the 396 controls. The OR of B-NHL (patients vs controls), adjusted by age, sex, level of education, and place of birth, was 3.1 (95% confidence interval [CI], 1.8-5.2); an OR indicative of positive association was found for indolent and aggressive B-NHL. The estimated AR was 4.6%. This study confirms an association between HCV and B-NHL. In Italy, 1 of 20 instances of B-NHL may be attributable to HCV infection and may, thus, benefit from antiviral treatment.

Adolescent↗

Factors affecting the compliance of the antenatal hepatitis B screening programme in Italy.

The effectiveness in the prevention of perinatally transmitted HBV infection was assessed in 11858 pregnant women consecutively recruited in public and private hospitals in six Italian regions during a 2 months period in 2001. Of them 10881 (91.8%) attended HBsAg antenatal screening. The overall HBsAg prevalence was 1.7% (CI 95%: 1.4-1.9); it was 1.4% (CI 95%: 1.2-1.7) in pregnant women born in Italy but 5.9% (CI 95%: 4.1-8.1) in those born in Asia, Africa, central and south America, and eastern Europe. Results of multiple logistic regression analysis indicate that birth in foreign countries (OR 2.0; CI 95%: 1.3-3.0), family size with more than 4 members in the household (OR 3.5; CI 95%:2.7-4.6), and birth in a private hospital (OR 1.9; CI 95%: 1.3-2.8) were all independent predictors of lack of adherence to HBsAg screening. Out of the 182 new-borns of HBsAg positive mothers 172 (95.0%) were given active plus passive immunisation; this figure was 100% in new-borns of foreign mothers. These findings evidence a good effectiveness in the prevention of perinatally transmitted HBV in Italy. More efforts should be addressed to improve the effectiveness of the programme among foreign pregnant women who have high rate of HBsAg and more likely escape HBsAg screening than Italian pregnant women.

Adolescent↗