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Hepatitis B surface antigen (HBsAg) is considered the best marker for the diagnosis of hepatitis B virus (HBV) infection. Mutations of the s gene involving amino acid substitutions within the a determinant could affect the sensitivity of diagnostic tests. In the present study, HBsAg mutants were detected in 3 immunocompromised patients, previously found to be HBsAg negative and anti-HBs positive. All patients had high levels of HBV-DNA, whereas HBsAg tests gave discordant results. Immunosuppression can cause viral reactivation of occult HBV infection in these patients and favour the selection of HBsAg a determinant mutants. 2010 S. Karger AG, Basel.

A 56-year-old man developed disseminate lymphadenopathies, associated with hepato-splenomegaly, fever, nocturnal sweating and weight loss. Imaging studies in particular FDG-PET/CT raised the suspicion of a malignant disease. But blood flow cytometry assay for B/T cell clonality was negative and fine-needle biopsy of enlarged laterocervical lymph node showed a not specific "reactive hyperplasia". Four months later, the patient developed a non-itching rash; since a further anamnestic investigation revealed an history of high-risk sexual intercourse, the patient underwent serological tests for Treponema pallidum that were positive at high titer, after a first negative screening. Made the diagnosis of secondary syphilis, the patient responded to the treatment with benzyl penicillin with complete resolution of symptoms. This case highlights the importance of carefully screening the patients with suspected lymphoadenopathies also for lue, particularly in presence of behavioral risk factors.

OBJECTIVES: Historically, only 10% of patients with hepatocellular carcinoma (HCC) are diagnosed with early-stage, potentially curable disease. In this study, chronic hepatitis virus-infected patients were prospectively screened to determine: (i) the proportion of patients diagnosed with potentially curable HCC, and (ii) survival following curative therapy. METHODS: The study included 8900 chronic hepatitis virus-infected patients enrolled in a prospective screening programme, of whom 1335 (15.0%) were infected with hepatitis B virus (HBV), 7120 (80.0%) with hepatitis C virus (HCV), and 445 (5.0%) with both HBV and HCV. Screening was conducted every 6 months and included serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, radiofrequency ablation and/or ethanol injection. RESULTS: Hepatocellular carcinoma was diagnosed in 765 (8.6%) patients. Of 1602 patients with cirrhosis, 758 (47.3%) developed HCC. Curative treatment was possible in 523 (68.4%) of the 765 HCC patients. Two- and 5-year rates of overall survival in the curative treatment group were 65% and 28%, respectively, compared with 10% and 0% in the advanced disease group (P < 0.001). CONCLUSIONS: Prospective screening of patients at high risk for the development of HCC increases the proportion of patients diagnosed with potentially curable disease. This may result in an increase in the number of longterm survivors. Screening strategies should focus on patients with chronic HBV or HCV infection who have progressed to cirrhosis because more than 40% of these patients will develop HCC.

The reverse seroconversion to hepatitis B virus infection has been sporadically described in onco-haematological patients receiving cytotoxic therapy or allogeneic bone marrow transplantation and can be associated with the development of acute icteric hepatitis. We present a male HBsAg-negative, anti-HBc-positive patient with Hairy Cell Leukemia who developed acute B hepatitis more than 1 year after the last course of 2-CdA and 6 months after splenectomy, while the patient was receiving therapy with alphaIFNr. The acute B hepatitis promptly responded to lamivudine therapy followed by viral clearance.

Hepatitis C virus (HCV) affects millions of individuals worldwide. In most cases, HCV infection progresses to chronic liver disease and, subsequently, to liver cirrhosis and hepatocellular carcinoma. HCV is transmitted by the parenteral route, for example by transfusion of blood or blood products, injection during drug abuse, etc., and by the inapparent parenteral route (penetration of the virus through difficult-to-identify microlesions present on the skin or mucosae), for example, sexual exposure or household exposure to infected contacts, etc. The cost of chronic hepatitis C and its sequelae is high in both financial and human terms. At present, only anti-HCV screening of blood/organ/tissue donors and universal precautions for the prevention of blood-borne infections are recommended for HCV prevention. Before the discovery of the main aetiological agent of non-A, non-B hepatitis (HCV), several randomised controlled clinical trials demonstrated that standard intramuscular immunoglobulin exerted a preventive effect on post-transfusional and sexual and /or horizontal transmission of non-A, non-B hepatitis. When serological tests for HCV infection became available, bimonthly inoculation of standard unscreened intramuscular immunoglobulin (prepared from plasma pools containing about 2% of anti-HCV-positive units) was demonstrated to significantly prevent sexually transmitted HCV infection. The immunoglobulin used contained high titres of anti-HCV neutralising antibodies (anti-E2 neutralisation of binding assay), whereas currently available commercial screened immunoglobulin (prepared from anti-HCV-negative blood units) did not. This finding suggested that anti-HCV neutralising antibodies are concentrated only in anti-HCV-positive units (which are currently discarded). Thus, anti-HCV hyperimmune globulin (HCIg) can be produced only from anti-HCV-positive units. The neutralising titre can be increased by the exclusive use of units with higher titres of neutralising antibodies. Unlike other hyperimmune globulins, which are produced from a limited number of selected donors, HCIg should be produced from a large number of units so as to contain neutralising antibodies to the different HCV strains. HCIg will have a number of advantages: (i) it is easy to produce and inexpensive; (ii) it has a long half-life, allowing infrequent administration; (iii) new additional viral inactivation procedures have been introduced to eradicate transmission of infection, and (iv) it may be possible to neutralise all the emerging HCV strains. HCIg could be used in all individuals at risk of HCV infection (sexual partners, haemodialysis patients, etc), in preventing reinfection of transplanted livers, and perhaps also in the treatment of chronic hepatitis C, alone or associated with other drugs.

Lamivudine can select resistant hepatitis B virus (HBV) tyrosine-methionine-aspartate-aspartate aminoacid motif (YMDD) mutants, which usually disappear in few months after lamivudine withdrawal. We report an unusual case of a male adult patient who showed a prolonged persistence of the M204I mutation up to 24 months after lamivudine withdrawal followed by the emergence of new distinct YMDD mutants (namely M204V, V207L). Only 42 months after lamivudine withdrawal wild-type YMDD motif became dominant over the YMDD mutants. To our knowledge, a so prolonged persistence of a YMDD mutant and also the emergence of new YMDD mutants many months after drug withdrawal are unusual.

We report the case of a 42-year-old woman with chronic hepatitis C (genotype 1), who in June 2004 started therapy with pegylated interferon alpha (PEG-IFNalpha) plus ribavirin. Two months later, she discontinued treatment because of polydipsia, polyuria and vomiting leading to a marked dehydration. Biochemical data showed type 1 diabetes mellitus with ketoacidosis, and insulin therapy was started. The patient, who before starting PEG-IFN alpha plus ribavirin therapy tested negative for glutamic acid decarboxylase antibodies (GADAb) and islet cell (ICAb) antibodies, became strongly positive for both autoimmune markers. This case confirms that patients with chronic hepatitis C who do not have baseline markers of pancreatic autoimmunity may develop severe ketoacidosis during treatment with PEG-IFNalpha, as well as with standard IFNalpha. In order to avoid this complication, as no guidelines are available and the pancreatic autoimmunity markers are not routinely analysed, we suggest frequent monitoring (e.g., every one to two weeks) of glycaemic values: e.g., every one to two weeks during the first 3 months (when this complication occurs most frequently) and monthly thereafter so as to identify diabetes at an early stage and before the onset of the appearance of severe ketoacidosis, which is life-threatening.

The sexual transmission of hepatitis C virus (HCV) has long been debated. The prevalence of infected at-risk partners varies from 0% to 30%. In a prospective study, the risk of infection was quantified in steady heterosexual partners and the prophylactic effect of normal human polyvalent immune serum globulin (ISG) was evaluated. A total of 899 at-risk partners of HCV-infected patients were enrolled in a single-blind randomized controlled trial and assigned to receive every 2 months 4 mL of intramuscular ISG from unscreened donors (450 partners) or placebo (499 partners). Seven partners developed acute HCV infection (increased aminotransferase levels and appearance of HCV-RNA): six of the placebo group (incidence density [ID] 12.00/1,000 person year; 95% confidence interval [CI] 3.0 to 21.61), and only one of the ISG-treated group (ID 1.98/1,000 person year; 95% CI 0 to 5.86). The risk of infection was significantly higher in controls versus treated individuals (p = 0.03). Six couples had genotype 1b (85%), and one couple had genotype la; HCV sequence homology strongly supported sexual transmission. Our trial demonstrates that HCV infection can be sexually transmitted and quantifies the risk of sexual transmission: for every year of at-risk sexual relationship, almost 1% of the partners became infected. Intramuscular ISG is safe and well tolerated. Unlike ISG from screened donors, ISG from donors unscreened for anti-HCV contains high titers of anti-gpE1/gpE2 neutralizing antibodies and high neutralizing activity. Anti-HCV hyperimmune globulin could be prepared from anti-HCV-positive blood units and could be used to protect sexual partners and in other at-risk situations of exposure to HCV infection.

Worldwide the needlestick injuries of health care workers (HCWs) still represent a major health problem. The authors aimed to evaluate the risk of HCW needlestick injuries in a tertiary university hospital in southern Italy in relation to some HCW characteristics (age, sex, professional profile, work department) and the source of infection. All HCWs of the University Hospital "Federico II" in Naples, Italy, attending the Infectious Diseases Unit after potential accidental contact to blood-borne viruses through needlestick injuries were enrolled during a 22-year period. HCWs underwent clinical analysis and were administered a specific questionnaire to collect (in anonymous fashion) data about age, sex, professional profile and work department. From 1995 to 2016 1,477 needlestick injuries in the same number of people (one accident per person) were recorded by our service. The HCWs were predominately males (n = 806, 55%) and the mean age was 39.4 years (±10.1 SD). The job categories most involved were: physicians (41%), followed by nurses (33%) and healthcare assistants (HCAs, 10%). The incidence proportion was calculated for these highest-risk categories in three defined time points (at the beginning, in the middle and at the end of the study period): 104/2149 (4.86%) in 1995, 41/2498 (1.64%) in 2005 and 25/2057 (1.22%) in 2015. Most injuries occurred in General Surgery (14.21%), Gynecology and Obstetrics (9%) and Pediatrics (6.49%). In about 34% the HCWs had been exposed to HCV infected fluids. Over time, a significant decrease in accidental exposure was recorded for physicians (p= 0.019), nurses (p< 0.0001) and HCAs (p< 0.0001). Our results confirm that some profiles, namely physicians, nurses and healthcare assistants, are still at risk of needlestick injuries, especially in surgical areas, including obstetric wards. Further primary and secondary prevention strategies are needed to decrease the incidence of new cases of needlestick injuries.

Visceral leishmaniasis, a protozoan disease caused by Leishmania infantum, is endemic in the Mediterranean basin, especially southern and Tyrrhenian Italy. Its aetiological agent can also sporadically cause isolated laryngeal localization in at-risk patients (i.e., heavy smokers, immunocompromised patients). This rare localization is often pauci-symptomatic and thus can easily escape diagnosis. A case of isolated leishmaniasis limited to the left vocal cord in an immunocompetent Italian male without significant risk factors, randomly discovered upon histological examination, is described herein. We inquire how many patients affected by non-specific symptoms such as dysphonia and live in countries where Leishmania infantum infection is reported, could be truly affected by Leishmania spp infection.

Hepatitis A virus is a widely occurring disease, with different prevalence rates between countries in the North and West and those in the South and East. In Italy endemicity is low/medium, but not homogeneously distributed: in the northern/central regions a large hepatitis A outbreak due to genotype IA, related to the consumption of contaminated mixed frozen berries, occurred between 2013 and 2014, whereas in southern Italian regions recurrent outbreaks of hepatitis A, due to the IB genotype, still result from consumption of raw seafood. In 2014 an uncommon genotype IA strain was isolated from five patients (2 adults and 3 children) with hepatitis A, living in the surroundings of Naples (Campania) who did not have any of the most common risk factors for hepatitis A in Italy, such as consumption of raw shellfish or frozen berries, or travel to endemic countries. Moreover, based on the analysis of viral sequences obtained, this strain differed from several others in the national database, which had been recently isolated during Italian outbreaks. This case report reinforces the need to implement both information campaigns about the prevention of hepatitis A and vaccination programmes in childhood; in addition, it would be suitable to sequence strains routinely not only during large outbreaks of hepatitis A in order to obtain a more detailed national database of HAV strains circulating in Italy.

Objectives: To estimate the risk of sexual transmission of hepatitis C and to assess the value of prophylaxis with periodic intramuscular immune serum globulin administration. Methods: Of 1102 steady heterosexual partners of patients with antibodies to the hepatitis C virus (HCV), 899 were enrolled in a single-blind, randomized, controlled trial. All the partners tested negative for antibodies to HCV and had normal baseline serum aminotransferase concentrations. The partners were assigned to receive 4 mL of 16% polyvalent immune serum globulin prepared from unscreened donors every 2 months (n=450) or a placebo (n=449). Tests for HCV infection were performed every 4 months. Results: Eight hundred eighty-four partners completed the study. Seven partners became infected with HCV: 6 in the control group (incidence density, 12.00 per 1000 person-years; 95% confidence interval, 3.0-21.61) and 1 in the immune serum globulin group (incidence density, 1.98 per 1000 person-years; 95% confidence interval, 0-5.86). The risk of infection was significantly higher for partners in the control group ( P =.03): for each year approximately 1% of the partners became infected. Sequence homology studies strongly suggest the sexual transmission of HCV. All immune serum globulin lots used had high enzyme-linked immunosorbent assay titers of neutralizing antibodies to HCV envelope glycoproteins and high neutralization titers in the neutralization of binding assay. Conclusions: Hepatitis C can be sexually transmitted. Immune serum globulin prepared from unscreened donors significantly reduced the risk. The treatment was safe and well tolerated. Because only immune serum globulin from unscreened donors (and not from those screened for HCV) contain anti-HCV neutralizing antibodies, hyperimmune anti-HCV immune serum globulin should be prepared from blood testing positive for antibodies to HCV, which is currently discarded. Arch Intern Med. 1997;157:1537-1544

The effects of interferon-alpha (IFN-alpha), given at a dosage of 6 MU thrice weekly for 12 months, on gonadal function were investigated in 18 males affected by chronic hepatitis C. Periodically, all patients were clinically monitored and questioned about sexual function. Gonadotropin and serum androgen concentrations (follicle-stimulating hormone, luteinizing hormone, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin) were tested every 3 months. Ten of 18 patients (55%) responded to IFN-alpha therapy. Serum total testosterone and sex hormone binding globulin values decreased slightly at the third month of treatment, then returned to baseline values. Serum free testosterone and other sex hormones remained essentially unchanged during IFN-alpha therapy. Four patients (22.2%) complained of sexual dysfunction (impaired libido, erectile failure, and impaired ejaculation), which was unrelated to any significant hormonal change and resolved after IFN therapy was stopped. Serum sex hormones values did not differ between responders and nonresponders to IFN-alpha. This study indicates that 12 months treatment with 6 MU of IFN-alpha thrice weekly does not significantly affect gonadal function in men with chronic hepatitis C. The sexual dysfunction observed could be ascribed to such other side effects of IFN as asthenia, fatigue, or anxiety, or it could have a psychologic basis.