Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis.

BACKGROUND & AIM: An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. PATIENTS AND METHODS: A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. RESULTS: During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47-6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23-7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05-3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08-4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35-6.09; p = 0.006) were associated with HCC recurrence. CONCLUSION: An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. LAY SUMMARY: This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.

Modeling cost-effectiveness and health gains of a "universal" versus "prioritized" hepatitis C virus treatment policy in a real-life cohort.

We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected patients: policy 1, "universal," treat all patients, regardless of fibrosis stage; policy 2, treat only "prioritized" patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus-infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. CONCLUSION: Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017;66:1814-1825).

Forecasting Hepatitis C liver disease burden on real-life data. Does the hidden iceberg matter to reach the elimination goals?

BACKGROUND & AIMS: Advances in direct-acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked-to-care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030. METHODS: Using a modelling approach grounded in Italian real-life data of diagnosed and treated patients, different linkage-to-care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals. RESULTS: Under the 40% linked-to-care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948-1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0-F3 cases. Under the 60% linked-to-care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958-1978 birth cohorts could capture 55% of F0-F3 individuals. Under the 80% linked-to-care scenario, screening limited in 1968-1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals. CONCLUSION: In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required.

Prevalence and risk factors of erectile dysfunction in patients with hepatitis B virus or hepatitis C virus or chronic liver disease: results from a prospective study.

Background Approximately 300million people are affected by hepatitis B virus (HBV) or hepatitis C virus (HCV) infection worldwide. Erectile dysfunction (ED) is a frequent condition that impairs the quality of life and can be associated with several chronic disorders (type 2 diabetes mellitus, atherosclerosis, depression). Few studies have evaluated the prevalence of ED in patients with HBV and HCV chronic infection. The aim of this study was to evaluate the prevalence and the risk factors of ED in a cohort of patients with HBV or HCV-related chronic liver diseases. METHODS: Consecutive patients with HCV and HBV chronic infection were enrolled. RESULTS: In total, 89 out (49 with cirrhosis, 21 with HBV and 68 with HCV infection) were included in this study. ED was diagnosed in 76.4% of patients. The use of phosphodiesterase type 5 inhibitors was reported by 21.3% of patients. Patients with ED were older and had a higher rate of cirrhosis and diabetes mellitus compared with patients without ED. At multivariate analysis, diabetes mellitus and stage of liver disease (cirrhosis vs chronic hepatitis) were the only independent predictors of ED. CONCLUSION: Due to the high rate of ED in outpatients with viral-related liver disease and the underuse of phosphodiesterase type 5 inhibitors, a larger study focussed on these patients is needed.

Epidemiology and risk factors for hepatitis C virus genotypes in a high prevalence region in Italy.

Hepatitis C virus (HCV) is globally widespread. Southern Italy is a high prevalence region where the distribution of the HCV genotypes (GTs) is changing. Intravenous drug abuse is the only risk factor associated with a specific HCV GT (GT3). The aim of this study was to evaluate the distribution and the risk factors for specific HCV GTs. A total of 682 patients with measurable serum HCV-RNA were enrolled between January and March 2017. We recorded clinical information and the presence of risk factors for HCV. GT1b was the prevalent genotype in our patients (59.8%). HCV GT1a and GT3 infections were more frequent among patients aged ≤60 years (14.9% vs 2.2%, p<0.01 and 13.6% vs 0.8%, p<0.01, respectively). At multivariate analysis, intravenous drug abuse and age ≤60 years were associated with GT1a infection (OR: 4.79; 95% CI: 2.43-9.47, p <0.001 and OR: 5.07; 95CI: 2.25-11.40, p<0.001, respectively), while age ≤60 years was the only risk factor for GT3 (OR: 15.81; 95CI: 4.76-52.54, p <0.001). In the Campania region, we observed an increase in GT1a and GT3 rates compared with those observed in previous years. Age ≤60 was an independent risk factor for GT1a and GT3 infection. Intravenous drug use was independently associated with GT1a infection.

Sustained low influenza vaccination in health care workers after H1N1 pandemic: a cross sectional study in an Italian health care setting for at-risk patients.

BACKGROUND: Despite consistent recommendations by all Public Health Authorities in support of annual influenza vaccination for at-risk categories, there is still a low uptake of influenza vaccine in these groups including health care workers (HCWs). Aim of this observational two-phase study was to estimate the immunization rates for influenza in four subsequent seasons and for pandemic H1N1 influenza in HCWs of a University Hospital, and to investigate its distribution pattern and the main determinants of immunization. Phase 1 data collection was performed in 2009-2010, during the peak of H1N1 pandemic. Phase 2 data collection, aimed to investigate seasonal influenza vaccination coverage in the three seasons after pandemic, was performed in 2012-2013. METHODS: The overall H1N1 vaccination rate was derived by the Hospital immunization registry. In 2010, the personnel of three Departments (Infectious Diseases, Pediatrics and Gynecology/Obstetrics) completed a survey on influenza. A second-phase analysis was performed in 2012 to investigate influenza vaccination coverage in three consecutive seasons. RESULTS: The first-phase survey showed a low coverage for influenza in all categories (17 %), with the lowest rate in nurses (8.1 %). A total of 37 % of health care workers received H1N1 vaccine, with the highest rate among physicians and the lowest in nurses. H1N1 vaccination was closely related to the Department, being higher in the Department of Infectious Diseases (53.7 %) and Pediatrics (42.4 %) than in Gynecology/Obstetrics (8.3 %). The second-phase survey showed the lowest rate of influenza vaccination in 2012/13 season. The main reasons for not being vaccinated were "Unsure of the efficacy of vaccine" and "Feel not at-risk of getting influenza or its complications". Despite recommendations, influenza vaccine uptake remains poor. CONCLUSION: Immunization is largely perceived as a personal protection rather than a measure needed to prevent disease spreading to at-risk patients. Compulsory vaccination against influenza should be considered as a possible strategy, at least in health institutions where at-risk patients are admitted.

Resolution of autoimmune thrombocytopenia associated with raltegravir use in an HIV-positive patient.

About 10% of the human immunodeficiency virus (HIV) patients show thrombocytopenia. We describe the case of an HIV/HCV-positive patient whose autoimmune thrombocytopenia resolved with the addition of raltegravir to previous highly active antiretroviral therapy (HAART). It is noteworthy that the effect on platelet count appeared to be independent of viral load suppression, which was achieved with previous antiretroviral regimens. In fact, it has been suggested that the positive effect exerted by raltegravir on autoimmune diseases is due to its inhibition on herpes viruses, and hence on activation of endogenous human retroviruses. This consideration, if confirmed, could open new avenues in the treatment of autoimmune thrombocytopenia in the HIV setting.

Anti-HBc positivity was associated with histological cirrhosis in patients with chronic hepatitis C.

INTRODUCTION. In patients with chronic hepatitis C it is still debated whether previous exposure to the hepatitis B virus, diagnosed from the presence of the anti-HBc antibody, is linked to a greater risk of severe hepatitis. The aim of the study was to evaluate whether the presence of anti-HBc antibodies is associated with cirrhosis in patients with HBsAg-negative chronic hepatitis C. MATERIAL AND METHODS. Two hundred twenty-two consecutive HBsAg-negative patients with HCV-related chronic hepatitis were enrolled at their first liver biopsy. Ishak's scoring system was used to grade necroinflammation and fibrosis and the patients with stage 5 or 6 were considered as having histological cirrhosis. RESULTS. Patients with histological cirrhosis had a higher mean age, AST, ALT, a lower platelet count and prothrombin activity compared to those with milder fibrosis. The presence of anti-HBc was identified in 21 (63.6%) of the 33 patients with fibrosis score 5 or 6 and in 56 (29.6%; p < 0.001) of the 189 with score ≤ 4. Patients with cirrhosis had a significantly higher grading than those without cirrhosis (median = 8, IQR 6-11 vs. Median = 6, IQR = 4-8, respectively, p < 0.001). A multivariate logistic regression analysis showed that age, sex and anti-HBc positivity were independent predictors of histological cirrhosis. CONCLUSION. Our data support the idea that in patients with chronic hepatitis C the presence in serum of anti-HBc is associated with histological cirrhosis and is therefore a marker of clinical value.

Epidemiology, aetiology and treatment of skin and soft tissue infections: final report of a prospective multicentre national registry.

Skin and soft tissue infections (SSTIs) represent a heterogenous group of pathological conditions involving the skin or the underlying subcutaneous tissues, fascia and muscle, characterised by a considerable variety of clinical presentations, severity and possible aetiological pathogens. Although previous analyses on restricted types of SSTIs and population have already been published, we conducted a large nationwide surveillance program on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients and their management. Twenty-nine Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. We included in our database all cases managed by ID specialists participating to the study, independently from their severity or the setting of consultation. Here, we integrated previous preliminary results analysing and reporting data referring to a 3-year period (October 2016-October 2019). During this period, the study population included 478 adult patients with diagnosis of SSTI. The type of infection diagnosed, the aetiological agent involved and some notes on antimicrobial susceptibilities were collected and reported herein. We also analysed the most common co-morbidities, the type and duration of therapy executed, before and after ID intervention and the length of stay. The results of our study provide information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

Is the drug-induced hypersensitivity syndrome (DIHS) due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review.

BACKGROUND: Drug-Induced Hypersensitivity Syndrome (DIHS) is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug). We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug) interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases. CASE PRESENTATION: We report the case of a 26-year old woman with fever, systemic maculopapular rash, lymphadenopathy, hepatitis and eosinophilic leukocytosis. She had been treated with antibiotics that gave no benefit. She was taking escitalopram and lamotrigine for a bipolar disease 30 days before fever onset. Because the patient's general condition deteriorated, betamethasone and acyclovir were started. This treatment resulted in a mild improvement of symptoms. Steroids were rapidly tapered and this was followed with a relapse of fever and a worsening of laboratory parameters. Human herpesvirus 6 (HHV-6) DNA was positive as shown by PCR. Drug-Induced Hypersensitivity Syndrome (DIHS) was diagnosed. Symptoms regressed on prednisone (at a dose of 50 mg/die) that was tapered very slowly. The patient recovered completely. CONCLUSIONS: The search for rare causes of fever led to complete resolution of a very difficult case. As DIHS is a rare disease the most relevant issue is to suspect and include it in differential diagnosis of fevers of unknown origin. Once diagnosed, the therapy is easy (steroidal administration) and often successful. However our case strongly confirms that attention should be paid on the steroidal tapering that should be very slow to avoid a relapse.

Use of colistin in adult patients: A cross-sectional study.

OBJECTIVES: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). METHODS: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. RESULTS: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P = 0.024) was associated with use of colistin monotherapy. CONCLUSION: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Homocysteine levels and sustained virological response to pegylated-interferon alpha2b plus ribavirin therapy for chronic hepatitis C: a prospective study.

BACKGROUND: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate. AIMS: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment. METHODS: Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. RESULTS: Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR. CONCLUSIONS: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.

A simple noninvasive score predicts gastroesophageal varices in patients with chronic viral hepatitis.

BACKGROUND: Guidelines recommend upper endoscopic screening of cirrhotic patients for gastroesophageal varices. Cirrhosis is not always distinguishable from chronic hepatitis. GOALS: To identify low-risk patients who can be spared upper endoscopy irrespective of a diagnosis of cirrhosis. STUDY: We evaluated 13 nonendoscopic variables as predictors of esophagogastric varices in 254 patients with hepatitis B or hepatitis C-related chronic liver disease who underwent upper endoscopy. RESULTS: Any size varices occurred in 30.3% (77/254), and large varices in 12.2% of patients (31/254). Age >50 years [odds ratio (OR): 11.29; 95% confidence interval (CI): 2.33-54.67], platelet count <150,000/mmc (OR: 4.40; 95% CI: 1.85-10.45), albumin <3.6 g/dL (OR: 2.99; 95% CI: 1.31-6.79), and aspartate aminotransferase/alanine aminotransferase ratio >1 (OR: 2.83; 95% CI: 1.26-6.34) independently predicted varices by logistic regression. Using a score based on age >50 years, platelets <150,000/mmc, and aspartate aminotransferase/alanine aminotransferase ratio >1 (1 point/predictor), only 3.2% of patients with a score <2 had varices, all small. CONCLUSIONS: Patients with chronic viral hepatitis and a score <2 need not undergo upper endoscopy, as they are unlikely to have large varices. Because about 50% of our patients had this score, 50% of upper endoscopies may be safely avoided.

Iron depletion before HCV antiviral therapy: a pilot, randomized, controlled trial.

It is not known whether iron depletion before pegylated IFN or combination treatment improves sustained virological response (SVR) rate in patients with chronic hepatitis C, despite its use in clinical practice in this setting. We aimed to investigate whether blood letting improves the efficacy (SVR) and tolerability of PEG-IFNalpha2b + Ribavirin in chronic hepatitis C patients. Patients with chronic hepatitis C and ferritin >100 ng/mL were randomized to: (1) repeated phlebotomies to obtain a ferritin level <50 ng/mL followed by pegylated-Interferon alpha2b + ribavirin (active arm); or (2) pegylated-Interferon alpha2b + ribavirin (control arm). Primary endpoint was SVR rate, secondary endpoint was frequency of clinical and laboratory grade 3-4 adverse events. Thirty-three patients were enrolled in the study (19 in active arm, 14 in control arm). The 19 patients in the active arm underwent a median of 5 phlebotomies (range: 1-9) to achieve the targeted ferritin (<50 ng/mL). Phlebotomies significantly reduced ferritin, iron, transferrin saturation, aspartate aminotransferase, alanine aminotransferase, and hemoglobin levels. Platelet count significantly increased, whereas HCV-RNA levels remained unchanged. After antiviral therapy overall SVR was 31.6% in active arm and 21.4% in control arm (P = 0.698). Considering only the 18 patients who were naive to antiviral therapy, SVR was 60% in active arm versus 25% in control arm (P = 0.188). Tolerability, drug dose reduction or withdrawal were similar in the two arms. In conclusion phlebotomies do not increase the overall efficacy of antiviral therapy. However, the strong trend to higher SVR in naive patients undergoing phlebotomies warrants further investigation.

Real-World Efficacy and Safety of Pangenotypic Direct-Acting Antivirals Against Hepatitis C Virus Infection.

BACKGROUND: Advances in the development of Direct-Acting Antivirals (DAAs), particularly pangenotypic drugs, have led to a high rate of hepatitis C virus (HCV) eradication. Notably, real- world studies have confirmed the efficacy and safety of pangenotypic DAA combinations reported in registration trials. The aim of this study was to review the treatment recommendations, and the efficacy and safety data of anti-HCV pangenotypic drugs reported in registration clinical trials and in recent real-life cohort studies. METHODS: We reviewed the efficacy and safety data of pangenotypic anti-HCV drug combinations reported in original articles and in online conference abstracts. RESULTS: Current pangenotypic drug combinations resulted in very high rates of sustained virologic response and few adverse reactions in real-life settings. SVR12 rates in real-life studies ranged from 90-100% depending on the pangenotypic combination, the HCV genotype and the stage of liver disease. Most adverse reactions reported in real-life settings were mild in intensity and rarely led to treatment discontinuation. These results are in accordance with those of clinical trials. CONCLUSION: Pangenotypic DAAs result in very high rates of sustained virologic responses and are well tolerated. However, they are contraindicated in patients with decompensated cirrhosis or advanced chronic kidney disease who failed previous DDA-based treatment. Further research is required to customize treatment to "unpackage" current DAA combinations and to develop generic drugs against HCV.

Invasive pulmonary aspergillosis and pulmonary tuberculosis in a patient treated with infliximab for Crohn's disease.

We report a case of concurrent development of active pulmonary tuberculosis and invasive pulmonary aspergillosis (IPA) in a patient who received therapy with infliximab for Crohn's disease. He has been treated with antitubercular therapy and liposomal amphotericin B for 8 weeks. His clinical course was complicated by paroxysmal atrial fibrillation requiring maintenance therapy with amiodarone, respiratory failure due both to pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamases (ESBL)-producing Klebsiella pneumoniae and pleural effusion requiring chest drainage. At discharge, a maintenance regimen based on the administration of isavuconazole 200 mg daily, moxifloxacin 400 mg daily and isoniazid 300 mg daily was chosen to avoid multiple drug-drug interaction between rifamycins, antifungal triazole agents and antiarrhythmic drugs. At 3 months of follow-up his clinical conditions were dramatically improved, high resolution chest tomography (HRCT) showed reduction of parenchymal lesions and no changes both in sinus rhythm and QTc interval were noticed. Besides the complexity and the peculiarity of the clinical scenario, this case underlines the risk of invasive fungal infections linked to the administration of TNF-α antagonists in gastroenterological setting and the importance of accurate evaluation of drug-drug interactions when choosing the antimicrobial therapies.

Hepatitis C screening in the Emergency Department of a large hospital in southern Italy: results of a pilot study.

Around 71 million people worldwide are chronically infected with hepatitis C. HCV prevalence among individuals born in the United States between 1945 and 1965 is estimated to be about 3%. In Italy, about 2% of the population is chronically infected with HCV. Since chronic HCV infection is often asymptomatic, many patients require access to medical care only in an advanced phase of the disease. The best strategy for bringing out hidden chronic HCV infection remains uncertain. The aim of the study was to evaluate the feasibility of an FDA-approved rapid salivary, point-of-care (POC) assay for anti-HCV, performed in patients aged between 45 and 80 years old who were referred to the emergency department of a large hospital in southern Italy and were all unaware of their HCV serostatus. In all, 966 patients were interviewed during the study period. Among them, 220 patients were enrolled. Notably, 25/588 (4%) reported to be anti-HCV positive. Of these, 19 were already being treated with direct-acting antivirals (DAA). Among the enrolled patients, two (0.9%) tested anti-HCV positive and 218 (99.1%) were negative at screening. Both patients with a positive test were male, below the age of 54, with a previous history of intravenous drug abuse, a low level of education, and who had had at least one experience of unprotected sex. We scheduled a visit for treatment evaluation for every positive patient who was not on treatment. Neither of the two de novo patients and 3/6 (50%) patients who were aware of their anti-HCV positivity came to the follow-up visit. Our study shows that a screening strategy for HCV infection in ED is feasible and that about 1% of patients attending the ED and who are unaware of their conditions are anti-HCV positive. Moreover, a non-negligible proportion of subjects, though aware of their condition, was not linked to any hepatologic center.

Bacterial and CMV pneumonia in a patient treated with alemtuzumab for multiple sclerosis.

Alemtuzumab (a drug highly active in multiple sclerosis) is a humanized monoclonal antibody targeting the surface molecule CD52. It causes a rapid depletion of innate and adaptive immune cells with a peak during the first month after infusion. Infection rates in alemtuzumab-treated patients with multiple sclerosis in clinical trials were higher in than in interferon beta-treated patients. Cytomegalovirus (CMV) primary infections and reactivations have been reported in this setting of patients. We describe the case of a patient that developed both viral (CMV) and bacterial pneumonia one month after alemtuzumab infusion for multiple sclerosis. Physicians dealing with this drug should be aware of this serious but treatable complication.