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Background: Hepatitis C virus (HCV) infection affects lipid metabolism. We investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism in chronic hepatitis C (CHC), with a focus on the effects of anthropometric parameters and liver histology. We also analyzed the dynamics of metabolic indexes used to estimate cardiovascular risk.Methods: In 49 patients with CHC treated with DAAs, lipid metabolic changes, anthropometric parameters, liver histology and cardiovascular risk indexes, including triglyceride to HDL ratio (Tr/HDL), fatty liver index (FLI) and visceral adiposity index (VAI) were evaluated at baseline (BL), end of treatment (EOT) and 12 [sustained virological response (SVR) 12] and 24 (SVR24) weeks after EOT.Results: SVR occurred in 96% of cases. Total and LDL cholesterol and ApoB levels increased significantly between BL and EOT (P

Background Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,absence of serum HBsAg, low/undetectable serum HBVDNA. Reactivation of HBV infection may occur during immunosuppression, but few data are available in heart transplant. Objectives We followed-up heart recipients with or without markers of previous HBV infection,evaluating prevalence of HBV markers, incidence of HBV reactivation and its virological and clinical features. Study design Heart failure patients listed for heart transplant (2007–2013) were screened for current or past HBV infection. Transplanted patients with past HBV infection (anti-HBc+/±anti-HBs+/HBVDNA−) were followed up as cases, and an equal number of HBV negative patients as controls. Virological reactivation was detected by standard real-time and home-made highly sensitive PCR (surface/core HBVDNA regions). Clinical status and progression were assessed by liver histology, ultrasound or elastography. Results 67 patients underwent heart transplant, including 4 (5.9%) HBsAg+ subjects. Cases were 11/67 (16.4%). During a median follow-up of 30 months, only one of these 11 patients presented viral reactivation (HBVDNA 209 IU/mL) at month 22, and started antiviral treatment. Four other recipients showed virological events of uncertain significance (sensitive PCR-only intermittently positive). Clinical signs of liver disease were observed in only one case at the last follow-up. A nonsignificant difference in survival was observed between cases and all other heart recipients without prior HBV contact (death rate 5/11 vs 15/52, respectively; p = 0.097). Conclusions HBV genotypic reactivation in HBsAg−/anti-HBc+/HBVDNA− heart recipients is uncommon. Virological events of uncertain significance occur more frequently; their clinical impact seems to be negligible.

Cardiogenic liver disease is a common yet poorly characterized complication of advanced heart failure (HF), and may impact clinical management in the setting of heart transplant evaluation. In this retrospective study, we describe clinical and histopathological features of liver injury in advanced HF, with a focus on the role of liver biopsy. Included were 45 HF patients, assessed for possible heart transplant, who underwent liver biopsy for suspected liver disease. Median duration of HF symptoms was 5years. Most patients had stiff hepatomegaly and elevated bilirubin. Viral hepatitis (19 patients, 42.2%) was the most common cause of prior known liver disease. Sinusoidal dilatation was detected in the majority of patients (64.4%). Median necroinflammatory index was 3 and median fibrosis was 1, consistent with a small burden of histologically proven liver disease. Viral hepatitis was the only variable associated with a higher grade of necroinflammation and fibrosis. Nine of the 14 (64.3%) advanced fibrosis/cirrhosis patients had a viral hepatitis infection. Fibrosis was significantly associated with splenomegaly. The MELD score was not correlated with cardiac index. A coarse liver echo-pattern had a 29% positive and 63% negative predictive value for advanced fibrosis/cirrhosis. Severe liver disease is uncommon in patients with advanced HF in the absence of splenomegaly or primary causes of liver disease. Ultrasound data need to be carefully evaluated, as it may overstate the severity of liver disease. Liver biopsy may be needed to accurately stage liver disease before excluding patients from advanced treatment strategies.

Background: Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. Methods: In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB. Results: Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0–4). Glomerular filtration rate (GFR) was

Current interest in HCV therapy with direct acting antivirals is focused on shortening treatment length. We managed two cirrhotics who achieved virological cure after 4Â weeks of ombitasvir/paritaprevir/ritonavir, dasabuvir, ribavirin treatment. Analysis to identify potential predictive factors for a successful outcome with a shorter treatment course was conducted.

Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice-monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV-DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild-to-moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV-DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV-DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine-resistant chronic hepatitis B.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

Background Pneumocystis jiroveci pneumonia may be a life-threatening opportunistic infection in immunosuppressed solid organ transplant recipients. Despite effective treatment with high-dose trimethoprim-sulfamethoxazole and steroids, morbidity is often severe and lethality remains high. New therapeutic approaches are therefore warranted. Caspofungin, a beta-1,3-glucan synthesis inhibitor, has shown activity against the cyst forms of P. jiroveci in experimental animal models. We here report our preliminary clinical experience with caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen. Methods Four solid organ transplant patients with severe hypoxemic P. jiroveci pneumonia were treated with the combination of trimethoprim-sulfametoxazole and caspofungin. In two cases, caspofungin was added as salvage treatment due to failure of trimethoprim-sulfametoxazole monotherapy. Results In these four patients, the use of caspofungin as an additional drug to the standard trimethoprim-sulfamethoxazole regimen led to a rapid improvement and a complete cure of pneumonia. No side effects or drug interactions were observed. Discussion This preliminary clinical experience suggests that the addition of caspofungin to trimethoprim-sulfamethoxazole, which is active against trophic forms, may provide a synergistic activity against P. jiroveci by fully inhibiting the organism life cycle.

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Clinical and epidemiological characteristics of Streptococcus bovis endocarditis were prospectively studied among 199 patients with definite endocarditis. Thirty patients (15.1%) had S. bovis endocarditis. Compared with patients with non–S. bovis endocarditis, these 30 patients were older (mean age, 58.6*12.4 years vs. 46.0*17.0 years; P < .001) and had higher rates of bivalvular involvement (43.3% vs. 7.7%; P

Cryptococcosis primarily occurs in patients with impaired immune response. While pulmonary and/or cerebral involvement are more often described, there is limited experience of its presence in other sites. We present a case of hepatic cryptococcosis with possible pulmonary involvement in a 54-year-old male heart transplant recipient. Two months after heart transplantation, he developed a persistent, moderate dyspnea with fever and signs of liver damage. Diagnosis was made with liver biopsy for a concurrent reactivation of chronic hepatitis B virus (HBV) infection already present before transplant. Along with a mild chronic HBV hepatitis with fibrosis, we observed sinusoidal dilation and groups of bright, rounded, colorless cells with a central nucleus suggestive of cryptococci. Periodic acid–Schiff stain clearly showed encapsulated yeasts, which supported the diagnosis. Cryptococcal antigen was positive in serum and negative in the cerebrospinal fluid. Computed tomography scan of the chest demonstrated a mild interstitial infiltrate. The patient promptly responded to reduction of immunosuppressive therapy and antifungal treatment with amphotericin B lipid complex and flucytosine followed by maintenance treatment with fluconazole. Cryptococcosis should always be considered in the differential diagnosis in immunocompromised hosts with dyspnea and signs of extrapulmonary involvement. Diagnosis of extrapulmonary and extraneural cryptococcosis is difficult and often fortuitous; a histopathological examination of tissues involved is probably warranted.

We conducted a long-term prospective study of 89 cancer survivor children who had acquired hepatitis B virus (HBV) and/or hepatitis C virus (HCV) during treatment for neoplasia, the aim being to evaluate the natural history of the diseases and the effect of interferon (IFN) treatment. Patients were followed up for a median period of 13 years (range, 8 to 20); 46 were infected by HBV, 11 by HCV, and 32 coinfected by HBV and HCV. A spontaneous clearance of hepatitis B surface antigen (HBsAg) occurred more frequently in coinfected patients (19%) than in the HBV-infected (2%; P = .004), with an annual seroconversion rate of 2.1% and 0.2%, respectively (P= .008). Loss of hepatitis Be antigen (HBeAg) occurred in 44% of coinfected and in 28% of HBV-infected patients. Clearance of serum HCV-RNA was observed in 34% and 9%, respectively, of coinfected and HCV-infected patients. Seventeen HBV-infected, 4 HCV-infected, and 16 coinfected patients received -IFN treatment. In the HBV group, 6 patients (35%) cleared serum HBV DNA and seroconverted to anti-HBe; in the HCV-group, none cleared HCV-RNA. In the coinfected group, 1 patient cleared both HBV DNA and HCV-RNA, 6 patients cleared serum HCV-RNA alone, and 1 only HBV DNA and HBeAg. Overall, the diseases showed a mild histological course with no evidence of liver cirrhosis. A reciprocal interference on viral replication between HBV and HCV may occur in coinfected patients. Treatment seems to be effective for selected cases and is justified in view of the uncertain prognosis of the disease in these patients.

OBJECTIVE To evaluate the efficacy of a long-term course of alpha-interferon (alpha-IFN) in the treatment of HCV-related mixed cryoglobulinaemia and to determine the impact of cryoglobulinaemia on therapeutic response to IFN in chronic hepatitis C (CHC) patients. DESIGN Prospective controlled study. SETTING University Medical Centre. PARTICIPANTS Ninety consecutive CHC patients, 50 with cryoglobulinaemia (25 symptomatic and 25 asymptomatic; median cryocrit, 8%; chronic persistent hepatitis (CPH) 7, chronic active hepatitis (CAH) 27, cirrhosis 16) and 40 without cryoglobulinaemia (CPH 6, CAH 20, cirrhosis 14). HCV genotypes in the cryoglobulinaemic and non-cryoglobulinaemic groups were: 1b 40% and 45%; 2a 40% and 30%; others 20% and 25%, respectively. INTERVENTIONS Twelve-month course of alpha-IFN 2a, 3 MU, three times weekly. MAIN OUTCOME MEASURES Disappearance of cryoglobulinaemia and related syndrome, clearance of serum HCV RNA and normalization serum transaminase levels at the end of treatment (response) and after 12 months follow-up (sustained response). RESULTS Overall, cryoglobulinaemic patients showed a similar response to IFN to those without cryoglobulinaemia (44% vs. 42.5%, respectively). In the cryoglobulinaemic group, symptomatic patients showed a lower response rate than asymptomatic patients (28% vs. 60%, respectively; P

Objectives. Cytomegalovirus (CMV) disease often represents a serious complication that promotes opportunistic infections in heart transplant recipients. In this study we evaluated the impact of preemptive gancylovir therapy, guided by pp65 antigenemia on the morbidity associated with viral reactivation. Patients and methods. We have performed a CMV infection surveillance program since March 1999, with antigenemia pp65 determinations weekly for the first 2 months biweekly in the third months, and monthly to the sixth month. Patients with pp65 antigenemia value 10 positive cells per 2 10 5 polymorphonuclear cells (PMN) were treated with intravenous gancyclovir followed by 1 month of oral gancyclovir. Results. Among the 107 patients who underwent the virological monitoring, 80 were pp65 antigenemia-positive with preemptive therapy administered in 48 cases. Five patients displayed symptomatic CMV disease (4.7% vs 18% rate in the period of 1988 to 1998 before the introduction of virologic monitoring; P .01). We observed only one case of gancyclovir-resistant pneumonia which was successfully treated with foscarnet. CMV recurrence in 10 patients required a second cycle of gancyclovir treatment. Our experience included 13 opportunistic infections (12.7%) with 11 antigenemia-positive. Conclusions. Preemptive therapy drastically reduces the incidence of CMV disease and the associated morbidity. Compared to universal prophylaxis, this approach may avoid unnecessary pharmacologic treatment in more than 50% of transplant recipients. Indeed, preemptive therapy does not fully prevent CMV disease, because it may manifest at the first antigenemia determination, and furthermore may select gancyclovir-resistant strains.

Background Cardiac implantable electronic device (CIED)-related endocarditis is a growing challenge because of increasing incidence and significant mortality. Current treatment is based on complete hardware removal coupled with long-term administration of effective and safe antimicrobials. Daptomycin at the dose of 6 mg/kg/day has been found to be effective in staphylococcal endocarditis, but limited data exist on CIED endocarditis. Moreover, whether higher doses could be more effective but equally safe in this setting is currently unknown. Methods We report here our experience with high-dose daptomycin in the treatment of 25 cases of CIED endocarditis due to staphylococci. Results Patients were mostly elderly and male, with large lead vegetations and severe comorbidities. Pathogens were Staphylococcus epidermidis (56%), Staphylococcus aureus (28%), and other coagulase-negative staphylococci (16%). Only 4 patients (16%) had a normal pretreatment renal function. The median daptomycin daily dose was 8.3 mg/kg (range, 6.4-10.7). Daptomycin was administered for a median of 20 days (range, 8-52). Percutaneous lead extraction was performed in 88% of patients. Two patients (8%) failed to clear bacteremia. The overall clinical success of treatment was 80%, whereas a complete microbiological success was observed in 92% of patients. Creatine phosphokinase values were monitored and increased above normal in 5 cases (20%). No serious adverse event related to high-dose daptomycin was observed and no patient required discontinuation because of muscle toxicity. Conclusions Our experience suggests that high-dose daptomycin may be a safe therapeutic option in staphylococcal CIED endocarditis and may be associated with high microbiological responses and clinical success.

Background/aim The combination of pegylated interferon (PEG-IFN) and ribavirin (RBV) is the current treatment for chronic hepatitis C (CHC). The treatment is thought to suppress viral replication and induce viral clearance via immunomodulatory effects. For this reason, concern exists for the use of this treatment in recipients of a solid organ transplantation. We sought to evaluate the safety and efficacy of PEG-IFN/RBV in heart transplant recipients with CHC. Methods From June 2005 to September 2009, we treated three CHC patients with heart transplantation. PEG-IFN alpha2b and RBV doses and treatment duration were set according to the hepatitis C virus (HCV) genotype and body weight as per current recommendations. Dose reductions were dictated by individual patient tolerability. Cardiac safety was monitored by clinical examinations, echocardiography, and measurement of troponin I and B-type natriuretic peptide, as well as endomyocardial biopsies. Results All three patients, displayed HCV genotype 1b infection, viral loads of >5 logs, and a Scheuer fibrosis score ≥ 2. Two of them completed the prescribed treatment course becoming sustained virological responders. The other patient had an initial complete virological response, but subsequently experienced a viral breakthrough after reduction of PEG-IFN and withdrawal of RBV due to severe anemia. We observed no cardiovascular adverse events nor rejection episodes. Posttreatment clinical history and examination, electrocardiography, and echocardiography did not show any sign of graft dysfunction. Conclusions Treatment with PEG-IFN/RBV may be safely offered to stable heart transplant recipients with CHC and signs of liver disease progression. Close monitoring of treatment safety is mandatory.

Background Chronic hepatitis C patients with coexisting heart disease are often denied antiviral treatment due to safety concerns. However, this is not evidence-based. Aims To evaluate safety and efficacy of pegylated interferon and ribavirin in chronic hepatitis C patients with heart disease. Methods Patients with overt heart disease (ischaemic heart disease, prior mechanical heart valve replacement, chronic arrhythmias and cardiomyopathy) and chronic hepatitis C were treated with standard pegylated interferon/ribavirin doses for standard duration. Cardiovascular safety was monitored by electrocardiography, echocardiography and measurement of troponin and B-type natriuretic peptide. Results Twenty-three patients (65.2% male, median age 57 years, 47.8% genotype 1) were treated. Three patients (13%) suspended treatment prematurely; 52% obtained sustained virological response, 39% relapsed, 9% were non-responders. No serious adverse event was observed. Post-treatment clinical examination, electrocardiography and echocardiography did not show any sign of progression of the pre-existing heart disease. Conclusions Treatment with pegylated interferon/ribavirin may be safely offered to carefully selected chronic hepatitis C patients with coexisting, clinically significant heart disease. In these patients, the outcome of antiviral treatment overlaps that observed in other patient subgroups.

We evaluated clinical evolution and hepatitis B virus (HBV) molecular changes in heart recipients with chronic HBV infection before transplantation, and studied the effects of lamivudine treatment in patients who experienced HBV reactivation. Nine patients with chronic HBV infection who underwent heart transplantation were investigated. HBV surface/core-promoter/precore/core regions were sequenced. Prior to transplantation, all nine patients had consistently normal ALT and low HBV-DNA levels. Seven experienced HBV reactivation after transplantation (ALT elevated, HBV-DNA >200.000 cps/ml). Lamivudine treatment was initially effective in all patients; three patients during the second year of treatment developed lamivudine resistance-associated mutations (rt-L180M, rt-M204V) with severe disease reactivation, remitted after switch to adefovir treatment. No other significant HBV mutations were identified in the genomic regions studied. Immune suppression is crucial in the reactivation of previous inactive HBV infection and in the liver disease progression in heart recipients. Preemptive lamivudine treatment could be useful in the early management of these patients.

Objective This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. Patients and methods Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo = 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n = 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. Results The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P = .004 and P = .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P = .001 and P = .008). Conclusions The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

Background Infective endocarditis often is complicated by embolic events after hospital admission. Identifying patients at higher risk may improve the disease outcome. This study was aimed at identifying predictors of embolic risk among the clinical and laboratory data obtained on hospital admission in patients diagnosed as having definite infective endocarditis according to the Duke criteria. Methods Ninety-four patients were enrolled in a prospective study. The results of hematologic, echocardiographic, and microbiological investigations were analyzed, using statistical methods as appropriate. Multivariate analysis was applied to variables significantly associated with embolism in univariate analysis. Results Forty-six percent of patients had a major embolic complication after admission. No association was found between embolism and sex, site of infection, or microorganism involved. Patients with embolism were significantly younger, had larger vegetation, and showed a significantly higher level of serum C-reactive protein and lower albumin concentrations than those without embolism. Young age, larger vegetation size, and high levels of C-reactive protein were the independent variables associated with an increased incidence of embolic events in the multivariate logistic regression analysis. Conclusions Our data indicate that patients with infective endocarditis with young age and/or with large vegetation and/or with high serum levels of C-reactive protein are at increased risk of major embolic complications during the in-hospital course of the disease.

Described here is the first definite case of endocarditis due to Moraxella phenylpyruvica, which occurred in a 50-year-old male with a bicuspid aortic valve. The diagnosis was delayed because of the confounding positivity of the Widal and Wright tests. The patient was cured with surgical valve replacement and antibiotic treatment.

Objective The aim of this study was to assess the relationship between HCV genotype and histological liver injury. Design Prospective study on a cohort of patients with biopsy proven chronic hepatitis C. Setting University medical centre. Participants Enrolled were 324 consecutive patients (male 197, median age 52 years, range 19-68; chronic hepatitis, 224; cirrhosis, 100). Methods HCV genotype was determined by the INNO LiPA assay and HCV RNA levels by the bDNA assay. The histological features were scored according to the histology activity index. Results The distribution of HCV genotypes was 1 a, 4.6%; 1b, 52.4%; 2a/c, 27%; 3a, 8%; 4, 2%; mixed, 6%. Serum HCV RNA levels were similar for all genotypes. There was no difference in the distribution of HCV genotypes between patients with chronic hepatitis and those with cirrhosis. Patients with genotype 1 b and those with type 2a/c showed a similar prevalence of cases of cirrhosis (33% versus 31%, respectively). In addition, in a subgroup of 102 patients with an established date of infection, the progression to cirrhosis occurred with a similar length of time for HCV type 1 b and 2a/c (median 16 versus 15 years, respectively). Patients with HCV genotype 2a/c or mixed genotype showed a higher histology activity index than those with type 1b (P < 0.01), whereas there was no difference in the fibrosis score for the different genotypes. Patients with genotype 3a showed a significantly higher prevalence of steatosis compared to those infected with other genotypes. Alanine aminotransferase (ALT) values were higher in patients with HCV type 2a/c, 3a and mixed genotype than those with type 1 (P < 0.002). Conclusions The data indicate that there is no association between a particular HCV genotype and the progression to cirrhosis, and that specific genotypes are associated with distinct histopathological and biochemical manifestations although none of them is correlated with an increase of the fibrosis stage.