Benedetto Maurizio Celesia

Hepatic echinococcosis: Clinical and therapeutic aspects

Echinococcosis or hydatid disease (HD) is a zoonosis caused by the larval stages of taeniid cestodes belonging to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated into alveolar and cystic forms, associated with Echinoccus multilocularis (E. multilocularis) and Echinococcus granulosus (E. granulosus) infection, respectively. Cystic echinococcosis (CE) has a worldwide distribution, while hepatic alveolar echinococcosis (AE) is endemic in the Northern hemisphere, including North America and several Asian and European countries, like France, Germany and Austria. E. granulosus young cysts are spherical, unilocular vesicles, consisting of an internal germinal layer and an outer acellular layer. Cyst expansion is associated with a host immune reaction and the subsequent development of a fibrous layer, called the pericyst; old cysts typically present internal septations and daughter cysts. E. multilocularis has a tumor-like, infiltrative behavior, which is responsible for tissue destruction and finally for liver failure. The liver is the main site of HD involvement, for both alveolar and cystic hydatidosis. HD is usually asymptomatic for a long period of time, because cyst growth is commonly slow; the most frequent symptoms are fatigue and abdominal pain. Patients may also present jaundice, hepatomegaly or anaphylaxis, due to cyst leakage or rupture. HD diagnosis is usually accomplished with the combined use of ultrasonography and immunodiagnosis; furthermore, the improvement of surgical techniques, the introduction of minimally invasive treatments [such as puncture, aspiration, injection, re-aspiration (PAIR)] and more effective drugs (such as benzoimidazoles) have deeply changed life expectancy and quality of life of patients with HD. The aim of this article is to provide an up-to-date review of biological, diagnostic, clinical and therapeutic aspects of hepatic echinococcosis.

Microbial Translocation in Chronic Liver Diseases

The intestinal microflora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microflora may lead to microbial translocation, defined as the passage of viable microorganisms or bacterial products (i.e., LPS, lipopeptides) from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. The most recent evidence suggests that microbial translocation (MT) may occur not only in cirrhosis, but also in the early stage of several liver diseases, including alcoholic hepatopathy and nonalcoholic fatty liver disease. Different mechanisms, such as small intestinal bacterial overgrowth, increased permeability of intestinal mucosa, and impaired immunity, may favor MT. Furthermore, MT has been implicated in the pathogenesis of the complications of cirrhosis, which are a significant cause of morbidity and mortality in cirrhotic subjects. Therapeutic strategies aiming at modulating the gut microflora and reducing MT have focused on antibiotic-based options, such as selective intestinal decontamination, and nonantibiotic-based options, such as prokinetics and probiotics. In particular, probiotics may represent an attractive strategy, even though the promising results of experimental models and limited clinical studies need to be confirmed in larger randomized trials.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32–97), lowest in Northern Europe (median 44%, IQR 22–68%) and highest in Eastern Europe (median 99%, IQR 86–100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0–4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

Symmetric ambulatory arterial stiffness index and 24-h pulse pressure in HIV infection: results of a nationwide cross-sectional study.

Objective: HIV infection has been associated with increased cardiovascular risk. Twenty-four-hour ambulatory blood pressure (BP) is a more accurate and prognostically relevant measure of an individuals BP load than office BP, and the ambulatory BP-derived ambulatory arterial stiffness index (AASI) and symmetric AASI (s-AASI) are established cardiovascular risk factors. Methods: In the setting of the HIV and HYpertension (HIV-HY) study, an Italian nationwide survey on high BP in HIV infection, 100 HIV-infected patients with high-normal BP or untreated hypertension (72% men, age 48 ± 10 years, BP 142/91 ± 12/7 mmHg) and 325 HIV-negative individuals with comparable age, sex distribution, and office BP (68% men, age 48 ± 10 years, BP 141/90 ± 11/8 mmHg) underwent 24-h ambulatory BP monitoring. Results: Despite having similar office BP, HIV-infected individuals had higher 24-h SBP (130.6 ± 14 vs. 126.4 ± 10 mmHg) and pulse pressure (49.1 ± 9 vs. 45.9 ± 7 mmHg, both P < 0.001), and a lower day-night reduction of mean arterial pressure (14.3 ± 9 vs. 16.3 ± 7%, P = 0.025). Both s-AASI and AASI were significantly higher in HIV patients (s-AASI, 0.22 ± 0.18 vs. 0.11 ± 0.15; AASI, 0.46 ± 0.22 vs. 0.29 ± 0.17; both P <0.001). In a multivariate regression, s-AASI was independently predicted by HIV infection (&bgr; = 0.252, P <0.001), age, female sex, and 24-h SBP. In HIV patients, s-AASI had an inverse relation with CD4+ cell count (Spearmans &rgr; −0.24, P = 0.027). Conclusion: Individuals with HIV infection and borderline or definite hypertension have higher symmetric AASI and 24-h systolic and pulse pressures than HIV-uninfected controls matched by office BP. High ambulatory BP may play a role in the HIV-related increase in cardiovascular risk.

Switch to dolutegravir plus Rilpivirine dual therapy in cART-Experienced subjects: An observational cohort

Introduction Little information is available on the efficacy and safety of the dual combination of ripivirine plus dolutegravir. This work aims at beginning to fill this gap. Methods All HIV-1 infected subjects treated with ripivirine plus dolutegravir between October 2014 and September 2015 in eight Italian centres were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48. Results One hundred and thirty-two subjects were followed for a median of 24 months, mean 33 months. One subject discontinued the study drug at week 24 for headache, one for drug interaction and one died after week 24 of illicit drug abuse. The mean age was 51.8, females 31.7% and non-caucasians 10%. Fifty-seven (43.2%) had at least one failure in their treatment history. Reasons for switching were simplification (53.0%), toxicity (34.8%), drug interactions (n = 7), persistent low-level viremia (n = 4), non-adherence (n = 3) and viral failure (n = 2). Sixty patients (45.5%) had reverse transcriptase (RT) mutations and 69 (44,7%) had protease (PR) mutations. Sixteen had baseline viral replication, 27 had < 50 HIV-1 RNA copies/mL and in 89 (67.4%) no virus was detected (NVD, 0 copies/mL). At w4, 114 (86.4%) had NVD, 15 had 1 to 49 HIV-1 RNA copies/mL and 3 had 50 to 57 copies/mL. At week 24 one subject had viral rebound without mutations due to missed drug refill, 19 had 1 to 49 copies/mL, and 112 had NVD. All 132 subjects were tested at weeks 4 and 24. Of the 50 subjects who had a 48-week follow-up, one had a treatment interruption, four had 1 to 49 copies/mL and 45 had NVD. Among the entire population, one subject had low-level, one intermediate and 4 high-level resistance to rilpivirine: none failed by week 48. Mean serum creatinine increased by +0.1 mg/dL. During the follow-up one patient reported headache and insomnia. Conclusions Ripivirine plus dolutegravir proved safe and effective in this cohort of non-naïve HIV-1 infected subjects.

Muscle symptoms and creatine phosphokinase elevations in patients receiving raltegravir in clinical practice: Results from the SCOLTA project long-term surveillance

Muscle alterations ranging from asymptomatic creatine phosphokinase (CPK) increases to rhabdomyolysis and central nervous system (CNS) symptoms have been reported in patients receiving raltegravir. Muscle symptoms and CPK increases were investigated in a cohort of HIV-infected patients receiving raltegravir-based antiretroviral therapy, and possible associated predictors were evaluated. The SCOLTA Project is a prospective, observational, multicentre study created to assess the incidence of adverse events in patients receiving new antiretroviral drugs in clinical practice. In total, 496 HIV-infected patients were enrolled [333 (67.1%) male]. CDC stage was C in 196 patients (39.5%). Mean age at enrolment was 45.9 ± 9.3 years. Median follow-up was 21 months. Twenty-six patients (5.2%) reported muscle symptoms (16 muscle pain and 17 weakness; 7 had both). Of 342 patients with normal baseline CPK values, 72 (21.1%) had a CPK increase. Seven patients (1.4%) discontinued raltegravir because of muscular events (three for muscle pain/weakness and four CPK increases). No cases of rhabdomyolysis were observed. Patients with muscle symptoms were more frequently receiving in their regimen than those not receiving atazanavir (P=0.04) and were more likely to also report CNS symptoms (P<0.0001). Significant predictors of muscle symptoms were CNS symptoms and use of atazanavir. Female sex was associated with a reduced risk of CPK increase. In conclusion, muscle symptoms and CPK elevations occurred frequently and caused most discontinuations due to adverse events. Their monitoring in patients receiving raltegravir should be considered, especially when co-administered with atazanavir or when CNS symptoms are also present.

HCV and HBV infection among multitransfused thalassemics from eastern sicily

SummarySerum specimens from 152 Sicilian multitransfused thalassemic subjects were tested for antibodies to hepatitis C virus (anti- HCV) and for HBV markers by enzyme linked immunoassay and with reference to anti-HCV, confirmed by recombinant immunoblot assay. A high rate (47%) of subjects was anti-HCV positive. HBsAg was found in 8% of patients and 55% had anti-HBs or anti-HBc antibodies or both. Contrary to HBV infection, anti-HCV seropositivity was related to the number of transfused units. The highest anti-HCV prevalence was observed between 16 and 20 years; 100% of persons older than 50 years had at least one marker of HBV infection. In conclusion, HCV and HBV are widespread among multitransfused thalassemics. Probably in our area, particularly during the pre-HBsAg screening era, several multitransfused patients were infected by HBV more readily than by HCV.ZusammenfassungDie Seren von 152 Thalassämie-Patienten, die häufig Bluttransfusionen erhalten hatten, wurden auf Antikörper gegen Hepatitis-C-Virus und HBV-Marker getestet. Ein hoher Prozentsatz (47%) erwies sich als anti-HCV positiv, was mit RIBA bestätigt wurde. HBsAg wurde bei 8% der Patienten gefunden und 55% hatten anti-HBc-oder Anti-HBs-Antikörper. Die dominierende anti-HCV-Prävalenz stand in Beziehung zur Transfusionshäufigkeit und war zwischen dem 16. und 20. Lebensjahr am höchsten. Im Gegensatz dazu stand die HBV-Infektion nicht im Verhältnis zu der Anzahl der Bluttransfusionen; bei 100% der Patienten über 50 Jahre wurde mindestens ein HBV-Infektionsmarker beobachtet. Bei Thalassämie-Patienten sind HCV- und HBV-Infektionen verbreitet. Wahrscheinlich haben sich vor dem Beginn des HBsAg-Screening in den Blutbanken viele Patienten mit dem HB-Virus infiziert.

Safety and durability in a cohort of HIV-1 positive patients treated with once and twice daily darunavir-based therapy (SCOLTA project)

OBJECTIVE To evaluate safety and durability of once-daily and twice-daily darunavir/ritonavir (DRV/r)-based treatment in HIV patients in clinical practice. METHODS The Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) project is a prospective, observational, multicenter cohort created to assess the incidence of adverse events in patients receiving new antiretroviral drugs. Twenty-five Italian infectious diseases centers enroll patients and collect their data through this on-line system. Periodical evaluations of these patients, including physical examination and laboratory tests, were performed at baseline and every 6 months. RESULTS Four hundred and twenty-nine patients were enrolled since May 2006. Eighty-five patients (19.8%) were prescribed once-daily DRV/r; 31 of them were treatment-naïve (36.5%). Among 54 (63.5%) treatment-experienced patients, 21 (38.9%) had undetectable viral load and started once-daily DRV/r as a simplification regimen. Patients on twice-daily regimen were older, more frequently lipodystrophic, HCV-coinfected, and in CDC stage C. In the following 24 months of follow-up, the viral load steadily decreased as well as the CD4 cell count rose. The reason for discontinuation did not significantly differ between groups. Mean blood glucose (BG) change from baseline did not show significant difference between groups, as well as high density lipoprotein cholesterol (HDL-C), triglycerides (TGL) and alanine transaminase (ALT). The survival curve shows that patients in the once-daily regimen withdrew treatment more frequently than those on twice-daily regimen (Log Rank Chi(2)P=0.009). CONCLUSION Our study showed that DRV/r administrated both once daily or twice daily was safe and well tolerated with few discontinuations due to adverse events.

96 Week Follow-Up of HIV-Infected Patients in Rescue with Raltegravir Plus Optimized Backbone Regimens: A Multicentre Italian Experience

Background Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings. Methods Antiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96. Results Out of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm3; 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA <50 copies/mL). When analyzing the immuno-virologic outcome according to the number of drugs used in the regimen, 2 (n = 45), 3 (n = 111), 4 (n = 124), or >4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm3, respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL. Conclusions In a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events.

HCV and HIV infection among intravenous drug abusers in eastern Sicily.

In a study of 175 intravenous drug addicts from Eastern Sicily, 58.3% were found to be anti-HCV positive. In this population, the presence of anti-HCV was independent of HIV infection, age, duration of drug use and the practice of needle sharing. This may indicate that HCV is more readily transmitted (or spread earlier in this population) among drug addicts than is HIV.