Rapid ART initiation with bictegravir/emtricitabine/tenofovir alafenamide in individuals presenting with advanced HIV disease (Rainbow study).

BACKGROUND: A rapid ART initiation approach can be beneficial in people with advanced HIV disease, in consideration of their high morbidity and mortality. The aim of our study was to evaluate the feasibility, efficacy and safety of rapid ART start with BIC/FTC/TAF in this setting. METHODS: Pilot, single-centre, single-arm, prospective, phase IV clinical trial conducted in a tertiary Italian hospital. Thirty ART-naïve people presenting with advanced HIV-1 diagnosis (defined as the presence of an AIDS-defining event and/or CD4 cell count <200 µL), were enrolled. Main exclusion criteria were active tuberculosis, cryptococcosis and pregnant/breastfeeding women. BIC/FTC/TAF was started within 7 days from HIV diagnosis. The primary endpoint was clinical or virologic failure (VF). Immunological parameters, safety, feasibility, neurocognitive performances and patient-reported outcomes were assessed as well. RESULTS: Over the study period, 40 (34%) of 116 patients diagnosed with HIV infection at INMI Spallanzani had advanced disease, of whom 30 (26%) were enrolled. The proportion of participants with HIV-RNA <50 cp/mL was 9/30 (30%) at week (w) 4, 19/30 (63%) at w12, 24/30 (80%) at w24, 23/30 (77%) at w36 and 27/30 (90%) at w48. Two unconfirmed VF occurred. No ART discontinuation due to toxicity or VF was observed. No ART modification was performed based on the review of genotype and no mutations for the study drugs were detected. Mean CD4 cells count changed by 133 cells/µL at BL to 309 cells/µL at w 48 and 83% of participants had a CD4 > 200 cells/µL at w 48. Two participants developed IRIS and one was diagnosed with disseminated TB and needed an ART switch. INTERPRETATIONS: Our results support the feasibility, efficacy and safety of BIC/FTC/TAF as a rapid ART strategy in patients with advanced HIV disease.

Declining Prevalence of Human Immunodeficiency Virus (HIV)-Associated Neurocognitive Disorders in Recent Years and Associated Factors in a Large Cohort of Antiretroviral Therapy-Treated Individuals With HIV.

BACKGROUND: HIV-associated neurocognitive disorders (HAND) have been suggested as persistent even with effective antiretroviral therapy (ART). Aims were to evaluate HAND prevalence and associated factors, in a large cohort of people-with-HIV (PWH). METHODS: ART-treated PWH, underwent a neuropsychological examination through a battery of 12 tests exploring 5 different domains, between 2009 and 2020, were included in this cross-sectional analysis. HAND were classified according to Frascati's criteria. Participants were defined as complaining or not-complaining if a cognitive complaint was reported or not. Chi-square for trend and multivariable logistic regression were fitted. RESULTS: Overall, 1424 PWH were enrolled during four three-years periods. HAND prevalence was 24%; among complainers (572/1424), it was 38%, higher than among not-complainers (15%). Over the study period, a decreasing HAND prevalence was found in the entire population (P < 0.001) and in complaining (P < 0.001); in not-complaining it remained stable (P = 0.182). Factors associated with HAND were older age, lower educational level, lower current CD4+ T-cell count and HCV co-infection. Compared to nonnucleoside reverse transcriptase inhibitors, receiving dual and integrase strand transfer inhibitor (INSTI)-based therapies was associated with a decreased risk of HAND, as well as being tested in more recent years. CONCLUSIONS: In this large cohort of ART-treated PWH, mostly virologically suppressed, a remarkable decreasing HAND prevalence was observed. Besides HIV- and patient-related factors, the reduced risk of HAND found with dual and INSTI-based regimens along with a more recent ART initiation, could suggest a potential role of new treatment strategies in this decline, due to their greater virologic efficacy and better tolerability.

Virological and Immunological Outcomes of an Intensified Four-Drug versus a Standard Three-Drug Antiretroviral Regimen, Both Integrase Strand Transfer Inhibitor-Based, in Primary HIV Infection.

The optimal therapeutic approach for primary HIV infection (PHI) is still debated. We aimed to compare the viroimmunological response to a four- versus a three-drug regimen, both INSTI-based, in patients with PHI. This was a monocentric, prospective, observational study including all patients diagnosed with PHI from December 2014 to April 2018. Antiretroviral therapy (ART) was started, before genotype resistance test results, with tenofovir/emtricitabine and either raltegravir plus boosted darunavir or dolutegravir. Cumulative probability of virological suppression [VS] (HIV-1 RNA< 40 cp/mL), low-level HIV-1 DNA [LL-HIVDNA] (HIV-1 DNA < 200 copies/106PBMC), and CD4/CD8 ratio ≥1 were estimated using Kaplan−Meier curves. Factors associated with the achievement of VS, LL-HIVDNA, and CD4/CD8 ≥ 1 were assessed by a Cox regression model. We enrolled 144 patients (95.8% male, median age 34 years): 110 (76%) started a four-drug-based therapy, and 34 (24%) a three-drug regimen. Both treatment groups showed a comparable high probability of achieving VS and a similar probability of reaching LL-HIVDNA and a CD4/CD8 ratio ≥1 after 48 weeks from ART initiation. Higher baseline HIV-1 RNA and HIV-1 DNA levels lowered the chance of VS, whereas a better preserved immunocompetence increased that chance. Not statistically significant factors associated with LL-HIVDNA achievement were found, whereas a higher baseline CD4/CD8 ratio predicted the achievement of immune recovery. In PHI patients, the rapid initiation of either an intensified four-drug or a standard three-drug INSTI-based regimen showed comparable responses in terms of VS, viral reservoir size, and immunological recovery.

Humoral and Cellular Immune Response Elicited by mRNA Vaccination Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in People Living With Human Immunodeficiency Virus Receiving Antiretroviral Therapy Based on Current CD4 T-Lymphocyte Count.

BACKGROUND: Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count. METHODS: PLWH on ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: <200/mm3; intermediate CD4 recovery, ICDR: 200-500/mm3; high CD4 recovery, HCDR: >500/mm3). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used. FINDINGS: Among 166 PLWH, after 1 month from the booster dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2%, and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell <200/mm3 significantly predicted a poor magnitude of anti-RDB, nAbs and IFN-γ response. As compared with HCWs, PCDR elicited a consistently reduced immunogenicity for all parameters, ICDR only a reduced RBD-binding antibody response, whereas HCDR elicited a comparable immune response for all parameters. CONCLUSION: Humoral and cell-mediated immune response against SARS-CoV-2 were elicited in most of PLWH, albeit significantly poorer in those with CD4 T-cell <200/mm3 versus those with >500 cell/mm3 and HIV-negative controls. A lower RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm3, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm3 was comparable to HIV-negative population.

Association of Sofosbuvir and Daclatasvir Plasma Trough Concentrations with Patient-, Treatment-, and Disease-Related Factors Among HIV/HCV-Coinfected Persons.

BACKGROUND: Sofosbuvir plus daclatasvir achieves high rates of sustained virologic response (SVR), with no differences according to HIV serostatus. However, only limited information is available on the pharmacokinetic variability of sofosbuvir and daclatasvir in HIV/HCV-coinfected patients. OBJECTIVES: The aim of this study was to identify patient-, treatment-, and disease-related factors that are significantly associated with sofosbuvir and daclatasvir plasma trough concentrations (Ctrough), including liver and renal function, among HIV/HCV-coinfected persons. METHODS: In this observational cohort pilot study, HIV/HCV-coinfected patients undergoing sofosbuvir plus daclatasvir treatment were prospectively enrolled. Biochemical and viro-immunological parameters were assessed at baseline, week 4 (W4), end of treatment (EOT), and after EOT. The FIB-4 score and CKD-EPI equation were used to estimate liver disease and glomerular filtration rate (eGFR), respectively. For sofosbuvir, sofosbuvir metabolite (GS-331007), and daclatasvir, Ctrough was measured at W4 and week 8 (W8), and the mean of the values at those two time points (mean-Ctrough) was calculated. The Mann-Whitney test and Spearman's rank correlation were used to evaluate the correlations between the mean-Ctrough of each direct-acting antiviral (DAA) and the considered variables. RESULTS: Thirty-five patients were included (SVR 94%). An increased GS-331007 mean-Ctrough was significantly correlated with a decreased eGFR at W4 (rho = -0.36; p = 0.037) and EOT (rho = -0.34; p = 0.048). There was a significant correlation between daclatasvir mean-Ctrough and FIB-4 at all time points: baseline (rho = -0.35; p = 0.037), W4 (rho = -0.44; p = 0.008), EOT (rho = -0.40; p = 0.023), and after EOT (rho = -0.39; p = 0.028). CONCLUSIONS: In HIV/HCV-coinfected patients in a real-world setting, exposure to a high GS-331007 Ctrough was associated with a slight decrease in renal function, while advanced hepatic impairment was significantly associated with a lower daclatasvir Ctrough. Though the clinical and therapeutic relevance of these findings may be limited, increasing clinicians' knowledge regarding DAA exposure in difficult-to-treat patients could be relevant in single cases, and further investigations are warranted.

Late Relapse and Reinfection in HCV Patients Treated with Direct-Acting Antiviral (DAA) Drugs.

The risk of hepatitis C virus (HCV) recurrence after direct-acting antiviral (DAA) treatment is <0.5%. However, the distinction between HCV RNA late relapse and reinfection still represents a challenge in virological diagnostics. The aim of this study was to employ next-generation sequencing (NGS) to investigate HCV RNA recurrence in patients achieving a sustained virologic response (SVR) at least six months post-treatment. NGS was performed on plasma samples from six HCV-positive patients (Pt1-6) treated with DAA. NGS of HCV NS5B was analyzed before treatment (T0), after HCV RNA rebound (T1), and, for Pt3, after a second rebound (T2). Reinfection was confirmed for Pt5, and for the first rebound observed in Pt3. Conversely, viral relapse was observed when comparing T0 and T1 for Pt6 and T1 and T2 for Pt3. Z-scores were calculated and used to predict whether HCV-positive patient samples at different time points belonged to the same quasispecies population. A low Z-score of <2.58 confirmed that viral quasispecies detected at T0 and T1 were closely related for both Pt1 and Pt2, while the Z-score for Pt4 was suggestive of possible reinfection. NGS data analyses indicate that the Z-score may be a useful parameter for distinguishing late relapse from reinfection.

Effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients: Results of the Italian cohort of a post-marketing observational study.

BACKGROUND AND AIMS: The MARS post-marketing, observational study evaluates glecaprevir/pibrentasvir in a large population of Italian patients who are infected with HCV. PATIENTS AND METHODS: Achievement of SVR12 was the primary endpoint in the overall population and by subpopulations of interest (treatment-naïve and treatment-experienced patients, subjects infected with different HCV genotype/sub-genotype, cirrhotic and non-cirrhotic patients, patients with different severity of fibrosis, patients with an APRI score ≥1, subjects with comorbidities, HIV-coinfected patients, elderly patients and people who use drugs). Safety and quality of life (assessed by SF-36 and Work Productivity and Activity Impairment) were also evaluated. RESULTS: The SVR12 rate was 99.4% (319/321; 95% CI: 97.8-99.8%) in the core population with sufficient follow-up (n = 321), 99.7% (289/290) in 8-week treated patients, and high (>96%) across subgroups. Only three patients (0.9%) had treatment-related adverse events that led to treatment discontinuation. In total, 30.1% of patients showed an improvement of ≥2.5 points in the Physical Component Summary of the SF-36 from baseline to the end of treatment, and this figure raised to 37.5% with the achievement of SVR12. Corresponding values for MCS were 42.2% and 42.8%, respectively. CONCLUSION: Glecaprevir/pibrentasvir is safe and effective across subpopulations who are underserved in clinical trials.

Clinical management of imported malaria in Italy: results from a national cross-sectional survey in 2015.

In Italy, malaria continues to be one of the most common imported parasitoses; therefore, continuous surveillance of epidemiological data and clinical management is needed. In 2016, the National Institute for Infectious Diseases 'Lazzaro Spallanzani' in Rome promoted a retrospective questionnaire-based survey to assess the clinical management of imported malaria cases in Italy in 2015. The questionnaire was sent to 104 Tropical and/or Infectious Diseases Units in the country, and 37 of them filled out and returned the questionnaires. A total of 399 malaria cases were reported in 2015, mostly caused by Plasmodium falciparum and imported from Africa. Malaria chemoprophylaxis was correctly used by a minority of patients. Most patients presented with uncomplicated malaria and were treated orally. In severe cases, intravenous artesunate or quinine alone or in combination were administered, although one third of these severe cases received oral treatment. This retrospective survey reveals a lack of homogeneity in management of malaria-imported cases in Italy. Improvement of malaria chemoprophylaxis, standardization of clinical management of malaria cases and harmonization of oral and intravenous drug availability are needed throughout the country.

Cardiovascular risk in advanced naïve HIV-infected patients starting antiretroviral therapy: Comparison of three different regimens - PREVALEAT II cohort.

BACKGROUND AND AIMS: PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naïve patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk. METHODS: The study included all consecutive naïve patients with less than 200 CD4 cells/ml starting antiretroviral therapy. Our primary objective was to evaluate changes in carotid intima- media thickness (IMT). Secondary endpoints included changes in flow mediated vasodilation (FMD), inflammatory markers, triglycerides and cholesterol. Patients were evaluated at time 0, and after 3, 6 and 12 months. RESULTS: We enrolled 119 patients, stratified into three different groups: patients receiving atazanavir/ritonavir boosted (ATV/r) based regimens, efavirenz (EFV) based regimens and darunavir/ritonavir boosted (DRV/r) based regimens. At baseline, advanced naïve patients showed a relevant deterioration of CV conditions in terms of traditional CV risk factors, endothelial dysfunction and serum biomarkers. During the 12-month follow up period, mean blood lipids significantly increased: total cholesterol from 159 to 190 mg/dL, HDL-C from 31 to 41 mg/dL, and LDL-C from 99 to 117 mg/dL. D-dimers steadily decreased (median level 624 at baseline and 214 at T3), whereas ICAM and VCAM consistently raised. DRV/r and ATV/r determined a more marked decrease of D-dimers as compared to EFV. Regarding the epi-aortic changes (IMT >1 mm or presence of atherosclerotic plaques), patients in the DRV/r group were at risk of developing pathological IMT during the study (OR 6.0, 95% CI 0.9-36.9), as compared to EFV ones. CONCLUSIONS: CV risk was elevated in advanced naïve patients and tended to remain high in the first year of therapy.

Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV-infected patients: 24-weeks interim analysis from ATLAS-M trial.

INTRODUCTION: We report interim 24-weeks efficacy data of ATLAS-M trial, a phase IV, multicentre, open-label, randomized study designed to show 48-weeks, non-inferior efficacy (margin of -12%) of treatment simplification to atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3-drugs ATV/r-based cART. METHODS: Subjects on ATV/r+2 NRTIs, without previous treatment failure (TF), with HIV-RNA <50copies/mL for >3 months and CD4>200 cells/mm(3) for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one) or to maintain the original 3-drug regimen (arm two). PRIMARY ENDPOINT: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV-RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment of 266 patients was planned. RESULTS: A total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir-containing backbone) were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8-97.6) and 85.1% (95% CI 77.6-92.6) in arm one and two, respectively (difference +6.6%, 95% CI -2.9/+16.1). VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification) and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007). A greater increase in total cholesterol (+18 vs -2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences in other lipid parameters. Renal function showed a significant improvement in arm one (mean change in eGFR +5 vs -2 mL/min/1.73m(2) in arm two, p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between the two arms. CONCLUSIONS: This interim analysis suggests a 24-weeks non-inferior efficacy of treatment simplification to ATV/rit+3TC as compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients. Follow-up until 48-weeks is scheduled to confirm these data.

Clinical experience of colistin-glycopeptide combination in critically ill patients infected with Gram-negative bacteria.

A colistin-glycopeptide combination (CGC) has been shown in vitro to be synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB), especially Acinetobacter baumannii, and to prevent further resistance. However, clinical data are lacking. We carried out a retrospective multicenter study of patients hospitalized in intensive care units (ICUs) who received colistin for GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30-day mortality after treatment onset among patients treated with and without CGC for ≥48 h. Of the 184 patients treated with colistin, GNB infection was documented for 166. The main causative agents were MDR A. baumannii (59.6%), MDR Pseudomonas aeruginosa (18.7%), and carbapenem-resistant Klebsiella pneumoniae (14.5%); in 16.9% of patients, a Gram-positive bacterium (GPB) coinfection was documented. Overall, 68 patients (40.9%) received CGC. Comparison of patients treated with and without CGC showed significant differences for respiratory failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus 71.4%), MDR A. baumannii infection (70.6% versus 52%), and GPB coinfection (41.2% versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and 30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who survived for ≥5 days after treatment onset showed that the Charlson index (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44; P = 0.001) and MDR A. baumannii infection (HR, 2.51; 95% CI, 1.23 to 5.12; P = 0.01) were independent predictors of 30-day mortality, whereas receiving CGC for ≥5 days was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03). We found that CGC was not associated with higher nephrotoxicity and was a protective factor for mortality if administered for ≥5 days.

Appropriateness of surgical antimicrobial prophylaxis in the Latium region of Italy, 2008: a multicenter study.

BACKGROUND: There is still wide variability in surgical antimicrobial prophylaxis (SAP) practice by different surgical teams and specialties, with potential impact on adverse events and the emergence of antibiotic resistance. METHODS: We assessed SAP appropriateness in a regional prospective multicenter study on the basis of the agreement of the Surgical Care Improvement Project indicators (SCIP-Inf) with Italian guidelines (GL). RESULTS: Prophylaxis was administered in 2,664 of 2,835 procedures (94%): In 2,346 of 2,468 (95%) as indicated and in 318 of 367 (86.6%) in which they were not indicated. The SCIP-Inf1 (timing), SCIP-Inf2 (antibiotic choice), and SCIP-Inf3 (duration) were in agreement with GL in 1,172 (50%), 1,983 (84.5%), and 1,121 (48%) of 2,346 procedures, respectively. CONCLUSIONS: These results suggest the need for implementation of an antimicrobial stewardship program in this surgical setting.

Daptomycin efficacy in the central nervous system of a patient with disseminated methicillin-resistant Staphylococcus aureus infection: a case report.

INTRODUCTION: Staphylococcus aureus has emerged as a major nosocomial pathogen in the last decades and also represents the second most common pathogen isolated from patients in outpatient settings. Although methicillin-resistant S.aureus infections were traditionally limited to hospitals, community-associated cases of methicillin-resistant S.aureus infections have been reported. In our case, we observed an unexpected event during treatment. CASE PRESENTATION: A 60-year-old Caucasian man developed fever and multiple muscle and brain abscesses caused by Panton-Valentine leukocidin-negative community-associated methicillin-resistant S. aureus. CONCLUSION: Although our patient was given antimicrobials active against the isolated methicillin-resistant S. aureus strain, it was only after the introduction of daptomycin that his skin, soft tissue and muscle lesions and also brain manifestations improved.

Cytomegalovirus pneumonia in immunocompetent host: case report and literature review.

CMV infection is highly prevalent in general population and its clinical picture generally ranges from asymptomatic disease to mononucleosis-like syndrome. While severe life-threatening CMV disease is well documented in certain immunocompromised risk groups, severe infection with symptomatic pneumonia in immunocompetent hosts has been rarely documented. In this paper we describe a case of primary CMV infection, complicated by severe CMV pneumonia in an immunocompetent host, successfully treated with oral valganciclovir. Moreover, we reviewed CMV pneumonia cases in immunocompetent adults reported in the literature.

Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis.

OBJECTIVES: To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patients with Gram-positive infections. METHODS: MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration (C(min)) for InI and steady-state concentration (C(ss)) for CoI; area under the curve at 24 h (AUC(24)) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I(2) test was calculated to assess heterogeneity across studies. RESULTS: One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P = 0.02; I(2)= 0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P = 0.9; I(2)= 0). CONCLUSIONS: Our meta-analysis suggests that administration of vancomycin for the treatment of Gram-positive infections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug. RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio.

Acute hepatocellular and cholestatic injury during therapy with hydrochlorothiazide - clinicohistopathologic findings: a case report.

INTRODUCTION: Hydrochlorothiazide and thiazide-like diuretics are considered first-line drugs for initial therapy in uncomplicated arterial hypertension. Acute cholecystitis is a well-known complication during treatment with thiazide, and these drugs are also reported to be followed by pronounced insulin resistance. CASE PRESENTATION: We describe a case of acute cholestatic hepatitis in a 68-year-old Caucasian man who was receiving olmesartan and hydrochlorothiazide for arterial hypertension. From the clinical and histologic findings, we diagnosed him as having hepatocellular-cholestatic injury and a disorder of glucose metabolism in the liver. To the best of our knowledge, no histopathologic description of hydrochlorothiazide hepatotoxicity has previously been documented in the literature. CONCLUSION: In the differential diagnosis of cholestatic hepatitis, clinicians should be aware of the possibility of liver damage in patients receiving hydrochlorothiazide therapy.

Hemolytic anemia due to acute cytomegalovirus infection in an immunocompetent adult: a case report and review of the literature.

INTRODUCTION: Cytomegalovirus is a common virus responsible for a wide range of clinical manifestations. Hemolysis is a rare but potentially life-threatening complication of cytomegalovirus infection, described mostly in immunocompromised patients, the pathogenesis of which is still unclear.We performed a review of the literature regarding cases of hemolytic anemia during acute cytomegalovirus infection in apparently immunocompetent individuals. We searched for relevant articles in PubMed for the period of 1980 through 2008. CASE PRESENTATION: We describe a case of Coombs-negative hemolytic anemia in a 44-year-old Caucasian immunocompetent man with acute cytomegalovirus infection. CONCLUSION: Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in immunocompetent adults. Possible therapeutic options include antiviral therapy and steroids, although the best treatment strategy is still controversial.