Factors influencing liver fibrosis and necroinflammation in HIV/HCV coinfection and HCV monoinfection.

OBJECTIVES: To define differences in liver histology between HIV/HCV coinfection and HCV monoinfection, and to investigate possible causative factors. METHODS: Liver biopsies (LBs) from 440 consecutive HIV/HCV-coinfected patients (Group HIV/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of the clinical and laboratory data. All patients were HBsAg-negative, with no history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4% of patients in Group HIV/HCV were on an antiretroviral regimen. RESULTS: HIV/HCV-coinfected patients compared to the HCV-monoinfected patients were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell count: 518 ± 166 cells/mm(3)). Patients in Group HIV/HCV more frequently showed a fibrosis score ≥4 (27.5 vs. 20.6%, p < 0.05) and a necroinflammation score ≥9 (25.9 vs. 13.4%; p < 0.0001). The prevalence of patients with fibrosis score ≥4 was significantly higher in older age classes in both Group HIV/HCV (p < 0.005) and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher in older age classes only in Group HIV/HCV (p < 0.05). A multivariate analysis for Group HIV/HCV revealed that the patient age and nadir of CD4+ cell count were independently associated to higher degrees of fibrosis, the patient age and antiretroviral treatment were associated to higher degrees of necroinflammation, and HCV genotype 3 was associated to higher degrees of steatosis. CONCLUSION: The data suggest a need for early anti-HCV treatment in both HCV-monoinfected and HIV/HCV-coinfected patients.

Tolerability and efficacy of anti-HBV nucleos(t)ide analogues in HBV-DNA-positive cirrhotic patients with HBV/HCV dual infection.

We evaluated tolerability and virological and clinical impact of anti-Hepatitis B Virus (HBV) nucleos(t)ide analogues in cirrhotic patients with HBV/Hepatitis C Virus (HCV) coinfection. The virological and clinical course of 24 consecutive HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis was compared with that of 24 HBsAg/HBV-DNA-positive, anti-HCV-negative cirrhotic patients, pair-matched for age (±5 years), sex, HBeAg/anti-HBe status and Child-Pugh class. Patients in both groups were previously untreated with oral antiviral agents at enrollment and were treated for at least 24 months (range 24-54). At the 12th and 18th month of treatment, HBV-DNA was negative in 21 (87.5%) and 23 (95.8%) patients with hepatitis B and C and in 20 (83.3%) and 22 (91.6%) in patients with isolated HBV; all patients in both groups were HBV-DNA-negative at month 24 and at subsequent observations. Treatment was well tolerated by all patients in both groups. At the last observation (for co-infected patients, median 44 months and range 24-54; for mono-infected patients, median 40 months and range 24-54), a deterioration in Child class was observed in eight (47%) of 17 patients in patients with both HBV and HCV who were HCV-RNA-positive at baseline, but in none of seven HCV-RNA-negative patients in the same group, and in one patient (4.2%) in the mono-infected patients. Reactivation of HCV infection was relatively infrequent (12.5% of cases) and never associated with a clinical deterioration. Treatment with nucleotides in HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis showed a favourable virological effect in all cases, but a favourable clinical result only in the HCV-RNA-negative at baseline.

Virological patterns of hepatitis C virus patients with failure to the current-generation direct-acting antivirals.

There are few data on the virological characterisation of patients with failure to current-generation direct-acting antivirals (DAAs), namely elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir. This study aimed to characterise virological patterns in patients with failure to current DAA regimens as well as the efficacy of re-treatment. All 61 consecutive hepatitis C virus (HCV) treatment-naïve patients with failure to current DAAs from January 2018 to February 2019 were enrolled. Sanger sequencing of NS3, NS5A and NS5B proteins was performed using homemade protocols. NS5A resistance-associated substitutions (RASs) were more frequent in the 17 patients treated with sofosbuvir/velpatasvir (89.5%) and 33 patients treated with elbasvir/grazoprevir (97%) compared with the 11 patients treated with glecaprevir/pibrentasvir (18.2%) (P = 0.002 and 0.000, respectively). NS3 RASs were more often detected in the 33 patients with failure to elbasvir/grazoprevir (30.3%) than in the 11 patients treated with glecaprevir/pibrentasvir (9.1%). NS3 RASs were also detected in 12% of sofosbuvir/velpatasvir-treated patients. NS5B RASs were infrequently identified. Of the glecaprevir/pibrentasvir-treated patients, 73% did not show RASs in any HCV regions, a prevalence higher than that observed in those treated with elbasvir/grazoprevir (0%; P < 0.05) or sofosbuvir/velpatasvir (12%; P < 0.05). Of the 61 patients, 21 (34.4%) were re-treated with sofosbuvir/velpatasvir and voxilaprevir. All patients achieved sustained virological response at 12 weeks (SVR12). To our knowledge, this is one of the first real-life studies describing patients who failed current-generation DAAs; the prevalence of RASs differed according to the DAA regimen used, and the efficacy of re-treatment was high.

Heart failure and diabetes: left ventricular systolic function.

AIM: Heart failure is the main cause of mortality and morbidity in general population, annual mortality rate is 20%, in spite of pharmacological treatments or other therapies. Cardio-vascular events and diabetes tight correlation is well known, while it is less evaluated diabetes and heart failure correlation is less studied, heart failure as left ventricular systolic function impairment. Cardiovascular disease rate is decreasing, systolic heart failure rate is raising. Our study goal is to evaluate which role diabetes plays in determining systolic heart failure, diagnosed by echocardiographical examination. METHODS: Four hundred and fifty consecutive patients, systolic heart failure prone, diagnosed by left ventricular ejection fraction less than 40%, were included. Exclusion criteria were rheumatic or congenital valve diseases. Mean age was 78.3 years (53-93 years), 286 were women and 164 men. Statistical analysis were performed by parametric t-Student test and not parametric chi2 test. High significant difference was assessed for P<0.05. RESULTS: Seventy six (16.9%) patients were diabetes prone (D), 374 (83.1%) were diabetes free, so not diabetic (ND). Forty three men were D (56.5%), 131 ND (35%). Diabetic mean age was 74.7 years (52-88), not diabetic was 79.3 (53-93). Six D (7.8%) and 21 ND patients (5.6%) were hypercholesterolemia prone. Eight D (10.5%) and 18 ND (10.1%) patients were smokers. Twenty eight D (36.8%) and 107 ND patients (28.6%) were hypertensive. Thirty three D (43.4%) and 88 ND (26.4%) patients were coronary artery disease prone, 3 of 33 (3.9%) D and 28 of 88 (7.4%) ND ischemic patients were myocardial infarction prone. Twenty one D (27.6%) and 106 ND (28.3%) patients were atrial fibrillation prone. There were not statistical significant difference among D and ND patients for following variables: sex, smoke, total cholesterolemia, hypertension and atrial fibrillation. We found an high significant difference for mean age (P<0.005) and coronary artery disease prone patients (P<0.007), but not for myocardial infarction prone subjects (P<0.1). CONCLUSIONS: Diabetes, not depending by other common cardiovascular risk factors, causes systolic heart failure, in prone patients, on an younger age, and in the same time an higher coronary artery disease rate, but not an higher myocardial infarction rate, because the coronary artery disease is often a microvascular one, and it leads to heart failure rather than myocardial necrosis.

Evidence for laser cooling in a magnesium atomic beam.

Laser cooling in a Mg atomic beam is reported for the first time to our knowledge. Previous cooling experiments were performed by using visible or infrared lasers. The Mg atoms were cooled by using an intracavity frequency-doubled dye laser at 285 nm to reach the resonant (1)S(0)-(1)P(1) transition. Evidence of laser cooling was obtained even with the limited available laser power ( approximately 1-2 mW).