ObjectivesTo identify predictive factors for moderate/severe liver fibrosis and to analyse fibrosis progression in paired liver biopsies from HIV-positive patients with chronic hepatitis C virus (HCV) infection. MethodsHIV/HCV coinfected patients followed at the 2nd Department of Infectious Diseases of L. Sacco Hospital in Milan, Italy, with at least one liver biopsy specimen were retrospectively evaluated. ResultsA total of 110 patients were enrolled in the study. In a univariate analysis, predictive factors of Ishak-Knodell stage ! 3 were a history of alcohol abuse [odds ratio (OR) 3.6, P 5 0.004], alanine aminotransferase level 4100 IU/L at biopsy (OR 2.4, P 5 0.05), necro-inflammatory grade ! 9 (OR 37.14, Po0.0001) and CD4 count o350 cells/mL at nadir (OR 5.3, P 5 0.05). In a multivariate analysis, age 435 years (OR 3.19, P 5 0.04) and alcohol abuse (OR 4.36, P 5 0.002) remained independently associated with Ishak-Knodell stage. Paired liver biopsies were available in 36 patients; 18 showed an increase of at least one stage in the subsequent liver biopsy. Either in a univariate or in a multivariate analysis, a decrease of CD4 cell count of more than 10% between two biopsies (OR 6.85, P 5 0.002) was significantly associated with liver fibrosis progression. ConclusionOur findings highlight the relevance of encouraging a withdrawal of alcohol consumption in people with chronic HCV infection and of carrying out close follow-up of patients, especially if they are more than 35 years old. It is therefore mandatory to evaluate HIV/HCV coinfected patients for anti-HCV treatment and to increase CD4 cell count through antiretroviral therapy in order to reduce the risk of fibrosis progression and to slow the evolution of liver disease.

Since 1996, the introduction of protease inhibitors (PIs) has led to a dramatic decrease of human immunodeficiency virus-related Pneumocystis carinii pneumonia. This effect is clearly due, in large part, to the induction of immune reconstitution by highly active antiretroviral therapy (HAART). However, it is conceivable that PIs had other beneficial effects, including direct activity against Pneumocystis. In this study, the occurrence of specific aspartyl proteases in Pneumocystis is described. These protease targets seemed to be affected in vitro by antiretroviral PIs. These data suggest intriguing implications for the possible antipneumocystis benefit of receiving indinavir, ritonavir, nelfinavir, or saquinavir during HAART.

Background Hypoalbuminemia is frequently observed in patients with SARS‐CoV‐2 infection although its underlying mechanism and relationship with the clinical outcome still need to be clarified. Methods We retrospectively evaluated in patients with COVID‐19 hospitalised at the Fatebenefratelli‐Sacco Hospital in Milan, the prevalence of hypoalbuminemia, its association with the severity of COVID‐19, with the levels of C‐reactive protein, d‐dimer and interleukin‐6 and with clinical outcome over a follow‐up period of 30 days. Urinalysis was evaluated in a subgroup of patients. Results Serum albumin levels <30 g/L were found in 105/207 (50.7%) patients at hospital admission. Overall, the median albumin value was 29.5 g/L (IQR 25‐32.8). A negative association was found between albumin levels and severity of COVID‐19 ( P < .0001) and death ( P = .003). An inverse correlation was observed between albumin and both C‐reactive protein and D‐dimer at hospital admission ( r = −.487 and r = −.479, respectively; P < .0001). Finally, a positive correlation was found between albumin levels and eGFR ( r = .137; P = .049). Proteinuria was observed in 75% of patients with available data and it did not differ between patients with hypoalbuminemia and those with albumin ≥30 g/L (81% and 67%, respectively; P = .09). Conclusion In patients with COVID‐19, hypoalbuminemia is common and observed in quite an early stage of pulmonary disease. It is strictly associated with inflammation markers and clinical outcome. The common finding of proteinuria, even in the absence of creatinine increase, indicates protein loss as a possible biomarker of local and systemic inflammation worthwhile to evaluate disease severity in COVID‐19.

Chronic hepatitis C is frequent and aggressive among HIV-positive patients; evaluation for anti-hepatitis C virus (HCV)-specific therapy is mandatory, but it has many limitations, due to efficacy, tolerability but also applicability. The objective of our retrospective analysis was to evaluate the eligibility and feasibility of anti-HCV therapy in HIV/HCV-coinfected patients followed at the II Department of Infectious Diseases, L. Sacco Hospital, Milan, Italy, from 2000 to March 2010. In our database, 545 HIV/HCV-coinfected patients were present, representing 40% of our whole HIV population, and 421 included in the analysis. One hundred twenty-four patients were excluded because of loss to follow-up (81) or deceased (43). Forty-eight patients spontaneously cleared HCV during follow-up (11%). Ninety-nine patients received anti-HCV therapy (26%), while the majority was excluded for several reasons (mainly concomitant diseases and low CD4(+) cell count). Globally, we found that in at least one third of untreated patients modifiable barriers to treatment were present. The access to therapy was significantly associated with the absence of history of intravenous drug use (p=0.01), a higher CD4(+) cells count at nadir (p=0.01), the presence of more than 6 HAART regimens (p=0.04), higher alanine aminotransferase (ALT) levels (p<0.0001), HCV genotype 2 or 3 (p=0.005). In a multivariate analysis, the same factors remained significantly associated with anti-HCV therapy. In conclusion, the feasibility of anti-HCV therapy in HIV/HCV-coinfected patients, in our highly specialized center, is approximately 26%. Relative contraindications, such as substance abuses, mild and controlled concomitant conditions, and low compliance are common and modifiable in order to reconsider patients as suitable for therapy.

BACKGROUND Hypoalbuminemia is frequently observed in patients with SARS-CoV-2 infection although its underlying mechanism and relationship with clinical outcome still need to be clarified. METHODS We retrospectively evaluated in patients with COVID-19 hospitalized at the Fatebenefratelli-Sacco Hospital in Milan, the prevalence of hypoalbuminemia, its association with the severity of COVID-19, with the levels of C-reactive protein, d-dimer and interleukin-6 and with clinical outcome over a follow-up period of 30 days. Urinalysis was evaluated in a subgroup of patients. RESULTS Serum albumin levels < 30 g/L were found in 105/207 (50.7%) patients at hospital admission. Overall, the median albumin value was 29.5 g/L (IQR 25-32.8). A negative association was found between albumin levels and severity of COVID-19 (p<0.0001) and death (p=0.003). An inverse correlation was observed between albumin and both C-reactive protein and D-dimer at hospital admission (r =-0.487 and r =-0.479, respectively; p< 0.0001). Finally, a positive correlation was found between albumin levels and eGFR (r= 0.137; p=0.049). Proteinuria was observed in 75% of patients with available data and it did not differ between patients with hypoalbuminemia and those with albumin > 30 g/L (81% and 67%, respectively; p=0.09). CONCLUSION In patients with COVID-19 hypoalbuminemia is common and observed in quite an early stage of pulmonary disease. It is strictly associated with inflammation markers and clinical outcome. The common finding of proteinuria, even in the absence of creatinine increase, indicates protein loss as a possible biomarker of local and systemic inflammation worthwhile to evaluate disease severity in COVID-19.