Dysmetabolism, Diabetes and Clinical Outcomes in Patients Cured of Chronic Hepatitis C: A Real-Life Cohort Study.

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2 , 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20-3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16-6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11-0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi-disciplinary management approach may improve cardiovascular and possibly liver-related outcomes.

Transmitted HIV Type 1 drug resistance and Non-B subtypes prevalence among seroconverters and newly diagnosed patients from 1992 to 2005 in Italy.

The patterns of transmitted drug-resistant (TDR) HIV-1 variants, non-B subtype spread, and epidemiological trends were evaluated either in seroconverters or in newly diagnosed individuals in Italy over a 13-year period. We analyzed 119 seroconverters, enrolled from 1992 to 2003 for the CASCADE study, and 271 newly diagnosed individuals of the SPREAD study (2002-2005), of whom 42 had a known seroconversion date. Overall, TDR was 15.1% in the CASCADE and 12.2% in the SPREAD study. In the 1992-2003 period, men having sex with men (MSMs) and heterosexuals (HEs) were 48.7% and 36.8%, respectively; TDR was found to be higher in MSMs compared to HEs (78.9% vs. 21%, p = 0.006). The same groups were 39.1% and 53.3% in the SPREAD study; however, no association was detected between modality of infection and TDR. Overall, 9.2% and 22.1% of individuals harbored a non-B clade virus in the CASCADE and SPREAD study, respectively. As evidence of onward transmission, 40% (24/60) of non-B variants were carried by European individuals in the latter study; among these patients the F1 subtype was highly prevalent (p = 0.00001). One of every eight patients who received a diagnosis of HIV-1 in recent years harbored a resistant variant, reinforcing the arguments for baseline resistance testing to customize first-line therapy in newly infected individuals. The spread of non-B clades may act as a dilution factor of TDR concealing the proportion of TDR in seroconverters and MSMs.