10 Both HIV infection

Wnt signaling and chronic alcohol use are associated with increased gut permeability and elevated plasma levels of lipopolysaccharide, a central activator of inflammatory responses.10 For these reasons, alcohol consumption should be strongly discouraged and alcohol abuse should be diagnosed and aggressively treated in persons living with HIV. Soon after the introduction of first-generation anti-HIV protease inhibitors in 1996, various cohorts of HIV-infected patients were found to show a high prevalence of diabetes with an incidence of 4.4 and 5.7 per 1,000 person-years of follow-up.14 It was observed that diabetes occurred more frequently Pexidartinib in HIV-infected patients previously exposed to specific anti-HIV drugs (e.g., indinavir, stavudine, and didanosine) and persisted in most cases after drug withdrawal.14 Diabetes is associated with all-cause mortality in persons living with HIV and specifically with liver-related mortality.2 Most HIV-infected patients in developed

countries are currently treated with new-generation cART associated with a lower risk of diabetes; however, they are reaching older ages than before and often continue to gain weight, thus their case management should include measure of adiposity markers (i.e., waist circumference and body mass index) and fasting blood glucose at least yearly to identify at-risk patients.14 In the Ioannou series, a maximal CD4 count lower than 200 or a percentage of

CD4 lower than 14% were associated with an increased risk for HCC. Thus, there are good reasons to start antiretroviral therapy earlier in patients with HCV. However, Methocarbamol two studies showed an increased risk of liver-related death in those exposed for a longer time to antiretrovirals after adjusting for CD4 counts.2, 15Thus, it is still undefined whether antiretroviral therapy should be started independently from CD4 counts in HCV-coinfected patients or whether starting below 500 CD4 counts could be a better option. Randomized, controlled trials aimed to solve this issue are ongoing and they will probably answer this question. In conclusions, Ioannou et al.4 have reported a dramatic rise in the prevalence of end-stage complications of liver disease (e.g., cirrhosis, decompensated cirrhosis, and HCC) among HIV-infected patients, particularly in those coinfected with HCV. Thus, end-stage liver disease is likely to constitute one of the most important clinical problems for HIV-infected patients and their physicians during the decade 2010-2020. The availability of new anti-HCV drugs may have the potential for removing barriers to a comprehensive “test and treatment strategy” against HCV in persons living with HIV.