Liver resection of hepatocellular carcinoma in HIV-HCV co-infected patients: a retrospective case series

Abstract Introduction Despite the effectiveness of new therapies and awareness campaigns, the number of seropositive patients is increasing every year. Recently, other causes of death, not directly related to HIV, have emerged, such as chronic liver disease. The risk of hepatocellular carcinoma (HCC) is seven times greater in HIV patients than in noninfected patients, and it is especially attributable to HCV infection. The aim of our study was to evaluate clinical outcomes of HCC in HIV-HCV co-infected patients after liver resection (LR). Materials and methods The current study was conducted on a prospective database and reviewed retrospectively. All consecutive patients with HCC treated by LR from January 2013 to March 2019 at the Luigi Sacco University Hospital in Milan were enrolled. We included patients older than 18 years of age with HCV-related HCC, and in this set of patients, we identified two groups based on the presence of HIV infection. Results We identified 16 patients with HCV infection and precisely five with HIV-HCV co-infection and eleven with HCV infection alone. All HIV patients were male against 72.7% in the non-HIV group (p = 0.509). All patients had optimal HIV virologic control and a normal CD4 T-cell count. The mean diagnosis-to-treatment interval was statistically different between the two groups (HIV versus non-HIV: 1.2 ± 0.55 months versus 2.39 ± 1.09 months, p = 0.039). No other significant differences were found between HIV-HCV co-infected patients and HCV-infected patients. Long-term outcomes in terms of OS and RFS were similar between the two groups. Conclusions With a multidisciplinary approach and intensive support, LR can be a safe and efficacious procedure in HIV-HCV patients. For these reasons, we should not exclude potential patients merely on the basis of their HIV seropositivity

Fibrosis progression in paired liver biopsies from HIV/HCV co-infected patients

BACKGROUND: Chronic hepatitis C is more aggressive during HIV infection. Available data about risk factors of liver fibrosis in HIV/HCV co-infected patients derive from studies based on a single liver biopsy. OBJECTIVES: To evaluate the risk factors of liver fibrosis progression (LFP) and to investigate the role of antiretroviral therapy (ARV) in HIV/HCV patients who underwent paired liver biopsy. PATIENTS AND METHODS: We retrospectively studied 58 patients followed at two Infectious Diseases Departments in Northern Italy during the period 1988-2005. All specimens were double-blinded and centrally examined by two pathologists. LFP was defined when an increase of at least one stage occurred in the second biopsy, according to the Ishak-Knodell classification. RESULTS: In a univariate analysis, serum levels of alanine aminotransferase (ALT) > 150 IU/L at the first biopsy (P = 0.02), and a > 20% decrease in CD4+ cell count between the two biopsies (P = 0.007), were significantly associated with LFP. In multivariate analysis, a > 20% decrease in CD4+ cell count remained independently associated to LFP (Odds Ratio, 3.99; 95% confidence interval, 1.25-12.76; P < 0.02). Analysis of life survival curves confirmed the correlation between CD4+ cell count and LFP. CONCLUSIONS: Our findings highlight that in HIV/HCV coinfected patients, an effective antiretroviral therapy that assures a good immune-virological profile contributes to reducing the risk of LF

Different evolutionary rates and epidemic growth of hepatitis B virus genotypes A and D.

The epidemiological history of HBV genotypes A and D and subgenotypes A2 and D3 was studied on 132 isolates drawn between 1980 and 2005 from patients living in a homogenous geographical area. Evolutionary rates and divergence dates were estimated and HBV demographic history was reconstructed by using a statistical approach based on coalescent theory. The evolutionary rate of A2 was significantly lower than that of D3. The growth rate of D3 epidemic was significantly faster than that of A2; both subgenotypes showed a decreasing growth rate from the mid-1980s. Our data suggest that the important discrepancies observed in the evolutionary rates of HBV genotypes A and D may reflect different population dynamics of their epidemics. These results show the usefulness of phylodynamic studies in reconstructing the history of epidemics due to highly variable DNA viruses, and in evaluating the long-term efficacy of prophylactic measures

Atherosclerosis is associated with multiple pathogenic mechanisms in HIV-infected antiretroviral-naive or treated individuals

Objectives: HIV-infected patients have a greater burden of sub-clinical and clinical atherosclerotic disease compared to the general population. The primary objective of this study was to compare the relative roles of inflammation, endothelial alterations, and metabolic factors in the induction and maintenance of atherosclerosis in antiretroviral therapy (ART)-treated or ART-naive patients. Design: Cross-sectional study; 79 HIV-infected patients (55 ART-treated and 24 naive individuals) were consecutively enrolled. In both groups, nearly 50% of the individuals had a high cardiovascular risk (Framingham value &gt;20%). Methods: Echo-Doppler [intima-media thickness (IMT)], inflammatory, thrombophilic, endothelial, metabolic indexes, and cholesterol efflux molecules were evaluated. Multivariate analysis adjusted for age, CD4 nadir, BMI, and Framingham&apos;s score were used to analyze the results

High rates of sustained virological response despite premature discontinuation of directly acting antivirals in HCV-infected patients treated in a real-life setting

In routine clinical practice, HCV-infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE-Lombardia Network database from January 2015, who discontinued DAAs before the pre-defined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5 years and 53 (14.5%) patients were HIV-coinfected. Liver cirrhosis was observed in 251 (68.8%) subjects and the most represented genotypes were 1b (n=168, 46%) and 3 (n=59, 16.2%). DAA were discontinued a median of 1 (IQR 1-4) weeks before the pre-defined EOT, with 164 (44.9%) patients stopping DAAs at least two weeks before the planned schedule. In patients with F0-F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for <4 weeks: 50% (n=2/4) vs 99.1% (n=109/110) for ≥4 weeks, p=0.003. In patients with liver cirrhosis, lower rates of SVR12 were observed in patients treated <8 weeks: 83.3%(n=25/30) vs 94.6%(n=209/221) for ≥8 weeks, p=0.038. Despite premature discontinuation of DAA, high SVR12 rates were observed in a real-life setting for treatment lasting at least 4 weeks in patients with liver fibrosis F0-F3 and 8 weeks in those with liver cirrhosis. On this basis, feasibility of reducing DAA treatment duration should be explored in randomized clinical trials