Background and aimsIncreased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN).MethodssCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls.ResultsAt baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups.Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with high sCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize.ConclusionsThese results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection.
The occurrence of decompensation marks a crucial turning point in the course of cirrhosis. The purpose of this study was to assess the risk of mortality according to the clinical characteristics of fi rst decompensation, considering also the impact of acute-on-chronic liver failure (AoCLF). METHODS:We conducted a prospective nationwide inception cohort study in Italy. Decompensation was defi ned by the presence of ascites, either overt or detected by ultrasonography (UD), gastroesophageal variceal bleeding (GEVB), and hepatic encephalopathy (HE). AoCLF was defi ned according to the Asian Pacifi c Association for the Study of the Liver criteria. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or orthotopic liver transplantation (OLT)). RESULTS:A total of 490 consecutive cirrhotic patients (314 males, mean age 60.9 ± 12.6 years) fulfi lled the study criteria. AoCLF was identifi ed in 59 patients (12.0 % ). Among the remaining 431 patients, ascites were found in 330 patients (76.6 % ): in 257 (77.8 % ) as overt ascites and in 73 (22.2 % ) as UD ascites. GEVB was observed in 77 patients (17.9 % ) and HE in 30 patients (7.0 % ). After a median follow-up of 33 months, 24 patients underwent OLT and 125 died. The cumulative incidence of failure (death or OLT) after 1, 2, and 3 years was, respectively, 28, 53, and 62 % in patients with AoCLF; 10, 18, and 25 % in patients with UD ascites; 17, 31, and 41 % in patients with overt ascites; and 8, 12, and 24 % in patients with GEVB ( P < 0.0001).CONCLUSIONS: AoCLF is responsible for a relevant proportion of fi rst decompensation in cirrhotic patients and is associated with the poorest outcome. Patients with UD ascites do not have a negligible mortality rate and require clinical monitoring similar to that of patients with overt ascites .SUPPLEMENTARY MATERIAL is linked to the online version of the paper at
ASQ is a promising new ultrasound software programme which offers encouraging results in the diagnosis of both liver cirrhosis (F=4) and fibrosis (F≥1). However, to date it has not attained the same level of diagnostic performance as Fibroscan.
AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma (B-NHL) and diffuse large B-cell lymphoma (DL-BCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies. METHODS:A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared. RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related
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