Abstract Chronic viral hepatitis C (CHC) and its complications have a negative effect on patient’s quality of life. We evaluated the impact of a successful interferon-free treatment on the quality of life of patients with obesity and metabolic disorders in the context of immunological disturbances. Twenty overweight or obese (BMI > 25) patients with CHC were tested before the therapy and after a successful treatment regimen. After the therapy, patient’s emotional well-being improved (p = 0.02), while physical well-being remained unchanged. There was a decrease of patient’s liver fibrosis and an increase of steatosis along with body mass. Among HCV-infected individuals, the expression of toll-like receptor 3 (TLR3) on lymphocytes was higher than in the control group (p = 0.03), but it decreased (p = 0.001) after the treatment. There was also a decrease of the intensity of immunofluorescence of FoxP3+ after the treatment (p = 0.04). Our study showed an improvement in mental aspects of patient’s quality of life after the treatment. Unfortunately, probably due to rapid immunological changes, patient’s BMI, serum cholesterol levels and hepatic steatosis have a tendency to increase and may lead to cardiovascular and other complications, like hepatocellular carcinoma.
Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies.
Although the clinical course of chronic hepatitis B (CHB) is relatively mild in a majority of children, a certain proportion of patients develops chronic liver disease that finally results in serious liver injury. Reports regarding clinical outcome of infection are scarce.The aim of this study was to assess inflammatory activity, fibrosis, and their correlation to clinical data in children with CHB before antiviral treatment.The study included 200 children, aged 1.5-18 years (mean 7.49+/-4.01 years), with CHB hospitalized before liver biopsy between 1992 and 2003. History and clinical data were analyzed. Histopathological assessment was based on the modified Knodell system. Statistical analysis was performed, and results with P<0.05 were considered significant.Necroinflammatory activity was found to be mild in 115 children and moderate in 44. Ninety-three children had minimal fibrosis (S1), 62 children - S2, and the remaining 8 - S3-S4. Alanine aminotransferase (ALT) activity was proportional to staging (Kruskall-Wallis test H=10.84, P=0.028) and was significantly higher in the children with staging >or=S2, P=0.0008. Spontaneous hepatitis B early antigen seroconversion occurred in 30/200 children (15%) and was related to the shorter length of infection, P=0.008.Intensity of liver injury in children with CHB varies from minimal to marked necroinflammatory activity and fibrosis varies from none to advanced. Progression of liver fibrosis seems to be proportional to the age at infection. ALT activity appears to be higher in the children with significant (S2-S4) fibrosis. Spontaneous hepatitis B early antigen seroconversion is apparently related to the shorter length of infection and higher ALT activity.
Chronic hepatitis C (CHC) affects the activity of natural killer (NK) cells, but successful interferon- free treatment partially restores it. The goal of this study was to assess whether gender influences NK functionality. We examined 21 post-menopausal women and 24 men with CHC who were treated with direct-acting antivirals (DAA) and 33 healthy volunteers. Using flow cytometry, we analysed KIR2DS4, NKG2D, NKp30, KIR2DL2/DL3, NKG2A and TRAIL on the surface of NK cells. Intracellular granzyme B was also assessed and serum CXCL10 was quantified via ELISA. Overall, patients with CHC had higher expression of KIR2DS4, NKG2A, and NKp30 relative to the control group. Further, CHC patients had a lower percentage of NK cells among lymphocytes relative to the control group. After treatment, KIR2DS4, KIR2DL2/DL, NKG2A, TRAIL and NKp30 on NK cells were decreased whilst the percentage of NK cells and the expression of granzyme B and NKG2D increased. Prior to treatment, serum CXCL10 was elevated, but it was inhibited post-treatment. We observed gender-specific differences in the expression of KIR2DL2/DL3 (higher in women) and NKp30 (elevated in men) compared to CHC/control groups. After treatment, KIR2DL2/DL3, NKp30 and CXCL10 dropped only in the female group while granzyme B increased in the male group. In conclusion, the response of NK cells among men and women of post-menopausal ages with CHC differs. Our research may lead to more studies on the different nature of female and male immune systems in the context of HCV infection and treatment.
Abstract Chronic hepatitis C (CHC) affects the activity of NK cells, but successful interferon-free treatment partially restores it. The goal of the study was to assess whether gender influences those alterations. We examined 21 women after menopause and 24 men with CHC treated with directly acting antivirals (DAA), and 33 healthy volunteers. With flow cytometry, we analysed KIR2DS4, NKG2D, NKp30, KIR2DL2/DL3, NKG2A, TRAIL and granzyme B on the surface of NK cells, simultaneously we checked serum CXCL10 with ELISA. Overall, patients with CHC had higher expression of KIR2DS4, NKG2A, NKp30 and a lower percentage of NK cells among lymphocytes than the control group. After the treatment KIR2DS4, KIR2DL2/DL3 and NKG2A, TRAIL NKp30 on NK cells decreased, while the percentage of NK cells, expression of granzyme B and NKG2D increased. Serum CXCL10 was elevated before the treatment and dropped afterwards. We observed differences between genders in the expression of KIR2DL2/DL3 (higher in female) and NKp30 (elevated in men) comparing CHC/control groups. After the treatment of KIR2DL2/DL3, NKp30 and CXCL10 dropped only in female while granzyme B increased in male. In conclusion, the response of NK cells among men and women in post-menopausal age with CHC differs. Our research may lead to more studies on different nature of female and male immune systems in the context of HCV infection and treatment.
The aim of his study is to evaluate the influence of the baseline ALT activity, HCV viral load and genotype on the effects of the treatment with pegylated interferon alpha 2 b and ribavirin in children with CHC.Twenty children with chronic hepatitis C were enrolled to the study. All were treated with pegylated interferon alpha and ribavirin for 48 weeks. Viral genotype, advancement of changes in histopathological examination and ALT activity with HCV-RNA viral load in respective periods of the treatment were analyzed.All children were infected with genotype 1. The advancement of inflammatory changes and fibrosis in the liver was mediocre. On the basis of the outcome of treatment in the 24th week of the treatment the study group was divided to group A n = 17, which eliminated HCV, and group B n = 3 without elimination. In some of the patients n = 10 viral response was assessed directly after the therapy. In 8 children HCV elimination was confirmed, however in 2 patients replication was still present. ALT activity decreased with the decline of the viral load.During the treatment HCV RNA elimination occurs in 85% of children infected with genotype 1. ETR seem to achieve similar ratio. The influence of ALT activity, HCV viral load and the advancement of changes in histopathological examination on the HCV RNA elimination remains unclear. The adverse-effects are not significant and abnormalities in clinical chemistry do not cause permanent cease of the therapy.
ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Zientarska A, Kaczmarek M, Mozer-Lisewska I, Kowala-Piaskowska A, Witkowska A, Żeromski J. Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage. Clinical and Experimental Hepatology. 2021;7(2):196-204. doi:10.5114/ceh.2021.107122. APA Zientarska, A., Kaczmarek, M., Mozer-Lisewska, I., Kowala-Piaskowska, A., Witkowska, A., & Żeromski, J. (2021). Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage. Clinical and Experimental Hepatology, 7(2), 196-204. https://doi.org/10.5114/ceh.2021.107122 Chicago Zientarska, Agata, Mariusz Kaczmarek, Iwona Mozer-Lisewska, Arleta Kowala-Piaskowska, Aleksandra Witkowska, and Jan Żeromski. 2021. "Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage". Clinical and Experimental Hepatology 7 (2): 196-204. doi:10.5114/ceh.2021.107122. Harvard Zientarska, A., Kaczmarek, M., Mozer-Lisewska, I., Kowala-Piaskowska, A., Witkowska, A., and Żeromski, J. (2021). Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage. Clinical and Experimental Hepatology, 7(2), pp.196-204. https://doi.org/10.5114/ceh.2021.107122 MLA Zientarska, Agata et al. "Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage." Clinical and Experimental Hepatology, vol. 7, no. 2, 2021, pp. 196-204. doi:10.5114/ceh.2021.107122. Vancouver Zientarska A, Kaczmarek M, Mozer-Lisewska I, Kowala-Piaskowska A, Witkowska A, Żeromski J. Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage. Clinical and Experimental Hepatology. 2021;7(2):196-204. doi:10.5114/ceh.2021.107122.
