26 research outputs found

    Cholestasis-Induced Liver Injury

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    Hepatitis B virus-specific T-cell responses during IFN administration in a small cohort of chronic hepatitis B patients under nucleos(t)ide analogue treatment.

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    The effect of pegylated interferon-α (IFN) add-on therapy on HBV-specific T-cell responses was evaluated in 12 patients with stable, undetectable hepatitis B virus (HBV) load under nucleos(t)ide analogue therapy. Peripheral blood mononuclear cells were isolated at week 0, 4, 8, 12, 24 and 48 of IFN add-on therapy. Quantity and quality of circulating HBV S- and core-specific CD4 and CD8 T cells were analysed ex vivo by flow cytometry. HBV S- and core-specific CD4 T-cell numbers modestly increased within 8 weeks of IFN administration (P = 0.0391 and P = 0.0195), whereas HBV-specific CD8 T cells in general showed only minor changes under IFN add-on therapy. Functionality of HBV-specific CD4 but not CD8 T cells positively correlated with serum transaminase activity. In addition, we observed an increase in CD4 T cells producing tumour necrosis factor-α (TNFα) without antigen restimulation (P = 0.0039), which correlated with elevated transaminases. During IFN add-on therapy, two patients developed an anti-HBs seroconversion, only one of whom showed a relevant increase in HBV-specific T cells. In conclusion, IFN add-on therapy of chronic hepatitis B increased HBV-specific T-cell responses and affected a previously unrecognized TNFα-monofunctional CD4 T-cell population. Although the observed T-cell responses did not correlate with HBsAg seroconversion, we expect additional insights into the immunopathogenesis of hepatitis B, following the characterization of the newly identified TNF α-monofunctional T-cell population

    Health-related quality of life in patients with autoimmune hepatitis

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    Background!#!Autoimmune hepatitis (AIH) is a rare chronic liver disease. Impaired health-related quality of life (HRQL) contributes to the overall disease burden. At current, only limited data related to the impact of treatment response on HRQL are available.!##!Objective!#!The aim of the study was to determine the impact of biochemical remission on HRQL.!##!Methods!#!Patients with AIH were prospectively enrolled between July 2018 and June 2019. A liver disease-specific tool, the chronic liver disease questionnaire (CLDQ) and the generic EQ-5D-5L were used to quantify HRQL. Treatment response was assessed biochemically by measurement of immunoglobulin G, ALT and AST. The cohort was divided into two groups according to their biochemical remission status in either complete vs. incomplete remission. Clinical as well as laboratory parameters and comorbidities were analysed using univariable and multivariable analysis to identify predictors of poor HRQL.!##!Results!#!A total of 116 AIH patients were included (median age: 55; 77.6% female), of which 9.5% had liver cirrhosis. In this cohort, 38 (38.4%) showed a complete and 61 (61.6%) an incomplete biochemical remission at study entry. The HRQL was significantly higher in patients with a complete as compared to an incomplete biochemical remission (CLDQ overall score: 5.66 ± 1.15 vs. 5.10 ± 1.35; p = 0.03). In contrast, the generic EQ-5D-5L UI-value was not different between the groups. Multivariable analysis identified AST (p = 0.02) and an incomplete biochemical remission (p = 0.04) as independent predictors of reduced HRQL (CLDQ total value).!##!Conclusion!#!Patients with a complete biochemical remission had a significantly higher HRQL. Liver-related quality of life in patients living with AIH is dependent on the response to immunosuppressive treatment

    The Impact of Liver Cell Injury on Health-Related Quality of Life in Patients with Chronic Liver Disease.

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    Patients with chronic liver disease often suffer from unspecific symptoms and report severe impairment in the quality of life. The underlying mechanisms are multifactorial and include disease-specific but also liver related causes. The current analysis evaluated the association of hepatocellular apoptosis in non-viral chronic liver disease and health-related quality of life (HRQL). Furthermore we examined factors, which influence patient's physical and mental well-being.A total of 150 patients with non-infectious chronic liver disease were included between January 2014 and June 2015. The German version of the Chronic Liver Disease Questionnaire (CLDQ-D), a liver disease specific instrument to assess HRQL, was employed. Hepatocellular apoptosis was determined by measuring Cytokeratin 18 (CK18, M30 Apoptosense ELISA).Female gender (5.24 vs. 5.54, p = 0.04), diabetes mellitus type II (4.75 vs. 5.46, p<0.001) and daily drug intake (5.24 vs. 6.01, p = 0.003) were associated with a significant impairment in HRQL. HRQL was not significantly different between the examined liver diseases. Levels of CK18 were the highest in patients with NASH compared to all other disease entities (p<0.001). Interestingly, CK18 exhibited significant correlations with obesity (p<0.001) and hyperlipidemia (p<0.001). In patients with cirrhosis levels of CK18 correlated with the MELD score (r = 0.18, p = 0.03) and were significantly higher compared to patients without existing cirrhosis (265.5 U/l vs. 186.9U/l, p = 0.047). Additionally, CK18 showed a significant correlation with the presence and the degree of hepatic fibrosis (p = 0.003) and inflammation (p<0.001) in liver histology. Finally, there was a small negative association between CLDQ and CK18 (r = -0.16, p = 0.048).Different parameters are influencing HRQL and CK18 levels in chronic non-viral liver disease and the amount of hepatocellular apoptosis correlates with the impairment in HRQL in chronic non-viral liver diseases. These findings support the role of liver-protective therapies for the improvement of the quality of life in chronic liver disease
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