[Show abstract][Hide abstract] ABSTRACT: Objective and Methods. Although the interaction between fatigue and depression in patients with chronic hepatitis C infection (HCV) has been recognized, the biological correlates of this observation have yet to be reported. We addressed this issue by examining serotonin transporter- (SERT-) driven [(14)C]-serotonin uptake rate (SUR) and serotonin content in platelets of 65 untreated HCV patients and 65 healthy control subjects (HCS). All patients completed report questionnaires for fatigue, depression, and general psychopathology. Structured interviews were conducted by a board-certified psychiatrist. Results. Whereas 36 of the patients experienced fatigue of moderate-to-severe intensity, only 16 reported symptoms of depression (BDI score > 10). Mean SUR in patients with depressive symptoms was significantly higher relative to the HCS, corresponding to a large Cohen's effect size of d = 1.45 (95% CI = 0.66-1.83). Patients who rated their fatigue to have a marked impact on mood and activity displayed a moderate relationship between the BDI score and SUR (n = 18, r = 0.563, P = 0.015), which becomes stronger after controlling for age, gender, and thrombocytopenia (r part = 0.710, P = 0.003). In the univariate analysis, high fatigue interference score, thrombocytopenia, and high SUR were all significant predictors of depression. Conclusions. High SERT activity could be implicated in the expression of depressive symptoms especially in a subgroup of HCV patients who are feeling fatigue as markedly distressing.
Depression research and treatment 01/2014; 2014:821381.
[Show abstract][Hide abstract] ABSTRACT: Incomplete suppression of hepatitis C virus (HCV) replication with persistence of minimal viremia (partial virologic response) leading to treatment failure can be observed in a significant proportion of HCV type 1-infected patients during antiviral therapy. Recently, high-dose intravenous silibinin has demonstrated strong antiviral activity against HCV. We were therefore interested in whether patients with partial virologic response can be rescued by the on-treatment addition of a short-term course of high-dose intravenous silibinin infusions. Twenty patients who failed to achieve a complete virologic response to different interferon-based regimens qualified for the rescue strategy and received 1400 mg/day silibinin infusions on two consecutive days. Complete viral suppression (below the limit of detection <6 IU/mL, TMA assay) could be induced in 13 of 20 patients within the first week after the short-term silibinin infusion, and all but one of them also remained HCV RNA negative during the subsequent follow-up period on continued peginterferon plus ribavirin treatment. In the remaining seven patients, no complete suppression could be achieved although four showed a significant HCV RNA reduction in response to silibinin. Silibinin infusions were generally well tolerated, and activation of abdominal peristalsis with nausea, diarrhoea and vomiting were the most prominent side effects. Of the twelve patients who exhibited a durable response to peginterferon and ribavirin treatment, three achieved an SVR, two achieved a week 12 SVR and four suffered a viral relapse. Three patients could not complete the assigned antiviral treatment with peginterferon alpha and ribavirin for nonvirological reasons. Short-term administration of high-dose intravenous silibinin might be an interesting approach to rescue patients with ongoing minimal residual viremia while on interferon-based therapy. These preliminary findings may stimulate further studies to evaluate more refined therapeutic strategies.
Journal of Viral Hepatitis 08/2012; 19(8):547-53. · 3.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: Hepatitis C-virus-persistence after orthotopic liver transplant leads to reduced patient and graft survival compared to other indications. Current interferon-based antiviral therapy of hepatitis C-virus-infection posttransplant provides a sustained response rate of 30% to 40%. This study, performed in an hepatitis C-virus-reinfected liver transplant population, examines the antiviral effect of intravenously administered silibinin, recently reported to exhibit strong antiviral properties in the natural setting of hepatitis C-virus-related liver disease. Patients and Methods: Four patients after orthotopic liver transplant with hepatitis C-virus-recurrence, previously having not responded to peg-interferon-ribavirin therapy, were treated with intravenous silibinin and additionally, after the 10th day, with standard interferon-based therapy. Aminotransferases and hepatitis C-virus-RNA were measured during treatment. Results: All patients demonstrated normalization of liver enzymes and significant decline of hepatitis C-virus-RNA measured at day 10 (mean 2.8 logarithmic levels: 1.7, 2.3, 2.9, and 4.3) during silibinin monotherapy. One patient cleared hepatitis C-virus-RNA under silibinin monotherapy and another patient eliminated hepatitis C virus under subsequent interferon-based therapy. No adverse effects were observed during silibinin application. Conclusions: Intravenous silibinin is an effective therapeutic approach for treating hepatitis C-virus-reinfection after liver transplant and should be evaluated further.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 02/2011; 9(1):1-6.
[Show abstract][Hide abstract] ABSTRACT: To analyze the dynamics of the shear modulus of the liver to assess the optimal driving frequency and to determine the diagnostic accuracy of generalized frequency-independent elasticity cutoff values for staging hepatic fibrosis.
This institutional review board-approved prospective study included 16 healthy volunteers and 72 patients with biopsy-proved liver fibrosis. After obtaining written informed consent, imaging was performed at 1.5-T by using a motion-sensitized echo-planar imaging sequence. Wave excitation was performed by an actuator introducing a superposition of four frequencies (25.0, 37.5, 50.0, 62.5 Hz) of shear waves. The elasticity µ value and the structure geometry parameter α were calculated by using the two-parameter springpot model. The performance of magnetic resonance (MR) elastography in staging liver fibrosis was assessed with area under the receiver operating characteristic curve (AUROC) analysis and Spearman correlation analysis.
Elasticity increased with stage of fibrosis, with mean values as follows: for volunteers, 2.25 kPa ± 0.43 (standard deviation); stage F1, 2.61 kPa ± 0.43; stage F2, 3.00 kPa ± 0.63; stage F3, 3.86 kPa ± 0.61; and stage F4, 5.86 kPa ± 1.22. Frequency-independent cutoff values derived for fibrosis and AUROC values, respectively, were as follows: stage F1 or higher, 2.84 kPa and 0.9128; stage F2 or higher, 3.18 kPa and 0.9244; stage F3 or higher, 3.32 kPa and 0.9744; and equivalent to stage F4, 4.21 kPa and 0.9931. The geometry of the tissue (α value) did not correlate with fibrosis. Frequencies of 50.0 Hz and 62.5 Hz displayed the highest diagnostic accuracy.
The diagnostic performance of multifrequency MR elastography in determining the degree of hepatic fibrosis increases with stage of fibrosis. Metrics obtained at the higher frequencies provide better diagnostic performance compared with the lower frequencies. Results of the AUROC analysis demonstrate the high accuracy of frequency-independent cutoff values for staging higher grades of hepatic fibrosis.
[Show abstract][Hide abstract] ABSTRACT: Response to HCV treatment with pegylated interferon-alpha is variable but might at least in part depend on genetic host factors. The G protein beta3 unit (GNB3) C825T polymorphism has been shown to affect treatment response in HCV mono-infection. Here, we analyzed the impact of the GNB3 genotype in the context of HCV/HIV co-infection.
HIV/HCV co-infected (n=112) and HCV mono-infected patients (n=150), receiving therapy with pegylated IFN-alpha/ribavirin, were enrolled into this study. Furthermore, we analyzed 220 healthy and 92 HIV mono-infected patients. GNB3 genotype was defined and correlated with respect to treatment response.
GNB3 genotype distribution differed significantly between HIV/HCV co-infected patients and HIV-positive/HCV-negative (p=0.0002) or healthy controls (p=0.03). Patients with a GNB3 CC genotype had significantly lower SVR rates as compared to carriers of a non-CC genotype (52% versus 77%; p=0.018). In a logistic regression analysis the GNB3 genotype and the HCV genotype were significantly associated with response to treatment (p=0.018). In contrast to HIV/HCV co-infected patients, GNB3 genotype did not affect response to treatment in HCV mono-infected patients.
The GNB3 825 CC genotype is associated with poor SVR rates in HIV/HCV co-infected patients. This underlines the impact of genetic host factors for treatment response.
Journal of Hepatology 10/2007; 47(3):348-55. · 9.86 Impact Factor