Michael R. Kraus

Paroxetine for the treatment of interferon-α-induced depression in chronic hepatitis C

Background : Psychiatric side‐effects may require dose reduction or premature discontinuation of interferon therapy in chronic hepatitis C. New strategies are needed in order to prevent the premature termination of interferon therapy.

Therapy of interferon-induced depression in chronic hepatitis C with citalopram: a randomised, double-blind, placebo-controlled study

Background: Interferon-induced depression represents a major complication in antiviral treatment of chronic hepatitis C virus (HCV) infection. Aim: To evaluate in a placebo-controlled study the efficacy of a selective serotonin reuptake inhibitor (SSRI) in HCV patients on antiviral therapy with interferon-associated depression. Methods: 100 HCV outpatients were included in a randomised, double-blind, placebo-controlled study. During interferon therapy (peginterferon alfa-2b plus ribavirin), depression was monitored using the Hospital Anxiety and Depression Scale (HADS). Patients with clinically relevant interferon-induced depression (HADS ⩾9) were randomly assigned to placebo or citalopram (SSRI, 20 mg/day). Results: In 28 patients (28%), HADS scores increased to >8 during interferon therapy. They were treated with placebo (n  =  14) or SSRI (n  =  14). HADS scores declined significantly in SSRI patients within four weeks of therapy (p<0.001) but not in placebo patients. This difference between subgroups was statistically significant (p = 0.032). Unblinding became necessary in five placebo patients as a result of intolerable depression. Rescue medication (20 mg citalopram) led to a significant decrease in HADS scores (p = 0.008). All citalopram patients were able to complete interferon therapy as planned. As an interim analysis showed a significant superiority of SSRI over placebo, the study was terminated prematurely. Three patients, who became depressed afterwards, were treated in an unblinded fashion with citalopram. Conclusions: The findings demonstrate clearly that citalopram treatment is highly effective in HCV patients on interferon therapy, when initiated after the onset of clinically relevant depressive symptoms. This suggests that a general SSRI prophylaxis is not necessary in these patients.

Prophylactic SSRI during interferon alpha re‐therapy in patients with chronic hepatitis C and a history of interferon‐induced depression

Summary.  Only limited data are available on selective serotonin re‐uptake inhibitor (SSRI) prophylaxis for antiviral re‐treatment in hepatitis C patients with previous interferon‐induced major depressive episodes. Therefore, we investigated the efficacy and safety of secondary SSRI prophylaxis in these patients. In a prospective and longitudinal study, repeated psychometric testing (Hospital Anxiety and Depression Scale) was performed before, during, and after antiviral re‐treatment. Chronic hepatitis C virus (HCV)‐infected patients, who had been psychometrically monitored during an unsuccessful previous antiviral therapy, and had developed major depression were included. Interferon re‐therapy with SSRI prophylaxis was started (n = 8). The reference group was comprised of HCV patients without a history of interferon‐associated depression and also a group who were previously unsuccessfully treated with interferon and were re‐treated without SSRI prophylaxis (n = 9). All patients receiving SSRI prophylaxis were able to complete interferon re‐therapy as scheduled. As in the first therapeutic course, depression scores were significantly elevated during re‐treatment also (P < 0.001). Depression scores were significantly lower (P =0.036) during interferon re‐therapy with SSRI prophylaxis. Reference group subjects showed similar depression scores during first therapy and re‐therapy (P > 0.05). In conclusion, hepatitis C patients with a history of interferon‐induced major depression can be successfully re‐treated with peginterferon/ribavirin and concomitant SSRI prophylaxis. In these patients, SSRI prophylaxis is safe and efficacious and should be considered, if antiviral re‐therapy is indicated.

Reconstitution of Squamous Epithelium in Barrett's Oesophagus with Endoscopic Argon Plasma Coagulation: A Prospective Study

Background: Barretts oesophagus is a premalignant condition. Recent reports have suggested that laser coagulation or photodynamic therapy combined with acid suppression may induce reconstitution of squamous mucosa. However, a high percentage of residual glands remain in cases treated with both techniques. Argon plasma coagulation (APC) appears to be an attractive alternative to other thermoablative techniques. The aim of this study was to investigate the reconstitution of squamous epithelium in Barretts oesophagus after APC. Methods: Fifteen patients with histologically proven Barretts oesophagus were included in a prospective study. After base-line documentation by videotaping and biopsies, Barretts epithelium was treated by repeated APC at intervals of 4-6 weeks until complete squamous restoration was achieved. All patients were kept under high-dose proton pump inhibitor therapy. Results: In 13 patients complete reconstitution of squamous epithelium was achieved. Buried glands after squamous restora...

Compliance with Therapy in Patients with Chronic Hepatitis C: Associations with Psychiatric Symptoms, Interpersonal Problems, and Mode of Acquisition

Tolerance of interferon-α therapy for hepatitis C is often poor and medication is expensive. Compliance with diagnostic procedures and, even more important, with medical treatment is obviously critical to minimize the rate of dropouts and to maximize cost efficiency. Moreover, a good concordance with scheduled follow-ups is important for early recognition and treatment of interferon-associated side effects. Therefore, we investigated psychiatric symptoms, interpersonal problems, different modes of acquisition, and sociodemographic factors in HCV-infected patients as possible predictor variables of good versus poor compliance. In a longitudinal study, 74 patients with chronic hepatitis C (CHC) who fulfilled the criteria for treatment with interferon (IFN)-α-2b with or without ribavirin were investigated prospectively to identify those at risk for poor compliance during IFN medication. To assess predictive factors, we used both IIP-C (Inventory of Interpersonal Problems) and SCL-90-R (Symptom Check List 90 Items Revised) as psychometric instruments. Sociodemographic and somatic variables as well as compliance during IFN therapy were also evaluated. Poor compliance before or during medication was demonstrated by 23% (N = 17) of HCV patients. Sociodemographic factors and mode of acquisition, particularly former intravenous drug (IVD) abuse were not significantly linked with compliance. Logistic regression analysis demonstrated that the subgroup of patients with compliance problems was best identified by both pretherapeutic psychiatric symptoms and interpersonal problems. Predictive value was best and significant for anger-hostility (P = 0.009), intrusive (P = 0.014), depression (P = 0.015), and phobic anxiety (P = 0.049). Adopting this statistical prediction model, sensitivity was 47.1%, but specificity reached 98.3%. In total, 86.5% of cases were classified correctly. In situations of unclear indication for IFN therapy, psychological variables assessment of before the beginning of treatment may represent an additional decision-making factor.

Neurocognitive Changes in Patients with Hepatitis C Receiving Interferon alfa‐2b and Ribavirin

During antiviral therapy of chronic hepatitis C, patients frequently report impairment of concentration or memory. Therefore we prospectively investigated neurocognitive performance in patients receiving interferon alfa and ribavirin.

Glutathione peroxidase isoforms as part of the local antioxidative defense system in normal and Barrett's esophagus

The development of an oesophageal adenocarcinoma arising in Barretts mucosa is associated with a multistep process of genetic lesions that may be triggered by persistent oxidative damage. The glutathione peroxidase isoforms pGPx and GI‐GPx, which were identified recently in the mucosa of the esophagus, may play a role as defense factors to prevent such oxidative injury. To determine alterations of the expression of pGPx and GI‐GPx in Barretts mucosa as compared to primary and regenerative squamous epithelium. Biopsy samples of oesophageal mucosa of patients with Barretts esophagus (n = 12), patients with squamous restoration after thermal ablation (n = 10), and healthy controls (n = 5) were analyzed for pGPx and GI‐GPx mRNA expression by Northern blot and for glutathione peroxidase activity by enzymatic assay. Squamous regeneration was induced by argon plasma coagulation (APC) combined with proton pump inhibitor therapy. In Barretts epithelium mRNA levels of pGPx (the secreted isoform) were significantly reduced and of GI‐GPx (the intracellular isoform) significantly increased as compared to normal squamous mucosa. In squamous mucosa that had regenerated after APC, no significant differences compared to the expression pattern of primary squamous mucosa were found. Compared to squamous mucosa, Barretts metaplasia shows a different mRNA expression of pGPx and GI‐GPx that may be associated with increased susceptibility to oxidative damage.

Methodological approaches in the assessment of interferon‐alfa‐induced depression in patients with chronic hepatitis C – a critical review

In recent years, research on interferon (IFN)‐induced depressive symptoms in antivirally treated patients suffering from chronic hepatitis C (CHC) has considerably intensified. Profound scientific knowledge of this complication is of great relevance with regard to adherence, compliance, and premature therapy discontinuation.

Deterioration of health-related quality of life and fatigue in patients with chronic hepatitis C: Association with demographic factors, inflammatory activity, and degree of fibrosis

BACKGROUND/AIMS Health-related quality of life (HRQoL) is impaired in patients with chronic hepatitis C. We investigated HRQoL and fatigue in patients with chronic hepatitis C virus (HCV) infection in relation to the degree of fibrosis and inflammation, and controlled for the influence of relevant demographic and medical variables. METHODS We conducted a cross-sectional two-center study including 215 outpatients with chronic hepatitis C applying the Short-Form Health Survey (SF-36) and the Fatigue Impact Scale (FIS-D). The contribution to the variability of these psychometric scores was evaluated for the degree of fibrosis as well as viremia, gender, age, mode of transmission, genotype, and ALT. RESULTS There was a strong negative association between the degree of liver fibrosis and the physical SF-36 summary score (p=0.016). This was independent of the covariate age, also significantly predicting physical HRQoL (p=0.001). The absolute FIS score was significantly increased in patients with advanced fibrosis (p=0.043). In females, mental SF-36 summary score (p=0.007) and fatigue (p=0.017) were significantly more impaired. CONCLUSIONS Our study suggests a significant association of physical aspects of HRQoL and fatigue with the extent of fibrosis. Fibrosis stage should be considered for the identification and management of HCV patients at risk for reduced physical HRQoL.

High recurrence rate of Barrett's epithelium during long-term follow-up after argon plasma coagulation

Objective. Several studies have shown that argon plasma coagulation (APC) combined with proton-pump inhibitor (PPI) therapy is a suitable procedure to eradicate Barretts epithelium for a short-term follow-up. The real impact of this kind of management with respect to cancer risk and durability of squamous regeneration remains unclear. We present the follow-up data for up to 51 months after eradication of Barretts mucosa. Material and methods. In 1998–2001, 25 patients with Barretts esophagus were included in a prospective study. After baseline documentation, Barretts epithelium was treated with repeated APC until complete squamous restoration was reached. Thereafter, all patients were continuously treated with high-dose PPIs. Results. Each patient underwent a median of four APC sessions. Twenty-one (84%) of the patients had complete squamous regeneration at the end of treatment. During a follow-up of up to 51 months, Barretts epithelium was found to have recurred in 14/21 (66%) patients. Including the patients with initially incomplete squamous restoration, a long-lasting and complete effect was achieved in only 7 patients (28%) after a mean follow-up period of 30 months. Conclusions. So far, it is still not proven whether coagulation-induced squamous regeneration reduces the risk of Barretts carcinoma. Furthermore, the high relapse rate, the procedure-related risk, and the high costs incurred preclude the routine use of APC for the treatment of non-dysplastic Barretts esophagus. The different recurrence rates between published studies may be due to technical differences and PPI schedule. We suggest that optimal conditions for the procedure must be defined before further studies are undertaken.