[Managing psychiatric side effects of antiviral therapy in chronic hepatitis C]. / Management psychiatrischer Nebenwirkungen im Rahmen der antiviralen Therapie der chronischen Hepatitis-C-Virusinfektion.

The efficacy of antiviral therapy in patients with chronic hepatitis C virus (HCV) infection has largely improved over the last years. Rates of long-term therapy success (sustained virological response, SVR) clearly exceed 50% in the population of all antivirally treated HCV patients, even when including the less favourable virus genotypes 1 and 4. From recent research, it is well-known that adherence to current standard combination therapy (peginterferon alfa plus ribavirin) is crucial for the achievement of sustained response. Psychiatric adverse events, however, are subjectively very burdening and are among the most frequent reasons for premature discontinuation of antiviral therapy in HCV patients and therefore endanger therapy success. Therefore, effective side effect management regarding this branch of symptoms (e.g. depression, anger-hostility, anxiety) is to be considered crucial for the achievement of SVR. This review presents a current overview of the most relevant IFN-associated psychiatric side effects in antivirally treated patients with chronic hepatitis C infection. Moreover, various strategies for the management of these undesired conditions are reported: In particular, we address the issues of diagnostics and pretherapeutic screening for risk factors for the subsequent development of IFN-associated psychiatric symptoms. Moreover, we provide an overview of suitable instruments for the psychiatric monitoring of patients on antiviral therapy. We further discuss appropriate treatment strategies (e.g. prophylactic medication vs. medication only after the occurrence of symptoms) as well as indications for immediate therapy discontinuation due to serious psychiatric adverse events. In many cases, premature therapy discontinuation can be prevented by individual and adequate side effect management, provided that it is started in a timely manner. The continuing clinical relevance of psychiatric side effect management in this context is further backed up by the fact that also novel treatment strategies comprising protease or polymerase inhibitors will still include pegylated interferon alfa and ribavirin.

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 alpha-2b plus ribavirin), depression was monitored using the Hospital Anxiety and Depression Scale (HADS). Patients with clinically relevant interferon-induced depression (HADS >or=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.

Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional androgen deficiency or depression?

Decrease of libido and erectile dysfunction are reported by male patients during antiviral therapy of chronic hepatitis C, but therapy-associated underlying factors for sexual dysfunction are not well defined. To assess putative contributions of interferon-induced sex hormone changes to sexual dysfunction, we prospectively investigated changes in free testosterone, total testosterone, dehydroepiandrosterone sulfate, prolactin, sex hormone-binding globulin, FSH and LH levels and psychometric self-assessment scores in 34 male patients treated with interferon alfa-2b (5 MIU three times weekly) (n=19)+ ribavirin (n=15) for 6-12 months. Depression was measured by the Hospital Anxiety and Depression Scale. Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a five-point rating scale assessing sexual arousal disorder. Free and total testosterone decreased significantly during antiviral therapy in close correlation with libido/sexual function. Depression scores increased during therapy and were also significantly associated with sexual dysfunction. However, androgen levels displayed no significant correlation with depression. These results suggest that interferon-induced decrease in sexual function is associated - but not causally related -with both androgen reduction and increased depressive symptoms. These findings may affect care for male hepatitis C patients during interferon therapy.

Paroxetine for the treatment of interferon-alpha-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. AIM: To evaluate prospectively the efficacy and tolerability of antidepressant therapy (paroxetine, a selective serotonin reuptake inhibitor) in patients with chronic hepatitis C treated with interferon-alpha who have developed interferon-induced major depression. METHODS: A sub-group of 14 individuals from 121 consecutively treated hepatitis C patients developed substance-induced major depression without suicidal ideation during interferon-alpha treatment. The individuals in this sub-group received paroxetine after the occurrence of depression (20 mg daily until termination of interferon therapy). Diagnostic scores for depression (and anger-hostility) were obtained in a repeated measures design (Hospital Anxiety and Depression Scale and Symptom Checklist 90 Items Revised). RESULTS: Eleven of the 14 patients (78.6%) with interferon-induced major depression were able to complete interferon-alpha therapy as scheduled under concomitant paroxetine treatment (three dropouts: insufficient improvement of depression, occurrence of epileptic seizures, paroxetine-induced nausea/dizziness). Within 4 weeks after the start of paroxetine medication, depression scores declined significantly in all patients. CONCLUSIONS: Our data suggest that concomitant therapy with paroxetine is an effective way to treat interferon-induced depression in patients with chronic hepatitis C.

[Diagnosis and treatment of intrahepatic cholestasis syndrome]. / Diagnostik und Therapie der intrahepatischen Cholestasesyndrome. Lassen Sie es nicht zur biliären Zirrhose kommen.

Prompted by the histomorphological aspect of ductopenia, chronic intrahepatic liver diseases are increasingly being subsumed under the term vanishing bile duct syndrome. Classification by cholestasis syndromes in adults (e.g. primary biliary cirrhosis, primary sclerosing cholangitis) and in the newborn or children (e.g. alphal antitrypsin deficiency, cystic fibrosis) makes good sense. Decisive for the diagnosis are, depending on the disease presenting, a typical constellation of laboratory results, detection of autoantibodies, imaging procedures (e.g. ERC, MRI), liver biopsy where indicated, or suspected drug-induced cholestasis. Byway of treatment, ursodeoxycholic acid, an antibiotic in cholestasis, and liver transplantation in some cases, are possible options. Supportive treatment should be aimed at extrahepatic manifestations of cholestasis (e.g. osteoporosis, vitamin deficiency, pruritus).

[17-year-old patient with neutropenia and fever during therapy with analgesics]. / 17-Jähriger patient mit neutropenie und fieber unter therapie mit analgetika.

HISTORY AND ADMISSION FINDINGS: A 17-year-old patient was admitted to the hospital because of fever, shivering and odynophagia. After a pathologic fracture of the neck of the femur because of a preexisting bone cyst he had been taking a combined analgetic therapy with tilidin, metamizole and diclofenac for three weeks. Physical examination was completely normal. INVESTIGATIONS: The differential blood count revealed a severe neutropenia of < 100/µl and an elevated C-reactive protein. Several blood cultures were negative. Despite multiple diagnostic procedures no focus of infection could be detected. A bone marrow biopsy showed an impaired maturation of granulocyte precursor cells with a predominance of promyelocytes. Acute leukaemia could be excluded. This finding is typical for a e. g. metamizole-induced agranulocytosis. TREATMENT AND COURSE: Treatment consisted of reverse isolation, intravenous broad-spectrum antibiotics and granulocyte colony-stimulating factors. In the following days, the clinical condition of the patient improved considerably and the neutrophil blood count normalized. CONCLUSION: This case report presents the clinical course of an acute drug-induced agranulocytosis. This condition has to be considered as a rare but potentially life-threatening side effect of a variety of drugs, for example metamizole, and requires immediate treatment.

Giant fold gastritis with consecutive gastric carcinoma in a patient with peutz-jeghers syndrome.

We describe the case of a 36-year-old patient with Peutz-Jeghers syndrome and a very unusual gastric morphology resembling giant fold gastritis. The latter lacked additional features of Menetrier's syndrome, was not influenced by eradication of Helicobacter pylori and persisted for more than ten years under regular endoscopic surveillance. Histologically, foveolar hyperplasia was found in the enlarged folds. Endoscopic ultrasound documented a hyperechoic widening of the gastric mucosa without involvement of the deeper layers. However, despite annual control gastroscopies, an adenocarcinoma developed between the folds and was in an already advanced stage at diagnosis (UICC III). We suggest that a variant of Peutz-Jeghers syndrome may be characterised by marked foveolar hyperplasia similar to Menetrier disease, and that not conventional endoscopy alone, but rather endoscopic ultrasound may be considered in such patients.

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

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.

[Perspectives and time as relevant phenomena in the psychopathology of obsessive-compulsive neuroses]. / Perspektivität und Zeit als relevante Phänomene in der Psychopathologie der Zwangsneurose.

Perspectivity and time are central terms of the process of cognition in the phänomenological philosophy and anthropology. In this context, "perspective"' means the terms of freedom, act, orientation and sense. The "world of obessional neurotic" however is characterized by the lack of intersubjective relations, by loss of orientation and senselessness. The time, which the obessional neurotic experienced not as continual protention, but by compulsive rituals and compulsions of control, did deprive him of each liberal relation to future. From this context implications for a psychotherapeutic relation can be derived.

[Irritable colon and non-ulcer dyspepsia. Functional (somatoform) disorders of the gastrointestinal tract]. / Colon irritabile und Non-Ulcer-Dyspepsie. Funktionelle (somatoforme) Störungen des Gastrointestinaltrakts.

Among the functional (somatization) disorders seen in internal and general medicine, irritable colon and non-ulcerous dyspepsia are the most prevalent, forming the largest group of patients with gastroenterological problems. Psychosomatic aspects and the efficacy of psychotherapeutic measures are discussed, and common concurrent forms of morbidity presented. Functional disturbances of the gastrointestinal tract frequently prove to be the "chronicized" leading symptoms of a so-called somatization disorder (ICD-10 classification).

[Dying in the hospital. Medical and psychological aspects]. / Sterben in der Institution Krankenhaus. Medizinische und psychologische Aspekte.

For a variety of reasons, the process of dying is taking place ever more frequently in the institution hospital. Apart from the fact that the problem of death continues to be a taboo subject, this is leading to medico-somatic and psychological problems for both the dying person and the so-called "helper". To enable the latter to deal with this existential challenge, he or she must undergo adequate preparation.

Emotional state, coping styles, and somatic variables in patients with chronic hepatitis C.

The authors in a cross-sectional study examined 113 patients with chronic hepatitis C (CHC) without widely progressed or decompensated liver disease. The patients were investigated for emotional state (depression, anxiety, coping styles) and somatic/sociodemographic variables. A high percentage of patients had positive scores for depression (22.4%) and anxiety (15.2%). Mode of acquisition (e.g., former drug abuse) and histological grade of liver damage had no significant influence on emotional state or coping strategies. Older patients (> or = 50 years) were significantly more depressed (P = 0.024). Patients with a recently diagnosed CHC (> 4 weeks, < 6 months) had significantly lower scores for depression (P = 0.003) and anxiety (P = 0.001) than the subgroup with a time interval since initial diagnosis of more than 5 years. Recently diagnosed CHC patients also showed the highest levels of problem-solving behavior. Patients who were advised not to undergo an interferon therapy were significantly more depressed (P = 0.001) and anxious (P = 0.028). Older patients with CHC and patients with a long period since CHC diagnosis or who were advised not to undergo interferon therapy should be carefully and regularly assessed for depression, anxiety, and inappropriate coping styles.

Compliance with therapy in patients with chronic hepatitis C: associations with psychiatric symptoms, interpersonal problems, and mode of acquisition.

Tolerance of interferon-a 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)-alpha-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.

[Sarcoidosis in monozygotic twins]. / Sarkoidose bei eineiigen Zwillingen.

Identical (monozygotic) female twins both simultaneously developed acute sarcoidosis with unusual manifestations. Additional to pulmonary involvement they both also had hypercalcaemia with compensated renal failure. When seen at the age of 33 years, these findings were more marked in one of them (case 2) than in the other, and she also had granulomatous conjunctivitis, while in the other one (case 1) the dominant sign was widespread lymph node enlargement. Both were also found by magnetic resonance imaging to have multiple lesions in the white matter, interpreted as the morphological correlate of neurosarcoidosis. But they caused clinical symptoms (visual disorder, unsteady gait) in only one sister (case 1). Treatment with prednisolone largely normalized the lung functions in case 2, completely in case 1, and renal functions in both. But when the daily prednisolone dose was reduced to below 10 mg, the pulmonary symptoms recurred. These observations indicate that even in chronic sarcoidosis acute episodes may occur, with involvement of multiple organs and other rare complications. The manifestations of the underlying disease in identical twins and the similarities of its course in the two sisters underline the possible role of genetic factors in the pathogenesis of sarcoidosis.