Association of chronic hepatitis C with major depressive disorders: irrespective of interferon-alpha therapy.

BACKGROUND: Mood and anxiety symptoms in chronic hepatitis C (CHC) may be related to the patient awareness of the diagnosis and prognosis, to side effects induced by interferon (IFN)-alpha treatment, as well as to substance abuse. However, the observation of metabolic alterations in patients with CHC has led to hypothesize a direct effect of hepatitis C virus (HCV) on brain function. This study was aimed at elucidating whether CHC is associated with specific anxiety or mood disorders independently of confounding factors. METHODS: Patient cohort: consecutive patients, 135 with CHC and 76 with chronic hepatitis B (CHB). EXCLUSION CRITERIA: previous treatment with IFN-alpha, co-infection with HCV and hepatitis B virus, infection with human immunodeficiency virus, drug or alcohol abuse, or malignancies. CONTROLS: subjects without evidence of hepatitis randomly extracted from the database of a previous epidemiological study; they were divided into two groups of 540 (332 males) and 304 (220 males) as controls for patients with CHC and CHB, respectively. The psychiatric diagnosis was formulated by means of the Composite International Diagnostic Interview Simplified carried out by a physician according to DSM-IV criteria. RESULTS: A higher lifetime prevalence of major depressive disorder (MDD) was observed among CHC compared to CHB or controls. The risk of MDD was not statistically different between CHB and controls. Both the CHC and CHB groups showed a significantly higher frequency of panic disorder when compared to controls. No statistical differences were observed in the prevalence of general anxiety disorder and social phobia when CHC or CHB were compared to controls. CONCLUSION: The present study provides the first evidence of an association between CHC and MDD, diagnosed on the basis of well-defined international criteria. This association is independent of treatment with IFN-alpha and is not influenced by substance or alcohol abuse. By contrast, anxiety disorders do not appear to be specifically associated with CHC.

Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during treatment with peginterferon alfa-2a and ribavirin.

Peginterferon (Peg-IFN) alfa in combination with ribavirin represents the gold standard treatment for chronic hepatitis C, but is associated with various side effects, especially hematological abnormalities. We report here a case of severe autoimmune hemolytic anemia (AIHA) complicated by symptomatic myocardial ischemia in a patient with chronic hepatitis C during combination therapy. The worsening hemolysis after ribavirin withdrawal and exclusion of other causes implicated Peg-IFN alfa as the cause of AIHA. Our study demonstrates that in patients without preexisting immunological abnormalities Peg-IFN can de novo induce autoimmune complications that, albeit rarely, may be life-threatening.

[Amoxicillin-clavulanic acid and oral anticoagulants: a possible dangerous association]. / Amoxicillina-acido clavulanico ed anticoagulanti orali: un'associazione potenzialmente pericolosa.

We describe a 68-year-old male patient, treated with amoxicillin-clavulanic acid for 18 days and oral anticoagulants. He developed a cholestatic hepatitis with conjugated bilirubin of 11 mg/dL and a concomitant overdose of oral anticoagulants (INR 7). Nausea, vomiting, jaundice and large ecchymoses occurred 41 days after treatment with amoxicillin-clavulanic acid; the clinical manifestations resolved within 1 week and the liver tests returned to normal 48 days after therapy withdrawal. The mechanism of the amoxicillin-clavulanate-induced hepatitis is probably immunoallergic; this complication occurs mainly in subjects with a metabolic and/or immunologic idiosyncrasy. The pharmacokinetics of this antibiotic, which is not directly metabolized by cytochrome P450, may be affected by the concomitant use of drugs under cytochrome P450 control. When using amoxicillin-clavulanic acid, one should take into account its potential hepatic toxicity and possible interaction with oral anticoagulants. However, it appears to be crucial to follow the correct indications for both drugs. In fact, in the patient described above amoxicillin-clavulanic acid was wrongly administered as prophylaxis after a cutaneous biopsy of the nose. The same occurred with the oral anticoagulants prescribed to the patient for a single episode of paroxysmal atrial fibrillation which had occurred one year previously.

Allele 4G of gene PAI-1 associated with prothrombin mutation G20210A increases the risk for venous thrombosis.

Several studies have tried to clarify the role of polymorphism 4G/5G of the PAI-1 gene in venous thromboembolism without reaching any final conclusion. It has been demonstrated that this polymorphism may induce an increased risk for venous thromboembolism (VTE) in patients with thrombophilic defects. We studied the association of prothrombin mutation G20210A with 4G/5G polymorphism in 402 VTE patients and 466 healthy controls. Patients affected by prothrombin mutation G20210A, with or without the concomitant presence of allele 4G, had a 3.7 thrombotic risk (C.I. 95% 2.3-6.0; p<0.0001). Moreover, genotype 4G/4G is a mild risk factor for VTE, irrespectively of whether the prothrombin mutation was present. Logistic regression analysis showed that patients carrying the G20210A prothrombin mutation with allele 4G gave an odds ratio for VTE of 6.1 (C.I. 95% 3.2-11.4; p<0.001). The risk increased up to 13.0 (C.I. 95% 3.0-60.4; p<0.001) when we considered the association of the prothrombin mutation with genotype 4G/4G. The G20210A mutation without allele 4G (5G/5G) was not a risk factor for VTE. In conclusion, we believe that patients affected by VTE with concomitant presence of the G20210A prothrombin mutation could be tested for genotype 4G/4G to better define their thrombotic risk.

Oral anticoagulant therapy in the primary and secondary prophylaxis of stroke.

Stroke is the first cause of disability and the second cause of mortality in the world. Oral anticoagulants have been proved to be effective in the primary and secondary prophylaxis of stroke not only in cardiac conditions but also in other pathologies such as the antiphospholipid syndrome. Though the efficacy of oral anticoagulants in the prevention of stroke has been consolidated in several conditions such as mechanical prosthesis, atrial fibrillation, and the antiphospholipid syndrome, their role is less clear in patent foramen ovale, interatrial septal aneurysm, dilated cardiomyopathy, and aortic plaques. Nevertheless, oral anticoagulants have recently been re-evaluated in large clinical trials and have been shown to be effective in the secondary prevention of myocardial infarction and stroke. This review considers both the established and controversial aspects and the role of anticoagulation clinics in the practical approach to these patients, as well as their education and quality of life.