We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric-risk patients and controls with pegylated interferon alpha (pegIFN-␣) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders. Seventeen patients without psychiatric diseases or drug addiction (controls), 22 patients with psychiatric disorders, 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN-␣ plus ribavirin. Sustained virological response (SVR), adherence, and psychiatric side effects (using the MontgomeryAsberg Depression Rating Scale and the Brief Psychiatric Rating Scale) in the groups were compared. An SVR was found in 58.6% of all patients: 58.8% of the controls, 50% of psychiatric patients, 72.2% of methadone patients, and 53.8% of former drug users. Methadone-substituted patients and former drug users had significantly higher dropout rates. Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment. However, the controls had lower pretreatment scores, followed by a significant higher increase to maximum scores. A stepwise logistic regression model showed that only genotype, not group (control, psychiatric, methadone, or former drug abuse), type of psychiatric diagnosis (affective disorder, personality disorder, or schizophrenic disorder), depression scores before and during treatment, change in depression score, antidepressive treatment, sex, or liver enzymes before treatment, was associated with SVR. Conclusion: In an interdisciplinary treatment setting psychiatric diseases and/or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN-␣ and ribavirin. ( I t is estimated that 170 million people worldwide are infected with the hepatitis C virus (HCV). Although the prevalence in the general population ranges between 1% and 2.4%, 1,2 the prevalence of HCV infection in patients with a chronic psychiatric disorder has been found to be significantly higher-between 6.8% and 8.5%. 3,4 Moreover, between 60% and 98% of intravenous drug users are chronically infected with HCV. [5][6][7] Interferon alpha (IFN-␣) is still the only effective treatment for chronic hepatitis C infection. In 1998, 2 studies showed that a combined regimen of IFN-␣ with ribavirin increased the sustained virological response (SVR) from 10% to 40%. 8,9 The development of pegylated interferons (pegIFN alpha-2a and pegIFN alpha-2b), characterized by a significantly longer half-life that allowed subcutaneous injection only once a week, further significantly improved therapeutic outcome when used in treatment in combination with ribavirin. 10-12 SVR rates between 51% and 82% have been reported, depending on the virus genotype. 10,11 Antiviral treatment of chronic hepatitis C with IFN-␣ is associated with several neuropsychiatric side effects such as fatigue, anhedonia, depression, irritab...

The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the standard of care. The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay, and also by underestimation of the importance of baseline viremia.

No abstract

We describe the association of the CTLA4 -318C>T variation with chronic HBV infection and cryptogenic cirrhosis but find no association of the +49G>A variation with autoimmune liver disease.

An efficient immune response against hepatitis C virus (HCV) is necessary to clear infection. As HCV is a single-stranded RNA virus, a role for TLR7 in the immune response against HCV is possible, and early clinical studies have demonstrated an antiviral effect of TLR7 stimulation. We tested the hypothesis that genetic variations of TLR7 are associated with chronic HCV-infection and outcome of therapy. The prevalence of three TLR7 variations was analysed in 978 patients with chronic HCV-infection, 898 patients with chronic liver disease of other aetiologies, and in 203 healthy controls. The prevalence of TLR7 variations was correlated with the response to interferon-alpha-based treatment in 544 patients with chronic HCV-infection. We analysed TLR7 polymorphisms by melting curve analysis and reconstructed haplotypes. The c.32A>T variation was over-represented in female patients with chronic HCV-infection compared to patients with other chronic liver diseases and to healthy controls (P < 0.05). In contrast, c.2403 G>A was less prevalent in male patients with chronic HCV-infection (P < 0.05). No association was observed for the third variant, c.1-120T>G. Haplotype analysis confirmed the differential distribution of TLR7 variants between the groups. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-alpha therapy (P < 0.05). This study reports the association of TLR7 variants with chronic HCV-infection and with the response to interferon-alpha therapy in patients with chronic HCV-infection. Our results suggest that variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation.

No abstract

These findings prove the predictive sensitivity of GGT as an independent indicator of nonresponsiveness even at levels that are slightly above the normal range. This new predictive parameter may help to improve individualized therapy in HCV type-1 infection.

GH insufficiency is common in patients with chronic HCV infection. While GH secretion improves during antiviral therapy, IGF-1 remains low, indicating persistent GH resistance of hepatocytes. Whether improvement in GH secretion during treatment is due to a direct drug effect or related to the suppression of viral load could not be differentiated, as most patients demonstrated a positive virologic response.