Interferon-α Therapy For Hepatitis Research Articles

Preventing Relapse of Major Depression During Interferon-α Therapy for Hepatitis C—A Pilot Study

Depression is common in hepatitis C, exacerbated by interferon, and is a major reason for discontinuing interferon therapy. We aimed to determine (1) whether patients with a history of major depression could complete a course of peginterferon alpha-2a and ribavirin if pretreated with escitalopram and (2) the relapse rate of depression during the course of therapy in these subjects. Ten patients were enrolled in the study and treated with escitalopram. The Hamilton Depression Rating Scale (Ham-D) and other psychiatric scales were administered throughout the study. There were no statistically significant increases in mean Ham-D scores. No subjects were discontinued from the study due to depression relapse. Nine of 10 subjects maintained remission of depression throughout the study. We conclude that pretreatment with escitalopram in subjects with major depressive disorder in remission may prevent recurrence of major depression during a course of interferon and ribavirin therapy for hepatitis C.

Serum CXCL10 levels and occurrence of thyroid dysfunction in patients treated with interferon-α therapy for hepatitis C virus-related hepatitis

Thyroid autoimmunity is a common side effect of interferon-alpha (IFN-alpha) treatment for chronic hepatitis C. There are currently no reliable parameters to predict the occurrence of thyroid dysfunctions in patients undergoing IFN-alpha therapy. CXC chemokine ligand 10 (CXCL10) is a chemokine known to play a role in both thyroid autoimmune disease and hepatitis C virus (HCV) hepatitis. The aim of this study was to evaluate serum CXCL10 levels in HCV patients treated with IFN-alpha in relation to the occurrence of thyroid dysfunctions. Serum CXCL10 levels were assayed in 25 HCV patients (proven to be negative for serum thyroid antibodies) before and during IFN-alpha therapy (2, 4 and 6 months) and in 50 healthy controls. HCV patients were retrospectively selected according to the occurrence of IFN-alpha-induced thyroid dysfunction and were assigned to two groups. Group I included 15 patients who did not develop thyroid antibody positivity or dysfunction; group II included ten patients who showed the appearance of serum thyroid antibodies, followed by clinically overt thyroid dysfunction. Patients with HCV, regardless of the development of thyroid dysfunctions, had significantly higher serum CXCL10 than controls (261.6+/-123.4 vs 80.4+/-33.6 pg/ml; P<0.00001). Pretreatment mean serum CXCL10 levels were significantly higher in Group I versus Group II (308.6+/-130.7 vs 191.1+/-69.4 pg/ml; P<0.05). Groups I and II showed different rates of favourable response to IFN-alpha treatment (33 and 90% respectively). Our results suggest that measuring serum CXCL10 before IFN-alpha treatment may be helpful for identifying those patients with higher risk to develop thyroid dysfunction, and require a careful thyroid surveillance throughout the treatment.

Interferon-α therapy and Type 1 diabetes mellitus in patients with hepatitis C: pathophysiologic insights

Chronic hepatitis C virus infection is associated with an increased risk for the development of Type 2 diabetes mellitus. Proposed mechanisms include increased insulin resistance, development of nonalcoholic fatty liver disease and direct infection of the pancreas by hepatitis C virus. However, the development of Type 1 diabetes mellitus is usually associated with interferon-α therapy for hepatitis C virus infection with development of anti-islet cell antibodies. The pathogenetic mechanisms underlying this autoimmune destruction of the pancreas are not completely understood. In this review the authors discuss hepatitis C virus and Type 1 diabetes, highlighting the role of interferon-α therapy in the development of Type 1 diabetes in hepatitis C virus-infected patients. The mechanisms of action of interferon-α related to the development of Type 1 diabetes in this patient population will also be discussed.

Hepatic fibrosis: from bench to bedside.

Antifibrotic therapies are preferentially targeted to the activated mesenchymal cells in the liver that synthesize an excess of matrix proteins and resemble the myofibroblasts of healing wounds. These cells derive from normally quiescent hepatic stellate cells and (myo-) fibroblasts. Their activation is triggered and maintained by several fibrogenic modulators and cytokines, but also by mechanical stress. Whereas many agents inhibit stellate cell/myofibroblast proliferation and collagen synthesis in vitro, only few of them are tolerable or effective in suitable animal models in vivo. An antifibrotic effect was demonstrated for silymarin, a defined mixture of flavonoids, sho-saiko-to which contains the related compound baicalein, for halofuginone, another plant-derived agent, for the phosphodiesterase inhibitor pentoxifylline and for LU135252, an oral inhibitor of the endothelin-A-receptor. The retrospective finding that interferon-alpha therapy for hepatitis C may halt or even reverse fibrosis, has to be confirmed in prospective randomized trials. Strategies to inhibit the profibrogenic cytokines transforming growth factor (TGF)-beta or connective tissue growth factor (e.g. by soluble decoy receptors) are evolving, but have not been convincing yet. Drug targeting to the fibrogenic liver cells is now possible by use of cyclic peptides that bind to receptors which are specifically up-regulated on activated stellate cells, for example those for platelet-derived growth factors or collagen type VI. In addition, blockade of such activation receptors can induce stress-relaxation which reverts the fibrogenic cells to a fibrolytic, collagen degrading phenotype. Combined with the evolving validation of serological markers of fibrogenesis and fibrolysis an effective and individualized treatment of liver fibrosis can be anticipated.

Factors predictive of response to interferon-α therapy in hepatitis C virus infection

Factors predictive of response to interferon-α therapy in hepatitis C virus infection

Factors predictive of response to interferon-α therapy in hepatitis C virus infection

To determine the patient-dependent and virus-related factors that may predict sustained response to interferon-alpha therapy, we prospectively evaluated 60 consecutive patients with chronic hepatitis C who received a standardized treatment schedule of interferon-alpha. Twenty-eight patients achieved a long-term sustained remission, 14 patients had temporary responses during treatment but relapsed after completing it and 14 patients did not respond. Four patients dropped out because of severe side effects and were excluded from evaluation of efficacy. Twenty-one variables were chosen as possible predictors of sustained response and were analyzed by means of multivariate analysis. Variables related to the hepatitis C virus included genotype and concentration in serum before treatment. The former was determined by means of the polymerase chain reaction with genotype-specific primers for genotypes PT, K1, K2a and K2b, which were deduced from nonstructural region 5 of the hepatitis C virus genome. The latter was measured with a competitive polymerase chain reaction technique. Three variables were statistically significant (p < 0.05) on univariate analysis: viral genotype, pretreatment level of viremia and Knodell's fibrosis score. In multivariate analysis viral genotype and Knodell's fibrosis score were correlated independently with a sustained response (p < 0.05 for both). Incidence of sustained response was 40% and 91% in patients with genotypes K1 and K2a, respectively. We conclude that with the treatment schedule used, viral genotype was the most useful predictor of a sustained response to treatment with interferon-alpha.