Side Effect Of α-interferon On Treatment Of Chronic Hepatitis And Its Clinical Intervention

Background:Chronic virus hepatitis mainly including chronic hepatitis B and hepatitis C. Both of the viral hepatitis brings large damage and burden to human healthy in our country. An estimated400million people are chronically infected with Hepatitis B virus (HBV) in the world. Chronic Hepatitis B is the single most common cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. Hepatitis C viral (HCV) infection is a global health problem that effects approximately170million people word wide including about40million people in the china. Up to85%of HCV infected individuals may develop long term chronic hepatitis C (CHC), a disease state associated with serious clinical sequelae, including hepatitis fibrosis, cirrhosis of the liver, and hepatocelluar carcinoma. It has been estimated that up to20%of CHC patients will develop liver cirrhosis over a20to25year period, and these individuals are at increased risk for developing end liver disease and/or hepatocellular carcinoma. In fact, CHC is the leading cause of liver transplantation in the Western. Thus, aggressive antiviral treatments to successfully induce a viral remission constitute a major goal for reducing the morbidity and mortality associated with CHC. IFN-a now is considered to be efficiency in both HCV and HBV. IFNs have two mechanisms of action:a direct antiviral effect achieved inhibiting the synthesis of viral DNA and by activating antiviral enzymes, and a second mechanism that increase the cellular immune response against hepatocytes infected with HBV. The current standard of treatment for CHC consists of combination therapy with pegylated interferon-alpha (PegIFN-α) plus ribavirin. In clinical trails, more than50%of CHC patients treat with combination therapy achieved a sustained viral response (SVR). Despite the efficacy of these compounds in treating CHC, therapy with IFN is associated with considerable side effects that can interfere with a successful course of antiretroviral treatment. Most frequently reported side effects are flu like syndrome, fatigue, headache, and myalgia. Other clinical relevant side effects, such as depression, anorexia and insomnia occur less frequently. Cases of suicide attempt during IFN therapy have been reported. Thus, Aggressive management of potentially Treatment limiting adverse effects may improve patient quality of life during therapy, resulting in better treatment adherence and effectiveness. In this study, we summarize evidence of the association between IFN treatment and the onset of depression in CHC patients, the potential neurobiological mechanisms by which depression may raise, and evaluated the pharmacological agents currently used in the treatment of depression in these patientsObjective1. To analyze characteristics and differences of myelosuppression caused by pegylated interferon α(Peg-IFN a) or conventional interferon α(IFN a) therapy, to explore correlation of myelosuppression with efficacy of interferon (IFN).To compare the efficacy of oral drugs and rhG-CSF in raising the neutrophile count in Hepatitis B infected patients receiving interferon therapy.2. To explore the risk factors of psychiatric side effects of pegylated interferon alfa-2a on treatment of patients with chronic hepatitis C and to discuss the efficacy of Escitalopram on treatment of such side effect. Methods1.We Retrospectively Studied252patients suffered with chronic hepatitis B treated with Peg-IFN or IFN-a for48weeks in outpatient and ward in our hepatology center from June2008to June2010.This retrospective nonrandomized study include2consecutive treatment groups.(Conventional n=116with Hepatitis e antigen positive87) and Pegylated (n=136with Hepatitis e antigen positive103). According to the changing recommendations in China during the study period, patients were treat with interferon-a(3/5MIUthics weekly) or pegylated interferon(135/180ug weekly according to their body weight). Hematological system adverse events reported monthly visits in a standardized way. The reported adverse events were also assessed in their relation to therapy by the treating physician and reported as unrelated, possible related, probably related or related to therapy. Blood routine test were compared to analysis the variation tendency of the2kinds of IFNs treatment of CHB. The relationship between hematologic abnormalities and the efficacy of IFNs was evaluated in the sub-groups divided by the lowest blood cell counting during first24weeks of IFNs therapy..Patients suffered neutropenia were given oral drugs and rhG-CSF randomly to evaluate the efficacy of the two kinds of drugs in serious adverse reaction induced by IFNs.2. Seventy-six patients with chronic hepatitis C and pegylated interferon-a based therapy plus ribavirin were consecutively enrolled in a longitudinal study. The patients were divided into post IVDU group (n=32) and post transfusion group(n=44) according to the different mode of transmission, All patients received oral ribavirin in a dose according to their body weight (daily dose:800mg for<60Kg;1000mg for65-85Kg;1200mg for>85Kg). If the blood hemoglobin concentration fell below10g%, the daily ribabirin dose was reduced by200-400mg. Before study design all eligible patients participated in a manualized structured interview sociodemographic factors recored include gender and age. Data on the course of the disease and mode of transmission were also obtained. Blood sample were obtained during the patients’ medical visits at baseline and12th week evaluate the following parameters:blood cell count, level of thyroid hormone, ALT/AST, HCV genotype indentification, HCV RNA.B ultrasonic and fibroscan was performed to evaluate whether t he patients has cirrhosis or not.Depression was evaluated at12th week during antiviral therapy by the Symptom Checklist-90Items Revised (SCL-90-R)to compare the difference between the two groups in SCL-90-R.The relationship between risk factors and the presence of either anxiety or depression disorders was calculated using binary logistics regression. Covariates are cirrhosis, gender, HCV genotype, mode of transmission, and thyroid dysfunction.In patients suffered depression, Antidepressant Escitalopram was given after obtaining informed consent, Repeated psychometric testing was performed after4wk,8wk by SCL-90-R scale to evaluate its clinical therapeutic effect. We focus on the depression, anxiety, morpheus quality and hostility.Statistic analysis Data were analyzed with SPSS13.0software with one-way ANOVA, student’s test or LSD test, confidence intervals for proportions were calculated using Wilson’s method. Relationships between risk factors and psychiatric disorders are expressed as odds ratios. The relationship between risk factors and the presence of either anxiety or depression disorders was calculated using binary logistics regression. This allows the assessment of how each risk factor effect the probability of each the two disorders relative to the probability of each of the two disorders relative to the probability of neither disorder. P<0.05was regards as significant. ResultsAfter48weeks of therapy, the rate of HBsAg clearance,4.4%(6/136) versus2.6%(3/116) The mean rate of HBeAg loss was41.7%(43/103) versus39.1%(34/87), the rate clearance of HBV DNA was was59.2%(61/103) versus40.2%(35/87) in the Peg IFN group versus IFN-a group. There are significant difference in rate of clearance of HBV DNA (P=0.009), in the two different group, but the rate of loss HBeAg and HbsAg was no evidence difference.During the antivirus therapy,105(77.2%) leucopenia124(91.2%) granulocytopenia55(40.5%) thrombocytopenia were occurred in Peg IFN group, compare to69(59.4%) leucopenia,110(94.8%) granulocytopenia,25(21.5%) thrombocytopenia in IFN-a groupThere was significant difference in the rate of leucopenia, thrombopenia and Neu≤0.75×109/L between Peg-IFNa group and IFNa group (P<0.05). To evaluate the relationship between the leucopenia and the effect of the IFNs,We divided the white cell count into different subgroup. Of sub-groups,3.6×109/L> WBC≥2.5×109/L sub-group had higher clearance rate of HBeAg(19/56VS41/80) and HBV NDA (25/56VS49/80) than WBC>3.6×109/L sub-group Both of them difference are significantly(χ2=4.009, P<0.05)and(χ2=6.08, P<0.05;1.5×109/L>Neu≥0.75×109/L sub-group had higher clearance rate of HBeAg than Neu>1.5×109/L sub-group (P<0.05).3. Compared to the Oral drugs, the efficacy of rhG-CSF was fast but transient, there were significant differences in neutrophile counting and effectiveness at lweek and1month between the patients treated with rhG-CSF and oral drugs (P<0.05).A total of76participants enrolled in the open-label cross-sectional study. Included26female (34.2%),44had infected HCV through post transfusion,34through injecting drug use,49subjects infected with HCV genotype lb and16with 6a. In the two groups of patients, intravenous drug addiction group mainly infected with genotype6a (10/1662.5%), blood transfusion group dominantly with1b (31/4963.2%), genotype distribution statistically significant between two of the groups.8patients (10.5%) complicated with mild cirrhosis at baseline. After12weeks of therapy, anemia occurred in22(28.9%) patients,13(17.1%) patients has their thyroid malfunctions. IVDU group produces comparable scores for depression as comparable to Post transfusion group in depression anxiety hostility evaluated by SCL-90all of such items are statistically significant (P<0.05). Relationships between risk factors and psychiatric disorders are expressed as odds ratios. The relationship between risk factors and the presence of either anxiety or depression disorders was calculated using binary logistics regression.Post IVDU is a risk factors inducing depression like symptom in CHC patients receiving Peg IFN therapy (OR=3.6095%CI1.06-12.16Cox and Snell R2=0.215Nagelkerke R2=0.287Overall percentage76.3%).In patients suffered depression, Antidepressant Escitalopram was given after obtaining informed consent in23patients with10mg per/day for8weeks, Repeated psychometric testing was performed after4wk,8wk by SCL-90-R scale to evaluate its clinical therapeutic effect, assessment of efficacy is according to Chinese normal. The clinical data show that total cure rate is91.3%(21/23). Escitalopram was very effective on improve patients anxiety, depression scale scores, with significant difference between baseline and8weeks therapy. But the quality of sleeping scale score was improved slowly in this study. ConclusionsHematologic abnormalities more frequently in CHB patients treated with Peg-IFN than with IFN-a. The moderate decline level of WBC count may be the effective predictor of the efficacy of IFN treatment with CHB. rhG-CSF may be safe and effective in raising neutrophile cunts in HBV infected patients undergoing antiviral therapy with IFNs. Nevertheless, future research will be important to better understand the clinical implications of neutropenia in thesepatients. IVDU group produces comparable scores for depression as comparable to Post transfusion group in depression anxiety hostility evaluated by SCL-90all of such items are statistically significant (P<0.05)Post IVDU is a risk factors inducing depression like symptom in CHC patients receiving Peg IFN therapy (OR=3.06,95%CI:1.06-12.16).5. Escitalopram is effective and safe treatment for neuropsychiatric side effects of interferon based therapy for HCV patients, but its effect on improving sleep quality which also caused by interferon is poor.