Chronic Hepatitis C Infection Research Articles

Advancing Service Integration in Opioid Treatment Progams for the Care and Treatment of Hepatitis C Infection

It is estimated that approximately 200 million people globally are infected with the hepatitis C virus and that roughly half of these people live in Asia. Without treatment, it is estimated that roughly twenty percent of those infected with hepatitis C virus progress to chronic liver disease, then subsequently, end-stage liver disease. Thus, access to hepatitis C testing and subsequent care and treatment of chronic hepatitis C infection are essential to address the global burden of disease. In the United States, the Center for Disease Control and Prevention estimates that 60% of new cases of hepatitis infection are due to injection drug use. Opioid Treatment Programs (OTP’s) dispense methadone and buprenorphine under specific federal regulations to injection drug users diagnosed with opioid dependence. OTPs are developing comprehensive care and treatment model programs that integrate general medical and infectious disease-related medical care with substance abuse and mental health services. Integrating hepatitis care services and treatment in the substance abuse treatment settings foster access to care for patients with hepatitis C infection, many who otherwise would not receive needed care and treatment. This may serve as a national model for highly cost-efficient healthcare that has a measurable outcome of improved public health with reduced hepatitis C prevalence.

Hepatitis C and lipid metabolism, hepatic steatosis, and NAFLD: still important in the era of direct acting antiviral therapy?

Chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) have an individual prevalence of 1.8-3% and at least 30%, respectively, in the United States. It is therefore not surprising that there is overlap between these two common chronic liver diseases, although the relationship appears to go beyond isolated co-existence. Hepatic steatosis is a common feature of CHC infection and can be related to both metabolic and viral specific factors. Steatosis in the setting of nongenotype 3 CHC has been predictive of response to therapy prior to the advent of the direct acting antiviral medications (DAAs). Similarly, lipid metabolism appears important in response to CHC treatment. The pathways for both lipid homeostasis and NAFLD as it pertains to CHC infection as well as the utilization of statin therapy in CHC infection will be reviewed with a focus on the relevance of these topics in the era of DAA therapy.

Limited Access to Protease Inhibitors Therapy for Chronic HCV in the Region: YES

An estimated 6.8–8.9 million individuals in Latin-America are projected to have chronic hepatitis C (CHC) infection, genotype 1 (G1) being the most prevalent. The diagnosis rate and number of treated patients in South American countries is low, therefore CHC infection prevalence is expected to increase. An accurate estimation of disease burden is critical for decisions makers on a national level to develop adequate health policies, therefore there is an unmet need to improve regional prevalence and incidence registries to be able to develop and feed Markov models. Mechanisms for accelerated access to simplified treatment of HCV infection will then be prioritized. This review only pretends to give general insights about the limited access to protease inhibitors for the treatment of chronic hepatitis C and also recommendations to overcome the identified barriers to access.

Chronic hepatitis C as a risk factor for colorectal adenoma

Over the last decade, epidemiologic studies have determined a relationship between chronic hepatitis C (CHC) and malignancies other than hepatocellular carcinoma (HCC), particularly in gastrointestinal malignancies. This study aims to evaluate the incidence of colorectal adenomas and advanced neoplasia in CHC patients compared to the general population and to evaluate whether CHC infection is an independent risk factor for colorectal adenomas and advanced neoplasia. This is a retrospective, case-control study. CHC patients who underwent screening colonoscopy between September 2006 and September 2010 were compared to randomly selected non-hepatitis C controls undergoing screening colonoscopy during the same period. Multivariate analysis was performed taking into account the known risk factors for colorectal adenoma. Two hundred thirty-three CHC patients and 466 controls that underwent screening colonoscopy were included in the study. CHC patients were younger and more likely to be male, smoker and have HIV infection compared to the control group (p < 0.05). CHC group had a significantly higher number of patients with adenomas (adenoma detection rate of 37.8 vs. 30.3 %; p = 0.04) and hyperplastic polyps (p = 0.01) detected on screening colonoscopy. The total number of adenomas detected was also higher in the CHC group; however, this was not statistically significant (0.69 vs. 0.58 per patient; p > 0.05). CHC patients were twice more likely to have advanced neoplasia detected compared to non-hepatitis C patients (odds ratio 2.04, 95 % confidence interval = 1.20-3.49; p = 0.03). CHC group was also more likely to have adenomas of ≥6 mm (p = 0.005) and macroadenomas of ≥1 cm (p = 0.02). Limitations include the single-center, retrospective design of the study. Our study is the first to demonstrate a significantly higher rate of adenomas, advanced neoplasia, and hyperplastic polyps in CHC patients compared to the general population. On multivariate analysis, CHC infection was found to be an independent risk factor for colorectal adenoma, particularly advanced neoplasia. Larger prospective studies are needed to strengthen our findings which may have implications for colorectal cancer screening.

Epidermal growth factor, its receptor and transforming growth factor-β1 in the diagnosis of HCV-induced hepatocellular carcinoma

In this article, we present a study on the levels of epidermal growth factor (EGF), its phosphorylated receptor (p-EGFR) and transforming growth factor-β1 (TGF-β1) in the sera of patients with hepatocellular carcinoma (HCC) and chronic hepatitis C (CHC) infection. The results reveal significant higher serum levels of EGF and TGF-β1 in patients with HCC compared to their level in patients with CHC infection and control subjects. The levels of p-EGFR in HCC and CHC patients show a highly significant difference between patients. Based on the best cutoff value of 914pg/ml, EGF shows 63.3% sensitivity and 87.5% specificity for HCC patients where the area under the curve is 0.81. The p-EGFR shows sensitivity of 63.3% and specificity of 100% where the area under the curve is 0.87 for HCC patients based on the best cutoff value of 39U/mg protein. The best cutoff value (370pg/ml) for serum TGF-β1 displays sensitivity of 86.7% and specificity of 100%, where the area under the curve is 0.97 for HCC patients.

Influence of chronic hepatitis C infection on cytochrome P450 3a4 activity using midazolam as an in vivo probe substrate

Inflammation-related changes in pharmacokinetics have been described for a number of disease-states including cancer, infection, and autoimmune disorders. This study examined the impact of chronic hepatitis C infection (CHC) on the pharmacokinetics of the cytochrome P450 3A probe midazolam in patients without significant liver disease who were either treatment naïve or prior interferon null-responders. Data were pooled from three studies which compared the pharmacokinetics of oral midazolam in healthy volunteers (n = 107) and in treatment-naive patients (n = 35) and interferon-null responders (n = 24) with CHC but without significant liver disease. Oral midazolam was administered as a single 2 mg oral dose, followed by frequent pharmacokinetic sampling and determination of the pharmacokinetics of midazolam and its α-hydroxy metabolite. CYP3A activity was determined by the metabolic ratio (MR) of the AUC metabolite/AUC parent and compared across groups as the mean effect ratio (test/reference). The midazolam MR was lower in treatment-naïve patients with CHC than in health volunteers with a mean effect ratio of 0.63 [90 % confidence interval (CI) 0.56-0.72]. The effect was more pronounced in null-responders, who demonstrated a mean MR effect ratio of 0.46 (90 % CI 0.39-0.53) compared to volunteers. The mean area under the concentration-time curve (AUCinf) for midazolam in healthy volunteers, naïve patients, and null-responders was 32.3 [coefficient of variation (CV%) 41], 36.5 (CV% 33.5), and 55.3 (CV% 36.9) ng.h/mL, respectively. The results of this study demonstrate a reduction in CYP3A4 activity between healthy volunteers and patients with CHC, with interferon null-responders demonstrating the most substantial difference. These results may have implications for the pharmacotherapy of patients infected with CHC.

Prevalence of transfusion-acquired hepatitis C in an Australian bleeding disorders population

In Australia prior to 1992, many patients with bleeding disorders were exposed to hepatitis C through blood products. However, the incidence, complications and response to treatment of chronic hepatitis C (CHC) in this population are poorly characterized. The aim of this study was to examine the prevalence of CHC and response to treatment in an Australian bleeding disorders population. Demographic data, virological data and liver disease status from these 700 patients with inherited bleeding disorders were analysed. Of these 700 patients, 424 (61%) had been tested for CHC infection and 219 (52%) were hepatitis C antibody positive, with the prevalence approaching 100% in patients with severe bleeding disorders. Of 219 patients, 73 (33%) had received treatment for their infection with a response rate of 33/73 (45%) across all genotypes. Of 219 patients, 34 (16%) had spontaneous viral clearance. When measured with transient elastography, 44/98 (45%) patients with CHC had significant liver fibrosis and 15/98 (15%) had liver cirrhosis. Of 130 patients, 38 (29%) with CHC infection had no evidence of follow-up with an appropriate clinician in the past 2 years. This study demonstrates that testing for CHC in this population is incomplete and treatment rates are low. Given the substantial morbidity and mortality associated with CHC and new therapeutic options becoming available, it seems important to reengage patients to diagnose, offer treatment and monitor this infection.

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

BackgroundTo treat viral infection of chronic hepatitis C (CHC) is a main strategy to prevent progression of liver disease, and cancer. Some patients with CHC have failed to respond to the common antiviral therapy in different populations.ObjectivesIn the current study it was aimed to find out the possible role of multiple drug resistance gene1 (MDR1) in non-responder patients with CHC infection in Turkish population.Patients and MethodsPeripheral blood-EDTA samples were used for total genomic DNA isolation. In total of 55 patients with chronic hepatitis C and positive results for genotype 1 [31 male (56.4%), 24 female (43.6%) and mean age-min-max; 56.9 ± 9.66 (39-71)]; 19 responder (34.5%), 21 non responder (38.2%), and 15 recurrence (27.3%) were included in the presented results. Functional MDR1 gene was genotyped by multiplex PCR-based reverse-hybridization Strip Assay method, and some samples were confirmed by direct sequencing.ResultsOur results indicate that MDR1 gene polymorphism is strongly associated with non-responder patients and those with recurrent chronic hepatitis C during conventional drug therapy when compared to the responder patients. Homozygous of the TT genotype for MDR1 exon 26 polymorphism was at 2.0-fold higher risk of non-responder than patients with CC and CT.ConclusionsThe homozygous MDR1 3435TT genotype which encodes the xenobiotic transporter P-glycoprotein may be associated with a poor antiviral response in HCV chronicity during conventional therapy, and large-scale studies are needed to validate this association.

The comparison of chronic hepatitis C treatment outcome between intravenous drug users and non-intravenous drug users

Despite the fact that the majority of prevalent and incident cases of HCV are associated with intravenous drug use (IVDU), these patients have largely been excluded from HCV care. The aim of this study was to examine the treatment outcome of chronic hepatitis C in IVDUs compared to non-IVDUs. Patients and methodsPatients with chronic hepatitis C (CHC) who initiated and completed combination antiviral therapy with pegilated interferon and ribavirin, at the Hepatology Department of the University Hospital for Infectious and Tropical Diseases in Belgrade, were retrospectively analyzed. The study included a series of 254 patients of which 100 (39.4%) were former IVDU. ResultsSustained virological response (SVR) was recorded in a total of 172 patients (67.7%). The analyses of the favorable treatment outcome, regarding particular viral genotypes, revealed that among those with genotype 1 and/or 4, including patients with genotype 1 recombinants with genotype 3, SVR was achieved in 114 (63.3%), while it was almost equally distributed between subgroups of former IVDU and all others (P=0.079). Among patients infected with HCV genotypes 2 and/or 3 the SVR rate was as high as 86.6%. ConclusionIVDU with CHC infection should be treated with standard combination antiviral therapy for CHC, since the success rate is equal or even better than in non-IVDU patients.

Commentary on: The optimal Dose of Ribavirin for Chronic Hepatitis C: From Literature Evidence to Clinical Practice

Commentary on: The optimal Dose of Ribavirin for Chronic Hepatitis C: From Literature Evidence to Clinical Practice

Outcome after Orthotopic Liver Transplantation in 33 Human Immunodeficiency Virus (HIV)-Positive Patients in Germany: Recurrence of Chronic Hepatitis-C Infection after Transplantation

Background: The introduction of HAART has led to a dramatic reduction in HIV-associated morbidity and mortality. As a consequence liver disease associated complications have become an increasing clinical challenge. With one third of European HIV-patients having hepatitis C co-infection and 6-9 % hepatits B co-infection a rising need for liver organ transplantation (OLTX) has emerged. The current study evaluates the outcome of OLTX in HIV-patients in Germany. Methods: Retrospective chart analysis of 33 HIV-positive patients who were liver transplanted in 9 German transplant centers (Bonn n=11, Essen n=8, Heidelberg n=4, Hamburg n=3, Frankfurt n=2, Mainz n=1, Tübingen n=1, Regensburg n=2, Hannover n=1) between 1997-2010. Results: Reasons for OLTX were end-stage liver disease (ESLD) due to hepatitis C (n =15, with 4 having additionally HCC) ESLD due to HBV (n =9, one with additional alcoholic cirrhosis and one with HCC), one with Budd-Chiari syndrome (n=1) and HBV/HCV/HDV-coinfection (n=1). The median CD4 T-cell count before transplantation was 223/μl (IQR,158-372). Of all transplanted patients 17/26 are still alive in 2010 with a median survival of 30 months (IQR,1-153). 9/33 patients died, 5 in the early post-transplantation period within 3 months, one due to organ rejection and acute renal failure, the other because of intrathoracal hemorrhage and 3 of septicemia. 4 patients died after 8, 10, 31 and 56 months respectively, 1 due to anastamotic leak with massive bleeding, 2 because of secondary graft failure and 1 after re-re-transplantation of septicaemia. Recurrent hepatitis B infection was efficiently prevented in 8/9 patients, whereas hepatitis C reinfection occurred in all patients. Conclusion: OLTX is a feasible approach in HIV-infected patients with ESLD in Germany with overall acceptable survival rates. Reinfection with HCV remains one of the biggest clinical challenges after OLTX in HIV/HCV coinfection.

Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis

The progression of liver fibrosis in patients with chronic hepatitis C (CHC) is important to decide on the treatment of the virus. As liver biopsy and liver stiffness measurement for staging of fibrosis present limitations, circulating levels of miR-122 have been suggested as a novel biomarker to predict the extent of liver injury. We evaluated the potential of miR-122 as an indicator of fibrosis progression in CHC infection and performed, for the first time, a comprehensive analysis of hepatic and circulating miR-122 levels in patients with CHC. Patients with well-documented CHC infection were selected from the database of HepNet, the German-Competence-Network on Viral Hepatitis. All patients underwent blood sampling and liver biopsy with grading of inflammation and staging of fibrosis. RNA was extracted from 84 liver biopsies and 164 serum samples of CHC patients. miR-122 levels in liver and serum samples were quantified by real-time PCR normalized to RNU6 or spiked-in RNA, respectively. Hepatic levels of miR-122 decreased significantly with the severity of fibrosis (p = 0.001). In addition, circulating miR-122 levels correlated negatively with increasing stages of fibrosis, although the inverse correlation was moderate due to a two-phase miR-122 pattern during fibrosis progression. Thus, circulating miR-122 levels decreased in patients with severe fibrosis (F3, F4), while at early stages with distinct fibrotic structures (F2) and high inflammatory activity, miR-122 serum levels were elevated. We conclude that during progression of fibrosis less miR-122 is released into the blood stream due to the loss of liver cells and the decrease of hepatic miR-122 levels. Although the release of circulating miR-122 possibly mirrors acute liver injury, in chronic liver disease and fibrosis, the loss of liver cells and the decreased hepatocellular miR-122 expression render miR-122 an inappropriate marker, when exclusively used for interpretation of fibrosis progression.

Does IL28B genotyping still have a role in the era of direct‐acting antiviral therapy for chronic hepatitis C infection?

IL28B genotype has been shown to be the strongest pretreatment predictor of sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C infection (CHC) treated with pegylated interferon (peg-IFN) and ribavirin (RBV). Patients carrying the good response genotype have a two- to threefold higher chance of SVR than those with a poor response genotype, manifest as dramatically improved early viral kinetics. However, the treatment paradigm for CHC is changing with the introduction of potent direct-acting antivirals (DAAs). IL28B genotype remains relevant to both telaprevir and boceprevir treatment regimens, although the strength of association with virological response is attenuated. The association between IL28B genotype and outcomes of treatment regimens that involve peg-IFN plus combination DAA therapy, or IFN-free regimens, is currently being evaluated. IL28B genotype may remain relevant to individualizing the choice of treatment regimen in the future.

Prolidase and Oxidative Stress in Chronic Hepatitis C

Hepatitis C infection represents a common healthcare issue worldwide. The present trial was designed to investigate the role of prolidase, an enzyme that is significantly involved in the biosynthesis of collagen, and of the oxidative stress that is considered to be involved in the pathogenesis of various diseases, in the chronic hepatitis C infection. The trial was performed to assess the serum prolidase enzyme level and the oxidative-antioxidative status and to determine the relation between the serum prolidase activity and the oxidative stress parameters. A total of 95 individuals, including 55 patients with chronic hepatitis C infection (CHC) and 40 healthy adults, were enrolled in the trial. The values for prolidase, the total antioxidant status (TAS), the total oxidative stress (TOS), the oxidative stress index (OSI), sulfhydryl (SH), lipid peroxidation LOOH, catalase (CAT), and ceruloplasmin were measured and compared between the patient groups. The prolidase, TOS, LOOH, CAT, and the OSI values were higher in the chronic hepatitis C group compared to the control group (P < 0.001). The TAS, SH, and ceruloplasmin levels were lower in the CHC group relative to the control group (P < 0.001). We suppose that the values of prolidase and the oxidative stress are increased while the antioxidant levels are decreased in CHC. As a result, prolidase and the oxidative stress seem to be related with the progression of the disease.

Picolinic acid in patients with chronic hepatitis C infection: a preliminary report.

Macrophage activation seems to be a feature of chronic liver diseases. Picolinic acid (PA) as a macrophage secondary signal causes the activation of interferon-gamma- (IFN-γ-) prime macrophage and triggers cytokine-driven inflammatory reactions. The rationale for seeking increased PA formation in chronic viral hepatitis is based on the involvement of activated macrophages in chronic viral hepatitis-associated inflammation. The aim of this study was to determine serum PA levels in patients with chronic hepatitis C infection, taking into account the presence of diabetes. We assessed PA and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation in 51 patients with chronic hepatitis C infection (CHC), both with and without diabetes and 40 controls. Compared with the controls, the patients with CHC showed a significant increase in plasma concentrations of PA and hsCRP (P < 0.01 and P < 0.05, resp.). The values of PA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were between PA and hsCRP levels (P < 0.05) and the presence of diabetes (P < 0.001). We documented that significant elevation in serum PA levels is associated with diabetes prevalence and increased inflammatory response reflected in hsCRP levels in CHC patients.

P-708 - Genetic risk factors for interferon-alpha induced depression

Background/aims Chronic hepatitis C infection (CHC) represents a public health problem that affects around 3% of population worldwide. Pegylated Interferon-alpha (PegIFN-α) and Ribavirin (RBV) is the recommended treatment reaching about 40–80% of sustained virological response. However, a common treatment side-effect is induced-depression that impairs patient's quality of life and treatment adherence (1,2). This paper showed polymorphisms in HTR1A, NCR1, TPH2 genes as predictive variables of IFN-induced depression. Material/methods 396 consecutive, euthymic, CHC outpatients treated with PegIFN-α/RBV were included. Patients were assessed at baseline, 4, 12, 24 and 48 weeks of treatment using PHQ and MINI-DSM-IV-R interview to diagnose depression. Survival analysis was performed. In the univariated analysis functions were compared using logrank test. Significative variables (0.1 level) were extracted for the multivariated model, using a Weibull regression model. Results The incidence of induced-depression along the treatment was 39.4%. Polimorphisms on HTR1A (P = 0.0104), TPH2 (P = 0.0231) and NRC1 (P = 0.0702) genes predicted IFN-induced depression. Conclusions Genes related with serotonine and inflamation system may play an important role in the pathogenesis of IFN-induced depression. Knowledge of predictive variables for IFN-induced depression may help to better manage patients at risk.

Serum lipids and chronic hepatitis C genotype 4: interaction and significance

Background & aim. Metabolic abnormalities are common in chronic hepatitis C infection (CHC). However, the genotypic differences of these disarrangements in patients infected with CHC genotype 4 (HCV-4) and its association with liver histology and viral loads remain unknown.Material and methods. We consecutively enrolled 183 HCV-4 patients and 106 healthy matched controls; to compare metabolic profiles and assess pattern of association of HCV RNA levels as well as histological factors with the serum lipid profile.Results. HCV-4 infection is associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) index, despite that, a favourable lipid pattern, consisting of an elevation in HDLC and a reduction in serum cholesterol (TC), LDL-C and triglyceride (TG) levels, in comparison with normal matched adults. Significant fibrosis was independently associated with HOMA-IR, portal/periportal inflammation grade, serum cholesterol and age. Univariate association was elucidated between lower LDL-C and TC and Metavir activity score and between higher TG and TC and steatosis. In multivariate analysis, severe hepatitis activity, milder hepatic fibrosis, and triglyceride levels are associated with higher HCV RNA levels.Conclusion. HCV-4 is associated with wide metabolic changes. A proportional relationship is found between serum lipid profiles and hepatitis C viral load and liver histology in patients with HCV-4.

Hematological Adverse Events and Sustained Viral Response in Children Undergoing Therapy for Chronic Hepatitis C Infection

Treatment of hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin (RBV) is associated with adverse events, which may affect the patient's adherence to the treatment regimen and the treatment efficacy. The aim of this study was to assess the sustained viral response (SVR) and interdependence between the haematological characteristics (leukocyte count, platelet count, and haemoglobin levels) in patients with chronic hepatitis C (CHC) infection during treatment with IFN and RBV. We conducted a retrospective cohort study of 170 children with CHC infection who completed treatment with IFN-α and RBV. The children were divided into 2 groups: the first group (group I, n = 119) underwent a 48-week course of treatment with recombinant IFN α-2b (Intron A) at a dosage of 3 MU 3 times a week subcutaneously and RBV at a dosage of 15 mg/kg per day orally, and the second group (group II, n = 51) was administered pegylated IFN (peg-IFN)-α-2b (PegIntron) at a dosage of 1.5 μg/kg per week subcutaneously and RBV at a dosage of 15 mg/kg per day orally for 48 weeks. The dose of IFN was not adjusted but that of ribavirin was in 2 children from group II. Hematological growth factors and erythropoietin were not used. SVR was defined as undetectable serum HCV RNA 24 weeks after the end of treatment (study week 72). Serum HCV RNA was determined by performing polymerase chain reaction, and the HCV genotypes and hematological parameters were evaluated. Serum HCV RNA levels were analysed by descriptive statistics. Means and standard deviations were calculated for values collected at the baseline, on the 12th and 48th weeks during treatment, and after 24 weeks of untreated follow-up (study week 72). Eighty-six (50%) of the 170 patients who underwent treatment achieved SVR: 62 (51%) out of 119 children from group I and 24 (47%) out of 51 from group II. The mean serum hemoglobin levels and leukocyte and platelet counts at week 12 were significantly lower than the baseline values in both responders and non-responders from both the groups (P < 0.05). In the responders in group I, the mean levels of serum hemoglobin after 24 weeks of treatment and at the end of therapy were significantly lower than the mean levels at baseline. In the group treated with peg-IFN-α-2b and RBV (group II), the mean serum hemoglobin levels at week 12 was lower in the responders than in the non-responders (P < 0.05). The decrease in the hemoglobin levels was associated with viral response. In both the responders and non-responders from both the groups, leukocyte counts decreased during treatment, and after 12 weeks, they were more significantly lower than the baseline value. The decrease was more marked in children treated with peg-IFN-α-2b + RBV (P < 0.05). After 12 weeks of treatment, the platelet count was low in children from group II who had achieved SVR. A mild decrease in hemoglobin levels and leukocyte and platelet counts during treatment with IFN and RBV in children with CHC infection may be factors responsible for SVR induction.

Hematological Adverse events and Sustained Viral Response in Children Undergoing Therapy for Chronic Hepatitis C Infection

: Background: Treatment of hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin (RBV) is associated with adverse events, which may affect the patient's adherence to the treatment regimen and the treatment efficacy.Objectives: The aim of this study was to assess the sustained viral response (SVR) and interdependence between the haematological characteristics (leukocyte count, platelet count, and haemoglobin levels) in patients with chronic hepatitis C (CHC) infection during treatment with IFN and RBV.Patients and Methods: We conducted a retrospective cohort study of 170 children with CHC infection who completed treatment with IFN-α and RBV. The children were divided into 2 groups: the first group (group I, n = 119) underwent a 48-week course of treatment with recombinant IFN α-2b (Intron A) at a dosage of 3 MU 3 times a week subcutaneously and RBV at a dosage of 15 mg/kg per day orally, and the second group (group II, n = 51) was administered pegylated IFN (peg-IFN)-α-2b (PegIntron) at a dosage of 1.5 μg/kg per week subcutaneously and RBV at a dosage of 15 mg/kg per day orally for 48 weeks. The dose of IFN was not adjusted but that of ribavirin was in 2 children from group II. Hematological growth factors and erythropoietin were not used. SVR was defined as undetectable serum HCV RNA 24 weeks after the end of treatment (study week 72). Serum HCV RNA was determined by performing polymerase chain reaction, and the HCV genotypes and hematological parameters were evaluated. Serum HCV RNA levels were analysed by descriptive statistics. Means and standard deviations were calculated for values collected at the baseline, on the 12th and 48th weeks during treatment, and after 24 weeks of untreated follow-up (study week 72).Results: Eighty-six (50%) of the 170 patients who underwent treatment achieved SVR: 62 (51%) out of 119 children from group I and 24 (47%) out of 51 from group II. The mean serum hemoglobin levels and leukocyte and platelet counts at week 12 were significantly lower than the baseline values in both responders and non-responders from both the groups (P < 0.05). In the responders in group I, the mean levels of serum hemoglobin after 24 weeks of treatment and at the end of therapy were significantly lower than the mean levels at baseline. In the group treated with peg-IFN-α-2b and RBV (group II), the mean serum hemoglobin levels at week 12 was lower in the responders than in the non-responders (P < 0.05). The decrease in the hemoglobin levels was associated with viral response. In both the responders and non-responders from both the groups, leukocyte counts decreased during treatment, and after 12 weeks, they were more significantly lower than the baseline value. The decrease was more marked in children treated with peg-IFN-α-2b + RBV (P < 0.05). After 12 weeks of treatment, the platelet count was low in children from group II who had achieved SVR.Conclusions: A mild decrease in hemoglobin levels and leukocyte and platelet counts during treatment with IFN and RBV in children with CHC infection may be factors responsible for SVR induction. Implication for health policy/practice/research/medical education:The aim of the study was to assess the dependences between the kinetics of haematological exponents (leukocytes count, platelets count,haemoglobin level) during CHC treatment with interferon and ribavirin and viral response.our data has demonstrated that mild decrease of hemoglobin levels, leukocytes and platelets counts during treatment with IFn and ribavirin of chronic hepatitis C in children may constitute the factors of achieving sustained virologic response. Thus, close monitoring of blood counts during treatment is necessary. This article is important for hepatologists and pediatric medicine doctors, who treat patients with chronic hepatitis C. Please cite this paper as:pawlowska M, pilarczyk M, Foksinska A, Smukalska e, HalotaW. Hematological Adverse events and Sustained Viral Response in Children Undergoing Therapy for Chronic Hepatitis C Infection. Hepat Mon. 2011;11(12):968-74. DoI: 10.5812/kowsar.1735143X.789

Peginterferon alfa‐2b plus weight‐based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 μg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR.