Therapy In HCV-infected Patients Research Articles

Real-world experience with direct-acting antiviral therapy in HCV-infected patients with cirrhosis and esophageal varices

BackgroundHepatitis C virus (HCV) infection affects 50 million people worldwide with around 242,000 deaths annually, mainly due to complications such as cirrhosis and hepatocellular carcinoma (HCC). Portal hypertension (PH) caused by cirrhosis leads to severe consequences, including esophageal varices (EV). This study aimed to evaluate the effectiveness and safety of direct-acting antiviral (DAA) treatment in patients with and without EV.MethodsThis retrospective analysis involved consecutive HCV-infected adults undergoing DAA therapy at 22 Polish hepatology centers from July 1, 2015, to December 31, 2022. Patients with cirrhosis were categorized based on the presence of EV diagnosed by gastroscopy. Treatment effectiveness was measured by sustained virologic response (SVR), with safety outcomes monitored for 12 weeks post-treatment.ResultsA population of 3393 HCV-infected patients with cirrhosis was divided into groups with (A, n = 976) and without (B, n = 2417) EV. Group A showed a significantly higher prevalence of comorbidities and concomitant medications. Genotype (GT)1b infections predominated in both groups, and GT3 infections were more common in the EV group. Group A exhibited more severe liver disease, and higher rates of decompensation, HCC, and HBV co-infection. SVR was significantly higher in group B (91.5% vs. 96.3%, p < 0.0001). Male gender, GT3, EV presence, and Child-Pugh grade B were identified as independent negative SVR predictors. Group A had a worse safety profile, with notably higher adverse event incidence and mortality.ConclusionsDAA therapies are highly effective and well tolerated in patients with cirrhosis, but EV presence predicts poorer virologic responses.

Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals.

Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population. The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023. The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively. A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.

Short-term changes of liver fibrosis in patients with HCV genotype 1b – related compensated cirrhosis after sustained virologic response

Several studies suggested a regression of liver fibrosis (LF) over time after successful therapy in HCV infected patients. The aim of this study was to assess the changes of fibrosis occurring after successful direct acting antiviral (DAA) treatment using transient elastography (TE) and FIB-4 score in patients with HCV genotype 1 b compensated cirrhosis. Material and methods: LF were evaluated by TE and FIB-4 at baseline, sustained virological response (SVR) and 12 months after end of treatment (EOT). LF regression was defined as an improvement of ≥ 30% in Fibroscan® score at follow-up compared to baseline. Results: There were 98 patients with HCV-related compensated liver cirrhosis who achieved SVR after DAAs, most female (65.3%), aged 60.64 ± 9.56 years. Overall, LF had a significant improvement with a median (IQR) regression of 4.5 (1.8-7.8) from baseline to SVR and 5.1 (2.5-8.65) from baseline to 12 months after EOT (p &lt;0.001). Also, the FIB-4 score significantly decreased at SVR and 12 months after EOT, similar to LSM values [median (IQR) at SVR 2.27 (1.55-3.26) and 2.21 (1.51-3.28) at 12 months after EOT (p &lt;0.001)]. Conclusions: We demonstrated that achieving SVR with DAA-based regimens was associated with significant improvement of liver stiffness measured by TE, and liver function monitored by FIB-4 index, but the regression of fibrosis must be constantly evaluated in dynamic thus further studies are warranted to confirm these findings in other populations.

Association of ITPA Gene Expression and Hematological Abnormalities Induced by Dual therapy in HCV-infected Patients

Association of ITPA Gene Expression and Hematological Abnormalities Induced by Dual therapy in HCV-infected Patients

The Predictive Factors for Favorable Outcomes of Peginterferon and Ribavirin Combination Therapy in HCV-Infected Patients

We aimed to investigate the association of pretreatment host and/or viral related factors with sustained virological response (SVR) rate in chronic hepatitis C (CHC) infected patients. This cohort study was performed on 200 IFN-naïve Iranian CHC patients who were treated with pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV). Pretreatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood sugar (FBS), HCV load and genotype were determined, and the pattern of changes was monitored throughout the course of treatment. The baseline FBS value in the non-responder group was significantly higher than that of the SVR group. The SVR group showed a rapid and continuous decline of ALT/AST activity from the beginning of the treatment, while the ALT level was fluctuating in non-responder and relapse groups. Persistent normalization of transaminases during combination antiviral therapy was significantly associated with SVR rate. Besides, age and FBS levels had the greatest impact on SVR. Minocycline seems to be a safe and effective adjuvant in the management of patients with schizophrenia.

Role of Eltrompobag in treatment of thrombocytopenia associated with chronic Hepatitis C Virus

Background: Thrombocytopenia is a common hematological abnormality observed in patients infected with hepatitis C virus (HCV). Thrombocytopenia is a well-known relative contraindication for the initiation of antiviral therapy in HCV-infected patients and may also result in the postponement of many invasive procedures that chronic liver disease (CLD) patients may need to undergo. This study aiming to determine the platelet response to eltrombopag and side effects of eltrombopag therapy in patients with HCV-associated thrombocytopenia. Patients and methods: This prospective study was carried out on 30 patients with chronic HCVassociated thrombocytopenia ( 100,000×109/L) required to initiate antiviral therapy and any surgical intervention. Results: Treatment response was achieved in 29 (96.7%) patients. This prospective study showed That when the dependent variable was the increased platelet count at second week of treatment while the independent variables are: age, albumin level, gender, platelet count before treatment, AST, and WBC count. The only significant positive predictive factor was the platelet count before treatment. Conclusion:Eltrombopag causes significant elevation of platelet count in patients with HCV related thrombocytopenia, so that Eltrombopag could be used prior to and during treatment with antiviral therapy when thrombocytopenia become confronting problem as well as before surgical interventions.

Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients.

Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r=0.384, P=0.009) and glutamic-pyruvic transaminase (r=0.293, P=0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.

FRI-406 - Changes in liver steatosis and lipid metabolism accompanied by successful interferon-free DAAs therapy in HCV infected patients; a comprehensive analysis

FRI-406 - Changes in liver steatosis and lipid metabolism accompanied by successful interferon-free DAAs therapy in HCV infected patients; a comprehensive analysis

HCC recurrence under all-oral DAAs-based antiviral therapy in HCV-infected patients: data from Navigatore web platform

HCC recurrence under all-oral DAAs-based antiviral therapy in HCV-infected patients: data from Navigatore web platform

Quantitative measurement of HCV core antigen for management of interferon-free therapy in HCV-infected patients.

According to current recommendations diagnosis and management of HCV infection need detection and quantification of nucleic acids. In the era of direct-acting antivirals (DAA) it is essential to develop an inexpensive and simple method replacing polymerase chain reaction. Since there is no available data on HCV core antigen (HCVcAg) versus HCV RNA kinetics in the early phase of treatment with DAA, we carried out this study to evaluate the possible application of HCVcAg quantitative measurement for management of HCV infection. 33 patients with HCV infection were enrolled and treated with either ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PRV/r±DSV±RBV) or ledipasvir/sofosbuvir (LDV/SOF). Samples for quantitative HCV RNA and HCVcAg measurement were collected at the baseline, after 1, 7, 28 days and at the end of treatment, and then after 12 and 24 weeks of post-treatment follow-up. There was positive correlation between HCVcAg and HCV RNA levels at the baseline and after 1 day of treatment. Mean HCVcAg concentration declined faster than HCV RNA levels during the treatment phase. At week 4 HCV RNA was undetectable in 24, whereas HCVcAg in 28 patients. At the end of treatment and after 12 weeks of follow-up all patients were undetectable for both HCV RNA and HCVcAg. HCVcAg concentration and its early on-treatment testing can predict virological response. Simple testing procedures and significantly lower cost compared to HCV RNA testing support possible replacement of the viral load measurement in management of the majority of HCV-infected patients.

Correction: Quantitative measurement of HCV core antigen for management of interferon-free therapy in HCV-infected patients.

Correction: Quantitative measurement of HCV core antigen for management of interferon-free therapy in HCV-infected patients.

Both Hepatitis C Virus-Specific T Cell Responses and IL28B rs12979860 Single-Nucleotide Polymorphism Genotype Influence Antihepatitis C Virus Treatment Outcome in Patients with Chronic Hepatitis C.

Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy. The interdependence and roles of T cell-mediated immune responses and IL28B rs12979860 single-nucleotide polymorphism genotype as predictors of virological response to anti-HCV treatment in patients with chronic hepatitis C were evaluated using nonparametric tests. Factors associated with rapid virological response (RVR) in univariate analysis were presence of CD4 T cell response against NS3 HCV protein, low baseline HCV-RNA, and IL28B CC genotype. Factors associated with sustained virological response (SVR) in univariate analysis were IL28B CC genotype, low baseline HCV-RNA, and presence of CD4 response against NS2. In the multivariate analysis, low baseline HCV-RNA and NS3-specific CD4 response showed a clear trend toward association with RVR (P = 0.09 and P = 0.07, respectively). Regarding SVR, IL28B CC genotype was the strongest predictor (P = 0.02), with presence of NS2-specific CD4 response showing a clear trend (P = 0.09). HCV-specific T cell response influences the outcome of pegIFNα/RBV therapy regardless of IL28B genotype. HCV-specific T cell responses (adaptive immunity) seem to influence viral clearance both in the short and long term during therapy (RVR and SVR), whereas the influence of the IL28B genotype (innate immunity) may be more relevant to the long-lasting therapeutic effect (SVR).

SAT-204 - Resistance analysis in the MAGELLAN-1 Study (Part 2): glecaprevir/pibrentasvir therapy in HCV-infected patients who had failed prior DAA regimens containing NS3/4A protease and/or NS5A inhibitors

SAT-204 - Resistance analysis in the MAGELLAN-1 Study (Part 2): glecaprevir/pibrentasvir therapy in HCV-infected patients who had failed prior DAA regimens containing NS3/4A protease and/or NS5A inhibitors

Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients.

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.

Sofosbuvir-based treatment is safe and effective in patients with chronic hepatitis C infection and end stage renal disease: a case series.

Interferon and ribavirin-free regimens to treat chronic hepatitis C virus (HCV) infection in patients with end stage renal disease are not approved and represent an area of unmet clinical need. We report our experience on the safety and efficacy of sofosbuvir/simeprevir and sofosbuvir/ledipasvir therapy in patients on haemodialysis. Patients with chronic HCV infection on haemodialysis were included in this study. Patients were started on either sofosbuvir/simeprevir or sofosbuvir/ledipasvir. Routine clinical and laboratory data were collected at baseline and during treatment. The primary outcome was sustained virological response at week 12 (SVR12). Eight patients with mean age 56.8 ± 20 years were included in this study. Seven were treatment naïve and one was a priori null responder to interferon-based therapy. Four patients were started on sofosbuvir/simeprevir and four on sofosbuvir/ledipasvir for 12 weeks. Therapy was well tolerated overall with nausea/vomiting, pruritus, headache and a 2 g/dl drop in haemoglobin developing in one patient each. No patient discontinued therapy because of side effects. Comparison of labs at baseline and nadir levels during treatment revealed no significant change in haemoglobin (10.8 ± 2.4 g/dl vs 10.3 ± 1.6 g/dl), platelet count (198 ± 164 k/μl vs 184.5 ± 162/μl) and bilirubin (0.3 ± 0.4 mg/dl vs 0.25 ± 0.15 mg/dl). Eight of eight patients had undetectable HCV RNA at the end of treatment. One patient was lost to follow up and the remaining seven achieved SVR12. Full dose sofosbuvir/simeprevir or sofosbuvir/ledipasvir therapy for HCV-infected patients with end stage renal disease was well tolerated with no discontinuation owing to side effects and no significant adverse events.

Study the Role of Prometheus Index in Prediction of Response to Treatment in Hepatitis C Patients of Genotype 4

Background and study aim : Because of pegylated interferon (Peg-IFN)/ribavirin therapy is poorly tolerated and rates of response are lower in hepatitis C virus (HCV) infected patients of genotype 4, the recognition of predictors of response is a high priority in this population. We aimed to use a baseline noninvasive index to predict early virological response (EVR) to Peg-IFN/ribavirin in HCV-infected individuals, the score included 4 variables: 2 host-related variables (IL28B SNP rs12979860 and liver stiffness) and 2 HCV-related variables (genotype and viral load). Patients and Methods: 96 treatment-naive HCV-infected patients receiving Peg-IFN/ribavirin were analysed and predictive model was used. The areas under the receiver operating characteristic (AUROC) curves (95% CI), sensitivity and specificity, as well as negative and positive predictive values, were calculated. Only individuals who had completed a course of Peg-IFN-RBV therapy were considered. Results: EVR was achieved in (60.4 %) of patients. The area under the receiver operating characteristic curve (AUROC) was 0.849 (0.762-0.914). Using three cut-off values, maximum specificity and sensitivity were 81.5% and 77.5%, respectively, with a negative predictive value for EVR of 80% and a positive predictive value of 83.6%. Seventeen individuals were misclassified using optimal cut-off values. Conclusion: The probability of achieving EVR with Peg-IFN-RBV therapy in HCV-infected patients can be reliably estimated prior to initiation of therapy using Prometheus index that includes 4 noninvasive parameters. Prometheus index represents a reliable and easily applicable tool to individually evaluate the probability of achieving an EVR to Peg-IFN/ribavirin among HCV-infected patients.

Sofosbuvir-Based Treatment Is Safe and Effective in Patients With Chronic Hepatitis C Infection and End-Stage Renal Disease

Introduction: Interferon and ribavirin-free regimens to treat chronic hepatitis C infection in patients with end-stage renal disease (ESRD) are not available and represent an area of unmet clinical needs due to the significant and serious side effects associated with both interferon and ribavirin in this population. Some of these patients may develop liver cirrhosis with the requirement for combined liver and kidney transplantation. We report our experience on the safety and efficacy of sofosbuvir/simeprevir or sofosbuvir/ledipasvir -based therapy in patients on hemodialysis in the setting of ESRD. Methods: Patients with chronic HCV infection on hemodialysis were included in this study. Patients were started on either sofosbuvir/simeprevir or sofosbuvir/ledipasvir. Routine clinical and laboratory data were collected on all patients at baseline and during treatment. Results: Eight patients (6 female, 6 with GT1, one with GT4, and one with GT3), mean age 56.8 ± 20 years, mean time on dialysis of 5.5 years, and mean fibrosis stage of 1.625 ± 1.4 (two with cirrhosis) were included in the study. Seven patients were HCV treatment naïve and one was a prior null responder to interferon-based therapy. Four patients were started on sofosbuvir/simeprevir and 4 patients were started on sofosbuvir/ledipasvir for 12 weeks. Therapy was well tolerated overall with pruritus/ headache developing in one patient each. No patient discontinued therapy due to side effects. Baseline hemoglobin was at 10.8 ± 2.4 g/dL with no significant change during treatment (10.9 ± 1.7 g/dL). Similarly, there was no significant change in platelet count or bilirubin levels with sofosbuvir/ simeprevir or sofosbuvir/ledipasvir treatment (198 ± 164 k/uL at baseline and 188 ± 165 on treatment for platelets; 0.3 ± 0.4 mg/dL and 0.25 ± 0.15 for bilirubin). 4 out of 4 patients who completed treatment (100%) achieved SVR 12, 4 patients are still currently on treatment of these 3 achieved undetectable HCV RNA at week 4 of therapy. Conclusion: Full dose sofosbuvir/simeprevir or sofosbuvir/ledipasvir therapy for HCV-infected patients with ESRD was well-tolerated with no discontinuation due to side effects and no significant hematological adverse events.

Epstein–Barr virus and Interleukin-28B polymorphism in the prediction of response to interferon therapy in hepatitis C patients

Background and study aimsIn chronic hepatitis C virus (HCV), viral and host factors are known to be predictors for anti-viral therapy. IL-28B genotype strongly influences treatment outcome, while Epstein–Barr virus (EBV) co-infection could accelerate the course of chronic HCV infection. This study was conducted to assess whether EBV co-infection adds to the predictive value of IL-28B. Patients and methodsA total of 105 patients with chronic HCV were classified according to their response to treatment into two groups: 38 sustained virological responders (SVRs) and 67 nonresponders (NRs). Collected sera at baseline and follow-up (FUP) were used for assessing EBV antibodies by enzyme-linked immunosorbent assay (ELISA) and the expression of EBV genes (BNLF-1, BZLF-1, and EBER-2) by polymerase chain reaction (PCR). Collected peripheral blood was used for detecting IL-28B rs.12979860 single-nucleotide polymorphism. ResultsRegarding IL-28B genotype frequencies, a significant difference (p=0.003) was observed between SVRs (C/C=51.4%, C/T=48.6%, T/T=0%) and NRs (C/C=25%, C/T=55%, T/T=20%). On assessing EBV infection at baseline and FUP, it was found that 61% and 55% were positive, respectively, with no significant difference between SVRs and NRs. As for anti-viral capsid antigen (VCA) antibodies, the NRs had significantly higher baseline anti-VCA immunoglobulin M (IgM) levels than SVRs (p=0.01). While FUP anti-Epstein–Barr nuclear antigen-1 (EBNA-1) IgG reported a significant decline within SVR patients (p=0.02), neither baseline nor FUP anti-VCA IgG levels showed a statistically significant viral response. Finally, on comparing EBV markers with CC versus CT and TT genotypes, it was found that FUP anti-VCA IgG levels were significantly increased in CC genotype (p=0.003). ConclusionInterleukin-28B polymorphism could be a possible predictor of response to pegylated interferon/ribavirin therapy (PEG-IFN/RBV). Furthermore, co-infection with EBV did not affect the response to IFN-based therapy in HCV-infected patients.

Interferon-Free Sofosbuvir-Based Anti-HCV Therapy After Liver Transplantation.

Therapy for HCV-infected patients after orthotopic liver transplantation (OLT) is based on interferon (IFN) as the gold standard, but sustained virologic response (SVR) and safety profiles of the IFN-based therapies are very unsatisfactory. The aim of this continuing analysis is evaluation of the impact of an IFN-free sofosbuvir (SOF)-based therapy in HCV-infected liver transplant recipients. Post-OLT patients with a proven recurrence of HCV were treated with SOF and ribavirin (RBV) for 24 weeks (n=10). Laboratory parameters and FibroScan® are continuously evaluated at weeks 0, 12, 24, and 36. A retrospectively analyzed HCV patient cohort who received antiviral therapy with pegylated INF and RBV± telaprevir (TLV) were used as a control group. All patients who finished their treatment with SOF/RBV at least 12 weeks ago showed an SVR. The SOF-based therapy showed a significantly higher rate of rapid virologic response (RVR) and sustained virologic response (SVR) compared to the IFN-based therapies (RVR: p=0.007; SVR: p=0.009). According to temporary data on FibroScan® analysis, regression of fibrosis was observed in 8 patients treated with SOF/RBV. No premature termination of SOF became necessary. In this small group of patients, the preliminary results indicate that a regression of fibrosis is achievable within 24 weeks of therapy with SOF after OLT. SOF seems to be effective and safe in the treatment of OLT patients infected with HCV and will likely improve patient and transplant survival.

Correlation between genetic variations and serum level of interleukin 28B with virus genotypes and disease progression in chronic hepatitis C virus infection.

Recent studies have demonstrated that polymorphisms near the interleukin-28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B serum level was detected and variations at five single nucleotide polymorphisms (SNPs) in IL28B gene region were genotyped and analyzed. The variation of IL28B genetic polymorphisms was found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all P values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (P = 0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P = 0.005 and 0.003, resp.). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. This study indicates that variation at SNP rs8099917 could predict the serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level may serve as a useful marker for the development of HCV-associated sequelae.