Therapy In Hepatitis C Virus Patients Research Articles

Systemic Lupus Erythematosus and Virus C Infection - Diagnosis, Evolution and Treatment Particularities

Abstract Lupus erythematosus (SLE) is an autoimmune disease with a broad spectrum of clinical and immunologic manifestations. Hepatitis C virus (HCV) has been postulated as a potential etiologic or triggering agent among other viruses and it appears to be associated with the presence of autoimmune disorders, even mimicking SLE clinically and serologically. Data on the association between HCV infection and SLE are scarce, but an interaction between these two conditions seems possible. As for treatment options, it is well known that the classic antiviral therapy with interferon may aggravate preexisting autoimmunity, unmask previously silent autoimmune processes, or even cause the emergence of de novo autoimmune disease, including SLE. Interferon-free treatment seems to be more efficacious, safer and more tolerable. However, it is important that clinicians be aware that DAAs (direct acting antivirals) can also trigger lupus-like immune complex-mediated glomerulonephritis. There is scant data on the use of immunosuppressive drug therapy in HCV patients. It seems that enhanced HCV replication due to immunosuppression does not lead to clinically significant sequelae and growing evidence has been reported that supports its efficacy and safety. Patients with SLE and virus C infection are a special category, a fact that the clinician needs to take in consideration in order to a better approach, all the more as these patients are at increased risk for developing end-stage renal disease and have a lower survival rate than general population.

Outcomes of antiviral treatment in hepatitis C virus liver transplant patients off immunosuppression in the direct acting antivirals era: A case series.

Clearance of hepatitis C virus (HCV) under antiviral therapy, including direct-acting antivirals (DAAs), has been associated with higher risk of rejection. Whether patients who are not on immunosuppression (IS) during DAA therapy are at higher risk of rejection is unknown. Four transplant recipients who were off IS and treated with DAA therapy were identified. All patients were genotype 1 infection and treated for 12weeks with sofosbuvir/ledipasvir/ribavirin. At the time of DAA therapy, patients were off IS for a median of 9.5years. Time from liver transplant (LT) to treatment was 12.9 years.Median baseline ALT was 70 IU/L, at follow-up week 12 was 18 IU/L. No signs of rejection were observed during DAA therapy or follow-up after the end of therapy. All 4 patients obtained sustained virological response. Direct-acting antivirals therapy in HCV patients off IS post-LT can be successfully undertaken without the need to restart IS.

Vitamin D in Standard HCV Regimen (PEG-Interferon Plus Ribavirin), Its Effect on the Early Virologic Response Rate: A Clinical Trial

Background: Patients chronically infected with the hepatitis C virus (HCV) are more likely to have vitamin D deficiency Recent studies revealed that vitamin D has immunomodulator and antiviral properties and can enhance the effect of interferon on the HCV virus.Objectives: We aimed to assess the influence of vitamin D supplementation on viral response to PegINF/RBV therapy.Patients and Methods: In a randomized-controlled trial 66 patients with HCV (30 with genotype 1or 4 and 36 with genotype 2 or 3) were randomly divided into two groups in gastroenterology clinic: the study group (n = 34) received oral vitamin D supplementation (1600 IU/day) to maintain serum levels > 30 ng/mL besides the routine treatment of 180 g PegINF- 2a plus oral ribavirin. The control group (n = 32) received the same treatment without vitamin D supplementation. The primary outcome was undetectable HCV-RNA at week 12 of treatment, referred to as complete early viral response (cEVR). Real-time polymerase chain reaction (sensitivity: 10 IU/mL) was used to assess HCV RNA. Serum Vitamin D levels were measured at baseline and weeks 4, 8, 12 and 24 of treatment.Spearman’s correlation showed that baseline vitamin D correlated with the stage of liver fibrosis in both study and control group (P = 0.04, r = 0.57).Results: There were no significant differences in baseline characteristics between two groups except serum AST level. Complete EVR rate at week 12 in the vitamin D group was significantly higher than the controls (100% vs 84.4%; P = 0.023) whereas this figure was not significant when genotypes 1 and 4 or 2 and 3 in the test group were compared to those of the control (100% vs 86.7%; P = 0.19 and 100% vs 82.4%; P = 0.22). Serum vitamin D levels were lowest at baseline (2215 ng/mL), but increased after 12 weeks of vitamin D therapy to a mean level of 5238 ng/mL (P = 0.02) in study group.Conclusions: The addition of vitamin D to conventional PegIFN/RBV therapy in HCV patients may significantly improve the viral response.

A clinical study investigating the impact of adding silymarin to combined therapy (pegylated interferon+ribavirin) on hepatitis C virus viremia

Objectives: The aim of the study was to evaluate the impact of oral silymarin in hepatitis C virus (HCV) infection when added to conventional treatment [pegylated interferon (IFN)+ribavirin]. Background: Oral silymarin is widely used for the treatment of HCV as an additive to the conventional therapy but its efficacy is unclear. Participants and methods: Sixty consecutive HCV patients referred to our clinic for treatment were recruited. All patients were on combined 180 μg of IFN subcutaneous weekly injection and 800–1200 mg/day ribavirin orally. Patients were randomized into two groups each of 30 patients: the first group received silymarin 140 mg/day orally, whereas the other group did not. Patients had their liver enzymes [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and complete blood count checked at baseline and at 12 weeks from the start of treatment. PCR was performed at 12 and 24 weeks from the start of treatment and at 24 weeks after treatment completion. Results: The mean age was 37.6 ± 7.9 years, and 23 (38%) patients were female. There was no significant difference between groups regarding their age, sex, AST, ALT, or complete blood count. Compared with patients who did not have silymarin, patients who had silymarin showed significantly lower ALT (29.5 ± 15.7 vs. 44.4 ± 30.4 U/l, P = 0.021), lower AST (26.6 ± 11.5 vs. 40 ± 31 U/l, P = 0.03), similar hemoglobin (11 ± 1.1 vs. 10.6 ± 0.9 g/dl, P = 0.1), higher platelets (170.1 ± 61.9 vs. 133.6 ± 43 × 103/mm3, P = 0.011), and a higher white cell count (3.6 ± 1.1 vs. 2.9 ± 0.8 × 103/mm3, P = 0.011). According to PCR, 24 (80%) patients who received silymarin showed an early virologic response at 12 weeks, whereas only 18 (60%) patients who did not receive silymarin showed early virologic response (P = 0.09). Twenty-four weeks after the completion of therapy, sustained virologic response occurred in all silymarin patients and in only 13 (43%) patients who did not have silymarin (P = 0.003). Conclusion: Silymarin may increase the antiviral response and adds a protective benefit against side effects of the conventional IFN/ribavirin therapy in HCV patients.

Outcome of Therapy in HCV Patients in a Public Health Tertiary Care Center

Background: To find the outcome of therapy in HCV reactive patients. To study gender, age group of patients received therapy. Genotypes based on treatment outcome, patients achieved SVR, type of HCV therapy, outcome of HCV therapy based on weeks and adverse effects. Previous studies shown, PINFA-2a was treatment of choice for HCV and our new findings were PINFA-2A+RIBA treatment outcome and their success rate, treatment failure and relapse. Percentage of patients achieved SVR and treatment outcome based on weeks. Methods: 187 patients received therapy for Hepatitis C Virus (HCV) in Rajiv Gandhi Government General Hospital-Chennai. Patient’s samples were collected, tests performed and recorded. Real Time-Polymerase chain reaction (RT-PCR) was done in the 4th week, 12th, 24th and 48th week. Results: 187 eligible patients [M-77% and F-23%] received treatment. Age groups [M-40-50, F-30-40]. PINFA-2a+RIBA were common. Pegylated-interferon-α-2a + ribavirin (PINFA-2a+RIBA) Based on treatment outcome, patients were categorized into 3 groups (treatment success group, relapse and treatment failure). Overall treatment success rate were 76.5%, treatment failure were 5.9% and relapse cases were 17.6%. In both gender genotype-1 was in higher number. Achieved SVR,(genotype-1-73.5%, genotype-2-100%, genotype-3-76.9% and genotype-4-93.3%).Treatment success rate dropped in 24 th week, higher number relapse in 24th week and treatment failure in 24 th week. 40.6% achieved TND in 12th week of treatment, 26.1% in 4th, 20.8% and 12.5% in the weeks of 24 and 48 respectively. 96.5% no side effects. 2.7% had abdominal pain and 0.7% vomiting.

Study of the effect of combined interferon and ribavirin therapy on the hearing profile of hepatitis C virus patients

Abstract This study aimed to study the effect of combined pegylated interferon and ribavirin (Peg-IFN/RBV) therapy on the hearing profile of patients with hepatitis C virus (HCV). The auditory system of a total of 74 chronic HCV patients was assessed using pure tone audiometry (conventional and high frequency) and distortion product otoacoustic emissions (DPOAEs in the form of a DP-gram) immediately before therapy and at the end of the 12th and 24th weeks. Vestibulocochlear adverse effects including hearing loss, tinnitus, vertigo, and otalgia were also considered. Significant elevations in hearing thresholds were found on comparing thresholds at the 12th and 24th weeks with those at the onset of the study. The elevations were mostly at higher frequencies (3000, 4000, 6000, 8000, 9000, 10 000, 11 200, and 12 500 Hz), and did not affect speech perception. For DPOAE, significant differences were observed at all F2 frequencies on comparing both amplitudes and signal to noise ratios at the 12th and 24th weeks with those before therapy, with significance appearing earlier for higher F2 frequencies. Otologic complaints were insignificant, except for tinnitus; a significant increase in tinnitus was observed from 0 to 31.1% by the end of the study. Significant auditory adverse effects may result from combined Peg-IFN/RBV therapy in HCV patients, highlighting the importance of prompt monitoring of auditory functions in these patients.

MHC class I-related chain B gene polymorphism is associated with virological response to pegylated interferon plus ribavirin therapy in patients with chronic hepatitis C infection

The outcome of antiviral therapy is associated with viral and host factors. In the present study, the association between MHC class I-related chain B (MICB) genotypes and therapeutic response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy was investigated in hepatitis C virus (HCV)-infected patients. In total, 107 patients with chronic HCV infection (74 with HCV serotype 1 and 33 with serotype 2) were enrolled. Genotyping of MICB single-nucleotide polymorphism (SNP) rs3828913 and interleukin-28B (IL28B) SNP rs8099917 was performed using TaqMan® SNP genotyping assays. The genotype distribution of the MICB alleles was: CC, 79.4%; CA, 17.8%; and AA, 2.8%. Sustained virological response (SVR) was achieved by 55.1% (59/107) of the HCV patients. The SVR rate of patients with MICB major (CC) alleles was 62.3% and this rate was significantly higher than that of the patients with MICB minor (CA and AA) alleles (27.2%) (P=0.0068). A multivariate logistic model showed that the MICB major genotype was an independent factor contributing to SVR (OR, 4.47; 95% CI, 1.46-13.70; P=0.009). In addition, the MICB genotype was identified as the sole independent factor contributing to SVR and non-virological response in HCV serotype 1 patients with the IL28B major genotype. In HCV serotype 2 patients, the MICB genotype was the sole significant factor contributing to SVR (OR, 30.68; 95% CI, 2.72-346.3; P=0.006). In conclusion, the MICB genotype is a strong predictive factor for virological response to PEG-IFN/RBV therapy in HCV patients.

Structural and molecular basis of interaction of HCV non-structural protein 5A with human casein kinase 1α and PKR

BackgroundInteraction of non-structural protein 5A (NS5A) of Hepatitis C virus (HCV) with human kinases namely, casein kinase 1α (ck1α) and protein kinase R (PKR) have different functional implications such as regulation of viral replication and evasion of interferon induced immune response respectively. Understanding the structural and molecular basis of interactions of the viral protein with two different human kinases can be useful in developing strategies for treatment against HCV.ResultsSerine 232 of NS5A is known to be phosphorylated by human ck1α. A structural model of NS5A peptide containing phosphoacceptor residue Serine 232 bound to ck1α has been generated using the known 3-D structures of kinase-peptide complexes. The substrate interacting residues in ck1α has been identified from the model and these are found to be conserved well in the ck1 family. ck1α – substrate peptide complex has also been used to understand the structural basis of association between ck1α and its other viral stress induced substrate, tumour suppressor p53 transactivation domain which has a crystal structure available.Interaction of NS5A with another human kinase PKR is primarily genotype specific. NS5A from genotype 1b has been shown to interact and inhibit PKR whereas NS5A from genotype 2a/3a are unable to bind and inhibit PKR efficiently. This is one of the main reasons for the varied response to interferon therapy in HCV patients across different genotypes. Using PKR crystal structure, sequence alignment and evolutionary trace analysis some of the critical residues responsible for the interaction of NS5A 1b with PKR have been identified.ConclusionsThe substrate interacting residues in ck1α have been identified using the structural model of kinase - substrate peptide. The PKR interacting NS5A 1b residues have also been predicted using PKR crystal structure, NS5A sequence analysis along with known experimental results. Functional significance and nature of interaction of interferon sensitivity determining region and variable region 3 of NS5A in different genotypes with PKR which was experimentally shown are also supported by the findings of evolutionary trace analysis. Designing inhibitors to prevent this interaction could enable the HCV genotype 1 infected patients respond well to interferon therapy.

Management psychiatrischer Nebenwirkungen im Rahmen der antiviralen Therapie der chronischen Hepatitis-C-Virusinfektion

The efficacy of antiviral therapy in patients with chronic hepatitis C virus (HCV) infection has largely improved over the last years. Rates of long-term therapy success (sustained virological response, SVR) clearly exceed 50% in the population of all antivirally treated HCV patients, even when including the less favourable virus genotypes 1 and 4. From recent research, it is well-known that adherence to current standard combination therapy (peginterferon alfa plus ribavirin) is crucial for the achievement of sustained response. Psychiatric adverse events, however, are subjectively very burdening and are among the most frequent reasons for premature discontinuation of antiviral therapy in HCV patients and therefore endanger therapy success. Therefore, effective side effect management regarding this branch of symptoms (e.g. depression, anger-hostility, anxiety) is to be considered crucial for the achievement of SVR. This review presents a current overview of the most relevant IFN-associated psychiatric side effects in antivirally treated patients with chronic hepatitis C infection. Moreover, various strategies for the management of these undesired conditions are reported: In particular, we address the issues of diagnostics and pretherapeutic screening for risk factors for the subsequent development of IFN-associated psychiatric symptoms. Moreover, we provide an overview of suitable instruments for the psychiatric monitoring of patients on antiviral therapy. We further discuss appropriate treatment strategies (e.g. prophylactic medication vs. medication only after the occurrence of symptoms) as well as indications for immediate therapy discontinuation due to serious psychiatric adverse events. In many cases, premature therapy discontinuation can be prevented by individual and adequate side effect management, provided that it is started in a timely manner. The continuing clinical relevance of psychiatric side effect management in this context is further backed up by the fact that also novel treatment strategies comprising protease or polymerase inhibitors will still include pegylated interferon alfa and ribavirin.

Neopterin as a Marker of Response to Antiviral Therapy in Hepatitis C Virus Patients

Predicting the efficacy of antiviral treatment of hepatitis C virus (HCV) is of importance for both patient well-being and health care expense. The expression of interferon-stimulated genes (IFN-SGs) in the liver was suggested as a marker of response to anti-viral therapy. IFN-SGs encode the guanosine triphosphate cyclohydrolase 1 (GTPCH), a rate-limiting enzyme of pteridines biosynthesis. Neopterin, a stable byproduct of GTPCH-catalyzed reaction, is used as a marker of interferon-induced GTPCH activation. We hypothesized that assessment of neopterin concentrations might predict the response to antiviral therapy. Neopterin concentrations were evaluated in 260 HCV patients treated by pegylated interferon combined with ribavirin. Mean and median pretreatment neopterin concentrations were lower in patients with sustained virological response than in nonresponders. The rate of response was twofold higher among patients with pretreatment neopterin levels <16 nmol/L than in patients with neopterin levels ≥16 nmol/L, even after controlling for HCV genotype status. Our study suggests that the pretreatment level of neopterin might be used in routine clinical practice as rapid and cost-effective marker to predict the response to antiviral therapy in HCV patients.

Serum Mannan-Binding Lectin in Egyptian Patients With Chronic Hepatitis C: Its Relation to Disease Progression and Response to Treatment

: Background: Chronic hepatitis C virus (HCV) infection is a major worldwide public health problem. Egypt has the highest prevalence of adult HCV infection in the world, averaging 15%–25% in rural communities. Mannan-binding lectin (MBL) is a liver-derived pluripotent serum lectin that plays a role in the innate immune system of the host. It is an acute-phase protein that is involved in the activation of the classical complement pathway. MBL may play a defensive role in HCV infection.Objectives: To investigate the relationship between MBL concentration and HCV infection in Egyptian patients suffering chronic hepatitis C.Patients and Methods: Serum samples obtained from 35 Egyptian hepatitis C patients and 30 normal controls were assayed for MBL. MBL concentrations were correlated to disease characteristics and treatment response.Results: Serum MBL was significantly higher in HCV patients than in controls, but no relationship was found between MBL concentration and disease progression in terms of hepatic fibrosis and inflammation. Responders to interferon (INF)-based therapy had significantly higher serum MBL than non-responders.Conclusions: We found no association between serum MBL concentration and progression of HCV related liver disease. Responders to INF-based therapy had significantly higher serum MBL than non-responders. Implication for health policy/practice/research/medical education:MBL may be considered as a predictor of response to antiviral therapy in HCV patients and MBL replacement therapy may improve the response to antiviral therapy in these patients. Please cite this paper as:Esmat S, Omran D, Sleem GA, Rashed L. Serum Mannan-Binding Lectin in Egyptian Patients With Chronic Hepatitis C: Its Relation to Disease Progression and Response to Treatment. Hepat Mon. 2012;12(4):259-64. DOI: 10.5812/hepatmon.704 Copyright © 2012 Kowsar Corp. All rights reserved.

The prognostic value of changes in serum ferritin levels during therapy for hepatitis C virus infection

An increase in serum ferritin levels during combined interferon-ribavirin treatment in chronic patients infected with hepatitis C virus (HCV) can occur. A study was conducted to determine whether observing the kinetics of serum ferritin levels during antiviral therapy, may assist in predicting the rate of sustained virological response. The kinetics of serum ferritin levels during antiviral therapy in treatment-naive, adherent patients with chronic HCV who had early virological response were characterized. Thirteen patients achieved sustained virological response (group 1) while eight patients did not (group 2). Pre-treatment serum ferritin levels were higher in group 2 patients. During antiviral therapy, serum ferritin levels increased in both groups. On treatment, the median increase (compared to baseline) and the calculated rate of the increase in serum ferritin levels was higher in group 1 patients (874% vs. 272%, P < 0.05, 63%/week vs. 13%/week, P = 0.024, respectively). Red blood cell lysis did not contribute to the increase in serum ferritin level. Post-treatment (1st month) serum ferritin levels in group 1 patients were lower than in group 2 patients. In addition, the degree of decline in the 1st month serum ferritin levels (from peak levels) in group 1 patients was higher (76% vs. 49%, P = 0.039). Measuring serum ferritin levels during antiviral therapy in HCV patients who had an early virological response may assist in predicting sustained virological response.

Assessment of liver stiffness in patients after living donor liver transplantation by transient elastography

Objective. Recurrence of hepatitis and progression of fibrosis are major problems in liver transplantation (LT) for patients with hepatitis C. Liver stiffness measurement (LSM) by transient elastography correlates well with histologic liver fibrosis stages in chronic liver diseases. The aim of this study was to evaluate the usefulness of transient elastography for the assessment of fibrosis in patients after living donor LT. Material and methods. Seventy-nine patients who visited our institution, and in whom LSM was successfully evaluated, were enrolled in the study. The patients were divided into three groups according to positivity for hepatitis C antibody and hepatitis B surface antigen as the hepatitis C virus (HCV) group (n=37), the hepatitis B virus (HBV) group (n=10), and the NBNC (negative for both hepatitis B and C) group (n=32). The correlation between LSM and histologic fibrosis stage was assessed in 36 patients. LSM was also compared with regard to the effect of interferon therapy in HCV patients. Results. The median value for liver stiffness was 6.8 kPa and the median time from LT was 3.1 years. In patients who underwent liver biopsy, stiffness was significantly correlated with the stages of fibrosis (p<0.001, rho = 0.848). In patients who received interferon therapy after LT, the LSM decreased over time in those with a sustained virological response, whereas LSM increased in patients without a response. Conclusion. Transient elastography may be an appropriate non-invasive procedure to sequentially assess the progression of liver fibrosis in patients after LT.

Intrahepatic expression of interferon alpha &amp; interferon alpha receptor m-RNA can be used as predictors to interferon response in HCV and HCC patients

Chronic hepatitis C Virus (HCV) is the leading cause of liver cirrhosis worldwide and in Egypt. Patients with cirrhosis secondary to chronic HCV infection are at increased risk for developing Hepatocellular carcinoma (HCC) in which Interferon therapy is the only effective anti-viral therapy. The current study aimed to investigate the expression IFN-&#945;and IFN-&#945;Receptor genes in liver biopsies from patients with HCV and HCC. Correlation of their expression with the clinical, histopathological progress of the disease and the effectiveness of IFN therapy in HCV patients after a period of 6 months follow-up was done. Expression of IFN-&#945; and IFN&#945;-Rc m-RNA was investigated by RT-PCR using liver biopsy specimens from 30 HCV patients including 7 patients complicated with HCC. Liver biopsies were also subjected to formalin fixation for complete histopathological examination. Ninety seven percent of patients expressed Interferon Alpha m-RNA while 30% only expressed Interferon Alpha Receptor m-RNA. Responders and non-responders to Interferon therapy were divided according to their HCV RNA after six-months follow up period of interferon therapy. Responders showed significantly lower mean age, better histopathological states and higher incidence of expression of IFN Alpha Receptor mRNA. Regardless of the response to interferon, histological activity index scores and the degree of fibrosis showed a significant inverse correlation to the presence of IFN&#945;-R m-RNA. IFN&#945;-R mRNA expression decreases with the histological progress of the disease, suggesting that lower expression of the IFN&#945;-Rc may be partially responsible for the unfavorable response to interferon in these patients. African Journal of Health Sciences Vol. 14 (1-2) 2007: pp. 86-96

Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C

Interferon signaling pathway genes (IPGs) and interferon-stimulated genes (ISGs) are associated with the host response to hepatitis C virus (HCV) infection. We studied single nucleotide polymorphisms (SNPs) in IPGs and ISGs for their associations with response to pegylated interferon alpha-2a (Peg-IFN-alpha) plus ribavirin therapy in HCV genotype-1 infected patients. A two-stage study design was used. First, out of 118 SNPs selected, 91 SNPs from 5 IPGs and 12 ISGs were genotyped in a cohort of 374 treatment-naïve HCV patients and assessed for association with sustained virologic response (SVR). Next, 14 potentially functional SNPs from the OASL gene were studied in this cohort. Three OASL SNPs (rs3213545 and rs1169279 from stage I, and rs2859398 from stage II), were significantly associated with SVR [rs3213545: p=0.03, RR=1.27 (1.03-1.58); rs1169279: p=0.02, RR=1.32 (1.05-1.65) p=0.02; rs2859398: p=0.02, RR=1.29 (1.04-1.61)] after adjusting for other covariates. Further analysis showed that these three SNPs independently associated with SVR. Additionally, a similar trend towards the associations of these three SNPs with SVR was observed in a smaller, independent HCV cohort consisting of subjects from a number of clinical practice settings. Our study suggests that OASL variants are involved in the host response to IFN-based therapy in HCV patients.

Liver expression of proteins controlling interferon‐mediated signalling as predictive factors in the response to therapy in patients with hepatitis C virus infection

Combination therapy with interferon-alpha (IFNalpha) and ribavirin is the current treatment of choice for hepatitis C virus (HCV) infection. However, an important number of patients fail to respond to this therapeutic strategy. Factors determining IFN responsiveness are not well understood, and assessment of biomarkers that predict the response to IFN therapy in HCV patients is necessary. Several studies show that particular HCV proteins are able to block IFN function through interaction with important IFN-signal mediators, such as signal transducers and activators of transcription (STATs). We performed immunostaining analysis of STATs in liver tissue from IFN-responder vs. non-responder HCV patients in order to compare the expression profile of these proteins between both groups. Tissue arrays of liver biopsies were used to study the expression of STAT1, STAT2, STAT5 and PIAS1 (protein inhibitor of activated STAT1). Robust and higher expression levels of STAT1, STAT2 and STAT5 in liver tissue from HCV patients were found when compared with samples from healthy donors. However, no significant differences were observed between IFN-responder and -non-responder groups, but rather increasing levels of STAT1, STAT2 and STAT5 paralleled the degree of liver injury. Importantly, PIAS1 expression in the nucleus of most hepatocytes in HCV tissue biopsy sections, particularly of non-responder HCV patients, strongly indicated a regulatory effect on STAT1-DNA binding, likely affecting the IFN late signalling. In conclusion, our evidence indicates that intense PIAS1 nuclear staining, widely distributed in hepatocytes of infected livers, could be a good predictive factor of a defective response to IFN treatment, and a biomarker that is easily detectable by immunostaining during standard histopathological liver biopsy analysis.