Interferon Therapy For Chronic Hepatitis Research Articles

The Role of Interferon Lambda 3 Genetic Polymorphisms in Response to Interferon Therapy in Chronic Hepatitis B Patients: An Updated Meta-Analysis.

ContextPolymorphisms of the interferon lambda 3 (IFNL3) gene have been proposed to be associated with drug-induced clearance of the hepatitis C virus (HCV). However, the role of IFNL3 polymorphisms in the prediction of treatment on chronic hepatitis B (CHB) patients have yielded controversial results. The aim of this study was to clarify the role of IFNL3 polymorphisms (rs12979860, rs8099917, and rs12980275) in the treatment response of CHB patients to interferon (IFN).Evidence AcquisitionEMBASE and PUBMED/MEDLINE were searched to identify relevant studies from January 2009 to March 2015. The search used the keyword “interferon lambda 3” or “IFNL3,” combined with the following terms: “interferon therapy,” “hepatitis,” and “polymorphisms.” Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were used to assess the strength of the associations between the polymorphisms and the response to IFN therapy.ResultsNine studies of 1602 CHB patients receiving IFN treatment were included. Under the random-effects model, patients expressing the variant rs12980275 showed a significantly increased response to IFN therapy (OR = 2.85; 95% CI = 1.14 - 4.60). In the subgroup analyses by antiviral agents, the patients carrying the rs8099917T allele in the IFN-only treatment group showed a significantly increased response to IFN therapy (OR for the dominant model = 2.03; 95% CI = 1.24 - 3.31), whereas those in the mixed treatment group showed a significantly decreased response (OR for the dominant model = 0.30; 95% CI = 0.10 - 0.90).ConclusionsThis study supports the idea that the IFNL3 gene is an important predictor of the response of CHB patients to IFN therapy.

Ophthalmological side effects of interferon therapy of chronic hepatitis C.

Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity. We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment. IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy. Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately it's asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important.

FREQUENCY OF DEPRESSION

Combine Pegylated interferon therapy and ribavirin is most commonly usedtreatment in chronic hepatitis C patients. Along with other complications, different psychiatricdisorders are observed during combination therapy including depression. Depression is themajor morbidity as it may lead to different destructive ideation including suicide among patientson treatment. We have tried to calculate the frequency of depression along with associatedfactors in our present study. Objectives: To find out the frequency of depression duringPegylated interferon therapy for chronic hepatitis C. Study Design: Descriptive study. Setting:Liaquat University of Medical & Health Sciences, Jamshoro / Hyderabad Duration: The durationof study was six months starting from 01-01-2014 to 31-06-2014. Methodology: Two hundredand fifty two cases of chronic hepatitis C on the basis of anti HCV (ELISA) and PCR positivewere selected in this study. Results: Out of 252 patients, 111 (44%) were males and 141(56%)were females. Most of the patients belonged to 26 to 50 years of age. The duration of treatmentwas 12 weeks. Two hundred & eight (82.5%) patients had ever married while the remaining17.5% were unmarried. Out of 106 (42%) depressed patients, 39 (37%) had mild, 31 (29%) hadmoderate, 20 (19%) had moderately severe and 15 (15%) had severe depression. Conclusion:It was observed that depression is a common during combination therapy with Peg interferonand the ribavirin in chronic HCV patients.

English

Combine Pegylated interferon therapy and ribavirin is most commonly usedtreatment in chronic hepatitis C patients. Along with other complications, different psychiatricdisorders are observed during combination therapy including depression. Depression is themajor morbidity as it may lead to different destructive ideation including suicide among patientson treatment. We have tried to calculate the frequency of depression along with associatedfactors in our present study. Objectives: To find out the frequency of depression duringPegylated interferon therapy for chronic hepatitis C. Study Design: Descriptive study. Setting:Liaquat University of Medical & Health Sciences, Jamshoro / Hyderabad Duration: The durationof study was six months starting from 01-01-2014 to 31-06-2014. Methodology: Two hundredand fifty two cases of chronic hepatitis C on the basis of anti HCV (ELISA) and PCR positivewere selected in this study. Results: Out of 252 patients, 111 (44%) were males and 141(56%)were females. Most of the patients belonged to 26 to 50 years of age. The duration of treatmentwas 12 weeks. Two hundred & eight (82.5%) patients had ever married while the remaining17.5% were unmarried. Out of 106 (42%) depressed patients, 39 (37%) had mild, 31 (29%) hadmoderate, 20 (19%) had moderately severe and 15 (15%) had severe depression. Conclusion:It was observed that depression is a common during combination therapy with Peg interferonand the ribavirin in chronic HCV patients.

Association of hepatic oxidative stress and iron dysregulation with HCC development after interferon therapy in chronic hepatitis C

BackgroundOxidative stress may play pathogenic roles in the mechanisms underlying chronic hepatitis C (CHC). The impact of excessive oxidative stress and iron dysregulation on the development of hepatocellular carcinoma (HCC)...

Regional disparities in interferon therapy for chronic hepatitis C in Japan: a nationwide retrospective cohort study.

BackgroundMany patients with chronic hepatitis C have been treated with interferon (IFN) therapy in Japan, especially after the introduction of subsidies for medical expenses in 2008. However, its performance and outcome have never been evaluated. Therefore, a nationwide, mail-based, retrospective cohort study was conducted.MethodsRegional disparities in the demographic features, treatment performance, and virological response were evaluated using an intent-to-treat design. The participating prefectures were classified into nine regions from north to south (Hokkaido/Tohoku, Kanto, Shin-etsu, Hokuriku, Tokai, Kinki, Chugoku, Shikoku, and Kyushu). Multivariate logistic regression analysis was performed to select predictive factors for treatment performance and outcome.ResultsFrom December 2009 to May 2013, 16,854 patients with chronic hepatitis C were registered from 37 prefectures in Japan (median age: 60 years; 50.4 % male; 74.8 % IFN-naïve; HCV genotype [1 or 2]/viral load [high (≥5 log IU/mL) or low (<5 log IU/mL)]: 1/high = 58.2 %, 1/low = 5.2 %, 2/high = 27.3 %, 2/low = 7.5 %; 83.4 % treated with peginterferon-α and ribavirin). Mean age, proportion of elderly patients (≥65 years), male sex, IFN-experienced, and HCV genotype were significantly different among the nine regions (all P < 0.001). Regional disparities were independently selected as one of the predictive factors for treatment performance and outcome in patients treated with peginterferon-α and ribavirin, which revealed two regions that required further investigation.ConclusionsRegional disparities still exist in IFN therapy, and are strongly associated with treatment performance and outcome. Since the accessibility to medical resources for individual patients seemed to be different among the nine regions, public health actions should be focused on how to construct and properly manage consultation networks between base hospitals and local clinics, especially in those regions with low population density.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-1891-2) contains supplementary material, which is available to authorized users.

Serum interferon-related microRNAs as biomarkers to predict the response to interferon therapy in chronic hepatitis C genotype 4.

MicroRNAs are messengers during interferon-virus interplay and are involved in antiviral immunity, however, little is known about interferon-related microRNAs regarding their detection in serum and their potential use as non-invasive diagnostic and prognostic biomarkers in chronic hepatitis C (CHC). To elucidate some of the molecular aspects underlying failure of pegylated interferon-α/ribavirin therapy, we investigated pretreatment expression profiles of seven selected interferon-related microRNAs (miR-146a, miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296) by quantitative RT-PCR custom array technology in serum of Egyptian CHC genotype 4 patients and whether their pretreatment levels would predict patient response to the combination therapy. One hundred and six CHC patients and forty matched healthy controls were included. Patients were divided into sustained virological response (SVR) and non-responder (NR) groups. Serum miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296 were upregulated, whereas serum miR-146a was downregulated in CHC compared to controls. Significant correlations were found between expression levels of studied microRNAs and also with clinical data. Pretreatment levels of miR-34a, miR-130a, and miR-195 were significantly higher, whereas miR-192 and miR-296 levels were significantly lower in SVR than NR patients. miR-19a and miR-146a levels were not significantly different between the two groups. miR-34a was superior to differentiate CHC from controls, whereas miR-296 was superior to discriminate SVR from NR patients by receiver operating characteristic analysis. Multivariate logistic analysis revealed miR-34a and miR-195 as independent predictors for SVR and miR-192 as an independent variable for non-response. In conclusion, pretreatment expression profiles of five interferon-related microRNAs are associated with treatment outcome in CHC. Of these, miR-34a, miR-195, and miR-192 could predict treatment response. The profiling results could be used as novel non-invasive diagnostic and prognostic pharmacogenetic biomarkers for treatment personalization in CHC and could help to identify new microRNA-based antivirals.

Pegylated interferon therapy of chronic hepatitis D: In need of revision

Pegylated interferon therapy of chronic hepatitis D: In need of revision

Role of Neopterin in Determining the Efficacy of Interferon Therapy in Chronic Hepatitis B and C

Neopterin (NP) is a pteridine derivative that is secreted as a response to gamma interferon stimulation. The purpose in this study was to investigate the relationship between the NP levels and the disease and determining the efficacy of an interferon (IFN) therapy in patients with chronic hepatitis B (CHB) and C (CHC). The study was conducted on 49 cases with CHB, 30 cases with CHC and 72 healthy individuals. Serum samples were taken from the patients receiving treatment at the beginning and at the end of the treatment and only once from the healthy individuals in the control group. The NP levels were found significantly higher in the patients with CHB and CHC than those in the control group. When the pre and post-treatment serum NP levels of the patients who received an interferon therapy were compared, the post-treatment NP levels of the patients who responded to the treatment were significantly higher. When a comparison was made before and after treatment, a decrease was seen in the NP levels in most of the infections due to decreased activation of the immune system. However, when the disease was treated with an IFN therapy, which is a treatment stimulating the immune system, the post-treatment NP level remained high.

The close linkage between the elasticity modulus measured by real-time mapping shear wave elastography and the presence of hepatocellular carcinoma in patients with a sustained virological response to interferon for chronic hepatitis C.

Some patients develop hepatocellular carcinoma (HCC) after sustained virological response (SVR) to interferon therapy for chronic hepatitis C (CH-C). The aim of this study was to examine the linkage between liver elasticity and the presence/absence of HCC in patients after SVR. We enrolled 42 patients who underwent real-time mapping shear wave elastography (SWE) after SVR to interferon therapy for CH-C. Of the 42 patients, six had HCC and 36 did not. We retrospectively compared the elasticity modulus and other clinical parameters between patients with and without HCC. Elasticity modulus measured by SWE, age, and serum albumin was significantly different between patients with and without HCC. Age, Fibrosis-4 index, serum gamma-globulin, total protein, and albumin levels were significantly correlated with the elasticity modulus. Areas under receiver operating characteristic curves of elasticity modulus, gamma-globulin, and age for the presence of HCC were 0.963, 0.888, and 0.778, respectively. In patients with an elasticity modulus ≥6.5 kPa, both sensitivity and specificity for the presence of HCC were 83.3 %. The study demonstrated the close linkage between the elasticity modulus measured by SWE and the presence of HCC in patients after SVR.

LecT-Hepa facilitates estimating treatment outcome during interferon therapy in chronic hepatitis C patients.

BackgroundA combination treatment of interferon and ribavirin is the standard and the commonly used treatment for chronic hepatitis C (CHC). Developing noninvasive tests like serum indicators that can predict treatment outcome at an early stage of therapy is beneficial for individualized treatment and management of CHC. A glyco-indicator based on the glyco-alteration of serum α1-acid glycoprotein, LecT-Hepa, was discovered by glycomics technologies as a robust indicator of liver fibrosis. Here, we investigated the clinical utility of LecT-Hepa for evaluation of treatment outcome.ResultsFirstly, ninety-seven patients with CHC were used for comparison of LecT-Hepa in serum and plasma. We found no significant difference in the concentrations of LecT-Hepa in serum and plasma. And then, 213 serum specimens from 45 patients who received 48 weeks of treatment with interferon and ribavirin were followed up for 96 weeks, and were used for evaluation of the role of LecT-Hepa. We found that LecT-Hepa might reflect the change in fibrosis regression during the treatment process. Moreover, the change of LecT-Hepa at the first 12 weeks of treatment could already predict the antiviral treatment response, which was more superior to FIB-4 index and aspartate aminotransferase-to-platelet ratio index (APRI) in this study.ConclusionsThese results provide a new perspective that serum glycoprotein could be used as a joint diagnosis indicator for estimation treatment outcome of viral hepatitis at earlier stage of therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/1559-0275-11-44) contains supplementary material, which is available to authorized users.

Determination of Whether Vitiligo is a Contraindication to Interferon Therapy in Chronic Hepatitis C

Determination of Whether Vitiligo is a Contraindication to Interferon Therapy in Chronic Hepatitis C

Impact of IL28B Genetic Variation on HCV-Induced Liver Fibrosis, Inflammation, and Steatosis: A Meta-Analysis

Background & AimsIL28B polymorphisms were shown to be strongly associated with the response to interferon therapy in chronic hepatitis C (CHC) and spontaneous viral clearance. However, little is known about how these polymorphisms affect the natural course of the disease. Thus, we conducted the present meta-analysis to assess the impact of IL28B polymorphisms on disease progression.MethodsA literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library. Integrated odds ratios (OR) were calculated with a fixed-effects or random-effects model based on heterogeneity analyses.ResultsWe identified 28 studies that included 10,024 patients. The pooled results indicated that the rs12979860 genotype CC was significantly associated (vs. genotype CT/TT; OR, 1.122; 95%CI, 1.003–1.254; P = 0.044), and that the rs8099917 genotype TT tended to be (vs. genotype TG/GG; OR, 1.126; 95%CI, 0.988–1.284; P = 0.076) associated, with an increased possibility of severe fibrosis. Both rs12979860 CC (vs. CT/TT; OR, 1.288; 95%CI, 1.050–1.581; P = 0.015) and rs8099917 TT (vs. TG/GG; OR, 1.324; 95%CI, 1.110–1.579; P = 0.002) were significantly associated with a higher possibility of severe inflammation activity. Rs8099917 TT was also significantly associated with a lower possibility of severe steatosis (vs. TG/GG; OR, 0.580; 95%CI, 0.351–0.959; P = 0.034), whereas rs12979860 CC was not associated with hepatic steatosis (vs. CT/TT; OR, 1.062; 95%CI, 0.415–2.717; P = 0.901).ConclusionsIL28B polymorphisms appeared to modify the natural course of disease in patients with CHC. Disease progression seems to be promoted in patients with the rs12979860 CC and rs8099917 TT genotypes.

The beginning of the end: What is the future of interferon therapy for chronic hepatitis C?

Interferon has been the backbone of therapy for hepatitis C virus (HCV) infection for over 20years. Initial response rates were poor, however they have slowly but steadily improved, such that with the addition of the nucleotide analogue ribavirin and the pegylation of interferon, over 50% of infected individuals could be cured with a course of therapy. However, interferon therapy is not ideal, requiring up to a year of weekly injections and associated with numerous systemic side effects. Advances in understanding of the HCV lifecycle have led to the development of numerous highly effective, well-tolerated oral direct acting antivirals (DAAs). Although the first DAAs were combined with peginterferon and ribavirin, with the rapid progress in the field, it is likely that interferon-free therapy will be available for most patients in the relatively near future. In the short term, peginterferon will be required with either the protease inhibitor simeprevir, or the nucleotide analogue polymerase inhibitor, sofosbuvir, for the treatment of genotype 1 infection. Peginterferon also appears to be a useful adjunct to sofosbuvir and ribavirin for patients with genotype 3 infection, particularly those with cirrhosis. In the future, once combination DAA therapies are available, peginterferon will serve a smaller and smaller role. Peginterferon may be useful as part of QUAD therapy with 2 DAAs and ribavirin in prior null responders or in patients who fail DAA regimens with multi-drug resistant HCV. Peginterferon may also have a role in resource-limited regions to reduce the number and/or duration of DAAs required. Ultimately, although peginterferon will remain a salvage therapy, its days as a mainstay of therapy are definitely numbered.

Short- and long-term outcome of interferon therapy for chronic hepatitis B infection.

Hepatitis B virus (HBV) infection is a serious clinical problem worldwide. Conventional interferon (IFN)-α has been approved for the treatment of chronic hepatitis B (CHB). Short-term studies have demonstrated that IFN-based therapy is moderately effective in inducing the loss of hepatitis e antigen (HBeAg) or seroconversion (30%-40%) in HBeAg-positive patients and also produces sustained HBV DNA suppression (20%-30%) in HBeAg-negative patients. Many studies have reported a correlation between the HBV genotype and response to IFN treatment. The highest response rate to IFN treatment was found in patients infected with HBV genotype A, followed by HBV genotypes B, C, and D. The long-term effect of IFN-α on CHB has not yet been elucidated. The ability of IFN-α treatment to prevent new cirrhosis, complications associated with cirrhosis, and development of hepatocellular carcinoma (HCC) is controversial. The beneficial effect of IFN-α treatment in reducing the development of HCC has mainly been observed in treatment responders who already have cirrhosis. These inconsistent findings may be attributed to the inevitable limitations of comparisons across studies, including differences in the baseline characteristics of the study and the moderate suppression of HBV replication by IFN-α relative to nucleoside/nucleos(t)ide analogs.

End treatment response and sustained viral response in hepatitis C virus genotype 3 among Pakistani population

BACKGROUND AND OBJECTIVESThis study aimed to determine the end treatment response (ETR) and sustained viral response (SVR) to interferon (IFN) and ribavirin in hepatitis C virus (HCV) genotype 3 in the Pakistani population.DESIGN AND SETTINGSThis is an interventional study conducted from January 2010 to December 2012 in Lyari General Hospital and Abbasi Shaheed Hospital, Karachi, outpatients department.METHODSAll patients with chronic hepatitis C genotype 3 infections were included. Patients with decompensated chronic liver disease, or having coexisting hepatitis B virus/human immunodeficiency virus were excluded. All patients received IFN alpha, 3 million international units (MIU), subcutaneously 3 times weekly and ribavirin >800 mg/d for a period of 6 months. Outcome parameters included ETR (negative polymerase chain reaction [PCR] at the end of therapy), SVR (negative PCR both at the end of treatment and 6 months later), and relapse (PCR negative at the end of treatment but positive 6 months later) were determined.RESULTSA total of 1170 patients were included with a female to male ratio of 1.64:1 and a mean age of 31.6 (8.4) years. Among 1170 patients, 985 completed the therapy as per the protocol, 119 were defaulted (treatment abandoned before completion), and 66 had to stop treatment due to side effects. ETR was 74.1%, SVR was 98%, relapse rate was 1.5%, and 10.1% were nonresponders. SVR was seen only in patients who had achieved an ETR (n=867). SVR was achieved in 848 patients (out of 867) (98%), relapse was seen in 13 (1.5%), and 6 (0.7%) patients lost follow-up after stopping treatment. Patients achieving ETR and SVR had a mean serum alanine aminotransferase of 71.3 (57.1) and 71.0 (56.5), respectively, which is approximately twice the upper normal limit.CONCLUSIONThe conventional IFN and ribavirin therapy in genotype 3 chronic HCV-infected patients gives an ETR and SVR of 74.1% and 98%, respectively.

Rétinopathie dysorique à l’interféron au cours de l’hépatite chronique virale C. À propos d’un cas et revue de la littérature

IntroductionThe ophthalmic complications following interferon therapy in chronic hepatitis C are rare. The most common adverse ophthalmic outcome is the dysoric retinopathy characterized by the presence at the fundus examination of cotton wool spots and retinal hemorrhages particularly around the optic disc. Case reportA 63-year-old man presented to the hepatology department with a compensated cirrhosis C. His medical history was positive for hypertension controlled by medical treatment. A combined treatment with pegylated interferon α2a plus ribavirin was initiated. Three months later, the patient reported a sudden decreased vision in both eyes. Fundus examination revealed cotton wool spots with retinal hemorrhage. The diagnosis of dysoric retinopathy was established. The antiviral treatment was discontinued. One month later, the patient was asymptomatic and the ocular lesions have disappeared. ConclusionDysoric retinopathy is a non-specific complication of interferon therapy in chronic hepatitis C. Despite its good prognosis, a careful fundus examination is required before and during the treatment especially for the patients with risk factors for this adverse event (advanced age, diabetes and high blood pressure).

La maladie de basedow compliquant le traitement par interféron de l'hépatite chronique C

The interferon is naturally induced proteins by the immune system. They have biologic and clinical demonstrations of auto–immunity. Among these demonstrations thyroid anti–body apparition and emergence of dysthyroidism notably the Graves disease. We presented a case of a woman followed for a chronic hepatitis C. Her treatment was interferon and ribavirine and that developed a hyperthyroidism.The stop of the antiviral treatment and the administration of anti tyhyroid of synthesis were sufficient to treat this affection. It can be encouraged by factors notably age sex and presence of TPO antibody. The C virus can induce dysthyroidism. The clinical and biological symptom were similar to the spontaneous Graves disease. The follow up of interferon therapy for chronic hepatitis C was very important.

Serum microRNA-122 level correlates with virologic responses to pegylated interferon therapy in chronic hepatitis C

MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, γ-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon-based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa-2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real-time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide -155, -443 and -1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at -443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide -443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment.