Predictors Of Sustained Viral Response Research Articles

Hepatocellular Carcinoma Is a Negative Predictor of Sustained Viral Response in Liver Transplant Recipients With Hepatitis C Treated With Direct-Acting Antivirals

IntroductionTreatment with direct-acting antivirals (DAA) for hepatitis C (HCV) in liver transplant (LTX) recipients is very effective, but some studies showed that the treatment effectiveness might be impaired in patients with hepatocellular carcinoma (HCC). The study aimed to evaluate the predictors of DAA treatment failure in LTX recipients. MethodsLiver biopsy was done before the treatment in 107 of the 120 patients included. All patients had an abdominal ultrasound and liver elastography performed before and after the therapy. Blood HCV polymerase chain reaction was done before; during; and at 4, 12, and 24 weeks after the treatment. ResultsOverall sustained viral response 24 weeks after treatment (SVR24) was 96%. There were 2 patients with HCC at the start of the DAA treatment and 3 cases of HCC recurrence during a 1-year follow-up. Treatment failure was observed in 1/115 (0.9%) patients without HCC and 4/5 (80%) with active HCC (P = .0001). Liver fibrosis and previous interferon treatment had no impact on treatment efficacy. Time to viremia elimination on treatment was shorter in the responder versus nonresponder group (28 vs 58 days, P = .03). ConclusionsHCC is a negative predictor of DAA therapy success in LTX recipients.

Interferon-Lambda 4 Gene Polymorphisms Predict Treatment Response in Egyptian HCV Genotype 4 Patients Exposed to Radiation

Background: Direct-acting antivirals (DAAs) has seen a significant increase of the count of patients with hepatitis C virus (HCV) clearing their infection. Interferon Lambda Four (IFNL4) polymorphism plays a distinguished role in spontaneous and treatment-output clearance of HCV infection. Aim of this Work: This study aimed to assess IFNL4 polymorphism among hepatitis C Egyptian patients who were exposed to radiation, compared to normal by a polymerase chain reaction with restriction of fragment length polymorphism (PCR-RFLP) technique. Materials and Method: This study included 50 HCV-positive Egyptian patients working in Egyptian Nuclear materials Authority treated with DAAs therapy. According to treatment, they were split into two groups. Group I included 40 patients with sustained viral response (SVR). Group II included 10 patients with no response (nSVR). Fifty healthy people served as controls. Liver function tests, complete blood count, evaluation of viral markers, HCVRNA by PCR, and evaluation for IFNL4 single nucleotide polymorphisms for rs368234815 were performed by PCRRFLP in all patients. Results: Of the 50 patients, 40 (80%) achieved sustained virological response (SVR). Of the 23 patients with rs368234815 TT/TT genotype, 21 (91.3%) achieved SVR, while in 27 patients with non‑ TT/TT genotypes, 19 (70.4%) achieved SVR. The rs368234815 was a powerful predictor of SVR. However, in the present research individuals, the predictive power of this SNP was the same as that of rs12979860 SNP. Conclusion: In Egyptian HCV-positive patients with genotype 4, IFNL4 rs368234815 SNP is an autonomous predictor of SVR to DAAs treatment.

Association of vitamin D binding protein polymorphisms with response to therapy in Egyptian chronic hepatitis C patients.

Vitamin D binding protein (VDBP) is a potential modulator of immune response and is associated with clinical progression of many diseases. Our aim was to assess influence of baseline 25-hydroxyvitamin D levels and VDBP single nucleotide polymorphisms (SNPs), rs4588 (C > A) and rs7041 (G > T), on baseline clinical parameters and response to interferon based therapy in chronic hepatitis C patients in Egypt. Genotyping was performed by RFLP (Restriction Fragment Length Polymorphism) in 112 treatment naïve hepatitis C patients and 50 healthy controls. Vitamin D levels were assessed by ELISA. HCV RNA quantification was performed by PCR to assess therapy outcome. Patients with VDBP WT+ diplotype (3 or 4 VDBP major alleles) had higher viral response rates at weeks 12, 48, and 72 (p = 0.046, 0.034 and 0.029, respectively) and lower base line viral load (p = 0.016). Multivariate logistic regression identified VDBP WT+ diplotype as an independent predictor of sustained viral response (SVR; p = 0.014, RR = 4.716, 95% CI = 1.371 - 16.609). Interestingly, WT- diplotype (less than 3 VDBP major alleles) was associated with significant liver fibrosis (p = 0.045). VDBP WT+ diplotype is associated with lower baseline viral load and better therapy outcome in HCV treatment naïve patients. The rs4588 genotype is associated with SVR in the Egyptian population.

Association of interleukin-28B rs12979860 and rs8099917 polymorphisms with sustained viral response in hepatitis C virus genotype 1 and 3 infected patients from the Indian subcontinent

Background: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) have been shown to impact treatment responses in hepatitis C virus (HCV) infected patients. The association of these polymorphisms with sustained viral response (SVR) has been studied in HCV genotype 3 infected patients in India, but not in genotype 1. Objectives: This study aimed to determine the association of IL28B gene polymorphisms and other host and viral factors with treatment response in patients with HCV genotype 1 and 3 infection. Materials and Methods: DNA from 42 HCV-infected patients on antiviral therapy was analysed for the IL28B polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Bidirectional sequencing was performed on a subset of samples for verification of PCR-RFLP results. Information on age, weight, height, diabetic status, pre-treatment viral load and alanine aminotransferase (ALT) levels was obtained from clinical records. The IL28B genotypes and the other factors were analysed for their association with SVR. Results: The frequency distribution of rs12979860 CC/CT/TT genotypes was found to be 66.7%, 26.2% and 7.1%, respectively. For rs8099917 genotype, the TT/GT/GG distribution was 73.8%, 21.4% and 4.8%, respectively. SVR was seen in 61.9% of cases (55.6% in genotype 1 and 62.5% in genotype 3). CC genotype at rs12979860 and TT genotype at rs8099917 were significantly higher in responders (P = 0.013 and 0.042, respectively). Lower baseline ALT and rapid viral response were also found to be associated with SVR. On logistic regression analysis, CC genotype at rs12979860 emerged as the most powerful predictor of treatment response. Conclusion: IL28B polymorphisms are strong predictors of SVR in patients from the Indian subcontinent infected with HCV genotype 3 and genotype 1.

Association of IFNL3 and IFNL4 polymorphisms with hepatitis C virus infection in a population from southeastern Brazil.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated complications such as liver cirrhosis and hepatocellular carcinoma (HCC). Viral and host factors are known to be predictors for antiviral therapy. Host factors that are predictors of sustained viral response (SVR) were discovered by genome-wide association studies (GWAS), including single-nucleotide polymorphisms (SNPs) in or near the interferon lambda gene (rs8099917, rs12979860 and rs368234815). The aim of the present study was to verify the genotype frequencies of SNPs rs8099917, rs12979860 and rs368234815 and to evaluate the association between SNPs and the outcome of HCV infection, taking into account the population ancestry. In this study, there was an association of the three polymorphisms with both clinical outcome and response to treatment with PEG-IFN and RBV. The polymorphisms rs12979860 and rs368234815 were associated with increased sensitivity (97.7%, 95% CI 87.2-100, and 93.3%, 95% CI 81.3-98.3; respectively) and with a greater predictive value of a positive response to treatment. In multivariable analysis adjusted by gender, age and ancestry, the haplotype G/T/ΔG was related to non-response to treatment (OR = 21.09, 95% CI 5.33-83.51; p < 0.001) and to a higher chance of developing chronic infection (OR = 5.46, 95% CI 2.06-14.46; p = 0.001) when compared to the haplotype T/C/TT. These findings may help to adjust our treatment policies for HCV infection based on greater certainty in studies with populations with such genetic characteristics, as well as allowing us to get to know the genetic profile of our population for these polymorphisms.

P-B4 Predictors of sustained viral response to 4–6 week duration therapy with Ledipasvir + Sofosbuvir + Gs-9451 +/− Gs-9669 in early and advanced fibrosis (Nih-Ihv synergy trial)

P-B4 Predictors of sustained viral response to 4–6 week duration therapy with Ledipasvir + Sofosbuvir + Gs-9451 +/− Gs-9669 in early and advanced fibrosis (Nih-Ihv synergy trial)

Low-Dose Pegylated Interferon α-2b Plus Ribavirin for Elderly and/or Cirrhotic Patients with Genotype 2 Hepatitis C Virus.

Background/AimsThis study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks.MethodsLow-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured.ResultsThe patients’ median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively.ConclusionsLow-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.

The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients.

Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P<0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.

P1262 : An accurate score for the prediction of sustained viral response under protease inhibitor-based triple therapy in cirrhotic patients: The cupic algorithm – the ANRS CO20 CUPIC study

P1262 : An accurate score for the prediction of sustained viral response under protease inhibitor-based triple therapy in cirrhotic patients: The cupic algorithm – the ANRS CO20 CUPIC study

P0875 : Predictors of sustained viral response to 4–6 week duration therapy with ledipasvir + sofosbuvir + GS-9451 +/− GS-9669 in early and advanced fibrosis (NIH/UMD synergy trial)

Dietrich D et al., 2014 Mixed Multicenter Yes 276 Mean 59 181 (57) 145 (45) Modi AA et al., 2014 Community Multicenter Yes 32 Median 59 34 (76) − Bichoupan K et al., 2014 University Single center No 181 Median 62 96 (53) Capraru CI et al., 2014 University Single center No 34 Mean 57.7 31 (66) − Roytman M et al., 2014 University Single center No 52 Mean 61.5 63 (64) 63 (64) Lin MV et al., 2014 University Multicenter No 121 Mean 57.7 103 (70) 84 (57) Lingala S et al., 2014 University Single center No 19 Mean 59 16 (64) −

Factors Affecting the Response to Interferon Alpha Therapy in Egyptian HCV Patients

Hepatitis C Virus (HCV) infection is one of the main causes of chronic liver disease worldwide. Egypt has the highest prevalence of Hepatitis C Virus (HCV) in the world, estimated nationally at 14.7%. knowledge of the predictors of Sustained Viral Response (SVR) to Pegylated Interferon (PEG-INF) and Ribavirin (RBV) therapy in patients with chronic hepatitis C is crucial for selecting patients who would benefit most from therapy especially in developing country as Egypt where the highest percentage of treatment cost funded by government. This study was performed on Egyptian patients with chronic active hepatitis C who were prepared for receiving a course of treatment with: Interferon (PEG IFN) and ribavirin for 48 weeks. We aimed to find more predictive markers those can help clinicians to choose the most effective treatment program for each patient. Assessment of HLA-DRB1, HLA-DQB1 genes by Sequence Specific Primer (SSP) PCR, interleukin-10 (IL-10) by ELISA technique and Serum HCV RNA load by TaqMan Real Time RT-PCR technology were done. We found that sustained responders were significantly among DRB1*13 allele and DQB1*02 typing (p<0.001). DRB1*07 allele only appeared with responded patients. Relations were found between response to treatment and lower IL-10 level and lower Body Mass Index (BMI) but not sufficient to reach to significant value. In conclusion, we emphasize the importance of the use of pharmacogenomic data in the treatment of patients. HLA-DRB1*07, HLA-DRB1*13 and HLA-DQ02 alleles can predict the response to HCV combined therapy. The data generated from our study may be helpful in future for clinicians to predict the treatment outcome for HCV-seropositive individuals in Egypt.

The birth and potential death of IL28B genotyping for hepatitis C therapy.

The birth and potential death of IL28B genotyping for hepatitis C therapy.

Boceprevir and telaprevir for chronic genotype 1 hepatitis C virus infection. A systematic review and meta-analysis

Background. Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability.Aim. Assess benefits and harms of boceprevir (BOC) and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit.Material and methods. Search from 2009-2013 in PubMed, EMBASE, and “gray literature” of published and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines were applied. Comparisons between PI + PR vs. PR were performed. Main outcomes were expressed as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed.Results. 33 studies (10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95% CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis, statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels. In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed superior response rates. Specific predictors will determine the best candidates for treatments that will offer real-life therapeutic alternatives.

PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.

Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.

Predicting Therapeutic Results of Interferon Based Treatment by Modeling the First Week Viral Kinetics in Patients with Chronic Hepatitis C

Background: The present study aimed to develop an optimal model predictive of the treatment response one week after initiating antiviral therapy. Patients and Methods: In all, 166 patients completed the treatment and were followed up for six months. Results: A viral response was achieved in 14 (8.4%) genotype 1 (G1) and 32 (19.3%) non-genotype 1 (G0) patients at week one after initiation of therapy and 45 (27.1%) G1 and 90 (54.2%) G0 patients at week four. A sustained viral response (SVR) was achieved in 50 (30.1%) G1 and 83 (50.0%) G0 patients, in 13 (29.5%) G1 and 31 (70.5%) G0 patients whose antiviral response was achieved at one week, and in 37 G1 (32.2%) and 78 G0 (67.8%) patients whose antiviral response was achieved at four weeks. The HCV viral kinetic parameter π (i.e., 1: α, α was defined as the area under the line y [viral load]=– a[x{time}] between week 0 and week 1) was found to be the best performing test for predicting SVR (p<0.0001). Regression analysis identified π as the only independent predictor of SVR (p=0.043). Conclusions: The use of bio-mathematical models of HCV kinetics can reliably predict SVR one week after starting therapy.

A polymorphism in the microsomal triglyceride transfer protein can predict the response to antiviral therapy in Egyptian patients with chronic hepatitis C virus genotype 4 infection.

Background/AimsA polymorphism in the microsomal triglyceride transfer protein (MTP) is associated with hepatic fibrosis, and carriers showed higher levels of steatosis, higher levels of hepatitis C virus (HCV) RNA and advanced fibrosis. The aim of this study was to study MTP expression pattern in HCV patients and impact of the MTP polymorphism on the response to antiviral therapy.MethodsOne hundred consecutive naive HCV genotype 4 patients were recruited to receive antiviral therapy, and 40 control subjects were also recruited. Demographic, laboratory, and histopathology data were collected. DNA was isolated, and the samples were subjected to polymerase chain reaction analysis and genotyping for MTP by restriction fragment length polymorphism analysis.ResultsPatients and controls were age- and sex-matched (male/female, 56/44, age, 39.2±7.8 years for patients with HCV; male/female, 18/22, age, 38.1±8.1 years for controls). MTP single nucleotide polymorphisms (SNPs) (GG, GT, TT) and alleles (G, T) in the patients versus the controls were 70%, 21%, 9% & 80.5%, 19.5% versus 10%, 87.5%, 2.5% & 53.8%, 46.3%, respectively (p=0.0001). The sustained viral response (SVR) of the patients was 60%. SNPs in MTP genotypes (GG, GT, and TT) and alleles (G and T) in the responders and nonresponders were 71.7%, 25%, 3.3% & 84.2%, 15.8% versus 67.5%, 15%, 17.5% & 75%, 25% (p=0.038 and p=0.109, respectively). A multivariate analysis showed that the GT genotype was an independent predictor of SVR (area under the curve 90% and p=0.0001).ConclusionsMTP could be a new predictor for SVR to antiviral therapy in patients with HCV genotype 4 infection.

Re-treatment of chronic HCV infection in HIV co-infected patients and predictors of sustained viral response

In HIV-HCV co-infected patients who failed to achieve sustained viral response (SVR) with PEG-IFN + RBV, data on SVR rate after re-treatment with Peginterferon (PEG-IFN) + ribavirin (RBV) are scarce. The aim of this study was to identify factors predictive of SVR after re-treatment in a large cohort of HIV/HCV co-infected patients - the ANRS-CO7 Ribavic cohort study, which is a long term follow-up study of patients who were included in the randomized controlled trial ANRS-HC02 RIBAVIC. Among the 176 patients who did not achieve a SVR during the RIBAVIC trial, sixty-six patients (38%) experienced a re-treatment with PEG-IFN + RBV. The SVR observed to the second course of HCV treatment was 44% overall, i.e. 93% in patients who were relapsers and 29% in nonresponders. In the nonresponders subgroup, the SVR rate was 42% in patients with genotype 2-3 and 26% in patients with genotype 1-4. In multivariate analysis, age ≤ 40 years (OR 12.4 95% CI 1.9-171, p = 0.003), genotype 2-3 versus 1-4 (OR 8.1 95% CI 8.1 1.2-97, p = 0.002) and relapser status at first treatment (OR 32.9 95% CI 3.2-278, p < 0.0001) were significantly associated with SVR. Our findings strongly suggest that patients who relapse after first treatment, particularly those infected with HCV genotype 2-3, or living in countries with no access to the direct acting antiviral drugs for HCV, could be successfully re-treated with standard bi-therapy of PEG-IFN + RBV regimen.

Correlations between noninvasive tests as predictors of liver fibrosis and of viral response in chronic hepatitis C patients

Background The noninvasive assessment of liver fibrosis in chronic hepatitis C patients is very important as it dictates the disease prognosis and the indication for therapy, narrowing down the use of the liver biopsy. Standardized scores (FibroTest, FibroMax) and imaging techniques (FibroScan) have been validated in this respect. As for the noninvasive prediction of the sustained viral response (SVR), GenoFibroTest and Prometheus are two indexes that may be used. This study’s aim is to compare several biological scores with these standardized scores for evaluating fibrosis and the two indexes for prediction of SVR.

Thyroid disorders associated with hepatitis C or interferon based therapies

Sener Barut, OZGUR GUNAL Several extrahepatic diseases have been associated with chronic hepatitis C virus (HCV) infection (i.e. hematologic diseases, renal disease, dermatologic conditions). It has also been shown that HCV infection is associated with increased incidence of clinical and subclinical autoimmune thyroid disorders. Moreover, interferon (IFN)-a therapy of chronic HCV infection is associated with subclinical or clinical thyroiditis in up to 40% of cases. Interferon induced thyroiditis (IIT) can be classified as autoimmune type and non-autoimmune type. Current studies indicate that viral load, viral genotype and therapeutic regimen do not influence development of IIT in chronic hepatitis C patients thus, and development of IIT is not a predictor of sustained viral response. However, evidence suggests that genetic factors, gender, HCV infection and positivity of thyroid antibodies may play role.

Sequencing Assays for Failed Genotyping with the Versant Hepatitis C Virus Genotype Assay (LiPA), Version 2.0

For optimal antiviral therapy, the hepatitis C virus (HCV) genotype needs to be determined, as it remains a strong predictor of sustained viral response. In this study, we assessed the number of HCV genotyping results that could not be determined using the commercially available line probe assay (LiPA) (Versant hepatitis C virus genotype 2.0 assay) in a large international panel of samples from 9,874 HCV-positive patients. In-house sequencing assays targeting the 5' untranslated region (UTR), core region, NS3 region, and NS5B region of the HCV genome and phylogenetic analyses were used to resolve these LiPA failures. Among all cases, the genotypes of 51 samples (0.52%) could not be determined with the LiPA. These undetermined results were observed more frequently among samples from non-European regions (mainly the Arabian Peninsula). The use of sequencing assays coupled with phylogenetic analysis provided reliable genotype results for 86% of the LiPA failures, which exhibited higher rates of genotypes 4, 5, and 6 than did LiPA-resolved genotypes. As expected, the 5' UTR was not sufficiently variable for clear discrimination between genotypes 1 and 6, but it also resulted in errors in classification of some genotype 3 and 4 cases using well-known Web-based BLAST programs. This study demonstrates the low frequency of genotyping failures with the Versant hepatitis C virus genotype 2.0 assay (LiPA) and also underlines the need for a complex combination of sequences and phylogenetic analyses in order to genotype these particular HCV strains correctly.