Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load

Kim, Soo Ryang; El-Shamy, Ahmed; Imoto, Susumu; Kim, Ke Ih; Ide, Yoshihiro; Deng, Lin; Shoji, Ikuo; Tanaka, Yasuhito; Ota, Mitsuhiro; Hotta, Hak

doi:10.1007/s00535-012-0578-z

Cited by 16 publications

(17 citation statements)

References 33 publications

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“…Because of the small number of RVR patients in our data, we were not able to carry out multivariate analysis for identifying RVR predictors. Our results support a previous study [12], and by univariate analysis we demonstrated a significant correlation between high pretreatment IFN-λ1 serum levels and SVR, but were unable to do so by multivariate analysis. On the other hand, although we were unable to demonstrate IL-28B as a predictor of SVR, some studies have demonstrated it as a positive predictive factor [2,13,14].…”

Section: Discussionsupporting

confidence: 82%

Factors of Response to Pegylated Interferon/Ribavirin Combination Therapy and Mechanism of Viral Clearance

Sugimoto

Kim²,

El-Shamy³

et al. 2013

Dig Dis

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Objectives: This study explores viral factors of the interferon (IFN) and ribavirin (RBV) resistance-determining region (IRRDR), the IFN sensitivity-determining region (ISDR) and the core protein, and host factor interleukin 28B associated with response to pegylated IFN (PEG-IFN) and RBV combination therapy, and the correlation of viral and host factors with IFN-λ1. Methods: A total of 58 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. The pretreatment factors associated with rapid virological response (RVR) and sustained virological response (SVR) were analyzed. Pretreatment IFN-λ1 serum levels were compared with the viral and host factors. Results: Univariate analysis showed that IRRDR ≥6 and ISDR ≥2 were significant pretreatment predictors of RVR, and multivariate analysis identified IRRDR ≥6 and hemoglobin as significant predictors of SVR. Pretreatment IFN-λ1 was significantly higher in the SVR group than in the non-SVR group and also in the IRRDR ≥6 group than in the IRRDR ≤5 group. Conclusions: IRRDR ≥6 was the only significant predictor of SVR and was correlated with IFN-λ1. High serum levels of IFN-λ1 may be conducive to effective PEG-IFN/RBV combination therapy because of the immunomodulatory system.

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Section: Discussionsupporting

confidence: 82%

Factors of Response to Pegylated Interferon/Ribavirin Combination Therapy and Mechanism of Viral Clearance

Sugimoto

Kim²,

El-Shamy³

et al. 2013

Dig Dis

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“…Unlike our study, it has been reported that high ALT and initial viral load reduced the SVR rate (8,10,12,13,14).…”

Section: Discussioncontrasting

confidence: 53%

“…Male gender and older age have been reported to associate with poor outcome of therapy (8,10,11). We found no difference in SVR rate between genders.…”

Section: Discussioncontrasting

confidence: 42%

“…Strong predictors of SVR are HCV genotype and the initial virologic response to treatment (10). A number of pre-treatment factors, such as older age, presence of cirrhosis or advanced fibrosis, African-American race, overweight, genotype, viral load, low level of ALT, and low platelet count are known to reduce the SVR rate (10,11).…”

Section: Discussionmentioning

confidence: 99%

“…Use of this molecule with RBV has shown to increase SVR rates. Afterwards, combinations with specifically targeted antiviral therapy have been developed (10). Clinical trials have suggested that protease inhibitors (telaprevir or boceprevir) combined with PEG-IFNα+RBV could produce increase of SVR rates but discontinuation of treatment because of adverse events was more frequent (10).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Chronic Hepatitis C Patients from Different Aspects Before the Use of Direct Acting Antivirals

Kaya¹,

Mete²,

Kaya³

et al. 2017

vhd

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ÖZObjective: Chronic hepatitis C (CHC) virus infection is one of the leading causes of chronic liver disease in all over the world. The prevalence of CHC is almost 0.5-1% in Turkey. Until recently, pegylated-interferon (PEG IFN) alpha in combination with ribavirin was the main treatment of CHC. The aim of the study was to evaluate the real life data of CHC patients. Materials and Methods:We retrospectively evaluated the demographical data and treatment responses of patients with CHC who were followed and treated in our clinic between January 2008 and December 2015.Results: A total of 117 patients (67 female and 50 male) with a mean age of 48 (15-65) were included in the study. 105 patients were genotype 1, 3 were genotype 2 and 9 were with genotype 3. The patients were treated with PEG IFN alpha-2a (81/117) or alpha-2b (36/117) combined with ribavirin. We observed sustained virologic response (SVR) in 68% of all genotype 1 patients. While relapse was observed in only 1 patient among those with genotype 2 and 3, SVR was achieved in 11. The rate of SVR was only 42% among patients older than 60 years of age, whereas SVR was achieved in all young patients (range: 15-30). The overall SVR rate was 70%. Conclusion:As CHC can result in long-term complications (cirrhosis, terminal liver failure and hepatocellular carcinoma), patients without therapy remain at risk of developing progressive liver disease. Since advanced fibrosis is a predictor for poor prognosis and insufficient therapy outcome, early treatment is required to efficiently cope with this health problem, Although the rates of SVR with direct acting antivirals are very high, starting treatment in early stage could reduce the complications of CHC and transmission of the disease.

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Polymorphisms of the Core, NS3, and NS5a Proteins of Hepatitis C Virus Genotype 1b Associate With Development of Hepatocellular Carcinoma

et al. 2013

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Hepatocellular carcinoma (HCC) is one of the common sequelae of hepatitis C virus (HCV) infection. It remains controversial, however, whether HCV itself plays a direct role in the development of HCC. Although HCV core, NS3, and NS5A proteins were reported to display tumorigenic activities in cell culture and experimental animal systems, their clinical impact on HCC development in humans is still unclear. In this study we investigated sequence polymorphisms in the core protein, NS3, and NS5A of HCV genotype 1b (HCV‐1b) in 49 patients who later developed HCC during a follow‐up of an average of 6.5 years and in 100 patients who did not develop HCC after a 15‐year follow‐up. Sequence analysis revealed that Gln at position 70 of the core protein (core‐Gln70), Tyr at position 1082 plus Gln at 1112 of NS3 (NS3‐Tyr1082/Gln1112), and six or more mutations in the interferon/ribavirin resistance‐determining region of NS5A (NS5A‐IRRDR≥6) were significantly associated with development of HCC. Multivariate analysis identified core‐Gln70, NS3‐Tyr1082/Gln1112, and α‐fetoprotein (AFP) levels (>20 ng/L) as independent factors associated with HCC. Kaplan‐Meier analysis revealed a higher cumulative incidence of HCC for patients infected with HCV isolates with core‐Gln70, NS3‐Tyr1082/Gln1112 or both than for those with non‐(Gln70 plus NS3‐Tyr1082/Gln1112). In most cases, neither the residues at position 70 of the core protein nor positions 1082 and 1112 of the NS3 protein changed during the observation period. Conclusion: HCV isolates with core‐Gln70 and/or NS3‐Tyr1082/Gln1112 are more closely associated with HCC development compared to those with non‐(Gln70 plus NS3‐Tyr1082/Gln1112). (HEPATOLOGY 2013;58:555‐563)

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Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load

Cited by 16 publications

References 33 publications

Factors of Response to Pegylated Interferon/Ribavirin Combination Therapy and Mechanism of Viral Clearance

Factors of Response to Pegylated Interferon/Ribavirin Combination Therapy and Mechanism of Viral Clearance

Evaluation of Chronic Hepatitis C Patients from Different Aspects Before the Use of Direct Acting Antivirals

Polymorphisms of the Core, NS3, and NS5a Proteins of Hepatitis C Virus Genotype 1b Associate With Development of Hepatocellular Carcinoma

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