Predictors of treatment efficacy and ALT non‐normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2

Watanabe, Takao; Terada, Yoshio; Joko, Kouji; Michitaka, Kojiro; Horiike, Norio; Tanaka, Yoshinori; Tada, Fujimasa; Kisaka, Yoshiyasu; Nakanishi, Seiji; Nonaka, Takashi; Yamauchi, Kazuhiko; Hirooka, Masashi; Abe, Masanori; Hiasa, Yoichi

doi:10.1002/jmv.24776

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…The clinical impact of DAA RASs in the HCV NS5B region on sofosbuvir/ribavirin treatment failure is still unclear (5)(6)(7)25). The two patients who experienced relapse had cirrhosis, which is also one of the risk factors for HCV RNA reappearance (6), and did not have any RASs in the HCV NS5B polymerase region, which had been previously reported (25).…”

Section: Discussionmentioning

confidence: 89%

Follow-up Results of HCV GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC

et al. 2019

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Background: We examined treatment the efficacy and data on long-term outcomes in real-world Japanese patients infected with hepatitis C virus (HCV) genotype 2 treated with 12-week sofosbuvir/ribavirin combination therapy. Patients and Methods: In a total of 86 patients who were treated with sofosbuvir/ribavirin, sustained virological response (SVR) rates and long-term-outcomes were retrospectively analyzed. Results: The adherence to this combination therapy was 98.8%. The rates of SVR at week 24 (SVR24) achieved with this treatment according to the 'intention-to-treat' and 'per-protocol' analyses were 89.5% and 96.2%, respectively. Two patients who experienced relapse did not have any previously reported resistance-associated substitutions in the HCV non-structural protein 5B (NS5B) polymerase region. We did not observe any patients who experienced late relapse but did observe that 50% and 1.3% of patients with and without a previous history of hepatocellular carcinoma (HCC), respectively, developed HCC after achieving SVR24 (with a mean follow-up period of 2.7±0.8 years). Conclusion: Patients with SVR should be carefully followed-up to screen for the occurrence of HCC, although it is infrequent. Chronic hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) and end-stage liver disease in Japan and Southern Europe (1, 2). Recent interferon-free therapy with direct-acting antivirals (DAAs) against HCV resulted in higher sustained virological response (SVR) rates with shorter treatment durations and few adverse events (3). In Japan, the estimated proportion of the general population with HCV infection is 1.0-2.0%, and HCV genotype 2 (GT2) accounts for 30% of chronic HCV infections (4). The 12-week combination therapy of the HCV non-structural protein 5B (NS5B) inhibitors sofosbuvir and ribavirin was supported by the Japanese health insurance system as the very first DAA therapy for HCV GT2-infected patients (3, 5-7). However, the efficacy and follow-up data of this treatment in a group of real-world Japanese patients infected with HCV GT2 are limited and complex (5-7). Although there are different results between phase III clinical trials and real-world data, the 12-week combination therapy of sofosbuvir/ribavirin led to 90-95% SVR rates in Japanese DAA-naïve patients infected with HCV GT2 (3, 5-7). Recently, pan-genotypic interferon-free therapies became approved in Japan. The 12-week combination of sofosbuvir/HCV NS5A inhibitor ledipasvir without ribavirin has been available for both HCV GT1 and GT2 infection (8, 9). This combination led to 100% and 96% SVR rates in patients infected with HCV GT1 and GT2, respectively (8, 9). The 8-week combination of the HCV NS3 inhibitor glecaprevir/HCV NS5A inhibitor pibrentasvir without ribavirin has also been available for patients without cirrhosis infected with both HCV GT1 and GT2 (10). This combination led to 99.2% and 98.2% SVR rates in patients infected with HCV GT1 and GT2, respectively (10). Thus, 3855 This article is freely accessible o...

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Section: Discussionmentioning

confidence: 89%

Follow-up Results of HCV GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC

et al. 2019

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“…Recently, the serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) has emerged as a novel non‐invasive marker for liver fibrosis, particularly in patients with chronic HCV infection 17,18 . In addition, M2BPGi can also be used to predict HCV treatment outcome, including regimens with PEG‐IFN‐ or DAA‐based therapies 19–21 . Despite these data, there are limited studies that directly examine the usefulness of serial M2BPGi in monitoring fibrosis regression following DAA treatment.…”

Section: Introductionmentioning

confidence: 99%

“…17,18 In addition, M2BPGi can also be used to predict HCV treatment outcome, including regimens with PEG-IFN-or DAA-based therapies. [19][20][21] Despite these data, there are limited studies that directly examine the usefulness of serial M2BPGi in monitoring fibrosis regression following DAA treatment. Therefore, this study was aimed at investigating the clinical utility of serum M2BPGi kinetics during elbasvir/grazoprevir (EBR/GZR) therapy in HCV mono-infected and HIV/HCV co-infected patients.…”

Section: Introductionmentioning

confidence: 99%

Liver fibrosis improvement assessed by magnetic resonance elastography and Mac‐2‐binding protein glycosylation isomer in patients with hepatitis C virus infection receiving direct‐acting antivirals

Chuaypen

Chittmittrapap

Avihingsanon

et al. 2021

Hepatology Research

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Aim Fibrosis regression has been observed in patients with chronic hepatitis C virus (HCV) infection treated with direct‐acting antivirals. This study was aimed at evaluating dynamic changes of serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) in patients with HCV genotype 1 receiving elbasvir/grazoprevir. Methods M2BPGi were serially measured at baseline, during and after therapy. Its diagnostic performance at baseline and sustained virological response at 24 weeks after treatment (SVR24) were compared with transient elastography (TE) and the aspartate aminotransferase/platelet ratio index (APRI) using magnetic resonance elastography (MRE) as a reference. Results Overall, 60 HCV mono‐infected and 36 HCV/HIV co‐infected patients were included with SVR24 rates of 93.3% and 97.2%, respectively. At baseline, TE, M2BPGi and APRI were correlated with MRE (r = 0.788, r = 0.703 and r = 0.564, respectively, p < 0.001). The area under the receiver operator characteristics curves for TE, M2BPGi and APRI in differentiating significant fibrosis were 0.88 (95% confidence interval; 0.81–0.95, p < 0.001), 0.86 (0.79–0.94, p < 0.001) and 0.74 (0.64–0.83, p < 0.001), respectively. The corresponding figures for cirrhosis were 0.95 (0.90–1.00, p < 0.001), 0.96 (0.92–1.00, p < 0.001) and 0.88 (0.79–0.97, p < 0.001), respectively. Compared with baseline, all fibrosis markers significantly declined after achieving SVR24. The correlations of TE, M2BPGi and APRI with MRE at time of SVR24 were r = 0.587 (p < 0.001), r = 0.457 (p < 0.001) and r = 0.293 (p = 0.004), respectively. In multivariate analysis, high baseline alanine aminotransferase level, HCV mono‐infection and advanced fibrosis were factors associated with M2BPGi reduction. Conclusions HCV eradication is associated with liver fibrosis improvement. M2BPGi has a better performance than APRI in monitoring liver fibrosis in patients treated with direct‐acting antivirals. This marker is applicable in resource‐limited settings where imaging‐based modalities are not widely accessible.

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“…[ 57 ] Watanabe et al assessed the potential predictive factors associated with SVR-12: they found that independent predictive factors were gender, age, body mass index, baseline values for ALT, White blood cells, platelet counts, total bilirubin, albumin, prothrombin time, α-fetoprotein, HCV-RNA, type-4 collagen, hyaluronic acid, HbA1c, naïve treatment versus re-treatment, RBV adherence, and chronic hepatitis/cirrhosis. [ 59 ] The differences between these studies could be explained by the different sample sizes, virus genotypes, clinical situations of the patients, types of patients regarding previous experience to antivirals, and the addition of SOF.…”

Section: Discussionmentioning

confidence: 99%

Prediction of response to sofosbuvir-based therapy using serum interleukin-12 and single nucleotide polymorphism of the interleukin 28B gene as predictive factors in HCV positive genotype-4 patients

Mohamed Abdelnajid,

Elmowafy,

Rostaing

et al. 2023

Medicine

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Some hepatitis-C virus patients have resistance to direct-acting-antivirals (DAAs). Genetic polymorphisms have been associated with drug resistance. This study aimed to evaluate the role of interleukin (IL)-28B gene polymorphism and IL-12 levels as predictors for a response to sofosbuvir/ribavirin (SOF/RBV) with (triple-therapy) or without (dual-therapy) Peg-alpha-interferon. 92 hepatitis C virus (HCV)/RNA (+)-patients treated with dual (n = 72) or triple (n = 20) therapy. IL28B genetic polymorphism and IL-12 level assessments. 30.4% of the patients were IL28B C/C genotype, 56.5% C/T-genotype, and 13% T/T-genotype. Mean baseline IL-12 levels were 27.5 ± 3.0 pg/mL. Rapid viral response was achieved in 86/92 patients. All patients achieved end-of-treatment virologic response. The 12- and 24-week sustained virologic responses (SVR) were achieved in 76 patients (82.6%), that is, a relapse was found in 16 patients (17.4%). 8 and 12-weeks after antiviral therapy, IL-12 levels decreased significantly, and became comparable to those of the control-group. That drop in IL-12 levels was similar across the dual- and triple-therapy patients. Finally, logistic regression analysis showed that the increase in baseline aspartate aminotransferase (AST) and T/T genotyping had an independent effect on increasing the probability a SVR failing in both dual- and triple-therapy groups (P = .0007 and P = .02, respectively). Single-nucleotide polymorphism (SNP) in IL-28B and IL-12 levels play roles as predictors in DAAs resistance.

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Predictors of treatment efficacy and ALT non‐normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2

Cited by 8 publications

References 22 publications

Follow-up Results of HCV GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC

Follow-up Results of HCV GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC

Liver fibrosis improvement assessed by magnetic resonance elastography and Mac‐2‐binding protein glycosylation isomer in patients with hepatitis C virus infection receiving direct‐acting antivirals

Prediction of response to sofosbuvir-based therapy using serum interleukin-12 and single nucleotide polymorphism of the interleukin 28B gene as predictive factors in HCV positive genotype-4 patients

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