Chisa Kondo

An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin.

Summary.  Pegylated interferon (PEG‐IFN)/ribavirin combination therapy is the standard‐of‐care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG‐IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open‐labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG‐IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non‐fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non‐fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non‐fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin‐combined with PEG‐IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.

Combination of fluvastatin with pegylated interferon/ribavirin therapy reduces viral relapse in chronic hepatitis C infected with HCV genotype 1b

Although the anti‐hepatitis C virus (HCV) effect of statins in vitro and clinical efficacy of fluvastatin combined with Pegylated interferon (PEG‐IFN)/ribavirin therapy for chronic hepatitis C (CHC) have been reported, the details of clinical presentation are largely unknown. We focused on viral relapse that influences treatment outcome, and performed a post‐hoc analysis by using data from a randomized controlled trial.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients with genotype 1b chronic hepatitis C

From a pharmacokinetic viewpoint, the use of ombitasvir/paritaprevir/ritonavir, one of the standards of care for genotype 1b chronic hepatitis C in Japan, could be possible in patients with impaired renal function. The aim of this study was to assess the efficacy and safety of this combination that have not yet been addressed in patients undergoing dialysis.

Daclatasvir and asunaprevir for genotype 1b chronic hepatitis C patients with chronic kidney disease

To evaluate the efficacy and safety of daclatasvir and asunaprevir combined therapy in genotype 1b chronic hepatitis C patients with non‐dialysis chronic kidney disease (CKD).

Serum 25(OH)D3 levels affect treatment outcomes for telaprevir/peg-interferon/ribavirin combination therapy in genotype 1b chronic hepatitis C

BACKGROUND Close relationships between chronic hepatitis C and vitamin D levels have been reported. For genotype 1b infection, the current standard of care is pegylated interferon/ribavirin therapy combined with a protease inhibitor. The present study analyzed the relationship between outcomes of triple therapy and serum 25(OH)D3 levels. METHODS Factors contributing to sustained virological response were investigated in 177 patients with chronic hepatitis C who received telaprevir-based triple therapy in this prospective study. RESULTS The sustained virological response rate was 86.9% in patients with 25(OH)D3 levels of >18 ng/ml; this was higher than the 66.7% in patients with 25(OH)D3 levels of ≤ 18 ng/ml (P=0.003). 25(OH)D3 levels and IL28B genotype were identified as significantly independent factors contributing to sustained virological response. The sustained virological response rate did not differ according to 25(OH)D3 levels in patients with the IL28B major genotype. The sustained virological response rate was 64.9% in patients with the IL28B minor genotype and 25(OH)D3 levels of >18 ng/ml, and was 38.5% in those with decreased 25(OH)D3 levels (P=0.045). CONCLUSIONS In triple therapy, 25(OH)D3 levels were an independent factor contributing to sustained virological response. Of particular note, the sustained virological response rate was significantly lower in patients with the IL28B minor genotype.

Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin

Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non‐TT. Among such treatment‐refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non‐TT.

Serum 25-hydroxyvitamin D3 levels affect treatment outcome in pegylated interferon/ribavirin combination therapy for compensated cirrhotic patients with hepatitis C virus genotype 1b and high viral load

Much is unknown about the effect of 25‐hydroxyvitamin D3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus‐related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25‐hydroxyvitamin D3, that contribute to a sustained virological response (SVR) in patients with cirrhosis.

α-Fetoprotein is a surrogate marker for predicting treatment failure in telaprevir-based triple combination therapy for genotype 1b chronic hepatitis C Japanese patients with the IL28B minor genotype

Even when treated with telaprevir‐based triple therapy, some patients fail to achieve a sustained virological response. This study identified factors related closely to treatment failure. A total of 146 Japanese genotype 1b chronic hepatitis C patients were enrolled in this prospective, multicenter study and received a 24‐week regimen of triple therapy. The end‐of‐treatment response rate was significantly lower in patients with the interleukin 28B (IL28B) (rs8099917) non‐TT genotype (85.2%) than in those with the TT genotype (100%, P = 0.0002). Multiple logistic regression analysis identified high α‐fetoprotein levels as an independent factor related to non‐end‐of‐treatment response in patients with the non‐TT genotype. A cut‐off value of 20 ng/ml was determined for a non‐end‐of‐treatment response; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 75.0%, 95.7%, 75.0%, 75.0%, and 92.6%, respectively. Multiple logistic regression analysis for a sustained virological response identified the IL28B TT genotype, low α‐fetoprotein levels, non‐responders, and a rapid virological response. The sustained virological response rate was significantly lower in patients with the non‐TT genotype (59.3%) than in those with the TT genotype (96.7%, P < 0.0001). In patients with the non‐TT genotype, α‐fetoprotein was the most significant predictor for non‐sustained virological response by univariate analysis. A cut‐off value of 7.4 ng/ml α‐fetoprotein was determined for non‐sustained virological response; sensitivity, specificity, PPV, NPV, and accuracy were 63.6%, 87.5%, 77.8%, 77.8%, and 77.8%, respectively. For the non‐TT patients, serum α‐fetoprotein levels may be a surrogate marker for predicting treatment failure in telaprevir‐based therapy for genotype 1b chronic hepatitis C. J. Med. Virol. 86:461–472, 2014.

EFFICACY OF ALFACALCIDOL ON PEG-IFN/ RIBAVIRIN COMBINATION THERAPY FOR ELDERLY PATIENTS WITH CHRONIC HEPATITIS C: A PILOT STUDY

Background Serum vitamin D concentration is reported to show a decrease in older age. Patients with chronic hepatitis C (CHC) in Japan are older on average than those in Western countries. Moreover, the outcome of pegylated-interferon (PEG-IFN)/ ribavirin therapy combined with vitamin D in elderly patients is unclear. Objectives This pilot study explored the efficacy and safety of alfacalcidol as vitamin D source in PEG-IFN/ ribavirin combination therapy for elderly CHC patients infected with hepatitis C virus genotype 1b. Patients and Methods Consecutive twenty CHC patients aged ≥ 65 years were enrolled in this pilot study. Fifteen patients met the inclusion criteria and received PEG-IFN/ ribavirin therapy combined with alfacalcidol. Four-week lead-in of oral alfacalcidol was conducted, and it was subsequently and concurrently administered in PEG-IFN/ ribavirin combination therapy (vitamin D group). Age, gender, and IL28B genotype-matched patients, who received PEG-IFN/ ribavirin alone, were saved as control group (n = 15) to compare the treatment outcome with the vitamin D group. Results Subjects consisted of 14 males and 16 females, with a median age of 70 years (65-78). The serum 25 (OH) D3 concentration in females (20 ng/ml, 11-37) was significantly lower than males (27 ng/mL, 13-49) (P = 0.004). Sustained virological response (SVR) rates were 33.3% (5/15) in the control group and 80.0% (12/15) in the vitamin D group, respectively (P = 0.025). While no significant difference was shown in the (SVR) rate between the two groups among males (P = 0.592), in females the SVR rate was significantly higher in the vitamin D group (87.5%, 7/8) than the control group (25.0%, 2/8) (P = 0.041). The relapse rates in the groups with and without alfacalcidol were 7.7% (1/13) and 61.5% (8/13), respectively (P = 0.011). Interestingly, in females, the relapse in the control group was shown in 5 of 7 (71.4%), whereas in the vitamin D group the relapse rate was decreased (1/8, 12.5%) (P = 0.041). No specific adverse events were observed in the vitamin D group. Conclusions PEG-IFN/ ribavirin combined with alfacalcidol may be effective and safe in elderly CHC patients. In particular, concomitant administration of alfacalcidol may lead to a reduced relapse rate, and consequently improving the SVR rate in elderly females.

Predictive factors for improvement of ascites after transjugular intrahepatic portosystemic shunt in patients with refractory ascites

The aim of this study was to investigate the predictive factors for the response of ascites to a transjugular intrahepatic portosystemic shunt (TIPS) and the impact of improvement of ascites on the overall prognosis of patients with cirrhosis and refractory ascites.