Keizo Kato

Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

Summary.  Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG‐IFN‐alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non‐SVR patients with greater accuracy.

Clinical Evaluation of Sofosbuvir/Ledipasvir in Chronic Hepatitis C Genotype 1 with and without Prior Daclatasvir/Asnaprevir Therapy.

This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy.

Clinical evaluation of sofosbuvir/ledipasvir in patients with chronic hepatitis C genotype 1 with and without prior daclatasvir/asunaprevir therapy

This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy.

Impact of IL28B polymorphisms on 24‐week telaprevir‐based combination therapy for Asian chronic hepatitis C patients with hepatitis C virus genotype 1b

The aim of this study was to clarify which or how factors could influence the probability of sustained virological response (SVR) in 24‐week telaprevir‐based triple combination therapy for East Asian chronic hepatitis C patients infected with hepatitis C virus genotype 1b.

Occurrence of Hepatocellular Carcinoma Was Not a Rare Event during and Immediately after Antiviral Treatment in Japanese HCV-Positive Patients

Advanced chronic hepatitis C patients with sustained virolological response by antivirals remain at risk for hepatocellular carcinoma (HCC). We investigated the incidence of HCC during and immediately after peginterferon-alfa-2a and ribavirin (RBV) treatment in patients with chronic hepatitis C in Japan. HCC was detected in 8 of 238 patients during and after these treatments (mean follow-up period: 572 ± 252 days). In conclusion, occurrence of HCC is not a rare event during and immediately after peginterferon-alfa-2a plus RBV treatment. In cases with cirrhosis, higher α-fetoprotein levels, old age, or a previous history of HCC treatment, clinicians should be especially alert for the possible development of HCC during and immediately after peginterferon-alfa-2a and RBV treatment. Clinicians should regularly check for the possible development of HCC even in chronic hepatitis C patients under treatment.

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.

New Proposal for Response-Guided Peg-Interferon- Plus-Ribavirin Combination Therapy for Chronic Hepatitis C Virus Genotype 2 Infection

This study aimed to determine the most suitable duration of pegylated‐interferon (Peg‐IFN)‐plus‐ribavirin combination therapy in patients infected with hepatitis C virus (HCV) genotype 2 who had not achieved rapid virological response (serum HCV RNA disappearance after 4 weeks of therapy). HCV genotype 2 patients (n = 182) with a high viral load received >80% of the standard Peg‐IFN‐plus‐ribavirin dose for at least 24 weeks, and their final virological responses were studied. Patients were classified into “rapid virological response” and “non‐rapid virological response” groups. The non‐rapid virological response group was further divided into a “virological response at 8 weeks” (serum HCV RNA disappearance after 8 weeks of therapy) and a “non‐virological response at 8 weeks” group. Factors related to rapid virological response and optimal therapy duration in the non‐rapid virological response group were evaluated. Multivariate logistic regression analysis showed that subtype HCV genotype 2a (P = 0.0015) and low concentration of pretreatment serum HCV RNA (P = 0.0058) were independent factors in a rapid virological response. In the virological response at 8 weeks group, the sustained virological response rate after 24 weeks of therapy was significantly lower than after 36 weeks (P = 0.044) or after 48 weeks (P = 0.006), and was similar for 36‐ and 48‐weeks. The cost for achieving (CAS) one sustained virological response was lowest with 36‐week therapy. Prolongation of Peg‐IFN‐plus‐ribavirin combination therapy to 36 weeks is suitable for achieving virological response at 8 weeks, given the high, sustained virological response rate and cost benefit. J. Med. Virol. 85:1523–1533, 2013.

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.

Platelet count and sustained virological response in hepatitis C treatment

AIM To examine the epidemiological data, hematological safety and treatment responses of peginterferon-alpha 2a plus ribavirin therapy for hepatitis C. METHODS Between March 2008 and February 2011, 196 hepatitis C virus (HCV) genotype 1 infected Japanese (127 treatment-naive and 69 treatment-experienced patients) patients treated with peginterferon-alpha 2a plus ribavirin were enrolled. We examined the epidemiological data and treatment responses were retrospectively analyzed in terms of hematological safety. HCV RNA was measured by the COBAS TaqMan HCV test. RESULTS Overall sustained virological response (SVR) rates of treatment-naive and treatment-experienced patients were 56% and 39%, respectively. Multivariate logistic regression analysis showed that SVR was attained independently of early virological response in both treatment-naive and treatment-experienced patients. SVR rates did not differ between the pretreatment hemoglobin < 13 g/dL and ≥ 13 g/dL groups. However, in treatment-naive patients, the SVR rate of the pretreatment platelet count < 130000/µL group was significantly lower than that of the pretreatment platelet count ≥ 130000/µL group. CONCLUSION Attention should be paid to potential thrombocytopenia in the treatment of chronic hepatitis C patients.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir combination therapy for genotype 1b chronic hepatitis C patients complicated with chronic kidney disease: Ombitasvir/paritaprevir/ritonavir for CHC patients with CKD

The aim of this study was to clarify the effects and safety of ombitasvir/paritaprevir/ritonavir (OBT/PTV/r) therapy in genotype 1b chronic hepatitis C patients with non‐dialysis chronic kidney disease (CKD).