Tomomi Okubo

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).

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.

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).

Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients

AIM To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention. METHODS We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response. RESULTS Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10(-6)) and -1.3 kg (P = 1.83 × 10(-5)), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors. CONCLUSION The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.

Effectiveness and safety of community-based treatment with sofosbuvir plus ribavirin for elderly patients with genotype 2 chronic hepatitis C

BACKGROUND The aim of this study was to clarify the effectiveness and safety of sofosbuvir/ribavirin therapy for elderly patients with genotype 2-infected chronic hepatitis C (CHC) in Japan. METHODS A multicenter, retrospective study evaluated the effectiveness and safety of sofosbuvir/ribavirin based on real-world clinical data. RESULTS The subjects consisted of 270 patients, 47.0% of whom were aged ≥65 years. The sustained virological response rates in patients aged <65 and ≥65 years were 98.6% and 95.3%, respectively. Hemoglobin levels decreased during treatment due to ribavirin-related hemolysis, and were significantly lower in patients aged ≥65 years than those aged <65 years at all time-points. A reduction in ribavirin dose was necessary in 31.0% (26/84) of patients with hemoglobin levels <13.0g/dL and in 70.7% (39/127) of those aged >65 years. Although the most frequent adverse event was anemia, no patients discontinued the use of either ribavirin or sofosbuvir. The incidence of ribavirin-related anemia in patients aged ≥65 years was 34.6% and significantly higher compared with that in patients aged <65 years (2.8%). CONCLUSIONS Treatment with sofosbuvir/ribavirin for genotype 2-infected CHC was effective and safe even for elderly patients, although the incidence of adverse events including ribavirin-related anemia was relatively high.

Vitamin D-related gene polymorphisms do not influence the outcome and serum vitamin D level in pegylated interferon/ribavirin therapy combined with protease inhibitor for patients with genotype 1b chronic hepatitis C

Although several vitamin D‐related gene polymorphisms were reported to affect the outcome of pegylated interferon/ribavirin (PR) therapy in chronic hepatitis C patients, there are no reports on the impact of the vitamin D‐related gene polymorphisms in PR therapy combined with protease inhibitor (PI). Vitamin D‐related gene polymorphisms were determined in 177 genotype 1b‐infected chronic hepatitis C patients who received 12 weeks of PR therapy with telaprevir, a first‐generation PI, followed by 12 weeks of PR therapy. The sustained virologic response (SVR) rate was 83.1% (147 of 177 patients). The frequencies of vitamin D‐related gene polymorphisms were: 83 non‐TT and 94 TT genotypes for GC, 97 non‐AA and 80 AA genotypes for DHCR7, 151 non‐AA and 26 AA genotypes for CYP2R1, 162 non‐GG and 15 GG genotypes for CYP27B1, and 105 non‐GG and 72 GG genotypes for VDR gene. Multivariate analysis extracted IL28B TT genotype (P = 2.05×10−6) and serum 25(OH) D3 level (P = 0.024) as independent factors contributing to the achieving of SVR. The SVR rate in IL28B TT genotype patients with serum 25(OH) D3 level of <25 ng/ml was significantly low compared to other patients. None of the vitamin D‐related gene polymorphisms affected the treatment outcome and serum 25(OH) D3 level. In conclusions, the IL28B polymorphism and serum 25(OH) D3 level contributed significantly and independently to SVR in PR combined with PI for genotype 1b‐infected chronic hepatitis C patients. However, none of vitamin D‐related gene polymorphisms had an impact on the treatment outcome and serum 25(OH) D3 level. J. Med. Virol. 87:1904–1912, 2015.

Analysis of factors predicting the response to tolvaptan in patients with liver cirrhosis and hepatic edema: Factors predicting the response to tolvaptan

This study aimed to clarify the factors predictive of treatment response to tolvaptan (V2‐receptor antagonist) for cirrhotic patients with hepatic edema in a real‐world setting.

Real-world virological efficacy and safety of elbasvir and grazoprevir in patients with chronic hepatitis C virus genotype 1 infection in Japan

BackgroundThe real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1.MethodsThe rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics.ResultsOverall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment.ConclusionsThe EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.

Association between vitamin D deficiency and pre-existing resistance-associated hepatitis C virus NS5A variants: Vitamin D and resistance-associated variants

Although interferon‐free therapy with direct‐acting antivirals has developed as a standard of care for chronic hepatitis C, the existence of resistance‐associated variants (RAVs) has a negative impact on treatment results. Recently, several studies indicated a relationship between chronic hepatitis C and serum vitamin D levels. However, the relationship between RAVs at the hepatitis C virus non‐structure 5A (NS5A) region and serum vitamin D level has not yet been examined.