Triple Therapy For Chronic Hepatitis Research Articles

Regional Differences in the Safety of Telaprevir-Based Triple Therapy for Chronic Hepatitis C in Japan:

Regional Differences in the Safety of Telaprevir-Based Triple Therapy for Chronic Hepatitis C in Japan:

Telaprevir-based Triple Therapy for Retreatment of Chronic Hepatitis C Patients with Genotype Four Followed in Our Clinic

OZ Objective: Telaprevir-based triple therapy for chronic hepatitis C virus (HCV) patients with genotype 4 is not recommended potently by the guidelines. There are few studies in the literature related to this issue. This study showed the antiviral activity and safety of telaprevir-based regimens in the treatment of treatmentexperienced genotype 4 chronic HCV-infected patients. Materials and Methods: This retrospective study consisted of 12 genotype 4 HCV-infected patients. All patients received 12 weeks of telaprevir in combination with 24 weeks of pegylated interferon (PEG-IFN) alpha and ribavirin (RBV). Results: The sustained virological response (SVR) rate was six of 12 (50%). Notably, the rate of SVR in prior relapsers was 75% (6 of 8). SVR could not be achieved in non-responders. Conclusion: Telaprevir, a potent HCV NS3-4A protease inhibitor, has been used as monotherapy and in combination with PEG-IFN/RBV in patients infected with genotype 1, 2 and 3 HCV. Limited clinical data suggest that telaprevir has activity against genotype 4 HCV. In this study, it was observed that the addition of telaprevir to the standard regimen had a greater activity on treatment relapse patients with genotype 4.

Difficult management of triple therapy for chronic hepatitis C in a patient on haemodialysis

Difficult management of triple therapy for chronic hepatitis C in a patient on haemodialysis

Analysis of renal function during telaprevir-based triple therapy for chronic hepatitis C.

Telaprevir (TVR) is used for the treatment of chronic hepatitis C in a combination therapy with pegylated-interferon and ribavirin. Although renal dysfunction is one of the critical adverse outcomes of this treatment, little is known regarding the mechanism of its onset. The present study assessed the association of renal function with TVR dose and viral response. Hematological, biochemical, urinary and virological parameters of renal function were examined during the TVR-based triple therapy of patients infected with hepatitis C virus (HCV) genotype 1b. Serum creatinine levels were increased and the estimated glomerular filtration rate (eGFR) was decreased in every patient during TVR administration, but these values recovered to normal levels following cessation of TVR. Fractional excretion of sodium was <1% at days 3 and 7, appearing similar regardless of baseline renal function. Urinary β2-microglobulin levels were elevated and were significantly higher in patients with renal dysfunction, as compared with those not exhibiting renal dysfunction (P<0.05). The reduction in renal function was milder in patients treated with a reduced TVR dose, and these patients had a significantly lower risk of developing renal dysfunction (P<0.05). Using a multivariate analysis, TVR dose and eGFR at the initiation of treatment were identified as significant contributory factors in the development of renal dysfunction. Reduction in TVR dose did not lead to a significant increase in the viral kinetics of HCV or detrimental effects on the sustained viral response (SVR) rate. It is hypothesized that renal dysfunction during TVR treatment is caused by damage of the renal tubule, in addition to pre-renal dysfunction, and that reduction in TVR dose reduces the rate of renal dysfunction without causing a significant decrease in the SVR rate.

Out with the old: what new HCV drugs mean for patients

Gastrointestinal NursingVol. 13, No. Sup5 BASLNF NotesOut with the old: what new HCV drugs mean for patientsSally BuftonSally BuftonSearch for more papers by this authorSally BuftonPublished Online:19 Jun 2015https://doi.org/10.12968/gasn.2015.13.Sup5.S8AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Harris RJ, Ramsay M, Hope VD et al. (2012) Hepatitis C prevalence in England remains low and varies by ethnicity: an updated evidence synthesis. Eur J Public Health 22(2): 187–92. doi: https://doi.org/10.1093/eurpub/ckr083 Crossref, Google ScholarJack K (2014) Hepatitis C: from discovery to eradication. Gastrointestinal Nursing 12(7): 28–35. doi: https://doi.org/10.12968/gasn.2014.12.7.26 Link, Google ScholarMauss SD, Hueppe C, John J et al. (2011) Estimating the likelihood of sustained virological response in chronic hepatitis C therapy. J Viral Hepat 18(4): 81–90. doi: https://doi.org/10.1111/j.1365-2893.2010.01372.x Crossref, Google ScholarMoss P, Foster G, British Infection Association (2015) NHS England Approved Update Statement - Treatment Access for Cirrhotic Patients. http://bit.ly/1APuZnY (accessed 12 June 2015) Google ScholarNHS England (2014) Interim Clinical Commissioning Policy Statement: Sofosbuvir + Daclatasvir/Ledipasvir +/ Ribivirin for defined patients with Hepatitis C April 2014. http://bit.ly/1taPoNp (accessed 1 June 2015) Google ScholarNational Institute for Health and Care Excellence (2015) NICE guidance recommends sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen) for treating hepatitis C. http://bit.ly/1LGT01W (accessed 4 June 2015) Google ScholarPublic Health England (2014). Hepatitis C in the UK: 2014. http://bit.ly/1oC1aBq (accessed 1 June 2015) Google ScholarPublic Health England (2015) Hepatitis C in London: annual review. http://bit.ly/1v4jelh (accessed 1 June 2015) Google ScholarVirlogeux V, Pradat P, Bailly F et al. (2014) Boceprevir and Telaprevir–based triple therapy for chronic hepatitis C: virological efficacy and impact on kidney function and model for end-stage liver disease score. J Viral Hepat 21(9): 98–107. doi: https://doi.org/10.1111/jvh.12237 Crossref, Google Scholar FiguresReferencesRelatedDetails 1 June 2015Volume 13Issue Sup5ISSN (print): 1479-5248ISSN (online): 2052-2835 Metrics History Published online 19 June 2015 Published in print 1 June 2015 Information© MA Healthcare LimitedAcknowledgementsI would like to thank Professor D Mutimer and Dr A El-SharkawyPDF download

Sa1114 Early Improvement of Liver Stiffness Measured by ARFI During Protease Inhibitor Based Triple Therapy for Chronic Hepatitis C

Sa1114 Early Improvement of Liver Stiffness Measured by ARFI During Protease Inhibitor Based Triple Therapy for Chronic Hepatitis C

Postmarketing surveillance of telaprevir-based triple therapy for chronic hepatitis C in Japan.

An observational postmarketing study was conducted to evaluate the real-world safety and efficacy of an NS3-4A protease inhibitor, telaprevir (TVR), in combination with pegylated interferon-α-2b (PEG IFN) and ribavirin (RBV), for patients with chronic hepatitis C (CHC). Here, we report an interim analysis of data from 3563 patients. Patients were treated with TVR, PEG IFN and RBV for 12 weeks, followed by PEG IFN and RBV for 12 weeks (triple therapy). Safety was evaluated throughout the 24-week treatment period. Risk factors for development of the three important adverse drug reactions (ADR), skin disorders, grade 3 anemia (hemoglobin level <8 g/dL) and serious renal dysfunction, were analyzed using a multivariate logistic regression model. Efficacy was assessed on the basis of sustained virological response (SVR) after treatment completion. Total and serious ADR were observed in 96.5% and 35.7% of patients, respectively. ADR related to skin disorders and anemia were frequently observed in this study and in the phase III clinical studies, whereas those related to serious renal dysfunction were new observations. Concomitantly, various predictive risk factors for development of the three important ADR were identified. The SVR rate was 87.7% in all patients. When patients were grouped by previous treatment history, SVR rates were 91.8% in naive patients, 91.0% in relapsers and 70.6% in non-responders. Although many ADR were observed, they can be controllable with appropriate risk management strategies based on the predictive risk factors for important ADR. Furthermore, the efficacy of the triple therapy was found to be favorable.

Safety and efficacy of partial splenic embolization in telaprevir-based triple therapy for chronic hepatitis C.

Pegylated-interferon/ribavirin (peg-IFN/RBV) therapy with a protease inhibitor is the standard therapy for genotype 1b chronic hepatitis C. Despite improving treatment outcomes, patients with thrombocytopenia are often difficult to treat because interferon commonly exacerbates thrombocytopenia. In this study, partial splenic embolization (PSE) was performed in patients with hypersplenism-induced thrombocytopenia to determine the effectiveness of this method as a potential treatment. Patients were pretreated with PSE and then received triple combination therapy. The safety and efficacy of PSE was evaluated. Eighteen patients were analyzed, including 12 patients with the interleukin 28B (IL28B) major genotype and 12 patients with the inosine triphosphatase (ITPA) major genotype. The median embolization rate with PSE was 70% (range: 40-85%). PSE increased the patients' platelet counts from 71.5×10(3) /μL (53-99×10(3) /μL) to 121.5×10(3) /μL (70-194×10(3) /μL; p=0.0002). The patients' platelet counts fluctuated above 50×10(3) /μL during the treatment. Specifically, the increase in the platelet count was significantly associated with the ITPA major genotype compared with the minor genotype (p=0.0057 at 2 weeks, p=0.0031 at 3 weeks, and p=0.0148 at 4 weeks). Adherence to peg-IFN-α2b was sufficient (1.38 μg/kg/week). The rapid viral response rate was 72.2% (13/18), the end of treatment response rate was 88.9% (16/18), and the sustained virological response (SVR) rate was 66.7% (12/18). The SVR rate for patients with the IL28B major genotype was 83.3% (10/12). No adverse effect due to PSE pretreatment was found in any patients. Furthermore, no patient discontinued treatment due to thrombocytopenia. PSE, in conjunction with triple combination therapy, is a useful and safe method to treat genotype 1b chronic hepatitis C patients with hypersplenism-induced thrombocytopenia.

Renal dysfunction associated with telaprevir-containing triple therapy for chronic hepatitis C: is early prediction possible?

Renal dysfunction has recently been described as a potential complication of tritherapy with telaprevir (TVR) in patients with chronic hepatitis C. This study aimed to identify predictive factors for and consequences of TVR-associated renal dysfunction. A retrospective-prospective study was carried out in 96 patients with chronic hepatitis C, genotype 1, treated with TVR-based tritherapy in 2012-2013, in whom regular serum creatinine measurements were performed during the first 12 weeks of treatment. The patients received standard doses of peginterferon, ribavirin and TVR (2250 mg/day). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. eGFR decreased significantly from baseline at weeks 4, 8 and 12, the mean maximum decrease being 22.0±23.6 ml/min, with a significant correlation between baseline and minimum eGFR (r=0.58, P<10), stronger between week 2 and minimum eGFR in the subgroup of 62 patients in whom creatinine measurement was performed at week 2. Thirteen patients had an eGFR below 60 ml/min during treatment. Age and baseline eGFR were independent predictors of eGFR below 60 ml/min in the entire population, and only week 2 eGFR when available. The decrease in haemoglobin was significantly correlated with the decrease in eGFR. Age, baseline haemoglobin and the maximum variation in eGFR were independent predictors for minimum haemoglobin. The patients with decreased eGFR had more severe anaemia, and received more blood transfusions and erythropoietin. Renal dysfunction regressed in all patients after stopping TVR. The reversible decrease in eGFR in patients receiving TVR-containing tritherapy can be predicted early, possibly allowing measures aimed at preventing anaemia.

Factors associated with sustained virological response in 24‐week telaprevir‐based triple therapy for chronic hepatitis C genotype 1b patients with the IL28B minor genotype

Single nucleotide polymorphisms (SNP) near the interleukin-28B (IL28B) gene affect the outcome of 24-week telaprevir-based triple therapy with telaprevir, pegylated interferon-α and ribavirin for chronic hepatitis C virus (HCV) genotype 1b patients. We aimed to identify factors associated with treatment outcomes in patients with the unfavorable minor IL28B SNP genotype, who have poor response to combination therapy. Pretreatment and on-treatment factors associated with sustained virological response (SVR) for 24-week telaprevir-based triple therapy were analyzed using multiple logistic regression analysis in 106 HCV genotype 1b patients with the minor IL28B SNP rs8099917 genotype (non-TT). Of the 106 non-TT patients, 62 (58.5%) achieved SVR. Of the 44 remaining patients, 22 experienced relapse, 13 experienced viral breakthrough and nine were non-responders. Pretreatment factors such as treatment-naïve/prior treatment response (P = 0.0041), high fasting serum low-density lipoprotein cholesterol (LDL-C) concentration (P = 0.0068) and low serum HCV RNA levels (P = 0.0088) were significantly and independently associated with SVR. On-treatment factors such as achievement of rapid virological response (RVR) were significantly and independently associated with SVR (P = 0.0001). For both pre- and on-treatment factors, treatment-naïve/prior treatment response (P = 0.0018), low pretreatment serum fasting LDL-C (P = 0.0062) and achieving RVR (P = 0.0021) were significantly and independently associated with SVR. In HCV genotype 1b patients with the minor IL28B SNP rs8099917 genotype, evaluating prior treatment response and achieving RVR and pretreatment serum fasting LDL-C concentrations were useful for predicting SVR achievement after 24-week telaprevir-based triple therapy.

Sa1314 Triple Therapy for Chronic Hepatitis C (HCV) Infection: Experience in an Urban Community Setting

Sa1314 Triple Therapy for Chronic Hepatitis C (HCV) Infection: Experience in an Urban Community Setting

Mo1313 Pyloroplasty Combined With Gastric Electrical Stimulation-Is This the Final Solution for Refractory Gastroparesis?

G A A b st ra ct s test, r = -0.49, p < 0.05). The levels of acyl-ghrelin and desacyl-ghrelin did not show a significant change, in contrast, the leptin level at 2 weeks after the start of treatment (5.3 ± 2.4 ng/ml) was lower than that of before (7.5 ± 3.3 ng/ml) with a significant difference (p < 0.01, paired t-test). [Conclusions] Telaprevir-based triple therapy for chronic hepatitis C patients caused loss of food intake and body weight, and worsened GE. The deterioration of GE is one of the major causes of loss of food intake. The use of drugs to improve GE could avoid the loss of appetite and body weight, which might result in raising the rate of accomplishing treatment and sustained viral response.

Sa1318 Improvement of Liver Stiffness Measured by ARFI During Telaprevir-Based Triple Therapy for Chronic Hepatitis C

Sa1318 Improvement of Liver Stiffness Measured by ARFI During Telaprevir-Based Triple Therapy for Chronic Hepatitis C

Boceprevir and telaprevir‐based triple therapy for chronic hepatitis C: virological efficacy and impact on kidney function and model for end‐stage liver disease score

Triple therapy using telaprevir or boceprevir [hepatitis C virus (HCV)-NS3/NS4A protease inhibitors (PI)] in association with PEG-IFN/ribavirin has recently become the new standard of care (SOC) for treatment of HCV genotype 1 patients. Our objective was to assess the efficacy and tolerance of triple therapy in routine clinical practice. A total of 186 consecutive HCV patients initiating triple therapy were enrolled in a single centre study. Clinical, biological and virological data were collected at baseline and during follow-up as well as tolerance and side effect details. Among 186 HCV patients initiating triple therapy, 69% received telaprevir and 31% boceprevir. Sixty-one per cent of patients had cirrhosis. The overall extended rapid virological response (eRVR) rate and sustained virological response (SVR) rate were 57.0% and 59.7%, respectively. IL28B CC phenotype was associated with increased probability of achieving eRVR and SVR, whereas previous non-response was associated with low eRVR and SVR rates. The SVR rate increased from 30.8% in previously non-responders to 59.1% in partial non-responders and 75% in relapsers. SVR rate in naive patients was 62.5%. Glomerular filtration rate assessed by MDRD after 12 weeks of therapy was significantly reduced for both PI (P < 0.001). The model for end-stage liver disease (MELD) score was significantly increased at W12 for telaprevir (P = 0.008) and at W24 for boceprevir (P = 0.027). PI-based triple therapy leads to high rates of virological response even in previously non-responder patients. Renal function after triple therapy is impaired as well as MELD score in all patients. Cautious clinical monitoring should focus not only on haematological and dermatological side effects but also on renal function.

CP-007 Haematological side effects of telaprevir-based triple therapy in patients with chronic hepatitis C monoinfection

BackgroundIt is necessary to know the impact of the haematological toxicity in patients starting treatment with triple therapy for chronic hepatitis C in daily clinical practice.PurposeTo check the haematological side...

Therapeutic drug monitoring of telaprevir in chronic hepatitis C patients receiving telaprevir-based triple therapy is useful for predicting virological response

This prospective, pharmacokinetic study was done to investigate the impact of telaprevir plasma trough concentration (Ctrough) in the early stage of treatment on the response to telaprevir-based triple therapy for chronic hepatitis C patients. Participants were 70 chronic hepatitis C patients infected with genotype 1. All patients received 12 week triple therapy that included telaprevir (2250 mg/day), pegylated interferon-α2b (pegylated-IFNα2b) (60-150 μg/week) and ribavirin (600-1000 mg/day) followed by a 12 week dual therapy that included pegylated-IFNα2b and ribavirin. Plasma telaprevir Ctrough was determined by a validated assay using HPLC at days 3, 7 and 14. The study was registered as a clinical trial on the University Hospital Medical Information Network (ID 000009656). The rates of undetectable hepatitis C virus RNA at week 4 [rapid virological response (RVR)] and at 24 weeks after therapy [sustained virological response (SVR)] were 71.4% and 82.9%, respectively. Of the patients with RVR, 90% achieved SVR. The mean telaprevir Ctrough levels at days 3, 7 and 14 of SVR patients (2.748, 2.733 and 2.999 μg/mL, respectively) were significantly higher than those of non-SVR patients (1.616, 1.788 and 2.314 μg/mL, respectively) (all P < 0.05). Multiple logistic regression analysis of possible predictors of SVR extracted higher telaprevir Ctrough at day 3 (OR 1.012 by 0.001 μg/mL, P < 0.0001) and interleukin 28B (rs8099917) TT allele (OR 6.16 versus non-TT alleles, P < 0.0001). Therapeutic drug monitoring of telaprevir in the early stage of treatment is useful in clinical practice for predicting the virological response of patients receiving telaprevir-based triple therapy.

Optimal dosage of telaprevir in triple therapy for chronic hepatitis C in view of virological response and anemic severity

Optimal dosage of telaprevir in triple therapy for chronic hepatitis C in view of virological response and anemic severity

Telaprevir-based triple therapy for chronic hepatitis C patients with advanced fibrosis: a prospective clinical study

Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis-related complications. To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients with advanced fibrosis in a clinical practice setting. This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3-4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin (RBV). The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment-naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG-IFNα2b (≥1.2 μg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight-adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection. The great gain in the SVR rate by telaprevir-based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment-naïve and prior relapse.

Dermatological side‐effects of telaprevir‐based triple therapy for chronic hepatitis C in phase III trials in Japan

Telaprevir-based triple therapy is highly effective for chronic hepatitis C. However, concern has been expressed over the high frequency and severity of its dermatological side-effects compared with those associated with peginterferon (PEG-IFN) and ribavirin (RBV) therapy. Thus, here, we evaluated the dermatological adverse reactions of telaprevir-based triple therapy in Japanese multicenter phase III clinical trials in an attempt to characterize the dermatological side-effects and establish appropriate management plans. In these trials, 126 treatment-naïve patients and 141 treatment-failure patients were administrated telaprevir, PEG-IFN-α-2b and RBV for 12weeks followed by PEG-IFN-α-2b and RBV for another 12weeks (T12/PR24 group), and 63 treatment-naïve patients were administrated PEG-IFN-α-2b and RBV for 48weeks (PR48 group). Dermatological adverse reactions developed in over 80% patients in both groups, and most of them were grade 1 or 2. In the T12/PR24 group, there were more grade 2 or grade 3 events, and the time to onset was earlier than that in the PR48 group. Most reactions could be managed with topical corticosteroids and oral antihistamines, and the rates of discontinuation due to dermatological reactions were not high even in the T12/PR24 group. In the T12/PR24 group, however, two cases of Stevens-Johnson syndrome and one case of drug rash with eosinophilia and systemic symptoms, which corresponds to drug-induced hypersensitivity syndrome in Japan, were reported. For appropriate treatments of individual dermatological adverse reactions, the judgment of discontinuation of antiviral drugs and treatment based on the severity are extremely important in this triple therapy.

C型慢性肝炎に対する3剤併用治療中に発症したアメーバ性肝膿瘍の1例

症例は58歳の男性．1型，高ウイルス量のC型慢性肝炎に対し，3剤併用療法を開始した．投与1カ月後にはHCVRNAは検出されず，副作用もなく経過していたが，投与開始約4カ月目に食思不振，発熱，右季肋部痛が出現した．白血球数9,100/μl，CRP 15.17 mg/dlと炎症所見を呈し，超音波検査，断層撮影検査にて多発性の肝膿瘍を認めた．細菌性肝膿瘍を疑い，抗生剤の投与を開始したが，解熱は得られず，肝膿瘍は増大し，一部は腹腔へ膨出した．入院時の血清アメーバ抗体価が高値を示し，肝膿瘍の穿刺内容液は粘稠で白色～薄黄緑色のクリーム状を呈した．穿刺内容液中に赤痢アメーバ虫体を確認し，アメーバ性肝膿瘍と診断した．メトロニダゾールの投与ならびに経皮的ドレナージにて速やかな解熱，膿瘍の縮小が得られた．患者は3剤併用治療の開始5カ月前に原因不明の下痢を来し，大腸内視鏡検査にて大腸に多発するアフタ性病変が認められていたことが後に判明した．遡及的診断ではアメーバ腸炎と考えられたが，感染経路は不明であった．C型慢性肝炎に対する3剤併用療法時の併発感染症疾患のひとつとしてアメーバ性肝膿瘍も念頭に置く必要がある．アメーバ性肝膿瘍の迅速な診断，問診の重要性があらためて認識された．