Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients

Sasaki, Reina; Meyer, Keith; Moriyama, Mitsuhiko; Kato, Naoya; Yokosuka, Osamu; Ray, Ratna B.; Aurora, Rajeev

doi:10.1002/jmv.25310

Cited by 20 publications

(24 citation statements)

References 40 publications

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“…It is possible that the results after achieving SVR with interferon-free therapy may be different from those after achieving SVR with interferon-containing treatment because the population is aging in Japan (6) and rapid immunological changes are also observed (11). Unexpectedly high rates of early tumor recurrence and occurrence have been reported in patients with HCV-related HCC undergoing interferon-free therapy (12,13), although they are a controversial (14).…”

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confidence: 99%

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

et al. 2019

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“…The unexpected, peculiar fluctuating profile of psoriasis lesions in DAA‐cured HCV patients that has emerged from this clinical study cannot easily be interpreted using current knowledge. Much evidence suggests that psoriasis has a T‐lymphocyte‐based immunopathogenesis, with an important role played by a dysregulation of complex interactions and balances among different cytokines in the tissue lesions . Chronic HCV infection is known to quite extensively affect the innate immune response, with an upregulation of interferon‐stimulated genes (ISG) both at intrahepatic and peripheral levels .…”

Section: Discussionmentioning

confidence: 99%

“…Much evidence suggests that psoriasis has a T‐lymphocyte‐based immunopathogenesis, with an important role played by a dysregulation of complex interactions and balances among different cytokines in the tissue lesions . Chronic HCV infection is known to quite extensively affect the innate immune response, with an upregulation of interferon‐stimulated genes (ISG) both at intrahepatic and peripheral levels . Notably, a very recent study showed dynamic changes of the innate immune response in HCV patients under DAA treatment, with decreased levels of circulating ISG‐related chemokines at week 2 of therapy followed by a significant increase at weeks 4/8 .…”

Section: Discussionmentioning

confidence: 99%

“…HCV infection is known to quite extensively affect the innate immune response, with an upregulation of interferon-stimulated genes (ISG) both at intrahepatic and peripheral levels. 6,7 Notably, a very recent study showed dynamic changes of the innate immune response in HCV patients under DAA treatment, with decreased levels of circulating ISG-related chemokines at week 2 of therapy followed by a significant increase at weeks 4/8. 8,9 Thus, the very potent and rapid effect of the DAA cure may provoke changes in the innate im- during and after DAA treatment with the hope for obtaining important information about the pathogenesis of cutaneous psoriasis and possible new routes of therapeutic approaches for its cure.…”

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confidence: 99%

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Outcome of cutaneous psoriasis in hepatitis C virus‐infected patients treated with Direct‐Acting Antiviral therapy

Cacciola

Borgia

Filomia

et al. 2019

Journal of Viral Hepatitis

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Apart from chronic liver disease, hepatitis C virus (HCV) may be responsible for several extra‐hepatic manifestations. Its involvement in psoriasis development is still controversial. The aim of this study was to evaluate the possible effect of anti‐HCV direct‐acting antiviral (DAA) treatment on cutaneous psoriasis. Thirty‐seven consecutive HCV patients with cutaneous psoriasis underwent efficacious DAA treatment, and all of them were efficiently cured as shown by HCV RNA negativity 24 weeks after stopping therapy (PT24W). An expert dermatologist evaluated the skin lesions at baseline, end of treatment (EOT) and PT24W using the psoriasis area severity index (PASI) scoring system. The impact on quality of life was measured with the Dermatologic Quality of Life Index (DLQI). Six patients had a stable disease throughout the study period, whereas 31/37 patients (83.8%) showed a significant improvement of the skin lesions at EOT (P < .0001). However, 24 of these 31 patients (77.4%) had a dramatic worsening of the psoriatic lesions at PT24W compared with EOT (P < .001), with lesion severity comparable to baseline. The outcome of psoriasis during and after treatment was independent of baseline PASI score, age, sex, HCV genotype, liver disease stage and of the presence of arterial hypertension, diabetes and autoimmune diseases. In conclusion, DAA‐based HCV cure has only a transient effect on skin lesions of patients with concomitant cutaneous psoriasis.

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“…Inflammation associated with chronic HCV infection accelerates hepatocyte damage, and could affect liver uptake and reduce drug metabolizing enzyme activity, resulting in decreased clearance of drugs that undergo hepatic metabolism . HCV infection rapidly clears from the plasma and liver with DAA therapy . In another substudy of A5329, the early plasma and intrahepatic kinetics of HCV were assessed over the first week of starting OBV/PTV/r + DSV.…”

Section: Discussionmentioning

confidence: 99%

Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus‐1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub‐study A5334s

Venuto

Cramer

Rosenkranz

et al. 2019

Brit J Clinical Pharma

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Aims: AIDS Clinical Trials Group study A5334s evaluated the pharmacokinetics of raltegravir before and during combined administration of ombitasvir, paritaprevir/ritonavir, plus dasabuvir (OBV/PTV/r + DSV) and weight-based ribavirin in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected adults.The pharmacokinetics of OBV/PTV/r + DSV during raltegravir coadministration were also characterized. Methods:Adults living with HIV/HCV coinfection receiving steady-state raltegravir (400 mg twice daily) with 2 nucleos(t)ide analogues were enrolled. Pharmacokinetics of raltegravir were assessed prior to HCV therapy, and 4 weeks later following initiation of OBV/PTV/r (25/150/100 mg) once daily + DSV (250 mg) twice daily. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were used to compare the following: raltegravir pharmacokinetics with HCV therapy (week 4) vs before HCV therapy (week 0); OBV/PTV/r and DSV pharmacokinetics vs historical healthy controls; raltegravir pharmacokinetics at week 0 vs historical control adults living with HIV. Results: Eight of 11 participants had decreased raltegravir exposures after initiation of HCV therapy. The GMRs (90% CI) for maximum concentration and area under the concentration-time curve of raltegravir with vs without HCV therapy were 0.68 (0.38-1.19) and 0.82 (0.58-1.17), respectively. Comparing OBV/PTV/r pharmacokinetics in healthy controls, A5334s study participants demonstrated generally lower maximum concentration and area under the concentration-time curve values by 41-82% and 4-73%, respectively. Raltegravir exposures tended to be higher in A5334s study participants compared to adults living with HIV.

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Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients

Cited by 20 publications

References 40 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

Outcome of cutaneous psoriasis in hepatitis C virus‐infected patients treated with Direct‐Acting Antiviral therapy

Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus‐1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub‐study A5334s

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