Improvement of liver stiffness in patients with hepatitis C virus infection who received direct‐acting antiviral therapy and achieved sustained virological response

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yoshitsugu; Kataoka, Saki; Hashinokuchi, Shinichi

doi:10.1111/jgh.13788

Cited by 99 publications

(91 citation statements)

References 29 publications

(50 reference statements)

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“…For LS evaluation, the transient elastography method was used in the studies described above and, according our knowledge, there are insufficient trials in which the SWE method was used in patients with antiviral treatment. In the Tada et al study, the results of 210 patients treated with daclatasvir and asunaprevir were analyzed, and it was found that the average LS decreased by 1.4 kPa between baseline and EOT and 2.6 kPa between baseline and FU24, which is consistent with our results [40]. It should be noted that the type of DAA regimen used made no difference.…”

Section: Discussionsupporting

confidence: 81%

“…In the Miyaki et al study, they found that in patients who achieved SVR, a reduction in the AFP level, ALT activity, and platelet count were observed [46]. In a larger group of patients, in a more detailed analysis, this observation was confirmed by Tada et al [40]. In our group of patients, we found improvement in albumin and ALT levels.…”

Section: Discussionsupporting

confidence: 79%

“…In our group of patients, we found improvement in albumin and ALT levels. However, the level of platelets did not change significantly, which is in contrast to some of the previous studies [35,40]. Probably due to the transient hyperbilirubinemia associated with the treatment (OMB/PRV/rtv ± DSV ± RBV), a statistically significant decrease in the level of bilirubin between baseline and FU24 and FU96 was observed.…”

Section: Discussioncontrasting

confidence: 54%

“…In the previously mentioned Arima et al study and the Chekuri et al study, no further decrease in LS was observed after treatment in long-term follow-up-no change between in LS between 1 and 2 years of follow-up [35,37]. Conversely, in the Tada et al study, as mentioned above, an LS decrease was also observed 24 weeks after therapy completion [40]. In the Taachi et al trial in patients undergoing simeprevir combined with pegINF and RBV, similar results were obtained (after FU24 LS decreased by 14%) using the acoustic radiation force impulse elastography technique [41].…”

Section: Discussionmentioning

confidence: 45%

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Effect of HCV Core Antigen and RNA Clearance during Therapy with Direct Acting Antivirals on Hepatic Stiffness Measured with Shear Wave Elastography in Patients with Chronic Viral Hepatitis C

Łucejko

Flisiak

2018

Applied Sciences

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Abstract:To assess a combination of novel measures of therapeutic success in the treatment of chronic hepatitis C (CHC) infection, we evaluated liver stiffness (LS) with shear wave elastography and hepatitis C virus core antigen (HCVcAg) concentrations. We followed 34 patients during and after treatment with direct acting antivirals. All patients achieved a sustained virologic and serologic response and a significant increase of albumin levels. Decreases of alanine aminotransferase (ALT) activity and alpha-fetoprotein (AFP) level were observed during the treatment and follow-up period. A significant decrease in LS was observed between baseline, end of treatment (EOT), and at 24-and 96-week post-treatment follow-up. LS decline between EOT and 96-week follow-up (FU96) was observed in 79% of patients. Significant LS changes were seen in patients with advanced fibrosis, particularly in cirrhotics and in patients with ALT exceeding 100 IU/mL. There was a positive correlation between ALT activity and LS changes at the baseline versus FU96. A negative correlation was demonstrated between individual HCVcAg baseline concentrations and reduction of LS at the baseline versus FU96. In conclusion, we observed that LS significantly declined during and after antiviral treatment. It was accompanied by improvement in some liver function measures, and disappearance of both HCVcAg and HCV ribonucleic acid (HCV RNA).

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 79%

Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 45%

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Effect of HCV Core Antigen and RNA Clearance during Therapy with Direct Acting Antivirals on Hepatic Stiffness Measured with Shear Wave Elastography in Patients with Chronic Viral Hepatitis C

Łucejko

Flisiak

2018

Applied Sciences

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“…However, LS measurements may also be affected by factors other than fibrosis stage, for example, inflammatory activity,28, 29 and intrahepatic pressure. There are a few studies demonstrating a decrease in LS in patients on eradication of HCV where both pre‐ and post‐treatment ARFI elastography assessments were available 30. It is probable that such reduction in ARFI elastography values indicates not only the improvement in fibrosis but also inflammation in the liver because of treatment.…”

Section: Discussionmentioning

confidence: 99%

Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct‐acting antivirals

et al. 2017

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Background and AimPredictive factors for hepatocarcinogenesis following eradication of hepatitis C virus by direct‐acting antivirals (DAAs) are unknown. The aim of the study was to investigate the relationships between liver stiffness (LS) using acoustic radiation force impulse (ARFI) erastograghy and the development of hepatocellular carcinoma (HCC) in patients who achieved sustained virological response (SVR) treated with DAA.MethodsIn this prospective study, we enrolled 263 hepatitis C patients with SVR who underwent ARFI before DAA treatment. Thirty patients had previous HCC.ResultsThe median LS value according to ARFI measurements was 1.34 m/s (range: 0.67–4.35). During the follow‐up period (median: 18.1 months), development of HCC occurred in 19 patients (7.2%; HCC occurrence in 7 patients and HCC recurrence in 12 patients). By multivariate Cox regression analysis, HCC history (hazard ratio [HR]: 10.634; 95% confidence interval [CI]: 4.13–27.37; P = 0.001), older age (HR: 4.638; 95% CI: 1.63–13.61; P = 0.004) and higher total bilirubin levels (HR: 4.189; 95% CI: 1.66–10.60; P = 0.002) were independent predictors for the development of HCC, and higher LS value (≥1.73 m/s) at baseline was an independent predictor for HCC occurrence (HR: 8.350; 95% CI: 1.62–43.09; P = 0.011). The cumulative recurrence of HCC was statistically similar according to the degree of LS in patients who were previously treated for HCC.ConclusionThe LS value at baseline is useful for predicting HCC occurrence. Thus, even if SVR is achieved, patients with higher LS at baseline must be followed carefully for HCC occurrence.

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Morphometry Confirms Fibrosis Regression From Sustained Virologic Response to Direct‐Acting Antivirals for Hepatitis C

Pan

Bao

et al. 2018

Hepatology Communications

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Sustained virologic response (SVR) after direct‐acting antiviral (DAA) therapy for chronic hepatitis C results in significant decreases in liver stiffness measured by transient elastography (TE). The aim of this study was to clarify if TE can guide post‐SVR management in patients with advanced fibrosis or cirrhosis prior to treatment as current guidelines are unclear on the role of TE after SVR. In total, 84 patients with hepatitis C virus and advanced fibrosis or cirrhosis and from a single center underwent DAA treatment and achieved SVR. Overall, 62% had improved liver stiffness that was consistent with regression of at least one stage of fibrosis. In the cirrhosis group, 48% showed fibrosis regression by at least two stages by TE (<9.5 kPa). In the F3 fibrosis group, 39% regressed by at least two stages (<7 kPa). The median time from SVR to regression by TE was 1 year. Fifteen patients with liver biopsies prior to SVR underwent a biopsy after SVR; 13 of these patients had improved liver stiffness (to <9.5 kPa). The post‐SVR liver biopsies of only 4 patients showed F1‐F2 while 11 patients showed F3‐F4; however, morphometry of the first 11 biopsied patients revealed that 10 patients had an average 46% decrease in collagen content. Conclusion: This is the first DAA study that also has paired liver biopsies showing fibrosis regression. After SVR is achieved, improvements in liver stiffness measured by TE are seen in a majority of patients with advanced fibrosis/cirrhosis within 2 years. TE improvements are overstated when compared to histologic staging but confirmed with morphometric analysis. It is unclear whether TE following SVR can reliably predict when patients no longer require advanced fibrosis/cirrhosis monitoring after SVR.

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Improvement of liver stiffness in patients with hepatitis C virus infection who received direct‐acting antiviral therapy and achieved sustained virological response

Abstract: These results suggest that early improvement of liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis.

Cited by 99 publications

References 29 publications

Effect of HCV Core Antigen and RNA Clearance during Therapy with Direct Acting Antivirals on Hepatic Stiffness Measured with Shear Wave Elastography in Patients with Chronic Viral Hepatitis C

Effect of HCV Core Antigen and RNA Clearance during Therapy with Direct Acting Antivirals on Hepatic Stiffness Measured with Shear Wave Elastography in Patients with Chronic Viral Hepatitis C

Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct‐acting antivirals

Morphometry Confirms Fibrosis Regression From Sustained Virologic Response to Direct‐Acting Antivirals for Hepatitis C

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