Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus

<div><p>Background and Aim</p><p>To investigate the impact of a sustained virological response (SVR) to hepatitis C virus (HCV) treatment on liver stiffness (LS).</p><p>Methods</p><p>LS, measured by transient elastography (FibroScan), demographic and laboratory data of patients treated with interferon (IFN)-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment) were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant.</p><p>Results</p><p>The median age of the patients (n = 100) was 60 years [IQR (interquartile range) 54–64); 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25–18.60) pre-treatment to 7.60 kPa (IQR: 5.60–12.38) at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60%) of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 –-0.38) versus -2.40 kPa (IQR: -7.70 –-0.23), p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98–0.5) during a median follow-up time of 1.17 (IQR: 0.88–1.63) years, which was not a statistically significant decrease (p = 0.99).</p><p>Conclusions</p><p>LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease.</p></div

Model of changes in liver stiffness overtime.

<p>This model graph shows a percentage decrease in liver stiffness from pre-treatment to post-SVR24. The initial decline in liver stiffness is most likely due to regression of liver inflammation. After SVR24 there was little change in liver stiffness over time as indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159413#pone.0159413.g003" target="_blank">Fig 3</a>.</p

Changes in Liver Stiffness (pre-treatment to SVR24): IFN vs IFN-free Regimens.

<p>Changes in Liver Stiffness (pre-treatment to SVR24): IFN vs IFN-free Regimens.</p

Comparison of Pre-treatment and SVR24 Clinical Laboratory Values.

<p>Comparison of Pre-treatment and SVR24 Clinical Laboratory Values.</p

Median Change in LS from Pre-treatment to SVR24 Stratified by Pre-treatment Estimated Fibrosis Stage using FibroScan.

<p>Median Change in LS from Pre-treatment to SVR24 Stratified by Pre-treatment Estimated Fibrosis Stage using FibroScan.</p

Pre-treatment versus SVR24 liver stiffness.

<p>Comparison of pre-treatment to SVR24 LS in kPa stratified by METAVIR fibrosis stage with (A) depicting median and interquartile ranges for pre-treatment scores and (B) depicting median and interquartile ranges for SVR24 scores. The vertical axis is the liver stiffness in kPa and the horizontal axis is the METAVIR fibrosis stage and the number of patients in each fibrosis stage. The top and bottom boxes represent interquartile ranges (interquartile 1 and interquartile 3 respectively). The lines through the boxes represent median values. The whiskers at the end of the box represent the maximum and minimum values.</p

Liver stiffness changes during follow-up post-SVR24.

<p>The graph shows FibroScan scores in 56 patients who had an additional measurement afterSVR24. 0 on the horizontal axis indicates SVR24. Stiffness decreased over time, but the change was not significant as demonstrated by linear regression with a p-value = 0.9. The colors indicate the pre-treatment fibrosis stage as estimated from the LS score, green (F0-1), yellow (F2), orange (F3), red (F4).</p

Percent changes of pre-treatment versus SVR24 liver stiffness liver.

<p>The figure shows the median percent change of LS for each METAVIR fibrosis stage stratified by the pre-treatment LS score.</p

Estimated Fibrosis Stage using Fibroscan at SVR24 Stratified by the Pre-treatment Stiffness Score.

<p>Estimated Fibrosis Stage using Fibroscan at SVR24 Stratified by the Pre-treatment Stiffness Score.</p

Pre-treatment Patient Characteristics.

<p>Pre-treatment Patient Characteristics.</p