Research ArticleSustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension
Graphical abstract
Introduction
Portal pressure, assessed by hepatic venous pressure gradient (HVPG) measurement, drives the development of liver-related complications and mortality in patients advanced chronic liver disease (ACLD) [1], [2], [3]. Since a decrease in HVPG translates into a clinically meaningful benefit, it is an acceptable surrogate endpoint [1], [2], [3].
Hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PegIFN/RBV) has been shown to ameliorate portal hypertension in patients with HCV-monoinfection [4], [5] and HIV/HCV-coinfection [6]. In patients with a HVPG ⩾12 mmHg and sustained virologic response (SVR) to PegIFN/RBV, a HVPG decrease ⩾20% or to <12 mmHg was observed in 82% [4] and 71% [5] of patients, indicating an important change in the natural history of the disease [1], [2], [3]. Together with modest efficacy, substantial rates of serious adverse events greatly limited the use of interferon (IFN)-based therapies in patients with portal hypertension [7], [8]. In contrast, IFN-free regimens are highly effective and generally well tolerated, even in patients with cirrhosis [9]. In addition to improvement in liver function [10], [11], [12], [13], [14], HCV eradication was associated with an increase in platelet count, which was paralleled by a decrease in liver stiffness, suggesting an anti-portal hypertensive effect [11]. However, in a recent study by Afdhal and co-workers [15], only 24% of HCV-monoinfected patients with a HVPG ⩾12 mmHg treated with 48 weeks of sofosbuvir (SOF)/RBV achieved a HVPG decrease ⩾20% and none of the patients had a follow-up (FU) HVPG <12 mmHg.
We aimed to (i) investigate the impact of SVR to IFN-free therapies on HCV-induced portal hypertension and (ii) elucidate predictors of HVPG decrease, as well as to (iii) evaluate the usefulness of transient elastography (TE) for the non-invasive evaluation of portal hypertension after SVR.
Section snippets
Study design and population
One hundred and four patients with portal hypertension (HVPG ⩾6 mmHg [8]) who underwent HVPG and TE before IFN-free therapy (baseline [BL]) were retrospectively studied (Fig. 1).
The effect of SVR on portal pressure was investigated in patients with SVR who also underwent FU HVPG and TE after IFN-free therapy (group A; n = 60). To demonstrate the generalizability of our results, we included a second group (group B; n = 40), comprising all patients who achieved SVR, but did not undergo FU HVPG
Results
A comparison of characteristics of patients with suspected/confirmed ACLD due to hepatitis C who underwent IFN-free therapy and were included or excluded from the study is shown in Supplementary Table 1.
Discussion
With the availability of highly effective and well tolerated IFN-free regimens, focus of attention has shifted to the regression of liver fibrosis and portal hypertension after HCV eradication in patients with HCV-induced cirrhosis [20], [21].
Even after achieving SVR, patients with CSPH remain at considerable risk for complications related to portal hypertension [22]. Recent observations [23] suggest that portal hypertension may persist despite normalization of liver function tests. On the
Conflict of interest
M.M. received honoraria for consulting from Janssen, payments for lectures from Boehringer Ingelheim, Bristol-Myers Squibb, Janssen and Roche, as well as travel support from AbbVie, Gilead, MSD and Roche. K.K. received travel support from AbbVie, Bristol-Myers Squibb and Gilead. P.S. received payments for lectures from Roche and travel support from Janssen and Roche. C.F. received travel support from Gilead and Janssen. R.ST. received travel support from AbbVie. A.F.S. received honoraria for
Authors’ contributions
All authors contributed either to research design (M.M., K.K., T.R., H.H. and P.F), or the acquisition (M.M., K.K., P.S., C.F., R.S.C., R.ST., D.C., A.F.S., T.R., S.B., W.S., H.H., A.F., P.F. and M.P.), analysis (M.M.) or interpretation (all authors) of data. M.M. and K.K. drafted the manuscript, which was then critically revised by all other authors. All authors gave approval of the submitted version of the manuscript.
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These authors contributed equally as joint first authors.