Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension

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• 作者：Mattias Mandorfer¹ ; ² ; ^&dagger ; ; Karin Kozbial¹ ; ^&dagger ; ; Philipp Schwabl¹ ; ² ; Clarissa Freissmuth¹ ; Ré ; my Schwarzer¹ ; ² ; Rafael Stern¹ ; David Chromy¹ ; ² ; Albert Friedrich Stä ; ttermayer¹ ; Thomas Reiberger¹ ; ² ; Sandra Beinhardt¹ ; Wolfgang Sieghart¹ ; ² ; Michael Trauner¹ ; Harald Hofer¹ ; Arnulf Ferlitsch¹ ; ² ; Peter Ferenci¹ ; Markus Peck-Radosavljevic¹ ; ² ; ^{markus.peck@meduniwien.ac.at" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HVPG ; hepatic venous pressure gradient ; ACLD ; advanced chronic liver disease ; HCV ; hepatitis C virus ; PegIFN/RBV ; pegylated interferon and ribavirin ; SVR ; sustained virologic response ; IFN ; interferon ; SOF ; sofosbuvir ; TE ; transient elastography ; BL ; baseline ; MELD ; model for end-stage liver disease ; CP ; Child-Pugh ; SMV ; simeprevir ; DCV ; daclatasvir ; LDV ; ledipasvir ; NSBB ; non-selective beta blocker ; CSPH ; clinically significant portal hypertension ; NPV ; negative predictive value ; PPV ; positive
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：65
• 期：4
• 页码：692-699
• 全文大小：834 K

文摘

We aimed to investigate the impact of sustained virologic response (SVR) to interferon (IFN)-free therapies on portal hypertension in patients with paired hepatic venous pressure gradient (HVPG) measurements.

Methods

One hundred and four patients with portal hypertension (HVPG ⩾6 mmHg) who underwent HVPG and liver stiffness measurement before IFN-free therapy (baseline [BL]) were retrospectively studied. Among 100 patients who achieved SVR, 60 patients underwent HVPG and transient elastography (TE) after antiviral therapy (follow-up [FU]).

Results

SVR to IFN-free therapies significantly decreased HVPG across all BL HVPG strata: 6–9 mmHg (BL: 7.37 ± 0.28 vs. FU: 5.11 ± 0.38 mmHg; −2.26 ± 0.42 mmHg; p <0.001), 10–15 mmHg (BL: 12.2 ± 0.4 vs. FU: 8.91 ± 0.62 mmHg; −3.29 ± 0.59 mmHg; p <0.001) and ⩾16 mmHg (BL: 19.4 ± 0.73 vs. FU: 17.1 ± 1.21 mmHg; −2.3 ± 0.89 mmHg; p = 0.018).

In the subgroup of patients with BL HVPG of 6–9 mmHg, HVPG normalized (<6 mmHg) in 63% (12/19) of patients, while no patient progressed to ⩾10 mmHg. Among patients with BL HVPG ⩾10 mmHg, a clinically relevant HVPG decrease ⩾10% was observed in 63% (26/41); 24% (10/41) had a FU HVPG <10 mmHg.

Patients with Child-Pugh stage B were less likely to have a HVPG decrease (hazard ratio [HR]: 0.103; 95% confidence interval [CI]: 0.02–0.514; p = 0.006), when compared to Child-Pugh A patients. In the subgroup of patients with BL CSPH, the relative change in liver stiffness (per %; HR: 0.972; 95% CI: 0.945–0.999; p = 0.044) was a predictor of a HVPG decrease ⩾10%.

The area under the receiver operating characteristic curve for the diagnosis of FU CSPH by FU liver stiffness was 0.931 (95% CI: 0.865–0.997).

Conclusions

SVR to IFN-free therapies might ameliorate portal hypertension across all BL HVPG strata. However, changes in HVPG seemed to be more heterogeneous among patients with BL HVPG of ⩾16 mmHg and a HVPG decrease was less likely in patients with more advanced liver dysfunction. TE might be useful for the non-invasive evaluation of portal hypertension after SVR.

Lay summary

We investigated the impact of curing hepatitis C using novel interferon-free treatments on portal hypertension, which drives the development of liver-related complications and mortality. Cure of hepatitis C decreased portal pressure, but a decrease was less likely among patients with more pronounced hepatic dysfunction. Transient elastography, which is commonly used for the non-invasive staging of liver disease, might identify patients without clinically significant portal hypertension after successful treatment.