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

被引:236
作者
Mandorfer, Mattias [1 ,2 ]
Kozbial, Karin [1 ]
Schwabl, Philipp [1 ,2 ]
Freissmuth, Clarissa [1 ]
Schwarzer, Remy [1 ,2 ]
Stern, Rafael [1 ]
Chromy, David [1 ,2 ]
Staettermayer, Albert Friedrich [1 ]
Reiberger, Thomas [1 ,2 ]
Beinhardt, Sandra [1 ]
Sieghart, Wolfgang [1 ,2 ]
Trauner, Michael [1 ]
Hofer, Harald [1 ]
Ferlitsch, Arnulf [1 ,2 ]
Ferenci, Peter [1 ]
Peck-Radosavljevic, Markus [1 ,2 ]
机构
[1] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria
[2] Med Univ Vienna, Vienna Hepat Hemodynam Lab, Vienna, Austria
关键词
Cirrhosis; Hepatitis C; Liver fibrosis; Portal hypertension; Viral hepatitis; VENOUS-PRESSURE GRADIENT; SOFOSBUVIR PLUS RIBAVIRIN; INDICATE INCREASED RISK; CHRONIC HEPATITIS-C; LIVER FIBROSIS; ANTIVIRAL THERAPY; GENOTYPE; CIRRHOSIS; INFECTION; LEDIPASVIR;
D O I
10.1016/j.jhep.2016.05.027
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: 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. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:692 / 699
页数:8
相关论文
共 34 条
[1]   Measurement of Portal Pressure [J].
Abraldes, Juan G. ;
Sarlieve, Philippe ;
Tandon, Puneeta .
CLINICS IN LIVER DISEASE, 2014, 18 (04) :779-+
[2]   HCV ERADICATION RESULTS IN REDUCTION OF HEPATIC VENOUS PRESSURE GRADIENT 48 WEEKS AFTER END OF TREATMENT; FINAL RESULTS OF THE STUDY OF SOFOSBUVIR PLUS RIBAVIRIN IN PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION [J].
Afdhal, N. ;
Asselah, T. ;
Everson, G. T. ;
Bosch, J. ;
De-Oertel, S. ;
Brainard, D. M. ;
McHutchison, J. G. ;
Yang, Y. ;
Watt, K. D. ;
Curry, M. ;
Gane, E. .
JOURNAL OF HEPATOLOGY, 2016, 64 :S221-S222
[3]   EFFECT OF LONG TERM VIRAL SUPPRESSION WITH SOFOSBUVIR plus RIBAVIRIN ON HEPATIC VENOUS PRESSURE GRADIENT IN HCV-INFECTED PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION [J].
Afdhal, N. ;
Everson, G. T. ;
Calleja, J. L. ;
McCaughan, G. ;
Bosch, J. ;
Denning, J. ;
Brainard, D. M. ;
McHutchison, J. G. ;
Brandt-Sarif, T. ;
An, D. ;
Charlton, M. ;
Reddy, K. R. ;
Asselah, T. ;
Gane, E. ;
Forns, X. .
JOURNAL OF HEPATOLOGY, 2015, 62 :S269-S270
[4]   Prognostic value of a single HVPG measurement and Doppler-ultrasound evaluation in patients with cirrhosis and portal hypertension [J].
Berzigotti, Annalisa ;
Rossi, Valentina ;
Tiani, Carolina ;
Pierpaoli, Lucia ;
Zappoli, Paola ;
Riili, Anna ;
Serra, Carla ;
Andreone, Pietro ;
Morelli, Maria Cristina ;
Golfieri, Rita ;
Rossi, Cristina ;
Magalotti, Donatella ;
Zoli, Marco .
JOURNAL OF GASTROENTEROLOGY, 2011, 46 (05) :687-695
[5]   Liver Fibrosis: Noninvasive Assessment with Acoustic Radiation Force Impulse Elastography-Comparison with FibroScan M and XL Probes and FibroTest in Patients with Chronic Liver Disease [J].
Cassinotto, Christophe ;
Lapuyade, Bruno ;
Ait-Ali, Ania ;
Vergniol, Julien ;
Gaye, Delphine ;
Foucher, Juliette ;
Bailacq-Auder, Claire ;
Chermak, Faiza ;
Le Bail, Brigitte ;
de Ledinghen, Victor .
RADIOLOGY, 2013, 269 (01) :283-292
[6]   Non invasive evaluation of portal hypertension using transient elastography [J].
Castera, Laurent ;
Pinzani, Massimo ;
Bosch, Jaime .
JOURNAL OF HEPATOLOGY, 2012, 56 (03) :696-703
[7]   Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease [J].
Charlton, Michael ;
Everson, Gregory T. ;
Flamm, Steven L. ;
Kumar, Princy ;
Landis, Charles ;
Brown, Robert S., Jr. ;
Fried, Michael W. ;
Terrault, Norah A. ;
O'Leary, Jacqueline G. ;
Vargas, Hugo E. ;
Kuo, Alexander ;
Schiff, Eugene ;
Sulkowski, Mark S. ;
Gilroy, Richard ;
Watt, Kymberly D. ;
Brown, Kimberly ;
Kwo, Paul ;
Pungpapong, Surakit ;
Korenblat, Kevin M. ;
Muir, Andrew J. ;
Teperman, Lewis ;
Fontana, Robert J. ;
Denning, Jill ;
Arterburn, Sarah ;
Dvory-Sobol, Hadas ;
Brandt-Sarif, Theo ;
Pang, Phillip S. ;
McHutchison, John G. ;
Reddy, K. Rajender ;
Afdhal, Nezam .
GASTROENTEROLOGY, 2015, 149 (03) :649-659
[9]   Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: Comparison between M and XL probe of FibroScan® [J].
de Ledinghen, Victor ;
Wong, Vincent Wai-Sun ;
Vergniol, Julien ;
Wong, Grace Lai-Hung ;
Foucher, Juliette ;
Chu, Shirley Ho-Ting ;
Le Bail, Brigitte ;
Choi, Paul Cheung-Lung ;
Chermak, Faiza ;
Yiu, Karen Kar-Lum ;
Merrouche, Wassil ;
Chan, Henry Lik-Yuen .
JOURNAL OF HEPATOLOGY, 2012, 56 (04) :833-839
[10]   Improvement of liver function parameters in advanced HCV-associated liver cirrhosis by IFN-free antiviral therapies [J].
Deterding, K. ;
Siederdissen, C. Hoener Zu ;
Port, K. ;
Solbach, P. ;
Sollik, L. ;
Kirschner, J. ;
Mix, C. ;
Cornberg, J. ;
Worzala, D. ;
Mix, H. ;
Manns, M. P. ;
Cornberg, M. ;
Wedemeyer, H. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2015, 42 (07) :889-901