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BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.
This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.
“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”
To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.
Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).
While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.
“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.
Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.
“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”
In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.
“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”
The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.
SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.
BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.
This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.
“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”
To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.
Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).
While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.
“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.
Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.
“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”
In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.
“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”
The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.
SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.
BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.
This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.
“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”
To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.
Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).
While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.
“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.
Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.
“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”
In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.
“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”
The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.
SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.
REPORTING FROM THE LIVER MEETING 2019