Meeting News

DAAs may impact inflammatory markers in cirrhosis, HCC surveillance

AMSTERDAM — Curing patients with cirrhosis of hepatitis C virus could alter the inflammatory milieu and have an impact on the way CD8+ T-cells surveil potential carcinoma, according to data presented at the International Liver Congress.

“Interferon-free cure of HCV alters the inflammatory milieu, which could impact HCC,” Solomon Owusu Sekyere, MD, of the department of gastroenterology, hepatology and endocrinology, at Hannover Medical School, Hannover, 3TTU-IICH and the German Center for Infectious Diseases in Hannover-Braunschweig, Germany, said during his presentation. “HCC occurrence after HCV clearance is still conflicting.”

Sekyere and colleagues, aimed to determine whether changes in soluble inflammatory mediators impact tumor-specific immune responses that, in turn, influence progression to HCC in patients with cirrhosis and HCV. The study included 24 patients who achieved SVR with DAA therapies. There were 17 patients with HCC and seven patients without HCC.

The group analyzed serum concentrations of 50 inflammatory mediators. Specifically, they analyzed T-cell responses to a panel of Glypican-3-derived overlapping peptides, according to Sekyere. This was done at time points on short-term culture of peripheral blood mononuclear cells (PBMCs). He added that CD8+ T-cell responses to HLA-A2 epitopes of AFP, NY-ESO-1, MAGE-A3, MAGE-A10, SSX-2 and p53 underwent analysis, as did NS31073, NS31406, Core132 and NS5B2594 in vitro.

Results indicated different soluble inflammatory marker concentrations among patients in the HCC group compared to the non-HCC group.

HCC-specific T-cell responses were observed, according to Sekyere. “DAA therapy significantly decreased HCC-specific CD8+ T-cell response,” he said. “We observed a decline in activation at the end of therapy and through follow-up.”

This phenomenon was not observed for CD4+ responses.

The group then aimed to see if this was replicated at the epitope-specific level. “At end of therapy and follow-up, the response was completely abrogated,” Sekyere said.

The group also analyzed cytokine production. “We observed robust production in cirrhotic patients compared with cirrhotic controls,” Sekyere said.

A decrease in CFSE intensity can be used as a proliferative marker, Sekyere added.

“Serum concentrations of various soluble inflammatory mediators are altered in patients with HCV-related cirrhosis.” Sekyere concluded, “HCC-specific T-cell responses are readily detectable in patients with liver cirrhosis relative to non-cirrhotic controls. Cirrhotic patients who further developed HCC upon DAA therapy display weak HCC-specific T-cell responses prior to treatment. As a result of the impact of DAA therapy, close HCC screening is recommended in cirrhotic patients with HCV clearance.” – by Rob Volansky

Reference: Sekyere SO, et al. Abstract #GS-003. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.

Disclosure: Sekyere reports no relevant financial disclosures.

AMSTERDAM — Curing patients with cirrhosis of hepatitis C virus could alter the inflammatory milieu and have an impact on the way CD8+ T-cells surveil potential carcinoma, according to data presented at the International Liver Congress.

“Interferon-free cure of HCV alters the inflammatory milieu, which could impact HCC,” Solomon Owusu Sekyere, MD, of the department of gastroenterology, hepatology and endocrinology, at Hannover Medical School, Hannover, 3TTU-IICH and the German Center for Infectious Diseases in Hannover-Braunschweig, Germany, said during his presentation. “HCC occurrence after HCV clearance is still conflicting.”

Sekyere and colleagues, aimed to determine whether changes in soluble inflammatory mediators impact tumor-specific immune responses that, in turn, influence progression to HCC in patients with cirrhosis and HCV. The study included 24 patients who achieved SVR with DAA therapies. There were 17 patients with HCC and seven patients without HCC.

The group analyzed serum concentrations of 50 inflammatory mediators. Specifically, they analyzed T-cell responses to a panel of Glypican-3-derived overlapping peptides, according to Sekyere. This was done at time points on short-term culture of peripheral blood mononuclear cells (PBMCs). He added that CD8+ T-cell responses to HLA-A2 epitopes of AFP, NY-ESO-1, MAGE-A3, MAGE-A10, SSX-2 and p53 underwent analysis, as did NS31073, NS31406, Core132 and NS5B2594 in vitro.

Results indicated different soluble inflammatory marker concentrations among patients in the HCC group compared to the non-HCC group.

HCC-specific T-cell responses were observed, according to Sekyere. “DAA therapy significantly decreased HCC-specific CD8+ T-cell response,” he said. “We observed a decline in activation at the end of therapy and through follow-up.”

This phenomenon was not observed for CD4+ responses.

The group then aimed to see if this was replicated at the epitope-specific level. “At end of therapy and follow-up, the response was completely abrogated,” Sekyere said.

The group also analyzed cytokine production. “We observed robust production in cirrhotic patients compared with cirrhotic controls,” Sekyere said.

A decrease in CFSE intensity can be used as a proliferative marker, Sekyere added.

“Serum concentrations of various soluble inflammatory mediators are altered in patients with HCV-related cirrhosis.” Sekyere concluded, “HCC-specific T-cell responses are readily detectable in patients with liver cirrhosis relative to non-cirrhotic controls. Cirrhotic patients who further developed HCC upon DAA therapy display weak HCC-specific T-cell responses prior to treatment. As a result of the impact of DAA therapy, close HCC screening is recommended in cirrhotic patients with HCV clearance.” – by Rob Volansky

Reference: Sekyere SO, et al. Abstract #GS-003. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.

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Disclosure: Sekyere reports no relevant financial disclosures.

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