Gut Dysbiosis and Fecal Calprotectin Predict Response to Immune Checkpoint Inhibitors in Patients With Hepatocellular Carcinoma

• DOI: 10.1002/hep4.1905
• Publication Date: 2022-03-09T08:38:44Z
• Authors: Francesca Romana ...; Angela De Luca; Anna Picca; Emanuele Marzetti; Valentina Petito; Federica Del Chie...; Sofia Reddel; Francesco Paroni ...; Maurizio Sanguinetti; Lorenza Putignani; Antonio Gasbarrini; Maurizio Pompili
• Keywords: Dysbiosis

The gut microbiota is a well-known prognostic factor and modulator of treatment sensitivity in patients with cancers treated immune checkpoint inhibitors. However, data on hepatocellular carcinoma (HCC) are lacking. This study aimed to evaluate the role changes produced by immunotherapy intestinal environment cirrhosis HCC. Eleven Tremelimumab and/or Durvalumab were included analysis. All participants underwent profiling, quantification fecal calprotectin, serum levels zonulin-1, lipopolysaccharide binding protein (LBP), programmed death-ligand 1 (PD-L1) at baseline each cycle until third cycle, then every three cycles discontinuation or last visit. 6 who achieved disease control (DC) showed lower pretreatment calprotectin (median, 12.5; interquartile range [IQR], 5-29 vs. median, 116; IQR, 59-129 µg/g; P = 0.047) PD-L1 0.08; 0.07-0.09 1.04; 0.17-1.95 ng/mL; 0.02) than nonresponders. relative abundance Akkermansia (log2 fold change [FC], 2.72; adjusted [Padj] 0.012) was increased, whereas that Enterobacteriaceae FC, -2.34; Padj 0.04) reduced DC group. During treatment, temporal evolution opposite ratio alpha diversity, but similar zonulin-1 LBP. Bifidobacterium had stable behavior long follow-up, while more variable. patterns causative relationships Prevotella, Veillonella, Ruminococcus, Roseburia, Lachnospira, Faecalibacterium, Clostridium. Conclusion: A favorable composition low inflammation associated achieving DC. dynamically during therapy.