The Impact of Modern Chemotherapy and Chemotherapy-Associated Liver Injuries (CALI) on Liver Function: Value of 99mTc-La
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ORIGINAL ARTICLE – HEPATOBILIARY TUMORS
The Impact of Modern Chemotherapy and ChemotherapyAssociated Liver Injuries (CALI) on Liver Function: Value of 99mTc-Labelled-Mebrofenin SPECT-Hepatobiliary Scintigraphy Ste´phanie Truant, MD, PhD1,2, Clio Baillet, MD3, Viviane Gnemmi, MD, PhD4, Maxence Fulbert, MD1, Anthony Turpin, MD, PhD5, Sabrina Dardenne, MD1, Emmanuelle Leteurtre, MD, PhD4, Mehdi El Amrani, MD, PhD1,2, Se´bastien Dharancy, MD, PhD6,7, Laurent Dubuquoy, PhD6,7, Damien Huglo, MD, PhD3, Christophe Chesne´, PhD8, and Franc¸ois-Rene´ Pruvot, MD, PhD1 1
Department of Digestive Surgery and Transplantation, Univ. Lille, CHRU Lille, Lille, France; 2CANTHER laboratory Cancer Heterogeneity, Plasticity and Resistance to Therapies UMR-S1277 INSERM, Team Mucins, Cancer and Drug Resistance, Lille, France; 3Department of Nuclear Medicine, Univ. Lille, Lille, France; 4Department of Pathology, Univ. Lille, Lille, France; 5Department of Medical Oncology, Univ. Lille, Lille, France; 6Hepatology Unit, Univ. Lille, Lille, France; 7LIRIC-Lille Inflammation Research International Center-U995, Univ. Lille, Inserm, CHU Lille, Lille, France; 8 Biopredic Laboratory, Rennes, France
ABSTRACT Background. Chemotherapy is increasingly used before hepatic resection, with controversial impact regarding liver function. This study aimed to assess the capacity of 99mTc-labelled-mebrofenin SPECT-hepatobiliary scintigraphy (HBS) to predict liver dysfunction due to chemotherapy and/or chemotherapeutic-associated liver injuries (CALI), such as sinusoidal obstruction syndrome (SOS) and nonalcoholic steatohepatitis (NASH) activity score (NAS). Methods. From 2011 to 2015, all consecutive noncirrhotic patients scheduled for a major hepatectomy (C 3 segments) gave informed consent for preoperative SPECT-HBS allowing measurements of segmental liver function. As primary endpoint, HBS results were compared between patients with versus without (1) preoperative chemotherapy (B 3 months); and (2) CALI, mainly steatosis, NAS (Kleiner), or SOS (Rubbia-Brandt). Secondary endpoints were (1) other factors impairing function; and (2) impact of
chemotherapy, and/or CALI on hepatocyte isolation outcome via liver tissues. Results. Among 115 patients, 55 (47.8%) received chemotherapy. Sixteen developed SOS and 35 NAS, with worse postoperative outcome. Overall, chemotherapy had no impact on liver function, except above 12 cycles. In patients with CALI, a steatosis C 30% significantly compromised function, as well as NAS, especially grades 2–5. Conversely, SOS had no impact, although subjected to very low patients number with severe SOS. Other factors impairing function were diabetes, overweight/obesity, or fibrosis. Similarly, chemotherapy in 73 of 164 patients had no effect on hepatocytes isolation outcome; regarding CALI, steatosis C 30% and NAS impaired the yield and/or viability of hepatocytes, but not SOS. Conclusions. In this first large, prospective study, HBS appeared to be a valuable tool to select heavily treated patients at risk of liver dysfunction t
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