title: Reversibility of chemotherapy-related liver injury.
abstract: Chemotherapy-associated liver injury (CALI) increases the risk of liver resection and may prejudice further surgery and chemotherapy. The reversibility of CALI is therefore important; however, no data concerning this are available. This study aimed to retrospectively analyze the reversibility of CALI in patients undergoing liver resection for colorectal metastases.
  
  
  
  All resections of colorectal liver metastases after oxaliplatin and/or irinotecan-based chemotherapy were included. First, liver resections were stratified by time between end of chemotherapy and hepatectomy and several possible cut-off values tested. CALI prevalence in various groups was compared. Second, CALI in the two specimens from each patient who had undergone repeat liver resections without interval chemotherapy were compared.
  
  
  
  Overall, 524 liver resections in 429 patients were analyzed. The median interval chemotherapy-surgery was 56days (15-1264). CALI prevalence did not differ significantly between groups with a chemotherapy-surgery interval <270days. Grade 2-3 sinusoidal dilatation (SOS, 19.4% vs. 40.0%, p=0.022) and nodular regenerative hyperplasia (NRH, 6.5% vs. 20.1%, p=0.063) occurred less frequently in patients with an interval >270days (n=31); prevalence of steatosis and steatohepatitis was similar in all groups. A chemotherapy-surgery interval >270days was an independent protector against Grade 2-3 SOS (p=0.009). Forty-seven patients had repeat liver resection without interval chemotherapy. CALI differed between surgeries only for a chemotherapy-surgery interval >270days (n=15), Grade 2-3 SOS having regressed in 4/5 patients and NRH in 7/8; whereas steatosis and steatohepatitis had persisted.
  
  
  
  CALI persists for a long time after chemotherapy. SOS and NRH regress only after nine months without chemotherapy, whereas steatosis and steatohepatitis persist.
  
  
  
  The patients affected by colorectal liver metastases often receive chemotherapy before liver resection, but chemotherapy causes liver injuries that may increase operative risks and reduce tolerance to further chemotherapy. The authors analyzed the reversibility of the liver injuries after the chemotherapy interruption. Liver injuries persist for a long time after chemotherapy. Sinusoidal dilatation and nodular regenerative hyperplasia regress only nine months after the end of chemotherapy, whereas steatosis and steatohepatitis persist even after this long interval.
authors.affiliation: Dept. of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center, Rozzano (MI), Italy. Electronic address: luca.vigano@humanitas.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Vigano
authors.affiliation: Dept. of Pathology, Ospedale Mauriziano Umberto I, Torino, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Rosa
authors.affiliation: Dept. of Visceral and Transplantation Surgery, University Hospitals, Geneva, Switzerland; Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.affiliation: Dept. of Visceral and Transplantation Surgery, University Hospitals, Geneva, Switzerland; Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Andres
authors.affiliation: Dept. of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Torino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferrero
authors.affiliation: Dept. of Oncology, University Hospitals, Geneva, Switzerland; Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Roth
authors.affiliation: Dept. of Oncology, Ospedale Mauriziano Umberto I, Torino, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sperti
authors.affiliation: Dept. of Visceral and Transplantation Surgery, University Hospitals, Geneva, Switzerland; Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Pietro
authors.initials: P
authors.lastname: Majno
authors.affiliation: Dept. of Clinical Pathology, Geneva, Switzerland; Hepato-Pancreato-Biliary Centre, University Hospitals, Geneva, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents
keywords: Chemotherapy-associated liver injury; Liver failure; Liver surgery for colorectal metastases; Nodular regenerative hyperplasia; Reversibility of liver injury; Sinusoidal dilatation; Steatohepatitis; Steatosis