Ann Hepatobiliary Pancreat Surg.  2018 Nov;22(4):297-304. 10.14701/ahbps.2018.22.4.297.

Absence of antitumor effects of metformin in sorafenib-treated patients with hepatocellular carcinoma recurrence after hepatic resection and liver transplantation

• Chung YK
• Hwang S
• Song GW
• Lee YJ
• Kim KH
• Ahn CS
• Moon DB
• Ha TY
• Jung DH
• Park GC
• Ryoo BY
• Lee SG

• KMID: 2427359
• DOI: http://doi.org/10.14701/ahbps.2018.22.4.297

Abstract

BACKGROUNDS/AIMS
Hepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) and liver transplantation (LT) remains a great concern. We assessed the antitumor effects of metformin in patients treated with sorafenib for HCC recurrence after HR or LT.
METHODS
The two clinical retrospective studies involved metformin therapy of 304 HR patients and 74 LT recipients who were treated with sorafenib.
RESULTS
In the study involving patients who had undergone HR, death occurred in 245 of the 304 patients (80.6%) during a median follow-up of 10.2 months after sorafenib administration. The metformin HR group (group 1; n=40) showed no prognostic difference in progression-free and overall survival rates compared with the all-HR control group (group 3; n=241) and propensity score-matched HR control group (group 4; n=80). In the clinical study of recipients exposed to LT, death occurred in 62 of the 74 patients (83.8%) during a median follow-up of 13.6 months (range: 3-76 months) after sorafenib administration. The metformin LT group (group 5; n=14) showed no prognostic difference in progression-free and overall survival rates compared with the all-LT control group (group 7; n=43) and propensity score-matched LT control group (group 8; n=28).
CONCLUSIONS
Our clinical studies demonstrated absence of synergistic antitumor effects of metformin. Further high-volume studies are necessary to assess the role of metformin in patients treated with sorafenib for advanced HCC.

Keyword

Diabetic mellitus; Hepatic resection; Metformin; Recurrence

MeSH Terms

Carcinoma, Hepatocellular*
Clinical Study
Follow-Up Studies
Humans
Liver Transplantation*
Liver*
Metformin*
Recurrence*
Retrospective Studies
Survival Rate
Metformin

Figure

• 

  Fig. 1 Selection of patients following hepatic resection (HR) and liver transplantation (LT).

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  Fig. 2 Comparison of the progression-free survival (A) and overall survival (B) curves after sorafenib administration in hepatic resection groups 1, 2, and 3. After propensity score matching, the progression-free survival (C) and overall survival (D) curves were compared between HR groups 1 and 4.

• 

  Fig. 3 Comparison of the progression-free survival (A) and overall survival (B) curves after sorafenib administration in liver transplantation groups 5, 6, and 7. Following propensity score matching, the progression-free survival (C) and overall survival (D) curves were compared between LT groups 5 and 8.

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