Perioperative Changes in Serum Transaminases Levels Predicts Long-Term Survival Following Liver Resection of Hepatocellular Carcinoma

We sought to define whether and how hepatic ischemia/reperfusion (I/R) as manifested by perioperative aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels impact long-term outcomes after curative-intent resection of hepatocellular carcinoma (HCC).

Intrasplenic injection of HCC cells was used to establish a murine model of HCC recurrence with versus without I/R injury. Patients who underwent curative resection for HCC were identified from a multi-institutional derivative cohort (DC) and separate external validation (VC) cohort. Perioperative changes of transaminase levels were examined relative to the recurrence-free (RFS) and overall survival (OS) among patients following HCC resection.

Mice exposed to hepatic I/R injury were more likely to experience tumor recurrence, as well as higher luminescence signal intensity (all p < 0.05) versus mice with no I/R injury. Relative changes between AST and ALT (sum of AST/ALT ratios, SAAR) on postoperative day (POD) 1 and POD 3 \(\left( {\frac{{{\text{AST}}_{1} }}{{{\text{ALT}}_{1} }}{\text{ and}} \frac{{{\text{AST}}_{3} }}{{{\text{ALT}}_{3} }}} \right)\) $\left(\frac{{\text{AST}}_1}{{\text{ALT}}_1}\text{and}\frac{{\text{AST}}_3}{{\text{ALT}}_3}\right)$ were calculated using the formula: \({\text{SAAR}} = \frac{1}{\sqrt 2 }\left( {\frac{{{\text{AST}}_{1} }}{{{\text{ALT}}_{1} }} + \frac{{{\text{AST}}_{3} }}{{{\text{ALT}}_{3} }}} \right)\) $\text{SAAR}=\frac{1}{\sqrt{2}}\left(\frac{{\text{AST}}_1}{{\text{ALT}}_1}+\frac{{\text{AST}}_3}{{\text{ALT}}_3}\right)$ via Fourier transform theory. Among 734 patients in DC, the median SAAR was 2.1. After adjusting for other competing risk factors, SAAR \(\ge\) $\ge$ 2.0 remained strongly associated with risk of postoperative recurrence (ref. SAAR < 2.0, HR 1.32, p = 0.03), whereas SAAR \(\ge\) $\ge$ 3.5 was associated with risk of postoperative mortality (ref. SAAR < 3.5, HR 1.86, p < 0.01). SAAR demonstrated good accuracy to predict postoperative recurrence (c-index 0.724, 0.731) and mortality (c-index 0.655, 0.765) in DC and VC, respectively.

Use of routine labs such as AST and ALT can help identify patients at high risk of recurrence and mortality following HCC resection.