*Purpose: Functional recovery in liver transplant recipients is commonly confounded by weight changes relating to various aspects of liver disease such as cachexia, ascites and immunosuppressive medication. The full spectrum of these changes and implications for cancer recurrence are undefined. We aim to systematically examine changes in body weight following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) and to assess its independent association with HCC recurrence.

*Methods: All patients undergoing OLT for HCC from January 2002 to December 2018 were studied within a prospectively maintained institutional database. Serial weight data was collated at several time points: preoperatively, 1 month, 3 months, 6 months and 12 months postoperatively. Weight change was defined as post-operative weights minus the preoperative weight. Area under the growth curve (AUC) adopting an integral calculus formula based on the fixed and random-effect parameters of the growth curve was used to evaluate cumulative weight change over the 1-year post-transplant period. A multivariable Cox proportional hazard model was used to assess the association of AUC with HCC recurrence, adjusted for patient demographics (including preoperative BMI) and clinical characteristics at transplant.

*Results: 466 consecutive patients were studied (mean age 59 years; 80% male; mean preoperative MELD score 25). Thirty-three patients developed HCC recurrence post-transplant (median time to recurrence 5.3yrs). Thirteen percent of patients demonstrated >20% weight gain during the 1-year post-operative period. In the multivariable analysis, cumulative weight increase was associated with a lower risk of HCC recurrence (multivariable-adjusted HR: 0.997, 95% confidence interval: 0.995-0.999, p=0.004, per 1 lb/month increase). In the subgroup of patients who gained >20% weight over the 12-month post-operative period, the association still remained (p=0.031).

*Conclusions: Post-operative weight gain in HCC patients during the initial 12 months following liver transplantation may reflect nutritional and functional recovery. “Healthy” weight gain appears to correlate with a lower risk of recurrence and may represent a surrogate marker of survival advantage. These findings highlight a potentially modifiable and predictive marker of nutritional rehabilitation and cancer risk that could be monitored and incorporated clinically.

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