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Page 6 of 15 Bhangui et al. Hepatoma Res 2020;6:71 I http://dx.doi.org/10.20517/2394-5079.2020.67

Table 1. Patient demographics and tumour characteristics in 100 patients with HCC recurrence post LDLT
Patient demographics and tumour characteristics (n = 100) Values
Age in years at the time of LDLT (mean ± standard deviation) 53 ± 8
Gender
Male/Female 88/12
Etiology of underlying cirrhosis
HBV/HCV/HBV + HCV 32%/34%/4%
Cryptogenic 6%
Ethanol 12%
NASH/NAFLD 10%
Others 25%
Non tumour MELD score (mean ± standard deviation) 12 ± 6
Pre-LT treatment for HCC
TACE 22
RFA 6
Resection 6
Pre-LT AFP ng/mL Mean ± SD 788 ± 1,985
Tumour characteristics
Within UCSF/Beyond UCSF 36%/64%
Within Milan/Beyond Milan 29%/71%
Tumour FDG-18 PET avidity Non Avid vs. Avid in those who had a PET scan before LT 23%/67%
HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HCV: hepatitis C virus; NASH: non alcoholic steatohepatitis; NAFLD: non
alcoholic fatty liver disease; MELD: Model for End Stage Liver Disease; TACE: transarterial chemoembolization; RFA: radiofrequency
ablation; AFP: alpha feto-protein; UCSF: University of California, San Francisco; FDG-18 PET: 18-fluoro deoxy-glucose positron emission
tomography; LT: liver transplantation

(n = 54; 54%), liver only recurrence was seen in 15 patients, and in 21 patients, recurrence occurred in the
liver as well as extrahepatic sites. Thirty-six patients presented with HCC recurrence at more than one site
and the three most common sites of disease recurrence were lungs (53%), liver (37%), and bone (21%).
Thirty-two percent of patients had a single nodule recurrence, whereas 68% of patients presented with two
or more tumour nodules (at one or multiple sites) when they recurred [Table 2].

One patient developed an abdominal wall squamous cell carcinoma post LDLT and subsequently
underwent excision. Two other HCC patients (in the overall cohort of 435 patients) developed de novo
malignancies during follow up (one patient had an inflammatory myofibroblastic tumour of the colon, and
another developed a brain cancer).

Management of HCC recurrence
Ninety five patients with recurrence were put on sorafenib of which in 20 patients dose adjustment was
required due to adverse effects. mTOR inhibitors were used in 62 patients. In 38 patients, they were started
“de principe” within 6 months of LDLT, as our protocol from 2012 onwards included switch to mTORI
and mycophenolate based immunosuppression with CNI reduction early after LDLT. The other 24 patients
were switched over to mTORi’s later, either pre emptively (11 patients), or after developing recurrence (13
patients). All patients except one received Sirolimus (1 patient received Everolimus). Thirty-two patients
received tyrosine kinase inhibitors (TKI’s) alone, and 36 received both TKI’s and mTORi’s [Table 2].

Surgical excision of lung metastases was performed using VATS in 5 patients, and limited hepatectomy was
performed for liver recurrence in 3 patients. Scar site excision (n = 3), laminectomy, mediastinal tumour
excision, and supraadrenal metastatectomy (one each), were the other surgical procedures performed.
Fifteen patients received stereotactic radiotherapy (for bone/lung/liver/soft tissue lesions), 10 underwent
RFA or microwave ablation (MWA) of liver/lungs/bone metastases, 5 underwent TACE for liver lesions,
and 3 had percutaneous ethanol injection in metastatic lymph nodes [Table 2].

Thirty-two patients received tyrosine kinase inhibitors with/without mTORi’s and other modalities (surgery
and/or ablative therapy and/or radiotherapy).