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Page 4 of 15 Bhangui et al. Hepatoma Res 2020;6:71 I http://dx.doi.org/10.20517/2394-5079.2020.67

Symptoms suggestive of metastases such as chest symptoms or bone pains were evaluated as indicated. All
cases with suspected recurrence were discussed at a multidisciplinary meeting. Patients with an increased
AFP underwent triphasic PET CT scans for radiological confirmation of HCC recurrence; histological
confirmation was obtained only where the diagnosis was doubtful.

Management of recurrence
Different treatment options were discussed in a multidisciplinary team meeting which included surgeons,
radiologists, hepatologists, and oncologists. All patients were treated with sorafenib (after 2009), either
alone (when other loco regional therapy or surgical resection were not possible), or in combination with
surgery/ablation/radiotherapy. Resection was proposed in patients whenever technically feasible, especially
in patients with isolated metatases in the lungs [video assisted thoracoscopic surgery (VATS), liver, bone,
or scar site. Ablative therapy included transarterial chemoembolisation (TACE) for liver recurrence, or
radiofrequency ablation (RFA)] for liver, lung or bone lesions. Stereotactic body radiotherapy was used for
bone, lung, or hepatic recurrence in some cases.

Statistical analysis
Continuous variables are expressed as mean ± SD or median (range, IQR) as appropriate. Categorical data
are presented as frequency and percentage. For outcomes post LDLT, overall survival (OS) was calculated
from the date of transplant to the date of death or last follow up, whereas recurrence-free survival (RFS)
was calculated from the date of transplant to the date of first recurrence, or last follow up whichever
was earlier. Post-recurrence was calculated from the time of detection of recurrence till death, or last
follow up. The Chi-square test was used for categorical variables, and independent t-test or ANNOVA for
continuous variables. The Kaplan-Meier method was used for survival analysis, and the survival curves
were compared by using the log-rank test. Univariate and multivariate analysis of risk factors associated
with post recurrence survival was performed using Cox proportional hazard model. A P value of < 0.05
was considered statistically significant. All statistical analyses were performed using SPSS version 20.0 for
Windows statistical software (SPSS Inc., Chicago, IL, USA).

The study was performed in accordance with the Declaration of Helsinki. Since this was a retrospective
review and analysis of prospectively maintained data at our Institute, no consent was required for inclusion
in this study. However, all patients who had undergone LDLT or any procedure/therapy for recurrence
were consented at every stage.

RESULTS
The overall and recurrence-free 5 year survival in our cohort of 435 patients was 64%, and 70%, respectively
[Figure 2A and B]. Prognostic factors for OS included pre-LT AFP > 100 ng/mL and tumour FDG-18 PET
avidity. Predictors of recurrence following multivariate analysis included UCSF criteria on imaging, serum
AFP level > 100 ng/mL before LDLT, and tumour FDG-18 PET avidity.

The baseline clinico-pathological characteristics of 100 HCC-cirr patients who developed recurrence post
LDLT are summarised in Table 1. The mean age of the studied population was 53 years of which 88% were
males. The most common underlying causes of cirrhosis were HCV (34%) and HBV (32%) cirrhosis. The
median pre-LDLT AFP was 96 ng/mL (range 1-11200), and mean was 788 ± 1985 ng/mL; 64% of patients
had tumours beyond UCSF, and 71% beyond Milan criteria. 67% of tumours were FDG-18 PET scan avid.
The characteristics in the entire cohort of 435 patients are detailed in Supplementary Table 1.

In the 100 patients with recurrence, the median time to HCC recurrence after LDLT was 16 months (range
2-108 months), mean AFP at recurrence was 80 ± 11,796 ng/mL and majority of the recurrences (68%) were
detected within first two years after LDLT. At the time of diagnosis, most recurrences were extrahepatic