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Zhang et al. Late recurrence of hepatocellular carcinoma

Table 5: Review of literature on the incidence of recurrence of HCC after LT
Authors Year Area No. of LT patients Recurrence rate Median follow-up Mean follow-up
Roayaie et al. [4] 2004 USA (NY) 311 18.3% 51.9 months
Hwang et al. [9] 2011 Korea 87 1.3% 75 months
Lee et al. [10] 2014 Korea 69 44.9% 24.5 months
Schraiber et al. [11] 2016 Brazil 206 15.5% 43.6 months 49.8 months
Hanouneh et al. [12] 2011 USA (OH) 92 13.0% 19.5 months
Andreou et al. [13] 2016 Germany 364 25.0% 78 months
Kondili et al. [14] 2007 UK 104 11.5% 36 months 47 months
Escartin et al. [15] 2007 Spain 184 15.2%
Varona et al. [16] 2015 Spain 109 7.0% 42 months
Lai et al. [19] 2013 Italy, Brussels 422 14.5% 4.9 years
Agopian et al. [20] 2015 USA (CA) 865 13.5% 29.7 months
Parfitt et al. [21] 2007 Spain 75 26.7% 8 years
Chok et al. [23] 2011 Hong Kong 139 17.3% 55 months
Zou et al. [26] 2008 China 303 15.8%
Rodriguez-Peralvarez et al. [27] 2013 Spain 219 17.6% 51 months
Nissen et al. [28] 2011 USA (CA) 122 10.7% 32.7 months
Pfiffer et al. [29] 2011 Germany 139 17.3% 37.2 months
Marelli et al. [30] 2008 UK 100 18.0% 29 months
Sharma et al. [40] 2012 USA (MI) 94 18.0% 2.2 years
Wai et al. [41] 2012 Singapore 77 38.0% 953 days
Iacob et al. [42] 2013 Romania 38 13.2% 22 months
HCC: hepatocellular carcinoma; LT: liver transplantation

globulin injections. Approximately 13.5 years after include major vascular invasion, poorly-differentiated
LT, he complained of persistent cough and was tumor, unresectable disease, and bone metastases. [4,25]
found to have a large pleural effusion. CT scan Our small study is consistent with these larger studies
showed multiple small pulmonary nodules and hilar/ in that larger tumors and microvascular invasion on
mediastinal lymphadenopathy. CT guided biopsy the explanted liver were associated with increased
of a chest wall mass showed metastatic HCC. A recurrence. Four patients with late recurrence died
video-assisted thoracoscopy and pleurodesis was within 18 months, suggesting that although their initial
performed. The patient opted not to have any further course after transplantation appeared to be favorable,
treatment and died in hospice about 2 months after recurrence at any time threatens survival.
diagnosis of recurrent HCC.
Recurrent HCC tends to occur early or within 2 years
DISCUSSION of LT. There have been reported cases of recurrent
HCC beyond 5 years; however these cases may
LT is the best treatment for localized HCC in terms of become more prevalent as more patients are living
long-term disease free survival. Despite this, patients longer after LT for HCC. Table 5 demonstrates the
do have a chance of recurrent HCC that varies from current literature on recurrence after LT for HCC,
1.3% to 44.9% depending on individual series. [9,13] which may suggest a trend toward a higher proportion
Multiple studies have determined that microvascular of recurrences with longer follow-up when all cases
invasion, poor tumor grade, larger tumor diameter, are considered. [26-30] Castroagudin et al. [31] in 165
and higher AFP are associated with increased cases, reported a 10.9% recurrence with 78% of these
recurrence after transplant. [14-18] Other factors that recurrences occurring within the first 3 years, but they
have been reported to contribute include age, bilobar had 3 recipients that had recurrences after 7, 9, and
involvement, multiple lesions, absence of necrosis, 10 years. In our study, the recurrence rate was 17%
tumor beyond Milan criteria, elevated neutrophil-to- with a third of our recurrence cases occurring beyond
lymphocyte ratio, microsatellitosis, and previous liver 5 years.
resection. [19-22] Two studies have found that the time
between LT and HCC recurrence affects prognosis, In terms of the site of recurrence, most of the cases of
with worse outcomes associated with early recurrence recurrent HCC after LT have been reported to involve
within 2 years. [23,24] extrahepatic (38.5-53%) or both extrahepatic and
intrahepatic sites (31-38.5%). In general, intrahepatic
Once a patient develops a recurrence after transplant, recurrence is more common in cases of early
prognostic factors associated with decreased survival recurrence, while more extrahepatic involvement is

Hepatoma Research ¦ Volume 3 ¦ April 10, 2017 63