Liver transplantation offers the best chance of cure for early unresectable HCC. However, its role has been limited by the shortage of deceased donor liver grafts, which is particularly severe in Asia, where the deceased donor organ rates are fewer than 5 donors per million population, compared with 10–35 donors per million population in Western countries.15
In most Asian countries, HCC is the most common cancer and the most frequent indication for OLT, aggravating the unmet demand for liver grafts. The development of living donor liver transplantation (LDLT), especially adult-to-adult right lobe liver transplantation, has allowed more patients with HCC to benefit from OLT.16
LDLT can theoretically provide an unlimited source of liver grafts and eliminate the uncertainty of prolonged waiting times and the risk of dropout due to tumor progression. However, LDLT is a novel treatment for HCC with unresolved issues regarding indications and results.
Recent studies on LDLT for HCC suggest favorable long-term survival results.17
However, it remains unclear whether the outcome after LDLT for HCC is equivalent to that of deceased donor liver transplantation (DDLT). A study from a Korean group reported similar 3-year survival rates after LDLT and DDLT (91.4 vs 89.9%) in patients with tumors fulfilling the Milan criteria, after excluding perioperative mortality.13
However, others have found significantly higher rates of tumor recurrence after LDLT compared with DDLT for HCC.19
This may be related to selection bias, as LDLT eliminates the waiting period for grafts. In DDLT the waiting period provides time for a natural selection process in which patients with biologically more aggressive tumors drop out due to tumor progression. In addition, the ischemic-reperfusion injury associated with small-for-size grafts in LDLT and angiogenesis associated with liver regeneration may theoretically promote growth of tumors in the transplanted liver after LDLT, although the actual clinical impact of such biological processes remains unclear.20
Liver transplantation is conventionally offered to Child-Pugh class C patients with unresectable early HCC. Recently, there have been heated debates on whether liver transplantation should be used as first-line therapy for Child-Pugh class A patients with early HCC.22
While some previous studies showed that liver transplantation for early HCC may achieve better survival compared with resection, this may be partly related to selection bias in favor of transplantation because patients with more aggressive tumors drop off the waiting list for DDLT.19
Recent studies suggest that for patients with preserved liver function and early stage HCC, hepatic resection can achieve a 5-year survival rate of 70%, comparable to that after OLT.13
The availability of grafts from dedicated live donors has been considered one of the main arguments favoring LDLT as primary therapy for patients with early HCC and preserved liver function. However, even in Asian countries where LDLT is commonly performed, up to half of the patients with early HCC may not have suitable living donors for various reasons, including ABO-incompatibility, hepatitis serology, and patient refusal to accept living donation.18
Furthermore, the risks of donor hepatectomy, with morbidity and mortality rates of 14–21% and 0.25–1%, respectively, should be carefully balanced against the benefit of LDLT.19
Risking the life of a donor for HCC patients who have an alternative option of hepatic resection, which achieves long-term survival equivalent to LDLT, is ethically not acceptable to many Asian surgeons. Most Asian centers still consider resection as first-line treatment for HCC patients with preserved liver function and reserve LDLT as an option for salvage transplantation in patients with recurrent tumors.13
Another matter of debate in LDLT involves expanding the indications beyond the CMC or UCSF criteria. LDLT is currently being performed in some Asian centers for patients with HCC beyond the Milan criteria, with results that are expectedly worse than those for patients within the Milan criteria.13
Some transplant surgeons argue that despite the poorer results, LDLT for advanced HCC may be justified, since donors voluntarily accept the risks of donor hepatectomy to dedicate a graft for HCC patients, who may otherwise have no effective treatment options. However, others argue that the medical profession should not relegate the issue to individual donor autonomy.25
With the lack of clear data showing benefits of LDLT for advanced HCC, the medical community should take a conservative moral stand and limit the use of LDLT for HCC that meets the same criteria as DDLT.