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Page 4 of 14 Cullen et al. Hepatoma Res 2020;6:76 I http://dx.doi.org/10.20517/2394-5079.2020.69
[25]
treated with palliative therapies that carry a 3-year survival rate of just 30% . LDLT is now an option for
these patients that offers superior outcomes compared with palliative therapy.

A concise pre-operative evaluation is critical. Imaging techniques including CT and MRI are among the
most used diagnostic tools. However, characterization of tumor properties such as invasion into segmental
[26]
branches of the portal vein can be difficult to assess with these modalities alone . While biomarkers and
cutoff levels vary among centers and within the literature, the most widely used are AFP, PIVKA-II, γ-GT/
ALT ratio, and recently proposed inflammatory markers including CRP, neutrophil-to-lymphocyte ratio,
and platelet-to-lymphocyte ratio [22,26-28] .

[28]
A multicenter retrospective study in South Korea evaluated the outcomes of LT for extremely advanced
HCC patients (n = 169), using AFP and PIVKA-II as a selection strategy to decide whether those patients
were suitable for LT. The authors found that patients with AFP + PIVKA‐II ≤ 300 showed a 5-year overall
and recurrence-free survival rate of 47.8% and 53.4%, respectively. These values were significantly superior
to those of patients with AFP (ng/mL) + PIVKA‐II (mAU/mL) > 300 (21.0% and 10.8%, respectively; P <
0.001). The authors concluded that that if tumor biology is favorable regardless of tumor size and number,
acceptable long-term survival after LT can be expected.

[27]
Recently, Kornberg et al. analyzed 119 LT patients with advanced HCC to determine the prognostic
impact of clinical and histopathologic factors including pre-LT serum AFP and CRP values. The authors
identified that pre-transplant serum levels of AFP > 100 ng/mL (OR = 13.31) and CRP > 0.8 mg/dL (OR
= 13.97) were independent predictors of HCC recurrence. The group proposed a serological risk index
based on the mentioned biomarkers. A cumulative risk of HCC relapse at 5 years post-LT was determined
to be 2.3% in low serological tumor activity (STA) index (AFP ≤ 100 ng/mL + CRP ≤ 0.8 mg/dL), 17.1% in
intermediate STA (AFP ≤ 100 ng/mL or CRP ≤ 0.8 mg/dL), and 91.6% in high STA index (AFP > 100 ng/mL
+ CRP > 0.8 mg/dL; P < 0.001). Prospective randomized studies that provide validation and present
reproducible results are needed.

Despite being a promising therapeutic approach for advance HCC, evidence suggest that absolute
contraindications for transplant, includes presence of extrahepatic metastasis such as suspicious porta
hepatic nodal diseases, massive infiltrative type, major vascular invasion, and cases with ruptured HCC [29,30] .

Vascular invasion
Portal vein tumor thrombosis (PVTT) is seen in up to 60% of HCC patients, and considered a marker
of systemic disease associated with a high rate of post-transplant recurrence [31-33] . Because of this, PVTT
has been traditionally considered a contraindication to liver transplantation. However, new studies are
challenging this convention based upon the PVTT classification. There are several classifications for PVTT
based on the portal vein segment involved. However, two classifications are currently valid to effectively
[34]
assess prognosis and provide guidance for surgical treatment . The Liver Cancer Study Group of Japan
differentiates PVTT in four main categories of portal vein invasion, VP1, VP2, VP3, and VP4 [34-36] . In a
[34]
similar fashion, Cheng et al. proposed a four-category classification, with the distinction of a category
for microscopic portal vein invasion and the allusion of the extension of PVTT involving the superior
mesenteric vein or inferior vena cava [37,38] [Figure 1].

[39]
The prognosis of patients with HCC and PVTT is known to be deleterious , and the BCLC
recommendation indicates Sorafenib as the only treatment option [33,40] . However, depending on the PVTT
classification, different treatment options are available and survival rates vary among the literature. A
summary of treatment strategies according to PVTT is provided in Figure 1 [26,34,35,38,41] . In terms of LDLT,
within the scope of the present review, recent studies demonstrated LDLT is a viable option to improve