Living donor liver transplantation for hepatocellular carcinoma: the impact of neo-adjuvant treatments on the long term results

Background/Aims: LDLT may represent a valid therapeutic option allowing several advantages for patients affected by HCC and waiting for liver transplantation (LT). However, some reports show a worse long term survival and disease free survival among patients treated by LDLT for HCC than deceased donor liver transplantation (DDLT) recipients. Methodology: Among 1145 LT patients, 63 received LDLT. From January 2000 to December 2008, 179 patients underwent LT due to HCC, 30 (16.7%) received LDLT and 154 (86.0%) received DDLT. Patients were selected based on the Milan criteria. TACE, radiofrequency ablation, percutaneous alcoholization, or liver resection were applied as downstaging procedures, while on the waiting list. Results: Overall 3- and 5-year survival rate was 77.3% and 68.7% vs. 82.8% and 76.7%, respectively for LDLT and DDLT recipient with not significant differences. Moreover, 3- and 5- years of recurrence free survival rate was 95.5% (LDLT) vs. 90.5% and 89.4% (DDLT) and resulted not significantly different. Conclusions: LDLT guarantees same long term results than DDLT if the selection criteria of candidates are analogues. Milan criteria remains a valid candidate selection tool to obtain optimal long term results in LDLT. An aggressive downstaging policy seems to improve the long-term results in LDLT, thus LRT may be considered useful to prevent tumor progression waiting for transplantation as well as a neoadjuvant therapy for HCC. A literature detailed meta-analysis could definitely clarify if LDLT is an independent risk factor for HCC recurrence.     

The evolution of liver transplantation for hepatocellular carcinoma (past, present, and future)

Over the past quarter-century, liver transplantation (LT) has been established as a durable therapy for all forms of end-stage liver disease. LT appears ideally suited for hepatocellular carcinoma (HCC), as it involves complete oncologic resection and correction of the underlying liver dysfunction. Since LT based on the Milan criteria has been shown to provide good diseasefree survival, LT is considered the optimal treatment for small HCC, especially in patients with underlying chronic liver disease. However, because there is a severe shortage of organ donors, not all patients in need can be offered LT. Transplant listing criteria must simultaneously determine the greatest number of suitable candidates for LT while rejecting the smallest number of those who could benefit from LT. The amended model for end-stage liver disease allocation policy has had a positive effect on liver transplant candidates with HCC, and their number has been increasing significantly over the past several years. To minimize dropout from the waiting list, the treatment of HCC with procedures such as chemoembolization, radiofrequency ablation, or ethanol injection in patients awaiting LT have become widespread. It is currently accepted that liver resection is the best option for the treatment of small HCC when liver function is well preserved, and that LT is preferred when liver function is severely impaired (Child-Pugh class B or C). However, the question arises as to what is the best option for Child-Pugh class A patients with early HCC eligible for both resection and LT, especially in Western countries. HCC is a major indication for living donor liver transplantation (LDLT), because the risk of dropout while waiting is negligible. Extension of the Milan criteria in the setting of LDLT may offer more patients a potentially curative treatment without reducing the donor pool of organs for patients on the waiting list with nonmalignant liver disease. However, imprudent expansion of the selection criteria may result in more patients with HCC being cured at the expense of a higher incidence of recurrence.     

Liver transplant recipient survival benefit with living donation in the model for endstage liver disease allocation era

Receipt of a living donor liver transplant (LDLT) has been associated with improved survival compared with waiting for a deceased donor liver transplant (DDLT). However, the survival benefit of liver transplant has been questioned for candidates with Model for Endstage Liver Disease (MELD) scores <15, and the survival advantage of LDLT has not been demonstrated during the MELD allocation era, especially for low MELD patients. Transplant candidates enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study after February 28, 2002 were followed for a median of 4.6 years. Starting at the time of presentation of the first potential living donor, mortality for LDLT recipients was compared to mortality for patients who remained on the waiting list or received DDLT (no LDLT group) according to categories of MELD score (<15 or ≥ 15) and diagnosis of hepatocellular carcinoma (HCC). Of 868 potential LDLT recipients (453 with MELD <15; 415 with MELD ≥ 15 at entry), 712 underwent transplantation (406 LDLT; 306 DDLT), 83 died without transplant, and 73 were alive without transplant at last follow-up. Overall, LDLT recipients had 56% lower mortality (hazard ratio [HR] = 0.44, 95% confidence interval [CI] 0.32-0.60; P < 0.0001). Among candidates without HCC, mortality benefit was seen both with MELD <15 (HR = 0.39; P = 0.0003) and MELD ≥ 15 (HR = 0.42; P = 0.0006). Among candidates with HCC, a benefit of LDLT was not seen for MELD <15 (HR = 0.82, P = 0.65) but was seen for MELD ≥ 15 (HR = 0.29, P = 0.043). CONCLUSION: Across the range of MELD scores, patients without HCC derived a significant survival benefit when undergoing LDLT rather than waiting for DDLT in the MELD liver allocation era. Low MELD candidates with HCC may not benefit from LDLT.     

Does living donation have advantages over deceased donation in liver transplantation?

Liver transplantation (LT) is the best treatment option for patients with end-stage liver disease. Living donor LT (LDLT) has developed as an alternative to deceased donor LT (DDLT) in order to overcome the critical shortage of deceased organ donations, particularly in Asia. LDLT offers several advantages over DDLT. The major advantage of LDLT is the reduction in waiting time mortality. Especially among patients with hepatocellular carcinoma (HCC), LDLT can shorten the waiting time and lower the dropout rate. The Hong Kong group reported that median waiting time was significantly shorter for LDLT than for DDLT. Intention-to-treat survival rates of HCC patients with voluntary live donors were significantly higher than those of patients without voluntary live donors. In contrast, a multicenter adult-to-adult LDLT retrospective cohort study reported that LDLT recipients displayed a significantly higher rate of HCC recurrence than DDLT recipients, although LDLT recipients had shorter waiting times than DDLT recipients. The advantage of LDLT involves the more liberal criteria for HCC compared with those for DDLT. Various preoperative interventions including nutritional treatment can also be planned for both the donor and recipient in LDLT. Conversely, LDLT has marked unfavorable characteristics in terms of donor risks. Donor morbidity is not infrequent and the donor mortality rate is estimated at around 0.1-0.3%. In conclusion, living donation is not necessarily advantageous over deceased donation in LT. Taking the advantages and disadvantages of each option into consideration, LDLT and DDLT should both be used to facilitate effective LT for patients requiring transplant.     

Living-donor vs deceased-donor liver transplantation for patients with hepatocellular carcinoma

With the increasing prevalence of living-donor liver transplantation(LDLT) for patients with hepatocellular carcinoma(HCC),some authors have reported a potential increase in the HCC recurrence rates among LDLT recipients compared to deceased-donor liver transplantation(DDLT) recipients.The aim of this review is to encompass current opinions and clinical reports regarding differences in the outcome,especially the recurrence of HCC,between LDLT and DDLT.While some studies report impaired recurrence- free survival and increased recurrence rates among LDLT recipients,others,including large database studies,report comparable recurrence- free survival and recurrence rates between LDLT and DDLT.Studies supporting the increased recurrence in LDLT have linked graft regeneration to tumor progression,but we found no association between graft regeneration/initial graft volume and tumor recurrence among our 125 consecutive LDLTs for HCC cases.In the absence of a prospective study regarding the use of LDLT vs DDLT for HCC patients,there is no evidence to support the higher HCC recurrence after LDLT than DDLT,and LDLT remains a reasonable treatment option for HCC patients with cirrhosis.     

Liver transplantation for hepatocellular carcinoma: Korean experience

Hepatocellular carcinoma (HCC) is the second most common cause of male cancer death in Korea, where the major etiology, chronic hepatitis B virus infection, is endemic. With a high incidence of unresectable HCCs and a low cadaveric organ donation rate, the number of adult living-donor liver transplantations (LDLTs) has increased rapidly, by tenfold, over the past 10 years, as an alternative to deceased-donor liver transplantation (DDLT) in Asia, including Korea. Currently, HCC accounts for more than 40% of the indications for adult LDLT as the associated decompensation cirrhosis or unresectable HCC with 2.8% perioperative mortality at our institute. In determining eligibility for LDLT, the Milan criteria, which have a major aim of reducing the wastage of cadaveric liver grafts, still remain the gold standard. Our published results with 168 adult LDLTs show no difference from the results with DDLT for HCC that meets the Milan criteria. However, since a substantial proportion of adult LDLT patients not fulfilling the Milan criteria have been found to survive for longer than expected, and because a live donor organ is a private gift, most LDLT programs in Korea accept HCC patients beyond the Milan criteria, and the reported 3-year survival rates for such patients are approximately 63%. Our new proposal for expanded criteria (Asan criteria; tumor diameter ≤5 cm, number of lesions ≤6, no gross vascular invasion) in LDLT has focused on extending the number limits but keeping the maximum tumor size at 5 cm, because even modest expansion of tumor size limits beyond the Milan criteria adversely affected survival. The overall 5-year patient survival rates were 76.3 and only 18.9% within and beyond the Asan criteria, respectively; these criteria broaden the indications for patient selection and can more accurately identify patients who will benefit from LDLT than the conventional Milan criteria and the University of California at San Francisco criteria. In Asia, where the option for DDLT is minimal or negligible, LDLT with the modest expanded selection criteria will continue to provide a chance of long-term survival for some patients with advanced HCC.     

Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation

AIM: To evaluated patterns and outcomes of hepatocellular carcinoma(HCC) recurrence after living donor liver transplantation(LDLT).METHODS: From 2001 to 2014, 293 patients underwent LDLT for HCC at our transplant center. We retrospectively reviewed 54(18.4%) patients with HCC recurrence after LDLT. We evaluated patterns and outcomes of HCC recurrence after LDLT, with particular attention to the Milan criteria at transplantation, treatments for HCC-recurrent patients, and factors related to survival after HCC recurrence. Furthermore, we evaluated the efficacy of combination treatment of sorafenib and an mT OR inhibitor.RESULTS: The 1-, 2-, and 3-year overall survival rates after HCC recurrence were 41.1%, 20.5%, and 15.4%, respectively. The median time interval between LDLT and HCC recurrence was 6.5 mo. Although recurrence rates according to the Milan criteria at LDLT were significantly different, HCC recurrence patterns and survival rates after HCC recurrence were not significantly different between the two groups. Time to recurrence 12 mo(P = 0.048), multiple recurrences at HCC recurrence(P = 0.038), and palliative treatment for recurrent tumors(P = 0.003) were significant independent prognostic factors for poor survival after HCC recurrence in a multivariate analysis. The combination treatment of sorafenib and sirolimus showedsurvival benefits in the palliative treatment group(P = 0.005).CONCLUSION: Curative treatment for recurrent HCC after LDLT is the most important factor in survival rates after HCC recurrence and combination treatments of sorafenib and an m TOR inhibitor could have survival benefits in patients with HCC recurrence after LT in the palliative treatment group.     

Liver transplantation for hepatocellular carcinoma: current topics in France

Background

Excellent survival obtained with liver transplantation (LT) for limited hepatocellular carcinoma (HCC) in patients with chronic liver disease is still challenged by the increasing discrepancy between candidates and grafts available. We review the current strategy of LT for HCC in our country highlighting the tendency: (1) to expand recipient selection beyond the Milan criteria, (2) to use systematic pre-LT treatments with a greater number of resections and (3) new rules for graft attribution.

Results

Although the vast majority of cirrhotic patients with HCC are transplanted within the Milan criteria; the number of candidates is continually rising, while the number of grafts available is stable with a disappearance of adult LDLTs. Moreover, the new rules for organ allocations, mainly based on the MELD score, minimize the accessibility to liver grafts for patients with HCC and compensated liver disease. For these reasons, in France we have observed an increase in waiting time for HCC patients, leading to the extensive use of pre-LT treatments in order to limit the list dropouts. Many studies have been performed on transarterial chemo-embolization (TACE) and supraselective TACE. Moreover, the use of liver resection (LR) as a bridge therapy, showing that initial resection does not impair short- and long-term survival, led French surgeons to develop the concept of LR as a way to select patients who might benefit from LT and to use it, in selected cases, as a primary therapy, considering LT as salvage treatment in case of recurrence.

Conclusions

The number of HCC candidates who cannot benefit from a LT is increasing worldwide. The French answer to this situation involves pre-LT treatments, particularly partial LR, based mainly on the excellent Japanese results in this field. Moreover, the country of « égalité » is actually modifying the rules of graft attribution in order to reduce the inequality between the HCC patients with poor and good liver function.     

Living donor liver transplantation does not increase tumor recurrence of hepatocellular carcinoma compared to deceased donor transplantation

AIM: To compare the recurrence-free survival (RFS) and overall survival (OS) of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT).METHODS: We retrospectively collected clinical data from 408 liver cancer patients from February 1999 to September 2012. We used the chi-squared test or Fisher’s exact test to analyze the characteristics of LDLT and DDLT. Kaplan-Meier analysis was used to compare the RFS and OS in HCC.RESULTS: Three hundred sixty HBV-positive patients (276 DDLT and 84 LDLT) were included in this study. The mean follow-up time was 27.1 mo (range 1.1-130.8 mo). One hundred eighty-five (51.2%) patients died during follow-up. The 1-, 3-, and 5-year RFS rates for LDLT were 85.2%, 55.7%, and 52.9%, respectively; for DDLT, the RFS rates were 73.2%, 49.1%, and 45.3% (P = 0.115). The OS rates were similar between the LDLT and DDLT recipients, with 1-, 3-, and 5-year survival rates of 81.8%, 49.5%, and 43.0% vs 69.5%, 43.0%, and 38.3%, respectively (P = 0.30). The outcomes of HCC according to the Milan criteria after LDLT and DDLT were not significantly different (for LDLT: 1-, 3-, and 5-year RFS: 94.7%, 78.7%, and 78.7% vs 89.2%, 77.5%, and 74.5%, P = 0.50; for DDLT: 86.1%, 68.8%, and 68.8% vs 80.5%, 62.2%, and 59.8% P = 0.53).CONCLUSION: The outcomes of LDLT for HCC are not worse compared to the outcomes of DDLT. LDLT does not increase tumor recurrence of HCC compared to DDLT.     

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.     

Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation

AIM:To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma(HCC)patients in living-donor liver transplantation(LDLT).METHODS:From October 2000 to November 2011,224 patients who underwent living donor liver transplantation for HCC at our institution were enrolled in this study.We analyzed disease-free survival(DFS)and overall survival(OS)after LT in patients with HCC and designed a new score model using pretransplant neutrophil-lymphocyte ratio(NLR)and C-reactive protein(CRP).RESULTS:The DFS and OS in patients with an NLR level≥6.0 or CRP level≥1.0 were significantly worse than those of patients with an NLR level<6.0 or CRP level<1.0(P=0.049,P=0.003 for NLR and P=0.010,P<0.001 for CRP,respectively).Using a new score model using the pretransplant NLR and CRP,we can differentiate HCC patients beyond the Milan criteria with agood prognosis from those with a poor prognosis.CONCLUSION:Combined with the Milan criteria,new score model using NLR and CRP represent new selection criteria for LDLT candidates with HCC,especially beyond the Milan criteria.     

Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: the controversies continue

Liver transplantation has now become a favored option for patients with early-stage hepatocellular carcinoma (HCC) with or without impaired hepatic function as a complication of underlying cirrhosis. To overcome the persistent donor organ shortage, the use of adult-to-adult living donor liver transplantation (LDLT) has recently increased, especially in Asian countries. In the use of LDLT, several controversies remain including the safety of living donation and expanding the current Milan criteria. Most physicians agree that criteria for transplanting patients with HCC should be expanded beyond the Milan criteria because the Milan criteria miss a number of patients who may benefit from LDLT; however, the expanded criteria proposed were different (the size and number of HCCs and the biologic markers) from one center to the other. When we consider LDLT as a treatment option for patients with HCC, donor safety should be kept in mind first, and the wishes of both patient and donor should be weighed against the potential (if small) risk for the donor. In contrast to deceased donor liver transplantation, the benefit of LDLT is better appreciated in terms of gain in life expectancy than in terms of survival when the wishes of both patient and donor outweigh the donor risk. Further research on the predictors of benefit of LDLT to HCC patients other than the size and number of HCC such as molecular profiling of HCC are necessary to finally reach a consensus.     

Liver transplantation for hepatocellular carcinoma: the Japanese experience

Despite the wide spectrum of selection criteria used by living donor liver transplantation (LDLT) centers in Japan, LDLT for hepatocellular carcinoma (HCC) can achieve an acceptable outcome comparable to the outcome for deceased donor liver transplantation (DDLT) for HCC. One of the most crucial considerations in liver transplantation for HCC is the advent of expanded criteria that allow more patients with HCC to receive the organs and offer similar or even better results compared to the Milan of UCSF criteria. Expanded criteria for HCC are proposed from three single-center and one multicenter study in Japan. These criteria are based on the independent predictors for outcome derived from the analyses of the pretransplant factors and explant pathology. The beneficial effect of those proposed criteria can be predicted by the inclusion rates of the patients compared to the Milan or UCSF criteria in the same cohort and the outcome for those included patients. While application of the UCSF criteria increases the inclusion rate compared to the Milan criteria by 5–10%, these proposed criteria increase the inclusion rates by 5–54% compared to the Milan criteria. The higher inclusion rates compared to the application of the Milan criteria are achieved by criteria including tumor markers, either AFP or PIVKA II or both. Inclusion of tumor markers in addition to parameters of tumor morphology might be the key to establish the best criteria for liver transplantation for HCC.     

Living donor liver transplantation in hepatocellular carcinoma beyond the Milan criteria

Background/Aims: In patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria, the recurrence rate after liver transplantation is over 50%. We investigated pretransplant factor(s) that could predict recurrence after living donor liver transplantation (LDLT) in patients with HCC exceeding the Milan criteria. Methods: Pre‐operative imaging showed that, of the 111 HCC patients who underwent LDLT between June 1995 and January 2006, 37 exceeded the Milan criteria. Clinical factors before LDLT were evaluated. Results: The 1‐ and 3‐year cumulative recurrence rates were 35 and 55% respectively. Pretransplant risk factors for HCC recurrence were large tumour size (>6 cm, P=0.001), tumour exposed to the liver surface (P=0.014) and progressive disease after pretransplant treatment (P=0.038). The 2‐year HCC recurrence rates in patients with 0, 1, 2 and 3 factors were 0% (0/4), 9% (1/16), 80% (8/10) and 100% (7/7) respectively (P<0.001). The 2‐year survival rate was significantly higher in patients with 0 or 1 factor than in patients with two or more factors (P=0.022). Conclusions: In patients with HCC exceeding the Milan criteria, the three pretransplant factors that may be useful for identifying those with high HCC recurrence potential after LDLT are tumour size >6 cm, progressive disease after pretransplant treatment and tumour exposed to the liver surface.     

Incidence and risk factors of hepatocellular carcinoma recurrence after liver transplantation in the MELD era

Background and Aims  

Deceased donor liver transplantation (DDLT) rates for candidates with hepatocellular carcinoma (HCC) have significantly increased in the MELD era because of the extra priority given to these candidates. We examined the incidence and pre-DDLT radiological and donor factors associated with post-DDLT HCC recurrence in the MELD era.     

Live-donor liver transplantation for hepatocellular carcinoma

Live-donor liver transplantation (LDLT) is a valuable option for patients with hepatocellular carcinoma (HCC) because compared with deceased-donor liver transplantation (DDLT), the tumor could be eradicated early. However, a higher incidence of recurrence is observed when the result is compared with DDLT. The difference is explained by the timing of transplant because only patients with slow HCC growth (and probably less aggressive tumors) can wait for DDLT. Nevertheless, arecent survey of results of LDLT for HCC in Asia indicated that the 3-year survival rate is approximately 60–80%, which is better than that of any treatment modalities for inoperable HCC associated with poor liver function. LDLT for HCC is still worthwhile to pursue and deserves further evaluation.     

Liver transplantation for hepatocellular carcinoma

The role of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) has evolved over the past two decades, and transplantation has become one of the few curative treatment modalities for patients with HCC. Early results were poor, but the current restrictive selection criteria can yield excellent results. This review will discuss recent issues in the field, including (1) factors affecting the recurrence of HCC after LT; (2) the effect of downstaging HCC before LT, including transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA); and (3) living-donor versus deceased-donor liver transplantation for HCC patients. The most important factors that have been described to affect LT survival include the tumor size, vascular invasion, and the degree of tumor differentiation. Recently, tumor markers, including alpha-fetoprotein and des-gamma carboxy prothrombin, were reported as predictors of HCC recurrence after LT. Furthermore, the experience accumulated with locoregional therapies such as TACE and RFA as bridging procedures to LT, along with the reduced waiting time under the HCC-adjusted MELD (model for endstage liver disease) system for organ allocation has led to improved outcomes. With the recent advances in adult living-donor liver transplantation (LDLT), there may be a marked change in the role of liver transplantation for hepatic malignancies, in particular for HCC.     

High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.     

Liver transplantation for hepatocellular carcinoma: the Hong Kong experience

Orthotopic liver transplantation (OLT) is the best treatment option for selected patients with hepatocellular carcinoma (HCC) with the background of cirrhosis since this treatment modality can cure both diseases at once. Over the years, the applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a shortage of deceased donor liver grafts is a universal problem having to be faced in all transplant centers. Living-donor liver transplant (LDLT) has therefore been developed to counteract organ shortage and the high prevalence of HCC. The application of LDLT for HCC is a complex process involving donor voluntarism, selection criteria for the recipient and justification with respect to long-term survival in comparison to the result of deceased donor liver transplant. This article reviews the authors’ experience with OLT for HCC patients in Hong Kong, with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism has a significant impact on the application of LDLT. “Fast-track” LDLT in the setting of recurrence following curative treatment carries a high risk of recurrence even though the tumor stage fulfills the standard criteria. Although the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still the main treatment option for patients with transplantable HCC in Hong Kong, and a reasonable survival outcome can be achieved in selected patients with extended indications. It is particularly true that LDLT provides the only hope for patients with advanced HCC under the constricting problem of organ shortage.     

Liver Transplantation in the MELD Era: A Single-Center Experience

Model for Endstage Liver Disease (MELD) score has been used to allocate organs since February 2002. This policy allocates organs to candidates with regard to severity of their underlying liver disease except in the case of hepatocellular carcinoma (HCC) patients. The purpose of this study was to determine the impact of MELD on waiting times, dropout rates, and transplantation rates in all patients awaiting liver transplantation at our center. The records of all patients listed for liver transplantation between May 28, 1999, and February 27, 2004, at the Mayo Clinic, Scottsdale, Arizona, were reviewed. Candidates were grouped by two time periods as pre-MELD or post-MELD based on date of MELD implementation (February 27, 2002). The incidence of deceased donor liver transplantation (DDLT), waiting time to DDLT, dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting for or after DDLT were determined for each group. Three hundred fifty-one patients were listed for liver transplantation (195 pre-MELD, 156 post-MELD) during the study period. HCC patients had an improved rate of transplantation after MELD (pre-MELD, 1.39 persons per year; post-MELD, 3.48 persons per year). In all groups, with the exception of hepatitis C virus, the transplantation rates were the same for both categories. The hepatitis C virus group also had improved transplantation rates in the post-MELD period. HCC candidates under the new allocation policy have an increased incidence of DDLT in our institution. However, this has not disadvantaged patients with non-HCC diagnoses. Thus, the new MELD-based allocation policy has benefited all candidates by allowing more timely transplants.