Donor Factors Similarly Impact Survival Outcome After Liver Transplantation in Hepatocellular Carcinoma and Non-hepatocellular Carcinoma Patients

Background

Many have advocated the preferential use of high risk allografts for hepatocellular carcinoma patients undergoing liver transplantation. Hepatocellular carcinoma (HCC) patients tend to have relatively preserved liver function, and their outcome is felt to be driven largely by tumor-related factors.

Aim

The aim of this study was to compare the relative importance of donor versus recipient factors on post-orthotopic liver transplantation survival among HCC and non-HCC recipients.

Methods

The study group included Scientific Registry of Transplant Recipients data on adult recipients of deceased donor liver transplants from February 2002 through December 2008. Recipients were classified as HCC based on MELD exception applications and were compared to all other recipients. Predictors of post-LT survival were identified by Cox regression. To test whether donor factors have less impact on survival in HCC patients, interaction terms were created between HCC diagnosis and donor factors.

Results

Of the 40,212 DDLTs during the study period, 29,020 (72 %) met study criteria. A total of 7,786 (27 %) were transplanted with a diagnosis of HCC. The mean donor risk index was 1.5 in both cohorts. The 1-/5-year survival was 88 %/68 % and 87 %/74 % among HCC and non-HCC recipients, respectively (p < 0.0001). On multivariate analysis, there was no statistically significant interaction between HCC diagnosis and DRI (HR 0.94, p = 0.317). Likewise, no interaction was seen between HCC diagnosis and individual donor factors. In both groups, donor and recipient factors carried similar weight in determining post-LT survival.

Conclusions

Contrary to previous assumptions, donor factors play a similar role in determining survival post-LT among HCC patients and non-HCC patients.     

De novo Hepatocellular Carcinoma after Liver Transplantation

Liver transplantation is the definitive therapy for patients with advanced liver disease and its complications. Patients who are transplanted with a diagnosis of hepatocellular carcinoma (HCC) are at risk of recurrent cancer, and these patients are monitored on a regular basis for recurrence. In contrast, de novo HCC following liver transplantation is a very rare complication, and recipients without HCC at the time of transplantation are not screened. We describe the clinical features of de novo HCC over a decade after achieving a sustained viral response with treatment of hepatitis C and two decades after liver transplantation. Our case highlights the necessity of screening for HCC in the post-transplant patient with advanced liver disease even after viral clearance.     

Combined Transcatheter Arterial Embolization and Expanded Liver Resection for Hepatocellular Carcinoma with Multiple Intrahepatic Metastasis

After repeated transcatheter arterial embolization, a patient with hepatocellular carcinoma with multiple intrahepatic metastases in the entire lobe was successfully treated by extended right lobectomy with resection of the retrohepatic inferior vena cava under extracorporeal venovenous bypass.     

Hepatocellular Carcinoma and Liver Transplantation: State of the Art

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in chronic liver disease and cirrhosis. The incidence of HCC is growing worldwide.With respect to any other available treatment for liver cancer, liver transplantation (LT) has the highest potential to cure. LT allows for removal at once of both the tumor (“seed”) and the damaged-hepatic tissue (“soil”) where cancerogenesis and chronic liver disorders have progressed together. The Milan criteria (MC) have been applied worldwide to select patients with HCC for LT, yielding a 4-year survival rate of 75%. These criteria represent the benchmark for patient selection and are the basis for comparison with any other suggested criteria.However, MC are often considered to be too restrictive, and recent data show that between 25% and 50% of patients with HCC are currently transplanted beyond conventional indications. Consequently, any unrestricted expansion of selection criteria will increase the need for donor organs, lengthen waiting periods, increase drop-out rates, and impair outcomes on intention-to-treat analysis. Management of HCC recurrence after LT is challenging. There are a few reports available regarding the safety and efficacy of sorafenib for HCC recurrence after LT, but the data are heterogeneous. A multi-center prospective randomized controlled trial comparing placebo with sorafenib is advised. Alternatively, a meta-analysis of patient survival with sorafenib for HCC recurrence after LT could be helpful to characterize the therapeutic benefit and safety of sorafenib.Here, we review the use of LT for HCC, with particular emphasis on the selection criteria for transplantation in patients with HCC and management of HCC recurrence after LT.     

Hepatocellular Carcinoma: Downstaging to Liver Transplantation as Curative Therapy

Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.     

Ethnic Differences in Hepatocellular Carcinoma: Implications for Liver Transplantation

Liver transplantation (LT) as a treatment for Hepatocellular Carcinoma (HCC) provides excellent outcomes if restricted to patients who meet the Milan criteria (MC). The aim of this study was to evaluate the influence of ethnicity on eligibility for LT based on the MC. This is a retrospective cohort study of patients diagnosed with HCC at our institution between January 2000 and September 2005. We identified 169 patients, of whom 135 were male (80%), 108 were Caucasian (64%), 29% were African American (AA) and 7% were of other ethnicity. Eighty two patients (49%) met the MC at diagnosis. Age, gender, severity of liver disease or insurance status was not predictive of meeting MC at diagnosis. Ethnicity was the only significant predictor for failure to meet MC. Significantly fewer Caucasians exceeded the MC compared to AA (44 vs. 71%; P = 0.0015). Conclusion AA are more likely to present with HCC that exceeds the MC.     

Negative Impact of Preoperative Platelet-Lymphocyte Ratio on Outcome After Hepatic Resection for Intrahepatic Cholangiocarcinoma

The elevated platelet-to-lymphocyte ratio (PLR), determined using an easy blood test based on platelet and lymphocyte counts, is reported to be a predictor of poor survival in patients with several cancers. The prognostic role of preoperative PLR in patients with intrahepatic cholangiocarcinoma (ICC) has, until now, been rarely investigated. The purpose of our study was to evaluate the prognostic significance of PLR in a large cohort of ICC patients after hepatic resection.We obtained data from 322 consecutive nonmetastatic ICC patients who underwent hepatectomy without preoperative therapy between 2005 and 2011. Clinicopathological parameters, including PLR, were evaluated. Overall survival (OS) and recurrence-free survival (RFS) were assessed using the Kaplan–Meier method. Using multivariate Cox regression models, the independent prognostic value of preoperative PLR was determined.Our results showed that PLR represents an independent adverse prognostic factor for OS and RFS in ICC patients using univariate and multivariate analyses. The optimal PLR cutoff value was 123 using receiver operating curve analyses. The 5-year OS and RFS rates after hepatectomy were 30.3% and 28.9% for the group with PLR 123 greater, compared with 46.2% and 39.4% for the group with PLR less than 123 (P = 0.0058 and 0.0153, respectively). In addition, high PLR values were associated with tumor size (P = 0.020).Our results suggest that preoperative PLR might represent a novel independent prognostic factor for OS and RFS in ICC patients with hepatic resection.     

Therapeutic Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma Recurrence After Liver Transplantation: A Systematic Review and Meta-Analysis

Background: Hepatocellular carcinoma (HCC) recurrence is still threatening patient survival after liver transplantation (LT). The efficacy and safety of sorafenib in the setting of post-LT recurrence are still equivocal. This study aims to disclose the efficacy and safety profile of sorafenib in treating post-LT HCC recurrence.Materials and Methods: Electronic databases were searched to retrieve relevant publications suitable for inclusion. Data from 23 studies containing 411 patients were analyzed. The primary outcome of interest was 1-year survival rate after sorafenib treatment, and the secondary endpoints included median overall survival (OS), time to progression (TTP), treatment response, and adverse events.Results: Patients with HCC recurrence after LT treated with sorafenib achieved a 1-year survival rate of 56.8%, with a median OS of 12.8 months and a median TTP of 6.0 months. Univariate logistic regression analysis showed that male gender (P = .048), TTP (P = .021), median duration of sorafenib (P = .021), diarrhea (P = .027), fatigue (P = .044), and partial response (P = .026) were associated with a better 1-year survival rate. In addition, sorafenib exerted a significant superior effect on OS compared with best supportive care in the setting of untreatable post-LT HCC recurrence.Conclusions: Based on the results of this meta-analysis, sorafenib therapy seems to be safe and feasible and exhibits survival benefit in patients with post-LT HCC recurrence. However, prospective randomized controlled trials with larger sample sizes and more rigorous study design are required to confirm the efficacy of sorafenib.     

Liberal Policy in Living Donor Liver Transplantation for Hepatocellular Carcinoma: Lessons Learned

Background Living donor liver transplantation (LDLT) in cases of hepatocellular carcinoma (HCC) that do not fulfil accepted tumor criteria continues to be a matter of controversy. The aim of this study was to evaluate survival and prognostic factors associated with a liberal exclusionary policy. Material and Methods This is an analysis of data collected prospectively on 57 HCC patients who underwent LDLT at our institution between April 1998 and January 2007. Results Overall 3-year survival was 62%; this increased to 71% when 45-day mortality was excluded from the analysis. Age proved to be a predictor of survival irrespective of the 45-day mortality. In contrast, the Model for End stage Liver Disease (MELD) score predicted survival only when 45-day mortality was included in the analysis, while alpha fetoprotein (AFP) level predicted survival only when it was excluded. Significant cut-off values were patient age of over 60 years, MELD score above 22, and AFP level greater than 400 ng/ml. A scoring system was developed. Survival rate at 3 years—including 45-day mortality—was 72% for score =2 and 41% for score >2 (P = 0.0146). When 45-day mortality was excluded, the survival rate at 3 years was 90% for score =2 and 32% for score >2 (P = 0.00002). Conclusions Our results could further enhance current guidelines on age, MELD score, and AFP level for patients with HCC being evaluated to undergo LDLT.     

Primary Surgical Resection Versus Liver Transplantation for Transplant-Eligible Hepatocellular Carcinoma Patients

Background

Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.

Aim

The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.

Methods

The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.

Results

The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08–6.86).

Conclusion

Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.