Liver Transplantation For Hepatocellular Carcinoma Research Articles

Liver transplantation for hepatocellular carcinoma in the present era

Liver transplantation for hepatocellular carcinoma in the present era

Sarcopenia Is Associated with Higher AFP Levels in Patients with Hepatocellular Carcinoma (HCC)

Background: Sarcopenia is one of the main limitations in the postoperative course after liver resection. It has been linked to higher AFP levels in liver transplantation for HCC. We aimed to evaluate patients who underwent liver resection for histologically proven HCC in our center with respect to patients` preoperative condition, AFP levels and outcome.

Changing Map of Liver Transplantation for HCC Following Implementation of New Acuity Circle Allocation System – Efforts to Overcome Disparities by Creating a New One

Introduction: The introduction of acuity circles-based allocation and change in the model for end-stage liver disease (MELD) exception points for hepatocellular carcinoma (HCC) has created a difference in transplant opportunity for hepatocellular carcinoma (HCC) patients.

Liver cancer understaging in liver transplantation in the current era of radiologic imaging and newer generation locoregional therapies

Background: Discordance in hepatocellular carcinoma (HCC) staging between pre-transplant imaging and explant pathology is associated with an increased risk of recurrence and death. Our aim was to evaluate variables that predicted concordance/discordance in the era of new generation locoregional therapies (LRT) and improved radiologic technology in diagnosis. Methods: A single-center retrospective study was performed on patients who received a liver transplant for HCC between 2008-2019. Pre- and post-LT variables, including type of LRT, downstaging (DS), transplant time period, and radiologic response to LRT, were analyzed for concordance/discordance. Kaplan-Meier analysis was used to assess post-LT survival. Results: Of 146 patients transplanted within Milan Criteria (MC), discordance rates (understaged) were 45%. Discordance was associated with ≥ 3 HCC lesions at diagnosis but not newer generation LRT (transarterial radioembolization/ stereotactic body radiation therapy), traditional LRT or combination. No differences in discordance were seen between transplant periods (2008-2013 vs. 2014-2019), but those within MC in the earlier period had higher concordance rates. A trend was observed between DS and discordance. Conclusion: HCC stage discordance remains common and poorly predictable. Discordance was associated with three or more HCC lesions at the time of diagnosis. Patients within MC transplanted between 2008-2013 was associated with concordance, while a trend was noted between DS and discordance. No other pre- or post- LT variables predicted discordance/ concordance. Discordance was associated with decreased survival.

What Is the Optimal Bridging Therapy for Patients with Hepatitis C-associated Hepatocellular Carcinoma Awaiting Liver Transplant? An Analysis of the United States HCC Liver Transplantation Consortium

Introduction: Patients with hepatitis C (HCV)-associated hepatocellular carcinoma (HCC) often receive bridging therapy in the form of liver-directed therapy (LDT) while awaiting liver transplant (LT). The optimal modality of LDT, with respect to both cancer outcomes and response to direct-acting antiviral (DAA) therapy, remains unknown. Methods: The United States HCC Liver Transplantation Consortium was queried for patients with primary HCV-associated HCC within Milan criteria who completed DAA therapy and underwent LT. Primary outcomes were HCC recurrence-free survival (RFS) and overall survival (OS). Secondary outcome was sustained virologic response (SVR) as indicator of efficacy of DAA therapy. Results: Of 857 patients, 753 met inclusion criteria. LDT consisted of radiofrequency ablation (RFA,13.3%,N=100), transarterial chemoembolization (TACE,44.1%,N=332), yttrium-90 (Y90,4.8%,N=36), and stereotactic body radiation therapy (SBRT,2.9%,N=22). Eighty-one(10.8%) patients received no LDT and 182(24.2%) received multiple modalities. SBRT patients had the highest 5-year RFS(100%) followed by those receiving TACE(94%), Y90(91.4%), RFA(89.9%), and multiple therapies(88.2%) (p=0.048, Figure 1A). OS was higher among patients who received SBRT, but not statistically significant (p=0.685, Figure 1B). SVR rate was lower among radiation-based therapy groups (Y90 73.5%, SBRT 78.9%, others≥88%; p=0.046). Conclusions: In a homogeneous population of HCV-associated HCC patients within Milan criteria who received bridging therapy while awaiting LT, SBRT was associated with increased RFS and trended towards increased OS. However, radiation-based therapy was associated with decreased efficacy of DAA as measured by lower SVR rates. The optimal choice of bridging therapy to liver transplant must balance oncologic and virologic outcomes, but these findings seem to favor SBRT.

Influence of the ABO Blood Group System on Hepatocellular Carcinoma Recurrence After Liver Transplantation.

The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed. All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching. Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002). ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.

Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation.

Simple SummaryCurrently, most transplant centres worldwide accept patients with hepatocellular carcinoma who underwent successful downstaging. Concurrently, the effectiveness of radiological and systemic therapies used for the downstaging of hepatocellular carcinoma are increasing. It is now more frequently observed that candidates for liver transplantation have an excellent response to downstaging, even if the baseline stage was well beyond the transplantable tumour. Downstaged patients have a higher risk of dropout from the waiting list and post-transplant recurrence if not transplanted in a short time. Since an increasing number of downstaged patients affects the waitlist dynamics, the definition of upper limits of downstaging is becoming a crucial issue. In this narrative review, we summarise current evidence on the downstaging of hepatocellular carcinoma for liver transplantation, including downstaging of patients with macrovascular invasion or extrahepatic metastasis at presentation and employment of the new systemic treatments for hepatocellular carcinoma.In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.

Liver Transplantation for Hepatocellular Carcinoma after Downstaging or Bridging Therapy with Immune Checkpoint Inhibitors.

Simple SummaryImmune checkpoint inhibitors (ICI) have revolutionized the treatment of hepatocellular carcinoma (HCC). In addition to their role in advanced HCC, there is considerable interest in using ICIs in the neoadjuvant setting, either as a downstaging or bridging therapy, prior to potentially curative liver transplantation. In this article, we reviewed all the available literature on ICI use in this context. We postulate that ICIs may be utilized safely prior to liver transplant; however, further research is needed in this area.Liver transplantation offers excellent outcomes for patients with HCC. For those who initially present within the Milan criteria, bridging therapy is essential to control disease while awaiting liver transplant. For those who present beyond the Milan criteria, a liver transplant may still be considered following successful downstaging. Since the introduction of atezolizumab as part of the first-line treatment for HCC in 2020, there has been increasing interest in the use of ICIs as bridging or downstaging therapies prior to liver transplant. A total of six case reports/series have been published on this topic, with mixed outcomes. Overall, liver transplantation can be performed safely following prolonged ICI use, though ICIs may increase the risk of fulminant acute rejection early in the post-operative period. A minimal washout period between the last dose of ICI and liver transplantation has been identified as an important factor predicting transplant outcomes; however, further research is needed.

Living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria: outcome of expanded criteria in tumor size

BackgroundThe Milan criteria are the universal standard of liver transplantation for hepatocellular carcinoma (HCC). Numerous expanded criteria have shown outcomes as good as the Milan criteria. In Taiwan, living donor liver transplant (LDLT) accounts for the majority of transplantations due to organ shortages.MethodsWe retrospectively enrolled 155 patients who underwent LDLT for HCC from July 2005 to June 2017 and were followed up for at least 2 years. Patients beyond the Milan criteria (n = 78) were grouped as recurrent or nonrecurrent, and we established new expanded criteria based on these data.ResultsPatients beyond the Milan criteria with recurrence (n = 31) had a significantly larger maximal tumor diameter (4.13 ± 1.96 cm versus 6.10 ± 3.41 cm, p = 0.006) and total tumor diameter (7.19 ± 4.13 cm versus 10.21 ± 5.01 cm, p = 0.005). Therefore, we established expanded criteria involving maximal tumor diameter ≤ 6 cm and total tumor diameter < 10 cm. The 5-year survival rate of patients who met these criteria (n = 134) was 77.3%, and the 5-year recurrence rate was 20.5%; both showed no significant differences from those of the Milan criteria. Under the expanded criteria, the pool of eligible recipients was 35% larger than that of the Milan criteria.ConclusionCurrently, patients with HCC who undergo LDLT can achieve good outcomes even when they are beyond the Milan criteria. Under the new expanded criteria, patients can achieve outcomes as good as those with the Milan criteria and more patients can benefit.

The distinct responsiveness of cytokeratin 19-positive hepatocellular carcinoma to regorafenib

Cytokeratin 19-positive (CK19+) hepatocellular carcinoma (HCC) is an aggressive subtype characterized by early recurrence and chemotherapy tolerance. However, there is no specific therapeutic option for CK19+ HCC. The correlation between tumor recurrence and expression status of CK19 were studied in 206 patients undergoing liver transplantation for HCC. CK19−/+ HCC cells were isolated to screen effective antitumor drugs. The therapeutic effects of regorafenib were evaluated in patient-derived xenograft (PDX) models from 10 HCC patients. The mechanism of regorafenib on CK19+ HCC was investigated. CK19 positiveness indicated aggressiveness of tumor and higher recurrence risk of HCC after liver transplantation. The isolated CK19+ HCC cells had more aggressive behaviors than CK19− cells. Regorafenib preferentially increased the growth inhibition and apoptosis of CK19+ cells in vitro, whereas sorafenib, apatinib, and 5-fluorouracil did not. In PDX models from CK19−/+ HCC patients, the tumor control rate of regorafenib achieved 80% for CK19+ HCCs, whereas 0% for CK19− HCCs. RNA-sequencing revealed that CK19+ cells had elevated expression of mitochondrial ribosomal proteins, which are essential for mitochondrial function. Further experiments confirmed that regorafenib attenuated the mitochondrial respiratory capacity in CK19+ cells. However, the mitochondrial respiration in CK19− cells were faint and hardly repressed by regorafenib. The mitochondrial respiration was regulated by the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which was inhibited by regorafenib in CK19+ cells. Hence, CK19 could be a potential marker of the therapeutic benefit of regorafenib, which facilitates the individualized therapy for HCC. STAT3/mitochondria axis determines the distinct response of CK19+ cells to regorafenib treatment.

Safety of intra-operative blood salvage during liver transplantation in patients with hepatocellular carcinoma, a propensity score-matched survival analysis.

Intra-operative blood salvage (IBS) reduces the use of allogeneic blood transfusion. However, safety of IBS during liver transplantation (LT) for hepatocellular carcinoma (HCC) is questioned due to fear for dissemination of circulating malignant cells. This study aims to assess safety of IBS. HCC patients who underwent LT from January 2006 through December 2019 were included. Patients in whom IBS was used were propensity score matched (1:1) to control patients. Disease-free survival and time to HCC recurrence were assessed with Cox regression models and competing risk models. IBS was used in 192/378 HCC LT recipients, and 127 patients were propensity score matched. Cumulative disease-free survival at 12 and 60months was 85% and 63% for the IBS group versus 90% and 68% for the no-IBS group. Use of IBS was not associated with impaired disease-free survival (HR 1.07, 95%CI: 0.65-1.76, P=0.800) nor with increased HCC recurrence (Cause-specific cox model: HR 0.79, 95%CI: 0.36-1.73, P=0.549, Fine and Gray model: HR: 0.79, 95%CI 0.40-1.57, P=0.50). In conclusion, IBS during LT did not increase the risk for HCC recurrence. IBS is a safe procedure in HCC LT recipients to reduce the need for allogenic blood transfusion.

The Toronto Postliver Transplantation Hepatocellular Carcinoma Recurrence Calculator: A Machine Learning Approach.

Liver transplantation (LT) listing criteria for hepatocellular carcinoma (HCC) remain controversial. To optimize the utility of limited donor organs, this study aims to leverage machine learning to develop an accurate posttransplantation HCC recurrence prediction calculator. Patients with HCC listed for LT from 2000 to 2016 were identified, with 739 patients who underwent LT used for modeling. Data included serial imaging, alpha-fetoprotein (AFP), locoregional therapies, treatment response, and posttransplantation outcomes. We compared the CoxNet (regularized Cox regression), survival random forest, survival support vector machine, and DeepSurv machine learning algorithms via the mean cross-validated concordance index. We validated the selected CoxNet model by comparing it with other currently available recurrence risk algorithms on a held-out test set (AFP, Model of Recurrence After Liver Transplant [MORAL], and Hazard Associated with liver Transplantation for Hepatocellular Carcinoma [HALT-HCC score]). The developed CoxNet-based recurrence prediction model showed a satisfying overall concordance score of 0.75 (95% confidence interval [CI], 0.64-0.84). In comparison, the recalibrated risk algorithms' concordance scores were as follows: AFP score 0.64 (outperformed by the CoxNet model, 1-sided 95% CI, >0.01; P=0.04) and MORAL score 0.64 (outperformed by the CoxNet model 1-sided 95% CI, >0.02; P=0.03). The recalibrated HALT-HCC score performed well with a concordance of 0.72 (95% CI, 0.63-0.81) and was not significantly outperformed (1-sided 95% CI, ≥0.05; P=0.29). Developing a comprehensive posttransplantation HCC recurrence risk calculator using machine learning is feasible and can yield higher accuracy than other available risk scores. Further research is needed to confirm the utility of machine learning in this setting.

Are the criteria always right? Assessment of hepatocellular carcinoma cases in living donor liver transplantation at a high-volume center

Background/aimWith the increased experience in living donor liver transplantation (LDLT), it has been adopted for the treatment of hepatocellular carcinoma (HCC), with emerging discussions of criteria beyond tumor size and number. In contrast to deceased donor liver transplantation (DDLT), recipient selection for LDLT is not limited by organ allocation systems. We discuss herein the assessment, criteria, and experience with liver transplantation (LT) in HCC cases at a high-volume LDLT center.Material and methods: Between August 2006 and December 2017, 191 adult LT HCC recipients with at least one-year follow-up were retrospectively analyzed.Results In 191 patients, one-, three- and five-year survival rates were 87.2%, 81.6%, and 76.2%, respectively, including early postoperative mortality. In 174 patients with long-term follow-up, one-, three- and five-year disease-free survival rates were 91.6%, 87.7%, and 84.4%, respectively. When multivariate analysis was utilized, tumor differentiation was the only factor which statistically affected survival (p = 0.025). Conclusion LDLT allows us to push the limits forward and the question “Are the criteria always right?” is always on the table. We can conclude that, with the advantage of LDLT, every HCC patient deserves a case-by-case basis discussion for LT under scientific literature support. In borderline cases, tumor biopsy might help determine the decision for LT.

Sex-based Disparities in Hepatocellular Carcinoma Recurrence After Liver Transplantation.

Women with chronic liver disease have lower rates of hepatocellular carcinoma (HCC) as compared to men; it is unknown if there are sex-based differences in HCC recurrence postliver transplant. We conducted an analysis of patients who underwent liver transplant for HCC in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2012 through December 31, 2017. A total of 12 711 patients underwent liver transplant for HCC: 2909 (23%) women and 9802 (73%) men. Women had significantly lower rates of postliver transplant HCC recurrence than men (4.0% versus 5.4%, P = 0.002). A cox-regression analysis for postliver transplant HCC recurrence highlighted that even after accounting for etiology of cirrhosis, alpha-fetoprotein at liver transplant, tumor diameter, tumor pathology, and vascular invasion, female sex was associated with a 25% lower risk of postliver transplant HCC recurrence (95% confidence interval: 0.57-0.99). There were no interactions between female sex and the following variables: age, type of locoregional therapy, alpha-fetoprotein, donor sex, body mass index, or nonalcoholic steatohepatitis etiology (P > 0.05 for each). This study demonstrates an independent effect of sex on risk for HCC recurrence postliver transplant. Our data highlight an opportunity to better understand HCC tumor biology by investigating the drivers of this sex-based difference in HCC recurrence.

From the Editor’s desk…

From the Editor’s desk…

Stereotactic ablative body radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma: preliminary results of Baskent University experience

Stereotactic ablative body radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma: preliminary results of Baskent University experience

S3398 Glecaprevir/Pibrentasvir Is an Effective Treatment for Patients Receiving HCV Positive Liver Transplants

Introduction: Liver transplantation (LT) from HCV positive donors has become an option to expand a limited donor pool with the advent of Direct-Acting Antiviral therapy (DAA). Current guidelines for post-LT Hepatitis C treatment includes Glecaprevir/Pibrentasvir (Mavyret). Our study focuses on Glecaprevir/Pibrentasvir’s efficacy in achieving a Sustained Virological Response (SVR) and undetectable Viral Load (VL) in HCV Donor (D+)/Recipient (R-) transplanted patients. Methods: We performed a retrospective cohort review of 13 HCV D+/R- patients who underwent LT at our institution from January 2019 to November 2020. Patient demographics, co-morbidities, liver cirrhosis etiology, HCV VL and genotype was recorded. Patients received a standard 12 weeks of Glecaprevir/Pibrentasvir initiated at the time of VL detection on post-op day 3. Other data included post-LT complications, mortality, graft rejection, time to achieve undetectable VL, and liver function tests at first and last clinic visits post-LT. Results: Our cohort consisted of 13 HCV D+/R- patients; 92% male, 62% white, 12 orthotopic liver transplants, and 1 simultaneous liver kidney transplant with an average age 58 +/- 11, BMI of 30 +/- 6 and MELD-Na 27 +/- 8. Liver cirrhosis etiology included NASH (50%), Alcohol (33%), NASH/Alcohol (8%) and other (9%). HCV genotypes at the time of VL detection included 1a (54%), 2 (8%), and 3 (31%). All patients completed treatment and 92% (n = 12) achieved SVR at 12 weeks. Mean VL detected within the first week post-LT was 10.7 million +/- 9.7 million and mean undetectable VL was achieved within 34 +/- 21 days. Mean ALT and AST at the first clinic visit during the first three to five weeks of Glecaprevir/Pibrentasvir initiation was 27.8 +/- 17.8 and 22.2 +/- 12.6 respectively and mean ALT and AST at the last clinic visit 7-17 months post-LT following Glecaprevir/Pibrentasvir completion was 17.8 +/- 9.3 and 24.1 +/- 24.3 respectively. Following treatment, one patient had graft rejection and one patient mortality was noted due to events following post-operative complications. Conclusion: Patients treated with Glecaprevir/Pibrentasvir following LT from HCV positive donors had overall excellent graft survival with most patients achieving SVR at 12 weeks and maintaining undetectable VL post-transplantation without significant elevations in liver function tests during treatment and after completion. Glecaprevir/Pibrentasvir is an effective treatment for patients receiving LT from HCV positive donors.Table 1.: HCV D+/R- transplanted patients receiving Glecaprevir/Pibrentasvir. CKD = Chronic Kidney Disease CAD = Coronary Artery Disease HCC = Hepatocellular Carcinoma LT = Liver Transplant AKI = Acute Kidney Injury LFT = Liver Function Tests Data represented as averages and mean +/- standard deviation.

Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma.

The proportion of liver transplantation (LT) for hepatocellular carcinoma (HCC) has kept on increasing over the past years and account for 20%-40% of all LT. Post-transplant HCC recurrence is considered the most important factor affecting the long-term survival of patients. The use of different types of immunosuppressive agents after LT is closely associated with an increased risk for HCC recurrence. The most commonly used conventional immunosuppressive drugs include the calcineurin inhibitors tacrolimus (FK506) and mammalian target of rapamycin inhibitor rapamycin (RAPA). Compared with tacrolimus, RAPA may carry an advantage in survival benefit because of its anti-tumor effects. However, no sufficient evidence to date has proven that RAPA could increase long-term recurrence-free survival and its anti-tumor mechanism of combined therapy remains incompletely clear. In this review, we will focus on recent advances in clinical application experience and basic research results of RAPA in patients undergoing LT for HCC to further guide the clinical practice.

Liver Transplantation for HCC in HIV-Infected Patients: Long-Term Single-Center Experience.

Simple SummaryHCC are now emerging as leading causes of morbidity in HIV-infected patients since HAART has made it possible to achieve long life expectation by reducing AIDS-related complications. The results of liver transplantation for HCC in HIV-infected patients are still contradictory. In this paper we demonstrated in a cohort of 32 HIV-infected patients undergoing LT for HCC that the post-LT outcomes are comparable to the controlled cohort of uninfected recipients. Long survival rates were observed for HIV-infected LT patients with HCC.Background: HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. Aim: To address the results of liver transplantation (LT) for HCC in HIV-infected patients. Methods: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post-LT recurrence. Results: Among 1010 LT, 32 were HIV-infected recipients. With an average follow-up of 62 ± 51 months, 5-year overall survival in LT recipients with and without HIV-infection was 71.6% and 69.9%, respectively (p = ns), whereas 5-year graft survival in HIV-infected and HIV-non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83, p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18, p< 0.001), HCC diameter (HR 1.16, p = 0.028), and number of HCC nodules (HR 1.26, p = 0.003) were predictors of recurrence post-LT. Conclusion: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post-LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.

Stick to Milan: Infeasibility of the Brazil-Milan Criteria in recommending patients with hepatocellular carcinoma for liver transplantation

This article discusses the infeasibility of adhering to the Brazil-Milan Criteria for determining whether patients with hepatocellular carcinoma (HCC) should be offered liver transplantation. The Criteria are currently used widely in Brazil. However, since they expand the net of the transplant-eligible population, and that transplantation is shown to improve clinical outcomes in HCC patients relative to other treatments, they are inherently attractive and may be adopted by other countries in determining whether HCC patients should receive liver transplantation. I argue that the Criteria unjustifiably disregard the number of tumour nodules found in the patient. This number may be indicative of the recurrence potential of the disease, since these nodules can originate from different clonal populations. The greater the number, the higher the risk these nodules are associated with clones which contain genetic mutations conferring even greater potential for proliferation and dissemination. Clusters of tumour cells may be micro-disseminated to vascular structures surrounding the liver, as well as extrahepatic systems. This increases recurrence potential and reduces the benefit of liver transplantation in these patients. Thus, HCC patients harbouring fewer but larger tumour nodules may present with a more favourable genomic and epigenomic profile than those with more, albeit smaller, tumour nodules. Patients with more tumour nodules may reap greater clinical benefit if initiated on systemic therapy early, rather than wait for a suitable donor liver. Although the Criteria are reached by consensus, with reference to findings from recent studies, as well as scientific theory, it is ripe for review.