Risk Of Hepatocellular Carcinoma Recurrence Research Articles

A National Survey of Hepatocellular Carcinoma Surveillance Practices Following Liver Transplantation.

Background.Recurrence of hepatocellular carcinoma (HCC) is an important predictor of survival after liver transplantation (LT). Recent studies show that early diagnosis, aggressive treatment, and surveillance may improve outcomes after HCC recurrence. We sought to determine the current practices and policies regarding surveillance for HCC recurrence after LT.Methods.We conducted a web-based national survey of adult liver transplant centers in the United States to capture center-specific details of HCC surveillance post-LT. Responses were analyzed to generate numerical and graphical summaries.Results.Of 101 eligible adult liver transplant centers, 48 (48%) centers across the United States responded to the survey. Among the participating centers, 79% stratified transplant recipients for HCC recurrence risk, while 19% did not have any risk stratification protocol. Explant microvascular invasion (mVI) was the most common factor used in risk stratification. Use of pretransplant serum biomarkers such as alpha-fetoprotein (AFP) was variable, with only 48% of the participating centers reporting specific “cutoff” values. While a majority of centers (88%) reported having a routine imaging protocol for HCC recurrence surveillance, there was considerable heterogeneity in terms of frequency and duration of such surveillance. Of the centers that did risk stratify patients to identify those at higher risk of HCC recurrence, about 50% did not change their surveillance protocol.Conclusions.Our study affirms significant variability in center practices, and our results reflect the need for high-quality studies to guide risk stratification and surveillance for HCC recurrence.

Timing of DAA Initiation After Curative Treatment and Its Relationship with the Recurrence of HCV-Related HCC.

Hepatitis C virus infection is a major cause of chronic hepatitis, leading to cirrhosis and hepatocellular carcinoma (HCC). Many studies agree that interferon (IFN)-based antiviral therapy can reduce the risk of HCC recurrence in patients with chronic hepatitis C who have achieved a sustained virological response (SVR). The recent introduction of direct-acting antivirals (DAA) has resulted in excitingly high SVR rates. However, as an IFN-free regimen, DAAs only exert antiviral activity without an immune response. The benefit of DAA-based regimens for HCC recurrence in patients with cirrhosis and following successful curative treatment remains controversial. Additionally, the time span between curative-intent therapy and the DAA regimen is an independent risk factor for HCC recurrence, irrespective of the DAA response. HCC patients who are eligible for potentially curative therapy by liver resection or ablation should defer DAA therapy; however, the accurate timing remains unclear. In this study, we reviewed the timing of DAA initiation after curative treatment and its effect on the recurrence of related HCC.

The Mutational and Transcriptional Landscapes of Hepatocarcinogenesis in a Rat Model.

SummaryHepatocellular carcinoma (HCC) initiation is characterized by stepwise accumulation of molecular alterations, during which the early events are largely unknown. Here, we presented a comprehensive genomic and transcriptomic landscape at stages of hepatitis, cirrhosis, and HCC by using a diethylnitrosamine-induced rat HCC model. We observed the early occurrence of gene instability and aberrant cancer associated signaling pathways in liver hepatitis. We further characterized the progressive molecular changes during hepatocarcinogenesis, wherein the intense rivalry between tumor-suppressive and oncogenic strengths occurred in cirrhosis stage. Despite the significant pathological difference, mutation signatures and expression landscape are highly similar between hepatitis and cirrhosis stages. Furthermore, we identified PI3K-Akt signaling pathway as a key pathway in the process of hepatocarcinogenesis through integrative analysis, and PIK3CD is a potential biomarker indicating HCC recurrence. The dynamic immune response during hepatocarcinogenesis, such as continuous decline of monocytes, suggests an immunological intervention strategy beyond chemoprevention for liver cancer.

Hepatocellular carcinoma from the view of gastroenterologist/hepatologist

Hepatocellular carcinoma (HCC) is one of the major complications of chronic liver disease, mostly of liver cirrhosis. Liver diseases from different causes differ in the risks of HCC development. Different mechanisms of carcinogenesis are involved in HCC development in different liver diseases as well. Generally, two main pathways are distinguished: the cause of liver disease itself (e.g. viral infections, accumulation of heavy metals etc.) and chronic liver inflammation and fibrogenesis, including mechanisms of oxidative stress. Rare cases of HCC in liver without underlying cirrhosis are likely the consequences of the mechanisms directly linked with particular etiological factor (e.g. protein X in chronic hepatitis B virus (HBV) infection). The key approach which can lead to significantly better results of any treatment used in HCC cases is HCC screening and surveillance. The appropriate method of HCC surveillance is abdominal ultrasonography in 6-month intervals. There is still one question to be solved: the correct definition of target population which should undergo this method of surveillance. Currently, the target population in the developed world is defined as all patients with liver cirrhosis. Unfortunately, the only method of primary prevention of HCC is available: universal HBV vaccination. Antiviral treatment of hepatitis B or C is considered as a method of secondary prevention. Adjuvant therapy of HCC after its primary therapy (antiviral therapy after HCC resection etc.) and other measures able to reduce HCC recurrence risk are usually mentioned as tertiary prevention approach. The BCLC staging system is the most common system used in Europe for the classification of HCC at the dia-gnosis. This classification combines the stage of HCC itself with other parameters, such as liver disease severity (Child - Pugh classification), portal hypertension etc. BCLC is a system which guides the physicians to optimal treatment options in every HCC stage. The only potentially curable approaches are surgical resection or liver transplantation. These options may be used in 1/3 of all HCC patients. Unfortunately, the vast majority of HCC patients can be treated only by palliative treatment options with transarterial chemoembolisation being the most common one.

Influence of aspirin use on clinical outcomes of patients with hepatocellular carcinoma: a meta-analysis

Aspirin use has been suggested to reduce cancer risk. However, previous studies showed inconsistent results as for the association between aspirin use and mortality in patients with hepatocellular carcinoma (HCC). The aim of the study was to evaluate the influence of aspirin use on clinical outcomes of patients with HCC in a meta-analysis. Studies were obtained via systematic search of PubMed, Cochrane's Library, and Embase databases. A random-effect model, which incorporated the potential heterogeneity, was used to pool the results. Six retrospective cohort studies including 18,855 HCC patients that underwent liver resection or transarterial chemoembolization were included. Pooled results showed that compared to the non-users, aspirin users of HCC had significantly reduced risk of HCC recurrence (risk ratio [RR]: 0.74, 95% confidence interval [CI]: 0.59-0.93, p = 0.01; I2 = 34%) and all-cause mortality (RR: 0.59, 95% CI: 0.47-0.73, p < 0.001; I2 = 0%) after controlling of potential confounding factors. In addition, pooled results showed that aspirin use was not associated with a significantly increased risk of major bleeding events (RR: 1.42, 95% CI: 0.81-2.51, p = 0.22; I2 = 29%) in patients with HCC. Evidence from retrospective studies suggests that aspirin use is associated with reduced recurrence and all-cause mortality of HCC. These results should be validated in prospective cohort studies and randomized controlled trials.

Clinical value of circulating tumor cells for the diagnosis and prognosis of hepatocellular carcinoma (HCC): A systematic review and meta-analysis.

Background:To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC).Methods:Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis.Results:Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57–0.63), 0.95 (95%CI = 0.93–0.96), 0.36 (95%CI = 0.28–0.48), 11.64 (95%CI = 5.85–23.14), and 38.94 (95%CI = 18.33–82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55–3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89–4.86; P < .01).Conclusion:CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.

Clinical efficacy of direct-acting antiviral therapy for recurrent hepatitis C virus infection after liver transplantation in patients with hepatocellular carcinoma.

BACKGROUNDRecurrent hepatitis C virus (HCV) infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation. Direct-acting antiviral (DAA) therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting. However, there are insufficient data regarding its efficacy in liver transplant (LT) recipients with a history of hepatocellular carcinoma (HCC), and the risk of HCC recurrence after DAA therapy is unknown.AIMTo demonstrate predictors of DAA treatment failure and HCC recurrence in LT recipients.METHODSA total of 106 LT recipients given DAAs for recurrent HCV infection from 2015 to 2019 were identified (68 with and 38 without HCC). Descriptive statistics and logistic regression models were used to estimate the multivariate odds ratios and respective 95% confidence intervals for predictors of treatment failure and HCC recurrence.RESULTSSix patients (6%) experienced DAA therapy failure post-LT and 100 (94%) had a sustained virologic response at follow-up week 12. A high alanine transaminase level > 35 U/L at treatment week 4 was a significant predictor of treatment failure. Relapse to pre-LT DAA therapy is a predictor of post-LT HCC recurrence, P = 0.04. DAA relapse post-LT was also associated with post-transplantation HCC recurrence, P = 0.05.CONCLUSIONDAAs are effective and safe in the treatment of recurrent HCV infection in LT recipients with history of HCC. Relapse to pre- and post-LT DAA therapy is associated with post-transplantation HCC recurrence.

Preoperative prediction score of hepatocellular carcinoma recurrence in living donor liver transplantation: Validation of SNAPP score developed at Asan Medical Center

Preoperative prediction score of hepatocellular carcinoma recurrence in living donor liver transplantation: Validation of SNAPP score developed at Asan Medical Center

Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients.

Background/AimsAlthough hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown.MethodsA total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed.ResultsDuring a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years.ConclusionsThe HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.

Hepatitis B Virus Pre-S Mutants as Biomarkers and Targets for the Development and Recurrence of Hepatocellular Carcinoma.

Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), the leading cause of cancer-related death worldwide. Despite progress in the prevention and therapy of HCC, high incidence and recurrence rates of HCC remain big threats, resulting in poor patient survival. Effective biomarkers and targets of HCC are therefore urgently needed for better management and to improve patient outcomes. Pre-S mutants have been well demonstrated as HBV oncoproteins that play important roles in HCC development through activation of multiple oncogenic signal pathways in hepatocytes, in vitro and in vivo. The presence of pre-S mutants in patients with chronic HBV infection and HBV-related HCC has been associated with a significantly higher risk of HCC development and recurrence after curative surgical resection, respectively. In this review, we summarize the roles of pre-S mutants as biomarkers for predicting HBV-related HCC development and recurrence, and highlight the pre-S mutants-activated oncogenic signal pathways as potential targets for preventing HBV-related HCC development.

Change in the Recurrence Pattern and Predictors over Time after Complete Cure of Hepatocellular Carcinoma.

Background/AimsWe investigated changes in recurrence rates and significant recurrence predictors over time after complete cure of hepatocellular carcinoma (HCC).MethodsA total of 1,491 patients with first-time diagnosis of Barcelona Clinic Liver Cancer stage A HCC, completely cured by treatment between 2007 and 2016, were recruited from two Korean tertiary institutes.ResultsThe mean age of the population (1,144 men and 347 women) was 58.6 years. Of the total population, 914 patients (61.3%) had liver cirrhosis. Nine-hundred and forty-one (63.1%) and 550 (36.9%) patients were treated with surgical resection and radiofrequency ablation (RFA), respectively. One-year cumulative incidences of HCC recurrence were 14.3%, 9.9%, and 5.1% from the time of treatment, 3 years after treatment, and 5 years after treatment, respectively. Upon multivariate analysis, multiple tumors, maximal tumor size ≥3 cm, and high Model for End-Stage Liver Disease scores were independently associated with increased HCC recurrence risk from the time of treatment and 1 and 2 years after curative treatment (all p<0.05, except for maximal tumor size ≥3 cm for recurrence 2 years after treatment). Meanwhile, liver cirrhosis and RFA were independently associated with the increased HCC recurrence risk for almost all time points (liver cirrhosis all p<0.05; RFA all p<0.005 except for recurrence from 5 years after treatment).ConclusionsThe recurrence rate of HCC after curative treatment gradually decreased over time. Two years after treatment, when tumor-related factors lose their prognostic implications, may be used as a cutoff to define the boundary between early and late recurrence of HCC. (Gut Liver 2021;15-429)

Abstract 2345: Statin use associated with reduced risk of hepatocellular carcinoma recurrence following liver resection: A systematic review and meta-analysis

Abstract The effect of statins in preventing hepatocellular carcinoma (HCC) recurrence after curative liver resection has been controversial. Some retrospective studies identified perioperative use of statins was associated with significantly lower risk of HCC recurrence and improve recurrence-free survival (RFS) after liver resection, among patients with or without chronic hepatitis viral infection in multivariate survival analysis. However, a recent single-center study enrolled 430 cases in Taiwan revealed that the protective effect of statins was only significant in univariate analysis but not significant in multivariate analyses. To evaluate the effect of statins on the risk of HCC recurrence after curative liver resections, we performed a systematic review and meta-analysis on this topic. A systematic search of Medline, Embase, and Web of Science was conducted through December 2019. Studies were included if they evaluated perioperative exposure to statins, reported the recurrence of HCC after curative resection, and reported hazard ratios (HR) of multivariable analysis by Cox proportional hazards model. Summary HR estimates with 95% confidence intervals (CI) were calculated using the random-effects model. The analysis included 5 studies reporting the recurrence of HCC among 8,586 patients after liver resection, in which 411 of them received perioperative statins treatments. A meta-analysis of the studies showed a significant (39%) reduction in the risk of HCC recurrence among patients who took statins (adjusted HR, 0.61; 95% CI, 0.49-0.76), with no or little heterogeneity among studies (χ2=5.58, df=4, I2=28%). In conclusion, perioperative statins use may improve recurrence-free survival and decrease the risk of HCC recurrence after curative liver resection. Further prospective studies and larger randomized controlled trials (RCTs) are warranted to validate the conclusion. Statin usersNon-statin usersAdjusted Hazard RatioStudyTotalTotalWeightIV, Random, 95%CIYear of publicationWu 2012175439437.6%0.68 (0.53-0.87)2012Lee 2016132207831.2%0.66 (0.49-0.90)2016Kawaguchi 2017317037.0%0.34 (0.12-0.75)2017Nishio 20184360014.5%0.42 (0.25-0.71)2018Young 2019304009.8%0.79 (0.41-1.52)2019Total (95% CI)4118175100.0%0.61 (0.49-0.76)Heterogeneity: Tau2=0.02; Chi2=5.58, df=4 (p=0.23); I2=28%Test for overall effect: Z=4.43 (p&amp;lt;0.00001) Citation Format: Chun Philip Yeung, Siu Tim Cheung, Kwok Chai Kelvin Ng, Bo San Paul Lai, Ching Ning Charing Chong. Statin use associated with reduced risk of hepatocellular carcinoma recurrence following liver resection: A systematic review and meta-analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2345.

Factors influencing early recurrence of hepatocellular carcinoma after curative resection.

ObjectiveTo identify the factors influencing early recurrence in patients with hepatocellular carcinoma (HCC) after curative resection.MethodsClinical data for 99 patients with HCC undergoing curative resection were analyzed. The clinicopathological factors influencing early recurrence were analyzed by Cox regression.ResultsTwenty-five of 99 patients (25.3%) suffered from early recurrence. There were significant differences between patients with and without recurrence in terms of tumor diameter, tumor capsular integrity, and preoperative alpha fetoprotein level. Cox regression analysis revealed that a tumor diameter >2.6 cm and preoperatively increased total bilirubin (TBL) level were risk factors for postoperative recurrence, while tumor capsular integrity had a protective effect on postoperative recurrence. After adjusting for preoperative TBL level and tumor capsular integrity, the risk of HCC recurrence was markedly increased in line with increasing tumor diameter in a non-linear manner.ConclusionTumor diameter >2.6 cm and preoperatively increased TBL level are associated with a higher risk of early recurrence after curative resection in patients with HCC, while tumor capsular integrity is associated with a lower risk of early recurrence.

THU488 - The risk of hepatocellular carcinoma recurrence following resection or ablation is dependent on underlying etiology

THU488 - The risk of hepatocellular carcinoma recurrence following resection or ablation is dependent on underlying etiology

Risk of hepatocellular carcinoma recurrence in patients treated with direct acting antiviral therapy

Risk of hepatocellular carcinoma recurrence in patients treated with direct acting antiviral therapy

Next-Generation Sequencing-Based Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma Predicts Hepatocellular Carcinoma Recurrence.

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner.

Donation After Circulatory Death Is Associated With Similar Posttransplant Survival in All but the Highest-Risk Hepatocellular Carcinoma Patients.

Liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) receive a higher proportion of livers from donation after circulatory death (DCD) donors compared with non-HCC etiologies. Nevertheless, data on outcomes in patients with HCC receiving DCD grafts are limited. We evaluated the influence of DCD livers on post-LT outcome among HCC patients. We identified 7563 patients in the United Network for Organ Sharing (UNOS) database who underwent LT with Model for End-Stage Liver Disease score exceptions from 2012 to 2016, including 567 (7.5%) who received a DCD donor organ and 6996 (92.5%) who received a donation after brain death (DBD) donor organ. Kaplan-Meier probabilities of post-LT HCC recurrence at 3years were 7.6% for DCD and 6.4% for DBD recipients (P=0.67) and post-LT survival at 3 years was 81.1% versus 85.5%, respectively (P=0.008). On multivariate analysis, DCD donor (hazard ratio, 1.38; P=0.005) was an independent predictor of post-LT mortality. However, a survival difference after LT was only observed in subgroups at higher risk for HCC recurrence including Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score ≥4 (DCD 57.0% versus DBD 72.6%; P=0.02), alpha-fetoprotein (AFP) ≥100 (60.1% versus 76.9%; P=0.049), and multiple viable tumors on last imaging before LT (69.9% versus 83.1%; P=0.002). In this analysis of HCC patients receiving DCD versus DBD livers in the UNOS database, we found that patients with a low-to-moderate risk of HCC recurrence (80%-90% of the DCD cohort) had equivalent survival regardless of donor type. It appears that DCD donation can best be used to increase the donor pool for HCC patients with decompensated cirrhosis or partial response/stable disease after locoregional therapy with AFP at LT <100ng/mL.

Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma recurrence

BackgroundThe impact of direct-acting antivirals (DAAs) remains a debate, whether they accelerate the recurrence rate of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative therapy. We evaluated the impact of direct-acting antiviral therapy on the rate of recurrence of HCV-related hepatocellular carcinoma following intervention in Egyptian patients.ResultsThe results of the study represented an HCC recurrence rate of 38% in patients who received direct-acting antiviral therapy after HCC intervention versus 62% in those who did not receive antiviral therapy. In group I, according to the Barcelona Clinic of Liver Cancer (BCLC) staging, a higher recurrence rate was observed (57.9%) among patients who were classified as BCLC stage B.ConclusionsHCC patients who did not receive direct-acting antiviral therapy after HCC intervention had a greater risk of HCC recurrence. DAAs did not increase the risk of HCC recurrence following HCC treatment; however, it did not abolish it. Close monitoring of patients after antiviral therapy is recommended.

AFP ratio predicts HCC recurrence after liver transplantation.

Background/aimsHepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels.MethodsWe performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence.Results19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5.ConclusionA rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.

Does graft hemodynamics affect the risk of hepatocellular carcinoma recurrence after liver transplantation?

Although experimental studies have reported that hepatic ischemia-reperfusion injury promotes tumor growth and metastases, the impact of graft hemodynamics on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is unclear. To investigate the association between graft hemodynamics and HCC recurrence after LT, we conducted a retrospective analysis of 279 patients who underwent LT for HCC. Graft hemodynamics including portal vein flow (PVF), hepatic artery flow (HAF), and total hepatic flow (THF) was analyzed as a predictor of HCC recurrence, using competing risk regression analyses. The cutoff values of PVF, HAF, and THF were set at the lower quartile of distribution. A cumulative recurrence curve demonstrated that low THF (<1511mL/min, P=.005) was significantly associated with increased recurrence, whereas neither low PVF (<1230mL/min, P=.150) nor low HAF (<164mL/min, P=.110) was significant. On multivariate analysis, outside Milan criteria (sub-hazard ratio [SHR]=3.742; P<.001), microvascular invasion (SHR=3.698; P<.001), and low THF (SHR=2.359; P=.010) were independently associated with increased HCC recurrence. In conclusion, our findings suggest that graft hemodynamics may play an important role in HCC recurrence after LT.