Developed Hepatocellular Carcinoma Recurrence Research Articles

Downstaging with Atezolizumab-Bevacizumab: A Case Series.

Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC (uHCC) for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezobev remains unknown. In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age: 58.5 years; women-17%; Barcelona Clinic Liver Cancer Stage System B/C:5/7) had received 3-12 cycles of atezo-bev, and 4 of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 (54-114) days following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 (4-30) months, none of the alive patients developed HCC recurrence or graft rejection. Surgical therapy, including LT, is possible after atezo-bev therapy in wellselected patients after downstaging.

Association between vessels that encapsulate tumour clusters vascular pattern and hepatocellular carcinoma recurrence following liver transplantation.

Vessels that encapsulate tumor clusters (VETC) is a novel vascular pattern seen on hepatocellular carcinoma (HCC) histology which has been shown to independently predict tumor recurrence and survival after liver resection. Its prognostic value in HCC patients receiving liver transplantation (LT) is unclear. We retrospectively studied consecutive adults who underwent deceased-donor LT with active HCC found on explant between 2010-2019. Tumor tissue was stained for CD34 and quantified for VETC. Primary and secondary endpoints were time to recurrence (TTR) and recurrence-free survival (RFS). During the study period, 158 patients received LT where HCC was present on explant. VETC pattern was seen in 76.5% of explants. Patients with VETC-positive tumors spent longer on the waitlist (6.4 vs. 4.1 months, P=0.048), had higher median tumor numbers (2 vs. 1, P=0.001) and larger tumor sizes (20mm vs. 13mm, P<0.001) on explant pathology compared to those with VETC-negative tumors. Correspondingly, VETC-positive patients were more likely to be outside of accepted LT criteria for HCC. After 56.4 months median follow-up, 8.2% of patients developed HCC recurrence post-LT. On multivariable Cox regression, presence of VETC pattern did not predict TTR or RFS. However, the number of VETC-positive tumors on explant was an independent predictor of TTR (hazard ratio [HR] 1.411, P=0.001) and RFS (HR 1.267, P=0.014) after adjusting for other significant variables. VETC pattern is commonly observed in HCC patients undergoing LT. The number of VETC-positive tumors, but not its presence, is an independent risk factor for TTR and RFS post-LT.

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection.

We assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection. Among 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay. HBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001. HBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.

Impact of HBsAg seroclearance on late recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection.

It is unknown whether HBsAg seroclearance affects the risk of hepatocellular carcinoma (HCC) recurrence after liver resection. We aimed to investigate the impact of HBsAg seroclearance on the recurrence of HCC after curative liver resection, with a focus on late recurrence. This study comprised 2,520 consecutive patients who received curative liver resection for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A in Korea between 2000 and 2017. To focus on late recurrence, patients with recurrence or a follow-up duration less than 2 years were excluded. The impact of HBsAg seroclearance on HCC recurrence was assessed by landmark analysis (2-, 5-and 8-year after liver resection), time-dependent Cox and multistate modeling. The mean patient age was 54.4 years and 75.7% were men. A total of 891 (35.4%) patients developed HCC recurrence at rates of 11.2%, 25.5%, and 46.8% at 3, 5, and 10 years after resection. HBsAg seroclearance was achieved in 172 (6.8%) patients during a median follow-up duration of 6.9 years after resection. HBsAg seroclearance, compared with persistent HBsAg positivity, was associated with a lower risk of late HCC recurrence in the 2-, 5-, and 8-year landmark analysis (p= 0.04, p= 0.02 and p= 0.03, respectively) and on time-dependent multivariable Cox modeling (adjusted hazard ratio 0.62; p= 0.005). Based on a 3-state unidirectional illness-death model, patients without HBsAg seroclearance transitioned to HCC recurrence more rapidly than patients who experienced HBsAg seroclearance. HBsAg seroclearance is associated with a lower risk of late recurrence of HBV-related HCC among Korean patients who undergo curative liver resection. Hepatitis B virus (HBV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma (HCC). Suppression of HBV replication is known to lower the risk of HCC recurrence after liver resection (a procedure used to treat and in some cases cure HCC). However, whether the loss of a specific HBV protein (hepatitis B surface antigen or HBsAg) has an impact on recurrence after liver resection remains unknown. Herein, we show that loss of HBsAg is associated with a reduce risk of late recurrence of HCC after liver resection in patients with HBV-related HCC.

Can Liver Ultrasound Elastography Predict the Risk of Hepatocellular Carcinoma Recurrence After Radiofrequency Ablation? A Systematic Review and Meta-Analysis.

The role of liver stiffness (LS) on ultrasound elastography in the prediction of hepatocellular carcinoma (HCC) recurrence after treatment with radiofrequency ablation (RFA) is still unclear. Our aim was to perform a systematic review and meta-analysis to assess whether LS can predict the recurrence of HCC after RFA. Medline via PubMed, Embase, Scopus, and Cochrane Library databases, and abstracts of international conference proceedings were searched up to June 30, 2020. Cohort studies were included if they assessed the association between LS values measured by ultrasound elastography before RFA and HCC recurrence. 9 studies including 1373 patients with HCC treated by RFA, 643 of whom developed HCC recurrence, were identified. The mean value of LS before RFA was significantly higher in patients who developed HCC recurrence than in those who did not (weighted mean difference=11.98 kPa, 95%CI: 7.60-16.35, I2=63.8%). There was a significant positive association between LS value and HCC recurrence both at univariate (unadjusted HR=1.03, 95%CI: 1.00-1.07, I2=72.7%) and multivariate analysis (adjusted HR=1.03, 95%CI: 1.02-1.04, I2=0). Patients with LS value ≥13-14 kPa or >1.5 m/s have a higher risk of both HCC recurrence (unadjusted HR=2.18, 95%CI: 1.46-3.25, I2=49.7%; adjusted HR=2.41, 95%CI: 1.53-3.79, I2=0) and overall mortality (adjusted HR=4.38; 95%CI: 2.33-8.25, I2=0) in comparison with those with LS below these cutoffs. Liver ultrasound elastography appears to be a reliable tool to predict HCC recurrence and overall survival after RFA. This technique may be useful for the management of patients with HCC treated by RFA.

Impact of MAFLD on HBV-Related Stage 0/A Hepatocellular Carcinoma after Curative Resection.

Backgrounds and Aim: Metabolic-associated fatty liver dis-ease (MAFLD) is a novel term proposed in 2020 to avoid the exclusion of certain subpopulations, though the application of this term in the real world is very limited. Here, we aimed to evaluate the impact of MAFLD on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. Methods: Patients with chronic hepatitis B (CHB)-related HCC who received hepatectomy between January 2010 and December 2019 were consecutively selected. The association between histologically proven concurrent MAFLD and clinical outcomes were retrospectively analyzed. Results: Among the 812 eligible patients with CHB-related HCC, 369 (45.4%) were diagnosed with concurrent MAFLD. After a mean follow-up of 65 months, 303 patients (37.3%) developed HCC recurrence, 111 (13.7%) died, and 12 (1.5%) received liver transplantation. Although no differences in the incidences of HCC recurrence (HR: 0.902, 95% CI: 0.719–1.131, p = 0.370) and death or liver transplantation (HR: 0.743, 95% CI: 0.518–1.006, p = 0.107) were observed between patients with and without MAFLD in multivariate analysis, the patients with MAFLD tended to achieve better recurrent-free survival compared to patients without MAFLD. Notably, lean MAFLD (BMI < 23 kg/m2) was a relative risk factor for tumor recurrence (HR: 2.030, 95% CI: 1.117–3.690, p = 0.020) among patients with MAFLD. Conclusions: The overall prognosis in HBV-related early-stage HCC, in terms of HCC recurrence and death or liver transplantation, was not significantly different between patients with and without MAFLD. Among patients with MALFD, lean-MAFLD was a risk factor for HCC recurrence. Further studies are warranted to validate these results.

Liver transplantation for hepatocellular carcinoma at Centro Médico Nacional 20 de Noviembre-México

Hepatocellular carcinoma (HCC) incidence is rising worldwide, actually it's the third cause of cancer associated death. The main risk factor are hepatitis B and C viral infection. In Mexico we have around 6,000 deaths each-yfrom HCC each-year. Liver transplantation for HCC within Milan criteria is the best curative intention. We conducted a descriptive analysis from cirrhotic HCC patients that underwent a liver transplantation (LT) between January 2015 to July 2019. Our policy for LT in HCC patients is Milan criteria, for patients beyond that we perform downstaging procedures such as transarterial chemoenbolization (TACE), microwave or radiofrequency ablation. We analyze disease free and overall survival, recurrence, morbidity and mortality. 15 patients underwent LT for HCC. We divide patients in two groups: Group 1 within Milan (n = 10) and Group 2 beyond Milan (n = 5). Group 2 patients underwent downstaging locoregional therapy by means of radiofrequency or microwave ablation and TACE. The disease free survival at 1-year was 100% in both groups. At 4-year follow up overall survival was 66.6%. During the follow up period none of the patients developed HCC recurrence. Overall 5-year survival for LT and HCC is reported 60-70% mostly associated to HCC recurrence but in our study global survival was 66.6% but no mortality was associated to HCC recurrence. Within Milan group showed better survival rates than downstaged group, but since both groups developed no HCC recurrence, we still believe downstaging policy is a good strategy for HCC beyond Milan criteria.

Early and late recurrence of surgically resected hepatitis B virus-related hepatocellular carcinoma on nucleos(t)ide analogues therapy

Hepatocellular carcinoma (HCC) is a highly recurrent tumor. Antiviral therapy with nucleos(t)ide analogues (NUCs) may reduce the risk of recurrence in hepatitis B virus (HBV)-related HCC. The risk factors associated with recurrence in HCC patients after surgical resection and with NUCs treatment should be delineated. Consecutive 339 HBV-related HCC patients receiving surgical resection of HCC with NUCs therapy (including 256 entecavir, 36 tenofovir, and 18 lamivudine) after the surgery were retrospectively reviewed. Factors related to the recurrence-free survival (RFS) and overall survival (OS) were evaluated. After a median of 48.5 months of follow-up, 183 (54%) patients developed HCC recurrence, with the 5-year RFS of 42.8% and OS of 79%. Male gender (HR=1.736, p=0.037), baseline HBsAg level >200 IU/ml (HR=1.748, p=0.008), platelet count ≦100 (109/L) (HR=1.592, p=0.023), presence of microscopic vascular invasion (MVI) (HR=1.499, p=0.026), safety cut margin of ≦0.5cm (HR=1.507, p=0.013), and Ishak fibrosis score 5-6 (HR=1.579, p=0.009) were independent factors associated with RFS in multivariate analysis. While tumor burden, platelet count, MVI, and safety cut margin were factors associated with early recurrence; baseline HBsAg level, and platelet count were independent factors associated with late recurrence. Ishak fibrosis score 5-6, poor differentiation, MVI, diabetes mellitus were factors associated with OS in multivariate analysis. For HBV-HCC patients on NUCs treatment, tumor factors are associated with early recurrence, while HBsAg level and thrombocytopenia determines late recurrence. For patient with a high baseline HBsAg level, warning of higher risk of recurrence is required even under NUCs treatment.

Recurrent Hepatocellular Carcinoma in an Adult With Alagille Syndrome Treated With Liver Resection Followed by Liver Transplantation: A Rare Case Report.

Alagille syndrome (AGS) is a disorder that affects the liver, heart, kidneys, and skeleton. Development of hepatocellular carcinoma (HCC) is rare in AGS. A 41-y-old male with AGS presented with a 6 × 8-cm HCC and underwent transarterial chemoembolization (TACE) followed by right hepatic lobectomy. One year later, he developed HCC recurrence within Milan’s criteria and received a deceased donor liver transplant. An interposition donor iliac artery graft from the supraceliac aorta to the donor hepatic artery was needed due to celiac axis occlusion noted on TACE. He subsequently underwent a Roux-en-Y hepaticojejunostomy for a bile leak. Surveillance imaging for HCC revealed a 3-cm pseudoaneurysm of his aortoiliac vascular anastomosis, 3 mo posttransplant. An infrarenal aortic jump graft to the donor hepatic artery and ligation of supraceliac aortic conduit was performed, followed by aortic stent-graft placement to occlude the pseudoaneurysm. He received a deceased donor kidney transplant 13 mo after the liver transplant. He remains HCC free with excellent liver and renal allograft function. Adults with AGS undergoing liver transplantation for HCC need special consideration due to related vascular, cardiac, and renal anomalies.

MAMMALIAN TARGET OF RAPAMYCIN INHIBITORS AFTER POST-TRANSPLANT HEPATOCELLULAR CARCINOMA RECURRENCE: IS IT TOO LATE?

Background: Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma (HCC). However, its role in established post-transplant HCC recurrence is uncertain. We investigate whether mTOR inhibitor offers survival benefit in this context. Methods: A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed. They were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression. The primary endpoint was post-recurrence survival. Results: Seventy-nine (55%) patients received mTOR inhibitor-based immunosuppressive regime while 64 (45%) of them did not. The mTOR inhibitor group had a lower number of recurrent tumours (2 vs. 5, p=0.02) and received more active treatments including radiotherapy (39 vs. 22%, p=0.03) and targeted therapy (59 vs. 23%, p<0.001). The median post-recurrence survival was 21.0±4.1 months in mTOR inhibitor group and 11.2±2.5 months in the control group. Multivariate cox regression analysis confirmed mTOR inhibitor was independently associated with improved post-recurrence survival (p=0.04, OR 0.482, 95%CI 0.241-0.966).Number of recurrent tumours and use of other treatment modalities did not affect survivals. There were no survival differences observed between mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor (CNI). Conclusions: mTOR inhibitors prolonged survival after post-transplant HCC recurrence.

Predictors of recurrence and survival of hepatocellular carcinoma: A prospective study including transient elastography and cancer stem cell markers

Background and Study AimsTo investigate whether the measurement of liver stiffness (LSM) using fibroscan and the serum Cancer Stem Cells (CSC): Ep-CAM and cytokeratin-19, could predict the recurrence of hepatocellular carcinoma (HCC) and their impact on clinical outcome and overall survival. Patients and MethodsThis is a prospective study, including 179 HCV-related HCC patients. All patients were treated following the BCLC guidelines. All HCC patients had transient elastography, measurements of Ep-CAM and cytokeratin-19 before and six months post-treatment. We looked for predictors of recurrence and performed a survival analysis using Kaplan-Meier estimates. ResultsTACE was the most common procedure (77.1%), followed by microwave ablation (15.6%). Complete ablation was achieved in 97 patients; 55 of them developed HCC recurrence. After treatment, LSM increased significantly with a significant reduction in CSCs levels in complete and partial response groups. The median time to observe any recurrence was 14 months. LSM increased significantly post-treatment in patients with recurrence versus no recurrence. Higher levels of CSCs were recorded at baseline and post-treatment in patients with recurrence but without statistical significance. We used univariate analysis to predict the time of recurrence by determining baseline CK-19 and platelet levels as the key factors, while the multivariate analysis determined platelet count as a single factor. The univariate analysis for prediction of overall survival included several factors, LSM and EpCAM (baseline and post-ablation) among them, while multivariate analysis included factors such as Child score B and incomplete ablation. ConclusionDynamic changes were observed in LSM and CSCs levels in response to HCC treatment and tumour recurrence. Child score and complete ablation are factors that significantly affect survival.

Mammalian target of rapamycin inhibitors after post-transplant hepatocellular carcinoma recurrence: Is it too late?

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma (HCC). However, their role in established post-transplant HCC recurrence is uncertain. To investigate whether mTOR inhibitor offers a survival benefit in post-transplant HCC recurrence. A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed. They were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression. The primary endpoint was post-recurrence survival. Seventy-nine (55%) patients received an mTOR inhibitor-based immunosuppressive regime, while 64 (45%) patients did not. The mTOR inhibitor group had a lower number of recurrent tumours (2 vs 5, P = 0.02) and received more active treatments including radiotherapy (39 vs 22%, P = 0.03) and targeted therapy (59 vs 23%, P < 0.001). The median post-recurrence survival was 21.0 ± 4.1 mo in the mTOR inhibitor group and 11.2 ± 2.5 mo in the control group. Multivariate Cox regression analysis confirmed that mTOR inhibitor therapy was independently associated with improved post-recurrence survival (P = 0.04, OR = 0.482, 95%CI: 0.241-0.966). The number of recurrent tumours and use of other treatment modalities did not affect survival. No survival difference was observed between mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor. mTOR inhibitors prolonged survival after post-transplant HCC recurrence.

Salvage Living Donor Liver Transplantation (SLDLT) as a Treatment Modality for Recurrent Hepatocellular Carcinoma (HCC)

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer all over the world. Salvage livingdonor liver transplantation (SLDLT) has been proposed for patients who developed HCC recurrence after primaryresection or liver deterioration in patients undergoing liver resection (LR).Aim of the work: The aim of this study is to compare and evaluate the patient survival and cancer recurrencerates between patients who underwent (SLDLT) and (PLT) in our centers between 2014 and 2018.Patients and methods: A retrospective study was conducted on total of 110 HCC patients who underwentLDLT for HCC from January 2014 till January 2018 by the same surgical team at 3 centers (Ain Shams UniversitySpecialized Hospital, Wadi-ElNile Hospital and Egypt Air Hospital). Patients were divided into two groups. Group Aincluded primary LDLT for 95 cases which were within Milan criteria and group B for SLDLT was performed in 15cases.Results: Among the 110 HCC patients, 95 (86.4%) underwent PLT, and 15 (13.6%) underwent SLT for HCCrecurrence after the primary resection. The operative time was significantly more (P value=0.001) in the SLTrecipients group, as the median operative time was (10) hours while it was (8) hours in the PLT recipients group. Forall post-operative complications, no statistical significant difference was found between the PLT and SLT recipients.Similar rates were observed as regard the overall survival between the SLT and PLT recipients. However, the 1year, 3 year and 5 year disease-free survival rates were 94.5%, 93.0%, and 92.1% in PLT recipients, compared torecurrence that occurred in 1 patient after 9 months (6.7 %) in SLT recipients which was not significantly differentstatistically.Conclusion: Our study shows that SLT is a safe and technically feasible procedure for patients who developed HCCrecurrence following primary liver resection. Also, the survival rates were similar to PLT.

Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C.

Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients' sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B - TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 - 18.297, p=0.024). IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

1007 Sex-Specific and Ethnicity-Specific Disparities in Receipt of Hepatocellular Carcinoma (HCC) Treatment Among a Cohort of Patients Who Developed HCC Recurrence

INTRODUCTION: Despite receiving cancer-directed therapies, there is a high rate of cancer recurrence among patients with hepatocellular carcinoma (HCC). Our study aims to focus on the subset of patients with HCC recurrence to evaluate sex- and ethnicity-specific disparities in receipt of treatment. METHODS: Adults with HCC who developed HCC recurrence were identified using 1973-2015 U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results cancer registry. HCC tumor stage was assessed with the SEER historic staging system (localized, regional, distant) and HCC treatment received was assessed with SEER’s site-specific surgery variable (no treatment, locoregional therapy, surgical resection, and liver transplantation (LT)). Comparisons of tumor stage at diagnosis and receipt of HCC treatment between groups were assessed using chi-square testing and multivariate logistic regression models. RESULTS: Among 275 patients with recurrence of HCC (76.7% male, 48.7% non-Hispanic Whites, 14.9% Hispanic, 27.6% Asian/Pacific Islanders), 24.6% did not receive any HCC-directed surgical treatment, 21.9% received locoregional therapies, 42.3% surgical resection, and 11.2% LT. Compared to women, men were significantly less likely to receive any HCC treatment after initial diagnosis of HCC (OR 0.33, 95% CI 0.14-0.76, P = 0.01), including surgical resection or LT (OR 0.53, 95% CI 0.29-0.96, P = 0.037). Compared to non-Hispanic Whites, significantly lower rates of any HCC treatment were observed in Hispanics (OR 0.40, 95% CI 0.19-0.84, P = 0.015) and higher rates of treatment were seen in Asian/Pacific Islanders (OR 2.28, 95% CI 1.02-5.12, P = 0.045). On multivariate analysis, there were significantly lower odds of receiving any therapy for the initial HCC diagnosis in men vs. women (OR 0.27, 95% CI 0.11-0.68, P &lt; 0.01) and in Hispanics vs. non-Hispanic Whites (OR 0.32, 95% CI 0.15-0.72, P &lt; 0.01). Asian/Pacific Islanders were more likely to receive treatment compared to non-Hispanic Whites (OR 2.72, 95% CI 1.15-6.44, P = 0.023). There were no significant differences in receipt of treatment for the HCC recurrence based on sex or ethnicity. CONCLUSION: Among U.S. adults with HCC who developed HCC recurrence, nearly one quarter did not receive any HCC-directed surgical therapies at initial diagnosis. Men and Hispanics were significantly less likely to receive any HCC-directed therapies for the initial HCC diagnosis.

Predicting Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Liver Resection for Solitary Hepatocellular Carcinoma

Background and PurposeSeveral hepatectomy patients with HCC who are initially transplantable (within MC) developed untransplantable HCC recurrence (beyond MC) after primary curative liver resection. The purpose of our study is to identify the risk factors of untransplantable hepatocellular carcinoma (HCC) recurrence after primary curative resection of solitary HCC and solitary HCC within Milan criteria (MC). MethodsWe retrospectively reviewed 592 patients with recurrent HCC who underwent liver resection due to solitary HCC between 2005 and 2011. ResultsAll patients were Child-Pugh class A. At primary curative hepatectomy, 411 patients (69.4%) were diagnosed with HCC within MC and 181 patients (30.6%) had HCC beyond MC. The mean time from primary hepatectomy to recurrence was 14 months (range, 1–116 months). At HCC recurrence, 93 patients (15.7%) were diagnosed beyond MC. Multivariate analysis showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with a high risk of HCC recurrence beyond MC in patients who had hepatectomy for solitary HCC. Of the 411 patients within MC at primary curative hepatectomy, 54 patients (13.9%) developed HCC recurrence beyond MC. Multivariate analysis also showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with HCC recurrence beyond MC in these patients. ConclusionsThe present study suggests that the presence of certain unfavorable histological factors in patients who underwent initial liver resection of transplantable HCC within MC with good liver function predicted the development of recurrent HCC beyond MC.

Long-term observation of hepatocellular carcinoma recurrence after liver transplantation at a European transplantation centre.

The recurrence of hepatocellular carcinoma (HCC) is the strongest survival-limiting factor after liver transplantation (LT) in patients with HCC. In the face of donor organ shortage, it is necessary to identify factors associated with HCC recurrence in order to maximize the utility of the available grafts. To study the phenomenon of HCC recurrence after LT at a European transplantation centre over the past 20 years. Data from 304 HCC patients who underwent LT were prospectively recorded. Clinical and pathological factors were assessed for their association with recurrence. Fifty-one patients (16.8%) had HCC recurrence after LT. Patients exceeding the Milan criteria developed HCC recurrence more frequently. The time point of recurrence did not affect survival after recurrence. Furthermore, there was no difference in survival between patients with intra- and extrahepatic recurrence. However, patients with recurrence due to needle tract seeding had a significantly better outcome than patients with other sites of recurrence. Our data support a restrictive use of patient selection criteria to help identify patients who have an increased risk of HCC recurrence after LT, and highlight the need to improve patient selection before LT in order to minimize the rate of HCC recurrence.

Reappraisal of Failures in Downstaging Treatment of Hepatocellular Carcinoma Prior to Liver Transplant—Preliminary Report on the Impact of Underestimations of Tumor Numbers and Tumor Sizes as Measured From Imaging Before Transplant

Downstaging treatment of hepatocellular carcinoma (HCC) prior to liver transplant (LT) is an accepted strategy to meet the Milan criteria. However, after transplant surgery, a reality is noted that the number or/and the size of some HCCs measured from the liver explants is different from that measured from the pre-LT imaging. If tumor number or tumor size measured from the liver explants was beyond that measured from pre-LT imaging, we define it as “failed downstaging.” Among 27 patients who received downstaging therapies, there are 11 “number reduction failures” and 6 “size reduction failures.” We attribute the discrepancy to 2 possible reasons; one is that the pre-LT imaging after downstaging could not completely detect all the HCC; the other is that the time interval between the downstaging and LT is long enough to develop new HCCs. After follow-up, 6 patients developed HCC recurrence. The significant factors affecting recurrence include tumor size from postdownstaging imaging (P = .048), tumor number ≥ 2 (P = .007), multiple sessions of downstaging (P = .03), ratio of neutrophil to lymphocyte (P = .047), and tumor number from liver explant (borderline P = .05). Tumor recurrence after LT is significantly higher in those with “size reduction failure” (P = .048). The interval between LT and tumor recurrence is significantly shorter in those with “size reduction failure” (P = .04). To decrease underestimations of HCC, combining various imaging studies including the computed tomographic scan, magnetic resonance imaging, and contrast ultrasonography is needed to increase the accuracy before LT. Repeated imaging studies at short intervals of no more than 3 months are necessary during a long wait. How to minimize the underestimations of HCC to determine the appropriate candidacy for LT is an important goal for transplantation surgeons.

Predictors of hepatocellular carcinoma recurrence associated with the use of direct-acting antiviral agent therapy for hepatitis C virus after curative treatment: A prospective multicenter cohort study.

BackgroundPrevious studies have suggested an association between the use of direct‐acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection and the resulting decrease in the incidence of hepatocellular carcinoma (HCC); however, it is unclear whether DAAs prevent the recurrence of HCC after curative treatment for HCC. This study aimed to prospectively investigate HCC recurrence and its predictors after curative treatment for HCC.MethodsA total of 3012 patients with chronic HCV infection, with or without cirrhosis, who were treated with DAAs were enrolled between January 1, 2015 and January 31, 2017 as per the institutional review board approved study protocol at 15 institutions, including 10 university hospitals and five high‐volume centers in the Kyusyu area of Japan. Of the 3012 patients, 459 patients who had HCC but were cured with surgery or ablation therapy (curative treatment) before the use of DAAs were included in the analysis.ResultsDuring a mean follow‐up period of 29.4 months, 217 (47.2%) patients developed HCC recurrence. The median time to recurrence was 34.0 months, and the 1‐, 2‐, and 3‐year cumulative HCC recurrence rates were 27.1%, 43.4%, and 50.8%, respectively. The risk factors for HCC recurrence were the α‐fetoprotein (AFP) level before DAA therapy (P = 0.0047) and the number of curative treatments for HCC before DAA therapy (P < 0.0001).ConclusionsA high AFP level and multiple occurrences of HCC before DAA therapy are associated with a high risk for HCC recurrence after curative treatment. Follow‐up after DAA therapy should include special attention to the abovementioned risk factors.

Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort.

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P<0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P=0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.