Gender disparity in hepatocellular carcinoma recurrence after curative hepatectomy

Introduction and objectivesWhether there is gender disparity in the recurrence of hepatocellular carcinoma (HCC) has been not fully addressed. This study aimed to investigate the impact of gender on HCC recurrence following curative hepatectomy.Patients and methodsThis retrospective cohort study included 1087 patients with HCC (917 males, 170 females) who underwent curative hepatectomy. Cox regression models were constructed to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the risk parameters associated with HCC recurrence. In the sensitivity analysis, subgroup analysis, and propensity score matching (PSM) analysis were used. Logistic regression models were used to assess the odds ratio (OR) and 95% CI of the risk parameters related to early and late recurrence.ResultsMale patients showed significantly higher risk for HCC recurrence than females, in both multivariate Cox regression analysis (HR [95% CI] = 1.480 [1.084–2.020], P = 0.014) and PSM analysis (HR [95% CI] = 1.589 [1.093–2.312], P = 0.015). Higher risk of HCC recurrence was again found in males in the subgroup analysis, but the effect of male versus female gender on HCC recurrence did not depend on any selected subgroups (all P for interaction > 0.05). Gender was an independent risk factor for early recurrence (OR [95% CI] = 1.864 [1.215–2.936], P = 0.006), but not for late recurrence.ConclusionsThere is gender disparity in the recurrence of patients with HCC after curative hepatectomy: males had a higher risk for HCC recurrence than females.     

Wait Time for Curative Intent Radio Frequency Ablation is Associated with Increased Mortality in Patients with Early Stage Hepatocellular Carcinoma

IntroductionRadiofrequency ablation (RFA) is a recommended curative intent treatment option for patients with early stage hepa-tocellular carcinoma (HCC). We investigated if wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death.Material and methodsWe conducted a retrospective study of patients diagnosed with HCC between January 2010 and December 2013 presenting to University Health Network (UHN) in Toronto, Canada. All patients receiving curative intent RFA for HCC were included. Multivariable Cox regression was used to determine if wait times were associated with clinical outcomes.Results219 patients were included in the study. 72.6% were male and the median age was 62.7 years (IQR 55.6-71). Median tumor size at diagnosis was 21.5 mm (IQR 17-26); median MELD was 8.7 (IQR 7.2-11.4) and 57.1% were Barcelona stage 0. The cause of liver disease was viral hepatitis in 73.5% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 96 days (IQR 75-139). In multivariate analysis, wait time was not associated with requiring liver transplant or tumor recurrence, however, each incremental 30-day wait time was associated with an increased risk of residual tumor (HR = 1.09; 95% CI 1.01-1.19; p = 0.033) as well as death (HR = 1.23; 95% CI 1.11-1.36; p ≤ 0.001).ConclusionIncremental 30-day wait times are associated with a 9% increased risk of residual tumor and a 23% increased risk of death. We have identified system gaps where quality improvement measures can be implemented to reduce wait times and allocate resources for future RFA treatment, which may improve both quality and efficiency of HCC care.     

Influence of hepatitis B virus reactivation on the recurrence of HBV‐related hepatocellular carcinoma after curative resection in patients with low viral load

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B‐related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV‐related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre‐operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV‐related HCC after curative resection were investigated. Fifty‐three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV‐related HCC in patients with low viral load.     

Effects of hepatitis B e‐antigen on recurrence of hepatitis B‐related hepatocellular carcinoma after curative resection: A meta‐analysis

Aim: The impact of hepatitis B e‐antigen (HBeAg) on recurrence of hepatocellular carcinoma (HCC) after curative resection remains controversial. This meta‐analysis aimed to determine whether the presence of HBeAg influenced the recurrence of HCC after curative resection. Methods: We performed a meta‐analysis including six studies (a total of 865 patients) to assess the effect of HBeAg on recurrence of HCC after curative resection. The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Database were searched for articles published from 1990 to March 2012. Sensitivity analysis and publication bias estimate were also performed to evaluate the potential risk bias in the overall results of pooled analysis. Results: Our results showed that the presence of HBeAg significantly increased the overall HCC recurrence risk after curative resection (OR = 1.63, 95% confidence interval (CI) = 1.11–2.40; P = 0.01). Pooled data from three studies on the risk of early recurrence among HBeAg positive patients compared with HBeAg negative patients showed an increased risk of early recurrence (OR = 1.50, 95% CI = 1.02–2.19; P = 0.04). However, there was no significant difference in late HCC recurrence between HBeAg positive and negative patients (OR = 1.17, 95% CI = 0.62–2.19; P = 0.62). Conclusion: The present study suggested that HBeAg positive patients had a significantly higher risk of early recurrence after curative resection of HCC.     

Predisposing factors for recurrence of HBV-related small hepatocellular carcinoma after percutaneous radiofrequency ablation

Abstract

Background. Radiofrequency ablation (RFA) as a curative therapy for hepatocellular carcinoma (HCC) is widely used. The aim of this study was to investigate predisposing factors for HCC recurrence in patients with hepatitis B virus (HBV)-related small HCC after RFA. Methods. A total of 170 patients underwent percutaneous RFA for HBV-related small HCC (≤3 cm in diameter) from January 2008 to December 2010 at Samsung Medical Center. We analyzed the risk factors for recurrence of HCC after RFA. Results. The median follow-up duration was 27.0 months. A total of 89 patients (52%) experienced recurrence after percutaneous RFA. Cumulative recurrence-free rates after RFA at 1-, 3-, and 5 years were 81.3%, 47.2% and 35.7%, respectively. Univariate analysis showed that predisposing factors for HCC recurrence were the multinodularity (hazard ratio (HR) 2.22, p = 0.005), pre-RFA HBV DNA levels ≥2000 IU/mL (HR 1.61, p = 0.025), and Barcelona Clinic Liver Cancer stage A (HR 1.54, p = 0.046). The independent risk factors for recurrence by multivariate analysis were the multinodularity (HR 1.94, p = 0.026) and pre-RFA HBV DNA levels ≥2000 IU/mL (HR 1.57, p = 0.039). Conclusion. Multinodularity and HBV DNA levels were associated with the recurrence of HBV-related small HCC after RFA.     

Risk factors of recurrence after curative resection of hepatocellular carcinoma in Taiwan

IntroductionThe purpose of this study was to explore the potential risk factors of hepatocellular carcinoma (HCC) recurrence after curative resection of primary HCC.MethodsThis was a hospital-based retrospective cohort study. The authors analyzed the medical records of all the subjects with HCC initially treated by hepatic resection at a medical center in Taiwan from 1995 to 2006. In all, 222 subjects were enrolled in this study. The total observational period was 3 years.resultsThere were 172 men (77.5%) and 50 women (22.5%). The mean age was 57.0 ± 13.7 years (range, 15–79 years). Among 222 subjects, the overall recurrence rates were 28.8% (64/222), 42.3% (94/222) and 47.7% (106/222) at 1, 2 and 3 years, respectively. Multivariate logistic regression analysis exhibited that tumor size ≥ 5 cm [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.27–4.17], liver cirrhosis (OR = 2.11, 95% CI = 1.18–3.79) and preoperative aspartate aminotransferase level ≥ 34IU/L (OR = 2.02, 95% CI = 1.01–4.04) were independent risk factors of HCC recurrence.conclusionPatients who have larger tumor size, liver cirrhosis and higher preoperative aspartate aminotransferase level should be carefully followed up because they are at high risk of HCC recurrence postoperatively.     

Sustained low hepatitis B viral load predicts good outcome after curative resection in patients with hepatocellular carcinoma

Background and Aim: Little is known about the role of hepatitis B virus (HBV) factors in the long‐term prognosis of hepatocellular carcinoma (HCC) after resection. The objective of the present study was to identify the changing patterns of HBV levels and its effect on outcome after resection. Methods: This study recruited 188 patients with HBV‐related HCC who underwent curative resection. Among the 188 patients, 115 were alive without recurrence at 12 months, and had serial measurements of viral levels. Results: The mean age was 53 years and the mean follow‐up period was 48.5 months. With multivariate analysis, tumor size > 5 cm (P = 0.047), Child‐Pugh class B (P = 0.017), vascular invasion (P = 0.028), and HBV DNA > 10⁴ copies/mL at the time of resection (P = 0.003) were independently predictive of HCC recurrence for the entire population. For the 115 patients with serial measurements of viral levels, tumor size > 5 cm, HBV DNA > 10⁴ copies/mL at resection, and the absence of sustained HBV DNA level < 10⁴ copies/mL, the presence of cirrhosis, and elevated aminotransferase levels (> 40 IU/L) were marginally or significantly associated with HCC recurrence and overall survival. However, on multivariate analysis, sustained HBV DNA level < 10⁴ copies/mL was the only factor for both low recurrence (P = 0.002; odds ratio [OR] 3.13; 95% confidence interval [CI] 1.55–6.35) and longer survival (P = 0.002; OR 3.76; 95% CI 1.61–8.78). Conclusions: A high HBV replication state is among the most important predictors of adverse outcome after resection of HBV‐related HCC. The sustained suppression of HBV below 10⁴ copies/mL is a strong protective factor for long‐term recurrence‐free and overall survival.     

The impact of sphingosine kinase 1 on the prognosis of hepatocellular carcinoma patients with portal vein tumor thrombus

Background. Though there is considerable evidence that sphingosine kinase 1(SPHK1) plays a key role in hepatocellular carcinoma(HCC) progression, the prognostic value of SPHK1 expression in HCC with portal vein tumor thrombus (PVTT) remains unclear.Aims. The purpose of this study was to investigate the relationship of SPHK1 expression with PVTT and HCC recurrence after hepatectomy.Methods. After screening of gene expression profiling of tumor cell lines, real-time PCR and immunohistochemistry were used to investigate the SPHK1 expression in PVTT and HCC samples. The clinical data of 199 HCC patients with nonmain PVTT who underwent liver resection with curative intention were studied.Results. We identified SPHK1 as the most over-expressed gene in PVTT via gene expression profiling of one human PVTT cell line (CSQT-2). SPHK1 expression was an independent factor affecting survival (hazard ratio [HR] 1.799, 95% confidence interval [CI] 1.337-2.368, P < 0.001) and tumor recurrence (HR 1.451, 95% CI 1.087-1.935, P = 0.011). Patients with SPHK1 over-expression had a poorer prognosis than those with SPHK1 under-expression (P < 0.001 and P = 0.011 for survival and tumor recurrence).Conclusions. SPHK1 might represent a novel and useful prognostic marker of HCC progression in patients with PVTT.     

Increased hepatocellular carcinoma recurrence in women compared to men with high alpha fetoprotein at liver transplant

Introduction. Men have higher risk for hepatocellular carcinoma (HCC) than women. Pre liver transplant (LT) alpha fetoprotein (AFP) levels strongly predict post LT HCC recurrence. Though women with HCC have higher AFP, the contribution of AFP level by gender to post LT HCC recurrence is unknown.Material and methods. In this UNOS-based, retrospective cohort study we investigate sex differences in HCC recurrence among LT recipients with MELD exception between 2006-2010. Covariates include race, disease etiology, co-morbidities, AFP at listing and LT, tumor burden, loco-regional therapy, and donor risk index. HCC recurrence was assessed by competing risks regression.Results. Of the eligible cohort (n = 5,002) included 3,872 men and 1,130 women. HCC recurred in 258 men (7%) and 66 women (6%). Median listing AFP was higher in women than men (14 vs. 11 ng/dL, p < 0.001). While no sex difference in overall HCC recurrence was detected (HR 0.9, 95% CI 0.7-1.2, p = 0.38), there was a strong interaction between gender and AFP on recurrence risk (p = 0.02). HCC recurrence was nearly three times higher in women (HR 4.2, 95% CI 2.2-8.2, p < 0.001) than men (HR 1.5, 95% CI 1.1-2.1, p = 0.02) with AFP at LT between 101-500 ng/dL.Conclusion. This study reveals novel sex differences in post LT HCC recurrence, which was nearly three times higher in women than men with high AFP at LT. Pre-LT AFP levels appear to carry a different prognosis in women than men, and a subset of female LT recipients may benefit from more intensive HCC surveillance after LT.     

Postoperative morbidity adversely impacts oncological prognosis after curative resection for hilar cholangiocarcinoma

BACKGROUNDPostoperative morbidity after curative resection for hilar cholangiocarcinoma (HCCA) is common; however, whether it has an impact on oncological prognosis is unknown.AIMTo evaluate the influence of postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA.METHODSPatients with recently diagnosed HCCA who had undergone curative resection between January 2010 and December 2017 at The First Affiliated Hospital of Army Medical University in China were enrolled. The independent risk factors for morbidity in the 30 d after surgery were investigated, and links between postoperative morbidity and patient characteristics and outcomes were assessed. Postoperative morbidities were divided into five grades based on the Clavien-Dindo classification, and major morbidities were defined as Clavien-Dindo ≥ 3. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence-free survival (RFS) and overall survival (OS).RESULTSPostoperative morbidity occurred in 146 out of 239 patients (61.1%). Multivariate logistic regression revealed that cirrhosis, intraoperative blood loss > 500 mL, diabetes mellitus, and obesity were independent risk factors. Postoperative morbidity was associated with decreased OS and RFS (OS: 18.0 mo vs 31.0 mo, respectively, P = 0.003; RFS: 16.0 mo vs 26.0 mo, respectively, P = 0.002). Multivariate Cox regression analysis indicated that postoperative morbidity was independently associated with decreased OS [hazard ratios (HR): 1.557, 95% confidence interval (CI): 1.119-2.167, P = 0.009] and RFS (HR: 1.535, 95%CI: 1.117-2.108, P = 0.008). Moreover, major morbidity was independently associated with decreased OS (HR: 2.175; 95%CI: 1.470-3.216, P < 0.001) and RFS (HR: 2.054; 95%CI: 1.400-3.014, P < 0.001) after curative resection for HCCA.CONCLUSIONPostoperative morbidity (especially major morbidity) may be an independent risk factor for unfavorable prognosis in HCCA patients following curative resection.     

Higher Risk of Tumor Recurrence in NASH-Related Hepatocellular Carcinoma Following Curative Resection

Background: The outcomes for patients with NASH-related HCC after curative resection have not been clarified. This study compared the overall survival (OS), time-to-tumor recurrence (TTR), and recurrence-free survival (RFS) associated with NASH-related HCC and virus-related HCC after resection. Methods: Patients with HCC who underwent curative resection were retrospectively enrolled. Baseline characteristics, including disease etiologies and clinical and tumor features, were reviewed. The primary outcomes were OS, TTR, and RFS. Results: Two hundred and six patients were enrolled (HBV: n = 121, HCV: n = 54, NASH: n = 31). Of those with virus-related HCC, 84.0% achieved viral suppression. In both the overall and propensity-score-matched cohorts, those with NASH-related HCC experienced recurrence significantly earlier than those with virus-related HCC (median TTR: 1108 days vs. non-reached; p = 0.03). Through multivariate analysis, NASH-related HCC (hazard ratio (HR), 2.27; 95% confidence interval (CI), 1.25–4.12) was independently associated with early recurrence. The unadjusted RFS rate of the NASH-related HCC group was lower than the virus-related HCC group. There was no difference in the OS between the two groups. Conclusions: NASH-related HCC was associated with earlier tumor recurrence following curative resection compared to virus-related HCC. Post-surgical surveillance is crucial for detecting early recurrence in patients with NASH-related HCC.     

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus

Purpose

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC).

Methods

A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n = 160) and those infected with other genotypes (n = 39).

Results

With a comparable median HCV viral load (6.0 vs. 5.8 log₁₀ IU/mL, p = 0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5-year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log₁₀ IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV viral load of 5.3 log₁₀ IU/mL.

Conclusions

The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.     

Prevalence and risk factors for viral blipping in chronic hepatitis B patients treated with nucleos (t) ide analogues

The clinical relevance of viral blipping during nucleos (t) ide analogue (NA) treatment is unclear in chronic hepatitis B (CHB). We investigated the prevalence, risk factors and clinical outcomes for those with viral blipping during NA treatment. A retrospective cohort study investigated consecutively treated CHB patients from May 2008 to February 2015 on the NAs such as entecavir (ETV), tenofovir (TDF) and lamivudine (LAM). Included patients were previously treatment naive. Viral blipping was defined as serum HBV DNA >20 IU/mL on one occasion, and not >200 IU/mL, with subsequent measurement returning to undetectable levels, that is <20 IU/mL. A total of 242 treatment‐compliant CHB patients were included with 44 (18.2%) experiencing viral blipping. In multivariable Cox regression, Asian race (HR=7.40, 95% CI 1.01–54.29, P<.049), LAM therapy (vs ETV/TDF, HR=2.53, 95% CI 1.29–4.95, P<.007), higher creatinine (per SD, HR=1.47, 95% CI 1.21–1.79, P<.001), HBeAg positivity (HR=2.68, 95% CI 1.39–5.03, P<.003) and longer time to achieve undetectable HBV DNA (per month, HR=1.05, 95% CI 1.02–1.08, P=.001) were associated with an increased risk of viral blipping. Viral blipping did not show any significant association with viral breakthrough, HBsAg loss, ALT flares or disease progression. Viral blipping is a frequent event during NA therapy; however, it did not lead to any clinically significant outcomes. Thus, it may not require more frequent blood work and patient visits in clinical practice.     

Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse Probability of Treatment Weighted Analysis

BackgroundEvidence supporting benefit of hepatocellular carcinoma (HCC) surveillance in reducing mortality is not well-established. The effect of HCC surveillance in reducing mortality was assessed by an inverse probability of treatment weighting (IPTW)-based analysis controlled for inherent bias and confounders in observational studies.Material and MethodsThis retrospective cohort study was conducted on 446 patients diagnosed with HCC between 2007 and 2013 at a major referral center. Surveillance was defined as having at least 1 ultrasound test within a year before HCC diagnosis. Primary outcome was survival estimated using the Kaplan-Meier method with lead-time bias adjustment and compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were computed using conventional Cox and weighted Cox proportional hazards analysis with IPTW adjustment.ResultsOf the 446 patients, 103 (23.1%) were diagnosed with HCC through surveillance. The surveillance group had more patients with the Barcelona-Clinic Liver Cancer stage A (80.6% vs. 33.8%, P < 0.0001), more patients eligible for potentially curative treatment (73.8% vs. 44.9%, P < 0.0001), and longer median survival (49.6 vs. 15.9 months, P < 0.0001). By conventional multivar-iate Cox analysis, HR (95% CI) of surveillance was 0.63 (0.45-0.87), P = 0.005. The estimated effect of surveillance remained similar in the IPTW-adjusted Cox analysis (HR: 0.57; 95% CI: 0.43-0.76, P < 0.001).ConclusionsHCC surveillance by ultrasound is associated with a 37% reduction in mortality. Even though surveillance is recommended in all guidelines, but in practice, it is underutilized. Interventions are needed to increase surveillance rate for improving HCC outcome.     

Expression of IL-26 predicts prognosis of patients with hepatocellular carcinoma after surgical resection

BackgroundThere is no data regarding prognostic impact of interleukin (IL)-26 on outcomes of patients with hepatocellular carcinoma (HCC). The present study aimed to evaluate the prognostic impact of IL-26 on HCC patients undergoing liver resection.MethodsFrom 2003 to 2008, 122 patients with HCC who received surgical curative resection were enrolled. Patients were stratified into IL-26-upper and -lower groups according to the median expression level from immunohistochemical staining of resected specimens. Prognostic impact of IL-26 was estimated using Kaplan–Meier curves. Univariate and multivariate analyses were performed to evaluate time-dependent prognostic impact and independency of IL-26. Demographic and clinical factors that were associated with IL-26 were comprehensively identified.ResultsPrognosis of the patients with high level of IL-26 revealed to be significantly unfavorable in both cumulative recurrence-free survival (P < 0.001) and overall survival (P = 0.002). Upper expression of IL-26 (HR: 1.643; 95% CI: 1.021 to 2.644; P = 0.041) and microvascular invasion (HR: 3.303; 95% CI: 1.255 to 8.696; P = 0.016) were identified as significant independent prognostic factors for overall survival in the multivariable analysis.ConclusionsIL-26 is a novel prognostic factor for HCC after resection. Evaluation of IL-26 expression may be potentially valuable in clinical therapy when planning individualized follow-up schedule and evaluating candidates for prophylactic adjuvant treatment to prevent recurrence.     

Imaging surveillance and multidisciplinary review improves curative therapy access and survival in HCC patients

Introduction. Imaging surveillance and multidisciplinary conference (MDC) review can potentially improve survival in patients with hepatocellular carcinoma (HCC) by increasing access to liver transplantation. Geographic disparities in donor organ availability may reduce this benefit. This study evaluated the impact of HCC surveillance on use of curative therapies and survival in a region with long transplant waiting times.Material and methods. 167 HCC patients were retrospectively studied. Subjects had an established HCC diagnosis or were diagnosed during hepatology follow-up. Collected data included patient demographics, HCC surveillance and MDC review status, portal hypertension complications, laboratory and radiologic parameters, tumor size, therapeutic interventions, tumor progression, and mortality. The primary outcome measures were use of curative treatments and survival. A Cox-regression model was constructed utilizing factors associated with survival in univariate analysis.Results. 58% of subjects underwent surveillance and MDC review of HCC. These patients were more likely to have received treatment with ablation or resection (16 vs. 3%, P = 0.006) and transplantation (23 vs. 4%, P = 0.001), and were less likely to develop tumor progression (45 vs. 68%, P = 0.005) or metastases (0 vs. 19%, P < 0.001). In multivariate analysis, surveillance and MDC review (P = 0.034, HR 0.520, 95% CI 0.284–0.952), tumor meeting Milan criteria (P < 0.001, HR 0.329, 95% CI 0.178–0.607), curative therapy application (P = 0.048, HR 0.130, 95% CI 0.017–0.979), and transplantation (P = 0.004, HR 0.236, 95% CI 0.088–0.632) were associated with survival.Conclusion. In conclusion, imaging surveillance and MDC review is associated with detection of early stage HCC, increased access to curative therapies and transplantation, and prolonged survival.     

Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals

BackgroundUnexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy.AimsWe evaluated the predictive value of albumin-bilirubin (ALBI) score and immune-inflammation indicators to identify the risk of occurrence or recurrence of HCC in patients treated with DAAs in a real life setting.MethodsIn this retrospective cohort study, we analysed data from 514 patients with cirrhosis who were prospectively enrolled for treatment with DAAs. We assessed baseline neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), aspartate aminotransferase-lymphocyte ratio (ALRI) index and ALBI score.ResultsIn patients with no history of HCC (N = 416), increased AST, bilirubin, ALRI, and ALBI score, and decreased albumin and platelets were significantly associated with an increased risk of HCC development, at univariate analysis. At multivariate analysis, increase in ALBI grade (p = 0.038, HR: 2.35, 95% CI: 1.05–5.25) and decrease in platelets (p = 0.048, HR: 0.92, 95% CI: 0.85–1.0) were independently associated with HCC development. In patients with previous HCC (N = 98), adjusting for the time from HCC treatment, increased ALRI (p = 0.008, HR: 1.05, 95% CI: 1.01–1.09) was significantly associated with a risk of recurrence.ConclusionALBI score, platelet count and ALRI are promising, easy to perform and inexpensive tools for identifying patients with higher risk of HCC after treatment with DAAs.     

Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis

BackgroundDebate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria.MethodsPatients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393). Short- and long-term outcomes were compared between patients who underwent preoperative TACE and patients who did not before and after propensity score matching (PSM). Factors associated with recurrence after resection were analyzed.Results100 patients (25.4%) underwent preoperative TACE. Recurrence-free survival (RFS) and overall survival (OS) were comparable with patients who underwent primary liver resection. 7 patients (7.0%) achieved total necrosis with better RFS compared with patients who had an incomplete response to TACE (P=0.041). PSM created 73 matched patient pairs. In the PSM cohort, preoperative TACE improved RFS (P=0.002) and OS (P=0.003). The maximum preoperatively diagnosed tumor diameter (HR 3.230, 95% CI: 1.116–9.353; P=0.031) and hepatitis B infection (HR 2.905, 95%CI: 1.281–6.589; P=0.011) were independently associated with favorable RFS after HCC resection.ConclusionPreoperative TACE made no significant difference to perioperative complications and was correlated with an improved prognosis after surgical resection for patients with HCC beyond the Milan criteria.     

Interval dynamics of transplantability for hepatocellular carcinoma after primary curative resection: risk factors for nontransplantable recurrence

BackgroundTo investigate the changes in transplantability between primary and recurrent Hepatocellular carcinoma (HCC) after hepatic resection (HR) and the risk factors for nontransplantable recurrence (NTR).MethodsConsecutive 3122 patients who received HR for primary HCC between 2001 and 2019 were analyzed for changes in transplantability. Predictors of survival and NTR were evaluated using a competing risk analysis.ResultsAfter a median follow-up of 78.3 months, the 5-year overall survival rate was 82.6%. Also, 58.2% of them developed recurrence after a median of 45.6 months. Recurrence occurred in 1205 and 611 patients with primary transplantable and nontransplantable HCC, respectively, of whom 26.1% and 63.2%, respectively, had NTR. Tumor diameter >3 cm [subdistribution hazard ratios (95% CI), 2.00 (1.62–2.48)], major resection [1.20 (1.00–1.43)], pathological grade >2 [1.28 (1.07–1.52)], microvascular invasion [1.74 (1.45–2.08)], and early recurrence (<1 year) [9.22 (7.83–10.87)] were associated with NTR. The overall transplantable pool increased from 72.3% to 77.5%.ConclusionMicrovascular invasion and early recurrence were risk factors for NTR. Nonetheless, the transplantable pool increased after HR, 41.8% of the patients had no recurrence and may not require liver transplantation. If the patient’s liver function is acceptable, HR should be considered the treatment of choice for HCC.     

Negative hepatitis B envelope antigen predicts intrahepatic recurrence in hepatitis B virus-related hepatocellular carcinoma after ablation therapy

Background and Aim: Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV‐related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation. Methods: Patients with HBV‐related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan–Meier method and Cox regression model to identify risk factors for intrahepatic recurrence. Results: A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥ 2000 IU/mL. The median follow‐up duration was 28.9 months (range, 12.0–57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P = 0.026) and late (≥ 1 year) recurrence (HR, 0.288; P = 0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P = 0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence. Conclusions: These findings show that HBeAg‐negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg‐negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV‐related HCC.