Time Of Hepatocellular Carcinoma Diagnosis Research Articles

Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma in Patients Previously Treated with Transarterial Embolization.

The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.

Preoperative detection of hepatocellular carcinoma's microvascular invasion on CT-scan by machine learning and radiomics: A preliminary analysis

IntroductionMicrovascular invasion (MVI) is the main risk factor for overall mortality and recurrence after surgery for hepatocellular carcinoma (HCC).The aim was to train machine-learning models to predict MVI on preoperative CT scan. Methods3-phases CT scans were retrospectively collected among 4 Italian centers. DICOM files were manually segmented to detect the liver and the tumor(s). Radiomics features were extracted from the tumoral, peritumoral and healthy liver areas in each phase. Principal component analysis (PCA) was performed to reduce the dimensions of the dataset. Data were divided between training (70%) and test (30%) sets. Random-Forest (RF), fully connected MLP Artificial neural network (neuralnet) and extreme gradient boosting (XGB) models were fitted to predict MVI. Prediction accuracy was estimated in the test set. ResultsBetween 2008 and 2022, 218 preoperative CT scans were collected. At the histological specimen, 72(33.02%) patients had MVI. First and second order radiomics features were extracted, obtaining 672 variables. PCA selected 58 dimensions explaining >95% of the variance.In the test set, the XGB model obtained Accuracy = 68.7% (Sens: 38.1%, Spec: 83.7%, PPV: 53.3% and NPV: 73.4%). The neuralnet showed an Accuracy = 50% (Sens: 52.3%, Spec: 48.8%, PPV: 33.3%, NPV: 67.7%). RF was the best performer (Acc = 96.8%, 95%CI: 0.91–0.99, Sens: 95.2%, Spec: 97.6%, PPV: 95.2% and NPV: 97.6%). ConclusionOur model allowed a high prediction accuracy of the presence of MVI at the time of HCC diagnosis. This could lead to change the treatment allocation, the surgical extension and the follow-up strategy for those patients.

Incidence, Risk Factors, and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases.

Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma (HCC). This study aimed to examine the age-related incidence, demographics, and survival of patients with HCC and brain metastases. Data of HCC patients from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) Registry were screened for the presence of brain metastases. They were stratified by age and ethnicity. Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival (OS) and liver cancer-specific survival (CSS), respectively. A total of 141 HCC patients presenting with brain metastases were identified, accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease. Among all HCC patients, the incidence rate was the highest among patients aged 30-49 years old (0.47%). Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African-American patients presented with a significantly lower disease-specific survival [median time: 1 month; interquartile range (IQR): 0-3.0 months)]. Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases [odds ratio (OR): 12.62, 95% confidence interval (CI): 8.40-18.97] but was not associated with a worse OS or CSS among those with brain metastases. This study identified the age-related incidence and risk factors of brain metastases in HCC patients. These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases, and influence the counseling of this patient population regarding their prognosis.

Unawareness of hepatitis B infection and lack of surveillance are associated with severity of hepatocellular carcinoma.

Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV-related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV-related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety-one (23%) of the HBV-aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.

Fibrosis-4 index, a predictor for prognosis of hepatocellular carcinoma patients after curative hepatectomy even in hepatitis B virus dominant populations.

Liver fibrosis plays an important role in the development of hepatocellular carcinoma (HCC) and determining its prognosis. Although many staging systems and liver reserve models have been developed without the intention of predicting prognosis of HCC, some studies have investigated their prognostic values in HCC after curative liver resection (LR). The aim of this study is to evaluate prognostic value of non-invasive biomarkers after curative LR. Between 2006 and 2013, HCC patients underwent LR were included and total 962 patients were enrolled. All non-invasive biomarkers (fibrosis 4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and albumin-bilirubin (ALBI) score) were measured at the time of HCC diagnosis. To binarize each biomarker, an optimal cut-off value for fibrosis stage was selected using the value of minimum distance from the left-upper corner of the receiver operating characteristic curve with a specificity >60%. We performed Cox regression analysis on 2-year recurrence-free survival (RFS) and overall survival (OS). The area under curve values for FIB-4 and APRI were the largest for fibrosis stage compared to other biomarkers, 0.669 (95% confidential interval (CI), 0.610-0.719) and 0.748 (95% CI, 0.692-0.800), respectively. Between those two indices, FIB-4 is considered a statistically significant prognostic factor of RFS in HCC patients after LR. The HR for 2-year RFS and OS were 1.81 (95% CI, 1.18-2.77; P = 0.007) and 2.36 (95% CI, 0.99-5.65; P = 0.054), respectively. FIB-4 is identified as a statistically significant predictor of HCC prognosis after curative LR even in HBV dominant populations.

Changing epidemiology of hepatocellular carcinoma in South America: A report from the South American liver research network

Introduction and ObjectivesMost epidemiological data on hepatocellular carcinoma (HCC) originate from resource-rich countries. We have previously described the epidemiology of HCC in South America through the South American Liver Research Network. Here, we provide an update on the changing epidemiology of HCC in the continent seven years since that report. Materials and MethodsWe evaluated all cases of HCC diagnosed between 2019 to 2021 in centers from six countries in South America. A templated, retrospective chart review of patient characteristics at the time of HCC diagnosis, including basic demographic, clinical and laboratory data, was completed. Diagnosis of HCC was made radiologically or histologically for all cases via institutional standards. ResultsCenters contributed to a total of 339 HCC cases. Peru accounted for 37% (n=125) of patients; Brazil 16% (n=57); Chile 15% (n=51); Colombia 14% (n=48); Argentina 9% (n=29); and Ecuador 9% (n=29). The median age at HCC diagnosis was 67 years (IQR 59-73) and 61% were male. The most common risk factor was nonalcoholic fatty liver disease (NAFLD, 37%), followed by hepatitis C (17%), alcohol use disorder (11%) and hepatitis B (12%). The majority of HCCs occurred in the setting of cirrhosis (80%). HBV-related HCC occurred at a younger age compared to other causes, with a median age of 46 years (IQR 36-64). ConclusionsWe report dramatic changes in the epidemiology of HCC in South America over the last decade, with a substantial increase in NAFLD-related HCC. HBV-related HCC still occurs at a much younger age when compared to other causes.

Incidence of hepatocellular carcinoma in chronic hepatitis B virus infection in those not meeting criteria for antiviral therapy.

Chronic hepatitis B virus (HBV) infection is the leading risk factor for hepatocellular carcinoma (HCC). The aim of this study was to explore the incidence of HCC in a cohort of subjects with HBV and correlate with HBV treatment current guidance. We identified 2846 subjects with HBV over the study period. HCC was diagnosed in 386 of 2846 (14%) subjects; 209 of 386 (54%) were on nucleos(t)ide analogue (NA) therapy at time of HCC diagnosis, and 177 of 386 (46%) were not on NA therapy. Of the 177 subjects not on NAs who developed HCC during follow‐up, 153 of 177 (86%) had cirrhosis. Within the 177 subjects not on NAs, 158 of 177 (89%) had undetectable HBV DNA, 10 of 177 (6%) had detectable HBV DNA < 2000 IU/L, and 9 of 177 (5%) had HBV DNA > 2000 IU/L. Of those with cirrhosis and undetectable HBV DNA, 115 of 141 had compensated cirrhosis, and 26 of 141 had decompensated cirrhosis. Significant predictors of HCC on time to event analysis included cirrhosis (hazard ratio [HR] 10, 95% confidence interval [CI] 5.8–17.5; p < 0.001), alanine aminotransferase level (HR 1.004, 95% CI 1.002–1.006; p < 0.001), age (HR 1.04, 95% CI 1.03–1.06; p < 0.001), (HR 1.9, 95% CI 1.2–3.1; p 0.007), and nonalcoholic fatty liver disease (HR 1.7, 95% CI 1.1–2.8; p 0.02). Kaplan–Meier analysis demonstrated the cumulative incidence of HCC in subjects with compensated cirrhosis receiving NA therapy was significantly lower compared to subjects with compensated cirrhosis outside current HBV treatment practice guidance (undetectable HBV DNA) (32% vs. 51%; p < 0.001). Conclusion: Those with untreated compensated cirrhosis with undetectable HBV DNA who do not meet current guidance for treatment had higher rates of HCC than those with compensated cirrhosis and suppressed HBV DNA by NA therapy. This study highlights the need for earlier diagnosis and treatment of HBV.

Development and validation of a therapy‐independent hepatocellular carcinoma survival prediction score

AbstractBackground &amp; AimsSurvival in hepatocellular carcinoma (HCC) is associated with several factors. Our aim was to develop and validate an HCC survival prediction score (HCC‐SPS) based on common clinical parameters and excluding the subsequent therapy received, which would be able to prognosticate all patients with HCC at the time of diagnosis.MethodsThe development cohort comprised 1270 patients with HCC seen in our department since January 1988. Univariate analysis was performed for known HCC prognostic parameters. Parameters with P &lt; .1 on univariate analysis were then included in a Cox regression with backward model selection. The HCC‐SPS was derived based on the coefficients estimated by Cox regression with selected parameters. The derived HCC‐SPS was then validated with 2 independent international cohorts of 220 patients from the United Kingdom and 90 patients from Hong Kong (HK). Points were allocated to the following variables: ALBI grade, AFP level, portal vein invasion, ECOG status and TNM stage.ResultsThe total score classified a patient into 3 distinct survival risk categories of low, medium and high risk with median survival (weeks) of 249 (95% CI 195–303), 45 (95% CI 38–52) and 9 (95% CI 8–10) respectively. The scoring system was validated by the cohorts from United Kingdom and HK.ConclusionsWe have formulated an HCC survival prediction score using readily available clinical parameters to risk stratify all HCC patients into distinct survival categories at the time of HCC diagnosis regardless of subsequent treatment received. The score was validated with other independent international cohorts of patients.

Transition of the tumor microenvironment with clonal evolution of hepatocellular carcinoma.

467 Background: The combination of atezolizumab and bevacizumab has become a standard treatment for advanced hepatocellular carcinoma (HCC). The indications for combination immunotherapy, including adjuvant therapy and combination with local therapy, are expected to expand in the future. Although exploring the tumor microenvironment has essential clinical implications in the era of combination immunotherapy, most studies on the tumor microenvironment in HCC are based on the analysis of archival samples at the time of HCC diagnosis. Considering the lengthy clinical course and characteristics of multicentric carcinogenesis, the tumor microenvironment may not be constant, but may differ from that at the time of advanced HCC. The present study aimed to assess the changes in the tumor microenvironment during the evolution to advanced HCC using archival samples and samples obtained prior to systemic therapy from the same patients. Methods: The tumor microenvironment was compared in 20 cases by immunohistochemical analyses of CD8, PD-L1, and VEGF expression. Levels of CD8-positive lymphocytes were defined as the mean number of CD8-positive lymphocytes in the tumor per 1 mm2 and classified as low or high infiltration using the median value. PD-L1 expression was classified as negative (&lt; 1%) or positive (≥1%). VEGF expression was classified as low (&lt; 50%) or high (≥50%). Of the 20 cases, gene expression analysis was performed by the PanCancer IO360 Panel in 14 cases. Results: Approximately 40% of the archived samples were obtained at the early stage. Comparison of the tumor microenvironment between the two time points showed that 35% of the patients changed to CD8-positive lymphocyte high infiltration, 20% to positive PD-L1 expression, and 29% to high VEGF expression. The result of comparing gene profile was different between the archival samples and those prior to systemic therapy in 64% of the patients on the expression heat map. Gene set enrichment analysis showed significant changes in T cell cytotoxicity between the two time points. Conclusions: The tumor microenvironment might not be constant, but may change during the evolution to advanced HCC. In the present study, based on the results of the gene mutation analysis using whole-exome sequencing, we also reported the analyses by carcinogenic patterns such as multicentric occurrence and intrahepatic metastasis.

Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis

Cancer cachexia is a wasting syndrome associated with functional impairment and reduced survival that impacts up to 50% of patients with gastrointestinal cancers. However, data are limited on the prevalence and clinical significance of cachexia in patients with hepatocellular carcinoma (HCC). We performed a retrospective cohort study of patients diagnosed with HCC at 2 United States health systems between 2008 and 2018. Patient weights were recorded 6 months prior to and at time of HCC diagnosis. Cachexia was defined as >5% weight loss (or >2% weight loss if body mass index <20 kg/m2), and precachexia was defined as 2% to 5% weight loss. We used multivariable logistic regression models to identify correlates of cachexia and multivariable Cox proportional hazard models to identify factors associated with overall survival. Of 604 patients with HCC, 201 (33.3%) had precachexia and 143 (23.7%) had cachexia at diagnosis, including 19.0%, 23.5%, 34.7%, and 34.0% of patients with Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. Patients with cachexia were less likely to receive HCC treatment (odds ratio, 0.38; 95% confidence interval, 0.21-0.71) and had worse survival than those with precachexia or stable weight (11.3 vs 20.4 vs 23.5 months, respectively; P < .001). Cachexia remained independently associated with worse survival (hazard ratio, 1.43; 95% confidence interval, 1.11-1.84) after adjusting for age, sex, race, ethnicity, Child Pugh class, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and HCC treatment. Nearly 1 in 4 patients with HCC present with cachexia, including many with compensated cirrhosis or early stage tumors. The presence of cancer-associated weight loss appears to be an early and independent predictor of worse outcomes in patients with HCC.

P-53 FAILURE IN ALL STEPS OF HEPATOCELLULAR CARCINOMA SURVEILLANCE PROCESS IS FREQUENT IN DAILY PRACTICE.

Failures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. We performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. Of 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (24.9%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43.2%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25.2%) patients. Patients under complete surveillance were significantly more likely to be diagnosed within Milan criteria than those without surveillance (75% vs. 50%, p<0.001),(Figure). Surveillance failure was significantly associated with alpha fetoprotein ≥20 ng/ml (OR 4.0, CI 95% 1.43-11.55). HCC surveillance failure was frequent in all the evaluated steps. These data should help guide strategies to improve the implementation and results of HCC surveillance in our country.

Failure in all steps of hepatocellular carcinoma surveillance process is frequent in daily practice

Introduction and objectivesFailures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. MethodsWe performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. ResultsOf 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (25%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25%) patients. Surveillance failure was significantly associated with alpha fetoprotein ≥20 ng/mL (OR 4.0, CI 95% 1.43−11.55). ConclusionsHCC surveillance failure was frequent in all the evaluated steps. These data should help guide strategies to improve the implementation and results of HCC surveillance in our country.

Hepatitis C-positive Black patients develop hepatocellular carcinoma at earlier stages of liver disease and present with a more aggressive phenotype.

In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts. Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.

Assessing efficacy of hepatocellular carcinoma prediction scores to prioritise hepatitis B surveillance in the COVID-19 era.

ObjectiveAn estimated 250 million people worldwide are chronically infected with hepatitis B virus (HBV), the leading cause of hepatocellular carcinoma (HCC) globally. The novel Sars‐cov2 virus continues to spread at an alarming rate, and with guidance at the onset of the pandemic recommending the deferral of HCC surveillance, the implications on liver cancer care are now emerging and highlight the urgent need for reorganisation of services.MethodsWe analysed how five HCC risk prediction scores could aid stratification of patients with chronic HBV. We calculated scores using parameters measured from 3 years prior (where available, n = 17) and at the time of HCC diagnosis in all adult patients with chronic HBV diagnosed with HCC (n = 46), and controls (n = 100). We compared the number of patients requiring cancer surveillance according to each score and regional surveillance guidance.ResultsThe aMAP score had the highest discriminatory performance in HCC risk prediction at 3 years (area under receiver‐operating characteristic curve (auROC) of 0.824), followed by the mREACH B score (auROC of 0.719), and mPAGE B score (auROC of 0.742). However, only the mREACH B score had a negative predictive value (NPV) >99%. Applying the mREACH B score to our HBV cohort identified 11 patients requiring HCC surveillance, compared with 62 under current guidelines.ConclusionThe use of HCC risk prediction scores could streamline the surveillance of patients with chronic HBV at a time of extremely limited resources. Overall, the mREACH B score had both a strong discriminatory performance and a high NPV, thus safely identifying low risk patients not requiring surveillance.

Treatment patterns and outcomes of hepatocellular carcinoma (HCC) patients (pts) in the CancerLinQ Research Database (CLQ).

283 Background: Treatment and management of pts with HCC is complicated by the presence of underlying chronic liver disease. Clinical trials with unresectable HCC pts are generally limited to Child-Pugh A or pts with good performance status. Therefore there is limited data for less fit HCC pts, particularly those treated in the community practice setting. Methods: The study design was a retrospective cohort study using the US-based CancerLinQ Discovery Database (CLQ). CLQ was launched by the American Society of Clinical Oncology in 2016 and consists of longitudinal, demographically, and geographically diverse data aggregated from oncology practice Electronic Health Record databases. Eligible pts were ≥18 years at time of HCC diagnosis, had a diagnosis of stage IV HCC within the record, and had ≥2 clinical encounters on separate dates during follow-up after the date of diagnosis. The study period and patient identification period was Jan 1997–Aug 2019; follow up continued through May 2020. Patient demographics, clinical characteristics, and general treatment characteristics were summarized using descriptive statistics. Results: 460 pts were eligible for analysis. Of these, 141 pts (31%) had a Child-Pugh score as reported in medical charts or imputed based on structured and curated data. 76 (54%) pts were Child-Pugh class A, 59 (42%) Child-Pugh class B, and 6 (4%) Child-Pugh class C. The proportion of pts with chronic hepatitis C infection and liver cirrhosis was higher in pts with Child-Pugh classes B and C compared to A. Time from diagnosis to first systemic therapy decreased from a median of 126 days for pts with Child-Pugh class A, to 47 and 16 days for class B and C, respectively. Sorafenib was the most common regimen regardless of line of therapy, followed by PD-1 pathway inhibitors and chemotherapy. Median duration of sorafenib therapy decreased from Child-Pugh class A to C (table). There was a similar decrease in duration of therapy for pts receiving PD-1 pathway inhibitors and chemotherapy when moving from class A to class C. Conclusions: This is the first published retrospective study in HCC using the CLQ. Pts with Child-Pugh class B or C, who are typically excluded from clinical trials, represented 48% of the pts with a Child-Pugh score included in this analysis. Duration of therapy was numerically lower for pts with Child-Pugh class B or C compared to Child-Pugh class A. Further research is needed to describe real-world evidence outside the context of a clinical trial for HCC pts. Funding: AstraZeneca. [Table: see text] Avg, average; obs, observed; TKI, tyrosine kinase inhibitor

The optimal timing and management of hepatitis B and C in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer related mortality worldwide, with the most common underlying etiologies being chronic hepatitis B and hepatitis C infections. Treatment of these viral hepatidities in the setting of HCC has been debated, and there is increasing study addressing this topic. Patients with advanced HCC of either etiology are unlikely to benefit from antiviral treatments, and futility should be considered prior to starting antiviral therapy. Hepatitis B treatment has demonstrated improved survival, decreased risk of hepatitis B reactivation, and decreased risk of late HCC recurrence. The mainstay treatment of chronic hepatitis B has been nucleos(t)ide analogues (NAs), and in the setting of HCC, entecavir and tenofovir are preferred given their higher potency and barriers to resistance. Those who were already on a NAs at the time of HCC diagnosis should be continued on them regardless of the HCC management planned. Patients who are suitable candidates to start NAs should start them at the time of HCC diagnosis. Direct-acting antivirals (DAAs) are the first line therapies for hepatitis C. Unlike with hepatitis B, those with HCV-associated HCC are recommended to start treatment 3-6 months after complete treatment of their HCC, given lower rates of sustained virologic response (SVR) with active HCC. There are also controversial concerns about DAAs contributing to a more aggressive HCC phenotype, but data are limited by retrospective studies, and more recent retrospective studies are more reassuring. In transplant candidates, starting DAAs may be deferred until after transplant depending on median regional wait times, availability of HCV positive organs, and the degree of the patient's liver dysfunction. Overall, in patients with HCC from hepatitis B or C, treatment of the underlying viral hepatitis should be considered unless advanced stage limits benefits and results in futility.

Hepatocellular Carcinoma in Korea between 2012 and 2014: an Analysis of Data from the Korean Nationwide Cancer Registry.

Considering the high prevalence and mortality of hepatocellular carcinoma (HCC) in Korea, accurate statistics for HCC are important. We evaluated the characteristics of Korean patients with newly diagnosed HCC. We retrospectively evaluated data from the Korean Primary Liver Cancer Registry (KPLCR). The baseline characteristics, treatment modalities, and overall survival (OS) of 4,572 patients with HCC registered in the KPLCR between 2012 and 2014 were investigated. At the time of HCC diagnosis, the median age was 60.0 years, with male predominance (79.6%). Hepatitis B virus infection was the most common etiology (59.1%). The rates of Barcelona Clinic Liver Cancer (BCLC) stages 0, A, B, C, and D at diagnosis were 3.9%, 36.9%, 12.5%, 39.4%, and 7.3%, respectively. The proportion of very early or early stage HCC at diagnosis (BCLC stage 0 or A) in the 2012-2014 cohort was significantly lower than that in the 2008-2011 cohort (40.8% vs. 48.3%, P<0.001). Transarterial therapy (37.5%) was the most commonly performed initial treatment, followed by surgical resection (19.8%), best supportive care (19.1%), and local ablation (10.6%). The median OS was 2.9 years, and the 1-, 3-, and 5-year OS rates were 67.7%, 49.3% and 41.9%, respectively. The OS rate of the 2012-2014 cohort was significantly higher than that of the 2008-2011 cohort (log-rank, P<0.001). The OS of HCC patients registered in the KPLCR between 2012 and 2014 significantly improved. Nevertheless, as about half of the HCC patients were diagnosed at an advanced stage, vigorous and optimized HCC screening strategies should be implemented.

TERT Promoter Mutation in Serum Cell-Free DNA Is a Diagnostic Marker of Primary Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease

Introduction: It remains unclear whether TERT promoter mutation (TERT C228T) in serum cell-free DNA (cfDNA) is useful for the diagnosis of hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Methods: In this retrospective study, we analyzed the relationships between TERT C228T in serum cfDNA and levels of AFP and PIVKAII in 57 Japanese patients with histopathologically confirmed NAFLD background, consisting of 36 patients with HCC and 21 without HCC. We also examined the liver-related survival rate and HCC recurrence rate after the initial treatment for HCC. TERT C228T was detected using a highly sensitive method based on wild-type blocking PCR (detection limit in excess of 0.7% mutant-type DNA). Results: In all of the 57 patients, multivariate analysis identified TERT C228T positive as significant determinant of primary HCC. In the 36 patients with HCC, the percentage of patients positive for TERT C228T was 63.9%. The percentage of patients positive for TERT C228T with normal AFP and PIVKAII was 35.3%. The positive predictive value and specificity for prediction of BCLC stage 0 or A were both high. In 6 patients, TERT C228T was repeatedly negative during follow-up but became positive at the time of HCC diagnosis. Four patients who underwent HCC surgical resection had well-differentiated solitary HCC measuring <30 mm, and all were TERT C228T positive with normal AFP and PIVKAII. TERT C228T status had no influence on the cumulative liver-related survival rate and HCC recurrence rate. Conclusions: Our results highlight the superiority of TERT C228T in serum cfDNA compared with AFP and PIVKAII in the early diagnosis of primary HCC in NAFLD patients.

Disparities in Presentation at Time of Hepatocellular Carcinoma Diagnosis: A United States Safety-Net Collaborative Study.

While hepatocellular carcinoma (HCC) is ideally diagnosed outpatient by screening at-risk patients, many are diagnosed in Emergency Departments (ED) due to undiagnosed liver disease and/or limited access-to-healthcare. This study aims to identify sociodemographic/clinical factors associated with being diagnosed with HCC in the ED to identify patients who may benefit from improved access-to-care. HCC patients diagnosed between 2012 and 2014 in the ED or an outpatient setting [Primary Care Physician (PCP) or hepatologist] were identified from the US Safety-Net Collaborative database and underwent retrospective chart-review. Multivariable regression identified predictors for an ED diagnosis. Among 1620 patients, median age was 60, 68% were diagnosed outpatient, and 32% were diagnosed in the ED. ED patients were more likely male, Black/Hispanic, uninsured, and presented with more decompensated liver disease, aggressive features, and advanced clinical stage. On multivariable regression, controlling for age, gender, race/ethnicity, poverty, insurance, and PCP/navigator access, predictors for ED diagnosis were male (odds ratio [OR] 1.6, 95% confidence interval [CI]: 1.1-2.2, p = 0.010), black (OR 1.7, 95% CI: 1.2-2.3, p = 0.002), Hispanic (OR 1.6, 95% CI: 1.1-2.6, p = 0.029), > 25% below poverty line (OR 1.4, 95% CI: 1.1-1.9, p = 0.019), uninsured (OR 3.9, 95% CI: 2.4-6.1, p < 0.001), and lack of PCP (OR 2.3, 95% CI: 1.5-3.6, p < 0.001) or navigator (OR 1.8, 95% CI: 1.3-2.5, p = 0.001). The sociodemographic/clinical profile of patients diagnosed with HCC in EDs differs significantly from those diagnosed outpatient. ED patients were more likely racial/ethnic minorities, uninsured, and had limited access to healthcare. This study highlights the importance of improved access-to-care in already vulnerable populations.

Hepatocellular carcinoma and the Fontan circulation: Clinical presentation and outcomes

BackgroundFontan-associated liver disease (FALD) is universal in patients with a Fontan circulation. Hepatocellular carcinoma (HCC) is one of its severe expressions, and, though rare, frequently fatal. The purpose of this study was to describe the clinical presentation, risk factors, and outcomes of HCC in patients with a Fontan circulation. MethodsA multicenter case series of Fontan patients with a diagnosis of HCC formed the basis of this study. The case series was extended by published cases and case reports. Clinical presentation, tumor characteristics, laboratory and hemodynamic findings as well as treatment types and outcomes, were described. ResultsFifty-four Fontan patients (50% female) with a diagnosis of HCC were included. Mean age at HCC diagnosis was 30 ± 9.4 years and mean duration from Fontan surgery to HCC diagnosis was 21.6 ± 7.4 years. Median HCC size at the time of diagnosis was 4 cm with a range of 1 to 22 cm. The tumor was located in the right hepatic lobe in 65% of the patients. Fifty-one percent had liver cirrhosis at the time of HCC diagnosis. Fifty percent of the patients had no symptoms related to HCC and alpha-fetoprotein was normal in 26% of the cases. Twenty-six patients (48%) died during a median follow-up duration of 10.6 (range 1–50) months. ConclusionsHCC in Fontan patients occurs at a young age with a 1-year survival rate of only 50%. Meticulous liver surveillance is crucial to detect small tumors in the early stage.