Hepatocellular Carcinoma Surveillance Research Articles

From the Editor's Desk…

From the Editor's Desk…

Racial and Sex Disparities in Hepatocellular Carcinoma in the USA.

In this review, we aim to provide a summary of the current literature on race and gender disparities in hepatocellular carcinoma (HCC) incidence, stage at diagnosis, treatment and prognosis in the United States. HCC incidence rates are rising in the U.S. in all racial/ethnic groups except for Asian/Pacific Islanders, with disproportionate rises and the highest rates among Hispanics compared to Blacks and non-Hispanic whites. There are striking sex disparities in HCC incidence and mortality; however, with the shifting epidemiology of HCC risk factors in the U.S, there is recent evidence that HCC is trending towards less male predominance, particularly among younger birth cohorts. Despite significant advances in HCC treatment over the past decade, disparities in HCC surveillance and treatment receipt persist among racial and ethnic minorities and the socioeconomically disadvantaged. Black patients continue to experience worse survival outcomes than non-Black patients with HCC. There are significant racial and gender disparities in HCC incidence, treatment, and mortality in the U.S. Though these disparities are well-documented, data are still limited on the specific determinants driving disparities in HCC. To achieve health equity for all patients with HCC, we must advance beyond simply reporting on disparities and begin implementing targeted interventions to eliminate disparities.

Value of Follow-Up Chest Computed Tomography in the Surveillance of Patients with Hepatocellular Carcinoma.

PurposeTo evaluate the value of follow-up chest CT in the surveillance of HCC patients.BackgroundImaging guidelines for the surveillance of hepatocellular carcinoma (HCC) patients recommend multiple follow-up computed tomography (CT) examinations of the chest, abdomen, and pelvis. Imaging studies are a major driver of rising healthcare costs. The appropriate use of imaging studies must be evaluated to provide valued health care.MethodsWe reviewed the radiology reports of baseline and follow-up chest, abdominal, and pelvic CT examinations of HCC patients. We categorized the incidence of malignancy in the chest and abdomen for the baseline and follow-up examinations. We also categorized the follow-up examinations as showing improved disease, stable disease, or disease progression. We correlated any progression of disease in the chest with progression of disease in the abdomen. We determined the extent to which disease progression in the chest occurred alongside that in the abdomen. Descriptive statistical analysis was carried out using R (version 3.5.2, R Development Core Team).ResultsOf the 226 patients included in our study, only 7 (3%) had disease progression in the chest without corresponding disease progression in the abdomen and pelvis on follow-up CT. Only 1.8% of patients with disease progression in the chest had a negative CT chest at baseline.ConclusionFollow-up chest CT has limited benefit in the surveillance of HCC patients, especially those with negative baseline chest CT findings.

Abbreviated MRI for Hepatocellular Carcinoma Screening and Surveillance.

To detect potentially curable hepatocellular carcinoma (HCC), clinical practice guidelines recommend semiannual surveillance US of the liver in adult patients at risk for developing this malignancy, such as those with cirrhosis and some patients with chronic hepatitis B infection. However, cirrhosis and a large body habitus, both of which are increasingly prevalent in the United States and the rest of the world, may impair US visualization of liver lesions and reduce the sensitivity of surveillance with this modality. The low sensitivity of US for detection of early-stage HCC contributes to delayed diagnosis and increased mortality. Abbreviated MRI, a shortened MRI protocol tailored for early-stage detection of HCC, has been proposed as an alternative surveillance option that provides high sensitivity and specificity. Abbreviated MRI protocols include fewer sequences than a complete multiphase MRI examination and are specifically designed to identify small potentially curable HCCs that may be missed at US. Three abbreviated MRI strategies have been studied: (a) nonenhanced, (b) dynamic contrast material-enhanced, and (c) hepatobiliary phase contrast-enhanced abbreviated MRI. Retrospective studies have shown that simulated abbreviated MRI provides high sensitivity and specificity for early-stage HCC, mostly in nonsurveillance cohorts. If it is supported by scientific evidence in surveillance populations, adoption of abbreviated MRI could advance clinical practice by increasing early detection of HCC, allowing effective treatment and potentially prolonging life in the growing number of individuals with this cancer. Online supplemental material is available for this article. ©RSNA, 2020.

Surveillance hepatocelulárneho karcinómu na Slovensku

Background: Certain trials have demonstrated that surveillance of hepatocellular carcinoma (HCC) lowers mortality via earlier dia­gnosis and therapy. We aimed to analyse surveillance performance in order to define targets for improvement. Methods: We retrospectively analysed consecutive patients (pts) ELIGIBLE for surveillance between January 2001 and December 2010, with three questions: 1. How many have had surveillance RECOMMENDED and 2. PERFORMED, and by which method and 3. with what outcome. We divided the pts into three groups by dia­gnosis of cirrhosis or HBV infection (ELIGIBLE), written recommendation for surveillance (RECOMMENDED) and ≥ 2 US or alpha-fetoprotein (AFP) exams six months apart (PERFORMED). We recorded the demographics, liver disease characteristics, ultrasound (US), AFP, new lesions, their size and mortality. We excluded patients without data for analysis. Results: We identified 445 and excluded 52 of the ELIGIBLE pts. The remaining 393 pts formed the RECOMMENDED group: 334 (85%) with cirrhosis, 59 (15%) with HBV infection. The median age was 55 years, 34% were females. The most prevalent aetiologies were alcohol-related liver disease (ALD, 46%), non-alcoholic steatohepatitis (NASH, 17%) and hepatitis C virus (HCV, 12%). Surveillance was PERFORMED in 322 (82%) of the RECOMMENDED pts by US only in 1%, AFP in 40% and US with AFP in 31% of the pts, respectively. New lesions were detected in 2.2% of the pts, aged 63.5 years (53–79), with diameter of 31.5 mm (9–120) in 8 surveillance pts and 75 mm (35–115) in 2 pts without surveillance (p = 0.296). Conclusion: This quality control study has shown that the uptake of HCC surveillance in pts with valid indication was suboptimal, the methods used deviated considerably from the guidelines and the diameter of newly-detected lesions was larger than would be required for surveillance to be effective.

ImmunoPET as Stoichiometric Sensor for Glypican-3 in Models of Hepatocellular Carcinoma

Background Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. While conventional imaging approaches like ultrasound, CT, and MRI play critical roles in the diagnosis and surveillance of HCC, improved methods for detection and assessment of treatment response are needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (immunoPET) imaging. Glypican-3 (GPC3) is a proteoglycan that is highly expressed in the majority of HCC tumors. GPC3-specific antibodies are used to diagnose HCC histopathologically, and have been proposed as a treatment of HCC. Here, we design, synthesize and demonstrate that our humanized immunoPET agent, [89Zr]Zr-DFO-TAB-H14, can stoichiometrically bind to models of human liver cancer with varied GPC3 expression. Methods: The GPC3-specific monoclonal humanized IgG1, TAB-H14, was used as a scaffold for engineering our immunoPET agent. Fluorescent and deferroxamine (DFO) chelate conjugates of TAB-H14 were characterized using mass spectrometry. Binding affinity of TAB-H14 and conjugates for GPC3 was determined in cell-free biolayer interferometry, and cell-based radioimmunoassays. GPC3-expression was assessed by flow cytometry and immunofluorescence using commercially available anti-GPC3 antibodies and TAB-H14 in GPC3−(A431) and GPC3+ cell lines including an engineered line (A431-GPC3+, G1) and liver cancer lines (HepG2, Hep3B, and Huh7). DFO-TAB-H14, was radiolabeled with Zr-89. Mice were subcutaneously engrafted with the aforementioned cell lines and in vivo target engagement of the immunoPET agent [89Zr]Zr-DFO-TAB-H14 was determined using PET/CT, quantitative biodistribution, and autoradiography. Results: TAB-H14 demonstrated subnanomolar to nanomolar affinity for human GPC3. Fluorescently tagged TAB-H14 was able to bind to GPC3 on cell membranes of GPC3-expressing lines by flow cytometry. These results were confirmed by immunofluorescence staining of A431, G1 HepG2, Hep3B, and Huh7 tumor sections. ImmunoPET imaging with [89Zr]Zr-DFO-TAB-H14 showed stoichiometric tumor uptake corresponding to the cell surface expression levels. Autoradiography and immunostaining confirmed in vivo findings. Conclusion: We systematically demonstrate that the humanized immnoPET agent [89Zr]Zr-DFO-TAB-H14 specifically and stoichiometrically binds to GPC3 in several models of human liver cancer, serving as a promising in vivo GPC3 sensor. This agent may provide utility in HCC diagnosis and surveillance, and the selection of candidates for GPC3-directed therapies.

Lnc-HOTAIR predicts hepatocellular carcinoma in chronic hepatitis C genotype 4 following direct-acting antivirals therapy.

Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.

Hepatocellular carcinoma from the view of gastroenterologist/hepatologist

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

PNPLA3 and HLA-DQB1 polymorphisms are associated with hepatocellular carcinoma after hepatitis C virus eradication.

Even though both interferon (IFN)-based and direct-acting antiviral (DAA) therapies against hepatitis C virus (HCV) reduce the risk of hepatocellular carcinoma (HCC), post-sustained virological response (SVR) patients remain at elevated risk of HCC. A total of 4620 patients who achieved SVR were enrolled in this retrospective cohort study. After excluding patients who had a history of HCC or developed HCC within 1year and whose follow-up period was less than 1year and who were positive for HBsAg, we investigated the association between clinical characteristics and HCC development after SVR in the remaining 3771 patients. Median observation period was 41months. We confirmed known risk factors. In addition, we found that PNPLA3 and HLA-DQB1 polymorphisms were associated with HCC after SVR. Finally, we propose an estimation model for the incidence of HCC after SVR. Based on gender, FIB-4 index, AFP, and PNPLA3 polymorphism, about 18% of all patients were classified as having high risk, with a cumulative incidence rate (CIR) at 5years of 16.5%. Another 17% were classified as having moderate risk with a CIR of 7.6%. The remaining 65% showed a CIR of 0.5%. The effect of PNPLA3 polymorphism might be more pronounced in patients with lower body mass index (BMI) and without diabetes mellitus compared to those with higher BMI and diabetes mellitus. We demonstrated that PNPLA3 and HLA-DQB1 polymorphisms were associated with HCC after SVR. These findings might be useful to inform risk stratification for HCC surveillance after SVR.

Modeling the time-related fluctuations of AFP and PIVKA-II serum levels in patients with cirrhosis undergoing surveillance for hepatocellular carcinoma.

The time-related variability of HCC biomarkers has not been investigated so far. To assess the changes of alpha-fetoprotein (AFP) and protein induced by vitamin-K absence/antagonist-II (PIVKA-II) in patients with HCC (HCC+) as compared to patients without HCC (HCC-). AFP and PIVKA-II were measured by a single laboratory using an automated chemiluminescent-enzyme-immunoassay (Fujirebio Inc., Tokyo, Japan) in 1163 sera of 418 cirrhotics (31.1% HBV, 58.6% HCV, 10.3% non-viral etiology) undergoing ultrasound HCC surveillance. The mean (range) number of effective time-points available for analysis was 2.8 (2.0 to 3.0); 124 patients with HCC were matched with 294 who remained HCC free for at least 12 months after the last specimen. AFP and PIVKA-II changes were estimated over time by means of a random-effect generalized least squares (RE-GLS) regression model under the missingness at random assumption. Patients with and without HCC had comparable chronic liver disease etiology and staging. AFP/PIVKA-II median (25th; 75th percentile) values at the latest time-point were 4.2 (2.6; 8.6) ng/mL/32 (25; 42) mAU/mL in HCC- and 8.4 (4.4; 32.1) ng/mL/66 (32; 192) mAU/mL in HCC+ (p< 0.001). Log10AFP and log10PIVKA-II time-changes differed in HCC+ and HCC- patients. In HCC+ patients, both log10AFP and log10PIVKA-II showed an increasing trend over time. In HCC- patients, log10PIVKA-II variations were minimal as compared to log10AFP variations. The percent increase of log10AFP at 6 months vs. baseline was 11% (95%CI 5 to 17%) and 5% (95%CI 1 to 8%) for log10PIVKA-II in HCC+vs. HCC- patients. The present retrospective study of the biological variability of AFP and PIVKA-II suggests that their time-related changes may serve as potential predictors of HCC. This topic needs to be addressed by longitudinal studies.

Utility of serological tumor biomarkers for surveillance of hepatocellular carcinoma in patients undergoing dialysis.

Patients undergoing dialysis are at risk of hepatocellular carcinoma (HCC) and preferably should undergo HCC surveillance. We investigated the utility of HCC tumor markers for HCC surveillance in patients undergoing dialysis. Three serum markers specific for HCC, namely alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and des-gamma-carboxy prothrombin (DCP), were measured in dialysis patients with and without a diagnosis of HCC (n = 60 and 507, respectively). The predictive value of each marker and that of a diagnostic score (GALAD score) based on patient age and gender as well as the same three markers were evaluated by receiver-operating characteristic (ROC) analysis, as well as sensitivity and specificity. AFP, DCP and the GALAD scores showed high predictive values for HCC, with areas under the ROC curve of >0.85. This effectiveness remained when focusing on small HCC (≤3 cm or ≤2 cm) or early-stage HCC (Stage I), as well as after propensity score matching of background characteristics of HCC and non-HCC patients. In particular, DCP and GALAD score had excellent predictive abilities for HCC. Measuring serum tumor markers for HCC can serve as a complement to imaging studies in the surveillance of HCC in patients undergoing dialysis, and reduce the likelihood of advanced HCC at detection and diagnosis.

S1145 Current Hepatocellular Carcinoma Screening Strategies for Nonalcoholic Fatty Liver Disease May Not Be Cost-Effective

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the leading cause of liver disease in the U.S., is associated with an increased risk of hepatocellular carcinoma (HCC), with ∼30% of NAFLD-associated HCC cases diagnosed in non-cirrhotic patients. HCC surveillance with twice-yearly (q6m) ultrasound (US) has been advocated for patients with stage 3 fibrosis (F3) and cirrhosis (F4). However, the cost-effectiveness (CE) of screening is unclear, particularly for F3 patients. Previous studies have found screening for F4 patients to be cost-effective, but they may have underestimated the costs associated with HCC treatment. We analyzed the CE of HCC screening in NAFLD incorporating recent HCC treatment cost data. METHODS: We created a novel microsimulation model of NAFLD and HCC natural history and surveillance. In a state-transition framework, 100,000 50-year-old patients progressed through the health states representing the development and growth of HCCs (with an annual HCC risk of 2.6% for F4, 0.02–0.9% for F3), screening for these tumors (comparing q6m US until age 70 to no screening), subsequent treatment, and long-term survival. Transition parameters were derived from published data. Each health state was associated with costs, with HCC treatment costing $130,240–$267,139 per a recent national VA study. We calculated incremental cost-effectiveness ratios (ICER) for several comparisons, determining acceptability of screening using a threshold of $100,000/life-year gained. We evaluated screening scenarios including q6m US for F3, F4 patients with follow-up of positive tests with MRI vs. CT, as well as q6m MRI for surveillance of F3 patients. RESULTS: The F4 NAFLD group screened with q6m US and followed up with MRI had an ICER of $178,270 with 3.2 average months of life gained. The F3 NAFLD group screened with q6m US (followed by MRI) had an ICER of $192,693 to $1,106,1878 and 0.07–2.3 months of life gained (for estimated annual HCC incidence of 0.02%–0.9%.) In the F3 NAFLD group screened with q6m MRI, the ICER was $289,375 with 1.3 months of life gained. CONCLUSION: We found that twice-yearly surveillance with US or MRI was associated with modest life-year gains for NAFLD patients with significant fibrosis, but surveillance was not cost-effective using contemporary willingness-to-pay thresholds. More individualized cost estimates based on HCC risk stratification, particularly among F3 patients, may be warranted.Table 1.: Cost-effectiveness analysis of HCC surveillance among F3 and F4 NAFLD patients by fibrosis stage and screening type

The value of serum abnormal prothrombin in clinical application of hepatocellular carcinoma

Objective: To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC). Methods: The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 μg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ(2) test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results: The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter (r(2)=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter (r(2)=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP (P<0.01) . Conclusions: PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.

S0995 Incidentally Diagnosed Hepatocellular Carcinoma: Root Cause Analysis and Characteristics

INTRODUCTION: Hepatocellular carcinoma (HCC) is the cause of 50-70% of liver-related deaths, with 85-95% of cases diagnosed in patients with underlying liver cirrhosis. The AASLD recommends using ultrasounds with or without tumor markers for HCC surveillance for patients with cirrhosis. We aim to identify the incidentally diagnosed cases, characterize them and perform a root cause analysis. METHODS: We performed a retrospective chart review. All radiological reports over 3 years with the word “hepatocellular carcinoma” were searched (n = 1750) and only those with a true diagnosis of HCC were included (n = 208). Patients were divided into group 1 (surveillance diagnosis) and group 2 (incidental diagnosis). Demographic data, details of cause analysis and baseline characteristics were collected. Results were compared by correlations and t-test using ‘R’ statistical software. RESULTS: We analyzed 208 patients, of which 43 (21%) were female, 157 (76%) were Caucasian and 41 (20%) were African American. Group 1 had 81 (38.9%) patients and group 2 had 127 (61.1%), with a higher number of females diagnosed via surveillance [P = 0.018]. It was found that most cases of incidentally diagnosed HCC occurred because of undiagnosed cirrhosis (47.6%), followed by patient attrition or failure to establish care (30.2%). 17.5% of patients had HCC with no underlying cirrhosis or hepatitis B infection. For patients diagnosed incidentally, most cases were diagnosed via abdominal CT (59.8%), followed by ultrasound (37.8%). The most common indications for imaging for these patients were abnormal liver function tests (29.9%) and abdominal pain (29.1%). We compared characteristics between groups and found that Group 1 had significantly lower metastases at diagnosis [P = 0.004], significantly lower number of index tumors at diagnosis [P = 0.001 (5.5–22.0)], lower mean tumor size [p=< 0.001 (2.01–3.77)] and a trend towards lower median AFP [P = 0.0726]. CONCLUSION: In our practice at an urban Midwestern tertiary care hospital, we found that a majority of cases of HCC had been diagnosed incidentally. Most cases had undiagnosed cirrhosis or poor patient follow-up and poorer prognostic features at diagnosis as compared to those diagnosed via surveillance. A stronger focus on recognizing early cirrhosis by clinicians and emphasizing follow-up and education in patients with cirrhosis will help improve HCC outcomes in this region.Table 1.: Baseline CharacteristicsTable 2.: Root Cause Analysis of Incidentally Diagnosed Hepatocellular Carcinoma

S2469 A Rare Case of Hepatocellular Carcinoma With Isolated Recurrence to the Stomach

INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth-most common cancer worldwide and fourth leading cause of cancer-related mortality according to the WHO. It primarily metastasizes to the lungs, lymph nodes, and bones. Metastases of HCC to the gastrointestinal (GI) tract and specifically to the stomach are very infrequent. In this report, we present a unique case of HCC metastatic to the stomach. CASE DESCRIPTION/METHODS: A 61-year-old African-American (AA) female with hepatitis C-related cirrhosis complicated by HCC, originally diagnosed in 2015 and managed by partial hepatic resection. In April 2020, she underwent routine HCC surveillance imaging. MRI abdomen and pelvis (Figure 1) demonstrated no new liver lesions but was significant for an isolated 3.4 × 2.7 cm mass that was identified at the greater curvature of the stomach. She underwent upper endoscopy with endoscopic ultrasound revealing a 3.1 × 2.9 cm hypoechoic mass (Figure 2). Fine needle aspiration biopsy was performed, and pathology demonstrated an epithelioid mass compatible with HCC. Immunohistochemistry staining was positive for Cam5.2, glypican-3, and hepatocyte (partial) positive, confirming metastatic HCC. CT chest was negative for intrathoracic metastasis. The patient underwent partial gastrectomy in May 2020 given the isolated metastatic gastric lesion. Surgical pathology confirmed the diagnosis of moderately-differentiated metastatic HCC. DISCUSSION: We report a very rare case of metastatic HCC in an asymptomatic AA female, diagnosed on routine surveillance imaging for HCC. To our knowledge, this is the first reported case of HCC metastatic to the stomach in an African-American. Cases of HCC metastatic to the GI tract are exceedingly rare. The majority of cases of HCC with metastatic lesions in the stomach occur by direct extension rather than by hematologic dissemination. In documented cases, patients have presented most frequently with either iron deficiency anemia or abdominal pain. Almost all the reported cases have occurred in non-white individuals, and most have occurred in patients of East Asian ethnicities.Figure 1.: Greater curvature gastric mass.Figure 2.: EUS image of gastric mass.

S2607 A Unique Case of Thrombopoietin Receptor Agonists-Induced Portal Vein Thrombosis

INTRODUCTION: It is well known that patients with cirrhosis develop thrombocytopenia secondary to their portal hypertension. Many patients with chronic liver disease induced thrombocytopenia (CLD-T) experience significant acute blood loss due to esophageal variceal bleeding, epistaxis, gingival bleeding, and other adverse bleeding events. Recently, thrombopoietin receptor agonists (TPORA), such as avatrombopag, have come into favor to use periprocedurally for patients with CLD-T. Here, we present a unique case of TPORA induced portal vein thrombosis (PVT). CASE DESCRIPTION/METHODS: A 64-year-old female with a history of decompensated alcohol liver cirrhosis, whose last drink was in December of 2016, presented to the hepatology clinic for routine follow up. One month prior, she was given avatrombopag prior to dental extractions with partial dentures for her thrombocytopenia since during her last dental procedures she had major bleeding requiring hospitalization with blood transfusions. Prior to her procedure her platelets were 81, INR 1.2 and comprehensive metabolic panel normal besides a bilirubin of 1.5. The patient was given avatrombopag 40 mg daily for five days prior to her dental procedure. There was no major bleeding or adverse events. As part of her routine follow up she had an abdominal ultrasound for hepatocellular carcinoma surveillance where she was found to have a new main PVT, compared to her prior abdominal ultrasound done nine months prior. An MRI performed to confirm this showed occlusion of the left portal vein and diminutive main and right portal veins without thrombus. She was started on direct oral anticoagulation with resolution of her left portal vein thrombus on repeat imaging six months later. DISCUSSION: Consideration of thrombosis after use of TPORA such as avatrombopag, especially with platelet counts above 50, is important as this can cause new onset ascites and preclude individuals from liver transplantation. Several peer reviewed articles suggest that there is no increase rate in PVT in patients with CLD-T who use these agents periprocedurally.1,2,3,4,5 Yet, there is a prescribing warning for these medications that PVT can occur in 2% of patients with CLD-T receiving these drugs.6 A high suspicion after utilization of these medications with symptoms such as abdominal pain, new ascites, or other clinical manifestations should warrant clinicians to rule out PVT after use of these medications and start appropriate anticoagulation as able.

Imaging Modalities for Hepatocellular Carcinoma Surveillance: Expanding Horizons beyond Ultrasound.

In Asian countries favoring loco-regional treatment such as surgical resection or ablation, very early-stage hepatocellular carcinoma (HCC) should be the main target for surveillance. Even though ultrasound (US) has been accepted as a primary imaging modality for HCC surveillance, its performance in detecting very early-stage HCCs is insufficient. Moreover, in more than 20% of patients at high risk for HCC, visualization of the liver on US may be limited owing to the advanced distortion and heterogeneity of the liver parenchyma. Recently revised HCC clinical guidelines allow the use of alternative surveillance tools including computed tomography or magnetic resonance imaging in patients with inadequate US exams. This paper summarizes the findings of recent studies using imaging modalities other than US as surveillance tools for HCC as well as strengths and limitations of these modalities.

Effects of Cirrhosis and Diagnosis Scenario in Metabolic-Associated Fatty Liver Disease-Related Hepatocellular Carcinoma.

Metabolic-associated fatty liver disease (MAFLD) is a major cause of liver-related complications, including hepatocellular carcinoma (HCC). While MAFLD-related HCC is known to occur in the absence of cirrhosis, our understanding of MAFLD-related HCC in this setting is limited. Here, we characterize MAFLD-related HCC and the impact of cirrhosis and screening on survival. This was a multicenter, retrospective, cohort study of MAFLD-related HCC. MAFLD was defined based on the presence of race-adjusted overweight, diabetes, or both hypertension and dyslipidemia in the absence of excess alcohol use or other underlying cause of liver disease. The primary outcome of interest was overall survival, and the primary dependent variables were cirrhosis status and prior HCC screening. We used Kaplan-Meier methods to estimate overall survival and Cox proportional hazards models and random forest machine learning to determine factors associated with prognosis. This study included 1,382 patients from 11 centers in the United States and East/Southeast Asia. Cirrhosis was present in 62% of patients, but under half of these patients had undergone imaging within 12months of HCC diagnosis. Patients with cirrhosis were more likely to have early stage disease but less often received curative therapy. After adjustment, cirrhosis was not associated with prognosis, but the presence of cancer-related symptoms at diagnosis was associated with poorer prognosis. Conclusion: Cirrhosis was not associated with overall survival in this cohort of MAFLD-related HCC, while diagnosis in the presence of symptoms was associated with poorer prognosis. The HCC surveillance rate in patients with MAFLD-related HCC was disappointingly low in a multicenter cohort.

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

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

A multi-centre study of trends in hepatitis B virus-related hepatocellular carcinoma risk over time during long-term entecavir therapy.

The risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is reduced by antiviral therapy. Here, we evaluated the chronological trends in HCC development risk starting in 2007, when entecavir reimbursement was first initiated in South Korea. Treatment-naïve patients with chronic hepatitis B (CHB) receiving entecavir 0.5mg/d were stratified into three groups according to entecavir start time: early (2007-2010), middle (2011-2012) and late (2013-2014) cohorts Among 2442 patients, cumulative probabilities of developing HCC after 1, 3 and 5years were, respectively, 1.7%, 5.1%, and 8.2% (early cohort; n=672); 1.5%, 5.1% and 8.9% (middle cohort; n=757); and 1.2%, 5.3% and 10.6% (late cohort; n=1013; P>.05 between each pair). Older age, male, positive hepatitis B e antigen, liver cirrhosis, Child-Pugh class B (vs A) and lower platelet count significantly predicted HCC development in univariate analysis (P<.001), whereas entecavir start time (early vs middle vs late cohorts) did not affect the risk of HCC development (P=.457). A multivariate analysis revealed that older age (adjusted hazard ratio [aHR]=1.041), male gender (aHR=2.069), liver cirrhosis (aHR=3.771) and Child-Pugh class B (vs A, aHR=1.548) were independently associated with an increased risk of HCC development, whereas higher platelet count was independently associated with a reduced risk of HCC development (aHR=0.993; all P<.05). In conclusion, the risk of developing HCC among patients receiving entecavir in South Korea has been stable since 2007. To establish more effective HCC surveillance programs, further studies regarding the carcinogenic roles of nonviral factors are required.