HCC Screening Research Articles

Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial

BackgroundHepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient...

National Liver Cancer Screening Trial (TRACER) study protocol.

Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice. The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5. The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel. NCT06084234. The TRACER Study is actively enrolling.

Comparative Study of Epidemiology of HCC in the (HCV) Patients in the Egyptian Population before and after Hepatitis C National Screening Program (100 Million Seha)

Abstract Background HCC is considerd one of the most common tumors in Egypt and one of the most common predisposing factors is HCV Objectives The aim of this study is to determine the clinical characteristics and relevance between HCC patients before and after national screening of HCV (two groups) according to child score, stage of disease, effect of treatment at clinical oncology department of Ain Shams University, Cairo, Egypt Subjects and Methods This retrospective analytical study included HCC patients (pathologically confirmed or diagnosed by radiological criteria) from Clinical Oncology Department, Ain Shams University Faculty of Medicine, Cairo, Egypt. from January 2017 to December 2020. and stratified into two groups 1stgroup was for patients who were diagnosed as HCC 2 years before national screening program of HCV (100 million seha), 2nd group was for patients who presented after national screening program Results In Group (1) most of the patients were diagnosed as HCV (86) patients (97.7%) of the patients with Co HBV infection (4) patients (4.2%), in Group (2) most of the patients were diagnosed as HCV (92) patients declined to (82.1%) while Co HBV declined to (1) patient (1%), number of patients who had Child A classification in Group (1) (36) patients and Child C (7) patients (10.9%), in Group (2) number of the patients who were Child A (62) patients (69.7%), Child C (3) patients (3.4%), in Group (1) number of patients who were ECOG PS 1 (26) patients (41.3%) while ECOG PS 4 were (4) patients (6.3%), On the other hand in Group 2 number of the patients who had ECOG PS1 (46) patients (46.5%) while ECOG PS 4 declined to (2) patients (2%), According to (BCLC) in Group 1, number of the patients with BCLC (C), (56) patients (63.6%), BCLC (A) were only (10) patients (11.4%) of the patients, BCLC (D) (5) patients (5.7%), in Group (2), BCLC (C) (62) patients declined to (54.4%), BCLC (A) increased to (32) patients (28.1%), BCLC (D) (3) patients (2.6%) of the total patients in Group 2. Conclusion our study demonstarted the efficacy of national screening program of HCV in the screening, diagnosis and treatment of HCC, we conducted that the results of the screening program could affect the diagnosis and treatment of HCC so its very considrable that discovery of HCC in earlier Child classification, Stage after national screening affected the treatment.

Efficacy of blood plasma spectroscopy for early liver cancer diagnostics in obese patients

Introduction and ObjectivesHepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. Material and MethodsWe employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. ResultsSensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). ConclusionsWe suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. Clinical trial registrationNCT04221347

Efficacy and safety in advanced hepatocellular carcinoma between patients with negative and positive APF treated with targeted and immunotherapy.

e16162 Background: Serum alpha-fetoprotein (AFP) is widely accepted as a crucial tool for clinical diagnosis and screening of HCC. However, there are cases where patients test negative for AFP but are confirmed to have Hepatocellular Carcinoma through imaging or pathological examinations. Despite these findings, there is limited research focusing on the medicine selection for AFP-negative patients. Methods: This retrospective cohort study, involving 223 untreated advanced HCC patients, and the first-line regimen consisted of targeted therapy and TKI+ICIs therapy. Patients are categorized into negative and positive AFP groups based on initial serum levels. Main efficacy endpoint was progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: According to the level of serum AFP, they were divided into negative group(100) and positive group(123). The two groups showed no statistically significant differences in age, gender, Child-Pugh score and other baseline clinical characteristics( P> 0.05). At data cut-off at February 2023, median OS was not matured and mPFS in negative group was higher than positive group(8.2 vs 5.3months, P< 0.0001). In the ICIs+TKI therapy cohort, mPFS in the negative AFP group(52) was significantly higher than in the positive AFP group(70) (10 vs. 5.8 months, P = 0.0021). Considering all patients in the negative AFP group as a subgroup, an analysis of survival benefits between those receiving targeted therapy and those receiving TKI+ICIs therapy revealed no significant difference in PFS( P> 0.05). Moreover, AEs were compared between the negative and positive group, with no significant differences observed in Any Grade or Grade 3/4( P> 0.05). Conclusions: Patients with negative AFP exhibited superior survival benefits compared to those with positive AFP in first-line therapy. Regarding PFS, the TKI+ICIS therapy did not demonstrate a better benefit over targeted therapy in the negative AFP subgroup.

The dynamic variation position and predominant quasispecies of hepatitis B virus: Novel predictors of early hepatocarcinoma

To find the predictors of early HCC based on the dynamic changes of HBV quasispecies, this study utilizing the second-generation sequencing (NGS) and high-order multiplex droplet digital PCR (ddPCR) technology to examine the HBV quasispecies in serum of total 247 subjects recruited from high-incidence area of HCC. In the discovery stage, 15 non-synonymous Single Nucleotide Polymorphisms (SNPs) with higher variant proportion in HCC case group were founded (all P<0.05). Furthermore, the variant proportions in some of these SNPs were observed changing regularly within 5 years before the onset of HCC, and 5 of them located in HBX, 2 in HBS and 2 in HBC. The HBV predominant quasispecies and their consensus sequences were identified by genetic evolution analysis, in which the high HBS and HBC quasispecies heterogeneity were found associated with the forming of multifarious quasispecies clones, and the HBX gene had the highest proportion of predominant quasispecies (46.7 % in HBX vs 12.7 % and 13.8 % in HBS and HBC respectively) with the key variations (G1512A, A1630G, T1753C/G/A, A1762T and G1764A) determined. In the validation stage, we confirmed that the combined double mutations of G1512A+A1630G, A1762T+G1764A, and the combined triple mutations of T1753C/G/A + A1762T+G1764A, all expressed higher in early HCC cases when comparing with control group (all P<0.05). We also demonstrated the advantages of ddPCR using in multi-variations detection in large-sample for early HCC surveillance and screening. So we think that the dynamic of key HBV variation positions and their different combinations determined by quasispecies anlysis in this study can act as the novel predictors of early hepatocarcinoma and suitable to popularize and apply in HCC screening.

Current updates in HCC screening and treatment.

Current updates in HCC screening and treatment.

S1714 Evaluation of a Trainee Physician-Led Outreach to Increase HCC Screening Rates in Veterans Using the RE-AIM Framework

S1714 Evaluation of a Trainee Physician-Led Outreach to Increase HCC Screening Rates in Veterans Using the RE-AIM Framework

S1494 Can We Get Veterans to Agree to Undergo HCC Screening? Quality Improvement Measures and a Survey Evaluating Barriers

S1494 Can We Get Veterans to Agree to Undergo HCC Screening? Quality Improvement Measures and a Survey Evaluating Barriers

Nanobody-Based ImmunoPET for Hepatocellular Carcinoma

HCC accounts for 75-90% of all primary liver cancers, the majority of which are treated with liver-directed therapy. Treatment response and recurrence are difficult to discern using conventional imaging with MR/CT. Tumor-selective PET imaging could help with clinical management in this setting. Here, we engineer HN3, a single-domain antibody (nanobody) specific to GPC3, a histopathologically-defining HCC marker, as an immunoPET agent. We compared both conventional and sortase-based site-specific modification methods for synthesizing HN3 immunoPET tracers. Stochastic lysine conjugation with deferoxamine (DFO-NCS) was done to synthesize nHN3-DFO. ssHN3-DFO was engineered utilizing sortase-mediated conjugation of HN3 containing an LPETG C-terminal tag and a triglycine-DFO chelator. Biolayer interferometry (BLI) and radioligand saturation assays were done to determine binding affinity pre- and post-Zirconium-89 labeling. Following, PET/CT with a terminal 3-hour biodistribution was done in mice inoculated with isogenic A431 and A431-GPC3+ xenografts to determine conjugate specificity for GPC3. Finally, conjugates were evaluated in a HepG2 liver cancer model via ex vivo biodistribution studies and a comparative PET/CT study in mice bearing HepG2 tumors that were imaged with both [18F]FDG and 89Zr-ssHN3. Both conjugates exhibited nanomolar binding affinity for GPC3 in vitro (11-30 nM for nHN3 and 10-15 nM for ssHN3). A431 and A431-GPC3+ PET/CT and biodistribution studies showed specificity to GPC3 by both probes, with more favorable tumor uptake by 89Zr-ssHN3 at 3 hours post-injection (14% IA/g vs. 7% IA/g for nHN3). Both tracers also displayed uptake in HepG2 (GPC3+) liver tumors, again with the site specifically conjugated probe having higher tumor accumulation and lower liver signal than the conventionally modified HN3 (7% IA/g vs. 5 % IA/g for tumor and 2% IA/g vs. 4% IA/g for liver at 1-hour post-injection). PET/CT studies in mice imaged with [18F]FDG and 89Zr-ssHN3 demonstrated more consistent tumor accumulation for the nanobody conjugate (4/4 mice had uptake by the tumor vs. 1/4 for FDG). We successfully designed, synthesized, and characterized novel GPC3-selective nanobody PET probes that can image liver tumors in vivo. The site-specifically conjugated tracer showed more favorable biodistribution and pharmacokinetic properties, resulting in a much higher tumor: liver signal compared to 89Zr-nHN3. We also show the superiority of the 89Zr-ssHN3 imaging over conventional [18F]FDG, highlighting a clear advantage in using targeted tumor imaging for this cancer type. Successful translation of the site-specifically conjugated nanobody may ultimately aid in characterizing lesions following liver-directed therapy and allow for more comprehensive screening, early diagnosis, and post-treatment surveillance of HCC.

THU-554 - The importance of regular screening for HCC in non-alcoholic steatohepatitis/non-alcoholic fatty liver disease

THU-554 - The importance of regular screening for HCC in non-alcoholic steatohepatitis/non-alcoholic fatty liver disease

Tubulovillous adenoma of the bile duct under direct cholangioscopy

A 56 year old male with chronic hepatitis B on entecavir therapy with a low viral load who underwent routine HCC screening with transabdominal ultrasound

Hepatocellular Carcinoma: A Cross-Sectional Analysis of Risk Factors

Background Hepatocellular carcinoma is the most prevalent primary liver cancer globally and the major cause of cancer-associated deaths. Method: A cross-sectional study was carried out at CMH Multan's Department of Histopathology. The individuals with HCC presented to CMH Multan's OPD or indoor general medicine department were selected. Informed consent was obtained. On a standardised proforma, all information such as gender, age groups, residence status, family history, diabetes, smoking, hypertension, and obesity was entered and analysed using the latest version of the SPSS. Results: 85 (67.5%) of the 126 study cases were male, whereas 41 (32.5%) were female. 72 (57.1%) were from metropolitan areas, while 54 (42.9%) were from rural areas. Smoking was found in 10 (7.9%), and diabetes was found in 43. (34.1%). Obesity was found in 18 (14.3%), and hypertension was present in 74 (58.7%). Only 5 (4%) of our study cases had a family history of HCC. Conclusion: HCC is more common in male patients, older patients, urban patients, and patients with diabetes, hypertension, and obesity. Individuals with diabetes, hypertension, and obesity undergo screening for HCC regularly. Further research is necessary to recognise the environmental and genetic variables that could contribute to developing HCC in various environments and populations. Keywords: Liver, Risk factors, Hepatocellular carcinoma, Liver neoplasms.

Opportunities to address gaps in early detection and improve outcomes of liver cancer.

Death rates from primary liver cancer (hepatocellular carcinoma [HCC]) have continued to rise in the United States over the recent decades despite the availability of an increasing range of treatment modalities, including new systemic therapies. Prognosis is strongly associated with tumor stage at diagnosis; however, most cases of HCC are diagnosed beyond an early stage. This lack of early detection has contributed to low survival rates. Professional society guidelines recommend semiannual ultrasound-based HCC screening for at-risk populations, yet HCC surveillance continues to be underused in clinical practice. On April 28, 2022, the Hepatitis B Foundation convened a workshop to discuss the most pressing challenges and barriers to early HCC detection and the need to better leverage existing and emerging tools and technologies that could improve HCC screening and early detection. In this commentary, we summarize technical, patient-level, provider-level, and system-level challenges and opportunities to improve processes and outcomes across the HCC screening continuum. We highlight promising approaches to HCC risk stratification and screening, including new biomarkers, advanced imaging incorporating artificial intelligence, and algorithms for risk stratification. Workshop participants emphasized that action to improve early detection and reduce HCC mortality is urgently needed, noting concern that many of the challenges we face today are the same or similar to those faced a decade ago and that HCC mortality rates have not meaningfully improved. Increasing the uptake of HCC screening was identified as a short-term priority while developing and validating better screening tests and risk-appropriate surveillance strategies.

The impact of HIV infection on clinical presentation and mortality among persons with hepatocellular carcinoma in Kampala, Uganda

BackgroundHIV infection is associated with more rapid progression of some comorbidities. This study assessed the impact of HIV-infection on the presentation and outcome of HCC.MethodsHCC patients attending the Mulago National Referral Hospital in Uganda were enrolled into a natural history study of HCC between March 2015 and February 2019. Standardized methods were used to collect clinical, ultrasound and laboratory data at enrolment. HCC cases were confirmed and enrolled based on a combination of clinical, ultrasound, tumor marker and pathology data. Follow-up contact was made at one, three, six, and twelve months post-enrolment to determine vital status. Symptoms and signs at diagnosis and subsequent survival were compared by HIV status. Kaplan Meier curves were used to assess HCC survival.ResultsOf 441 persons with HCC, 383 (87.0%) died within 12 months following HCC diagnosis. The median (IQR) survival was 42 (20, 106) days. HIV infection was present in 79 (18%) cases. After adjusting for baseline demographic and clinical characteristics, HIV infection was associated with increased mortality but only among those with severe HIV-associated immunosuppression (CD4 count < 200 cells per cubic milliliter), aHR (95% C) = 2.12 (1.23–3.53), p = 0.004, and not among PLWH with ≥ 200 CD4 cells per cubic milliliter, aHR (95% C) = 1.15 (0.82–1.60), p = 0.417.ConclusionAmong relatively young Ugandans, HCC is a devastating disease with rapid mortality that is especially rapid among people living with HIV(PLWH). HIV was associated with slightly higher mortality, notably among PLWH with lower CD4 cell counts. As a substantial majority of PLWH diagnosed with HCC were engaged in HIV care, further investigation should determine the effectiveness of incorporating screening and early identification of HCC among high-risk individuals into existing HIV care programs. Concurrent with growing access to curative localized treatment for HCC in sub-Saharan Africa, leveraging HIV care infrastructure affords opportunities for earlier HCC intervention.

A wide scan of plasma proteins demonstrates thioredoxin reductase 1 as a potential new diagnostic biomarker for hepatocellular carcinoma

Background Patients with liver cirrhosis are recommended ultrasonography screening for early detection of hepatocellular carcinoma to increase the chances of curative treatment. However, ultrasonography alone lacks in sensitivity. Adding plasma biomarkers may increase the detection rate. We performed a broad exploratory analysis to find new plasma proteins with potential applicability for HCC screening in patients with cirrhosis. Methods In a protein discovery cohort of 172 patients with cirrhosis or HCC, we screened for 481 proteins with suspension bead array or proximity extension assay. From these, 24 proteins were selected for further analysis in a protein verification cohort (n = 160), using ELISA, Luminex or an electrochemiluminescence platform. A cut-off model and a stepwise logistic regression model were used to find combinations of proteins with the best discriminatory performance between HCC and cirrhosis. Results Stepwise logistic regression revealed alpha-fetoprotein (AFP), decarboxy-prothrombin (DCP), thioredoxin reductase 1 (TXNRD1), and fibroblast growth factor 21 (FGF21) as the proteins with the best discriminatory performance between HCC and cirrhosis. Adding TXNRD1 to DCP and AFP increased the AUC from 0.844 to 0.878, and combining AFP, DCP and TXNRD1 with age and sex resulted in an AUC of 0.920. FGF21, however, did not further increase the performance when including age and sex. Conclusion In the present study, TXNRD1 improves the sensitivity and specificity of AFP and DCP as HCC screening tools in patients with cirrhosis. We suggest that TXNRD1 should be validated in prospective settings as a new complementary HCC biomarker together with AFP and DCP.

Abstract 5767: Pan-viral response in African Americans and European Americans with hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is often diagnosed at late-stages, with African Americans (AA) being diagnosed at a later stage with worse prognosis and high mortality rates. The poor screening and diagnosis of HCC and differences between racial/ethnic groups show a disproportion in mortality rates. Examining an individual’s viral exposure history might serve as a useful biomarker of early disease that could address and, potentially, alleviate this disparity. We aim to investigate whether viral features can be used to identify HCC and individuals at high risk (HR) of HCC. Additionally, we examine the racial/ethnic differences in viral exposures and whether viral exposure history accounts for epidemiological disparity described previously. Herein we use a technique called VirScan, which conjugates Phage Immunoprecipitation sequencing (PhIP-seq) and DNA sequencing, to profile an individual’s epitope antibody repertoire upon viral exposure. We performed VirScan on serum and plasma samples from 199 AA (130 HR and 79 HCC) and 260 European Americans (EA) (210 HR and 50 HCC) participants from the NCI-UMD cohort (NCT00913757; clinicaltrials.gov). We used a machine-learning XGBoost model to classify viral features that can discriminate HCC or HR. A composite viral score was generated using the SHAP value of the most significant viral features from the model with a higher score more predictive of HCC. Secondary analyses using Wilcoxon-Rank sums tests and Cox proportional hazard analysis revealed that while race/ethnicity did not differentially predict HCC in this cohort, the viral score was significantly higher in AA compared to EA in the HR group (p = 0.027). XGBoost search identified 235 important viral features which distinguish HCC from HR. Out of the 235 viral features, 20 viruses were different between AA and EA (FDR &amp;lt; 0.05). We also found the viral score was positively associated with incident mortality in HCC group over the study period of 8 years (p=0.03). Thus, we demonstrate that the viral history of an individual might be useful in early detection of HCC. This approach could be used to account for the disparities we see in both incidence and mortality of HCC between AA and EA. Citation Format: Theressa Ewa, Whitney L. Do, Limin Wang, Marshonna Forgues, Xin W. Wang. Pan-viral response in African Americans and European Americans with hepatocellular carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5767.

Current status and problems regarding HCC screening for the NAFLD patients

Current status and problems regarding HCC screening for the NAFLD patients

Development of a nurse-led decision counseling program for improving hepatocellular carcinoma screening: A typology-guided feasibility study

ObjectiveHepatocellular carcinoma (HCC) is frequently diagnosed late. Although ultrasound-based HCC screening is recommended, its effectiveness is restricted by underutilization. This study aimed to develop a nurse-led decision counseling program used to improve HCC screening in patients with hepatitis B and to evaluate its feasibility in terms of process, resources, management, and cultural acceptance. MethodsThe nurse-led decision counseling program was developed following the Medical Research Council framework and the preventive health model. Its components were informed by a systematic review and a qualitative study that had explored empirical HCC screening barriers. Guided by typology of Tickle-Degnen, a feasibility study was conducted among twenty eligible patients with hepatitis B, who were randomized to receive the intervention plus usual care or usual care only. Multisets of feasibility data were collected from interviews, field notes, and minutes of discussions with participants, family members, and clinical specialists. ResultsThe program consists of health education, tailored information, values clarification exercises, and exploring and addressing barriers, which help to achieve informed and value-based HCC screening utilization. Feasibility assessments identified and improved process issues, such as restrictive inclusion criteria and cultural challenges, including (1) default mistrust, (2) discrimination and confidentiality concerns, (3) cultural reluctance to open discussions about HCC screening, and (4) social influence under a collectivist culture. ConclusionsThe study informs an innovative feasibility typology for nursing interventions and contributes to a promising, feasible, and culturally relevant intervention to improve HCC screening and prevent advanced diagnosis in hepatitis B-induced HCC in China and other hepatitis B-prevalent Asian countries. Trial registrationClinicaltrials.gov: NCT04659005.

Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma in hepatitis C infection and non-alcoholic fatty liver disease-A population-based study.

Both non-alcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection commonly result in hepatic fibrosis and may lead to cirrhosis. This study aims to determine the incidence of HCC in patients with HCV or NAFLD complicated by advanced fibrosis, inferred from measurements of liver stiffness. Using Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), we identified a nationwide cohort of patients with an existing diagnosis of HCV or NAFLD with liver transient elastography (TE) testing from 2015 to 2019. HCC cases, along with a random sample of non-HCC patients, were identified and validated, leading to calculation of incidence rates for HCC after adjustment for confounders. 26,161 patients carried a diagnosis of HCV and 13,629 were diagnosed with NAFLD at the time of testing. In those with HCV, rates of HCC increased with liver stiffness with incidences of 0.28 (95% CI 0.24, 0.34), 0.93 (95% CI 0.72, 1.17), 1.28 (95% CI 0.89, 1.79), and 2.79 (95% CI 2.47, 3.14)/100,000 person years for TE score ranges <9.5 kPa, 9.5-12.5 kPa, 12.5-14.5 kPa and >14.5 kPa, respectively, after a median follow-up of 2.3 years. HCC incidence also increased with higher TE liver stiffness measures in NAFLD after a median follow-up of 1.1 years. In this retrospective cohort, the incidence of HCC in HCV and NAFLD increases with higher TE liver stiffness measures, confirming that advanced fibrosis portends risk in viral and non-viral fibrotic liver diseases. Additional comparative studies are needed to determine the optimal cut point of TE liver stiffness to inform HCC screening guidelines and approaches.