Hepatocellular Cancer Surveillance Research Articles

Contrast-Enhanced Ultrasound with Perfluorobutane for Hepatocellular Cancer Surveillance: Our Initial Local Experience

Contrast-Enhanced Ultrasound with Perfluorobutane for Hepatocellular Cancer Surveillance: Our Initial Local Experience

Implementation of a Hepatocellular Carcinoma Surveillance Program in a Community-Based Integrated Health System in Patients With Hepatitis C Cirrhosis.

Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score. Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems.

Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis

The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through2021. We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.

Etiologic fractions in patients of hepatocellular carcinoma in India with and without a background of cirrhosis: a multi-centric study.

Hepatocellular cancer (HCC) typically arises in the background of cirrhosis. The epidemiology of HCC has changed in recent years due to availability of newer antivirals, changing life-styles and greater possibility for early detection. We undertook a multicentric national sentinel surveillance for liver cirrhosis and HCC to assess the attributable risk factors for the development of HCC, both with and without a background of cirrhosis. Data from January 2017 till August 2022 from hospital-based records of eleven participating centers were included. Diagnosed cases of cirrhosis [radiological (multiphase and/or histopathological] and HCC [as per AASLD 2018] were included. History of significant alcohol intake was elicited by AUDIT-C questionnaire. Altogether 5798 enrolled patients were assessed, of which 2664 patients had HCC. The mean age was 58.2 ± 11.7years and 84.3% (n = 2247) were males. Diabetes was found in over a third of those with HCC (n = 1032;39.5%). The most common etiology of HCC was NAFLD (n = 927;35.5%) followed by viral hepatitis B and C and harmful levels of alcohol. Among those with HCC, 27.9% (n = 744) had no cirrhosis. Higher proportion of cirrhotic HCC patients had alcohol as an etiological factor as compared to non-cirrhotic (17.5 vs. 4.7%, p ≤ 0.001). NAFLD was an etiological factor for a higher proportion of non-cirrhotic HCC patients as compared to cirrhotic HCC (48.2 vs. 30.6%, p ≤0.001). Diabetics more commonly had non-cirrhotic HCC (50.5 vs. 35.2%). The following factors were associated with an occurrence of cirrhotic HCC: male gender (OR 1.372 and 95% CI 1.070-1.759), age above 60years (OR 1.409 and 95% CI 1.176-1.689), HBV (OR 1.164 and 95% CI 0.928-1.460), HCV (OR 1.228 and 95 CI 0.964-1.565) and harmful consumption of alcohol (OR 3.472 and 95% CI 2.388-5.047). The adjusted odds of non-cirrhotic patients having NAFLD was 1.553 (95% CI 1.290-1.869). This large multi-centric study demonstrates that NAFLD is the most important risk factor for development of both cirrhotic and non-cirrhotic HCC in India and has overtaken viral hepatitis. Awareness campaigns and large-scale screening are required to reduce the high burden of NAFLD-related HCC in India.

MRI for screening and surveillance for hepatocellular cancer in NAFLD and NASH

Chronic liver disease is an important risk factor for the development of hepatocellular carcinoma (HCC), with 80%-90% developing in the background of cirrhosis, primarily due to alcohol abuse and chronic viral infection with hepatitis B and C. Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) related HCC is rising due to the global epidemic of obesity and diabetes. NAFLD also potentiates other risk factors of HCC, such as chronic hepatitis C and alcoholic liver injury. Furthermore, HCC may complicate non-cirrhotic NAFLD, greatly expanding the population potentially at risk. Screening and surveillance for HCC with ultrasonography (US) in this patient population pose challenges related to body habitus, liver morphology, and co-morbidities. Magnetic resonance imaging (MRI) applying various image sequence protocols and contrast agents could aid in early detection and improved prognosis of HCC. It is of utmost importance to define the most cost-effective dynamic imaging protocol for use in patients where high-quality ultrasonography images cannot be obtained and for patients undergoing surveillance for lesions identified with US. Furthermore, standardization of MRI protocols will help to define potential unique HCC features in this population. A scoring system including patient-derived factors may help to identify high-risk patients. Standardized protocols as part of prospective cohort studies and randomized clinical trials will help to stratify high-risk patients and to aid the development of professional guidelines for screening and surveillance of HCC in patients with NAFLD and NASH using dynamic imagining techniques.

Barriers to surveillance for hepatocellular cancer among patients with chronic liver disease -providers' perspectives

Aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. While patients who are known to be at high risk for HCC should be under surveillance, only 20% of eligible patients in the United States are surveilled. The aim of this study was to identify providers’ perspectives about patient-, provider- and system-level barriers to surveillance for HCC among high-risk patients and to examine provider knowledge and attitudes related to HCC surveillance. We also explored interventions providers suggested as ways to improve HCC surveillance. Methods: Purposive sampling was used to recruit physicians and nurse practitioners in hepatology, gastroenterology, and primary care (internal and family medicine) from one academic medical center to participate in semi-structured interviews. Interviews were transcribed verbatim, and analyzed deductively and inductively to reveal emergent themes. Results: 22 informants were interviewed. During these interviews, several important themes emerged, including: (1) Provider comfort with managing chronic liver disease and the relationships between hepatology, gastroenterology, infectious disease, and primary care providers; (2) Provider knowledge of guidelines for HCC surveillance in high-risk patients and their knowledge about the impact that HCC surveillance can have; (3) How providers discuss HCC surveillance with their high-risk patients; (4) Provider-Level barriers to surveillance; (5) System-level barriers to surveillance; (6) COVID-19; (7) Patient-level barriers to surveillance, and (8) Suggested interventions to improve HCC surveillance rates. Conclusions: In designing interventions to improve HCC surveillance rates of high-risk patients in the United States, there are important targets at the patient, provider and system levels.

Tenofovir Induced Hepatitis B Surface Antigen Loss and Seroconversion in Two Patients with E-Antigen Negative Chronic Hepatitis B Infection: Case Series

Two cases of HBsAg seroconversion, following treatment with Tenofovir disoproxil fumarate, a nucleotide reverse transcriptase inhibitor, were reported amongst the patients with chronic hepatitis B infection attending gastrointestinal clinic in a tertiary hospital. The patients had liver biopsy done during their evaluation, following which they were commenced on the medication. Tenofovir was taken for four years and two years respectively before they lost the hepatitis B surface antigen and developed quantifiable antibodies to the surface antigen (Anti-HBs). Loss of HBsAg is a rare event, and seroconversion in patients with CHB is even less common. Studies have shown that HBsAg loss and seroconversion is less likely with patients on the oral antiviral agents compared with pegylated interferon. Although, both patients had very low pretreatment hepatitis B viral load which might indicate strong immune response to the virus, a factor that could have been partly responsible for the seroconversion. They however, had significant liver fibrosis on histology prior to their seroconversion and will require hepatocellular cancer surveillance until normalization of the liver histology can be ascertained

Metabolic Profiling Identified a Novel Biomarker Panel for Metabolic Syndrome-Positive Hepatocellular Cancer.

Metabolic syndrome (MetS) is an independent risk factor for hepatocellular cancer (HCC). Currently, there is no highly sensitive and specific biomarkers for HCC surveillance in MetS population. Metabolomics has been reported as a powerful technology for biomarker discovery. In the present study, we aimed to explore novel biomarkers with high sensitivity and specificity for MetS-positive [MetS(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in MetS(+) HCC individuals. Validation of the dysregulated metabolites by targeted metabolite analyses revealed that serum L-glutamic acid (L-glu), pipecolic acid (PA) and 7-methylguanine (7-mG) were increased in MetS(+) HCC compared to MetS group. Then a biomarker panel including L-glu, PA and alpha-fetoprotein (AFP) was identified as a novel biomarker for the diagnosis of MetS(+) HCC. Receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was 0.87 for discriminating MetS(+) HCC from MetS group. The biomarker panel was capable of detecting small (AUC = 0.82) and early-stage (AUC = 0.78) tumors as well. Moreover, it exhibited great diagnostic performance (AUC = 0.93) for discriminating MetS(+) HCC from other MetS-associated cancers, including colorectal cancer and gastric cancer. Collectively, our study establishes a novel diagnostic tool for MetS(+) HCC.

The erythrocyte sedimentation rate as a potential hepatocellular cancer surveillance tool

The erythrocyte sedimentation rate as a potential hepatocellular cancer surveillance tool

Patient Preferences for Hepatocellular Carcinoma Surveillance Parameters

Professional societies recommend abdominal ultrasound (US) with or without alpha fetoprotein (AFP) for hepatocellular cancer (HCC) surveillance; however, there are several emerging surveillance modalities, including abbreviated MRI and blood-based biomarker panels. Most studies have focused on provider perspectives for surveillance logistics, but few have assessed patient preferences. We aimed to measure preferences among patients with cirrhosis regarding HCC surveillance modalities. We conducted a choice-based conjoint survey to patients with cirrhosis at four institutions. Participants were provided 15 scenarios in which they were asked to choose surveillance modalities based on five test attributes: benefits, i.e. sensitivity for early HCC (range: 35-95%), physical harm, i.e. false positives requiring additional testing (range: 10-40%), financial harm, i.e. out-of-pocket costs (range: $10-100), test logistics and convenience, i.e. duration of testing (range: 10-60 min). Hierarchical Bayes discrete choice conjoint analysis was used to derive attribute importance, and preference shares were determined by simulation. In total 91% (182/199) of approached patients consented to participate in the study and 98% (n=179) successfully completed the survey. Surveillance benefits (importance: 51.3%, 95%CI: 49.0-53.4%) were valued more than risk of physical harm (importance: 7.6%, 95%CI 7.0-8.2%), financial harm (importance: 15.2%, 95%CI 14.0-16.3%), convenience (importance: 9.3%, 95%CI 8.5-10.1%) and test logistics (importance: 16.7%, 95%CI 15.4-18.1%). Based on simulations including all possible tests, patients preferred abbreviated MRI (29.0%), MRI (23.3%), or novel blood-based biomarkers (20.9%) to ultrasound alone (3.4%) or with AFP (8.8%). Patients with cirrhosis prioritize early HCC detection over potential surveillance-related harms or inconvenience.

WGO Guidance for the Care of Patients With COVID-19 and Liver Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver. Asymptomatic aminotransferase elevations are common in coronavirus disease 2019 (COVID-19) disease. Its pathogenesis may be multifactorial. It may involve primary liver injury and indirect effects such as “bystander hepatitis,” myositis, toxic liver injury, hypoxia, and preexisting liver disease. Higher aminotransferase elevations, lower albumin, and platelets have been reported in severe compared with mild COVID-19. Despite the dominance of respiratory disease, acute on chronic liver disease/acute hepatic decompensation have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a higher risk of respiratory disease progression than those without MAFLD. Alcohol-associated liver disease may be severely affected by COVID-19—such patients frequently have comorbidities including metabolic syndrome and smoking-induced chronic lung disease. World Gastroenterology Organization (WGO) recommends that interventional procedures such as endoscopy and endoscopic retrograde cholangiopancreatography should be performed in emergency cases or when they are considered strictly necessary such as high risk varices or cholangitis. Hepatocellular cancer surveillance may be postponed by 2 to 3 months. A short delay in treatment initiation and non-surgical approaches should be considered. Liver transplantation should be restricted to patients with high MELD scores, acute liver failure and hepatocellular cancer within Milan criteria. Donors and recipients should be tested for SARS-CoV-2 and if found positive donors should be excluded and liver transplantation postponed until recovery from infection.

S3280 Black-Identified Women With Chronic Hepatitis B Are More Under-Screened for Hepatocellular Cancer Compared to Other Racial Groups

INTRODUCTION: Chronic hepatitis B increases the risk of developing hepatocellular cancer (HCC) even outside the setting of cirrhosis. Prevalence of chronic hepatitis B is highest in those of Asian or immediate African descent, not African-Americans (AA), partially due to lack of universal vaccination, as opposed to genetic predisposition, given that race is not genetically bound. Early detection of HCC may improve prognosis and availability of therapies, leading many guidelines on HCC screening to include hepatitis B carriers who are Black/AA women of all ages, and Asian women over age 50. Despite these guidelines, HCC surveillance has been found to be under-utilized. In this retrospective review we examined differences in HCC screening related to electronic medical record (EMR)-identified race. METHODS: This IRB-approved study performed a retrospective chart review of patients who were seen at a single women’s gastroenterology clinic. Patient data was extracted from the EMR, between 2005-2020. 66 patients with chronic hepatitis B were included in the analysis, and grouped by race as identified in the EMR. Generalized linear mixed modeling was used to estimate the probability of receiving a screen by generic racial identification (categorized as Asian, Black/AA, or Other). RESULTS: Black/AA women were underscreened and their odds of receiving screening were statistically different from the group of non-black or Asian women (estimated log odds -4.1 (t (89.52) = -2.60, P = 0.0109, OR < 0.01)). Asian women were slightly underscreened but less so compared to the Other group (log odds -1.5 (t (119.30) = -2.09, P = 0.0391, OR = 0.08)). No women in the Other group of the data set met criteria for HCC screening. CONCLUSION: The under-utilization of screening ultrasounds for HCC in African and Asian women is concerning, especially given the AASLD guidelines to focus on such populations. Limitations of the study include small sample size, especially of Asian women needing screening, and inconsistent methods of determining race in the EMR, especially given that race is a social construct and cannot be determined visually. Possible factors for disparity in ordered screenings include provider unconscious bias and structural barriers around language. Possible factors for disparity in performed screenings include structural barriers surrounding transportation, language, and scheduling. Future studies should examine the systemic and structural barriers to the disparity in screenings being ordered and performed.Graph 1.: Comparison of observed HCC screens received versus recommended screening, by race.Graph 2.: Estimated log odds of performing HCC screen in women with hepatitis B, by race.

Issue Highlights

Endoscopic remission is associated with significant reduction in risk of clinical flare, unplanned healthcare utilization and surgery, and has emerged as a preferred treatment target in patients with inflammatory bowel diseases. To achieve this target with biologic therapy, an approach that combines pharmacodynamic effect of the drug (impact of drug on biomarkers of inflammation) and pharmacokinetic optimization of therapy (achieving optimal trough concentrations) has been proposed, but there is limited data on effectiveness of such an approach. In this issue of Clinical Gastroenterology and Hepatology, Dreesen and colleagues1Dressen E. Baert F. Laharie D. et al.Monitoring a combination of calprotectin and infliximab identifies patients with mucosal healing of Crohn’s disease.Clin Gastroenterol Hepatol. 2020; 18: 637-646Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar performed a post-hoc analysis of the TAILORIX trial to examine the role of combined pharmacodynamic and pharmacokinetic monitoring during infliximab induction and maintenance therapy for targeting endocopic outcomes in patients with Crohn’s disease. They observed that during induction and maintenance therapy, progressive decline in fecal calprotectin with infliximab therapy was associated with significantly higher rates of achieving endoscopic remission at week 12 and 54, respectively. They also observed clear relationship between infliximab trough concentration during induction therapy and endoscopic remission at week 12, identifying thresholds of 23.1 mg/L at week 2 and of 10.0 mg/L at week 6. Similarly, during maintenance therapy, infliximab thresholds of 10.0 mg/L were associated with achieving endoscopic remission. In patients with subtherapeutic trough concentration, infliximab dose escalation was effective in achieving endoscopic remission only if it was associated with a decline in fCal; persistent elevation of fCal despite achieving higher infliximab concentration was associated with lack of endoscopic remission. Taken together, these results strongly support an approach that combines pharmacodynamic monitoring (for improvement in biomarkers of inflammation) with pharmacokinetic monitoring for infliximab (checking trough concentration to ensure adequate trough concentration) to ensure optimal outcome in patients with moderate to severely active Crohn’s disease. See page 637. One of the key objectives of gastroenterology fellowship programs is training in basic endoscopic procedures. Traditionally, this has been based on the apprenticeship model in which fellows learn endoscopy through hands-on experience under the supervision of multiple faculty members. However, teaching endoscopy is very challenging, and there may be significant variations in teaching style and quality. An evidence-based set of endoscopy teaching best practices can provide a framework to promote effectiveness of individual endoscopy teachers. To develop these best practices in teaching endoscopy, Kumar and colleagues2Kumar N.L. Smith B.N. Lee L.S. et al.Best practices in teaching endoscopy based on a Delphi survey of gastroenterology program directors and experts in endoscopy education.Clin Gastroenterol Hepatol. 2020; 18: 574-579Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar performed a national Delphi survey of gastroenterology fellowship program directors (n = 34) and experts in endoscopy education (n = 2), in which experts rated each of 18 endoscopy teaching competencies (identified based on literature review, personal experience, and cognitive interviews with experts) as “essential,” “important, but not essential,” or “not important.” Based on 2 rounds of Delphi consensus, experts agreed on the top 10 essential list of endoscopy teaching competencies. These include: (before each session and procedure) 1) assessing trainee’s current procedural competency, 2) discussing patient’s history and plans for procedure with trainee, 3) confirming that patient is aware of trainee’s participation and role; (during endoscopic procedure) 4) maintaining attention throughout the case, 5) providing appropriate amount of feedback during the procedure, 6) using standardized endoscopic language to guide trainee through the procedure, 7) assuming control of procedure when trainee is unable to progress or if patient safety concerns arise; and (after each procedure and session) 8) discussing next steps in the management of patient, 9) reviewing procedure note and providing feedback as needed to the trainee, and 10) providing constructive feedback to trainee at end of the session. These competencies are specific, measurable, and relevant, and provide a framework for faculty development to improve the quality of endoscopic education within fellowship programs. See page 574. Colonoscopy is considered the reference standard for diagnosing colorectal cancer (CRC) and its precursor lesions and is advocated as one of the most favored tests for screening for CRC. However, it is invasive, resource- and cost-intensive and with non-trivial risks. Alternative CRC screening strategies such as flexible sigmoidoscopy and fecal immunochemical test (FIT) are also recommended as progressively less invasive, but less sensitive options. It is essential for policy makers to know the impact of different screening programs over multiple rounds with long-term follow up. In this issue of Clinical Gastroenterology and Hepatology, Grobbee, van der Vlugt and colleagues3Grobbee E.J. van der Vlugt M. van Vuuren A.J. et al.Diagnostic yield of one-time colonoscopy vs one-time flexible sigmoidoscopy vs multiple rounds of mailed fecal immunohistochemical tests in colorectal cancer screening.Clin Gastroenterol Hepatol. 2020; 18: 667-675Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar compared the diagnostic yield of once-only colonoscopy, once-only flexible sigmoidoscopy, and 4 rounds of FIT in population-based CRC screening, including interval cancer rate. Combining data from 3 population-based trials in the Netherlands, a total of 30,052 average risk persons were invited for CRC screening. Cumulative participation rate was significantly higher for FIT screening (77%) than for flexible sigmoidoscopy (31%; P < .001) or colonoscopy (24%; P <. 001). In the primary intention-to-screen analysis, the cumulative diagnostic yield of advanced neoplasia was highest with FIT screening (4.5%; 95% CI, 4.2–4.9) than with colonoscopy (2.2%; 95% CI, 1.8–2.6) or flexible sigmoidoscopy (2.3%; 95% CI, 2.0–2.7). This higher diagnostic yield was reached with significantly fewer colonoscopies for FIT screening and flexible sigmoidoscopy screening than colonoscopy screening. No differences were found regarding the detection of CRC between all three strategies. Between participants, colonoscopy had the highest diagnostic yield for advanced neoplasia, while also detecting greater numbers of non-advanced adenomas, which are of uncertain clinical importance. Through linkage with the Netherlands Cancer Registry, proportions of patients that developed interval CRC were 0.13% for persons with a negative result from the FIT, 0.09% for persons with a negative result from flexible sigmoidoscopy, and 0.01% for persons with a negative result from colonoscopy. These findings aid in deciding on choice of screening strategies worldwide, based on expected participation rates and available colonoscopy resources. This article is highlighted by an editorial by Kevin Selby and Manuel Zorbi.4Selby K. Zorzi M. Real-world strategies for colorectal cancer screening based on studies from the Netherlands.Clin Gastroenterol Hepatol. 2020; 18: 546-547Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar See page 667. The prevalence of nonalcoholic steatohepatitis (NASH)-associated hepatocellular cancer (HCC) is increasing. Ultrasound-based HCC surveillance strategies have important limitations, particularly in patients with NASH. To address the insufficient performance of ultrasound-based surveillance in HCC detection, the GALAD score (based on age, sex, serum levels of alpha-fetoprotein [AFP], AFP isoform L3 [AFP-L3], and des-gamma-carboxy prothrombin [DCP]) was developed and has been shown to be superior to ultrasound-based HCC surveillance in early detection of HCC. In this issue of Clinical Gastroenterology and Hepatology, Best and colleagues5Best J. Bechmann L.P. Sowa J.–P. et al.GALAD score detects early hepatocellular carcinoma in an international cohort of patients with nonalcoholic steatohepatitis.Clin Gastroenterol Hepatol. 2020; 18: 728-735Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar compared the performance of serum AFP, AFP-L3, or DCP vs GALAD score to identify patients with HCC, in an international multi-center case-control study (126 cases with HCC and 231 NASH controls without HCC). They observed that the GALAD score identified patients with any stage HCC with an AUC of 0.96, significantly greater than values for serum levels of AFP (AUC, 0.88), AFP-L3 (AUC, 0.86) or DCP (AUC, 0.87). These findings were consistent in patients with vs. without cirrhosis. A cut-off of GALAD score –0.63, the GALAD score achieved an AUC of 0.91, with a sensitivity of 68% and specificity of 95% for detecting HCC within Milan criteria. In a subsequent Japanese HCC surveillance cohort of 389 patients with NASH, the investigators confirmed that the mean GALAD score was higher in patients with NASH who developed HCC than in those who did not develop HCC as early as 1.5 years before HCC diagnosis, with a cut-off of –0.63 being identified approximately 200 days before HCC diagnosis. These data support further investigation of the GALAD score as a noninvasive surveillance tool for NASH patients at risk for HCC. See page 728. /cms/asset/32314abc-4a6a-45b1-b187-16233d15e11a/mmc1.mp3Loading ... Download .mp3 (21.04 MB) Help with .mp3 files Audio Best Practices in Teaching Endoscopy Based on a Delphi Survey of Gastroenterology Program Directors and Experts in Endoscopy EducationClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewTeaching endoscopy is a key objective of gastroenterology (GI) fellowship programs but the best approach is not known. We sought to characterize which teaching competencies experts considered most critical for endoscopy education. Full-Text PDF GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic SteatohepatitisClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewThe prevalence of nonalcoholic steatohepatitis (NASH) associated hepatocellular carcinoma (HCC) is increasing. However, strategies for detection of early-stage HCC in patients with NASH have limitations. We assessed the ability of the GALAD score, which determines risk of HCC based on patient sex; age; and serum levels of α-fetoprotein (AFP), AFP isoform L3 (AFP-L3), and des-gamma-carboxy prothrombin (DCP), to detect HCC in patients with NASH. Full-Text PDF Open AccessMonitoring a Combination of Calprotectin and Infliximab Identifies Patients With Mucosal Healing of Crohn’s DiseaseClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewIn the TAILORIX trial, no benefit could be shown by infliximab dose escalation based on pharmacokinetic (infliximab serum concentrations) and pharmacodynamic (biomarkers and symptoms) monitoring compared with dose escalation based on symptoms alone in patients with Crohn’s disease (CD). We investigated whether integration of pharmacokinetic and pharmacodynamic monitoring can be used to evaluate responses to infliximab induction and maintenance therapy, based on findings from endoscopy. Full-Text PDF Diagnostic Yield of One-Time Colonoscopy vs One-Time Flexible Sigmoidoscopy vs Multiple Rounds of Mailed Fecal Immunohistochemical Tests in Colorectal Cancer ScreeningClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewWe compared the diagnostic yields of colonoscopy, flexible sigmoidoscopy, and fecal immunochemical tests (FITs) in colorectal cancer (CRC) screening. Full-Text PDF

Setting ambitious targets for surveillance and treatment rates among patients with hepatitis C related cirrhosis impacts the cost-effectiveness of hepatocellular cancer surveillance and substantially increases life expectancy: A modeling study.

BackgroundHepatocelluar cancer (HCC) is the leading cause of death among people with hepatitis C virus (HCV)-related cirrhosis. Our aim was to determine the optimal surveillance frequency for patients with HCV-related compensated cirrhosis.MethodsWe developed a decision analytic Markov model and validated it against data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) study group and published epidemiologic studies. Four strategies of different surveillance intervals were compared: no surveillance and ultrasound surveillance every 12, 6, and 3 months. We estimated lifetime survival, life expectancy, quality adjusted life years (QALY), total costs associated with each strategy, and incremental cost effectiveness ratios. We applied a willingness to pay threshold of $100,000. Analysis was conducted for two scenarios: a scenario reflecting current HCV and HCC surveillance compliance rates and treatment use and an aspirational scenario.ResultsIn the current scenario the preferred strategy was 3-month surveillance with an incremental cost-effectiveness ratio (ICER) of $7,159/QALY. In the aspirational scenario, 6-month surveillance was preferred with an ICER of $82,807/QALY because treating more people with HCV led to a lower incidence of HCC. Sensitivity analyses suggested that surveillance every 12 months would suffice in the particular circumstance when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available. Compared with the current scenario, the aspirational scenario resulted in a 1.87 year gain in life expectancy for the cohort because of large reductions in decompensated cirrhosis and HCC incidence.ConclusionsHCC surveillance has good value for money for patients with HCV-related compensated cirrhosis. Investments to improve adherence to surveillance should be made when rates are suboptimal. Surveillance every 12 months will suffice when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available.

Long-Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents.

Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long-term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow-up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB-4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow-up. The cumulative 1, 2, and 3-year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio=4.13, 95% confidence interval=3.34-5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person-years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB-4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB-4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion: Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow-up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.

Surveillance for Hepatocellular Carcinoma: Current Best Practice and Future Direction.

Hepatocellular cancer (HCC) is the fourth leading cause of cancer-related deaths worldwide and the fastest growing cause of cancer deaths in the United States. The overall prognosis of HCC remains dismal, except for the subset of patients who are diagnosed at early stage and receive potentially curative therapies, such as surgical resection and liver transplantation. Given this, expert society guidelines recommend HCC surveillance every 6 months in at-risk individuals. Despite these recommendations, the effectiveness of HCC surveillance remains a subject of debate. We discuss current best practices for HCC surveillance and the evidence that support these recommendations. We also describe several initiatives that are underway to improve HCC surveillance and outline areas that may serve as high-yield targets for future research. Overall, we believe these efforts will help the field move toward precision surveillance, where surveillance tests and intervals are tailored to individual HCC risk. Doing so can maximize surveillance benefits, minimize surveillance harms, and optimize overall value for all patients.

Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

There are limited data on the risk of hepatocellular cancer (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to estimate the risk of incident HCC among patients with NAFLD. We conducted a retrospective cohort study from a total of 130 facilities in the Veterans Health Administration. Patients with NAFLD diagnosed between January 1, 2004 and December 31, 2008 were included and followed until HCC diagnosis, death, or December 31, 2015. We also identified a sex- and age-matched control cohort without NAFLD. We ascertained all new HCC cases from the Central Cancer Registry and manual chart reviews. We calculated incidence rates for HCC by NAFLD status, as well as in subgroups of NAFLD patients. We used competing risk models to compare the risk of HCC in patients with NAFLD vs those without NAFLD. We reviewed electronic medical records of all HCC cases that developed in NAFLD patients without cirrhosis. We compared 296,707 NAFLD patients with 296,707 matched controls. During 2,382,289 person-years [PYs] of follow-up, 490 NAFLD patients developed HCC (0.21/1000 PYs). HCC incidence was significantly higher among NAFLD patients vs controls (0.02/1000 PYs; hazard ratio, 7.62; 95% confidence interval, 5.76-10.09). Among patients with NAFLD, those with cirrhosis had the highest annual incidence of HCC (10.6/1000 PYs). Among patients with NAFLD cirrhosis, HCC risk ranged from 1.6 to 23.7 per 1000 PYs based on other demographic characteristics; risk of HCC was thehighest in older Hispanics with cirrhosis. In medical record reviews, 20% of NAFLD patients with HCC had no evidence of cirrhosis. Risk of HCC was higher in NAFLD patients than that observed in general clinical population. Most HCC cases in NAFLD developed in patients with cirrhosis. The absolute risk of HCC was higher than the accepted thresholds for HCC surveillance for most patients with NAFLD cirrhosis.

Gender differences in hepatocellular cancer: should females with nonalcoholic fatty liver disease and steatohepatitis undergo surveillance for hepatocellular cancer?

Gender differences in hepatocellular cancer: should females with nonalcoholic fatty liver disease and steatohepatitis undergo surveillance for hepatocellular cancer?

Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation.

Aim:Worldwide, hepatocellular cancer (HCC) is the fourth leading cause of cancer death and occurs 3 times more commonly in males than females. Current surveillance practices do not fully address gender differences in HCC.Methods:Clinical characteristics and survival were compared between males and females using a prospectively collected database of HCC patients.Results:In a cohort of 1206 patients, 307 (25%) were female who presented with older age, more non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH), family history of HCC, and hypertension. Males (75%) were more likely to use alcohol and cigarettes. Females were more likely to undergo HCC surveillance, have smaller tumor size at diagnosis, and less vascular involvement. Males who met Milan criteria were more likely to undergo liver transplant than women who met the criteria. Median/mean survival was similar between the genders. Multivariate analysis showed that NAFLD/NASH was predictive of mortality for both males and females, age and smoking were predictive of mortality for males, and transplant was predictive of survival for males.Conclusion:Gender differences in HCC appear related to both behavioral risk factors and biologic factors. Older females with HCC have more NAFLD/NASH and may be overlooked by current surveillance guidelines. These gender disparities may lend support to future studies of gender-based HCC screening.

Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents

The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct-acting antivirals (DAA) is unclear. Our aim was to examine the risk and determinants of HCC in patients cured with DAA. We conducted a retrospective cohort study of hepatitis C virus patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between January 1, 2015 and December 31, 2015. We calculated the annual incidence rates of HCC by SVR. We used Cox regression models to compare the risk of HCC in patients with vs those without SVR and to identify factors associated with incident HCC among patients with SVR. We reviewed a sample of HCC patients for tumor size and stage at diagnosis. Among 22,500 patients treated with DAA (19,518 with SVR; 2982 without SVR), the mean (standard deviation) age was 61.6 (6.1) years, and 39.0% had cirrhosis. There were 271 new cases of HCC, including 183 in patients with SVR. Compared with patients without SVR, those with SVR had a significantly reduced risk of HCC (0.90 vs 3.45 HCC/100 person-years; adjusted hazard ratio, 0.28, 95% CI=0.22-0.36). Patients with cirrhosis had the highest annual incidence of HCC after SVR (1.82 vs 0.34/100 person-years in patients without cirrhosis; adjusted hazard ratio, 4.73. 95% CI, 3.34-6.68). Most (>44.8%) HCC were classified as stage I. Maximum size of the largest lesion was ≤5 cm in over 75% of cases. Among patients treated with DAA, SVR was associated with a considerable reduction in the risk of HCC. We did not find any evidence to suggest that DAAs promote HCC. However, in patients with SVR, the absolute risk of HCC remained high in patients with established cirrhosis. These patients should be considered for ongoing HCC surveillance.