Trends Of Hepatocellular Carcinoma Research Articles

48 Analyzing Changing Trends in Hepatocellular Carcinoma

OBJECTIVES/GOALS: To quantify changing trends in hepatocellular carcinoma (HCC) etiologies, mainly hepatitis C related HCC (HCV-HCC), nonalcoholic fatty liver disease related HCC (NAFLD-HCC), and alcoholic liver disease related HCC (ALD-HCC), at a single center as well as compared to large national databases. METHODS/STUDY POPULATION: This is a retrospective longitudinal study using a single-center database of patients presenting with HCC from January 1995 to September 2023. Etiologies were confirmed through patient history, clinical exam, and viral serologies. Trends in rate of etiology were analyzed using linear regression. Further investigation will include survival analysis. To improve generalizability, the single-center data were supplemented with national cross-sectional data from the NHANES database on liver disease prevalence from March 1999 to August 2023. Data were provided through questionnaire, clinical exam, and viral serologies. Trends in rates will be analyzed using linear regression. RESULTS/ANTICIPATED RESULTS: Among the single center cohort, NAFLD-HCC increased at an average rate of 1.3% per year (95% Confidence Interval (CI) = 1.1% to 1.4%) and HCV-HCC decreased at an average rate of -0.56% per year (95% CI = -0.83% to -0.29%). Projecting the linear models for the past ten years forward, HCV-HCC is predicted to take up a lower proportion than NASH-HCC by 2026 and lower proportion than ALD-HCC by 2028. Future results will include analysis of the changing proportions of etiologies for liver transplant and survival analysis for HCC by etiology from the single center cohort. Additionally, national trends in HCC etiologies will be provided from the NHANES database. The trends from liver transplant etiology and NHANES are expected to parallel the preliminary results. DISCUSSION/SIGNIFICANCE: As the prevalence of NAFLD increases in the general population, more cases of NAFLD-HCC will be seen in the future. Understanding the changing trends can guide surveillance recommendations, shape treatment algorithms, and frame research priorities.

Trends of Hepatocellular Carcinoma (HCC) Inpatients Mortality and Financial Burden From 2011 to 2017: A Nationwide Analysis.

Liver cancer, including Hepatocellular carcinoma (HCC) is the seventh most common tumor worldwide. Previously, the financial burden of HCC in the United States between 2002 and 2011 was noted to be continuously increasing. This study aims to evaluate temporal trends of hospitalizations due to HCC. This is a retrospective analysis utilizing the National Inpatient Sample (NIS) database. All subjects admitted between 2011 and 2017 with a diagnosis of HCC were identified. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay. An increase in hospitalization from 67,779 (0.18%) admissions in 2011 to 84,580 (0.23%) admissions in 2017(P<0.05) was noted. Most patients were 45 to 64 years old (median 50%), predominantly men (median 68%) (P<0.05). The primary health care payer was Medicare (Median 49%) and Medicaid (Median 18%) (P<0.05). The most common geographical location was the south (Median 36%) (P<0.05). Most patients were admitted to large hospitals (Median 62%) in urban areas (P<0.05). The median inpatient mortality was estimated to be 9% in 2017 (P<0.05), which has decreased from 10%(P<0.05) in 2011. The total charges per admission have increased steadily from $58,406 in 2011 to $78,791 in 2017 (P<0.05). The median length of stay has increased from 5.79 (SD 6.93) in 2011 to 6.07 (SD 8.3) in 2017(P<0.05). The most common mortality risk factor was sepsis, Acute renal failure, and GI hemorrhage. HCC-related admissions continue to be on the rise. HCC mortality has decreased across the years with earlier diagnoses and advances in therapy. However, we observed a significant increase in financial burden on health care with increasing in-hospital costs, a finding that needs to be verified in prospective trials.

Evolving Trends in Hepatocellular Carcinoma in a Multi-Cultural Australian Tertiary Centre.

Evolving Trends in Hepatocellular Carcinoma in a Multi-Cultural Australian Tertiary Centre.

Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma.

Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.

Trends in hepatocellular carcinoma in Louisiana, 2005-2015.

Louisiana has one of the highest incidence and mortality rates of hepatocellular carcinoma (HCC) in the nation. The aim of this study was to analyze the trends in HCC incidence and relative survival rates in Louisiana and compare them with corresponding national rates, which can be used to formulate strategies to improve Louisiana HCC outcomes. Data on primary invasive HCC diagnosed in patients 20 years or older between 2005 and 2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) program and Louisiana Tumor Registry. Time trends in HCC incidence and 12-month relative survival were analyzed using Joinpoint regression. Case characteristics were compared on 2 time periods (2005-2009 and 2010-2015) using Chi-squared tests. Cause-specific survival was analyzed via log-rank and multivariable Cox proportional hazard model. Over the study period, the average annual percent change (AAPC) in age-adjusted HCC incidence in Louisiana was nearly double that of the national estimate, 6% (95% CI: 4.7, 7.3) compared to 3.1% (95% CI: 2.4, 3.7). 12-month relative survival among HCC patients in Louisiana was 40.7% (95% CI: 38.9, 42.4) which was significantly less than the US rate of 48.2% (95% CI: 47.8, 48.6). Relative survival did improve in Louisiana from 2000 to 2015 at a rate similar to that of the US (AAPC (95% CI): 2.9 (0.7, 5.2) vs. 2.7 (2.3, 3.1), p = 0.8). In multivariable survival analysis, factors amongst Louisianans associated with worse survival were older age at diagnosis, advanced stage of disease, and lack of surgical therapy. The incidence of HCC continues to rise more dramatically in Louisiana than in the US. While some modest improvements in HCC survival have been realized, outcomes remain dismal. Future work identifying the most at-risk populations are needed to inform statewide public health initiatives.

Patterns of Care Utilization and Hepatocellular Carcinoma Surveillance: Tracking Care Across the Pandemic.

We studied longitudinal trends in mortality, outpatient, and inpatient care for cirrhosis in a national cohort in the first 2 years of the coronavirus disease-2019 pandemic. We evaluated trends in hepatocellular carcinoma (HCC) surveillance and factors associated with completion. Within the national cirrhosis cohort in the Veterans Administration from 2020 to 2021, we captured mortality, outpatient primary care provider, gastroenterology/hepatology (GI/HEP) visits, and hospitalizations. HCC surveillance was computed as percentage of time up to date with surveillance every 6 months (PTUDS). Multivariable models for PTUDS were adjusted for patient demographics, clinical factors, and facility-level variables. The total cohort was 68,073; 28,678 were eligible for HCC surveillance. Outpatient primary care provider and GI/HEP appointment rates initially dropped from 30% to 7% with a rebound 1 year into the pandemic and steady subsequent use. Telemedicine monthly visit rates rose from less than 10% to a peak of 20% with a steady gradual decline. Nearly 70% of Veterans were up to date with HCC surveillance before the pandemic with an early pandemic nadir of approximately 50% and 60% PTUDS 2 years into the pandemic. In adjusted models, use of a population-based cirrhosis dashboard (β 8.5, 95% CI 6.9-10.2) and GI/HEP visits both in-person (β 3.2, 95% CI 2.9-3.6) and telemedicine (β 2.1, 95% CI 1.9-2.4) were associated with a higher PTUDS. Outpatient utilization and HCC surveillance rates have rebounded but remain below at baseline. Population-based approaches and specialty care for cirrhosis were associated with a higher completion of HCC surveillance.

Optimizing the Suboptimal: Hepatocellular Carcinoma Surveillance Guide for Primary Care Practitioners Based on a Medscape Education Online Activity.

The goal of this activity is to update primary care practitioners (PCPs) on risk factors and trends in hepatocellular carcinoma (HCC) development, as well as guideline recommendations and best practices for collaborating with specialists in HCC surveillance.

International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma

Biomarkers are key components of the clinical management of patients with cancer, as they have contributed to major survival improvements in these patients.1Robertson D.J. Lee J.K. Boland C.R. et al.Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2017; 152: 1217-1237.e3Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar According to the National Cancer Institute, a biomarker is a biological molecule found in blood, other body fluids (eg, urine), or tissues that is a sign of a normal or abnormal process, or of a condition or disease. They allow classification of patients based on common features and facilitate risk stratification, early detection, diagnosis, and prediction of prognosis or treatment response. In hepatocellular carcinoma (HCC), there are few biomarkers incorporated in clinical practice despite a need to better stratify patients at different steps of clinical management. However, this has been an extensive area of research in recent years, with increasing efforts to identify biomarkers across the cancer care continuum from risk stratification to early detection to prognostication and treatment response (Table 1, Figure 1).Table 1Types of BiomarkersType of biomarkerDefinitionRisk stratificationBiomarker that predicts the future development of HCC in an at-risk patientEarly detectionBiomarker that detects HCC at an early tumor stage, when therapy can be delivered which would reduce HCC-related mortalityDiagnosisBiomarker that can confirm or exclude presence of HCC in patients with a suspicious nodule or clinical concern for HCCPrognosisBiomarker that predicts overall cancer outcome, regardless of treatmentTreatment responseBiomarker that predicts favorable or unfavorable response to a specific treatmentHCC, hepatocellular carcinoma. Open table in a new tab HCC, hepatocellular carcinoma. One of the first systematic sets of recommendations dealing with biomarkers in cancer was introduced in 1996 by Hayes et al,2Hayes D.F. Bast R.C. Desch C.E. et al.Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers.J Natl Cancer Inst. 1996; 88: 1456-1466Crossref PubMed Scopus (618) Google Scholar known as the Tumor Marker Utility Grading System (TMGUS). These recommendations covered not only technical aspects of assay development, but also issues related to clinical utility and levels of evidence. TMGUS was later expanded by the Reporting recommendations for tumor marker prognostic studies (REMARK) guidelines,3McShane L.M. Altman D.G. Sauerbrei W. et al.Reporting recommendations for tumor marker prognostic studies (REMARK).J Natl Cancer Inst. 2005; 97: 1180-1184Crossref PubMed Scopus (1084) Google Scholar a more focused approach on recommendations for reporting prognostic biomarkers in oncology. There have also been specific initiatives to describe study design thoroughly for cancer biomarkers in specific clinical scenarios, such as the Early Detection Research Network (EDRN) publishing a framework for 5 phases of biomarker development and validation for cancer screening.4Pepe M.S. Etzioni R. Feng Z. et al.Phases of biomarker development for early detection of cancer.J Natl Cancer Inst. 2001; 93: 1054-1061Crossref PubMed Google Scholar In brief, these phases extend from biomarker discovery (phase I) to evaluation of biomarker performance (phases II-III) and clinical benefits and harms (phase IV-V) (Table 2).Table 2Outcomes, Study Design, and Analysis for Early Detection of HCCPhasesOutcomesStudy designAnalysis1Exploratory TPR and FPRPreclinical case-control study-TPR, FPR, ROC curves to identify potential biomarkers2Clinical assay TPR and FPRCase-control study-TPR, FPR, ROC curves-Comparison with AFP ± ultrasound-Combinations of markers-Impact of covariates on biomarker performance3Detection of preclinical HCCPRoBE (prospective specimen collection, retrospective blinded evaluation) design-TPR, FPR, ROC curves-Comparison with AFP ± ultrasound-Time between outcome and biomarker measurement-Combination of markers4HCC detection ratesProspective cohort-PPV-HCC Stage distribution-TPR, FPR, ROC curves-Benefits (early HCC detection) and harms (false positive rate)-Comparison with AFP ± ultrasound5Decrease in HCC mortalityRandomized study-Survival analysis and Cox regression-Cost and quality of life-Overdiagnosis and overtreatmentAFP, alpha-fetoprotein; FPR, false positive rate; HCC, hepatocellular carcinoma; PPV, positive predictive value; ROC, receiver operating characteristics curve; TPR, true positive rate. Open table in a new tab AFP, alpha-fetoprotein; FPR, false positive rate; HCC, hepatocellular carcinoma; PPV, positive predictive value; ROC, receiver operating characteristics curve; TPR, true positive rate. Although these guidelines provide a useful general framework of data elements required at each step, deviations from this framework may be possible or necessary in specific circumstances. Further, modifications may be required when applied to other clinical scenarios, including risk stratification and treatment response assessment. Finally, singularities unique to HCC, particularly the coexistence of chronic liver disease in most patients, lead to necessary considerations when designing biomarker studies. To address these issues, the International Liver Cancer Association has assembled a group of experts on biomarker development to provide a framework on best practices to design, execute, and interpret biomarker studies for risk stratification, early detection, diagnosis, prognostication, and treatment response assessment in HCC. Risk of HCC is elevated in patients with chronic liver disease, particularly those with cirrhosis from any etiology, and HCC is one of the leading causes of death in these patients.5Fujiwara N. Friedman S.L. Goossens N. et al.Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine.J Hepatol. 2018; 68: 526-549Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar Contemporary cohorts, which have higher numbers of patients with hepatitis C post-sustained viral response and those with nonalcoholic steatohepatitis (NASH), have demonstrated an annual HCC risk of 1% to 3%, substantially lower than the traditional annual HCC risk of 3% to 5% from older cohorts.6Moon A.M. Singal A.G. Tapper E.B. Contemporary epidemiology of chronic liver disease and cirrhosis.Clin Gastroenterol Hepatol. 2020; 18: 2650-2666Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar,7Goossens N. Bian C.B. Hoshida Y. Tailored algorithms for hepatocellular carcinoma surveillance: Is one-size-fits-all strategy outdated?.Curr Hepatol Rep. 2017; 16: 64-71Crossref PubMed Google Scholar However, patient characteristics, such as age, sex, race/ethnicity, and degree of fibrosis, introduce heterogeneity in HCC risk between patients.8Rich N.E. Hester C. Odewole M. et al.Racial and ethnic differences in presentation and outcomes of hepatocellular carcinoma.Clin Gastroenterol Hepatol. 2019; 17: 551-559.e1Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Subgroups of patients with chronic hepatitis B virus (HBV) infection without cirrhosis, such as Asian men older than 40 years and Asian women older than 50 years, have an annual HCC incidence of 0.4% to 0.6%, whereas younger individuals have a lower HCC incidence of 0.2%. Refined risk stratification could have several implications for clinical practice, such as tailoring of HCC surveillance intensity in the future and targeting chemoprevention efforts (eg, coffee, lipophilic statins, aspirin9Athuluri-Divakar S.K. Hoshida Y. Generic chemoprevention of hepatocellular carcinoma.Ann N Y Acad Sci. 2019; 1440: 23-35Crossref PubMed Scopus (9) Google Scholar) to high-risk persons. For example, the “one-size-fits-all” surveillance strategy of semi-annual ultrasound with or without alpha-fetoprotein (AFP) could be tailored based on the individual HCC risk in each patient.10Goossens N. Singal A.G. King L.Y. et al.Cost-effectiveness of risk score-stratified hepatocellular carcinoma screening in patients with cirrhosis.Clin Transl Gastroenterol. 2017; 8e101Crossref PubMed Google Scholar Further, risk stratification biomarkers could help select patients for chemoprevention clinical trials, thereby reducing necessary sample sizes and making these trials more feasible. In addition to patients with cirrhosis, risk stratification is also needed for patients with chronic HBV infection or with advanced fibrosis, particularly in the setting of NASH or post-sustained viral response. Although HCC can occur in the absence of cirrhosis,11Mittal S. El-Serag H.B. Sada Y.H. et al.Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease.Clin Gastroenterol Hepatol. 2016; 14: 124-131.e1Abstract Full Text Full Text PDF PubMed Scopus (273) Google Scholar patients without cirrhosis have a low annual HCC rate and surveillance is not cost-effective.12Loomba R. Lim J.K. Patton H. et al.AGA clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review.Gastroenterology. 2020; 158: 1822-1830Abstract Full Text Full Text PDF PubMed Google Scholar,13Farhang Zangneh H. Wong W.W.L. Sander B. et al.Cost effectiveness of hepatocellular carcinoma surveillance after a sustained virologic response to therapy in patients with hepatitis C virus infection and advanced fibrosis.Clin Gastroenterol Hepatol. 2019; 17: 1840-1849.e16Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Effective risk stratification biomarkers may identify subgroups of those with advanced fibrosis but not cirrhosis who would benefit from surveillance. The EDRN framework for phases of biomarker evaluation for early detection do not directly apply to risk stratification, although several of the concepts are similar. Derivation of risk stratification biomarkers can be done in a retrospective cohort and/or nested case-control study, in which the biomarker assay would be assessed at baseline, cases develop HCC during follow-up, and controls remain HCC-free over equivalent or longer follow-up. The time frame between biomarker assessment and HCC diagnosis should be long enough (eg, > 2 years) to minimize the likelihood of detecting preexisting undetected tumoral disease. A 2-year time frame is recommended given the low sensitivity of imaging to detect very early-stage HCC and some patients with HCC exhibiting indolent growth patterns, thereby potentially remaining subclinical for many months.14Nathani P. Gopal P. Rich N. et al.Hepatocellular carcinoma tumour volume doubling time: a systematic review and meta-analysis.Gut. 2021; 70: 401-407PubMed Google Scholar,15Rich N.E. John B.V. Parikh N.D. et al.Hepatocellular carcinoma demonstrates heterogeneous growth patterns in a multi-center cohort of patients with cirrhosis.Hepatology. 2020; 72: 1664-1665Crossref Scopus (43) Google Scholar Therefore, case-control studies with shorter periods between biomarker assessment and HCC diagnosis may confound a biomarker’s performance for risk stratification versus early detection (Figure 2). When selecting patients for a nested case-control design, cases and controls should be matched for known clinical risk factors, such as age, gender, and etiology and severity of liver disease. When available, archived biospecimens from a prospective cohort study (ie, prospective-retrospective design) would allow more reliable estimation of biomarker performance based on time-to-event data analysis.16Simon R.M. Paik S. Hayes D.F. Use of archived specimens in evaluation of prognostic and predictive biomarkers.J Natl Cancer Inst. 2009; 101: 1446-1452Crossref PubMed Scopus (742) Google Scholar As needed, early-phase validation can be conducted in independent nested case-control studies or cohorts, where model parameters and/or thresholds to define risk groups could be further optimized. Late-phase validation is then conducted in an adequately powered independent prospective-retrospective or prospective cohort to compare the HCC incidence rate between high-risk and low-risk groups or assess association of the biomarker and HCC incidence. Biomarker performance should be evaluated using a combination of several metrics. Overall model performance (degree of variation explained by the biomarker panel) is typically assessed by R2 or Brier scores. Discrimination (ability to distinguish between patients who develop versus do not develop HCC) is assessed by the magnitude of risk separation between high-risk and low-risk groups measured by fitness of the model determined by time-dependent area under the receiver operator characteristic curve, concordance index (c-index), and/or Akaike’s Information Criterion. Calibration (difference between observed and predicted event rates) is often assessed by the Hosmer-Lemeshow statistic and improvement of prediction (or reclassification) is assessed via net reclassification index misclassification tables or standardized net benefit. Following validation of risk-predictive capability, the implementation phase would evaluate the benefit of incorporating risk stratification biomarkers in an experimental system, for example, individual-risk-stratified HCC screening, for outcomes including early detection, overall survival (OS), and cost-effectiveness. This is a complex problem, for which simulation analyses such as cost-effectiveness models can be helfpul.7Goossens N. Bian C.B. Hoshida Y. Tailored algorithms for hepatocellular carcinoma surveillance: Is one-size-fits-all strategy outdated?.Curr Hepatol Rep. 2017; 16: 64-71Crossref PubMed Google Scholar Relevant variables to consider include performance of the biomarker to stratify HCC risk groups, HCC incidence in each risk group, costs for medical care including the biomarker, and benefits and harms of HCC screening in each risk group. These models can also provide information about desired biomarker performance and costs to meet the cost-effectiveness threshold. There are several analytical issues that should be considered including the following: (1) use of a continuous risk measure versus assigning risk categories, with the former providing more granular information but the latter being easier to interpret by providers; (2) evaluating a biomarker in isolation vs combining with clinical variables as an integrative risk score, with the latter likely being needed in light of the heterogeneity of cancer pathogenesis; (3) accounting for changes in risk over time due to natural disease progression or clinical interventions (eg, antiviral therapy); and (4) optimizing risk stratification models in specific clinical contexts defined by clinical characteristics such as liver disease etiology. Decisions regarding these model optimization issues must balance clinically meaningful benefit vs practical feasibility. HCC fulfills all of the World Health Organization criteria for a cancer screening program, including high morbidity and mortality, an identifiable target population, a recognizable preclinical stage, accepted recall procedures, and efficacious treatment. Therefore, professional society guidelines recommend semi-annual surveillance using abdominal ultrasound with or without AFP among at-risk patients, including subgroups of patients with chronic HBV infection and those with cirrhosis from any etiology.17Marrero J.A. Kulik L.M. Sirlin C.B. et al.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases.Hepatology. 2018; 68: 723-750Crossref PubMed Scopus (1290) Google Scholar,18Galle P.R. Forner A. Llovet J.M. et al.EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2018; 69: 182-236Abstract Full Text Full Text PDF PubMed Scopus (2663) Google Scholar Ultrasound and AFP are the only 2 surveillance tests recommended in guidelines and have been the long-standing cornerstone of HCC surveillance. However, ultrasound can have highly variable performance given its operator-dependent nature and the sensitivity of ultrasound with AFP, at a cutoff of 20 ng/mL, for early HCC detection is suboptimal, at only 63%.19Tzartzeva K. Obi J. Rich N.E. et al.Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis.Gastroenterology. 2018; 154: 1706-1718.e1Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar Evolving data also highlight the potential for poor ultrasound visualization, particularly among obese patients and those with NASH, as well as false positive or indeterminate results causing screening-related harms.20Simmons O. Fetzer D.T. Yokoo T. et al.Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis.Aliment Pharmacol Ther. 2017; 45: 169-177Crossref PubMed Google Scholar,21Atiq O. Tiro J. Yopp A.C. et al.An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis.Hepatology. 2017; 65: 1196-1205Crossref PubMed Scopus (100) Google Scholar Finally, ultrasound-based surveillance programs often require a separate appointment, creating potential barriers to adherence, contributing to underuse of HCC surveillance in clinical practice, occurring in less than 50% across geographic regions.22Singal A.G. Tiro J.A. Murphy C.C. et al.Patient-reported barriers are associated with receipt of hepatocellular carcinoma surveillance in a multi-center cohort of patients with cirrhosis.Clin Gastroenterol Hepatol. 2021; 19: 987-995.e1Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar,23Wolf E. Rich N.E. Marrero J.A. et al.Use of hepatocellular carcinoma surveillance in patients with cirrhosis: a systematic review and meta-analysis.Hepatology. 2021; 73: 713-725Crossref PubMed Scopus (30) Google Scholar Overall, the limitations of our current strategy highlight a strong need for alternative surveillance tests, particularly highly accurate blood-based biomarkers. Patients with cirrhosis from any etiology comprise the group with the highest risk for developing HCC and account for >90% of all cases in the United States and Europe, whereas chronic HBV infection remains the most common target population globally. Although contemporary cohorts suggest a lower annual HCC incidence of ∼2%,24Ioannou G.N. Beste L.A. Green P.K. et al.Increased risk for hepatocellular carcinoma persists up to 10 years after HCV eradication in patients with baseline cirrhosis or high FIB-4 Scores.Gastroenterology. 2019; 157: 1264-1278.e4Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar, 25Bertot L.C. Adams L.A. Trends in hepatocellular carcinoma due to non-alcoholic fatty liver disease.Expert Rev Gastroenterol Hepatol. 2019; 13: 179-187Crossref PubMed Scopus (20) Google Scholar, 26Ganne-Carrie N. Chaffaut C. Bourcier V. et al.Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis.J Hepatol. 2018; 69: 1274-1283Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar HCC incidence among patients with cirrhosis still exceeds the cost-effectiveness threshold of 1.5% per year.17Marrero J.A. Kulik L.M. Sirlin C.B. et al.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases.Hepatology. 2018; 68: 723-750Crossref PubMed Scopus (1290) Google Scholar,18Galle P.R. Forner A. Llovet J.M. et al.EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2018; 69: 182-236Abstract Full Text Full Text PDF PubMed Scopus (2663) Google Scholar,27Singal A.G. Parikh N.D. Hutton D.W. et al.Cost effectiveness of hepatocellular carcinoma surveillance: An assessment of benefits and harms.Am J Gastro. 2020; 115: 1642-1649Crossref PubMed Scopus (13) Google Scholar Similarly, annual HCC incidence in subgroups with chronic HBV infection exceeds the cost-effectiveness threshold of 0.2%. Therefore, patients with cirrhosis or chronic HBV infection should be the target population for studies examining HCC surveillance biomarkers.17Marrero J.A. Kulik L.M. Sirlin C.B. et al.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases.Hepatology. 2018; 68: 723-750Crossref PubMed Scopus (1290) Google Scholar Further, surveillance studies should be restricted to those who would potentially benefit from a therapeutic intervention. For example, surveillance is only of benefit in patients with preserved liver function, as those with significant hepatic decompensation (eg, Child Pugh C cirrhosis if not eligible for liver transplantation) or comorbidity have higher competing risk of non-HCC mortality. Patients with advanced fibrosis but not cirrhosis are known to develop HCC, but with incidence rates well below the threshold recommended for surveillance. Biomarker studies in HCC should not combine patients with cirrhosis and those with advanced fibrosis, as this will lead to underestimating sample size calculations, longer accrual to identify a sufficient number of HCC cases, and ultimately lead to biased conclusions and uncertainty if there is a benefit of the new biomarker. If an accurate risk stratification biomarker can identify a subset of patients with advanced fibrosis and similar HCC risk as those with cirrhosis, these patients may be included in early detection trials in the future. A frequent misconception in the field is the confusion between early detection and diagnostic biomarkers. As tools for cancer surveillance, early detection biomarkers will trigger a confirmatory diagnostic procedure, but per se, they are not sufficient to assign an HCC diagnosis. The appropriate study design and outcomes will be dependent on the phase of biomarker development (Table 2 and Figure 3).4Pepe M.S. Etzioni R. Feng Z. et al.Phases of biomarker development for early detection of cancer.J Natl Cancer Inst. 2001; 93: 1054-1061Crossref PubMed Google Scholar Phase 1 studies aim to identify biomarkers and determine how well they distinguish HCC and non-HCC controls, that is, the true positive rate (TPR) and false positive rate (FPR). These studies can include genes (single or array), proteins, and radiologic tests and may start with measurement of the biomarker at the tissue level, with or without correlation with serum or plasma. Phase 2 is the clinical assay development based on a specimen that can be obtained noninvasively. Outcomes at this phase are estimation of TPR and FPR or the receiver operating characteristics curve for the biomarker to distinguish subjects with HCC from those with cirrhosis but without HCC. The same analytic principles comparing cases and controls apply to phase 1 and phase 2 studies. However, phase 2 studies should be appropriately powered to not only estimate TPR, FPR, and area under the receiver operator characteristic curve but also determine the impact of covariates such as age, sex, etiology of liver disease, and degree of liver dysfunction on biomarker performance. These covariates of interest cannot be used as matching variables, as doing so would render their effects toward null. In a phase II study, HCC cases should be ideally restricted to those at an early stage, either defined by Barcelona Clinic Liver Cancer (BCLC) staging system or Milan Criteria, because the goal of HCC is detection of early-stage disease and biomarker performance would otherwise be overestimated.17Marrero J.A. Kulik L.M. Sirlin C.B. et al.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases.Hepatology. 2018; 68: 723-750Crossref PubMed Scopus (1290) Google Scholar,18Galle P.R. Forner A. Llovet J.M. et al.EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2018; 69: 182-236Abstract Full Text Full Text PDF PubMed Scopus (2663) Google Scholar It is at this stage that comparison with the current standard is performed and the study should be powered to compare the new biomarker to ultrasound with or without AFP, although it should be noted this comparison may have bias given ultrasound and AFP were likely to trigger diagnostic testing in a subset of the cohort. Depending on the biomarker, one may consider subgroup analyses of particular interest, such as among those with NASH cirrhosis. Similarly, one could consider subgroup analyses by baseline HCC risk if accurate risk stratification biomarkers are available in the future. Phase 3 studies leverage prospective cohort studies, in which samples are collected at regular semi-annual intervals, with the main outcome to evaluate the ability of the biomarker to detect preclinical HCC. The samples are stored initially and then analyzed using the PRoBE design (prospective specimen collection, retrospective blinded evaluation), allowing a nested case-control analysis.28Pepe M.S. Feng Z. Janes H. et al.Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design.J Natl Cancer Inst. 2008; 100: 1432-1438Crossref PubMed Scopus (452) Google Scholar Adequate sample size to facilitate a sufficient number of incident HCC and provide strong conclusions is critical, including facilitating subgroup analyses in subpopulations of interest to help determine the impact of covariates on the biomarker’s accuracy. Protocols should detail specimen handling (including collection, processing, storage, and retrieval), and there should be strict definitions for incident HCC, per guidelines,17Marrero J.A. Kulik L.M. Sirlin C.B. et al.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases.Hepatology. 2018; 68: 723-750Crossref PubMed Scopus (1290) Google Scholar,18Galle P.R. Forner A. Llovet J.M. et al.EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2018; 69: 182-236Abstract Full Text Full Text PDF PubMed Scopus (2663) Google Scholar including the use of a multidisciplinary tumor board or adjudication committee. Phase 3 studies should also incorporate end-of-study imaging or a follow-up period among non-HCC patients to minimize risk of ascertainment bias. It is important to identify if the biomarker will be used alone or combined with other markers or demographic information (such as age and sex, as has been done with GALAD).29Berhane S. Toyoda H. Tada T. et al.Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients.Clin Gastroenterol Hepatol. 2016; 14: 875-886.e6Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar Based on ultrasound and AFP performance, minimally acceptable TPR and FPR rates for new biomarkers for early HCC detection are approximately 65% and 10%, respectively, and these should be measured at preclinical lag times of interest (eg, at diagnosis, or 6 to 12 months before HCC diagnosis). Thresholds for TPR and FPR vary by population-level HCC risk in the local area, so strategies with higher TPR may be desired in areas with higher HCC risk populations. Phase 4 studies are prospective cohort studies in which the biomarker of interest is applied to individuals in real-time and diagnostic procedures are performed for those with a positive test. For such studies, the assay must be reliable and reproducible, and readily available to clinicians to make decisions for diagnosis and treatment. There are 4 potential outcomes at each surveillance interval: (1) the biomarker is positive and HCC is confirmed (true positive), (2) the biomarker is positive and HCC is not confirmed (false positive), (3) the biomarker is negative and HCC is discovered (false negative), and (4) the biomarker is negative and HCC is absent (true negative). Without adequate follow-up to confirm false negatives or true negatives, positive predictive value can be calculated after workup for test positives but sensitivity or specificity could not be calculated. Therefore, measures such as an additional follow-up period of 6 to 12 months with ultrasound-based surveillance, or diagnostic computed tomography (CT) or magnetic resonance imaging (MRI) in patients with negative surveillance tests, are needed to exclude HCC and minimize risk of ascertainment bias. Outcomes of interest from a phase IV biomarker study include the detection rate, that is, the proportion of cirrhotic subjects who tested positive and have HCC, and false-referral rate, that is, the proportion who have a positive surveillance test but do not have HCC on diagnostic imaging. Tumor characteristics including stage and any features of tumor biology should be collected to inform power calculations for a subsequent phase 5 study. An issue with phase 4 studies is that they can be costly and time-consuming, thereby delaying availability of new biomarkers for early detection of HCC. A well-performed phase 3 study may obviate the need for a phase 4 study if the following are present: (1) the biomarker is readily available and reproducible, (2) phase III study accounted for potential ascertainment bias in controls without HCC, (3) phase III study performed longitudinal evaluation of the biomarker in non-HCC patients to characterize FPR over time, (4) phase III study assessed biomarker performance at early detectable time points among HCC patients to characterize TPR, and (5) phase III

Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: a United States multicentre study.

Limited data exist on the burden and features of non-cirrhotic hepatocellular carcinoma (HCC) in the United States. To evaluate characteristics, aetiologies, trends and outcomes of non-cirrhotic HCC from 2000 to 2014 at five large US centres METHODS: Patient, tumour and liver disease aetiology data were collected. The presence of underlying cirrhosis was assessed based on published criteria. Of 5144 eligible patients with HCC, 11.7% had no underlying cirrhosis. Non-cirrhotic patients were older (64.1 vs 61.2years), more frequently females (33.9% vs 20.8%) and less frequently black (8.3% vs 12.4%) (P<.001 for all). Among non-cirrhotic patients, non-alcoholic fatty liver disease (NAFLD) was the most common liver disease (26.3%), followed by hepatitis C virus (HCV) (12.1%) and hepatitis B virus (HBV) (10%) infections. As of 2014, there was increased percentage of cirrhotic HCC and a decline in non-cirrhotic HCC mainly due to significant annual increases in cirrhotic HCC due to HCV (0.96% [P<.0001]) and NAFLD (0.66% [P=.003]). Patients with non-cirrhotic HCC had larger tumours (8.9 vs 5.3cm), were less frequently within Milan criteria (15% vs 39%), more frequently underwent resection (43.6% vs 8%) (P<.001 for all) and had better overall survival than cirrhotic HCC patients (median 1.8 vs 1.3years, P=.004). Nearly 12% of HCCs occurred in patients without underlying cirrhosis. NAFLD was the most common liver disease in these patients. During the study, the frequency of non-cirrhotic HCC decreased, whereas that of cirrhotic HCC increased. Although non-cirrhotic patients presented with more advanced HCC, their survival was better.

The Epidemiology of Hepatocellular Carcinoma in the USA.

To discuss current knowledge and recent findings regarding the epidemiology of hepatocellular carcinoma (HCC) in the USA. The US incidence rate of HCC is increasing, although the pace may have somewhat slowed since 2010. In 2012, incidence rates of HCC in Hispanics surpassed those of Asians. The recent epidemiological changes in major risk factors for HCC include increasing hepatitis C virus post-sustained virologic response, suppressed hepatitis B virus on nucleoside analogues, and alcoholic and non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease has the greatest proportion of the burden of the main risk factors for HCC in the USA, followed by alcoholic liver disease, and hepatitis C virus and hepatitis B virus infections. This review focuses on current knowledge regarding the recent epidemiological trends in HCC, with an emphasis on future directions.

Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: A National Inpatient Sample Study.

Among haemophilic (H) men, hepatitis C virus (HCV) is the leading cause of liver disease and mortality, but demographics and risks of hepatocellular carcinoma (HCC) in H are not well known. Adult discharges in H and non-haemophilic (NH) men, with and without HCC were identified in the National Inpatient Sample (NIS) between 1998 and 2014, using ICD-9 codes. Analyses included NIS-provided discharge-level weights to reflect national estimates. Categorical variables were assessed by Rao-Scott chi-square and continuous variables by weighted simple linear regression. HCC predictors were determined by weighted multivariable logistic regression. Of 18098 H, 144 (0.79%) had HCC between 1998 and 2014. Adjusted rates of HCC increased 3.0-fold in H vs 1.7-fold in NH (P=0.484). Among HCV+, HCC rates adjusted for HIV, increased 2.2-fold in H vs 1.7-fold in NH (P=0.740), while among HIV+, HCC increased 1.4-fold in H vs 0.2-fold in NH (P=0.448). Among those with HCC, H were older than NH (P<0.001), Caucasian (P=0.006), platelet transfusion recipients (P<0.001), with greater comorbidity (P<0.001) and mortality (P<0.006). H with HCC also had greater rates of HCV and HIV (each P<0.001), lower rates of alcoholism and hyperlipidemia (each P<0.001), and similar rates of HBV (P=0.866), smoking (P=0.507) and obesity (P=0.502). In multivariable logistic regression, HCV was a strong predictor for HCC in haemophilia, (OR: 15.42, 95% CI: 8.75-27.16). Haemophilic men have increasing rates of HCC, similar to men without haemophilia. HCV is the major predictor of HCC in haemophilia. Future trends in HCC will depend on the impact of newer HCV antiviral therapy.

Trends in hepatocellular carcinoma due to non-alcoholic fatty liver disease

ABSTRACTIntroduction: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is associated with hepatocellular carcinoma (HCC), the most frequent malignant liver tumor. The increasing prevalence of obesity and diabetes is influencing the epidemiology of HCC with the most dramatic increases in NAFLD-related HCC seen in Western countries. Although cirrhosis is the major risk factor for HCC in NAFLD, there is increasing recognition that NAFLD-HCC occurs in the absence of cirrhosis.Areas covered: The epidemiology of NAFLD related HCC and its impact on changing the incidence of HCC globally. We overview risk factors for NAFLD-HCC in the presence and absence of cirrhosis and examine trends in liver transplantation (LT) related to NAFLD-HCC.Expert commentary: The incidence of NAFLD-related cirrhosis will continue to rise globally in parallel with risk factors of obesity and diabetes. Consequently, NAFLD-related HCC will become an increasingly important cause of liver-related morbidity and mortality and a common indication for LT worldwide. Further identification of risk factors for NAFLD-HCC and effective treatments for NAFLD are required to reduce this future burden of disease.

Advanced Hepatocellular Carcinoma Tumor Stage at Diagnosis in the 1945-1965 Birth Cohort Reflects Poor Use of Hepatocellular Carcinoma Screening.

Individuals from the 1945‐1965 birth cohort account for the majority of hepatocellular carcinoma (HCC) cases in the United States. Understanding trends in HCC among this birth cohort is vital given the increasing burden of chronic liver disease among this group. We retrospectively evaluated trends and disparities in HCC tumor stage at the time of diagnosis among the 1945‐1965 birth cohort in the United States using the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Tumor stage at the time of HCC diagnosis was assessed using Milan criteria and SEER HCC staging systems. Among 38,045 patients with HCC within the 1945‐1965 birth cohort (81.6% male, 50.1% non‐Hispanic white, 16.2% African American, 12.6% Asian, 19.8% Hispanic), 66.2% had Medicare or commercial insurance, 27.2% had Medicaid, and 6.6% were uninsured. During the period 2004‐2006 to 2013‐2014, the number of patients with HCC from the 1945‐1965 birth cohort increased by 58.7% (5.9% increase per year). While the proportion of patients with HCC within the Milan criteria increased with time (36.4% in 2003‐2006 to 46.3% in 2013‐2014; P < 0.01), less than half were within the Milan criteria. On multivariate analysis within the Milan criteria, men were 12% less likely to have HCC compared to women, and African Americans were 27% less likely to have HCC compared to non‐Hispanic whites (odds ratio, 0.73; 95% confidence interval, 0.68‐0.78; P < 0.01). Conclusion: From 2004 to 2014, the burden of newly diagnosed HCC among the 1945‐1965 birth cohort increased by 5.9% per year. While improvements in earlier staged HCC at diagnosis were observed, the majority of patients with HCC among the 1945‐1965 birth cohort were beyond the Milan criteria at diagnosis; this may reflect poor utilization or suboptimal performance of HCC screening tests.

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades.

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers globally. With advances in therapy for chronic viral hepatitis, changing social circumstances, and increasing practice of HCC surveillance, the epidemiology of HCC is expected to change over time. We explored the temporal trends in HCC in Singapore, a multiethnic Asian country, over the last 3 decades. Patients with HCC were prospectively enrolled and stratified into two cohorts (C1, 1988‐2002; C2, 2003‐2016). Patient and tumor characteristics, management, and survival were compared between the two cohorts, and a survival census was performed on October 31, 2015. There were 1,401 patients, and the mean age at diagnosis of HCC for C1 and C2 was 60.1 and 63.5 years, respectively. Male patient preponderance decreased significantly, with the male to female ratio falling from 5.2:1 to 3.9:1 between C1 and C2. Hepatitis B, although still the predominant risk factor for HCC, showed a significant decline from C1 to C2 (76.5% to 68.2%), while the nonviral etiology increased significantly over the same period (14.4% versus 25.0%, respectively). Significantly more patients in C2 than C1 were diagnosed through surveillance (39.2% versus 11.3%, respectively) and had better physical performance (Eastern Cooperative Oncology Group 0, 62.1% versus 20.4%, respectively). While Child‐Pugh status was comparable, significantly more patients in C2 than C1 had early stage disease (Barcelona Clinic Liver Cancer 0‐A, 39.5% versus 7.4%, respectively), which translated into significantly higher median survival (18.6 months versus 3.8 months, respectively). Conclusion: Over the past 3 decades, hepatitis B‐related HCC has been decreasing while HCC due to nonviral etiology has been increasing significantly. Surveillance to diagnose early stage HCC is important in improving the outcome of HCC. (Hepatology Communications 2017;1:564–571)

Global trends and predictions in hepatocellular carcinoma mortality

Trends in hepatocellular carcinoma (HCC) mortality rates have increased over recent decades in most countries. It is also the third cause of cancer death worldwide. The aim of this study is to update global trends in HCC mortality to 2014, and predict trends in rates in the EU, USA and Japan to 2020. Death certification data for HCC over the 1990-2014 period from the World Health Organization database were analyzed. Sixteen European, five American countries, and six other countries worldwide were included, as well as the EU as a whole. In European men, mortality rates were stable during the last decade (3.5/100,000). HCC mortality increased in Northern and Central Europe, and decreased in Southern Europe. In the USA, HCC mortality increased by 35% between 2002 and 2012, reaching 3.1/100,000 men in 2012; it is predicted to remain stable to 2020. Reduced mortality rates were observed in East Asia, although they remained around 10-24/100,000 men. In Japan, HCC mortality is predicted to decrease (5.4/100,000 men in 2020). Trends were favorable in the young, but unfavorable in middle aged, except in East Asia. Mortality rates were 3- to 5-fold lower in women than men in most regions, but trends were similar. Control of hepatitis B (HBV) and hepatitis C virus (HCV) infections has contributed to the decrease in HCC-related mortality in East Asia and Southern Europe. Unfavorable trends in other regions can be attributed to HCV (and HBV) epidemics in the 1960s and 1980s, alcohol consumption, increased overweight/obesity, and diabetes. Better management of cirrhosis, HCC diagnosis and treatment are also influencing the mortality trends worldwide. Mortality rates due to HCC have increased in many countries over recent decades. In this study, we updated worldwide mortality trends for HCC from 1990 to 2014, and predicted trends for some countries to 2020. We observed unfavorable trends in Northern and Central Europe, North and Latin America. East Asia showed an improvement, however mortality rates in this region were 2- to 5-fold higher than in most European countries and the Americas. Steady declines to 2020 are predicted for East Asia but not for Europe and the Americas.

Trends in hepatocellular carcinoma among people with HBV or HCV notification in Australia (2000–2014)

This study evaluates trends in hepatocellular carcinoma (HCC) among people with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in New South Wales (NSW), Australia between 2000 and 2014. Data on HBV and HCV notifications between January 1993 and December 2012 were linked to the NSW Admitted Patients Data Collection database between July 2000 and June 2014 and NSW Registry of Births Deaths and Marriages. The burden, crude and age-standardised incidence of HCC based on first hospitalization were calculated. In NSW between 2000-2014, there were 54,399, 93,099 and 3,809 individuals notified with HBV, HCV and HBV/HCV coinfection respectively. There were 725 (1.3%) with HCC among those with HBV notification as compared to 1,309 with HCC (1.4%) in those with HCV notification. The population-level burden of new HCC cases per year has stabilised in the HBV cohort (53 in 2001 and 44 in 2013), but increased markedly in the HCV cohort (49 in 2001 to 151 in 2013). The age-standardised incidence rates of HCC (per 1,000 person-years) declined from 2.3 (95% confidence interval (CI) 1.4, 3.1) in 2001 to 0.9 (95% CI 0.6, 1.2) in 2012 among those with HBV and remained stable between 2001 (1.4; 95% CI 0.8, 1.9) and 2012 (1.5; 95% CI 1.2, 1.7) in those with HCV. Main factors associated with HCC in those with HBV included later study period (2005-2009; 2010-2014) (hazard ratio (HR)=0.54, 95% CI 0.42, 0.70), male gender (HR=4.50, 95% CI 3.6, 5.6), Asia-Pacific country of birth (HR=3.84, 95% CI 2.58, 5.71) and alcohol dependency (HR=2.84, 95% CI 1.95, 4.13). Main factors associated with HCC in those with HCV included male gender (HR=2.56, 95% CI 2.20, 2.98), rural place of residence (HR=0.73, 95% CI 0.62, 0.86), Asia-Pacific country of birth (HR=2.37, 95% CI 1.99, 2.82) and alcohol dependency (HR=3.90, 95% CI 3.39, 4.49). Individual-level risk of HBV-related HCC has declined, suggesting an impact of more effective antiviral therapy from mid-2000s. In contrast, the interferon-containing HCV treatment era had no impact on individual-level HCV-related HCC risk and has seen escalating population-level HCC burden. Individual-level risk of HBV-related HCC has declined, suggesting an impact of more effective antiviral therapy from mid-2000s. In contrast, the interferon-containing HCV treatment era had no impact on individual-level HCV-related HCC risk and has seen escalating population-level HCC burden.

Incidence of hepatocellular carcinoma in Texas Latinos, 1995-2010: an update.

BackgroundA previous study showed Hepatocellular Carcinoma (HCC) rates to be higher among Latinos in Texas and highest among South Texas Latinos compared to other non-Hispanic whites (NHW) and other Latinos in the United States (U.S.). We used more recent data to assess trends in HCC among Texas Latinos and to reassess the elevated HCC incidence rate in Texas Latinos.MethodsWe used data from the U.S. SEER Program and the Texas Cancer Registry to calculate annual and 3-year moving average age-specific and age-adjusted HCC incidence rates, annual percent changes (APCs), and their corresponding 95% confidence intervals for Latinos and NHW in the U.S., Texas and South Texas.ResultsTexas Latino male and female incidence rates were 3.1 and 4.0 times higher than their NHW counterparts in SEER regions. Latino males and females in South Texas had the highest rates of HCC incidence overall; rate ratios were 3.6 and 4.2 among South Texas Latino males and females compared to SEER NHW counterparts. There are statistically significant increases in HCC incidence rates in all groups (Texas and South Texas Latinos and NHW groups) and across all age groups. The elevated HCC rates in Texas Latinos are consistent over the 1995–2010 period.ConclusionsThe incidence of HCC among Latinos in South Texas remains higher than elsewhere in the U.S. and warrants closer investigation of potential risk factors related to prevailing conditions unique to the population including higher obesity and diabetes rates, environmental, cultural and socioeconomic factors and possibly genetic predisposition.

Emerging trends in hepatocellular carcinoma: focus on diagnosis and therapeutics.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and one of the deadliest. Patients with chronic liver disease are at the highest risk for developing this tumor. This link provides an opportunity for developing preventive strategies and surveillance that aims at early detection of this tumor and possibly improving outcomes. In this review, we will discuss the latest developments in surveillance strategies, diagnosis, and treatment of this tumor. HCC is the sixth most common cancer in the world, with 782,000 new cases occurring in 2012 worldwide. In 2012, there were 746,000 deaths from liver cancer.1 HCC is the third most fatal cancer in the world.2 The distribution of HCC, which varies geographically, is related to the prevalence of hepatotropic virus. The burden of the disease is the highest in Eastern Asia, sub-Saharan Africa, and Melanesia where hepatitis B (HBV) infection is endemic. Meanwhile, in Japan, United States, and Europe, hepatitis C (HCV) infection is prevalent, and subsequently, is the major risk factor for acquiring HCC in these regions.1,3 It is estimated that the incidence of HCC in Europe and United States will peak at 2020—there will be 78,000 new HCC cases in Europe and 27,000 in the United States—and decline thereafter.1 Indeed, in Japan, the incidence of HCC had already plateaued and started to slowly fall.4 Cirrhosis is the most important risk factor for HCC regardless of etiology and may be caused by chronic viral hepatitis (mainly HBV and HCV), alcoholic liver disease, autoimmune disease, Stage 4 primary biliary cirrhosis, and metabolic diseases such as hereditary hemochromatosis, alpha-1 antitrypsin deficiency, and non-alcoholic fatty liver disease. In the Western hemisphere, HCC occurs in a background of cirrhosis in 90% of the cases.5 Before concentrating on diagnosis and therapeutics, it is important to discuss surveillance for this tumor.

Incidence and management of hepatocellular carcinoma among Māori and non-Māori New Zealanders.

To investigate time trends in hepatocellular carcinoma (HCC) incidence disparities, and ethnic differences in risk factors, comorbidity and treatment pathways among HCC patients. Cohorts of the NZ population (1981-2004) were created and probabilistically linked to cancer registry records to investigate trends in incidence by ethnicity over time. Hospital notes of 97 Māori and 92 non-Māori HCC patients diagnosed between 01/01/2006 and 31/12/2008 in NZ's North Island were reviewed. Liver cancer incidence was higher among Māori for all time periods. Compared with non-Māori, Māori males had nearly five times the rate of liver cancer (pooled RR=4.79, 95% CI 4.14-5.54), and Māori females three times the rate (pooled RR= 3.02, 95% CI 2.33-3.92). There were no significant differences in tumour characteristics or treatment of Māori and non-Māori patients with HCC. Māori more commonly had hypertension (51% versus 25%) while more non-Māori had cirrhosis recorded (62% versus 41%). The prevalence of hepatitis B among Māori patients (56%; 95% CI 45%-67%) was more than double that of non-Māori (27%; 95% CI 19%-36%). The hazard ratio for cancer-specific death for Māori compared with non-Māori was 1.36 (95% CI 0.96-1.92). HCC remains an important health problem particularly for Māori men. Efforts to improve coverage of screening for hepatitis B and surveillance of those with chronic hepatitis should be a priority to address the large inequalities found in liver cancer epidemiology.

The risk of hepatocellular carcinoma among individuals with acquired immunodeficiency syndrome in the United States

Hepatocellular carcinoma (HCC) is a concern among individuals with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The authors analyzed population-based registry linkage data from the US HIV/AIDS Cancer Match Study (1980-2009) to examine the risk and trends of HCC among individuals with AIDS. Standardized incidence ratios (SIRs) were used to measure HCC risk relative to the general population, and Poisson regression was used to calculate incidence rate ratios (RR) comparing incidence among individuals with AIDS. People with AIDS were categorized according to their HIV risk group into high and low hepatitis C virus (HCV) prevalence groups based on their HIV transmission risk category. Among 615,150 individuals with AIDS, HCC risk was elevated almost 4 times compared with the risk in the general population (N = 366; SIR, 3.8; 95% confidence interval, 3.5-4.3). Although HCC incidence increased steadily across calendar periods (P(trend) < .0001; adjusted for sex and age), the excess risk in individuals with AIDS compared with the general population remained somewhat constant (SIRs range, 3.5-3.9) between the monotherapy/dual therapy era (1990-1995) and the recent highly active antiretroviral therapy era (2001-2009). In a multivariate model adjusting for sex, race/ethnicity, and attained calendar period, HCC incidence increased with advancing age (P(trend) < .0001) and was associated with HIV risk groups with a known higher prevalence of HCV (adjusted RR, 2.2; 95% confidence interval, 1.8-2.8). HCC incidence in individuals with AIDS has increased over time despite improved HIV treatment regimens, likely reflecting prolonged survival with chronic liver disease. The high incidence in older adults suggests that this cancer will increase in importance with aging of the HIV-infected population.