Analysis of primary care electronic health record data of people living with hepatitis B virus: infection and hepatocellular carcinoma risk associated with socio-economic deprivation.

OBJECTIVES: We set out to characterise chronic hepatitis B (CHB) in the primary care population in England and investigate risk factors for progression to hepatocellular carcinoma (HCC). STUDY DESIGN: Retrospective cohort study. METHODS: We identified 8039 individuals with CHB in individuals aged ≥18 years between 1999 and 2019 in the English primary care database QResearch. HCC risk factors were investigated using Cox proportional hazards modelling. RESULTS: Most of those with a record of CHB were males (60%) of non-White ethnicity (>70%), and a high proportion were in the most deprived Townsend deprivation quintile (44%). Among 7029 individuals with longitudinal data, 161 HCC cases occurred. Increased HCC hazards were significantly associated with male sex (adjusted hazards ratio [aHR] 3.17, 95% confidence interval [95% CI] 1.92-5.23), in the fifth deprivation quintile as compared to the third quintile (aHR 1.69, 95% CI 1.01-2.84), with older age (for age groups 56-65 and ≥66 years, compared to 26-35 years, aHRs 2.82 [95% CI 1.45-5.46] and 3.76 [95% CI 1.79-7.9], respectively), Caribbean ethnicity (aHR 3.32, 95% CI 1.43-7.71, compared to White ethnicity), ascites (aHR 3.15, 95% CI 1.30-7.67), cirrhosis (aHR 6.55, 95% CI 4.57-9.38) and peptic ulcer disease (aHR 2.26, 95% CI 1.45-3.51). CONCLUSIONS: Targeting interventions and HCC surveillance at vulnerable groups is essential to improve CHB outcomes and to support progress towards international goals for the elimination of hepatitis infection as a public health threat.

Community-Level Factors Associated with Hepatocellular Carcinoma Incidence and Mortality: An Observational Registry Study.

BACKGROUND: Hepatocellular carcinoma (HCC) incidence and outcomes vary across populations in the United States, but few studies evaluate local drivers of observed disparities. We measured HCC incidence at the community level and assessed community-level HCC risk factors with the goal of informing resource allocation to improve early case detection, which is associated with improved outcomes. METHODS: Clinical and demographic data including census tract of residence for all adults diagnosed with HCC in the Connecticut Tumor Registry between 2008 and 2019 were combined with publicly available U.S. Census and Centers for Disease Control and Prevention (CDC) data at the ZIP Code tabulation area (ZCTA) level. The average annual incidence of HCC was calculated for each ZCTA and associations between community-level characteristics, HCC incidence, stage at diagnosis, and survival were evaluated. RESULTS: Average annual HCC incidence during the study period was 8.9/100,000 adults and varied from 0 to 97.7 per 100,000 adults by ZCTA. At the community level, lower rates of high school graduation, higher rates of poverty, and rural community type were associated with higher HCC incidence. Persons with HCC living in the highest incidence ZCTAs were diagnosed at a younger age and were less likely to be alive at 1, 2, and 5 years after diagnosis. CONCLUSIONS: Community-level socioeconomic factors are strongly associated with HCC incidence and survival in Connecticut. IMPACT: This reproducible geo-localization approach using cancer registry, Census, and CDC data can be used to identify communities most likely to benefit from health system investments to reduce disparities in HCC.

Association between Patient Experience Scores and Low Utilization of Hepatocellular Carcinoma Treatment in the United States: A Surveillance, Epidemiology, and End Results-Consumer Assessment of Healthcare Providers and Systems Analysis (SEER-CAHPS).

PURPOSE: To study the experiences of patients with hepatocellular carcinoma (HCC) contributing to treatment discrepancy in the United States. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results data from National Cancer Institute (NCI), Medicare (2002-2015) beneficiaries with HCC who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey were included. Six CAHPS items (3 global scores: global care rating [GCR], primary doctor rating [PDR], and specialist rating [SR]; 3 composite scores: getting needed care [GNC], getting care quickly [GCQ], and doctor communication [DC]) assessed patient experience. Covariates assessed between treated and nontreated groups included patient, disease, hospital, and CAHPS items. RESULTS: Among 548 patients with HCC, 211 (39%) received treatment and 337 (61%) did not receive treatment. Forty-two percent (GCR), 29% (PDR), 30% (SR), 36% (GNC), 78% (GCQ), and 35% (DC) of patients reported less-than-excellent experiences on the respective CAHPS items. Chronic liver disease (CLD) was present in 52% and liver decompensation (LD) in 60%. A minority of the hospitals were NCI-designated cancer centers (47%), transplant centers (27%), and referral centers (9%). On univariable analysis, patients with at least a high school degree (odds ratio [OR], 1.9), admittance to a ≥400-bed hospital (OR, 2.7), CLD (OR, 3.0), or LD (OR, 1.7) were more likely to receive treatment, whereas older patients (≥75 years) (OR, 0.5) were less likely to receive treatment. On multivariable, patients with CLD (OR, 6.8) and an excellent experience in GNC with a specialist (OR, 10.6) were more likely to receive treatment. CONCLUSIONS: HCC treatment discrepancy may be associated with patient-related factors, such as lack of specialist care (GNC), and disease-related factors, such as absence of underlying CLD.

Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis.

Background/Aims: Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Methods: Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. Results: aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Conclusions: Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.

Impact of socio-economic environment on incidence of primary liver cancer in France between 2006 and 2016.

BACKGROUND AND AIMS: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHOD: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. RESULTS: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9-10.66] per 100 000 person-years, Q2 11.43 [10.48-12.47] (p < .0001), Q3 11.81 [10.82-12.89] (p < .0001), Q4 12.26 [11.25-13.37] (p < .001) and Q5 11.53 [10.57-12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). CONCLUSION: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies.

Diagnosis and assessment of disease severity in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and eventually cirrhosis and hepatocellular carcinoma (HCC). The diagnosis of NAFLD is based on the detection of excess fat disposition in the liver, which is the first step to trigger further evaluation of NAFLD, including necroinflammation and fibrosis. In this review, we discuss non-invasive biomarkers and imaging tools that are currently and potentially available for different features (steatosis, necroinflammation and fibrosis) and disease severity assessment of NAFLD. In the past 2 decades, advances in non-invasive tests of fibrosis have transformed the management of NAFLD. Blood and imaging biomarkers have already been evaluated in multiple studies for the diagnosis of fibrosis and cirrhosis. Among the various histological features of NAFLD, the degree of fibrosis has the strongest correlation with liver-related morbidity and mortality. Non-invasive tests of fibrosis have been shown to predict liver-related outcomes, both in the general population and among patients with NAFLD. What is lacking, however, is good data to support the use of non-invasive tests as monitoring and response biomarkers. With the conclusion of several large phase 3 studies in the next few years, the availability of paired liver biopsy, non-invasive test and clinical outcome data will likely advance the field and shed light on new biomarkers and the way to use various non-invasive tests in a longitudinal manner.

Assessment of TLL1 variant and risk of hepatocellular carcinoma in Latin Americans and Europeans.

INTRODUCTION AND OBJECTIVES: Tolloid like protein 1 (TLL1) rs17047200 has been reported to be associated with HCC development and liver fibrosis. However, to our knowledge, no studies have been performed on Latin Americans and comparative differences between TLL1 rs17047200 in HCC patients from Latin America and Europe are undefined. MATERIALS AND METHODS: Cross-sectional analysis was performed on Latin American and European individuals. We analyzed TLL1 rs17047200 on DNA from 1194 individuals, including 420 patients with HCC (86.0 % cirrhotics) and 774 without HCC (65.9 % cirrhotics). RESULTS: TLL1 rs17047200 genotype AT/TT was not associated with HCC development in Latin Americans (OR: 0.699, 95 %CI 0.456-1.072, p = 0.101) or Europeans (OR: 0.736, 95 %CI 0.447-1.211, p = 0.228). TLL1 AT/TT was not correlated with fibrosis stages among metabolic dysfunction-associated steatotic liver disease (MASLD) patients from Latin America (OR: 0.975, 95 %CI 0.496-1.918, p = 0.941). Among Europeans, alcohol-related HCC had lower TLL1 AT/TT frequencies than cirrhosis (18.3 % versus 42.3 %, OR: 0.273, 95 %CI 0.096-0.773, p = 0.015). CONCLUSIONS: We found no evidence that the TLL1 rs17047200 AT/TT genotype is a risk factor for HCC development in Latin Americans or Europeans. A larger study integrating ethnic and etiology backgrounds is needed to determine the importance of the TLL1 SNP in HCC development.

Construction of a hepatocellular carcinoma high-risk population rating scale and independent predictors' assessment.

BACKGROUND: With increasing mortality and incidence, hepatocellular carcinoma (HCC) has become a major public health problem. The early diagnosis of HCC can improve its prognosis. The aim of this study was to identify potential risk factors related to HCC development and to establish a high-risk population rating scale. METHODS: A total of 853 patients with chronic hepatitis B (CHB) were enrolled in this study, including 403 patients with HCC as the case group and others as the control group. Their demographic and clinical characteristics were compared and the independent risk factors for HCC were assessed. Then, the optimal cutoff levels of these factors were analyzed by the receiver operating characteristic (ROC) method. A high-risk population rating scale was constructed based on the factors and then evaluated in the modeling population. RESULTS: The factors that presented statistically significant differences between the two groups included age, smoking, alcohol abuse, body mass index, triglyceride, high‒density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, fasting plasma glucose, creatinine and uric acid. The ROC curve showed that the cutoff score for the HCC high risk population was 5 (AUC=0.74, P<0.001) and the Hosmer‒Lemeshow analysis showed that the fitting effect of this rating scale was good (P = 0.294). CONCLUSIONS: The integration of these factors can contribute to a prognostic score for the risk of HCC development, which offered certain clinical practicability.

Real-world epidemiology, treatment patterns and disease burden of patients diagnosed with chronic hepatitis B in Taiwan.

BACKGROUND AND AIMS: This study aimed to update the epidemiology, clinical, and economic outcomes of patients diagnosed with chronic hepatitis B (CHB) infection in Taiwan. METHODS: This is a retrospective observational study using claims data from the National Health Insurance Research Database. Cases were identified between 2010 and 2019 using CHB diagnosis codes and claims for alanine aminotransferase laboratory tests or CHB treatment within one year of the first CHB diagnosis. Patient characteristics, epidemiology, clinical, and economic outcomes were described. RESULTS: A total of 730 154 CHB-diagnosed cases were identified. The prevalence of diagnosed CHB increased from 1.13% in 2010 to 2.43% in 2019, with the highest occurring among those aged 55-64 years (4.76%) and 45-54 years (4.37%) and being higher in men (2.98%) than in women (2.21%). The majority of newly diagnosed CHB patients were 35 years of age or older (86.6%), with a median age of 49 years. After a median follow-up period of 6.42 years, 12.5%, 7.9%, 2.8%, and 0.35% were diagnosed with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation respectively. Among 456 706 incident CHB-diagnosed patients, 17.4% had received at least one CHB medication, with the majority taking entecavir (67.9%). Patients with increasing disease severity had higher healthcare resource utilization, and inpatient costs accounted for 48.9%-65.5% of the overall medical cost in different health states. CONCLUSION: Despite the decreasing incidence of newly diagnosed CHB, the prevalence of diagnosed CHB remains high and poses a significant healthcare challenge owing to the high economic burden associated with the complications of CHB.

Dynamic risk assessment for hepatocellular carcinoma in patients with chronic hepatitis C.

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring.

Incidence and Risk Factors for Hepatocellular Carcinoma in Cirrhosis: The Multicenter Hepatocellular Carcinoma Early Detection Strategy (HEDS) Study.

BACKGROUND & AIMS: Worldwide, hepatocellular carcinoma (HCC) is a common malignancy. We aimed to prospectively determine the incidence and risk factors of HCC in a U.S. METHODS: The multicenter Hepatocellular Carcinoma Early Detection Strategy study of the National Institutes of Health prospectively enrolled patients with cirrhosis who underwent standard surveillance for HCC. Demographics, medical and family history, etiology of liver disease, and clinical features were evaluated for associations with HCC. RESULTS: Between April 10, 2013 and December 31, 2021, 1723 patients were enrolled and confirmed eligible. During median follow-up of 2.2 years (range, 0-8.7 years), there were 109 incident cases of HCC for an incidence rate of 2.4 per 100 person-years: 88 (81%) patients with very early/early Barcelona Clinic Liver Cancer stage (0, A), 20 (18%) intermediate stage (B), and 1 (1%) unknown stage. Risk factor analyses were restricted to 1325 patients, including 95 incident HCC, with at least 6 months of follow-up. The majority were men (53.2%), obese or severely obese (median body mass index, 30.2 kg/m2), and white (86.3%); 42.0% had history of hepatitis C virus infection, 20.7% had alcoholic liver disease, and 24.9% had nonalcoholic fatty liver disease. Fourteen risk factors for HCC were significant (P < .05) in univariate analyses, and a multivariate subset was selected using stepwise logistic regression. The multivariate subset contained gender (P < .001; male; odds ratio [OR], 2.47; 95% confidence interval [CI], 1.54-4.07), years with cirrhosis (P = .004; OR, 1.06; 95% CI, 1.02-1.1), family history of liver cancer (P = .02; yes; OR, 2.69; 95% CI, 1.11-5.86), age (per 5 years; P = .02; OR, 1.17; 95% CI, 1.03-1.33), obesity (P = .02; yes; OR, 1.7; 95% CI, 1.08-2.73), aspartate aminotransferase (log(1+AST); P = .06; OR, 1.54; 95% CI, 0.97-2.42), alpha-fetoprotein (log(1+AFP); P = .07; OR, 1.32; 95% CI, 0.97-1.77), and albumin (P = .10; OR, 0.7; 95% CI, 0.46-1.07). CONCLUSIONS: Thus far, this is the largest prospective and geographically diverse study of a U.S. cohort of patients with cirrhosis that validates known risk factors for HCC (gender, age, obesity, years with cirrhosis, family history of liver cancer, baseline AFP, albumin, and AST). The incidence of HCC was 2.4% per 100 person-years.

Second order probabilistic assessment of chronic dietary exposure to aflatoxin M1 in Serbia.

Considering the genotoxic and cancerogenic nature of aflatoxin M1 (AFM1), its presence in milk and dairy products may pose health risks for consumers. The chronic exposure was calculated using a two-dimensional (second order) Monte Carlo model. Results of 13 722 milk and dairy product samples analysed in the 2015-2022 period were used. Milk and dairy products intake information was collected with a Food Frequency Questionnaire (FFQ) validated by a 24-h recall-based method. Risk characterization was done by calculation of the Margin of Exposure (MOE) and by calculation of AFM1 induced number of hepatocellular carcinoma (HCC) cases. Mean AFM1 Estimated Daily Intake (EDI) was highest in children at 0.336 (CI: 0.294-0.385) ng kg-1 bw day-1, followed by adolescents with 0.183 (CI: 0.164-0.204), then adult females with 0.161 (CI: 0.146-0.179) and finally adult males with lowest EDI of 0.126 (CI: 0.115-0.139) ng kg-1 bw day-1. MOE values based on mean EDI for all population groups were above risk associated threshold and the number of possible HCC cases was in the range of 0.0002-0.0021 cases per year for 105 individuals. The results suggest low health risks due to AFM1 exposure for the whole population. Still, this risk is not non-existent, especially for children as they have a higher ratio of the population exposed to risk associated AFM1 levels, with MOE values below risk indicating threshold starting at 77.5th percentile.

Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer death in Australia. A recent Australian consensus guidelines recommended HCC surveillance for cirrhotic patients and non-cirrhotic chronic hepatitis B (CHB) patients at gender and age specific cut-offs. A cost-effectiveness model was then developed to assess surveillance strategies in Australia. METHODS: A microsimulation model was used to evaluate three strategies: biannual ultrasound, biannual ultrasound with alpha-fetoprotein (AFP) and no formal surveillance for patients having one of the conditions: non-cirrhotic CHB, compensated cirrhosis or decompensated cirrhosis. One-way and probabilistic sensitivity analyses as well as scenario and threshold analyses were conducted to account for uncertainties: including exclusive surveillance of CHB, compensated cirrhosis or decompensated cirrhosis populations; impact of obesity on ultrasound sensitivity; real-world adherence rate; and different cohort's ranges of ages. RESULTS: Sixty HCC surveillance scenarios were considered for the baseline population. The ultrasound + AFP strategy was the most cost-effective with incremental cost-effectiveness ratios (ICER) compared to no surveillance falling below the willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY) at all age ranges. Ultrasound alone was also cost-effective, but the strategy was dominated by ultrasound + AFP. Surveillance was cost-effective in the compensated and decompensated cirrhosis populations alone (ICERs < $30,000), but not cost-effective in the CHB population (ICERs > $100,000). Obesity could decrease the diagnostic performance of ultrasound, which in turn, reduce the cost-effectiveness of ultrasound ± AFP, but the strategies remained cost-effective. CONCLUSIONS: HCC surveillance based on Australian recommendations using biannual ultrasound ± AFP was cost-effective.

Population-attributable risk of modifiable lifestyle factors to hepatocellular carcinoma: The multi-ethnic cohort.

BACKGROUND AND AIMS: Lifestyle factors are well associated with risk of hepatocellular carcinoma (HCC). However, the impact of reducing adverse lifestyle behaviours on population-level burden of HCC is uncertain. METHODS: We conducted prospective analysis of the population-based multi-ethnic cohort (MEC) with linkage to cancer registries. The association of lifestyle factors (smoking, alcohol, diet quality assessed by alternate Mediterranean diet score, coffee drinking, physical activity and body mass index) with HCC incidence was examined using Cox regression. Population-attributable risk (PAR, %) for the overall, lean and overweight/obese populations was determined. RESULTS: A total of 753 incident cases of HCC were identified in 181,346 participants over median follow-up of 23.1 years. Lifestyle factors associated with elevated HCC risk included former/current smoking, heavy alcohol use, poor diet quality, lower coffee intake and obesity, but not physical activity. The lifestyle factor with highest PAR was lower coffee intake (21.3%; 95% CI: 8.9%-33.0%), followed by current smoking (15.1%; 11.1%-19.0%), obesity (14.5%; 9.2%-19.8%), heavy alcohol use (7.1%; 3.5%-10.6%) and lower diet quality (4.1%; 0.1%-8.1%). The combined PAR of all high-risk lifestyle factors was 51.9% (95% CI: 30.1%-68.6%). A higher combined PAR was observed among lean (65.2%, 26.8%-85.7%) compared to overweight/obese (37.4%, 11.7%-58.3%) participants. Adjusting for viral hepatitis status in a linked MEC-Medicare dataset resulted in similar PAR results. CONCLUSIONS: Modifying lifestyle factors, particularly coffee intake, may have a substantial impact on HCC burden in diverse populations, with greater impact among lean adults. Diet and lifestyle counselling should be incorporated into HCC prevention strategies.

The high burden of comorbidities in Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B in Far North Queensland, Australia, and the implications for patient management.

BACKGROUND: Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B virus (HBV) infection have a significant burden of hepatocellular carcinoma (HCC). The prevalence of comorbidities that increase the risk of HCC in this population is incompletely defined. METHODS: This cross-sectional study was performed in remote tropical Queensland, Australia in January 2021. All individuals living with chronic HBV in the region were identified; the prevalence of relevant comorbidities was determined by reviewing medical records. RESULTS: All 236 individuals in the cohort identified as Aboriginal and Torres Strait Islander Australians; their median (interquartile range (IQR)) age was 48 (40-62) years; 120/236 (50.9%) were female. Of the 194/236 (82.2%) engaged in HBV care, 61 (31.4%) met criteria for HBV therapy and 38 (62.2%) were receiving it. However, 142/236 (60.2%) were obese, 73/236 (30.9%) were current smokers and 57/236 (24.2%) were drinking alcohol hazardously; 70/236 (29.7%) had ≥2 of these additional risk factors for HCC, only 43/236 (18.2%) had none. Among the 19 patients with confirmed cirrhosis, 9 (47%) were obese, 8 (42%) were currently-or had a history of-drinking alcohol hazardously and 5 (26.3%) were current smokers. Patients also had a median (IQR) of 3 (2-4) cardiovascular risk factors (cigarette smoking, hypertension, impaired glucose tolerance, dyslipidaemia, renal impairment/proteinuria). Only 9/236 (3.8%) did not have one of these 5 comorbidities. CONCLUSIONS: Aboriginal and Torres Strait Islander Australians living with chronic HBV in this region of remote Australia have a high engagement with HBV care and the majority of individuals eligible for antiviral therapy are receiving it. However, a significant comorbidity burden increases their risk of cirrhosis, HCC, and premature death. It is essential to integrate chronic HBV care with management of these comorbidities-rather than focusing on HBV alone-to achieve optimal health outcomes.

Cost of hepatocellular carcinoma to the national health service in England: a registry-based analysis.

OBJECTIVE: Hepatocellular carcinoma (HCC) incidence in the UK trebled between 1997 and 2017. With increasing numbers requiring treatment, understanding the likely impact on healthcare budgets can inform service planning and commissioning. The aim of this analysis was to use existing registry data to describe the direct healthcare costs of current treatments for HCC and estimate the impact on National Health Service (NHS) budgets. DESIGN: A retrospective data analysis based on the National Cancer Registration and Analysis Service cancer registry informed a decision-analytic model for England comparing patients by cirrhosis compensation status and those on palliative or curative treatment pathways. Potential cost drivers were investigated by undertaking a series of one-way sensitivity analyses. RESULTS: Between 1 January 2010 and 31 December 2016, 15 684 patients were diagnosed with HCC. The median cost per patient over 2 years was £9065 (IQR: £1965 to £20 491), 66% did not receive active therapy. The cost of HCC treatment for England over 5 years was estimated to be £245 million. CONCLUSION: The National Cancer Registration Dataset and linked data sets have enabled a comprehensive analysis of the resource use and costs of secondary and tertiary healthcare for HCC, providing an overview of the economic impact to the NHS England of treating HCC.

Healthcare Costs for Medicare Patients With Hepatocellular Carcinoma in the United States.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has an increasing mortality in the United States and is a leading cause of morbidity and mortality in patients with cirrhosis. We aimed to estimate the financial burden related to HCC in a large nationally representative United States cohort. METHODS: We used the Surveillance, Epidemiology, and End Results program (SEER)-Medicare database to identify 4525 adult patients who were diagnosed with HCC between 2011 and 2015. We generated a 1:1 propensity score-matched cohort of patients with cirrhosis but no HCC as a comparator group to define incremental HCC-specific costs beyond costs related to underlying cirrhosis. Our main outcomes were patient liabilities and Medicare payments in the first year after HCC diagnosis. RESULTS: Compared with patients with cirrhosis, those with HCC had higher incremental patient liabilities (median +$7166; interquartile range, $2401-$16,099) and Medicare payments (+$50,110; interquartile range, $142,42-$136,239; P < .001 for both) in the first year after diagnosis. Patients with HCC had significantly higher inpatient, outpatient, and physician service costs compared with the matched cohort with cirrhosis (P < .001 for all). Patients with early-stage HCC had lower incremental patient liabilities (median, $4195 vs $8238; P < .001) and Medicare payments (median, $28,207 vs $59,509; P < .001) than those with larger tumor burden. In multivariable median regression analysis, incremental patient liabilities and Medicare payments were significantly associated with the National Cancer Institute comorbidity index, nonalcoholic fatty liver disease etiology, presence of ascites, and presence of hepatic encephalopathy. CONCLUSIONS: Patients with HCC suffer from cancer-related financial burden, highlighting a need for policy interventions and financial support systems.

Racial, Ethnic, and Socioeconomic Disparities in Treatment Delay Among Patients With Hepatocellular Carcinoma in the United States.

BACKGROUND & AIMS: Failures have been reported across the cancer care continuum in patients with hepatocellular carcinoma (HCC); however, the impact of treatment delays on outcomes has not been well-characterized. We described the prevalence of treatment delays in a racially and ethnically diverse cohort of patients and its association with overall survival. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients diagnosed with HCC between 2001 and 2015. We performed multivariable logistic regression analysis to identify factors associated with treatment delay (ie, receipt of HCC-directed therapy >3 months after diagnosis). Cox proportional hazards regression analysis with a 5-month landmark was used to characterize the association between treatment delay and overall survival, accounting for immortal time bias. RESULTS: Of 8450 patients with treatment within 12 months of HCC diagnosis, 1205 (14.3%) experienced treatment delays. The proportion with treatment delays ranged from 6.8% of patients undergoing surgical resection to 21.6% of those undergoing liver transplantation. In multivariable analysis, Black patients (odds ratio, 1.96; 95% confidence interval [CI], 1.21-3.15) and those living in high poverty neighborhoods (odds ratio, 1.55; 95% CI, 1.25-1.92) were more likely to experience treatment delays than white patients and those living in low poverty neighborhoods, respectively. Treatment delay was independently associated with worse survival (hazard ratio 1.15, 95% CI, 1.05-1.25). CONCLUSIONS: Nearly 1 in 7 patients with HCC experience treatment delays, with higher odds in Black patients and those living in high poverty neighborhoods. Treatment delays are associated with worse survival, highlighting a need for interventions to improve time-to-treatment.