Current epidemiology in hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world. AREAS COVERED: This review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity. EXPERT OPINION: Interventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC.

Socioeconomic and racial/ethnic disparities in receipt of palliative care among patients with metastatic hepatocellular carcinoma.

BACKGROUND: Patients with metastatic hepatocellular carcinoma (HCC) suffer symptoms of both end-stage liver disease and cancer. Palliative care (PC) enhances the quality of life via symptom control and even improves survival for some cancers. Our study characterized rates of PC utilization among metastatic HCC patients and determined factors associated with PC receipt. METHODS: We conducted a retrospective review of adult National Cancer Database patients diagnosed with metastatic HCC between 2004 and 2016. Chi-square tests were used to analyze two cohorts: those who received PC and those who did not. Logistic regression was performed to assess the impact of clinicodemographic factors on the likelihood of receiving PC. RESULTS: PC utilization was low at just 17%. Later year of diagnosis, insured status, and higher education level were associated with an increased likelihood of receiving PC. Treatment at academic centers or integrated network cancer programs increased the likelihood of receiving PC compared to treatment at a community center (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.33 and OR = 1.25, 95% CI = 1.07-1.45; respectively). Hispanics were significantly less likely to received PC than non-Hispanic Whites (OR = 0.73, 95% CI = 0.64-0.82). CONCLUSIONS: PC utilization among patients with metastatic HCC remains low. Targeted efforts should be enacted to increase the delivery of PC in this group.

Health care costs associated with chronic hepatitis C virus infection in Ontario, Canada: a retrospective cohort study.

BACKGROUND: High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. METHODS: In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. RESULTS: We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. INTERPRETATION: Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Socioeconomic Deprivation Does Not Impact Liver Transplantation Outcome for HCC: A Survival Analysis From a National Database.

BACKGROUND: To investigate the value of European deprivation index (EDI) and hepatocellular carcinoma (HCC) characteristics and their relationships with outcome after liver transplantation (LT). METHODS: Patients undergoing LT for HCC were included from a national database (from "Agence de la Biomédecine" between 2006 and 2016. Characteristics of the patients were blindly extracted from the database. Thus, EDI was calculated in 5 quintiles and prognosis factors of survival were determined according to a Cox model. RESULTS: Among the 3865 included patients, 33.9% were in the fifth quintile (quintile 1, N = 562 [14.5%]; quintile 2, N = 647 [16.7%]; quintile 3, N = 654 [16.9%]; quintile 4, N = 688 [17.8%]). Patients in each quintile were comparable regarding HCC history, especially median size of HCC, number of nodules of HCC and alpha-fetoprotein score. In the univariate analysis of the crude survival, having >2 nodules of HCC before LT and time on waiting list were associated with a higher risk of death (P < 0.0001 and P = 0.03, respectively). EDI, size of HCC, model for end-stage liver disease score, Child-Pugh score were not statistically significant in the crude and net survival. In both survival, time on waiting list and number of HCC ≥2 were independent factor of mortality after LT for HCC (P = 0.009 and 0.001, respectively, and P = 0.03 and 0.02, respectively). CONCLUSIONS: EDI does not impact overall survival after LT for HCC. Number of HCC and time on waiting list are independent prognostic factors of survival after LT for HCC.

Comparative clinical outcomes of robot-assisted liver resection versus laparoscopic liver resection: A meta-analysis.

BACKGROUND: As an emerging technology, robot-assisted surgical system has some potential merits in many complicated endoscopic procedures compared with laparoscopic surgery. But robot-assisted liver resection is still a controversial problem on its advantages compared with laparoscopic liver resection. We aimed to perform the meta-analysis to assess and compare the clinical outcomes of robot-assisted and laparoscopic liver resection. METHODS: We searched PubMed, Cochrane Library, Embase databases, Clinicaltrials, and Opengrey through March 24, 2020, including references of qualifying articles. English-language, original investigations in humans about robot-assisted and laparoscopic hepatectomy were included. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Continuous and dichotomous variables were compared by the weighted mean difference (WMD) and odds ratio (OR), respectively. RESULTS: Of 936 titles identified in our original search, 28 articles met our criteria, involving 3544 patients. Compared with laparoscopy, the robot-assisted groups had longer operative time (WMD: 36.93; 95% CI, 19.74-54.12; P < 0.001), lower conversion rate (OR: 0.63; 95% CI, 0.46-0.87; P = 0.005), higher transfusion rate (WMD: 2.39; 95% CI, 1.51-3.76; P < 0.001) and higher total cost (WMD:0.49; 95% CI, 0.42-0.55; P < 0.001). In addition, the baseline characteristics of patients about largest tumor size was larger (WMD: 0.36; 95% CI, 0.16-0.56; P < 0.001) and malignant lesions rate was higher (WMD: 1.50; 95% CI, 1.21-1.86; P < 0.001) in the robot-assisted versus laparoscopic hepatectomy. The subgroup analysis of minor hepatectomy showed robot-assisted was associated with longer operative time (WMD: 36.00; 95% CI, 12.59-59.41; P = 0.003), longer length of stay (WMD: 0.51; 95% CI, 0.02-1.01; p = 0.04) and higher total cost (WMD: 0.48; 95% CI, 0.25-0.72; P < 0.001) (Table 3); while the subgroup analysis of major hepatectomy showed robot-assisted was associated with lower estimated blood loss (WMD: -122.43; 95% CI, -151.78--93.08; P < 0.001). CONCLUSIONS: Our meta-analysis revealed that robot-assisted was associated with longer operative time, lower conversion rate, higher transfusion rate and total cost, and robot-assisted has certain advantages in major hepatectomy compared with laparoscopic hepatectomy.

Dissecting disease, race, ethnicity, and socioeconomic factors for hepatocellular carcinoma: An analysis from the United States Safety Net Collaborative.

BACKGROUND: Racial/ethnic and socioeconomic disparities are assumed to negatively affect treatment and outcomes for hepatocellular carcinoma (HCC). Our aim was to investigate the interaction of racial/ethnic and socioeconomic factors with stage of disease and type of treatment facility in receipt of treatment and overall survival (OS) of patients with HCC. METHODS: All patients with primary HCC in the US Safety-Net Collaborative database (2012-2014) were included. Patients were categorized into "safety-net" or "tertiary referral center" based on where they received treatment. Socioeconomic factors were determined at the zip-code level and included median income and percent of adults who graduated from high-school. Primary outcomes were receipt of treatment and OS. RESULTS: On MV Cox regression, neither race/ethnicity, median income, nor care provided at a SNH were associated with decreased OS (all p > 0.05). Independent predictors of decreased OS included lack of insurance (HR 1.34), less educational attainment (HR 1.59) higher MELD score (HR 1.07), higher stage at diagnosis (II:HR 1.34, III:HR 2.87, IV:HR 3.23), and not receiving treatment (HR 3.94) (all p < 0.05). Factors associated with not receiving treatment included history of alcohol abuse (OR 0.682), increasing MELD (OR 0.874), higher stage at diagnosis (III: OR 0.234, IV: OR 0.210) and care at a safety net facility (OR 0.424) There were no racial/ethnic or socioeconomic disparities in receipt of treatment. CONCLUSIONS: There is no intrinsic or direct association of race/ethnicity, socioeconomic status, or being treated at select safety-net hospitals with worse outcomes. Poor liver function, no insurance, and advanced stage of presentation are the main determinants of not receiving treatment and decreased survival.

Treatment patterns and direct medical costs among patients with advanced hepatocellular carcinoma.

AIMS: This study assessed the real-world United States (US) treatment patterns and the associated economic burden in patients diagnosed with advanced hepatocellular carcinoma (HCC). METHODS: The MarketScan database was used to identify patients newly diagnosed with HCC who received systemic therapy between 2011 and 2018 and continuously enrolled for ≥6 months (baseline period) prior and ≥1 month following HCC diagnosis. Treatment patterns (systemic and locoregional therapy), healthcare resource utilization, and costs were reported during follow-up. RESULTS: The final sample included 1580 patients (median age, 61; 78% male; median follow up, 8.7 months). The most common first line of therapy (LOT) was sorafenib (78%). The median time from HCC diagnosis to start of sorafenib was 43 days, and the median duration of sorafenib therapy was 60 days. Only 17% of patients received second LOT, and non-sorafenib treatment use increased to 66% (mostly chemotherapy combination). Transarterial chemoembolization was the most commonly observed locoregional therapy prior to the first LOT. The multivariable-adjusted average all-cause total cost among sorafenib treated patients was $17,642 (95% CI: $16,711-$18,558) per-patient per-month), of which $11,393 were HCC-specific. CONCLUSIONS: In patients who received first-line therapy for HCC, the duration of therapy was short (potentially due to progression or tolerability). Most patients did not continue to second-line therapy. Despite the short duration of therapy, HCC patients still incur a high economic burden, and there is a need for more effective and tolerable treatments.

Sociodemographic Characteristics as Predictors of Outcomes in Hepatocellular Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Race, gender, insurance status, and income play important roles in predicting health care outcomes. However, the impact of these factors has yet to be fully elucidated in the setting of hepatocellular carcinoma (HCC). METHODS: We designed a retrospective cohort study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program to identify patients diagnosed with resectable HCC (N = 28,518). Demographic factors of interest included race (Asian/Pacific Islander [API], African American [AA], Native American/Alaska Native [NA], or White [WH]) and gender (male [M] or female [F]). Insurance classifications included those having Medicare/Private Insurance [ME/PI], Medicaid [MAID], or No Insurance [NI]. Median household income was estimated for all diagnosed with HCC. Endpoints included: (1) overall survival; (2) likelihood of receiving a recommendation for surgery; and (3) specific surgical intervention performed. Multivariate multinomial logistic regression for relative risk ratio (RRR) and Cox regression models were used to identify pertinent associations. RESULTS: Race, gender, insurance status, and income had statistically significant effects on the likelihood of surgical recommendation and overall survival. API were more likely to receive a recommendation for hepatic resection (RRR = 1.45; 95% CI: 1.31-1.61; Reference Race: AA) and exhibited prolonged overall survival (HR = 0.77; 95% CI: 0.73-0.82; Reference Race: AA) as compared to members of any other ethnic group; there was no difference in these endpoints between AA, NA, or WH individuals. Gender also had a significant effect on survival: Females exhibited superior overall survival (HR = 0.89; 95% CI: 0.85-0.93; Reference Gender: M) as compared to males. Patients who had ME/PI were more likely than those with MAID or NI to receive a surgical recommendation. ME/PI was also associated with superior overall survival. Conclusions: Race, gender, insurance status, and income have measurable effects on HCC management and outcomes. The underlying causes of these disparities warrant further investigation.

Differences in healthcare expenditure estimates according to statistical approach: A nationwide claims database study on patients with hepatocellular carcinoma.

AIM: Disease-associated healthcare expenditures are generally calculated using matched comparisons or regression-based analyses, but little is known about their differences in estimates. This aim of this study was to compare the differences between disease-associated healthcare expenditures estimated using these 2 methods. METHODS: In this retrospective cohort study, a matched comparison was first conducted by matching cases with controls using sex, age, and comorbidities to estimate disease-associated expenditures. The cases were then used in a fixed-effects analysis that compared expenditures before and after disease occurrence. The subjects were adults (≥20 years) with primary hepatocellular carcinoma (HCC) who underwent treatment (including surgical resection, locoregional therapy, transcatheter arterial chemoembolization, and transarterial embolization) at a Japanese hospital between April 2010 and March 2018. We calculated the total healthcare expenditures per patient per month according to treatment and disease phase (initial, continuing, and terminal). RESULTS: There were 14,923 cases in the initial/continuing phases and 15,968 cases in the terminal phase. In the initial/continuing phases, 3,552 patients underwent surgical resection only, with HCC-associated expenditures of $5,555 according to the matched comparison and $5,889 according to the fixed-effects analysis (proportional difference: 94.3%). The initial phase expenditures were approximately 9% higher in the fixed-effects analysis, whereas the continuing phase expenditures were approximately 7% higher in the matched comparison. The expenditures in the terminal phase were 93.1% higher in the fixed-effects analysis. CONCLUSIONS: The 2 methods produced similar estimates of HCC-associated healthcare expenditures in the initial/continuing phases. However, terminal phase expenditures were substantially different between the methods.

Laparoscopic versus open hemihepatectomy: comprehensive comparison of complications and costs at 90 days using a propensity method.

Laparoscopic hemihepatectomy (LHH) may offer advantages over open hemihepatectomy (OHH) in blood loss, recovery, and hospital stay. The aim of this study is to evaluate our recent experience performing hemihepatectomy and compare complications and costs up to 90 days following laparoscopic versus open procedures. Retrospective evaluation of patients undergoing hemihepatectomy at our center 01/2010-12/2018 was performed. Patient, tumor, and surgical characteristics; 90-day complications; and costs were analyzed. Inverse probability of treatment weighting (IPTW) was used to balance covariates. A total of 141 hemihepatectomies were included: 96 OHH and 45 LHH. While operative times were longer for LHH, blood loss and transfusions were less. At 90 days, there were similar rates of liver-specific and surgical complications but fewer medical complications following LHH. Medical complications that arose with greater frequency following OHH were primarily pulmonary complications and urinary and central venous catheter infections. Complications at 90 days were lower following LHH (Clavien-Dindo grade ≥ III OHH 23%, LHH 11%, p = 0.130; Comprehensive Complication Index OHH 20.0 ± 16.1, LHH 10.9 ± 14.2, p = 0.001). While operating costs were higher, costs for hospital stay and readmissions were lower with LHH. Patients undergoing LHH experience a significant reduction in postoperative medical complications and costs, resulting in 90-day cost equity compared with OHH.

Demographic and Clinicopathologic Factors of Patients With Hepatocellular Carcinoma in a Safety Net Hospital.

BACKGROUND: Safety net hospitals have historically cared for a disproportionate number of patients of low socioeconomic status, racial and ethnic minorities, and patients with cancer. These innate challenges make safety net hospitals important in understanding how to improve access to cancer care in order to fit the needs of vulnerable patients and ultimately improve their outcomes. The purpose of this study is to characterize the current state and treatment of hepatocellular carcinoma (HCC) at Ben Taub Hospital, a safety net hospital in Houston, Texas. MATERIALS AND METHODS: A retrospective chart review was performed to review the demographic characteristics, clinicopathologic data, treatment strategies, and outcomes of HCC patients at Ben Taub Hospital between January 2012 and December 2014. RESULTS: Two-hundred twenty-six men and 78 women with a mean age of 58 y underwent evaluation. Most (87%) were either uninsured or covered by Medicaid. The majority (69%) of patients presented with advanced (stage 2 or more) disease, with 58% of patients presenting with multiple lesions. Of the 40% that presented with a solitary lesion, the average size was 4.97 cm. Transarterial chemoembolization was used in 37% of patients and sorafenib was given to 26% of patients. Five patients underwent successful transplant. One hundred seventeen (38%) patients died of their disease, 25 patients are alive with no evidence of disease, and 159 patients have been lost to follow-up. CONCLUSIONS: Most patients with HCC presented to this safety net hospital with advanced disease; however, multiple local and systemic treatments were offered. Screening programs to detect HCC at an earlier stage are essential for successful long-term outcomes in a resource-strapped hospital with limited access to liver transplantation.

Robotic liver resection: Hurdles and beyond.

Laparoscopy is currently considered the standard of care for certain procedures such as left-lateral sectionectomies and wedge resections of anterior segments. The role of robotic liver surgery is still under debate, especially with regards to oncological outcomes. The purpose of this review is to describe how the field of robotic liver surgery has expanded, and to identify current limitations and future perspectives of the technology. Available evidences suggest that oncologic results after robotic liver resection are comparable to open and laparoscopic approaches for hepatocellular carcinoma and colorectal liver metastases, with identifiable advantages for cirrhotic patients and patients undergoing repeat resections. Excellent outcomes and optimal patient safety can be only achieved with specific hepato-biliary and general minimally invasive training to overcome the learning curve.

The Impact of Bt Corn on Aflatoxin-Related Insurance Claims in the United States.

Previous field studies have reached no collective consensus on whether Bt corn, the most commonly planted transgenic crop worldwide, has significantly lower aflatoxin levels than non-Bt isolines. Aflatoxin, a mycotoxin contaminating corn and other commodities, causes liver cancer in humans and can pose severe economic losses to farmers. We found that from 2001-2016, a significant inverse correlation existed between Bt corn planting and aflatoxin-related insurance claims in the United States, when controlling for temperature and drought. Estimated benefits of aflatoxin reduction resulting from Bt corn planting are about $120 million to $167 million per year over 16 states on average. These results suggest that Bt corn use is an important strategy in reducing aflatoxin risk, with corresponding economic benefits. If the same principles hold true in other world regions, then Bt corn hybrids adapted to diverse agronomic regions may have a role in reducing aflatoxin in areas prone to high aflatoxin contamination, and where corn is a dietary staple.

New insights on sorafenib resistance in liver cancer with correlation of individualized therapy.

Liver cancer is highly malignant and insensitive to cytotoxic chemotherapy and is associated with very poor patient prognosis. In 2007, the small-molecule targeted drug sorafenib was approved for the treatment of advanced liver cancer. In the subsequent ten years, sorafenib has been the only first-line therapeutic targeted drug for advanced hepatocellular carcinoma (HCC). However, a number of clinical studies show that a considerable percentage of patients with liver cancer are insensitive to sorafenib. The number of patients who actually benefit significantly from sorafenib treatment is very limited, and the overall efficacy of sorafenib is far from satisfactory, which has attracted the attention of researchers. Based on previous studies and reports, this article reviews the potential mechanisms of sorafenib resistance (SR) and summarizes the biomarkers and clinicopathological indicators that might be used for predicting sorafenib response and developing personalized therapy.

Cost-Effectiveness of Hepatocellular Carcinoma Surveillance: An Assessment of Benefits and Harms.

INTRODUCTION: The value of hepatocellular carcinoma (HCC) surveillance is defined by the balance of benefits, i.e., early tumor detection, and potential harms, related to false positive and indeterminate results. Although physical harms can be observed in 15%-20% of patients with cirrhosis undergoing HCC surveillance, previous cost-effectiveness analyses have not incorporated costs of harms. We aimed to evaluate the cost-effectiveness of HCC surveillance including both benefits and harms. DESIGN: We constructed a Markov model to compare surveillance strategies of ultrasound (US) alone, US and alpha fetoprotein (AFP), and no surveillance in 1 million simulated patients with compensated cirrhosis. Harms included imaging and biopsy in patients undergoing surveillance for HCC. Model inputs were based on literature review, and costs were derived from the Medicare fee schedule, with all costs inflated to 2018 dollars. The primary outcome was the incremental cost-effectiveness ratio per incremental quality-adjusted life-year. RESULTS: In the base case analysis, US with AFP was the dominant strategy over both US alone and no surveillance. In a probabilistic sensitivity analysis, US with AFP was the most cost-effective strategy in 80.1% of simulations at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. In our threshold analyses, an HCC incidence >0.4% per year and surveillance adherence >19.5% biannually were necessary for US with AFP to be cost-effective compared with no surveillance. DISCUSSION: Accounting for both surveillance-related benefits and harms, US and AFP is more cost-effective for HCC surveillance than US alone or no surveillance in patients with compensated cirrhosis.

Lenvatinib versus sorafenib for unresectable hepatocellular carcinoma: a cost-effectiveness analysis.

Aim: To investigate the cost-effectiveness of lenvatinib and sorafenib in the treatment of patients with nonresected hepatocellular carcinoma in China. Materials & methods: Markov model was used to simulate the direct medical cost and quality-adjusted life years (QALY) of patients with hepatocellular carcinoma. Clinical data were derived from the Phase 3 randomized clinical trial in a Chinese population. Results: Sorafenib treatment resulted in 1.794 QALYs at a cost of $43,780.73. Lenvatinib treatment resulted in 2.916 QALYs for patients weighing <60 and ≥60 kg at a cost of $57,049.43 and $75,900.36, The incremental cost-effectiveness ratio to the sorafenib treatment group was $11,825.94/QALY and $28,627.12/QALY, respectively. Conclusion: According to WHO's triple GDP per capita, the use of lenvatinib by providing drugs is a cost-effective strategy.

Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. METHODS AND RESULTS: Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. CONCLUSION: NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.

Comparative cost-effectiveness of cabozantinib as second-line therapy for patients with advanced hepatocellular carcinoma in Germany and the United States.

BACKGROUND: Cabozantinib was approved by the European Medicines Agency and the Federal Drug Administration as an option for sorafenib-resistant advanced hepatocellular carcinoma, increasing overall survival and progression-free survival compared with placebo. We evaluated the cost-effectiveness of cabozantinib in the second-line setting for patients with an advanced hepatocellular carcinoma from the German statutory health insurance perspective compared with an US scenario using US prices. METHODS: A Markov model was developed to compare the costs and effectiveness of cabozantinib with best supportive care in the second-line treatment of advanced hepatocellular carcinoma over a lifetime horizon. Health outcomes were measured in discounted life years and discounted quality-adjusted life years. Survival probabilities were estimated using parametric survival distributions based on CELESTIAL trial data. Utilities were derived from the literature. Costs contained drugs, monitoring and adverse events measured in US Dollars. Model robustness was addressed in univariable, scenario and probabilistic sensitivity analyses. RESULTS: Cabozantinib generated a gain of 0.18 life years (0.15 quality-adjusted life years) compared with best supportive care. The total mean cost per patient was $56,621 for cabozantinib and $2064 for best supportive care in the German model resulting in incremental cost-effectiveness ratios for cabozantinib of $306,778/life year and $375,470/quality-adjusted life year. Using US prices generated costs of $177,496 for cabozantinib and $4630 for best supportive care and incremental cost-effectiveness ratios of $972,049/life year and $1,189,706/quality-adjusted life year. CONCLUSIONS: Our analysis established that assuming a willingness-to-pay threshold of $163,371/life year (quality-adjusted life year) for the German model and $188,559/life year (quality-adjusted life year) for the US model, cabozantinib is not cost-effective compared with best supportive care. Sensitivity analyses showed that cabozantinib was not cost-effective in almost all our scenarios.