Disparities in Hepatocellular Carcinoma Survival by Insurance Status: A Population-Based Study in China.

Objective: Health disparities related to basic medical insurance in China have not been sufficiently examined, particularly among patients with hepatocellular carcinoma (HCC). This study aims to investigate the disparities in HCC survival by insurance status in Tianjin, China. Methods: This retrospective analysis used data from the Tianjin Basic Medical Insurance claims database, which consists of enrollees covered by Urban Employee Basic Medical Insurance (UEBMI) and Urban and Rural Resident Basic Medical Insurance (URRBMI). Adult patients newly diagnosed with HCC between 2011 and 2016 were identified and followed until death from any cause, withdrawal from UEBMI or URRBMI, or the latest data in the dataset (censoring as of December 31st 2017), whichever occurred first. Patients' overall survival during the follow-up was assessed using Kaplan-Meier and extrapolated by six parametric models. The hazard ratio (HR) and 95% confidence intervals (CI) were calculated with the adjusted Cox proportional hazards model including age at diagnosis, sex, baseline comorbidities and complications, baseline healthcare resources utilization and medical costs, tumor metastasis at diagnosis, the initial treatment after diagnosis and antiviral therapy during the follow-up. Results: Two thousand sixty eight patients covered by UEBMI (N = 1,468) and URRBMI (N = 570) were included (mean age: 60.6 vs. 60.9, p = 0.667; female: 31.8 vs. 27.7%, p = 0.074). The median survival time for patients within the UEBMI and URRBMI were 37.8 and 12.2 months, and the 1-, 3-, 5-, 10-year overall survival rates were 63.8, 50.2, 51.0, 33.4, and 44.4, 22.8, 31.5, 13.1%, respectively. Compared with UEBMI, patients covered by URRBMI had 72% (HR: 1.72; 95% CI: 1.47-2.00) higher risk of death after adjustments for measured confounders above. The survival difference was still statistically significant (HR: 1.49; 95% CI: 1.21-1.83) in sensitivity analysis based on propensity score matching. Conclusions: This study reveals that HCC patients covered by URRBMI may have worse survival than patients covered by UEBMI. Further efforts are warranted to understand healthcare disparities for patients covered by different basic medical insurance in China.

Therapeutic Underuse and Delay in Hepatocellular Carcinoma: Prevalence, Associated Factors, and Clinical Impact.

Prognosis of hepatocellular carcinoma (HCC) could be affected by lack of or delayed therapy. We aimed to characterize the prevalence, correlates, and clinical impact of therapeutic underuse and delay in patients with HCC. Patients with HCC diagnosed between 2010 and 2017 were analyzed from the United States National Cancer Database. Logistic regression analysis identified factors associated with no and delayed (>90 days after diagnosis) HCC treatment. Cox proportional hazards regression with landmark analysis assessed the association between therapeutic delay and overall survival (OS), accounting for immortal time bias. Of 116,299 patients with HCC, 24.2% received no treatment and 18.4% of treated patients had delayed treatment. Older age, Black, Hispanic, lower socioeconomic status, earlier year of diagnosis, treatment at nonacademic centers, Northeast region, increased medical comorbidity, worse liver dysfunction, and higher tumor burden were associated with no treatment. Among treated patients, younger age, Hispanic, Black, treatment at academic centers, West region, earlier tumor stage, and receipt of noncurative treatment were associated with treatment delays. In multivariable Cox regression with a landmark of 150 days, patients with and without treatment delays had similar OS (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], 0.98-1.04) with a median survival of 33.7 vs. 32.1 months, respectively. However, therapeutic delay was associated with worse OS in patients who had tumor, nodes, and metastases (TNM) stage 1 (aHR, 1.06; 95% CI, 1.01-1.11) or received curative treatment (aHR, 1.12; 95% CI, 1.05-1.18). Conclusion: One-fourth of patients with HCC receive no therapy and one-fifth of treated patients experience treatment delays. Both were associated with demographic, socioeconomic, and clinical characteristics of patients as well as facility type and region. The association between therapeutic delay and survival was stage and treatment dependent.

Hyperthermia ablation combined with transarterial chemoembolization versus monotherapy for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The existing evidence has indicated that hyperthermia ablation (HA) and HA combined with transarterial chemoembolization (HATACE) are the optimal alternative to surgical resection for patients with hepatocellular carcinoma (HCC) in the COVID-19 crisis. However, the evidence for decision-making is lacking in terms of comparison between HA and HATACE. Herein, a comprehensive evaluation was performed to compare the efficacy and safety of HATACE with monotherapy. MATERIALS AND METHODS: Worldwide studies were collected to evaluate the HATACE regimen for HCC due to the practical need for global extrapolation of applicative population. Meta-analyses were performed using the RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Thirty-six studies involving a large sample of 5036 patients were included finally. Compared with HA alone, HATACE produced the advantage of 5-year overall survival (OS) rate (OR:1.90; 95%CI:1.46,2.46; p < 0.05) without increasing toxicity (p ≥ 0.05). Compared with TACE alone, HATACE was associated with superior 5-year OS rate (OR:3.54; 95%CI:1.96,6.37; p < 0.05) and significantly reduced the incidences of severe liver damage (OR:0.32; 95%CI:0.11,0.96; p < 0.05) and ascites (OR:0.42; 95%CI:0.20,0.88; p < 0.05). Subgroup analysis results of small (≤3 cm) HCC revealed that there were no significant differences between the HATACE group and HA monotherapy group in regard to the OS rates (p ≥ 0.05). CONCLUSIONS: Compared with TACE alone, HATACE was more effective and safe for HCC. Compared with HA alone, HATACE was more effective for non-small-sized (>3 cm) HCC with comparable safety. However, the survival benefit of adjuvant TACE in HATACE regimen was not found for the patients with small (≤3 cm) HCC.

Australia could miss the WHO hepatitis C virus elimination targets due to declining treatment uptake and ongoing burden of advanced liver disease complications.

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia's progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.

COVID-19 pandemic: Impact on the management of patients with hepatocellular carcinoma at a tertiary care hospital.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital. METHODS: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020. RESULTS: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome. CONCLUSIONS: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.

Clinical significance and molecular mechanism of angiotensin-converting enzyme 2 in hepatocellular carcinoma tissues.

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.

COVID-19-Related Downscaling of In-Hospital Liver Care Decreased Patient Satisfaction and Increased Liver-Related Mortality.

The coronavirus disease 2019 (COVID-19) pandemic necessitated down-scaling of in-hospital care to prohibit the spread of severe acute respiratory syndrome-coronavirus-2. We (1) assessed patient perceptions on quality of care by telesurvey (cohort 1) and written questionnaire (cohort 2), and (2) analyzed trends in elective and nonelective admissions before (December 2019 to February 2020) and during (March to May 2020) the COVID-19 pandemic in Austria. A total of 279 outpatients were recruited into cohort 1 and 138 patients into cohort 2. All admissions from December 2019 to May 2020 to the Division of Gastroenterology/Hepatology at the Vienna General Hospital were analyzed. A total of 32.6% (n = 91 of 279) of cohort 1 and 72.5% (n = 95 of 131) of cohort 2 had telemedical contact, whereas 59.5% (n = 166 of 279) and 68.2% (n = 90 of 132) had face-to-face visits. A total of 24.1% (n = 32 of 133) needed acute medical help during health care restrictions; however, 57.3% (n = 51 of 89) reported that contacting their physician during COVID-19 was difficult or impossible. Patient-reported satisfaction with treatment decreased significantly during restrictions in cohort 1 (visual analog scale [VAS] 0-10: 9.0 ± 1.6 to 8.6 ± 2.2; P < 0.001) and insignificantly in cohort 2 (VAS 0-10: 8.9 ± 1.6 to 8.7 ± 2.1; P = 0.182). Despite fewer hospital admissions during COVID-19, the proportion of nonelective admissions (+6.3%) and intensive care unit admissions (+6.7%) increased. Patients with cirrhosis with nonelective admissions during COVID-19 had significantly higher Model for End-Stage Liver Disease (MELD) (25.5 [14.2] vs. 17.0 [interquartile range: 8.8]; P = 0.003) and ΔMELD (difference from last MELD: 3.9 ± 6.3 vs. 8.7 ± 6.4; P = 0.008), required immediate intensive care more frequently (26.7% vs. 5.6%; P = 0.034), and had significantly increased 30-day liver-related mortality (30.0% vs. 8.3%; P = 0.028). Conclusion: The COVID-19 pandemic's effects on quality of liver care is evident from decreased patient satisfaction, hospitalization of sicker patients with advanced chronic liver disease, and increased liver-related mortality. Strategies for improved telemedical liver care and preemptive treatment of cirrhosis-related complications are needed to counteract the COVID-19-associated restrictions of in-hospital care.

Impact of COVID-19 on global HCV elimination efforts.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) has placed a significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in HCV liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination programs. METHODS: Previously developed models were adapted for 110 countries to include a status quo or 'no delay' scenario and a '1-year delay' scenario assuming significant disruption in interventions (screening, diagnosis, and treatment) in the year 2020. Annual country-level model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the 'no-delay' estimates from the '1-year delay' estimates. RESULTS: The '1-year delay' scenario resulted in 44,800 (95% uncertainty interval [UI]: 43,800-49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600-79,400) excess liver-related deaths, relative to the 'no-delay' scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries. CONCLUSIONS: The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so. LAY SUMMARY: COVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate to do so.

Identification of SARS-CoV-2 Proteins Binding Human mRNAs As a Novel Signature Predicting Overall Survival in Hepatocellular Carcinoma.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus causing coronavirus disease 2019 (COVID-19), has been confirmed in cancers through binding specific mRNAs to invade human cells. Therefore, the aim of this study described here was to develop and validate novel SARS-CoV-2 proteins binding human mRNAs (SPBRs) signature to predict overall survival (OS) in hepatocellular carcinoma (HCC). Using multivariate Cox regression analysis, a set of SPBRs was identified to establish a multigene signature in the Cancer Genome Atlas repositories cohort. Furthermore, a nomogram was established based on the signature and clinical risk factors to improve risk stratification for individual patients. External validation was performed in the International Cancer Genome Consortium (ICGC) cohort. A six-SPBR signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all p < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Moreover, the signature presented an excellent diagnostic power in differentiating HCC and normal tissues. Gene set enrichment analysis demonstrated that high-risk group was closely enriched in cell cycle, DNA replication, microRNAs in cancer, and cytokine-cytokine receptor interaction. The novel signature demonstrated great clinical value in predicting the OS for patients with HCC, and will provide a good reference between cancer research and SARS-CoV-2 and help individualized treatment in HCC.