Longitudinal disparities in social determinants of health and COVID-19 incidence and mortality in the United States from the three largest waves of the pandemic.

The United States experienced at least five COVID-19 waves linked with different mutated SARS-CoV-2 variants including Alpha, Delta and Omicron. In addition to the variants, the intensity, geographical distribution, and risk factors related to those waves also vary within socio-demographic characteristics and timeframes. In this project, we have examined the spatial and temporal pattern of COVID-19 in the USA and its associations with Social Determinants of Health (SDoH) by utilizing the County Health Rankings & Roadmaps (CHRR) dataset. Our epidemiologic investigation at the county level showed that the burden of COVID-19 cases and deaths is higher in counties with high percentages of smoking, number of preventable hospital stays, primary care physician rate, the average daily density of PM2.5 and percentages of high proportions of Hispanic residents. In addition, the analysis also demonstrated that COVID-19 incidence and mortality had distinct characteristics in their association with SDoH variables. For example, the percentages of the population 65 and older had negative associations with incidence while a significant positive association with mortality. In addition to the elderly population, median household income, unemployment, and number of drug overdose deaths showed a mixed association with COVID-19 incidence and mortality. Our findings validate several influential factors found in the existing social epidemiology literature and highlight temporal associations between SDoH variables and COVID-19 incidence and mortality not yet frequently studied.

The viral hepatitis B care cascade: A population-based comparison of immigrant groups.

BACKGROUND AND AIMS: The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. APPROACH AND RESULTS: In this population-based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long-term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment >1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long-term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). CONCLUSIONS: In conclusion, immigrants fared well compared to long-term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.

Hepatocellular carcinoma screening and diagnosis.

All the major liver disease societies have recommended screening for hepatocellular carcinoma (HCC). The target population for HCC screening has been defined by cost-efficacy analyses and by risk scores. Risk scores have been developed for patients with hepatitis B, regardless of the presence of cirrhosis, and for other patients with cirrhosis. Screening is with ultrasound; however, in Asia biomarkers are also used. The additional value of biomarkers has not been demonstrated. The ideal screening interval is 6 months; in Japan shorter intervals are used. Screening detects small lesions that require confirmation of HCC. There are radiological criteria that help determine whether a biopsy is necessary. Special stains can determine whether a lesion that closely resembles normal or dysplastic tissue is HCC. All these tools should be used in the management of patients undergoing HCC screening.

Surveillance for hepatocellular carcinoma.

When hepatocellular carcinoma presents with symptoms cure is seldom possible and death usually follows within months. However, it is possible to detect HCC early, at which stage it is curable. This requires a surveillance program. The components of such a program include: identification of the at risk population, provision of appropriate surveillance tests, and an appropriate method of determining whether the abnormalities found on screening are cancer or not. Surveillance for liver cancer meets all these criteria. Unfortunately high quality evidence showing benefit of liver cancer surveillance is lacking, but lesser quality evidence is plentiful, including several cost efficacy analyses that all show that surveillance does decrease mortality. Therefore all the continental liver disease societies and all national liver disease societies have recommended that surveillance should be undertaken.

Burden of disease and cost of chronic hepatitis C infection in Canada.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation. OBJECTIVE: To estimate the burden of HCV-related disease and costs from a Canadian perspective. METHODS: Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, age- and sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals. RESULTS: The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694. CONCLUSIONS: Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease forecasting, resource planning and the development of rational management strategies for HCV in Canada.

Health care costs associated with hepatocellular carcinoma: a population-based study.

UNLABELLED: Although the burden of hepatocellular carcinoma (HCC) is an escalating public health problem, it has not been rigorously estimated within a Canadian context. We conducted a population-based study using Ontario Cancer Registry linked administrative data. The mean net costs of care due to HCC were estimated using a phase of care approach and generalized estimating equations. Using an incidence approach, the mean net costs of care were applied to survival probabilities of HCC patients to estimate 5-year net costs of care and extrapolated to the Canadian population of newly diagnosed HCC patients in 2009. During 2002-2008, 2,341 HCC cases were identified in Ontario. The mean (95% confidence interval [CI]) net costs of HCC care per 30 patient-days (2010 US dollars) were $3,204 ($2,863-$3,545) in the initial phase, $2,055 ($1,734-$2,375) in the continuing care phase, and $7,776 ($5,889-$9,663) in the terminal phase. The mean (95% CI) 5-year net cost of care was $77,509 ($60,410-$94,607) and the 5-year aggregate net cost of care was $106 million ($83-$130 million) (undiscounted). The net costs of patients receiving liver transplantation only and those undergoing surgical resection only were highest in the terminal phase. The net cost of patients receiving radiofrequency ablation as the only treatment was relatively low in the initial phase, and there were no significant differences in the continuing and terminal phases. CONCLUSION: Our findings suggest that costs attributable to HCC are significant in Canada and expected to increase. Our findings of phase-specific cost estimates by resource categories and type of treatment provide information for future cost-effectiveness analysis of potential innovative interventions, resource allocation, and health care budgeting, and public health policy to improve the health of the population.

Influence of socioeconomic status on survival of hepatocellular carcinoma in the Ontario population; a population-based study, 1990-2009.

BACKGROUND: Research has shown that people from higher socioeconomic status (SES) have better hepatocellular carcinoma (HCC) survival outcomes, although no such research has been carried out in Canada. We aimed to assess if an association between SES and HCC survival existed in the Canadian context. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based cohort study linking HCC cases identified in the Ontario Cancer Registry between 1990 and 2009 to administrative and hospital data. Logistic regression and chi-squared tests were used to evaluate associations between SES (income quintile) and covariates. The Kaplan-Meier method was used to estimate survival. Sequential analysis of the proportional-hazards models were used to determine the association between SES and HCC survival controlling for potential prognostic covariates. During the period 1990-2009, 5,481 cases of HCC were identified. A significant association was found between SES and curative treatment (p = 0.0003), but no association was found between SES and non-curative treatment (p = 0.064), palliative treatment (p = 0.680), or ultrasound screening (p = 0.615). The median survival for the lowest SES was 8.5 months, compared to 8.8 months for the highest SES group. The age- and sex-adjusted proportional-hazards model showed statistically significant difference in HCC survival among the SES groups, with hazard ratio 0.905 (95% confidence intervals 0.821, 0.998) when comparing highest to lowest SES group. Further adjustments indicated that potentially curative treatment was the likely explanation for the association between SES and HCC survival. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that a 10% HCC survival advantage exists for the higher SES groups. This association between SES and HCC survival is most likely a reflection of lack of access to care for low SES groups, revealing inequities in the Canadian healthcare system.

Cost effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B from a Canadian public payer perspective.

INTRODUCTION: Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe. AIM: Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers. METHODS: A Markov model was used to calculate the costs and benefits of nucleos(t)ide therapy in three groups of patients with hepatitis B e antigen (HBeAg)-positive and -negative CHB: nucleos(t)ide-naive patients without cirrhosis; nucleos(t)ide-naive patients with compensated cirrhosis; and lamivudine-resistant patients. Disease progression was modelled as annual transitions between 18 disease states. Transition probabilities, quality of life and costs were based on published studies. Health benefits were measured in QALYs. The reference year for costs was 2007 and costs and outcomes were discounted at 5% per annum. RESULTS: First-line tenofovir DF was the most effective nucleos(t)ide strategy for managing CHB, generating 6.85-9.39 QALYs per patient. First-line tenofovir DF was also the most cost-effective strategy in all patient subgroups investigated, costing between $Can43,758 and $Can48,015 per QALY gained compared with lamivudine then tenofovir. First-line tenofovir DF strongly dominated first-line entecavir. Giving tenofovir DF monotherapy immediately after lamivudine resistance developed was less costly and more effective than any other active treatment strategy investigated for lamivudine-resistant CHB, including second-line use of adefovir or adefovir + lamivudine. Probabilistic sensitivity analysis demonstrated 50% confidence that first-line tenofovir DF is the most cost-effective nucleos(t)ide strategy for treatment-naive patients with CHB, at a $Can50,000 per QALY threshold, and confirmed that first-line tenofovir DF has the highest expected net benefits. CONCLUSIONS: First-line tenofovir DF appears to be the most cost-effective nucleos(t)ide treatment for both cirrhotic and non-cirrhotic CHB patients in Canada, providing that society is willing to pay at least $Can48,015 per QALY gained, although sensitivity analyses highlighted uncertainty around the results.

Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): a cross-sectional study.

BACKGROUND/AIMS: Low hepatic n-6 and n-3 polyunsaturated fatty acid (PUFA) may contribute to steatosis and steatohepatitis and can be affected by diet and oxidative stress. METHODS: Seventy-three patients referred for elevated liver enzymes and suspected NAFLD were assessed. Nutritional assessment, hepatic FA composition and oxidative stress were compared between these groups: simple steatosis (SS, n=18), steatohepatitis (NASH, n=38) and minimal findings on liver biopsy (MF, n=17). RESULTS: Patients with NASH had higher: BMI, central obesity, body fat, insulin resistance, dyslipidemia and lower physical activity compared to the other groups. They also had relatively lower hepatic n-3 and n-6 PUFA, a decrease in the ratio of metabolites to essential FA precursors for both n-6 and n-3 FA (eicosapentaenoic+docosahexaenoic/linolenic and arachidonic/linoleic acid ratios) and higher liver lipid peroxides with lower antioxidant power, when compared to MF. Overall, there was no significant difference between SS and NASH in FA composition. Self-reported dietary intake and red blood cell FA composition were similar among the three groups. CONCLUSIONS: NASH patients have more metabolic abnormalities. This is associated with higher oxidative stress and lower n-3 and n-6 PUFA in the liver in the absence of any differences in dietary FA composition.

Management of solitary 1 cm to 2 cm liver nodules in patients with compensated cirrhosis: a decision analysis.

OBJECTIVES: Current guidelines, based on expert opinion, recommend that suspected 1 cm to 2 cm hepatocellular carcinoma (HCC) detected on screening be biopsied and, if positive, treated (eg, resection or transplantation). Alternative strategies are immediate treatment or observation until disease progression occurs. METHODS: A Markov decision model was developed that compared three management strategies - immediate resection, biopsy and resection if positive, and ultrasound surveillance every three months until disease progression - for a single 1 cm to 2 cm liver nodule suspicious for HCC following ultrasound screening and computed tomography confirmation. The cohort included 55-year-old patients with compensated cirrhosis and no significant comorbidities. The model used in the present study incorporated the probabilities of false-positive and false-negative results, needle-track seeding, HCC recurrence, cirrhosis progression and death. The quality-adjusted life expectancy (LE) and the unadjusted LE were evaluated and the model's strength was assessed with sensitivity analyses. RESULTS: In the base case analysis, biopsy, resection and surveillance yielded an unadjusted LE of 60.5, 59.7 and 56.6 months, respectively, and a quality-adjusted LE of 46.6, 45.6 and 43.8 months, respectively. In probabilistic sensitivity analyses, biopsy was the preferred strategy 69.5% of the time, resection 30.5% of the time and surveillance never. Resection was the optimal decision if the sensitivity of biopsy was very low (less than 0.45) or if the accuracy of the imaging tests resulted in a high percentage of HCC-positive patients (greater than 76%) in the screened cohort, as with expert interpretation of triphasic computed tomography. CONCLUSIONS: The present model suggests that biopsy is the preferred management strategy for these patients. When postimaging probability of HCC is high or pathology expertise is lacking, resection is the best alternative. Surveillance is never the optimal strategy.

Health-state utilities and quality of life in hepatitis C patients.

OBJECTIVE: Health-state utilities are global measurements of quality of life on a scale from 0 (death) to 1 (full health). Utilities are used to evaluate health outcomes and are the preferred outcome measure for policy models that determine the cost-effectiveness of treatments. Currently, utilities for hepatitis C virus (HCV)-infected patients have been estimated using expert judgments. The purpose of this study was to elicit HCV utilities directly from patients. METHODS: We assessed the utilities of 193 outpatients at various stages of chronic HCV progression by using a visual analog scale, the standard gamble technique, the Health Utilities Index Mark 3 survey, and the EuroQol Index survey. We also incorporated the nonutility-based Short Form-36v2 survey, which provides a detailed profile of health status. RESULTS: The mean standard gamble utilities were: 0.78 for patients without a recent liver biopsy and no signs of cirrhosis; 0.79 for mild to moderate chronic HCV infection; 0.80 for compensated cirrhosis; 0.60 for decompensated cirrhosis; 0.72 for hepatocellular carcinoma; 0.73 for transplant; and 0.86 for sustained virological responders to interferon +/- ribavirin treatment. The Health Utilities Index Mark 3 survey and the EuroQol Index survey utilities were lower than Canadian population norms (p < 0.001). Patient-elicited utilities were lower than previous expert estimates for mild/moderate chronic infection and sustained virological responders, but higher for decompensated cirrhosis and hepatocellular carcinoma. The Short Form-36v2 survey scores revealed several significant health impairments (p < 0.005) when compared with U.S. population norms. CONCLUSIONS: These findings 1) suggest that quality of life (QOL) differences across the HCV clinical spectrum are smaller than previously believed; 2) support other evidence suggesting that QOL is significantly diminished in HCV patients; and 3) provide utility values derived directly from HCV patients.