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. Author manuscript; available in PMC: 2026 May 13.
Published in final edited form as: J Med Surg Public Health. 2025 May 12;6:100199. doi: 10.1016/j.glmedi.2025.100199

Hepatitis C virus-related liver cancer among Medicaid recipients with schizophrenia, 2002–2012

Marilyn D Thomas a,b,i, Mandana Khalili c, Eric Vittinghoff b, Francine Cournos d,e, Mark Olfson d, Priya Dahiya a, Stephen Crystal f, Richard Hermida f, Christina Mangurian a,g,h,*
PMCID: PMC13155641  NIHMSID: NIHMS2163284  PMID: 42110699

Abstract

Nearly half of primary liver cancers are attributed to hepatitis C virus (HCV) infection. People living with schizophrenia have higher HCV prevalence and liver cancer mortality rates than the general population. Among Medicaid beneficiaries with HCV, we compared incident liver cancer diagnosis in recipients living with and without schizophrenia. Using Medicaid claims data, pooled logistic regression and time survival models we estimated adjusted incidence rates of liver cancer diagnosis and risk factors for those living with schizophrenia. During 2002–2012 (N = 104,469), incident liver cancer diagnosis ranged from 845 to 1602 per 100,000 person-years. Recipients living with versus without schizophrenia had lower diagnosis rates over the study period and lower cumulative incidence within common risk factors of liver disease progression (e.g., diabetes). However, rates were higher for those with comorbid human immunodeficiency virus (HIV) infection. Among recipients with schizophrenia, higher odds of liver cancer diagnosis was associated with having comorbid alcohol use disorder (OR=1.23; 95 % confidence interval [CI] =1.70–2.05), diabetes (OR=1.49; CI=1.36–1.64), hypertension (OR=1.49; CI=1.36–1.65), chronic hepatitis B (OR=2.57; CI=2.26–2.91), or ≥ 1 annual primary care visit (OR=1.65; CI=1.46–1.86). Black (versus White) recipients had lower odds of diagnosis (OR=0.77; CI=0.70–0.86). Given higher HCV prevalence and liver cancer mortality in this population, lower diagnosis rates may reflect insufficient liver cancer detection, potentially driving HCV-related excess mortality rates for individuals living with schizophrenia. Addressing metabolic abnormalities and alcohol use is critical to risk reduction in HCV-infected persons living with schizophrenia, especially those living with HCV-HIV coinfection or racially minoritized.

Keywords: Schizophrenia, HCV, Liver cancer, Medicaid, Public health insurance

1. Introduction

Primary liver cancer is a major contributor to morbidity and mortality [1,2]. The most common form of primary liver cancer is hepatocellular carcinoma, and in the US, 48 % of these cancers have been attributed to hepatitis C virus (HCV) infection [1–3]. Before the COVID-19 pandemic, acute HCV infections steadily increased, more than doubling from 2012 (~25,000) to 2019 (~58,000) [4] with new annual cases of hepatocellular carcinoma expected to vary across sociodemographic subgroups over time [5,6]. During the pandemic, HCV screening, detection, and treatment fell dramatically [7,8]. For instance, Kaufman et al. (2021) evaluated national clinical laboratory and pharmacy data and found that by July 2020, HCV testing and dispensed prescriptions fell by up to 11.8 % and 39.6 %, respectively [9]. Such large reductions in HCV detection and care may exacerbate estimated disparities in excess liver cancer incidence and mortality.

This study focused specifically on HCV infection and liver cancer diagnosis in US Medicaid recipients living with schizophrenia. The estimated prevalence of HCV infection among people living with schizophrenia is 6 times higher than the general population [7,10]. In the US, Medicaid insures two-thirds (67 %) of all adults living with schizophrenia [11]. Moreover, liver cancer mortality is 1.4 times higher for Medicaid recipients with schizophrenia than the general population [12]. Though universal HCV screening is now recommended [13], people insured through Medicaid have markedly low HCV screening rates (<10 %) [14,15]. This lack of screening can contribute to lower liver cancer detection and treatment yet higher related mortality for those living with comorbid schizophrenia and HCV infection.

People living with schizophrenia have increased rates of alcohol use disorder and metabolic abnormalities (e.g., diabetes, hypertension) [16–18], many of which are known risk factors for fatty liver disease (FLD), HCV disease progression, and liver cancer risk [19–21]. These risk factors are also strong predictors of HCV screening in this population [14,20,22]. In addition, people living with schizophrenia experience barriers to care (e.g., fragmented services, impaired cognition), contributing to lower HCV and cancer detection and treatment than the general population [14,19,21,23–25].

Direct acting antiviral (DAA) therapies with 95 % cure rates have been widely available since 2014, providing an incentive for improving HCV identification in people with schizophrenia. Prior to DAA therapy, treatment for HCV was considerably less effective and more toxic, and screening guidelines targeting high-risk populations did not include people with schizophrenia [26,27]. Although DAA treatment reduces the overall risk of liver cancer, prior HCV infection in those with liver cirrhosis remains a major risk factor for incident primary liver cancer [28,29] and subsequent survival [30].

DAA treatments are a revolutionary advance, yet the high cost and high demand initially led nearly all state Medicaid programs to implement guidelines and management practices that impeded care for high-risk groups, such as requiring people to be in treatment for substance use disorders to receive DAA [31]. However, some states have passed policies to improve DAA access as costs have gone down, making curative HCV treatment more available [32]. Because Medicaid data are not generally available until many years after it is collected, we have used data from 2002–2012 to gain key insights into national patterns of liver cancer diagnosis among people living with both schizophrenia and comorbid HCV infection regardless of HCV treatment status, which, to our knowledge, has not yet been reported.

In this longitudinal cohort of Medicaid recipients with HCV, we examined the effects of comorbid schizophrenia on incident liver cancer diagnoses, while accounting for other known liver disease risk factors. Based on recent evidence [22], we hypothesized a higher detection of new liver cancer (i.e., higher diagnosis) for those with (versus without) annual non-psychiatric primary care visits and diagnosed schizophrenia, FLD risk factors, and comorbid hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections [33,34]. Evidence also suggests Black Americans experience lower diagnosis of liver cancer than other racial/ethnic groups [35,36].

2. Methods

2.1. Study sample and design

Claims data were from the Medicaid Analytic eXtraction (MAX) files. Non-elderly patients (ages 15–64) with HCV diagnosis (ICD-9 70.51 70.41 V02.62 70.54 70.44 70.54 70.7 70.71) included recipients living with schizophrenia and frequency-matched controls during January 1, 2002 through December 31, 2012 (N = 12,059,870). HCV diagnosis was identified in the first observed year and carried forward each year that patients remained in the study sample. The matched analytic sample was restricted to Medicaid recipients who were non-dual eligible for Medicaid with a diagnosed HCV infection. First, we restricted to those who were not dually eligible for Medicare (62 %; 7478,951/12,059,870) to reduce under ascertainment due to liver cancer only documented in Medicare billing. Second, we further restricted to recipients with HCV infection (1.4 %; 104,469/7,7478,951) (Fig. 1). Data were deidentified thus the University of California San Francisco Institutional Review Board provided an expedited approval (17–21998). Study protocols are detailed elsewhere [22].

Fig. 1.

Fig. 1.

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Sample Selection: Non-Dually Eligible Medicaid Recipients Living with Hepatitis C Viral (HCV) infection, 2002–2010.

2.2. Study measures

Exposure Assessment. Recipients with schizophrenia had (a) ≥ 1 inpatient claim for schizophrenia (ICD-9-CM: 295.x) or (b) ≥ 2 outpatient claims for schizophrenia within any given 6-month period during the observed calendar year. Controls were frequency-matched 1:1 by age, sex, and race/ethnicity, stratified by year of first eligibility for selection. Controls were excluded on the date of an observed schizophrenia claim.

Outcome Assessment. Recipients with current or history of liver cancer (ICD-9-CM: 155.x, 570.x) were identified in the first year of the claim and carried forward each year that recipients remained in the study.

Covariates. Personal demographic confounders included sex (male, female), race/ethnicity (White, Black, Asian American or Pacific Islander, Hispanic or Latino, Multiracial, Unknown), and age (15–19, 20–29, 30–39, 40–49, 50–59, 60–64 years). Coexisting risk factors for liver disease progression included alcohol use disorder and metabolic abnormalities, specifically obesity, diabetes, dyslipidemia, and hypertension [37,38]. We assessed collinearity between metabolic conditions using chi-square tests to determine if excluding any strongly associated variable would avoid biased estimates. Because liver cirrhosis is the strongest risk factor for developing HCV-related liver cancer [39,40], it was considered a mediator and not included as a covariate. Despite evidence on the role of marijuana consumption in developing liver cancer is mixed at best [41,42], we included cannabis use disorder as a covariate. We also adjusted for co-occurring clinical diagnoses linked to liver disease risk: HIV, HBV, and health care utilization [33,43]. ICD-9 and CPT codes are presented in Supplemental Table 1.

2.3. Statistical analysis

Chi-square tests were used to assess differences in baseline sample characteristics between groups. Annual incidence of liver cancer diagnosis was calculated using pooled logistic regression with robust standard errors to account for individuals being followed over time. Also using pooled logistic regression, we applied discrete time-to-event (i.e., survival) models to estimate adjusted cumulative incidence of liver cancer diagnosis per 100,000 person-years, overall and within subgroups, as well as adjusted associations of covariates with liver cancer incidence among participants with schizophrenia [44]. Interactions were used to allow baseline incidence curves to differ by schizophrenia status. All statistical analyses were performed using STATA 17 (StataCorp, College Station, TX, USA). Adjusted incidence rates were estimated using the sts list command with the adjustfor option, and incidence curves were plotted using the sts graph command. The pooled logistic models were estimated using the logistic and margins commands. Methods used by these commands are described in detail in the extended STATA online help.

Sensitivity analyses were conducted to (1) omit medical visits, a possible mediator, from the model, (2) further adjust for HCV risk factors that may contribute to differential diagnosis of HCV between groups: substance use disorders (SUDs; opioid, cocaine, amphetamine, cannabis, other drugs) and sexually transmitted infections (STIs; herpes, chlamydia, syphilis, gonorrhea), and (3) assess comorbid anxiety and depression diagnoses that may impact HCV detection and treatment [14,20,45].

3. Results

3.1. Study sample characteristics

Table 1 presents the distribution of baseline study sample characteristics of Medicaid recipients with HCV infection during 2002–2012 (N = 104,469), stratified by schizophrenia status. In the analytic sample restricted to those with HCV infection, recipients living with schizophrenia outnumbered those in the control group by nearly 2–1 (63 % vs 37 %). Recipients with schizophrenia were also more likely to be diagnosed with common FLD risk factors (ranging 3.4–15.0 percentage points). The control group was more likely to have an annual primary care visit (84 % vs 78 %). Similarly, the proportion of liver cancer diagnosis was higher for the control group each year (1.1–1.6 %) compared to recipients with schizophrenia (0.8–1.4 %).

Table 1.

Baseline Characteristics of Nondual Medicaid Recipients with HCV, stratified by Schizophrenia and Control (N = 104,469).

Schizophrenia (n = 65,759) Control (n = 38,710)
Predictor Class Variable n % n %
Demographics
Sex Female 27,706 42.1 % 13,013 33.6 %
Male 38,053 57.9 % 25,697 66.4 %
Race/ethnicity White 27,333 41.6 % 19,437 50.2 %
Black 22,452 34.1 % 13,472 34.8 %
AI/AN 694 1.1 % 342 0.9 %
AAPI 920 1.4 % 580 1.5 %
Hispanic 9359 14.2 % 2640 6.8 %
Multiracial 186 0.3 % 54 0.1 %
Unknown 4815 7.3 % 2185 5.6 %
Age 15–19 197 0.3 % 52 0.1 %
20–29 3182 4.8 % 1115 2.9 %
30–39 9972 15.2 % 3989 10.3 %
40–49 25,866 39.3 % 14,914 38.5 %
50–59 23,018 35.0 % 15,988 41.3 %
60–64 3524 5.4 % 2642 6.8 %
FLD riskƗ
Use Disorder Alcohol 21,998 33.5 % 7156 18.5 %
Cannabis£ 6012 9.1 % 948 2.5 %
Body Weight Obesity 5379 8.2 % 1598 4.1 %
Metabolic Diabetes Mellitus 16,544 25.2 % 7516 19.4 %
Hypertension 30,240 50.0 % 16,093 41.6 %
Dyslipidemia 13,254 20.2 % 6423 16.6 %
ComorbiditiesƗ Hepatitis B 5533 8.4 % 2750 7.1 %
HIV 7994 12.2 % 4944 12.8 %
Primary Care ≥ 1 Annual Visit 51,333 78.1 % 32,490 83.9 %
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Abbreviations: FLD = metabolic-related or alcohol-related fatty liver disease and cancer risk factor; AI/AN = American Indian or Alaskan Native; AAPI = Asian American or Pacific Islander.

Ɨ

Totals are restricted to those with comorbidity, therefore columns will not total %100.

£

Risk factor for liver disease progression.

Note: All covariates significantly differed between subgroups (p < .01).

3.2. Regression model specification

As expected [46,47], dyslipidemia, diabetes, and hypertension were strongly correlated within the study sample (data available upon request). Since we could not distinguish between certain types of dyslipidemia related to metabolic liver disease in our data (e.g., low high-density lipids, high triglycerides) [48], we did not include dyslipidemia as a covariate in the regression models. To avoid small cell sizes (<2 %), Asian American, Pacific Islander, Multiracial, and the Unknown group were combined into one “Other” racial/ethnic category for analysis.

3.3. Annual incidence of liver cancer diagnosis, by schizophrenia status

Pooled regression models were minimally adjusted for a schizophrenia status and calendar year interaction term, sex, age, race/ethnicity, and for those who entered the first year of the study sample with a preexisting diagnosis of HCV infection (i.e., prevalent HCV). Liver cancer diagnosis rates ranged from 845 to 1602 per 100,000 person-years from 2002 to 2012 (Supplemental Figure 1). For both groups, rates initially decreased and then sharply increased after 2009. Over the study period, liver cancer incidence rates were slightly lower among participants living with schizophrenia compared to the control group, differing by no more than 506 diagnoses per 100,000. However, there was no meaningful difference in liver cancer diagnosis between groups by 2012 (both nearly 1500 per 100,000).

3.4. Cumulative incidence of liver cancer diagnosis, by schizophrenia status

Time-to-event models were adjusted for a schizophrenia status and calendar year interaction term, sex, age, race/ethnicity, prevalent HCV infection at study entry, alcohol use disorder, cannabis use disorder, obesity, diabetes, hypertension, HBV, HIV, and annual primary care visit. Lower cumulative incidence was observed for recipients living with (vs without) schizophrenia (Fig. 2) and within all common risk factors of liver disease progression (Supplemental Figure 2), except for those with comorbid HIV infection. Compared to the control group with comorbid HIV infection, recipients with schizophrenia and comorbid HIV infection had higher cumulative incidence of liver cancer diagnosis (Fig. 3).

Fig. 2.

Fig. 2.

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Liver Cancer Diagnosis by Schizophrenia Status, 2002–2012. Cumulative incidence of liver cancer diagnosis per 100 among non-dual Medicaid recipients with HCV infection comparing people living with schizophrenia and frequency-matched controls during 2002 through 2012.

Fig. 3.

Fig. 3.

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Liver Cancer Diagnosis and Comorbid HIV, 2002–2012. Cumulative incidence of liver cancer diagnosis per 100 among non-dual Medicaid recipients with HCV and HIV infection comparing people living with schizophrenia and frequency-matched controls during 2002 through 2012.

3.5. Risk factors for recipients living with schizophrenia

Table 2 presents odds ratio estimates from a fully adjusted pooled logistic regression model for incident liver cancer among recipients with schizophrenia. Being age ≥ 60 (vs <40) (OR=1.23; 95 % confidence interval [CI]= 1.02–1.49) and having comorbid alcohol use disorder (OR=1.23; CI=1.70–2.05), diabetes (OR=1.49; CI=1.36–1.64), hypertension (OR=1.49; CI=1.36–1.65), HBV (OR=2.57; CI=2.26–2.91), or at least one annual primary care visit (OR=1.65; CI=1.46–1.86) were associated with higher odds of liver cancer diagnosis. Compared to White recipients, recipients of Black (OR=0.77; CI=0.70–0.86) and Other racial/ethnic groups (OR=0.82; CI=0.70–0.96) had lower odds of liver cancer diagnosis. Apart from the imprecision of estimates for Hispanic recipients, sensitivity analyses showed no meaningful differences in models excluding medical visits or in models accounting for SUDs, STIs, and other psychiatric conditions (Supplemental Table 2).

Table 2.

Pooled Logistic Regression of Liver Cancer Incidence among Non-dual Medicaid Recipients with Schizophrenia and HCV Infection, 2002–2012 (N = 65,759).

Variable OR LB
95 % CI		 UB
95 % CI		 p-value
Female 1.00 REF
Male 1.00 0.91 1.09 0.991
White 1.00 REF
Black 0.77 0.70 0.86 0.000
Hispanic 0.88 0.77 1.00 0.057
Other 0.82 0.70 0.96 0.012
15–39 1.00 REF
40–49 0.87 0.76 1.00 0.052
50–59 1.03 0.89 1.18 0.710
60–64 1.23 1.02 1.49 0.030
Alcohol 1.87 1.70 2.05 0.000
Cannabis 1.08 0.93 1.25 0.340
Obesity 1.09 0.95 1.26 0.215
Diabetes Mellitus 1.49 1.36 1.64 0.000
Hypertension 1.49 1.36 1.65 0.000
Hepatitis B 2.57 2.26 2.91 0.000
HIV 1.00 0.87 1.15 0.973
≥ 1 Annual Visit 1.65 1.46 1.86 0.000
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Abbreviations: HCV = hepatitis C virus; OR = odds ratio; UB = upper bound; LB = lower bound; CI = confidence interval; REF = reference group; AI/AN = American Indian or Alaskan Native; AAPI = Asian American or Pacific Islander; SUD = substance use disorder; STI = sexually transmitted infection.

Note. All models are adjusted for those who entered the first year of the study sample with a preexisting diagnosis of HCV infection and calendar year.

4. Discussion

4.1. Summary of findings

In this retrospective study of non-elderly US Medicaid recipients with HCV infection, we estimated incident liver cancer diagnosis among those with and without schizophrenia. We found that overall annual incident diagnosis during 2002–2012 was quite high, ranging from 845 to 1602 per 100,000 person-years. Over the study period, liver cancer diagnosis was unexpectedly lower for recipients living with schizophrenia compared to the control group (≤506 per 100,000), even when controlling for known risk factors of HCV-related liver disease progression. However, we found no rate difference in diagnosis by the end of the study period. As hypothesized, we found that among recipients living with schizophrenia, those who were over age 59, had comorbid alcohol use disorder, diabetes, hypertension, HBV, or had at least one annual primary care visit had higher odds of liver cancer diagnosis. Compared to White recipients, Black recipients living with schizophrenia had lower odds, as expected. Cannabis use disorder was not associated with liver cancer diagnosis in the study sample.

4.2. Interpretation of findings

Although the annual proportion of incident liver cancer diagnosis in the overall study cohort was low (0.8–1.6 % per year), the incident rate per 100,000 person-years was at least 94 times higher than the general population (≥845 vs. ~9 respectively [49]). Given the lack of nuanced studies among Medicaid recipients with HCV infection, this finding, albeit novel and marked, aligns with prior research. Lam et al. (2021) reported that patients living with HCV infection had an estimated 31 times increased rate of incident liver cancer than those without HCV during 2015–2019 [50]. More recently, Karlitz et al. (2023) reported Medicaid recipients had nearly double the annual incidence of liver cancer than the general population during the same time period (16 per 100,000) [51]. Together, these results suggest that our study population is at extremely high risk when compared to the general population. Hence, future studies should investigate more complex social and structural intersections among people living with schizophrenia and comorbid HCV infection (e.g., race/ethnicity, health care utilization, medication use) that influence liver cancer diagnosis.

Our findings also suggest that people living with schizophrenia and comorbid HCV infection may be underdiagnosed for liver cancer: the control group had higher liver cancer detection than patients with schizophrenia. This finding is consistent with a meta-analysis suggesting liver cancer diagnosis is 20 % lower for this subgroup relative to the general population [48], despite having higher liver cancer mortality [12]. Given that people with schizophrenia are less likely to receive cancer screening than those without schizophrenia [25], the discrepancy between incidence and mortality might be explained by delays in diagnosis or disparities in treatment following incident liver cancer diagnosis. One recent study found that Medicaid patients with cancer were less likely to have their cancer detected, less likely to receive therapy, and had lower survival rates than patients with commercial (i.e., private) insurance [52]. This body of evidence suggests that HCV-related liver cancer may not be detected early or effectively treated in Medicaid recipients with schizophrenia, contributing to more extensive disease and subsequent excess mortality. This presumed mechanism is further supported by prior studies investigating breast cancer screening among people with schizophrenia. For instance, women with schizophrenia have lower mammography screening and higher breast cancer mortality than women in the general population [53]. Though we did not have the data required to test this hypothesis, future longitudinal studies should evaluate the link between liver cancer screening and related mortality among people living with schizophrenia, particularly Medicaid recipients with comorbid HCV infection.

Notably, the Medicaid incident liver cancer diagnosis gap by schizophrenia status may be narrowing. Despite the paradoxical relationship we found between schizophrenia and incident diagnosis, there was no rate difference between groups by the end of the study period. After 2009, trends in incident liver cancer diagnosis increased for both groups, which may be explained in part by updated practice guidelines on the management of hepatocellular carcinoma in 2010 by the American Association for the Study of Liver Diseases (AASLD) [54]. Improved diagnostic accuracy and cost-effectiveness may have contributed to higher liver cancer screening overall with greater benefits for recipients living with schizophrenia. AASLD guidelines were updated again in 2018. Additional research should build upon this work by investigating a causal relationship between AASLD guidelines and liver cancer screening or detection during and after the current study period.

Among Medicaid recipients with comorbid HIV, incident liver cancer diagnosis was higher for those with schizophrenia than controls. Though the mechanism is not fully established, HIV infection increases HCV-related liver cancer risk and mortality via lower CD4 cell counts [34, 55,56]. In 2006, the Center for Disease Control and Prevention updated HIV testing guidelines to recommend annual screening for high risk groups [57]. During this study period, Medicaid recipients living with schizophrenia had higher screening rates of HIV and HCV than those without schizophrenia [58]. Moreover, HCV screening was 6 times higher among recipients with comorbid HIV infection [22]. Because liver cancer can occur earlier for those with HIV, and people living with schizophrenia have higher prevalence of HIV infection than the general population, it is plausible that liver cancer is detected earlier among HIV-HCV coinfected recipients living with (vs without) schizophrenia. Given the common co-occurrence of viral hepatitis and HIV infection through shared transmission routes [56], policy and clinical practice improvements in HIV testing and care may have spillover effects contributing to improved liver cancer screening in this population.

Consistent with the literature, we also found incident liver cancer diagnosis to be lowest in Black recipients with schizophrenia, supporting a potential disparity in detection for Black patients. One meta-analysis reported that compared to White patients, early-stage detection of liver cancer is lower among Black patients, contributing to worse overall survival for Black patients than all other racial/ethnic groups [36]. HCV infection appears to exacerbate this racial inequity for those publicly insured: Evidence within the current study period (2000–2011) shows that the proportion of liver cancer attributed to HCV infection was highest for Black Medicare recipients (36 %) and lowest for White recipients (17 %) [59]. Apart from provider- and system-level determinants, pervasive racial differences in HCV-related liver cancer incidence are likely driven by inequities in individual- and neighborhood-level social determinants related to detection that we were not able to account for in our study, such as socioeconomic status and environmental exposures (e.g., access to transportation and health services), warranting deeper investigation.

4.3. Strengths and limitations

Our novel study findings have important contemporary implications and methodological considerations. First, this is the first study to report disproportionate incident liver cancer diagnosis for Medicaid recipients with schizophrenia and comorbid HCV infection. Because liver cancer mortality rates are higher for this population than the general population, our report provides key insights into potential drivers of and inequities in detection and treatment, which can inform policy makers and providers aiming to strengthen national healthcare delivery systems.

Second, our retrospective study design supports the robustness of findings. The sample was nationally representative and study results are generalizable to Medicaid recipients in the 45 states studied. However, findings do not reflect those dually enrolled in Medicare, uninsured or privately insured, or other hard to reach populations such as those who are incarcerated, likely resulting in underestimation of liver cancer diagnosis. Internal validity was enhanced by adjusting for known risk factors of liver cancer, although unmeasured confounding from variables not included in our dataset certainly exists (e.g., smoking, low-risk drinking). Any selection bias introduced by restricting the sample to nondual eligible recipients with HCV after frequency-matching was likely minimal given the similar distribution of matching factors between study groups. Additionally, adjusted pooled logistic regression with robust standard errors was a flexible estimation approach to analyze an open cohort and maximize statistical power.

Third, our observational study design warrants common concerns associated with analyzing claims data. Medicaid data on race/ethnicity is often incomplete or misclassified as “unknown” [60], plausibly contributing to smaller cell sizes for some groups and their subsequent collapse into one “Other” racial/ethnic category for regression analyses, which limits the validity and interpretability of its effect estimate. Similarly, underdiagnosis of HCV infection or incident liver cancer and inaccuracies in claims data are plausible but would be differential misclassification and result in underestimation. Under ascertainment of liver cancer risk factors, especially obesity and hypertension, is also possible, though not likely differential. It is not possible, however, to distinguish group differences in liver cancer diagnoses attributable to differences in liver cancer screening versus underlying prevalence with claims data. Furthermore, MAX claims data do not capture managed care enrollment, yet we have no reason to expect differential impacts on either study group.

Finally, delays in Medicaid data availability resulted in the most recent data being collected in 2012. Nevertheless, our study period aligned with our goal to evaluate the role of comorbid schizophrenia and HCV infection on incident liver cancer diagnosis to assess national patterns independent of care management given that treated HCV infection does not eliminate liver cancer risk.

5. Conclusions

Despite higher rates of liver cancer mortality than the general population, Medicaid recipients with HCV infection who live with schizophrenia have lower incident liver cancer diagnoses than recipients without schizophrenia. Insufficient liver cancer screening and detection are implicated as drivers of HCV-related excess mortality in this population. Structural-level racial discrimination and mental illness-related stigma operating within healthcare systems (e.g., late-stage detection) and societal institutions (e.g., access to services) likely interact and worsen inequities in incident liver cancer diagnoses. Addressing metabolic abnormalities and alcohol use is critical to risk reduction in HCV-infected persons living with schizophrenia. Moreover, spillover effects from efforts to improve HIV care may help increase liver cancer screening for those living with schizophrenia and HCV-HIV coinfection, warranting further investigation.

Supplementary Material

Supplemental Material

Funding

This work was supported by a grant from the National Institute of Mental Health (R01 MH112420).

Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.glmedi.2025.100199.

Footnotes

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Khalili is a recipient of research grant (to her institution) from Gilead Sciences Inc. and Intercept Pharmaceuticals and served as a consultant for Gilead Sciences Inc. Dr. Khalili was supported by the National Institute on Alcohol Abuse and Alcoholism (grant number: K24AA022523). Outside of this work, Dr. Mangurian is supported by several grants from the National Institutes of Health (NIMH; NIMHD; NIAID; NIDA), Department of Defense, the Doris Duke Charitable Foundation. The other authors have no disclosures to report.

Ethical clearance

The study met the institution’s or the data curator’s guidelines for protection of human subjects concerning their safety and privacy. IRB #: 17-21998; Reference #: 353647

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