Table 1.

Characteristics of Included Studies

Reference	Study Description	Study Design Setting/Data Source (Subjects, n)	Study Inclusion Criteria Participant Demographics	Financial Burden and Financial Distress Measures: Definition, Prevalence	Financial Toxicity Outcomes
Lago-Hernandez et al., 2021 (USA)32	To estimate the prevalence, risk factors, and consequences of cost-related medication non-adherence in individuals with chronic liver disease	Cross-sectional NHIS, 2014–2018 (n=3,237)	Patients with chronic liver disease 27% aged ≥ 65 y, 57% 40–64 y, 16% 18–39 y 48% men 67% non-Hispanic white, 18% Hispanic, 7% Black, 5% Asian 7% uninsured	Behavioral Financial Distress (Tradeoffs for Healthcare): Cost-related medication nonadherence Needed but could not afford medications Delayed filling prescriptions Took less medication to save Skipped medication doses to save Prevalence: 25% reported cost-related medication nonadherence Patients with chronic liver disease more likely to experience cost-related medication nonadherence than adults without chronic liver disease (aOR 1.40; 95% CI 1.22–1.61)	Among chronic liver disease patients, cost-related medication nonadherence was associated with: 5.1x higher odds of financial hardship from medical bills (aOR 5.05, 95% CI 3.73–6.83) 4.3x higher odds of financial distress (aOR 4.28, 95% CI 3.19–5.76) 9.3x higher odds of engaging in cost-reducing behaviors (aOR 9.3, 95% CI 6.9–12.7) 2.9x higher odds of food insecurity (aOR 2.85, 95% CI 2.02–4.01) 1.5x higher odds of emergency department visits (aOR 1.46, 95% CI 1.11–1.94) 1.6x higher odds of health-related work absenteeism (aOR 1.62, 95% CI 1.2–2.19)
Lago-Hernandez et al., 2021 (USA)25	To estimate the national burden and consequences of financial hardship from medical bills in individuals with chronic liver disease	Cross-sectional NHIS, 2014–2018 (n=3,666)	Patients with chronic liver disease 25% aged ≥ 65 y, 56% 40–64 y, 19% 18–39 y 50% male 65% non-Hispanic white, 19% Hispanic, 8% Black, 5% Asian 8% uninsured	Direct Financial Burden (Financial Hardship from Medical Bills): Having problems paying medical bills in the past 12 months Currently having medical bills being paid off over time Unable to pay medical bills at all Psychological Financial Distress (Worry about Affording Healthcare): Ability to pay medical costs of illness/accident, usual health care, rent/mortgage/housing costs, or monthly bills Save for retirement Maintain standard of living Prevalence: 37% of patient reported financial hardship from medical bills 14% of patient were unable to pay medical bills at all 36% reported high financial distress Patients with chronic liver disease more likely to experience hardship from medical bills than adults without chronic liver disease (aOR, 1.43; 95% CI, 1.27–1.62) Prevalence of financial hardship from medical bills for patients with chronic liver disease comparable to that observed among patients with Type 2 diabetes (aOR, 0.9; 95% CI, 0.8–1.1.) and chronic kidney disease (aOR, 1.1; 95% CI, 0.9–1.3) but lower than that observed among patients with cardiovascular disease (aOR, 1.4; 95% CI, 1.1–1.9)	Among chronic liver disease patients, being unable to pay medical bills was associated with: 8.4x higher odds of cost-related medication nonadherence (aOR 8.39, 95% CI 5.72–12.32) 6.3x higher odds of financial distress (aOR 6.33, 95% CI 4.44–9.03) 5.6x higher odds of food insecurity (aOR 5.59, 95% CI 3.74–8.37) 1.9x higher odds of emergency department visits (aOR 1.85, 95% CI 1.33–2.57) 1.8x higher odds of health-related work absenteeism (aOR 1.83, 95% CI 1.26–2.67)
Peretz et al., 2020 (Canada)23	To document the psychological and financial impact of having to travel long distances for liver transplantation in adult liver disease patients	Cross-sectional Health Sciences Center, Winnipeg, Manitoba, Canada; 2018–2019 (n=96)	Liver transplant recipients Mean age at transplant of 43 y (34% > 60 y) 59% male 18% HCV, 11% PSC, 10% AIH, 9% ALD, 7% PBC, 6% NAFLD, 38% unknown	Direct Financial Burden (Out-of-Pocket Healthcare Expenditures) for patients and/or their families/friends during the liver transplant hospitalization: Median out-of-pocket expenses was $4,645 CAD (range $0-$117,624) to cover needs such as transportation, accommodations, and food	N/A
Pol et al., 2019 (Canada)34	To increase understanding of the motivations and outcomes of organ transplantation crowdfunding	Mixed-methods Canadian adult liver transplantation campaigns posted to GoFundMe; May 2018 (n=134)	Adult liver transplant candidates	Behavioral Financial Distress (Support-Seeking): Crowdfunding On average liver campaigns received $8,346.77 CAD The majority of campaigns (78%) characterized liver transplantation as a financial burden, with the most common reasons for requesting funding as follows: caregiver expenses (38%), patient relocation expenses (34%), patient living expenses (32%)	N/A
Lu et al., 2019 (USA)63	To examine hepatitis C virus (HCV) medication use and costs in a commercially insured population	Retrospective Harvard Pilgrim Health Care medical and pharmacy claims data, 2012–2015 (n=3,091)	Patients with chronic HCV infection 8% aged ≥ 65 y, 62% 50–64 y, 20% 30–49 y, 10% 18–29 y 66% male 78% White, 20% mixed race, 2% Black	Direct Financial Burden (Out-of-Pocket Healthcare Expenditures) on HCV medications Following availability of new direct-acting antivirals, average yearly out-of-pocket spending on HCV medications increased from $41 USD to $94 USD per HCV-diagnosed member in the study population, with about 32% of members receiving HCV medications. In adjusted pre–post analyses, the absolute change was $53 USD (95% CI, $9 USD - $97 USD) per member per year and the relative change was 131% (95% CI, 15%−247%)	N/A
Beal et al., 2017 (USA)30	To examine patterns of employment discontinuity among liver transplant recipients and evaluate clinical, demographic, and economic factors that may contribute to delayed or unstable employment	Retrospective UNOS, 2002–2009 (n=12,998)	Deceased donor liver transplant recipients at least 5 years post-transplant Mean age at transplant 49 y 71% male 75% White, 9% Black, 16% Other 26% HCV, 10% cholestatic liver disease, 19% alcohol, 15% HCC, 30% other	Indirect Financial Burden (Worker Productivity Loss): Patient employment status after liver transplantation 36% of patients were never employed post-transplant 29% of patients returned to work within 2 years of transplant and remained employed 23% of patients returned to work within 2 years of transplant but subsequently became unemployed 12% of patients returned to work ≥ 3 years post-transplant	N/A
Singh et al., 2016 (India)26	To estimate the socioeconomic impact of alcohol use on patients with alcohol-related liver disease and their families	Cross-sectional Shrirama Chandra Bhanj Medical College and Hospital, Cuttack, Odisha, India, 2013–2014 (n=100)	Patients with alcohol-related liver disease 37% > 50 y, 60% 30–50y, 3% < 30 y 100% male	Indirect Financial Burden (Worker Productivity Loss): 80% were absent from their work due to alcohol-related problems with average duration of work absenteeism of 12 weeks Behavioral Financial Distress (Support-Seeking): Increased borrowing 86% of patients borrowed money from friends/relatives for treatment expenses Behavioral Financial Distress (Tradeoffs for Necessities): Tradeoffs for education For 43% of patients, their children were deprived of education due to financial burden	N/A
Stepanova et al., 2017 (USA)4	To assess the effects of chronic liver disease on quality of life and work productivity as well as its economic burden in the US	Cross-sectional MEPS, 2004–2013 and NHANES (1999–2012) (n=1,864)	Patients with chronic liver disease Mean age 54 y 49% male 70% non-Hispanic White, 10% Black, 13% Hispanic, 4% Asian 9% uninsured	Direct Financial Burden (Out-of-Pocket Healthcare Expenditures): Patients with chronic liver disease had annual healthcare expenses of $19,390 USD compared to $5,567 for adults without chronic liver disease Indirect Financial Burden (Worker Productivity Loss): 45% of chronic liver disease patients were employed (compared with 70% without liver disease, p < 0.0001) Patients with chronic liver disease were more likely to not work due to their illness or disability (31% vs. 7%) and had 3 times more disability days per year (10.2 days vs. 3.4 days) The presence of chronic liver disease was independent predictor of employment (OR 0.6, 95% CI 0.5–0.71)	Yearly health expenses (per $10,000 USD) were independently associated with a decrease in the Physical Component Score (Beta = −0.5 ± 0.09) and Mental Component Score (−0.25 ± 0.10) of the Short-Form 12 health-related quality of life survey
Che et al., 2016 (China)19	To investigate the financial burden of patients who had various stages of hepatitis B (HBV)-related diseases and the level of alleviation from financial burden by health insurance schemes in Yunnan province of China	Cross-sectional First Affiliated Hospital of Kunming Medical University, 2012–2013 (n=940)	Patients with chronic HBV, compensated HBV cirrhosis, decompensated HBV cirrhosis, and HBV with HCC Mean age 44 y 66% male 55% HBV, 10% compensated, 21% decompensated, 14% HCC	Direct Financial Burden (Catastrophic Financial Burden): Household’s out-of-pocket expenses exceeding 40% of household’s capacity to pay 36% compensated, 51% decompensated, 50% HCC patients had catastrophic health expenditures after health insurance reimbursement	N/A
Rakoski et al., 2012 (USA)21	To assess health status and functional disability of older individuals with cirrhosis and its complications, as well as estimate the burden and cost of informal caregiving in this population	Prospective longitudinal Health and Retirement survey linked to Center for Medicare and Medicaid Services, 1998–2008 (n=371)	Patients > 50y with cirrhosis Mean age 75 y 45% male 72% White, 14% Black, 13% Hispanic	Direct Financial Burden (Out-of-Pocket Healthcare Expenditures): Self-reported over the previous two years Median $2,150 USD ($526–$5,379) for patients with cirrhosis versus $1,459 USD ($433–$3,709) for those without cirrhosis, p<0.001 Indirect Financial Burden (Financial Costs of Informal Caregiving) Annual cost of informal caregiving for elderly individuals with cirrhosis was $4,700 USD per person (compared to $2,100 USD for age matched elderly individuals without cirrhosis)	N/A
Hareendran et al., 2020 (India)31	To study the quality of life, psychosocial burden and prevalence of mental health disorders among caregivers	Cross-sectional Government Medical College Trivandrum, South India, 2018–2019 (n=132)	Primary caregivers of patients with cirrhosis Mean caregiver age of 41 11% male	Behavioral Financial Distress (Support-Seeking): 25% of caregivers were forced to work due to financial constraints 20% of families had to take a loan to pay for medical expenses Behavioral Financial Distress (Tradeoffs for Necessities): 9% of families had their children’s education be hampered due to financial constraints	Increased cost of cirrhosis treatment was associated with an increased risk of depression and anxiety among caregivers
Rodrigue et al., 2007 (USA)24	To survey liver transplant and kidney transplant recipients about the financial impact of transplantation and to ascertain the strategies they used to manage non-reimbursed expenses related to transplantation	Cross-sectional University of Florida, 1995–2004 (n=333)	Liver transplant recipients Mean age 57 y 69% male 81% White	Direct Financial Burden (Out-of-Pocket Healthcare Expenditures): Estimated monthly out-of-pocket expenses Liver transplant recipients reported spending $540 USD/month on medical expenses Material Financial Distress (Loss of Savings/Assets, Medical Debt/Bankruptcy): To pay for out-of-pocket health expenses, patients reported the following: 57% used personal/family savings 24% used credit cards 8% declared bankruptcy	N/A
Shrestha et al., 2019 (India)27	To evaluate the burden on the informal caregivers of patients with cirrhosis and the factors responsible for this burden in a population in Northern India	Cross-sectional Post-graduate institute of Medical Education and Research, Northern India, 2015 (n=200; 100 patients and 100 caregivers)	Patients with cirrhosis and their informal caregivers Caregivers mean age 47 66% female	Indirect Financial Burden (Worker Productivity Loss): 44% of patients in the study were currently employed	N/A
Rahman et al., 2020 (Bangladesh)18	To estimate the cost of illnesses among a population in urban Bangladesh and to assess the household financial burden associated with these diseases	Cross-sectional Rajshahi, Bangladesh, 2011 (n=41)	Household members with self-reported liver disease	Direct Financial Burden (Catastrophic Financial Burden): Household’s out-of-pocket expenses exceeding 40% of household’s capacity to pay Incidence of catastrophic healthcare expenditure was 12.3% among individuals with liver disease	N/A
Federico et al., 2012 (Canada)22	To evaluate time costs (time spent seeking healthcare) and out-of-pocket costs for patients with hepatitis C (HCV) and their caregivers	Cross-sectional University of British Columbia, 2006–2008 (n=738)	Patients with HCV Chronic HCV infection (n=326), cirrhosis (n=135), HCC (n=21), transplant recipients (n=47) Mean age 54 y 60% male 86% White	Direct Financial Burden (Out-of-Pocket Healthcare Expenditures): Patients receiving active treatment and those with late-stage disease spent over $2000 CAD per year on HCV-related healthcare, which represented approximately 7% of their annual income. Indirect Financial Burden (Time Costs of Informal Caregiving): Patient and caregiver time costs (calculated time spent seeking healthcare by hourly value determined by patient/caregiver reported income and/or age- and gender-stratified wage rates). All time was valued as hours/weeks of employment The average annual time loss attributable to HCV and its treatment varied from 69 hours in early disease to 426 hours among transplant recipients. For transplant recipients, this represented over 10 weeks of working time, or 20% of the average number of working hours among employed Canadians annually. Caregivers of transplant recipients had an average of 3 weeks of annual time loss due to caregiving Indirect Financial Burden (Worker Productivity Loss): 48% of patients were unemployed	N/A
Bajaj et al., 2013 (USA)29	To investigate the association between socioeconomic status and cognition in a multicenter study of cirrhosis	Cross-sectional Multicenter (Virginia Commonwealth University, University of Rome, Case Western University), 2012 (n=236)	Patients with cirrhosis 14% had prior history of overt hepatic encephalopathy Mean age 58y	Indirect Financial Burden (Worker Productivity Loss): 37% of patients had been fully or partly employed over the past year Material Financial Distress (Loss of Savings/Assets): Median liquid assets for patients and their families ranged from $500 USD - $49,999 USD which was reduced to less than $500 USD if current debt was subtracted	N/A
Bajaj et al., 2011 (USA)28	To study the emotional and socioeconomic burden of cirrhosis and hepatic encephalopathy on patients and informal caregivers	Cross-sectional Virginia Commonwealth University, 2009–2010 (n=104)	Patients with cirrhosis and their informal caregivers Mean age 58 y 70% male 83% White, 12% Black, 5% Hispanic 44% HCV, 23% NASH, 11% EtOH + HCV, 7% EtOH, 15% others Median MELD 12 (range 6–20)	Material Financial Distress (Loss of Savings/Assets, Medical Debt/Bankruptcy): If patients lost all sources of income, they could maintain their current standard of living for 3–6 months. After liquidation of all resources, the median finances available would be reduced to $500 USD – $4,999 USD if current debt was subtracted Indirect Financial Burden (Worker Productivity Loss): 56% of patients had worked since their diagnosis and of these 53% had to decrease their hours Psychological Financial Distress (Worry about Affording Healthcare, General Financial Anxiety): 63% felt their financial status was significantly worse after the diagnosis of cirrhosis	N/A
Bolden and Wicks, 2010 (USA)35	To examine predictors of subjective burden and mental health status of family caregivers of persons with chronic liver disease	Cross-sectional University-based hepatology practice in a large southeastern US city, 2010 (n=73)	Family caregivers of patients with chronic liver disease Mean caregiver age 48 y 22% male 66% White, 30% Black, 4% Other Average of 6 years providing informal caregiving 38% of care recipients had cirrhosis	Indirect Financial Burden (Worker Productivity Loss): 26% of caregivers had experienced a decrease in their income 15% of caregivers were unemployed	Caregivers who experienced a decrease in their income were more likely to report depressive and anxiety symptoms and caregiver burden
Serper et al., 2017 (USA)33	To evaluate the association of “medication trade-offs”—defined as choosing to spend money on other expenses over medications—with medication nonadherence and transplant outcomes	Cross-sectional Two large US transplant centers, 2011–2012 (n=103)	Liver transplant recipients > 30 days post-transplant 51% 46–64 y 58% male 81% White, 14% Black, 6% Other	Indirect Financial Burden (Worker Productivity Loss): 73% of liver transplant recipients were unemployed Behavioral Financial Distress (Tradeoffs for Healthcare, Tradeoffs for Necessities): 17% of patients reported medication trade-offs; the most common trade-offs were inability to afford a prescription in the past 12 months and making choices between prescriptions and food	Patients with trade-offs were more likely to report nonadherence to medications (mean adherence: 77 ± 23% with trade-offs vs. 89 ± 19% without trade-offs, p < 0.01). The presence of medication trade-offs was associated with post-transplant hospital admissions (RR 1.64, 95% CI 1.14–2.35, p < 0.01)